http://bradner.dfci.harvard.edu/jq1.php
http://bradner.dfci.harvard.edu/JQ1-userguide-updated%20sept%202011.pdf


JQ1 – A first-in-class inhibitor of BET bromodomains (Nature, 2010)

http://www.guardian.co.uk/science/punctuated-equilibrium/2011/nov/03/1

How does cancer know it’s cancer? This is the question that cancer researcher, Jay Bradner and his colleagues have focused on in their research, and they think they may have found the answer: a molecule, which they call JQ1. But unlike the corporatocracy and its minions, which operate in secrecy, Dr Bradner and his colleagues chose to do something different. Engaging in an enlightened social experiment, they shared the news of this molecule by publishing their findings — and they mailed samples to 40 other labs to work with. In short, they open-sourced the information about this molecule and they crowd-sourced the testing and research.




TRANSCRIPT
http://dotsub.com/view/9ddedc52-8376-4526-8f97-b5a3181ed9de/viewTranscript/eng

I moved to Boston 10 years ago, from Chicago, with an interest in cancer and in chemistry. You might know that chemistry is the science of making molecules — or to my taste, new drugs for cancer. And you might also know that, for science and medicine, Boston is a bit of a candy store. You can’t roll a stop sign in Cambridge without hitting a graduate student. The bar is called the Miracle of Science. The billboards say “Lab Space Available.”

And it’s fair to say that in these 10 years, we’ve witnessed absolutely the start of a scientific revolution — that of genome medicine. We know more about the patients that enter our clinic now than ever before. And we’re able, finally, to answer the question that’s been so pressing for so many years: why do I have cancer? This information is also pretty staggering. You might know that, so far in just the dawn of this revolution, we know that there are perhaps 40,000 unique mutations affecting more than 10,000 genes, and that there are 500 of these genes that are bona-fide drivers, causes of cancer.

Yet comparatively, we have about a dozen targeted medications. And this inadequacy of cancer medicine really hit home when my father was diagnosed with pancreatic cancer. We didn’t fly him to Boston. We didn’t sequence his genome. It’s been known for decades what causes this malignancy. It’s three proteins — Ras, MIC and P53. This is old information we’ve known since about the 80s, yet there’s no medicine I can prescribe to a patient with this or any of the numerous solid tumors caused by these three horsemen of the apocalypse that is cancer. There’s no Ras, no MIC, no P53 drug.

And you might fairly ask: why is that? And the very unsatisfying, yet scientific, answer is it’s too hard. That for whatever reason, these three proteins have entered a space in the language of our field that’s called the undruggable genome — which is like calling a computer unsurfable or the Moon unwalkable. It’s a horrible term of trade. But what it means is that we fail to identify a greasy pocket in these proteins, into which we, like molecular locksmiths, can fashion an active, small, organic molecule or drug substance.

Now as I was training in clinical medicine and hematology and oncology and stem cell transplantation, what we had instead, cascading through the regulatory network at the FDA, were these substances — arsenic, thalidomide and this chemical derivative of nitrogen mustard gas. And this is the 21st century. And so, I guess you’d say, dissatisfied with the performance and quality of these medicines, I went back to school in chemistry with the idea that perhaps by learning the trade of discovery chemistry and approaching it in the context of this brave new world of the open-source, the crowd-source, the collaborative network that we have access to within academia, that we might more quickly bring powerful and targeted therapies to our patients.

And so please consider this a work in progress, but I’d like to tell you today a story about a very rare cancer called midline carcinoma, about the protein target, the undruggable protein target that causes this cancer, called BRD4, and about a molecule developed at my lab at Dana Farber Cancer Institute called JQ1, which we affectionately named for Jun Qi, the chemist that made this molecule. Now BRD4 is an interesting protein.

You might ask yourself, with all the things cancer’s trying to do to kill our patient, how does it remember it’s cancer? When it winds up its genome, divides into two cells and unwinds again, why does it not turn into an eye, into a liver, as it has all the genes necessary to do this? It remembers that it’s cancer. And the reason is that cancer, like every cell in the body, places little molecular bookmarks, little Post-it notes, that remind the cell “I’m cancer; I should keep growing.” And those Post-it notes involve this and other proteins of its class — so-called bromodomains. So we developed an idea, a rationale, that perhaps, if we made a molecule that prevented the posted note from sticking by entering into the little pocket at the base of this spinning protein, then maybe we could convince cancer cells, certainly those addicted to his BRD4 protein, that they’re not cancer.

And so we started to work on this problem. We developed libraries of compounds and eventually arrived at this and similar substances called JQ1. Now not being a drug company, we could do certain things, we had certain flexibilities, that I respect that a pharmaceutical industry doesn’t have. We just started mailing it to our friends. I have a small lab. We thought we’d just send it to people and see how the molecule behaves. And we sent it to Oxford, England where a group of talented crystallographers provided this picture, which helped us understand exactly how this molecule is so potent for this protein target. It’s what we call a perfect fit of shape complimentarity, or hand in glove.

Now this is a very rare cancer, this BRD4-addicted cancer. And so we worked with samples of material that were collected by young pathologists at Brigham Women’s Hospital. And as we treated these cells with this molecule, we observed something really striking. The cancer cells, small, round and rapidly dividing, grew these arms and extensions. They were changing shape. In effect, the cancer cell was forgetting it was cancer and becoming a normal cell.

This got us very excited. The next step would be to put this molecule into mice. The only problem was there’s no mouse model of this rare cancer. And so at the time that we were doing this research, I was caring for a 29 year-old firefighter from Connecticut who was very much at the end of life with this incurable cancer. This BRD4-addicted cancer was growing throughout his left lung, and he had a chest tube in that was draining little bits of debris. And every nursing shift we would throw this material out. And so we approached this patient and asked if he would collaborate with us. Could we take this precious and rare cancerous material from this chest tube and drive it across town and put it into mice and try to do a clinical trial and stage it with a prototype drug? Well that would be impossible and, rightly, illegal to do in humans. And he obliged us. At the Lurie Family Center for Animal Imaging, my colleague, Andrew Kung, grew this cancer successfully in mice without ever touching plastic.

And you can see this PET scan of a mouse — what we call a pet PET. The cancer is growing as this red, huge mass in the hind limb of this animal. And as we treat it with our compound, this addiction to sugar, this rapid growth, faded. And on the animal on the right, you see that the cancer was responding. We’ve completed now clinical trials in four mouse models of this disease. And every time, we see the same thing. The mice with this cancer that get the drug live, and the ones that don’t rapidly perish.

So we started to wonder, what would a drug company do at this point? Well they probably would keep this a secret until they turn a prototype drug into an active pharmaceutical substance. And so we did just the opposite. We published a paper that described this finding at the earliest prototype stage. We gave the world the chemical identity of this molecule, typically a secret in our discipline. We told people exactly how to make it. We gave them our email address, suggesting that, if they write us, we’ll send them a free molecule. We basically tried to create the most competitive environment for our lab as possible. And this was, unfortunately, successful.

Because now when we’ve shared this molecule, just since December of last year, with 40 laboratories in the United States and 30 more in Europe — many of them pharmaceutical companies seeking now to enter this space, to target this rare cancer that, thankfully right now, is quite desirable to study in that industry. But the science that’s coming back from all of these laboratories about the use of this molecule has provided us insights that we might not have had on our own. Leukemia cells treated with this compound turn into normal white blood cells. Mice with multiple myeloma, an incurable malignancy of the bone marrow, respond dramatically to the treatment with this drug. You might know that fat has memory. Nice to be able to demonstrate that for you. And in fact, this molecule prevents this adipocyte, this fat stem cell, from remembering how to make fat such that mice on a high fat diet, like the folks in my hometown of Chicago, fail to develop fatty liver, which is a major medical problem.

What this research taught us — not just my lab, but our institute, and Harvard Medical School more generally — is that we have unique resources in academia for drug discovery — that our center that has tested perhaps more cancer molecules in a scientific way than any other, never made one of its own. For all the reasons you see listed here, we think there’s a great opportunity for academic centers to participate in this earliest, conceptually-tricky and creative discipline of prototype drug discovery.

So what next? We have this molecule, but it’s not a pill yet. It’s not orally available. We need to fix it, so that we can deliver it to our patients. And everyone in the lab, especially following the interaction with these patients, feels quite compelled to deliver a drug substance based on this molecule. It’s here where I have to say that we could use your help and your insights, your collaborative participation. Unlike a drug company, we don’t have a pipeline that we can deposit these molecules into. We don’t have a team of salespeople and marketeers that can tell us how to position this drug against the other. What we do have is the flexibility of an academic center to work with competent, motivated, enthusiastic, hopefully well-funded people to carry these molecules forward into the clinic while preserving our ability to share the prototype drug worldwide.

This molecule will soon leave our benches and go into a small startup company called Tensha Therapeutics. And really this is the fourth of these molecules to kind of graduate from our little pipeline of drug discovery, two of which — a topical drug for lymphoma of the skin, an oral substance for the treatment of multiple myeloma — will actually come to the bedside for first clinical trial in July of this year. For us, a major and exciting milestone. I want to leave you with just two ideas. The first is if anything is unique about this research, it’s less the science than the strategy — that this for us was a social experiment, an experiment in what would happen if we were as open and honest at the earliest phase of discovery chemistry research as we could be.

This string of letters and numbers and symbols and parentheses that can be texted, I suppose, or Twittered worldwide, is the chemical identity of our pro compound. It’s the information that we most need from pharmaceutical companies, the information on how these early prototype drugs might work. Yet this information is largely a secret. And so we seek really to download from the amazing successes of the computer science industry two principles: that of opensource and that of crowdsourcing to quickly, responsibly accelerate the delivery of targeted therapeutics to patients with cancer.

Now the business model involves all of you. This research is funded by the public. It’s funded by foundations. And one thing I’ve learned in Boston is that you people will do anything for cancer — and I love that. You bike across the state. You walk up and down the river. (Laughter) I’ve never seen really anywhere this unique support for cancer research. And so I want to thank you for your participation, your collaboration and most of all for your confidence in our ideas.

http://bradner.dfci.harvard.edu/bradnerresearch.php

The Bradner Laboratory studies gene regulatory pathways using the emerging discipline of chemical biology. We focus on cancer, as cancer is a dreadful disease which remains largely incurable. We choose to study cancer biology with chemistry, because if we are successful in controlling cell identity in this manner, new types of chemical probes and therapeutics will emerge directly from these efforts.

We consider cancer as a disease of cell state, caused by genetic alterations but influenced also by the cell type of origin and the manner in which the genome is packaged. The insight that no known set of genetic alterations are capable of causing cancer in all cell types establishes the plausibility that reprogramming the cell’s fundamental identity may subvert the aggressive behavior of cancer. In addition, recent research has observed high genetic complexity, heterogeneity, plasticity and redundancy of signaling networks in cancer. These findings further establish the pressing need for molecules directed against the master regulatory proteins maintaining cancer cell identity.

We have initiated research aimed at three sets of targets:

1. Transcription Factors

2. Chromatin modifying enzymes

3. Histone binding modules

We perform this research at the Dana-Farber Cancer Institute and the Harvard Medical School, in close collaborative proximity of scientists, clinicians and patients.

In the post-genomic era, the discovery of cancer genes has become relatively straightforward. Cancer biologists and geneticists now race, like modern cartographers, to assimilate this information as a unified geography of cell signaling pathways. For the cancer patient, these advances allow a detailed, highly individualized understanding of cancer’s hard-wiring. Unfortunately, the delay in the discovery and delivery of targeted therapeutics remains a significant concern. We invoke a utilitarian model of drug discovery which is not restricted by any individual chemistry or technology. We support a collaborative, creative approach to drug discovery focused on the most pressing targets irrespective of perceived ‘druggability’ or profitability.

FELINE AIDS RESEARCH
http://www.guardian.co.uk/science/2011/sep/11/genetically-modified-glowing-cats
Glow cat: fluorescent green felines could help study of HIV
Scientists hope cloning technique that produced genetically modified cats will aid human and feline medical research
by Alok Jha / 11 September 2011

It is a rite of passage for any sufficiently advanced genetically modified animal: at some point scientists will insert a gene that makes you glow green. The latest addition to this ever-growing list – which includes fruit flies, mice, rabbits and pigs – is the domestic cat. US researcher Eric Poeschla has produced three glowing GM cats by using a virus to carry a gene, called green fluorescent protein (GFP), into the eggs from which the animals eventually grew. This method of genetic modification is simpler and more efficient than traditional cloning techniques, and results in fewer animals being needed in the process. The GFP gene, which has its origins in jellyfish, expresses proteins that fluoresce when illuminated with certain frequencies of light. Poeschla, of the Mayo Clinic in Rochester, Minnesota, reported his results in the journal Nature Methods. This function is regularly used by scientists to monitor the activity of individual genes or cells in a wide variety of animals. The development and refinement of the GFP technique earned its scientific pioneers the Nobel prize for chemistry in 2008.

In the case of the glowing cats, the scientists hope to use the GM animals in the study of HIV/Aids. “Cats are susceptible to feline immunodeficiency virus [FIV], a close relative of HIV, the cause of Aids,” said professors Helen Sang and Bruce Whitelaw of the Roslin Institute at the University of Edinburgh, where scientists cloned Dolly the sheep in 1996. “The application of the new technology suggested in this paper is to develop the use of genetically-modified cats for the study of FIV, providing valuable information for the study of Aids. “This is potentially valuable but the uses of genetically modified cats as models for human diseases are likely to be limited and only justified if other models – for example in more commonly used laboratory animals, like mice and rats – are not suitable.” Dr Robin Lovell-Badge, head of developmental genetics at the Medical Research Council’s national institute for medical research, said: “Cats are one of the few animal species that are normally susceptible to such viruses, and indeed they are subject to a pandemic, with symptoms as devastating to cats as they are to humans. “Understanding how to confer resistance is … of equal importance to cat health and human health.”

THAT GLOW GREEN
http://www.newscientist.com/article/dn20896-glowing-transgenic-cats-could-boost-aids-research.html?DCMP=OTC-rss&nsref=online-news
Glowing transgenic cats could boost AIDS research
by Andy Coghlan / 11 September 2011

Three cats genetically modified to resist feline immunodeficiency virus (FIV) have opened up new avenues for AIDS research. The research could also help veterinarians combat the virus, which kills millions of feral cats each year and also infects big cats, including lions. Prosaically named TgCat1, TgCat2 and TgCat3, the GM cats – now a year old – glow ghostly green under ultraviolet light because they have been given the green fluorescent protein (GFP) geneMovie Camera originating from jellyfish. The GM cats also carry an extra monkey gene, called TRIMCyp, which protects rhesus macaques from infection by feline immunodeficiency virus or FIV – responsible for cat AIDS. By giving the gene to the cats, the team hopes to offer the animals protection from FIV. Their study could help researchers develop and test similar approaches to protecting humans from infection with HIV.

Cat immunity
Already, the researchers have demonstrated that lab cultures of white blood cells from the cats are protected from FIV, and they hope to give the virus to the cats to check whether they are immune to it. “The animals clearly have the protective gene expressed in all their tissues including the lymph nodes, thymus and spleen,” says Eric Poeschla of the Mayo Clinic College of Medicine in Rochester, Minnesota, who led the research. “That’s crucial because that’s where the disease really happens, and where you see destruction of T-cells targeted by HIV in humans.” The animals are not the first GM cats, but the new method is far more efficient and versatile than previous techniques. The first cloned cat, born in 2001, was the only one to survive from 200 embryos, each created by taking an ear cell from cats, removing the nucleus and fusing it with a cat egg cell emptied of its own nucleus. Poeschla’s technique is far more direct, far more efficient and far simpler, and has already been used successfully to make GM mice, pigs, cows and monkeys. He loads genes of interest into a lentivirus, which he then introduces directly into a cat oocyte, or egg cell. The oocyte loaded with the new genes is then fertilised and placed in the womb of a foster mother. From 22 implantations, Poeschla achieved 12 fetuses in five pregnancies, and three live births. And out of the 12 fetuses, 11 successfully incorporated the new genes, demonstrating how efficient the method is. One surviving male kitten, TgCat1, has already mated with three normal females, siring eight healthy kittens that all carry the implanted genes as well, showing that they are inheritable. But there are doubts about whether cats will replace monkeys as the staples of HIV research. “It’s fantastic they’ve created GM cats,” says Theodora Hatziioannou of the Aaron Diamond AIDS Research Center in New York City. “But what makes research in monkeys so much better is that SIV in monkeys is much more closely related to HIV, so it’s more straightforward to draw conclusions than it would be with FIV.

 

THAT GLOW RED
http://news.nationalgeographic.com/news/2009/05/photogalleries/glowing-animal-pictures#/cats-cloned-glowing-animals_11832_600x450.jpg
May 14, 2009 / Photo by Choi Byung-kil/Yonhap via AP

How does it glow?
Red fluorescent protein, introduced via a virus into cloned DNA, which was implanted in cat eggs, then implanted in mother (2007)

What can we learn?
Scientists at Gyoengsang National University in South Korea both cloned a Turkish Angora house cat and made it fluorescent—as shown in the glowing cat (left) photographed in a dark room under ultraviolet light. (The nonfluorescent cat, at right, appears green in these conditions.) The scientists weren’t the first to clone a cat–they weren’t even the first to clone a fluorescent cat. But they were the first to clone a cat that fluoresces red. It’s hoped that the red glow, which appears in every organ of the cats, will improve the study of genetic diseases.


CONTACT
Eric Poeschla
http://mayoresearch.mayo.edu/mayo/research/poeschla/
http://mayoresearch.mayo.edu/staff/poeschla_em.cfm
email : Poeschla.Eric [at] mayo [dot] edu

PRESS RELEASE
http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.1703.html
http://www.mayoclinic.org/news2011-rst/6434.html
Mayo Clinic Teams with Glowing Cats Against AIDS, Other Diseases
New Technique Gives Cats Protection Genes / September 11, 2011

Mayo Clinic researchers have developed a genome-based immunization strategy to fight feline AIDS and illuminate ways to combat human HIV/AIDS and other diseases. The goal is to create cats with intrinsic immunity to the feline AIDS virus. The findings — called fascinating and landmark by one reviewer — appear in the current online issue of Nature Methods. Feline immunodeficiency virus (FIV) causes AIDS in cats as the human immunodeficiency virus (HIV) does in people: by depleting the body’s infection-fighting T-cells. The feline and human versions of key proteins that potently defend mammals against virus invasion — termed restriction factors — are ineffective against FIV and HIV respectively. The Mayo team of physicians, virologists, veterinarians and gene therapy researchers, along with collaborators in Japan, sought to mimic the way evolution normally gives rise over vast time spans to protective protein versions. They devised a way to insert effective monkey versions of them into the cat genome. “One of the best things about this biomedical research is that it is aimed at benefiting both human and feline health,” says Eric Poeschla, M.D., Mayo molecular biologist and leader of the international study. “It can help cats as much as people.”

Dr. Poeschla treats patients with HIV and researches how the virus replicates. HIV/AIDS has killed over 30 million people and left countless children orphaned, with no effective vaccine on the horizon. Less well known is that millions of cats also suffer and die from FIV/AIDS each year. Since the project concerns ways introduced genes can protect species against viruses, the knowledge and technology it produces might eventually assist conservation of wild feline species, all 36 of which are endangered. The technique is called gamete-targeted lentiviral transgenesis — essentially, inserting genes into feline oocytes (eggs) before sperm fertilization. Succeeding with it for the first time in a carnivore, the team inserted a gene for a rhesus macaque restriction factor known to block cell infection by FIV, as well as a jellyfish gene for tracking purposes. The latter makes the offspring cats glow green.

The macaque restriction factor, TRIMCyp, blocks FIV by attacking and disabling the virus’s outer shield as it tries to invade a cell. The researchers know that works well in a culture dish and want to determine how it will work in vivo. This specific transgenesis (genome modification) approach will not be used directly for treating people with HIV or cats with FIV, but it will help medical and veterinary researchers understand how restriction factors can be used to advance gene therapy for AIDS caused by either virus. The method for inserting genes into the feline genome is highly efficient, so that virtually all offspring have the genes. And the defense proteins are made throughout the cat’s body. The cats with the protective genes are thriving and have produced kittens whose cells make the proteins, thus proving that the inserted genes remain active in successive generations.

The other researchers are Pimprapar Wongsrikeao, D.V.M., Ph.D.; Dyana Saenz, Ph.D.; and Tommy Rinkoski, all of Mayo Clinic; and Takeshige Otoi, Ph.D., of Yamaguchi University, Japan. The research was supported by Mayo Clinic and the Helen C. Levitt Foundation. Grants from the National Institutes of Health supported key prior technology developments in the laboratory.


A ‘glow in the dark’ kitten viewed under a special blue light, next to a non-modified cat. Both cats’ fur looks the same under regular light. {Photograph: Mayo Clinic}

brain image
This study found reduced connectivity between an area of prefrontal cortex (PFC, red) and the amygdala (blue). The white matter pathway connecting the two structures (the uncinate fasciculus) is shown in green.

STRUCTURAL ABNORMALITIES
http://www.med.wisc.edu/news-events/news/psychopaths-brains-show-differences-in-structure-and-function/32979
Psychopaths’ Brains Show Differences in Structure and Function

Images of prisoners’ brains show important differences between those who are diagnosed as psychopaths and those who aren’t, according to a new study led by University of Wisconsin-Madison researchers. The results could help explain the callous and impulsive antisocial behavior exhibited by some psychopaths.The study showed that psychopaths have reduced connections between the ventromedial prefrontal cortex (vmPFC), the part of the brain responsible for sentiments such as empathy and guilt, and the amygdala, which mediates fear and anxiety.

Two types of brain images were collected. Diffusion tensor images (DTI) showed reduced structural integrity in the white matter fibers connecting the two areas, while a second type of image that maps brain activity, a functional magnetic resonance image (fMRI), showed less coordinated activity between the vmPFC and the amygdala. “This is the first study to show both structural and functional differences in the brains of people diagnosed with psychopathy,” says Michael Koenigs, assistant professor of psychiatry in the University of Wisconsin School of Medicine and Public Health. “Those two structures in the brain, which are believed to regulate emotion and social behavior, seem to not be communicating as they should.” The study, which took place in a medium-security prison in Wisconsin, is a unique collaborative between three laboratories, UW-Madison psychology Professor Joseph Newman has had a long term interest in studying and diagnosing those with psychopathy and has worked extensively in the Wisconsin corrections system. Dr. Kent Kiehl, of the University of New Mexico and the MIND Research Network, has a mobile MRI scanner that he brought to the prison and used to scan the prisoners’ brains. Koenigs and his graduate student, Julian Motzkin, led the analysis of the brain scans.


The video shows interactions between microglia (yellow) and dendritic spines (green) in the brain of a living mouse. Each frame is taken 5 minutes apart. The cell body of the microglia in the upper right corner is stable throughout the imaging session, but the microglial processes (looking like tentacles) are extremely dynamic, perpetually changing their morphology and dynamic interactions with small and transient dendritic spines over a span of minutes. http://www.med.wisc.edu/news-events/images-and-video-for-the-media/25328

The study compared the brains of 20 prisoners with a diagnosis of psychopathy with the brains of 20 other prisoners who committed similar crimes but were not diagnosed with psychopathy. “The combination of structural and functional abnormalities provides compelling evidence that the dysfunction observed in this crucial social-emotional circuitry is a stable characteristic of our psychopathic offenders,” Newman says. “I am optimistic that our ongoing collaborative work will shed more light on the source of this dysfunction and strategies for treating the problem.” Newman notes that none of this work would be possible without the extraordinary support provided by the Wisconsin Department of Corrections, which he called “the silent partner in this research.” He says the DOC has demonstrated an unprecedented commitment to supporting research designed to facilitate the differential diagnosis and treatment of prisoners. The study, published in the most recent Journal of Neuroscience, builds on earlier work by Newman and Koenigs that showed that psychopaths’ decision-making mirrors that of patients with known damage to their ventromedial prefrontal cortex (vmPFC). This bolsters evidence that problems in that part of the brain are connected to the disorder. “The decision-making study showed indirectly what this study shows directly – that there is a specific brain abnormality associated with criminal psychopathy,” Koenigs adds.



CRIMINAL JUSTICE IMPLICATIONS
http://www.thedailypage.com/daily/article.php?article=35292
UW-Madison Psychiatry imaging study finds brains of psychopaths are different
by Matt Hrodey  /  11/22/2011

The Koenigs Lab, an appendage of the University of Wisconsin Department of Psychiatry, says something about the multidisciplinary nature of neuroscience. Named for Michael Koenigs, an assistant professor of psychiatry, the lab includes a postdoctoral researcher with degrees in psychology and comparative religion, graduate students with backgrounds in biology, philosophy and English, and a scientist trained in applied math. Centered on the mind and nervous system, neuroscience is exploding, and there’s practically no topic it won’t take on, be it Shakespeare, meditation or consciousness itself. Or psychopathy.

In a paper to be published in the Nov. 30 Journal of Neuroscience, Koenigs, along with veteran UW psychopathy researcher Joseph Newman, will unveil new evidence of a physical basis for the disorder. In the study, Koenigs and Newman use brain scans of 40 inmates (20 psychopaths and 20 others) from Fox Lake Correctional Institution in Fox Lake, Wisconsin. In the scans of psychopathic brains, the researchers discovered poor connections between an important brain segment — the “ventromedial prefrontal cortex” (VMPFC) — and another crucial to emotional processing, the almond-shaped amygdala. The study will be the largest yet published that examines this link, according to Koenigs. Researchers used two types of brain scans: one testing the integrity of “white matter” structures connecting the VMPFC and the amygdala, and another tesing how well they communicate. Both types of scans found a weakened link in the brains of psychopaths.

Better understanding such abnormalities could, one day, reorder how the justice system responds to criminals who have them. “Can we hold them as accountable as someone who doesn’t have these abnormalities?” Koenigs asks. Scientists have studied the connection between the VMPFC and amygdala before. In one experiment using rodents, scientists found that stimulating the VMPFC suppressed the amygdala. Koenigs primarily studies brain injuries, particularly those in the VMPFC, where the brain is believed to regulate emotion, process threats, guide decision-making and direct social behavior. Damage to this segment, located just behind the forehead in the frontal lobes, tends to make patients more aggressive, irritable and less sensitive to others. “They’re not the same person they used to be,” Koenigs says. “They develop very striking personality changes reminiscent of psychopathy.”

Is a VMPFC deficiency to blame for psychopathy? It’s not clear. And scientists don’t know if the VMPFC is failing to regulate the amygdala or if the amydala is failing to send crucial emotional feedback to the VMPFC. “Normally, considering a decision [to rob someone] and the harm you would inflict would be marked with a negative emotional state,” says Koenigs. But in psychopaths, this affect is flat. To do their study at Fox Lake, Koenigs and Newman enlisted a mobile MRI lab run by Kent Kiehl, an associate professor of psychology at the University of New Mexico. The lab, pulled by a tractor trailer, brings the scanner to the inmates. Across the field of neuroscience, researchers are rapidly exploiting the powers of MRI scanning, particularly “functional” scanning, which tracks blood flow in the brain. This flow, because it is directed to busy neurons, is a precise indicator of brain activity. The new study is Newman’s first foray into brain imaging. “There’s a very strong bias toward using brain measurements,” he says, “and there’s been a lot of wonderful progress. People want to see how far we can go.”

Psychopathy is not as rare as some might believe. According to researchers, psychopaths make up an estimated 1% of the U.S. population and between 10% to 20% of the country’s prisoners. In his 30 years of studying psychopathy, Newman has theorized the existence of an “attention bottleneck” in the psychopathic mind that prevents it from fully receiving emotional and other inhibitory signals that say, “Stop! Reconsider! Reevaluate!” The conventional theory on psychopaths is that they lack emotion, be it fear, empathy or guilt, that would otherwise inform decision-making. Newman doesn’t deny that but insists on the importance of attention. “It feels like I’m trying to identify a learning disability,” he says. Our minds unconsciously monitor us. It happens in secret. Our conscious minds don’t know of it until the unconscious sounds an alarm — such as when a nagging suspicion of “having forgotten something” turns out to be true (the oven is still on; the keys were left on the car seat). The psychopathic brain may be very bad at automatically diverting attention to these types of cues if the psychopath is locked into “goal-driven” behavior, a kind of tunnel vision. Such an impairment, if it exists, doesn’t necessarily lead to crime. “Environmental factors are critical,” says Newman. They could be parental abuse, substance abuse or socioeconomic disadvantage. But once classified as a psychopath, an offender is two to five times more likely to reoffend than one who isn’t.

Newman tested his “attention bottleneck” theory in a study published earlier this year. In that study, 87 maximum-security inmates, some classified as psychopaths, sat down in front of computers. Two things appeared on the screen: a square, either red or green, and a letter, either uppercase or lowercase. In some of the trials, researchers startled inmates with a low-intensity shock after showing a red square. (Prisoners were told of the mild “buzzes” before they volunteered.) Each was shocked a total of 24 times, always after a red square. Then, to conclude the trials, the computer asked the prisoners to identify either the case of the letter or the color of the box. The human body, when conditioned to fear something, will startle at its appearance. This is called “fear-potentiated startle.” In the experiment, the red box primed the inmates to startle upon receiving the shock, and they did — with one major exception. In trials where psychopaths first saw the letter, followed by a red square, their startle was greatly diminished. Newman and the other researchers, Arielle Baskin-Sommers, a graduate student at UW-Madison, and John Curtin, a psychology professor, concluded that by presenting the letter first — thereby making the red square “secondary information that is not goal relevant” — the psychopaths fell victim to the “attention bottleneck” as theorized by Newman. They saw the square, but its meaning was not fully absorbed because the letter (and its case) had already won their attention.

There’s growing speculation today that neuroscience could revolutionize the U.S. criminal justice system, overthrowing the old precept of culpability. One indication of the promise of this growing field is a new dual degree program at UW-Madison that will train students in both neuroscience and the law. The “Neuroscience and the Law” track, part of the broader Neuroscience & Public Policyprogram, will allow students to earn a J.D. degree in law and a Ph.D. degree in neuroscience. Applications to join the new track’s first class come due this December. Professor Ron Kalil, a neuroscientist who studies brain injuries and the brain’s innate ability to repair itself, says the new program grew out of a 2010 meeting he had, over coffee, with Pilar Ossorio, an associate professor of law and bioethics. The two left with a “let’s do this” attitude, according to Kalil, but getting university approval for the new track didn’t happen overnight. To make the program official, they needed the approval of four university committees. They succeeded, adding “Neuroscience and the Law” to the existing tracks combining neuroscience and public policy and neuroscience and international public policy. Of neuroscience’s broad range, Kalil says, “At one end you have the study of molecules and proteins that make up parts of neurons, and at the other, the field tries to wrestle with issues that have been on the table since people started to think of themselves as human.” One of these is how to respond to crime, and what punishment is appropriate. “There are a lot of people who are not insane, but they’re not normal,” he says. “Where do we draw the line?”

YOUR BOSS is PSYCHO  (I KNOW, RIGHT?)
http://blogs.forbes.com/jeffbercovici/2011/06/14/why-some-psychopaths-make-great-ceos/
Why (Some) Psychopaths Make Great CEOs
by Jeff Bercovici / Jun 14 2011

British journalist Jon Ronson immersed himself in the world of mental health diagnosis and criminal profiling to understand what makes some people psychopaths — dangerous predators who lack the behavioral controls and tender feelings the rest of us take for granted. Among the things he learned while researching his new book, “The Psychopath Test: A Journey Through the Madness Industry”: the incidence of psychopathy among CEOs is about 4 percent, four times what it is in the population at large. I spoke with him recently about what that means and its implications for the business world and wider society.

Q. Are we really to understand that there’s some connection between what makes people psychopaths and what makes them CEO material?
A. At first I was really skeptical because it seemed like an easy thing to say, almost like a conspiracy theorist’s type of thing to say. I remember years and years ago a conspiracy theorist telling me the world was ruled by blood-drinking, baby-sacrificing lizards. These psychologists were essentially saying the same thing. Basically, when you get them talking, these people [ie. psychopaths] are different than human beings. They lack the things that make you human: empathy, remorse, loving kindness. So at first I thought this might just be psychologists feeling full of themselves with their big ideological notions. But then I met Al Dunlap. [That would be “Chainsaw” Al Dunlap, former CEO of Sunbeam and notorious downsizer.] He effortlessly turns the psychopath checklist into “Who Moved My Cheese?” Many items on the checklist he redefines into a manual of how to do well in capitalism. There was his reputation that he was a man who seemed to enjoy firing people, not to mention the stories from his first marriage — telling his first wife he wanted to know what human flesh tastes like, not going to his parents’ funerals. Then your realize that because of this dysfunctional capitalistic society we live in those things were positives. He was hailed and given high-powered jobs, and the more ruthlessly his administration behaved, the more his share price shot up.

Q. So you can just go down the list of Fortune 500 CEOs and say, “psychopath, psychopath, psychopath…”
A. Well, no. Dunlap was an exceptional figure, wasn’t he? An extreme figure. I think my book offers really good evidence that the way that capitalism is structured really is a physical manifestation of the brain anomaly known as psychopathy. However, I woudn’t say every Fortune 500 chief is a psychopath. That would turn me into an ideologue and I abhor ideologues.

Q. Is it an either/or thing? It seems to me, thinking about it, that a lot of the traits on the checklist would be be useful in a corporate ladder-climbing situation. So maybe there are a lot of CEOs who simply have some psychopathic tendencies.
A. It is a spectrum, but there’s a cutoff point. If you’re going by the Hare checklist [the standard inventory used in law enforcement, devised by leading researcher Robert Hare], where the top score is 40, the average anxiety-ridden business failure like me — although the fact that my book just made the Times best sellers list makes it difficult to call myself that — would score a 4 or 5. Somebody you have to be wary of would be in early 20s and a really hard core damaged person, a really dangerous psychopath, would score around a 30. In law the cutoff is 29. There are absolutes in psychopathy and the main absolute is a literal absence of empathy. It’s just not there. In higher-scoring psychopaths, what grows in the vacant field where that empathy should be is a joy in manipulating people, a lack of remorse, a lack of guilt. If you’ve got a little bit of empathy, you’re kind of not a psychopath.

Q. So maybe there’s a sweet spot? A point on the spectrum somewhere short of full-blown psychopathy that’s most conducive to success in business.
A. That’s possible. Obviously there are items on the checklist you don’t want to have if you’re a boss. You don’t want poor behavioral controls. It’d be better if you don’t have promiscuous behavior. It’d be better if you don’t have serious behavioral problems in childhood, because that will eventually come out. But you do want lack of empathy, lack of remorse, glibness, superficial charm, manipulativeness. I think the other positive traits for psychopaths in business is need for stimulation, proneness to boredom. You want somebody who can’t sit still, who’s constantly thinking about how to better things. A really interesting question is whether psychopathy can be a positive thing. Some psychologists would say yes, that there are certain attributes like coolness under pressure, which is sort of a fundamental positive. But Robert Hare would always say no, that in the absence of empathy, which is the definition in psychology of a psychopath, you will always get malevolence. Basically, high-scoring psychopaths can be brilliant bosses but only ever for short term. Just like Al Dunlap, they always want to make a killing and move on. And then you’ve got this question of what came first? Is society getting more and more psychopathic in its kind of desire for short-term killings? Is that because we kind of admire psychopaths in all their glib, superficial charm and ruthlessness?

Q. There’s a certain sour grapes aspect to accusing CEOs of being psychopaths. It’s very tempting to look at anyone more successful than you are and say, “It must be because he’s a monster.”
A. There’s a terribly seductive power in becoming a psychopath stalker. It can really dehumanize you. I can look at, say, Dominique Strauss Kahn, who, if one assumes that what one is hearing about him is true, certainly he hits a huge amount of items on the checklist — the $30,000 suits, the poor behavioral controls, the impulsivity, the promiscuous sexual behavior. But of course when you say this you’re in terrible danger of being seduced by the checklist, which I really like to add as a caveat. It kind of turns you into a bit of a psychopath yourself in that that you start to shove people into that box. It robs you of empathy and your connection to human beings. Which is why people like Robert Hare are kind of useful. I’m against the way that people like me can be seduced into misusing the checklist, but I’m not against the checklist.

PSYCHOPATHIC C.E.O.s
http://www.nytimes.com/2004/12/12/magazine/12PSYCHO.html
by Michael Steinberger / December 12, 2004

Ever wonder what leads a lavishly compensated C.E.O. to cheat, steal and lie? Perhaps he’s a psychopath, and now there is a test, the B-Scan 360, that can help make that determination. The B-Scan was conceived by Paul Babiak, an industrial psychologist, and Robert Hare, the creator of the standard tool for diagnosing psychopathic features in prison inmates. The B-Scan is the first formalized attempt to uncover similar tendencies in captains of industry, and it speaks to a growing suspicion that psychopaths may be especially adept at scaling the corporate ladder.

Indeed, Babiak and Hare could not have chosen a more propitious moment to roll out the B-Scan, which is now in the trial stage. The recent rash of damaging corporate scandals — combined with legislation making boards far more liable for executive malfeasance — has given companies good reason to screen current employees more rigorously. According to Babiak and Hare, white-collar psychopaths are not apt to become serial rapists or murderers. Rather, they are prone to being ”subcriminal” psychopaths: smooth-talking, energetic individuals who easily charm their way into jobs and promotions but who are also exceedingly manipulative, narcissistic and ruthless. The purpose of the B-Scan is to smoke out these “snakes in suits”. The individual being evaluated does not actually take the test. Instead, it is given to his or her superiors, subordinates and peers. They rate the subject in four broad categories — organizational maturity, personal style, emotional style and social style — and 16 subcategories, like reliability, honesty and sincerity.

Babiak and Hare say that decisions to promote or dismiss ought not to be made on the basis of the B-Scan alone and that it is possible, with good coaching and training, to turn a talented executive with mild psychopathic tendencies into an effective manager. They acknowledge too that strong corporate leadership may require a certain degree of guile, egoism and callousness. But they point out that the frenzied nature of modern business — the constant downsizing, the relentless merging and acquiring — provides a very fertile environment for havoc-wreaking psychopaths, who thrive on chaos and risk-taking. As Hare put it in one interview, ”If I couldn’t study psychopaths in prison, I would go down to the Stock Exchange.”

CONTACT
Paul Babiak
http://www.hrbackoffice.com/index-4.html
email : Inquiry [at] PaulBabiak [dot] com

Robert Hare
http://www.hare.org/
http://www.hare.org/links/media.html
http://www.hare.org/references/main.html
email : contact [at] hare [dot] org

PSYCHOPATHY CHECKLIST
http://en.wikipedia.org/wiki/Hare_Psychopathy_Checklist
http://www.hare.org/scales/
Psychopathy Scales

PCL-R   PCL:SV   P-SCAN   PCL:YV   APSD   TREATMENT GUIDELINES

“Dr. Hare has spent over 35 years researching psychopathy and is the developer of theHare Psychopathy Checklist-Revised (PCL-R), and a co-author of its derivatives, thePsychopathy Checklist: Screening Version (PCL:SV), the P-Scan, the Psychopathy Checklist: Youth Version (PCL:YV), and the Antisocial Process Screening Device(APSD). He is also a co-author of the Guidelines for a Psychopathy Treatment Program. The Hare Psychopathy Checklist-Revised, with demonstrated reliability and validity, is rapidly being adopted worldwide as the standard instrument for researchers and clinicians. The PCL-R and PCL:SV are strong predictors of recidivism, violence and response to therapeutic intervention. They play an important role in most recent risk-for-violence instruments. The PCL-R was reviewed in Buros Mental Measurements Yearbook (1995), as being the “state of the art” both clinically and in research use. In 2005, the Buros Mental Measurements Yearbook review listed the PCL-R as “a reliable and effective instrument for the measurement of psychopathy and is considered the ‘gold standard’ for measurement of psychopathy.”


Bison skull pile, 1870s

HR PROBLEM
http://www.humanresourcesmagazine.com.au/articles/51/0c030a51.asp
Catching the corporate psychopath
by Stuart Fagg / 15 June 2005

Rodney Adler, Ray Williams, Bernie Ebbers. These men have much in common. For a start they were once all hailed as successful businessmen and players of acumen, and secondly they are all now behind bars for their roles in the collapse of their companies. Of course they are not the only ones paying for their misdemeanours – there are plenty of share and policy holders who will attest to that. They also have one final thing in common – they all exhibit the behaviours of corporate psychopaths. According to Dr Robert Hogan, a US expert in personality profiling, however, it would seem that the likes of Adler are aberrations in the business world. But corporate psychopaths are far from unusual in the corporate world. By Hogan’s reckoning, the result of decades of research, incompetent and potentially damaging management accounts for some 60-70 per cent of the total pool in the US. When he brought these views to bear initially in the early 1990s, they were not popular and were dismissed by many that refused to believe that there were that many potential corporate psychopaths in US business. However, these days, and particularly having seen the damage wreaked by individuals after the scandals at Enron, WorldCom, OneTel and HIH, boards of directors and the share market are demanding more ethical executives. With the potential for increased liability under the Corporations Act, this trend may continue going forward. All well and good, but what is the impact of these corporate psychopaths? After all, some of the qualities that define such people also define some of the most successful people in business. “Researchers looked at Fortune 1000 companies that had 15 years of performance right at the average of their industry, and then a change and 15 subsequent years of sustained performance significantly above the average for the industry. Out of 1,000 companies they found 11,” Hogan said. “They investigated the 11 companies and found that the constant was the CEO. All 11 CEOs were understated and humble and that’s a stake in the heart for the theory of the celebrity CEO or charismatic leader.”

While background checks and screening are gaining popularity in Australian business, and in some cases being applied at higher executive levels, personality profiling remains a relatively unexplored concept in Australia. However, that may change. The Australian Prudential Regulation Authority, for example, is set to publish proposals for standards governing the fitness and propriety of responsible persons in financial institutions. The proposed standards are designed to weed out executives who have been declared bankrupt, failed to manage personal debts or held responsibility in a failed institution. Additionally anyone with a civil or criminal conviction related to dishonesty in dealings with financial institutions will also be barred. “The proposals are designed to reflect community expectations about persons who fill positions of responsibility in these industries and will set minimum benchmarks for people in, or wishing to enter, these industries at director, senior management or advisory level,” said Dr John Laker, APRA chairman. Traditionally, APRA has always focussed on the institution it is regulating, rather than the individuals running the institution. But, recent events in Australia and internationally have highlighted the importance of enuring that people in positions of power at companies are subject to the same scrutiny as the company itself. With regulated entities being required to develop their own policies, personality assessment may become more commonplace in sectors such as the insurance industry. But there is something of a grey area in the assessments. For example, financial markets traders must display some of the more undesirable qualities –ruthlessness, overt smartness and a tendency to gamble – for senior management to succeed in their positions. “We have a lot of data on traders and as a group they are real smart and really crazy,” said Hogan. “But don’t let them into management positions. People like that – Bill Clinton is a great example – tend to self nominate into leadership roles. They think they’re so hot they want to be in charge.”

Background checks and screening may not, however, detect these characteristics and head off the appointment of a potentially damaging executive. “The really bad guys will sail through a background check and will do really well in interviews. They do really well in assessment centres. The really dangerous ones are really smart, really charming and really fast on their feet and people love them.” This is where personality assessment earns its stripes, according to Hogan. Through developing his assessment system, Hogan has amassed an impressive data repository from the 3 million tests that have been carried out using his methodology. This data accurately tracks personality trends in business, and once companies see the data, said Hogan, it’s a relatively easy sell. But what happens if the CEO of the company is the corporate psychopath? “That’s our worst nightmare,” he told Human Resources. “When you assess the management team and see all these problems come from them, how can you fix that? But if you can find a company that’s willing to pay attention to data it’s an easy deal for us.”

“CHAINSAW” AL DUNLAP
http://www.portfolio.com/executives/2009/04/22/Al-Dunlap-Profile

“Picked by the board of Scott Paper Co. as the man to turn the struggling company around, Dunlap earned his nickname by slicing 11,000 employees. When Scott merged with Kimberly-Clark, Dunlap’s payoff was estimated at more than $100 million. Such scenarios are familiar. So are the debates over where to draw the line between painful-but-necessary restructuring and cold-hearted recklessness. Yet Dunlap stood out for the obvious joy he took in slamming his detractors as purveyors of “nonsense,” “rubbish,” and “socialism.” Chainsaw Al was the middle finger of the free market’s invisible hand.

Dunlap’s memoir-cum-manifesto, Mean Business, roughly coincided with his next CEO star turn, which was also to be his last. Sunbeam’s stock surged on the news that the Chainsaw was coming; massive workforce reductions and factory closures followed within months. His book clearly explained what set him apart from “addle-brained” and “weak” executives: “I’m a superstar in my field,” he wrote. Could there be a clearer sell signal? Unable to flip Sunbeam to a new buyer, as he’d done with Scott, Dunlap was stuck actually running the company. He failed spectacularly. Within two miserable years, the board fired him. The tactics he’d used to stave off losses—the company overstated its net income by $60 million, which was real money back then—earned him a civil suit from the SEC and a class-action suit by shareholders. Dunlap eventually settled both and was barred from serving as an officer or director of any public company. You could call Chainsaw Al’s story a fall from grace, but in his case, that’s probably not the proper word.”

UM, TOTALLY
http://www.fastcompany.com/magazine/96/open_boss.html
Is Your Boss a Psychopath?
by Alan Deutschman / December 19, 2007

One of the most provocative ideas about business in this decade so far surfaced in a most unlikely place. The forum wasn’t the Harvard Business School or one of those $4,000-a-head conferences where Silicon Valley’s venture capitalists search for the next big thing. It was a convention of Canadian cops in the far-flung province of Newfoundland. The speaker, a 71-year-old professor emeritus from the University of British Columbia, remains virtually unknown in the business realm. But he’s renowned in his own field: criminal psychology. Robert Hare is the creator of the Psychopathy Checklist. The 20-item personality evaluation has exerted enormous influence in its quarter-century history. It’s the standard tool for making clinical diagnoses of psychopaths — the 1% of the general population that isn’t burdened by conscience. Psychopaths have a profound lack of empathy. They use other people callously and remorselessly for their own ends. They seduce victims with a hypnotic charm that masks their true nature as pathological liars, master con artists, and heartless manipulators. Easily bored, they crave constant stimulation, so they seek thrills from real-life “games” they can win — and take pleasure from their power over other people.

On that August day in 2002, Hare gave a talk on psychopathy to about 150 police and law-enforcement officials. He was a legendary figure to that crowd. The FBI and the British justice system have long relied on his advice. He created the P-Scan, a test widely used by police departments to screen new recruits for psychopathy, and his ideas have inspired the testing of firefighters, teachers, and operators of nuclear power plants. According to the Canadian Press and Toronto Sun reporters who rescued the moment from obscurity, Hare began by talking about Mafia hit men and sex offenders, whose photos were projected on a large screen behind him. But then those images were replaced by pictures of top executives from WorldCom, which had just declared bankruptcy, and Enron, which imploded only months earlier. The securities frauds would eventually lead to long prison sentences for WorldCom CEO Bernard Ebbers and Enron CFO Andrew Fastow. “These are callous, cold-blooded individuals,” Hare said. “They don’t care that you have thoughts and feelings. They have no sense of guilt or remorse.” He talked about the pain and suffering the corporate rogues had inflicted on thousands of people who had lost their jobs, or their life’s savings. Some of those victims would succumb to heart attacks or commit suicide, he said.

Then Hare came out with a startling proposal. He said that the recent corporate scandals could have been prevented if CEOs were screened for psychopathic behavior. “Why wouldn’t we want to screen them?” he asked. “We screen police officers, teachers. Why not people who are going to handle billions of dollars?” It’s Hare’s latest contribution to the public awareness of “corporate psychopathy.” He appeared in the 2003 documentary The Corporation, giving authority to the film’s premise that corporations are “sociopathic” (a synonym for “psychopathic”) because they ruthlessly seek their own selfish interests — “shareholder value” — without regard for the harms they cause to others, such as environmental damage. Is Hare right? Are corporations fundamentally psychopathic organizations that attract similarly disposed people? It’s a compelling idea, especially given the recent evidence. Such scandals as Enron and WorldCom aren’t just aberrations; they represent what can happen when some basic currents in our business culture turn malignant. We’re worshipful of top executives who seem charismatic, visionary, and tough. So long as they’re lifting profits and stock prices, we’re willing to overlook that they can also be callous, conning, manipulative, deceitful, verbally and psychologically abusive, remorseless, exploitative, self-delusional, irresponsible, and megalomaniacal. So we collude in the elevation of leaders who are sadly insensitive to hurting others and society at large.

But wait, you say: Don’t bona fide psychopaths become serial killers or other kinds of violent criminals, rather than the guys in the next cubicle or the corner office? That was the conventional wisdom. Indeed, Hare began his work by studying men in prison. Granted, that’s still an unusually good place to look for the conscience-impaired. The average Psychopathy Checklist score for incarcerated male offenders in North America is 23.3, out of a possible 40. A score of around 20 qualifies as “moderately psychopathic.” Only 1% of the general population would score 30 or above, which is “highly psychopathic,” the range for the most violent offenders. Hare has said that the typical citizen would score a 3 or 4, while anything below that is “sliding into sainthood.” On the broad continuum between the ethical everyman and the predatory killer, there’s plenty of room for people who are ruthless but not violent. This is where you’re likely to find such people as Ebbers, Fastow, ImClone CEO Sam Waksal, and hotelier Leona Helmsley. We put several big-name CEOs through the checklist, and they scored as “moderately psychopathic”; our quiz on page 48 lets you try a similar exercise with your favorite boss. And this summer, together with New York industrial psychologist Paul Babiak, Hare begins marketing the B-Scan, a personality test that companies can use to spot job candidates who may have an MBA but lack a conscience. “I always said that if I wasn’t studying psychopaths in prison, I’d do it at the stock exchange,” Hare told Fast Company. “There are certainly more people in the business world who would score high in the psychopathic dimension than in the general population. You’ll find them in any organization where, by the nature of one’s position, you have power and control over other people and the opportunity to get something.”

There’s evidence that the business climate has become even more hospitable to psychopaths in recent years. In pioneering long-term studies of psychopaths in the workplace, Babiak focused on a half-dozen unnamed companies: One was a fast-growing high-tech firm, and the others were large multinationals undergoing dramatic organizational changes — severe downsizing, restructuring, mergers and acquisitions, and joint ventures. That’s just the sort of corporate tumult that has increasingly characterized the U.S. business landscape in the last couple of decades. And just as wars can produce exciting opportunities for murderous psychopaths to shine (think of Serbia’s Slobodan Milosevic and Radovan Karadzic), Babiak found that these organizational shake-ups created a welcoming environment for the corporate killer. “The psychopath has no difficulty dealing with the consequences of rapid change; in fact, he or she thrives on it,” Babiak claims. “Organizational chaos provides both the necessary stimulation for psychopathic thrill seeking and sufficient cover for psychopathic manipulation and abusive behavior.”

And you can make a compelling case that the New Economy, with its rule-breaking and roller-coaster results, is just dandy for folks with psychopathic traits too. A slow-moving old-economy corporation would be too boring for a psychopath, who needs constant stimulation. Its rigid structures and processes and predictable ways might stymie his unethical scheming. But a charge-ahead New Economy maverick — an Enron, for instance — would seem the ideal place for this kind of operator. But how can we recognize psychopathic types? Hare has revised his Psychopathy Checklist (known as the PCL-R, or simply “the Hare”) to make it easier to identify so-called subcriminal or corporate psychopaths. He has broken down the 20 personality characteristics into two subsets, or “factors.” Corporate psychopaths score high on Factor 1, the “selfish, callous, and remorseless use of others” category. It includes eight traits: glibness and superficial charm; grandiose sense of self-worth; pathological lying; conning and manipulativeness; lack of remorse or guilt; shallow affect (i.e., a coldness covered up by dramatic emotional displays that are actually playacting); callousness and lack of empathy; and the failure to accept responsibility for one’s own actions. Sound like anyone you know? (Corporate psychopaths score only low to moderate on Factor 2, which pinpoints “chronically unstable, antisocial, and socially deviant lifestyle,” the hallmarks of people who wind up in jail for rougher crimes than creative accounting.)

This view is supported by research by psychologists Belinda Board and Katarina Fritzon at the University of Surrey, who interviewed and gave personality tests to 39 high-level British executives and compared their profiles with those of criminals and psychiatric patients. The executives were even more likely to be superficially charming, egocentric, insincere, and manipulative, and just as likely to be grandiose, exploitative, and lacking in empathy. Board and Fritzon concluded that the businesspeople they studied might be called “successful psychopaths.” In contrast, the criminals — the “unsuccessful psychopaths” — were more impulsive and physically aggressive.

The Factor 1 psychopathic traits seem like the playbook of many corporate power brokers through the decades. Manipulative? Louis B. Mayer was said to be a better actor than any of the stars he employed at MGM, able to turn on the tears at will to evoke sympathy during salary negotiations with his actors. Callous? Henry Ford hired thugs to crush union organizers, deployed machine guns at his plants, and stockpiled tear gas. He cheated on his wife with his teenage personal assistant and then had the younger woman marry his chauffeur as a cover. Lacking empathy? Hotel magnate Leona Helmsley shouted profanities at and summarily fired hundreds of employees allegedly for trivialities, like a maid missing a piece of lint. Remorseless? Soon after Martin Davis ascended to the top position at Gulf & Western, a visitor asked why half the offices were empty on the top floor of the company’s Manhattan skyscraper. “Those were my enemies,” Davis said. “I got rid of them.” Deceitful? Oil baron Armand Hammer laundered money to pay for Soviet espionage. Grandiosity? Thy name is Trump.

In the most recent wave of scandals, Enron’s Fastow displayed many of the corporate psychopath’s traits. He pressured his bosses for a promotion to CFO even though he had a shaky grasp of the position’s basic responsibilities, such as accounting and treasury operations. Suffering delusions of grandeur after just a little time on the job, Fastow ordered Enron’s PR people to lobby CFO magazine to make him its CFO of the Year. But Fastow’s master manipulation was a scheme to loot Enron. He set up separate partnerships, secretly run by himself, to engage in deals with Enron. The deals quickly made tens of millions of dollars for Fastow — and prettified Enron’s financials in the short run by taking unwanted assets off its books. But they left Enron with time bombs that would ultimately cause the company’s total implosion — and lose shareholders billions. When Enron’s scandals were exposed, Fastow pleaded guilty to securities fraud and agreed to pay back nearly $24 million and serve 10 years in prison.

“Chainsaw” Al Dunlap might score impressively on the corporate Psychopathy Checklist too. What do you say about a guy who didn’t attend his own parents’ funerals? He allegedly threatened his first wife with guns and knives. She charged that he left her with no food and no access to their money while he was away for days. His divorce was granted on grounds of “extreme cruelty.” That’s the characteristic that endeared him to Wall Street, which applauded when he fired 11,000 workers at Scott Paper, then another 6,000 (half the labor force) at Sunbeam. Chainsaw hurled a chair at his human-resources chief, the very man who approved the handgun and bulletproof vest on his expense report. Dunlap needed the protection because so many people despised him. His plant closings kept up his reputation for ruthlessness but made no sense economically, and Sunbeam’s financial gains were really the result of Dunlap’s alleged book cooking. When he was finally exposed and booted, Dunlap had the nerve to demand severance pay and insist that the board reprice his stock options. Talk about failure to accept responsibility for one’s own actions. While knaves such as Fastow and Dunlap make the headlines, most horror stories of workplace psychopathy remain the stuff of frightened whispers. Insiders in the New York media business say the publisher of one of the nation’s most famous magazines broke the nose of one of his female sales reps in the 1990s. But he was considered so valuable to the organization that the incident didn’t impede his career.

Most criminals — whether psychopathic or not — are shaped by poverty and often childhood abuse as well. In contrast, corporate psychopaths typically grew up in stable, loving families that were middle class or affluent. But because they’re pathological liars, they tell romanticized tales of rising from tough, impoverished backgrounds. Dunlap pretended that he grew up as the son of a laid-off dockworker; in truth, his father worked steadily and raised his family in suburban comfort. The corporate psychopaths whom Babiak studied all went to college, and a couple even had PhDs. Their ruthless pursuit of self-interest was more easily accomplished in the white-collar realm, which their backgrounds had groomed them for, rather than the criminal one, which comes with much lousier odds. Psychopaths succeed in conventional society in large measure because few of us grasp that they are fundamentally different from ourselves. We assume that they, too, care about other people’s feelings. This makes it easier for them to “play” us. Although they lack empathy, they develop an actor’s expertise in evoking ours. While they don’t care about us, “they have an element of emotional intelligence, of being able to see our emotions very clearly and manipulate them,” says Michael Maccoby, a psychotherapist who has consulted for major corporations.

Psychopaths are typically very likable. They make us believe that they reciprocate our loyalty and friendship. When we realize that they were conning us all along, we feel betrayed and foolish. “People see sociopathy in their personal lives, and they don’t have a clue that it has a label or that others have encountered it,” says Martha Stout, a psychologist at the Harvard Medical School and the author of the recent best-seller The Sociopath Next Door: The Ruthless Versus the Rest of Us (Broadway Books, 2005). “It makes them feel crazy or alone. It goes against our intuition that a small percentage of people can be so different from the rest of us — and so evil. Good people don’t want to believe it.” Of course, cynics might say that it can be an advantage to lack a conscience. That’s probably why major investors installed Dunlap as the CEO of Sunbeam: He had no qualms about decimating the workforce to impress Wall Street. One reason outside executives get brought into troubled companies is that they lack the emotional stake in either the enterprise or its people. It’s easier for them to act callously and remorselessly, which is exactly what their backers want. The obvious danger of the new B-Scan test for psychopathic tendencies is that companies will hire or promote people with high scores rather than screen them out. Even Babiak, the test’s codeveloper, says that while “a high score is a red flag, sometimes middle scores are okay. Perhaps you don’t want the most honest and upfront salesman.”

Indeed, not every aberrant boss is necessarily a corporate psychopath. There’s another personality that’s often found in the executive suite: the narcissist. While many psychologists would call narcissism a disorder, this trait can be quite beneficial for top bosses, and it’s certainly less pathological than psychopathy. Maccoby’s book The Productive Narcissist: The Promise and Perils of Visionary Leadership (Broadway Books, 2003) portrays the narcissistic CEO as a grandiose egotist who is on a mission to help humanity in the abstract even though he’s often insensitive to the real people around him. Maccoby counts Apple’s Steve Jobs, General Electric’s Jack Welch, Intel’s Andy Grove, Microsoft’s Bill Gates, and Southwest Airlines’ Herb Kelleher as “productive narcissists,” or PNs. Narcissists are visionaries who attract hordes of followers, which can make them excel as innovators, but they’re poor listeners and they can be awfully touchy about criticism. “These people don’t have much empathy,” Maccoby says. “When Bill Gates tells someone, ‘That’s the stupidest thing I’ve ever heard,’ or Steve Jobs calls someone a bozo, they’re not concerned about people’s feelings. They see other people as a means toward their ends. But they do have a sense of changing the world — in their eyes, improving the world. They build their own view of what the world should be and get others recruited to their vision. Psychopaths, in contrast, are only interested in self.”

Maccoby concedes that productive narcissists can become “drunk with power” and turn destructive. The trick, he thinks, is to pair a productive narcissist with a “productive obsessive,” or conscientious, control-minded manager. Think of Grove when he was matched with chief operating officer Craig Barrett, Gates with president Steve Ballmer, Kelleher with COO Colleen Barrett, and Oracle’s Larry Ellison with COO Ray Lane and CFO Jeff Henley. In his remarkably successful second tour of duty at Apple, Jobs has been balanced by steady, competent behind-the-scenes players such as Timothy Cook, his executive vice president for sales and operations. But our culture’s embrace of narcissism as the hallmark of admired business leaders is dangerous, Babiak maintains, since “individuals who are really psychopaths are often mistaken for narcissists and chosen by the organization for leadership positions.” How does he distinguish the difference between the two types? “In the case of a narcissist, everything is me, me, me,” Babiak explains. “With a psychopath, it’s ‘Is it thrilling, is it a game I can win, and does it hurt others?’ My belief is a psychopath enjoys hurting others.”

Intriguingly, Babiak believes that it’s extremely unlikely for an entrepreneurial founder-CEO to be a corporate psychopath because the company is an extension of his own ego — something he promotes rather than plunders. “The psychopath has no allegiance to the company at all, just to self,” Babiak says. “A psychopath is playing a short-term parasitic game.” That was the profile of Fastow and Dunlap — guys out to profit for themselves without any concern for the companies and lives they were wrecking. In contrast, Jobs and Ellison want their own companies to thrive forever — indeed, to dominate their industries and take over other fields as well. “An entrepreneurial founder-CEO might have a narcissistic tendency that looks like psychopathy,” Babiak says. “But they have a vested interest: Their identity is wrapped up with the company’s existence. They’re loyal to the company.” So these types are ruthless not only for themselves but also for their companies, their extensions of self.

The issue is whether we will continue to elevate, celebrate, and reward so many executives who, however charismatic, remain indifferent to hurting other people. Babiak says that while the first line of defense against psychopaths in the workplace is screening job candidates, the second line is a “culture of openness and trust, especially when the company is undergoing intense, chaotic change.” Europe is far ahead of the United States in trying to deal with psychological abuse and manipulation at work. The “antibullying” movement in Europe has produced new laws in France and Sweden. Harvard’s Stout suggests that the relentlessly individualistic culture of the United States contributes a lot to our problems. She points out that psychopathy has a dramatically lower incidence in certain Asian cultures, where the heritage has emphasized community bonds rather than glorified self-interest. “If we continue to go this way in our Western culture,” she says, “evolutionarily speaking, it doesn’t end well.” The good news is that we can do something about corporate psychopaths. Scientific consensus says that only about 50% of personality is influenced by genetics, so psychopaths are molded by our culture just as much as they are born among us. But unless American business makes a dramatic shift, we’ll get more Enrons — and deserve them.

the PSYCHOPATH TEST
http://www.npr.org/2011/05/21/136462824/a-psychopath-walks-into-a-room-can-you-tell
http://www.thisamericanlife.org/radio-archives/episode/436/the-psychopath-test
aired 05.27.2011

Recently we heard about this test that could determine if someone was a psychopath. So, naturally, our staff decided to take it. This week we hear the results. Ira explains that when the radio staff decided to take a test that reveals who is a psychopath, very quickly everyone came to believe that the highest score would go to either Robyn, Jane, or him. (6 minutes)

Underachievement Test
NPR Science Correspondent Alix Spiegel tells the story of Robert Dixon, who’s in a maximum security prison in Vacaville California and is unlikely to ever get parole because of his score on the psychopath test. The test also is called “the checklist” or, more formally, the PCL-R, which stands for “Psychopathy Check List—Revised.” Alix tells the story of its creation and reports that the man who created the test, Bob Hare, is concerned at how it’s being used today in the criminal justice system. A version of this story aired on NPR’s All Things Considered. (28 minutes)

King of the Forest
Jon Ronson investigates whether corporate leaders can, in fact, be psychopaths by visiting a former Sunbeam CEO named Al Dunlap. This is an excerpt from Ronson’s book, The Psychopath Test. (15 minutes)Song: “If I Were King of the Forest”, Wizard of Oz Soundtrack

Results
Ira and the radio show staff get their results on the psychopath test from Dr. David Bernstein, ofForensic Consultants, LLC., who administered the test to them. (6 minutes)

TAKE the QUIZ
http://www.fastcompany.com/magazine/96/open_boss-quiz.html
by Fast Company Staff / July 1, 2005

The standard clinical test for psychopathy, Robert Hare’s PCL-R, evaluates 20 personality traits overall, but a subset of eight traits defines what he calls the “corporate psychopath” — the nonviolent person prone to the “selfish, callous, and remorseless use of others.” Does your boss fit the profile? Here’s our do-it-yourself quiz drawing on the test manual and Hare’s book Without Conscience. (Disclaimer: If you’re not a psychologist or psychiatrist, this will be a strictly amateur exercise.) We’ve used the pronoun “he,” but research suggests psychologists have underestimated the psychopathic propensity of women.

For each question, score two points for “yes,” one point for “somewhat” or “maybe,” and zero points for “no.”

[1] Is he glib and superficially charming?
Is he a likable personality and a terrific talker — entertaining, persuasive, but maybe a bit too smooth and slick? Can he pass himself off as a supposed expert in a business meeting even though he really doesn’t know much about the topic? Is he a flatterer? Seductive, but insincere? Does he tell amusing but unlikely anecdotes celebrating his own past? Can he persuade his colleagues to support a certain position this week — and then argue with equal conviction and persuasiveness for the opposite position next week? If he’s a CEO, can he appear on TV and somehow get away without answering the interviewer’s direct questions or saying anything truly substantive?
SCORE__

[2] Does he have a grandiose sense of self-worth?
Does he brag? Is he arrogant? Superior? Domineering? Does he feel he’s above the rules that apply to “little people”? Does he act as though everything revolves around him? Does he downplay his legal, financial, or personal problems, say they’re just temporary, or blame them on others?
SCORE__

[3] Is he a pathological liar?
Has he reinvented his own past in a more positive light — for example, claiming that he rose from a tough, poor background even though he really grew up middle class? Does he lie habitually even though he can easily be found out? When he’s exposed, does he still act unconcerned because he thinks he can weasel out of it? Does he enjoy lying? Is he proud of his knack for deceit? Is it hard to tell whether he knows he’s a liar or whether he deceives himself and believes his own bull?
SCORE__

[4] Is he a con artist or master manipulator?
Does he use his skill at lying to cheat or manipulate other people in his quest for money, power, status, and sex? Does he “use” people brilliantly? Does he engage in dishonest schemes such as cooking the books?
SCORE__

[5] When he harms other people, does he feel a lack of remorse or guilt?
Is he concerned about himself rather than the wreckage he inflicts on others or society at large? Does he say he feels bad but act as though he really doesn’t? Even if he has been convicted of a white-collar crime, such as securities fraud, does he not accept blame for what he did, even after getting out of prison? Does he blame others for the trouble he causes?
SCORE__

[6] Does he have a shallow affect?
Is he cold and detached, even when someone near him dies, suffers, or falls seriously ill — for example, does he visit the hospital or attend the funeral? Does he make brief, dramatic displays of emotion that are nothing more than putting on a theatrical mask and playacting for effect? Does he claim to be your friend but rarely or never ask about the details of your life or your emotional state? Is he one of those tough-guy executives who brag about how emotions are for whiners and losers?
SCORE__

[7] Is he callous and lacking in empathy?
Does he not give a damn about the feelings or well-being of other people? Is he profoundly selfish? Does he cruelly mock others? Is he emotionally or verbally abusive toward employees, “friends,” and family members? Can he fire employees without concern for how they’ll get by without the job? Can he profit from embezzlement or stock fraud without concern for the harm he’s doing to shareholders or pensioners who need their savings to pay for their retirements?
SCORE__

[8] Does he fail to accept responsibility for his own actions?
Does he always cook up some excuse? Does he blame others for what he’s done? If he’s under investigation or on trial for a corporate crime, like deceitful accounting or stock fraud, does he refuse to acknowledge wrongdoing even when the hard evidence is stacked against him?
SCORE__

Total____
If your boss scores:
1-4 | Be frustrated
5-7 | Be cautious
8-12 | Be afraid
13-16 | Be very afraid

SO CHARMING at FIRST
http://www.psychologytoday.com/articles/199401/charming-psychopath
by Robert Hare / January 01, 1994

A major part of my own quarter-century search for answers to this enigma has been a concerted effort to develop an accurate means of detecting the psychopaths among us. Measurement and categorization are, of course, fundamental to any scientific endeavor, but the implications of being able to identify psychopaths are as much practical as academic. To put it simply, if we can’t spot them, we are doomed to be their victims, both as individuals and as a society. My role in the search for psychopaths began in the 1960s at the psychology department of the University of British Columbia. There, my growing interest in psychopathy merged with my experience working with psychopaths in prison to form what was to become my life’s work. I assembled a team of clinicians who would identify psychopaths in the prison population by means of long, detailed interviews and close study of file information. From this eventually developed a highly reliable diagnostic tool that any clinician or researcher could use and that yielded a richly detailed profile of the personality disorder called psychopathy. We named this instrument the Psychopathy Checklist (Multi-Health Systems; 1991). The checklist is now used worldwide and provides clinicians and researchers with a way of distinguishing, with reasonable certainty, true psychopaths from those who merely break the rules.

What follows is a general summary of the key traits and behaviors of a psychopath. Do not use these symptoms to diagnose yourself or others. A diagnosis requires explicit training and access to the formal scoring manual. If you suspect that someone you know conforms to the profile described here, and if it is important for you to have an expert opinion, you should obtain the services of a qualified (registered) forensic psychologist or psychiatrist. Also, be aware that people who are not psychopaths may have some of the symptoms described here. Many people are impulsive, or glib, or cold and unfeeling, but this does not mean that they are psychopaths. Psychopathy is a syndrome—a cluster of related symptoms.

Key Symptoms of Psychopathy
Emotional/Interpersonal:

  • Glib and superficial
  • Egocentric and grandiose
  • Lack of remorse or guilt
  • Lack of empathy
  • Deceitful and manipulative
  • Shallow emotions

Social Deviance:

  • Impulsive
  • Poor behavior controls
  • Need for excitement
  • Lack of responsibility
  • Early behavior problems
  • Adult antisocial behavior

Glib and Superficial
Psychopaths are often voluble and verbally facile. They can be amusing and entertaining conversationalists, ready with a clever comeback, and are able to tell unlikely but convincing stories that cast themselves in a good light. They can be very effective in presenting themselves well and are often very likable and charming. One of my raters described an interview she did with a prisoner: “I sat down and took out my clipboard,” she said, “and the first thing this guy told me was what beautiful eyes I had. He managed to work quite a few compliments on my appearance into the interview, so by the time I wrapped things up, I was feeling unusually… well, pretty. I’m a wary person, especially on the job, and can usually spot a phony. When I got back outside, I couldn’t believe I’d fallen for a line like that.”

Egocentric and Grandiose
Psychopaths have a narcissistic and grossly inflated view of their own self-worth and importance, a truly astounding egocentricity and sense of entitlement, and see themselves as the center of the universe, justified in living according to their own rules. “It’s not that I don’t follow the law,” said one subject. “I follow my own laws. I never violate my own rules.” She then proceeded to describe these rules in terms of “looking out for number one.” Psychopaths often claim to have specific goals but show little appreciation regarding the qualifications required—they have no idea of how to achieve them and little or no chance of attaining these goals, given their track record and lack of sustained interest in formal education. The psychopathic inmate might outline vague plans to become a lawyer for the poor or a property tycoon. One inmate, not particularly literate, managed to copyright the title of a book he was planning to write about himself, already counting the fortune his best-selling book would bring.

Lack of Remorse or Guilt
Psychopaths show a stunning lack of concern for the effects their actions have on others, no matter how devastating these might be. They may appear completely forthright about the matter, calmly stating that they have no sense of guilt, are not sorry for the ensuing pain, and that there is no reason now to be concerned. When asked if he had any regrets about stabbing a robbery victim who subsequently spent time in the hospital as a result of his wounds, one of our subjects replied, “Get real! He spends a few months in hospital and I rot here. If I wanted to kill him I would have slit his throat. That’s the kind of guy I am; I gave him a break.” Their lack of remorse or guilt is associated with a remarkable ability to rationalize their behavior, to shrug off personal responsibility for actions that cause family, friends, and others to reel with shock and disappointment. They usually have handy excuses for their behavior, and in some cases deny that it happened at all.

Lack of Empathy
Many of the characteristics displayed by psychopaths are closely associated with a profound lack of empathy and inability to construct a mental and emotional “facsimile” of another person. They seem completely unable to “get into the skin” of others, except in a purely intellectual sense. They are completely indifferent to the rights and suffering of family and strangers alike. If they do maintain ties, it is only because they see family members as possessions. One of our subjects allowed her boyfriend to sexually molest her five-year-old daughter because “he wore me out. I wasn’t ready for more sex that night.” The woman found it hard to understand why the authorities took her child into care.

Deceitful and Manipulative
With their powers of imagination in gear and beamed on themselves, psychopaths appear amazingly unfazed by the possibility—or even by the certainty—of being found out. When caught in a lie or challenged with the truth, they seldom appear perplexed or embarrassed—they simply change their stories or attempt to rework the facts so they appear to be consistent with the lie. The result is a series of contradictory statements and a thoroughly confused listener. And psychopaths seem proud of their ability to lie. When asked if she lied easily, one woman laughed and replied, “I’m the best. I think it’s because I sometimes admit to something bad about myself. They think, well, if she’s admitting to that she must be telling the truth about the rest.”

Shallow Emotions
Psychopaths seem to suffer a kind of emotional poverty that limits the range and depth of their feelings. At times they appear to be cold and unemotional while nevertheless being prone to dramatic, shallow, and short-lived displays of feeling. Careful observers are left with the impression they are playacting and little is going on below the surface. A psychopath in our research said that he didn’t really understand what others meant by fear. “When I rob a bank,” he said, “I notice that the teller shakes. One barfed all over the money. She must have been pretty messed up inside, but I don’t know why. If someone pointed a gun at me I guess I’d be afraid, but I wouldn’t throw up.” When asked if he ever felt his heart pound or his stomach churn, he replied, “Of course! I’m not a robot. I really get pumped up when I have sex or when I get into a fight.”

Impulsive
Psychopaths are unlikely to spend much time weighing the pros and cons of a course of action or considering the possible consequences. “I did it because I felt like it,” is a common response. These impulsive acts often result from an aim that plays a central role in most of the psychopath’s behavior: to achieve immediate satisfaction, pleasure, or relief. So family members, relatives, employers, and coworkers typically find themselves standing around asking themselves what happened—jobs are quit, relationships broken off, plans changed, houses ransacked, people hurt, often for what appears as little more than a whim. As the husband of a psychopath I studied put it: “She got up and left the table, and that was the last I saw of her for two months.”

Poor Behavior Controls
Besides being impulsive, psychopaths are highly reactive to perceived insults or slights. Most of us have powerful inhibitory controls over our behavior; even if we would like to respond aggressively we are usually able to “keep the lid on.” In psychopaths, these inhibitory controls are weak, and the slightest provocation is sufficient to overcome them. As a result, psychopaths are short-tempered or hotheaded and tend to respond to frustration, failure, discipline, and criticism with sudden violence, threats or verbal abuse. But their outbursts, extreme as they may be, are often short-lived, and they quickly act as if nothing out of the ordinary has happened. For example, an inmate in line for dinner was accidentally bumped by another inmate, whom he proceeded to beat senseless. The attacker then stepped back into line as if nothing had happened. Despite the fact that he faced solitary confinement as punishment for the infraction, his only comment when asked to explain himself was, “I was pissed off. He stepped into my space. I did what I had to do. Although psychopaths have a “hair trigger,” their aggressive displays are “cold”; they lack the intense arousal experienced when other individuals lose their temper.

A Need for Excitement
Psychopaths have an ongoing and excessive need for excitement—they long to live in the fast lane or “on the edge,” where the action is. In many cases the action involves the breaking of rules. Many psychopaths describe “doing crime” for excitement or thrills. When asked if she ever did dangerous things just for fun, one of our female psychopaths replied, “Yeah, lots of things. But what I find most exciting is walking through airports with drugs. Christ! What a high!” The flip side of this yen for excitement is an inability to tolerate routine or monotony. Psychopaths are easily bored and are not likely to engage in activities that are dull, repetitive, or require intense concentration over long periods.

Lack of Responsibility
Obligations and commitments mean nothing to psychopaths. Their good intentions—”I’ll never cheat on you again”—are promises written on the wind. Horrendous credit histories, for example, reveal the lightly taken debt, the loan shrugged off, the empty pledge to contribute to a child’s support. Their performance on the job is erratic, with frequent absences, misuse of company resources, violations of company policy, and general untrustworthiness. They do not honor formal or implied commitments to people, organizations, or principles. Psychopaths are not deterred by the possibility that their actions mean hardship or risk for others. A 25-year-old inmate in our studies has received more than 20 convictions for dangerous driving, driving while impaired, leaving the scene of an accident, driving without a license, and criminal negligence causing death. When asked if he would continue to drive after his release from prison, he replied, “Why not? Sure, I drive fast, but I’m good at it. It takes two to have an accident.”

Early Behavior Problems
Most psychopaths begin to exhibit serious behavioral problems at an early age. These might include persistent lying, cheating, theft, arson, truancy, substance abuse, vandalism, and/or precocious sexuality. Because many children exhibit some of these behaviors at one time or another—especially children raised in violent neighborhoods or in disrupted or abusive families—it is important to emphasize that the psychopath’s history of such behaviors is more extensive and serious than most, even when compared with that of siblings and friends raised in similar settings. One subject, serving time for fraud, told us that as a child he would put a noose around the neck of a cat, tie the other end of the string to the top of a pole, and bat the cat around the pole with a tennis racket. Although not all adult psychopaths exhibited this degree of cruelty when in their youth, virtually all routinely got themselves into a wide range of difficulties.

Adult Antisocial Behavior
Psychopaths see the rules and expectations of society as inconvenient and unreasonable impediments to their own behavioral expression. They make their own rules, both as children and as adults. Many of the antisocial acts of psychopaths lead to criminal charges and convictions. Even within the criminal population, psychopaths stand out, largely because the antisocial and illegal activities of psychopaths are more varied and frequent than are those of other criminals. Psychopaths tend to have no particular affinity, or “specialty,” for one particular type of crime but tend to try everything. But not all psychopaths end up in jail. Many of the things they do escape detection or prosecution, or are on “the shady side of the law.” For them, antisocial behavior may consist of phony stock promotions, questionable business practices, spouse or child abuse, and so forth. Many others do things that, though not necessarily illegal, are nevertheless unethical, immoral, or harmful to others: philandering or cheating on a spouse to name a few.

Origins
Thinking about psychopathy leads us very quickly to a single fundamental question: Why are some people like this? Unfortunately, the forces that produce a psychopath are still obscure, an admission those looking for clear answers will find unsatisfying. Nevertheless, there are several rudimentary theories about the cause of psychopathy worth considering. At one end of the spectrum are theories that view psychopathy as largely the product of genetic or biological factors (nature), whereas theories at the other end posit that psychopathy results entirely from a faulty early social environment (nurture). The position that I favor is that psychopathy emerges from a complex—and poorly understood—interplay between biological factors and social forces. It is based on evidence that genetic factors contribute to the biological bases of brain function and to basic personality structure, which in turn influence the way an individual responds to, and interacts with, life experiences and the social environment. In effect, the core elements needed for the development of psychopathy—including a profound inability to experience empathy and the complete range of emotions, including fear—are in part provided by nature and possibly by some unknown biological influences on the developing fetus and neonate. As a result, the capacity for developing internal controls and conscience and for making emotional “connections” with others is greatly reduced.

Can Anything Be Done?
In their desperate search for solutions people trapped in a destructive and seemingly hopeless relationship with a psychopath frequently are told: Quit indulging him and send him for therapy. A basic assumption of psychotherapy is that the patient needs and wants help for distressing or painful psychological and emotional problems. Successful therapy also requires that the patient actively participate, along with the therapist, in the search for relief of his or her symptoms. In short, the patient must recognize there is a problem and must want to do something about it. But here is the crux: Psychopaths don’t feel they have psychological or emotional problems, and they see no reason to change their behavior to conform with societal standards they do not agree with. Thus, in spite of more than a century of clinical study and decades of research, the mystery of the psychopath still remains. Recent developments have provided us with new insights into the nature of this disturbing disorder, and its borders are becoming more defined. But compared with other major clinical disorders, little research has been devoted to psychopathy, even though it is responsible for more social distress and disruption than all other psychiatric disorders combined. So, rather than trying to pick up the pieces after the damage has been done, it would make far greater sense to increase our efforts to understand this perplexing disorder and to search for effective early interventions. The alternatives are to continue devoting massive resources to the prosecution, incarceration, and supervision of psychopaths after they have committed offenses against society and to continue to ignore the welfare and plight of their victims. We have to learn how to socialize them, not resocialize them. And this will require serious efforts at research and early intervention. It is imperative that we continue the search for clues.

{Excerpted from Without Conscience: The Disturbing World of the Psychopaths Among Us (Simon & Schuster) by Robert Hare, Ph.D. Copyright 1993.}

A Survival Guide
Although no one is completely immune to the devious machinations of the psychopath, there are some things you can do to reduce your vulnerability.

  • Know what you are dealing with. This sounds easy but in fact can be very difficult. All the reading in the world cannot immunize you from the devastating effects of psychopaths. Everyone, including the experts, can be taken in, conned, and left bewildered by them. A good psychopath can play a concerto on anyone’s heart strings.
  • Try not to be influenced by “props.” It is not easy to get beyond the winning smile, the captivating body language, the fast talk of the typical psychopath, all of which blind us to his or her real intentions. Many people find it difficult to deal with the intense, “predatory state” of the psychopath. The fixated stare, is more a prelude to self-gratification and the exercise of power rather than simple interest or empathic caring.
  • Don’t wear blinders. Enter new relationships with your eyes wide open. Like the rest of us, most psychopathic con artists and “love-thieves” initially hide their dark side by putting their “best foot forward.” Cracks may soon begin to appear in the mask they wear, but once trapped in their web, it will be difficult to escape financially and emotionally unscathed.
  • Keep your guard up in high-risk situations. Some situations are tailor-made for psychopaths: singles bars, ship cruises, foreign airports, etc. In each case, the potential victim is lonely, looking for a good time, excitement, or companionship, and there will usually be someone willing to oblige, for a hidden price.
  • Know yourself. Psychopaths are skilled at detecting and ruthlessly exploiting your weak spots. Your best defense is to understand what these spots are, and to be extremely wary of anyone who zeroes in on them.

Unfortunately, even the most careful precautions are no guarantee that you will be safe from a determined psychopath. In such cases, all you can do is try to exert some sort of damage control. This is not easy but some suggestions may be of help:

  • Obtain professional advice. Make sure the clinician you consult is familiar with the literature on psychopathy and has had experience in dealing with psychopaths.
  • Don’t blame yourself. Whatever the reasons for being involved with a psychopath, it is important that you not accept blame for his or her attitudes and behavior. Psychopaths play by the same rules—their rules—with everyone.
  • Be aware of who the victim is. Psychopaths often give the impression that it is they who are suffering and that the victims are to blame for their misery. Don’t waste your sympathy on them.
  • Recognize that you are not alone. Most psychopaths have lots of victims. It is certain that a psychopath who is causing you grief is also causing grief to others.
  • Be careful about power struggles. Keep in mind that psychopaths have a strong need for psychological and physical control over others. This doesn’t mean that you shouldn’t stand up for your rights, but it will probably be difficult to do so without risking serious emotional or physical trauma.
  • Set firm ground rules. Although power struggles with a psychopath are risky you may be able to set up some clear rules—both for yourself and for the psychopath—to make your life easier and begin the difficult transition from victim to a person looking out for yourself.
  • Don’t expect dramatic changes. To a large extent, the personality of psychopaths is “carved in stone.” There is little likelihood that anything you do will produce fundamental, sustained changes in how they see themselves or others.
  • Cut your losses. Most victims of psychopaths end up feeling confused and hopeless, and convinced that they are largely to blame for the problem. The more you give in the more you will be taken advantage of by the psychopath’s insatiable appetite for power and control.
  • Use support groups. By the time your suspicions have led you to seek a diagnosis, you already know that you’re in for a very long and bumpy ride. Make sure you have all the emotional support you can muster.

PRINT RIGHT onto the PATIENT
http://www.fastcompany.com/1734436/next-step-in-3d-printing-your-kidneys
Next Step in 3D Printing: Your Kidneys
by Anya Kamenetz / Mar 3, 2011

Dr. Anthony Atala, a regenerative medicine specialist at Wake Forest University, is pioneering the use of printing techniques to reconstruct and repair human flesh and organs. The basis is a combination of cultured human cells and scaffolding built or woven from organic material. In one staggering setup, a patient lies on a table and a flatbed scanner literally scans her wound, followed by a printer that adds just the right types of tissues back on at the right depth. “You can print right on the patient,” Dr. Atala told the TED audience on Thursday. “I know it sounds funny, but it’s true.” The next evolving step is the use of 3-D printers, which I wrote about on Tuesday, to rebuild human organs. Ninety percent of patients on the organ donation list are waiting for kidneys, a fist-size organ with a profusion of tiny blood vessels. To build a customized kidney, first you scan the patient with a CT scanner, then use 3D imaging techniques to create a computerized form that the printer can read, and finally build the organ layer by layer. Printing a new kidney takes about six hours, and it lasts for a lifetime–a young man came out on stage who had the surgery in the early days, 10 years ago.



EZ BAKE ORGANS
http://www.newyorker.com/online/video/conference/2007/atala
http://www.physorg.com/news/2011-03-surgeon-kidney-ted-stage.html
Surgeon Creates New Kidney Onstage / March 4, 2011

“It’s like baking a cake,” Anthony Atala of the Wake Forest Institute of Regenerative Medicine said as he cooked up a fresh kidney on stage at a TED Conference in the California city of Long Beach. Scanners are used to take a 3-D image of a kidney that needs replacing, then a tissue sample about half the size of postage stamp is used to seed the computerized process, Atala explained. The organ “printer” then works layer-by-layer to build a replacement kidney replicating the patient’s tissue. College student Luke Massella was among the first people to receive a printed kidney during experimental research a decade ago when he was just 10 years old. He said he was born with Spina Bifida and his kidneys were not working. “Now, I’m in college and basically trying to live life like a normal kid,” said Massella, who was reunited with Atala at TED “This surgery saved my life and made me who I am today.” About 90 percent of people waiting for transplants are in need of kidneys, and the need far outweighs the supply of donated organs, according to Atala. “There is a major health crisis today in terms of the shortage of organs,” Atala said. “Medicine has done a much better job of making us live longer, and as we age our organs don’t last.”

CONTACT
Anthony Atala
http://www.wfubmc.edu/faculty/Atala-Anthony-J.htm

BIOPRINTING
http://www.organovo.com/products/novogen-mmx-bioprinter
http://www.livescience.com/5977-device-prints-human-tissue.html
New Device Prints Human Tissue
by Bill Christensen / 29 December 2009

Invetech has delivered what it calls the “world`s first production model 3D bio-printer” to Organovo, developers of the proprietary NovoGen bioprinting technology. Organovo will in turn supply the devices to institutions investigating human tissue repair and organ replacement. Keith Murphy, CEO of Organovo, based in San Diego, said the units represent a breakthrough because they provide for the first time a flexible technology platform for organizations working on many different types of tissue construction and organ replacement. “Scientists and engineers can use the 3D bio printers to enable placing cells of almost any type into a desired pattern in 3D,” Murphy said. “Researchers can place liver cells on a preformed scaffold, support kidney cells with a co-printed scaffold, or form adjacent layers of epithelial and stromal soft tissue that grow into a mature tooth. Ultimately the idea would be for surgeons to have tissue on demand for various uses, and the best way to do that is get a number of bio-printers into the hands of researchers and give them the ability to make three dimensional tissues on demand.”

The 3D bio-printers include an intuitive software interface that allows engineers to build a model of the tissue construct before the printer commences the physical constructions of the organs cell-by-cell using automated, laser-calibrated print heads. “Building human organs cell-by-cell was considered science fiction not that long ago,” said Fred Davis, president of Invetech, which has offices in San Diego and Melbourne. “Through this clever combination of technology and science we have helped Organovo develop an instrument that will improve people’s lives, making the regenerative medicine that Organovo provides accessible to people around the world.” Science fiction, indeed. Artificial organs have been a science fiction staple since writer Philip K. Dick wrote about artiforgs (artificial organs) in his 1964 novel Cantata 140 and Larry Niven’sartificially grown organs in his 1968 novel A Gift From Earth.



SIR, YOUR LIVER is READY
http://www.wired.com/rawfile/2010/07/gallery-bio-printing/
Behind the Scenes of Bioprinting
by By Dave Bullock / July 11, 2010

Say goodbye to donor lists and organ shortages. A biotech firm has created a printer that prints veins using a patients’ own cells. The device could potentially create whole organs in the future. “Right now we’re really good at printing blood vessels,” says Ben Shepherd, senior research scientist at regenerative-medicine company Organovo. “We printed 10 this week. We’re still learning how to best condition them to be good, strong blood vessels.” Most organs in the body are filled with veins, so the ability to print vascular tissue is a critical building block for complete organs. The printed veins are about to start testing in animal trials, and eventually go through human clinical trials. If all goes well, in a few years you may be able to replace a vein that has deteriorated (due to frequent injections of chemo treatment, for example) with custom-printed tissue grown from your own cells. The barriers to full-organ printing are not just technological. The first organ-printing machine will cost hundreds of millions of dollars to develop, test, produce and market. Not to mention the difficulty any company will have getting FDA approval. “If Organovo will be able to raise enough money this company has [the] potential to succeed as [the] first bioprinting company but only time will show,” says Dr. Vladimir Mironov, director of advanced tissue biofabrication at the Medical University of South Carolina. Organovo walked Wired.com through the process it uses to print blood vessels on the custom bioprinter.

Bioreactor
Shepherd places a bioreactor inside an incubator where it will be pumped with a growth medium for a few days. The bioreactor uses a special mixture of chemicals that are similar to what cells would see when they grow inside the body, which will help the cells become strong vascular tissue.

Stem Cells
Senior research scientist Ben Shepherd removes stem cells from a bath of liquid nitrogen. The cells will be cultured to greatly increase their number before being loaded into the printer. Eventually these cells could be taken from a variety of places in a patient’s body –- fat, bone marrow and skin cells –- and made into a working vein.

After the cells are defrosted they are cultured in a growth medium (above). This allows the cells to multiply and grow so they can be used to form veins. The medium also uses special chemicals to tell the stem cells to grow into the cell type required, in this case blood-vessel cells. Once a enough cells are produced, they are separated from the growth medium using a centrifuge (below) and compressed into pellets.


photos: Dave Bullock/Wired.com

Hydrogel Scaffolding
The first step of the printing process is to lay down a material called hydrogel, which is used as a temporary scaffolding to support the vein tissue. The custom-made printer uses two pump heads that squirt out either the scaffolding structure or the cells into a petri dish. The pump heads are mounted on a precision robotic assembly for microscopic accuracy. The head on the right is dipping into the container of hydorogel in the photo above.

A chamber called a bioreactor is used to stimulate the vein. It’s prepared before the vein is printed. The bioreactor is a fairly standard piece of biotech machinery. It is machined out of a block of aluminum that surrounds a plastic container with various ports. These ports are used to pump in chemicals that will feed the growing vein.

Before printing the veins, tubes of the cultured cells are loaded into the print head manually, like a biomass print cartridge.

Hydrogel Mold for Blood Vessels
Lines of the hydrogel are laid down in parallel in a trough shape on the petri dish. Then cylinders of cell pellets are printed into the trough. One more cylinder of hydrogel is printed into the middle of the cells, which serves to create the hole inside the vein where blood will eventually flow (below).


Illustration courtesy Organovo

Growing Into Veins
The printed veins are then left in a different growth medium for several weeks. The cells soon release from the hydrogel, and a hollow tube of vascular cells is left behind.

Happy Veins
The printed cells in tubular form are then placed into the bioreactor. The bioreactor (above) pumps a special cocktail of proteins, buffers and various other chemicals (below) through the printed vein. This conditions the cells to be good, strong veins and keep them happy.

Finished Product
After their stay in the bioreactor, the pellets of cells grow together to form veins which can then be implanted in the patient. Because the veins are grown from the patient’s own cells, their body is more likely to accept the implanted vein.

NO TRANSPLANT NEEDED
http://www.unos.org/data/

MUST BE PLUGGED IN AT NIGHT

FUTURE CYBORG OVERLORD or VERY NEARLY DECEASED?  [ONLY TIME WILL TELL]
http://www.doctorzebra.com/prez/a_cheney.htm
http://s3.amazonaws.com/drz/cheney-ailmap-doctorzebra-B.mov
http://weblogs.baltimoresun.com/health/2010/07/cheneys_heart_doesnt_miss_a_sp.html
Cheney’s heart doesn’t miss a spin / July 15, 2010

After five heart attacks, former Vice President Dick Cheney’s ticker has taken a beating. Last week, he said that he underwent surgery to install a new heart pump. What he got was a LVAD, or left ventricular assist device, which is made for people like Cheney who need a little help pumping blood because their hearts aren’t keeping up. The pump runs something like a drill bit, continuously rotating at 9,000 rotations per minute rather than squeezing and releasing, so Cheney now officially has no pulse, according to Dr. Stuart D. Russell, chief of heart failure and transplantation at Johns Hopkins’ Comprehensive Transplant Center. But what he’s likely getting in return, says Russell, who is not involved in Cheney’s care, is a better quality and quantity of life. Cheney said in a statement that he had “increasing congestive heart failure,” which afflicts about 5 million Americans whose hearts have weakened over time. In most candidates for the device, the amount of blood squeezed out with each beat is significantly reduced – normal is 55 percent or greater and Cheney was likely more in the 10-15 percent range. That makes the people grow tired quickly after doing minor chores such as dressing.

Pumps have been around for about three decades, but this version by Thoratech Corp., at about five years old, gives people a 60 percent survival rates after 2 years. There’s not a lot of data on this pump after that. Drug therapy, in contrast, gives patients about a 10 percent survival rate. “That’s a lot better than 10 percent on the pills,” Russell said. “Some would say going from 10 percent to 60 percent is phenomenal.” Some patients use the device, Russell said, as a bridge to a transplant. But Cheney, at 69, might not be a candidate. In that case it’s a “destination therapy,” meaning this is his treatment destination. But Russell says that he could live 4,5 or 6 years with this pump and new ones already are in development. And “6 years for a 69-year-old who has had 5 heart attacks is significant,” he said.

Russell said those who get this pump are generally in the hospital 14 to 21 days and start to feel normal after two to three months. The device requires an energy source, so the people have a line coming out of their skin near their belly that need to be hooked up to a battery pack during the day — it can be worn holster-style if Cheney prefers. It also needs to be plugged into an energy source at night. It can’t get submerged, so wearers can’t swim but they can shower. They also need to take anti-coagulation drugs. They are also at increased risk of infection and gastrointestinal tract infections. “People generally can get back to a fairly normal lifestyle,” Russell said. “The vast majority do well.”

PREVIOUSLY on SPECTRE : PACEMAKER HACK
https://spectregroup.wordpress.com/2008/08/18/pacemaker-hack/

USB COMPATIBLE
http://www.medpagetoday.com/Blogs/21197
I turned to a journalist who knows a lot about such issues – Mary Knudson, co-author with Edward K. Kasper M.D. of Living Well with Heart Failure, the Misnamed, Misunderstood Condition. Here are Mary’s comments:

“The main problems I saw with coverage of former Vice President Dick Cheney getting a device implanted to treat his worsening heart failure was absence of reporting about the huge risks associated with this procedure. Below are some points to include in balanced reporting about an LVAD:

A left ventricular assist device (LVAD) can be an effective means of treating heart failure short term, but is much riskier and more complex than implanting a pacemaker. The LVAD is a pump that does the work for a weak left ventricle, removing blood from the left ventricle and pumping it into the aorta where it then flows to the rest of the body. The newer model smaller pump is implanted in the chest and has tubes leading to the left ventricle and aorta and another that goes outside the body to connect to a computerized controller. The controller can be worn on the waist and operated by batteries. The LVAD is used in people with heart failure that is so severe, medications do not prevent shortness of breath and fatigue. The device is used in someone with end-stage heart failure as a bridge to keep a person alive until he can get a heart transplant or as a final treatment that may prolong his life up to 10 months to two years or sometimes longer.

While the LVAD can dramatically improve the quality of a person’s life by relieving the symptoms that prevent activity, it is a procedure that carries a great deal of risk. Death can occur during the procedure, in the first few days after it, or after the person returns home. Risks include infection, blood clots, bleeding, device failure, and quite a few others. Using the newest model of LVAD, a person can go about daily activities by carrying with him a couple of sets of battery replacements and then at night connecting the LVAD to a laptop computer that is plugged in to an electrical outlet. Or the person might work at an office or at home with the LVAD plugged through the computer to an electrical outlet. The LVAD has come a long way from the noisy large stationary power sources patients were tethered to. Newer units are smaller, portable for hours, and quieter. But the risks are the same and this device is used as a last resort.”

LIFE SUPPORT
http://www.talkingpointsmemo.com/archives/2010/07/grim.php
“I’m a surgeon and just read your wire story about Dick Cheney getting a Left Ventricular Assist Device (LVAD) placed. The story downplays the seriousness of that procedures…once you’ve got an LVAD in place, it means your heart is essentially incapable of working on its own and has no potential to improve. While LVAD outcomes have been improving, and some patients live months or even years with one of these devices in place, this is a HUGE operation with MAJOR associated morbidity and mortality. If he’s not listed for a heart transplant, his days are seriously numbered. Life on an LVAD isn’t something I’d wish on my worst enemy…an axiom that this situation really tests. He’s in for a rough time.”

AM I BIONIC NOW? [YES]
http://video.about.com/heartdisease/LV-Assist-Device.htm
http://www.americanheart.org/presenter.jhtml?identifier=4599

What is a left ventricular assist device (LVAD)?
The left ventricle is the large, muscular chamber of the heart that pumps blood out to the body. A left ventricular assist device (LVAD) is a battery-operated, mechanical pump-type device that’s surgically implanted. It helps maintain the pumping ability of a heart that can’t effectively work on its own. These devices are available in most heart transplant centers.

When is an LVAD used?
This device is sometimes called a “bridge to transplant.” People awaiting a heart transplant often must wait a long time before a suitable heart becomes available. During this wait, the patient’s already-weakened heart may deteriorate and become unable to pump enough blood to sustain life. An LVAD can help a weak heart and “buy time” for the patient.

How does an LVAD work?
A common type of LVAD has a tube that pulls blood from the left ventricle into a pump. The pump then sends blood into the aorta (the large blood vessel leaving the left ventricle). This effectively helps the weakened ventricle. The pump is placed in the upper part of the abdomen. Another tube attached to the pump is brought out of the abdominal wall to the outside of the body and attached to the pump’s battery and control system. LVADs are now portable and are often used for weeks to months. Patients with LVADs can be discharged from the hospital and have an acceptable quality of life while waiting for a donor heart to become available.

Promising study results for LVADs
In a study published in Circulation in 2005, LVADs restored failing hearts in some patients with heart failure, eliminating the need for a transplant. According to an abstract presented at the American Heart Association’s 2005 Scientific Sessions, LVADs reduced the risk of death in end-stage heart failure patients by 50 percent at six and 12 months and extended the average life span from 3.1 months to more than 10 months.

HEART MATE II
http://www.thoratec.com/media/video-player.aspx?clip=HMII_HDRT_anim&KeepThis=true&TB_iframe=true&height=429&width=450
http://www.thoratec.com/media/video-player.aspx?clip=HMII_LVAD_anim&KeepThis=true&TB_iframe=true&height=429&width=450
http://www.thoratec.com/media/video-player.aspx?clip=XVE_Product&KeepThis=true&TB_iframe=true&height=429&width=450
http://www.thoratec.com/downloads/heartmate-ii-pivotal-clinical-trial-fact-sheet-111109.pdf
http://www.thoratec.com/downloads/heartmate-ii-fact-sheet-111109.pdf
http://www.thoratec.com/vad-trials-outcomes/index.aspx
http://www.thoratec.com/vad-trials-outcomes/patient-stories/index.aspx


Leonor Childers wearing her battery back, pictured with daughter and infant son

‘DESTINATION THERAPY’
http://www.scientificamerican.com/article.cfm?id=artificial-heart-power
http://www.cardiovascularbusiness.com/index.php?option=com_articles&view=article&id=22758
http://www.cardiologytoday.com/view.aspx?rid=60260
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198172.htm
DA Approves Left Ventricular Assist System for Severe Heart Failure Patients
Device Provides Support for Those Who Are Not Acceptable Transplant Candidates

The U.S. Food and Drug Administration today approved the HeartMate II, a continuous-flow, left ventricular assist system as a support for severe heart failure patients who are not acceptable candidates for heart transplantation. The HeartMate II is already FDA-approved for use in patients awaiting further, perhaps more complex treatment, such as transplants. Heart assist devices are surgically implanted mechanical pumps that help the heart’s ventricle pump blood to the rest of the body. HeartMate II consists of a small, lightweight blood pump implanted in a patient’s chest just below the heart. An electrical cable that powers the blood pump passes through the patient’s skin to an external controller worn around the patient’s waist.

A physician designates the pump’s speed based upon clinical need. The device is designed to sound an alarm upon malfunction or other potentially drastic changes that could impact the pump’s operation. “The approval of HeartMate II provides an option for heart failure patients who cannot receive a transplant,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “Its smaller size and mobility should allow more patients, including women and men of smaller stature, access to treatment.” In a randomized clinical study of 200 participants at 38 centers, 46 percent of 134 participants with the HeartMate II were still living after two years with no disabling stroke or need for a reoperation for device replacement or repair compared with 11 percent of 66 participants in the control group. In addition, data collected in a separate registry of smaller stature women and men indicated that the device worked well in this specific population. As a condition of the FDA’s approval, the company will conduct a post-approval study to further evaluate the device’s performance. The data will be recorded in the Interagency Registry of Mechanical Assisted Circulatory Support (INTERMACS) and made available when the post-approval study is concluded. The INTERMACS is a clinical outcomes registry managed by the FDA, the National Heart, Lung and Blood Institute at the National Institutes of Health, the Centers for Medicare & Medicaid Services and participating hospitals and companies.


FDA APPROVED as ‘PERMANENT’ FIX
http://www.healthcanal.com/surgery-rehabilitation/5759.html
FDA Approves New Device Investigated at AGH for Patients With Advanced Heart Failure / 17/02/2010

A revolutionary heart assist technology investigated for several years at Allegheny General Hospital (AGH) has been approved by the FDA for patients with advanced heart failure who do not qualify for heart transplantation. Called the Thoratec® HeartMate II® Left Ventricular Assist System (LVAS), the device is now available as “destination therapy” – or long-term treatment for those patients. Approximately six million Americans suffer from congestive heart failure and 600,000 new cases are diagnosed each year, according to the American Heart Association. The prognosis for patients with advanced heart failure is poor, with projected one-year mortality rates exceeding those of other terminal diseases such as AIDs, leukemia, and lung cancer. Though transplantation offers hope for approximately 2,000 advanced heart failure patients each year, more than 250,000 patients have no viable treatment option and are considered at high risk for repeated hospitalizations, severely diminished quality of life and limited life expectancy. For the 50,000-100,000 heart failure patients in the U.S. who do not qualify for a heart transplant, due to age or other extenuating circumstances, long-term therapy with HeartMate II may be a life-saving option, said Srinivas Murali, MD, director of AGH’s Division of Cardiovascular Medicine and Medical Director of AGH’s Gerald McGinnis Cardiovascular Institute.

HeartMate II is the first and only continuous flow chronic LVAS to receive FDA approval for both bridge-to-transplantation and destination therapy. AGH participated in the clinical trial of the device and is now one of a select number of advanced cardiac centers in the nation qualified to offer the state-of-the-art therapy on a routine basis. “This technology is a breakthrough for a large group of patients whose therapeutic options until now have been severely limited. The HeartMate II provides cost-effective, long-term circulatory support in a manner that does not merely keep a person with end stage heart failure alive, but maximizes their quality of life. We are thrilled to have played a role in the development this exciting new treatment alternative,” said Raymond Benza, MD, medical director of AGH’s Advanced Heart Failure, Transplantation, Mechanical Circulatory Support and Pulmonary Hypertension Program

In 2009, AGH performed 36 successful implantations of ventricular assist devices and currently has three patients using the HeartMate II as destination therapy. The hospital is recognized regionally and nationally as a leading center for the treatment of heart failure, offering heart transplantation services as well as access to an array of cutting edge investigational heart assist devices. The mechanical circulatory support program at AGH has Joint Commission accreditation and was one of the first programs in the country to receive this distinction. According to Stephen Bailey, MD, director of AGH’s Division of Cardiac Surgery and Surgical Director of Cardiac Transplantation and Mechanical Circulatory Support, LVADs take over the pumping ability of a weakened heart’s left ventricle, which pumps oxygen rich blood received from the lungs to the rest of the body.

Heartmate II is a fully portable LVAD that allows patients to remain active and lead a relatively normal life. Uniquely designed to have a much longer functional life than conventional pulsatile devices, HeartMate II is much lighter and quieter than its predecessors. The device is made of smooth titanium and powered by a rotary pumping mechanism with only one moving part. “The Heartmate II is capable of pumping up to 10 liters of blood per minute, covering the full output of a healthy heart. Its smaller size makes it easier to implant and allows us to use this device in women and small adults. The system’s transcutaneous lines are also much smaller and less prone to complications,” Dr. Bailey said. Weighing approximately 12 ounces and about the size of a D-cell battery, the HeartMate II connects to the heart via a polyester tube that is bored into the left ventricle. Blood dumps straight from the left ventricle into the pump, where a turbine spinning at 8,700 rpm propels blood through the aorta. The system is powered by a small battery pack the patient wears over his shoulders, which is connected to the internal device via a small catheter line threaded through the skin.

Approved as a bridge-to-transplantation device in 2008, HeartMate II’s recent approval by the FDA for destination therapy followed a successful clinical trial of 200 patients enrolled at 38 centers. The study was a prospective, randomized clinical trial. Patients, who did not qualify for heart transplantation, were assigned to treatment with HeartMate II LVAS or to treatment with the earlier generation HeartMate® XVE LVAS (control group) on a 2-1 basis, respectively. The study concluded that treating patients with HeartMate II leads to dramatically improved survival (68 and 58 percent at one and two years), functional capacity (80% restored to and sustained at NYHA Class I or II through two years; doubling in six-minute walk test) and substantial improvement in quality of life.

Additional positive results demonstrated with the device included:
• Dramatic improvements in functional capacity and quality life for both bridge-to-transplantation and destination therapy. At baseline, 96 percent of DT trial patients were NYHA Class IV/IIIB. Seventy five percent improved to Class I or II at 3 months and 80 percent were Class I or II at 24 months.
• Significant reduction of adverse events with HeartMate II , including bleeding, infection and stroke.
• Substantial and sustained improvement in the HM II patients’ 6-minute walk test. The number of meters walked at two years more than doubled from baseline. At two years, HeartMate II patients achieved a median 6-minute walk of 372 meters, more than the distance of 4 American football fields. This improvement in 6-minute walk is a 3-fold improvement observed in Class IV patients during a previous study with the earlier generation device.

FAKE HEART PARTS
http://www.jarvikheart.com/basic.asp?section=Jarvik+2000
http://www.micromedcv.com/united_states/heart-assist-5/small_and_light.html
http://www.abiomed.com/products/heart_replacement.cfm
http://www.texasheart.org/research/devices/abiocor.cfm

TEMPORARY TOTAL ARTIFICIAL HEART
http://www.syncardia.com/2010-Press-Release/worlds-first-freedom-patients.html
http://www.syncardia.com/News/vanessa-cirillo-organ-donation.html
http://www.scientificamerican.com/article.cfm?id=artificial-heart-power
Portable Power Source Lets Cardiac Patients Await a Permanent Donor at Home
A new artificial heart ventricular pump uses a power driver shrunken to 3 percent of its original weight, yet is able to generate enough energy to maintain optimum pumping capacity
by Larry Greenemeier / July 13, 2010

They say home is where the heart is, but until recently patients who had suffered biventricular failure could survive only with the help of an artificial heart tethered to large, immobile driver system to maintain blood circulation while they awaited a heart transplant. This could be changing; artificial heart–maker SynCardia Systems, Inc., in Tucson, Ariz., last month announced that three patients surgically implanted with the company’s technology have been able to walk out of their respective hospitals and wait for donated replacement hearts in the comfort of their own homes.

These departures were made possible by SynCardia’s six-kilogram Freedom portable driver, which blows packets of air through two clear tubes (each about one centimeter in diameter) connected to the company’s temporary Total Artificial Heart. These air packets force the blood in the implanted artificial heart’s ventricles to be pumped to the rest of the body. The 75-centimeter-long tubes run from the artificial ventricles, exiting the body just below the rib cage. They connect to the Freedom driver, which can be worn in a backpack or shoulder bag. SynCardia’s temporary Total Artificial Heart—previously known as the CardioWest temporary Total Artificial Heart—is designed to replace the two ventricles (lower chambers) of a person’s original heart while still relying on the natural left and right atria (upper chambers) and aorta (main artery) to supply the pumped blood to the rest of the body, says SynCardia CEO Rodger Ford. The pulmonary artery also remains intact. The company’s artificial heart, which costs about $125,000, has been approved by the U.S. Food and Drug Administration since October 2004 as a bridge for transplant patients dying from end-stage failure of their hearts’ right and left ventricles, which collect blood from the atria and pump it to the lungs and body, respectively.

The SynCardia’s artificial heart’s volume is 70 cubic centimeters, which Ford says is small enough to fit into about 75 percent of males and 25 percent of females. The company is developing a 50-cubic-centimeter heart expected to be small enough to fit all adults as well as some teenagers. SynCardia has received conditional approval from the FDA to conduct an Investigational Device Exemption (IDE) clinical study of the Freedom portable driver in the U.S. An IDE allows a device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application, which SynCardia obtained from the FDA. As part of that trial, 30 stable Total Artificial Heart patients (as opposed to those still recovering from surgery) must be discharged from the hospital using the Freedom driver for 90 days (or shorter if they can find a donor heart in that time frame).

The study’s purpose is to determine whether the Freedom driver is a suitable pneumatic pump for stable Total Artificial Heart patients, and if it can be safely used at home, Ford says. There are several portable Freedom drivers in use in Europe and one in the U.S. The company expects more to follow in the latter because 22 hospitals here are seeking permission from their institutional review boards to offer Freedoms to artificial heart patients. Originally, patients were tethered via a 1.5-meter-long tube to a 180-kilogram driver system—nicknamed “Big Blue”—until they could find a donor heart to replace SynCardia’s technology. The company saw the opportunity to create the Freedom while it was developing a 23-kilogram alternative in-hospital driver to the Big Blue system. The 23-kilogram Companion driver has been available in Europe since October 2009; SynCardia plans to submit it for FDA approval in September.

A challenge to shrinking down the driver technology to three percent of its original weight was to retain enough energy output to operate the artificial heart. The Freedom driver has a primary motor as well as a backup in case there is a problem with the main system; the motors operate a piston, which compresses air and then pushes it through the tubes to power the artificial heart. SynCardia has plans to further shrink its driver technology, although Ford says current technology would prevent the device from weighing less than four kilograms. The downsizing could be done over the next two years and would mostly come from using a smaller motor controller, smaller lithium ion batteries (the Freedom uses two) and replacing analogue components with digital technology.

SynCardia’s technology is one of a few available to people suffering from heart failure. The only other FDA-approved artificial heart is AbioMed’s AbioCor, which is a self-contained replacement heart with an internal battery charged by a transcutaneous energy transmission (TET) system, meaning that no wires or tubes penetrate the skin and therefore there is less risk of infection. The AbioCor is intended for end-stage heart failure patients who have a life expectancy of less than 30 days and are not eligible for a natural heart implant. Another technology, left ventricular assist devices (LVAD), have been on the market since 1994 for heart patients awaiting a permanent transplant, but they work only if a recipient’s heart can still function to some degree on its own. An LVAD generally consists of a tube that pulls blood from the damaged heart’s left ventricle into a pump, which then sends blood into the aorta, assisting the weakened ventricle. The pump, placed in the upper part of the abdomen, has a second tube that extends outside the body through the abdominal wall, where it is attached to the pump’s battery and control system.

THIS FIRST: the HAYFLICK LIMIT
http://www.mpib-berlin.mpg.de/en/aktuelles/hayflick.htm
http://en.wikipedia.org/wiki/Hayflick_limit
“…is the number of times a normal cell population will divide before it stops, presumably because the telomeres reach a critical length…”

A PERPLEXING DEATHLESSNESS
http://rebeccaskloot.com/book-special-features/audiovideo/
http://www.smithsonianmag.com/science-nature/Henrietta-Lacks-Immortal-Cells.html
Henrietta Lacks’ ‘Immortal’ Cells
by Sarah Zielinski / January 22, 2010

Medical researchers use laboratory-grown human cells to learn the intricacies of how cells work and test theories about the causes and treatment of diseases. The cell lines they need are “immortal”—they can grow indefinitely, be frozen for decades, divided into different batches and shared among scientists. In 1951, a scientist at Johns Hopkins Hospital in Baltimore, Maryland, created the first immortal human cell line with a tissue sample taken from a young black woman with cervical cancer. Those cells, called HeLa cells, quickly became invaluable to medical research—though their donor remained a mystery for decades. In her new book, The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells, Henrietta Lacks, and documents the cell line’s impact on both modern medicine and the Lacks family.

Q: Who was Henrietta Lacks?
A: She was a black tobacco farmer from southern Virginia who got cervical cancer when she was 30. A doctor at Johns Hopkins took a piece of her tumor without telling her and sent it down the hall to scientists there who had been trying to grow tissues in culture for decades without success. No one knows why, but her cells never died.

Q: Why are her cells so important?
A: Henrietta’s cells were the first immortal human cells ever grown in culture. They were essential to developing the polio vaccine. They went up in the first space missions to see what would happen to cells in zero gravity. Many scientific landmarks since then have used her cells, including cloning, gene mapping and in vitro fertilization.

Q: There has been a lot of confusion over the years about the source of HeLa cells. Why?
A: When the cells were taken, they were given the code name HeLa, for the first two letters in Henrietta and Lacks. Today, anonymizing samples is a very important part of doing research on cells. But that wasn’t something doctors worried about much in the 1950s, so they weren’t terribly careful about her identity. When some members of the press got close to finding Henrietta’s family, the researcher who’d grown the cells made up a pseudonym—Helen Lane—to throw the media off track. Other pseudonyms, like Helen Larsen, eventually showed up, too. Her real name didn’t really leak out into the world until the 1970s.

Q: How did you first get interested in this story?
A: I first learned about Henrietta in 1988. I was 16 and a student in a community college biology class. Everybody learns about these cells in basic biology, but what was unique about my situation was that my teacher actually knew Henrietta’s real name and that she was black. But that’s all he knew. The moment I heard about her, I became obsessed: Did she have any kids? What do they think about part of their mother being alive all these years after she died? Years later, when I started being interested in writing, one of the first stories I imagined myself writing was hers. But it wasn’t until I went to grad school that I thought about trying to track down her family.

Q: How did you win the trust of Henrietta’s family?
A: Part of it was that I just wouldn’t go away and was determined to tell the story. It took almost a year even to convince Henrietta’s daughter, Deborah, to talk to me. I knew she was desperate to learn about her mother. So when I started doing my own research, I’d tell her everything I found. I went down to Clover, Virginia, where Henrietta was raised, and tracked down her cousins, then called Deborah and left these stories about Henrietta on her voice mail. Because part of what I was trying to convey to her was I wasn’t hiding anything, that we could learn about her mother together. After a year, finally she said, fine, let’s do this thing.

Q: When did her family find out about Henrietta’s cells?
A: Twenty-five years after Henrietta died, a scientist discovered that many cell cultures thought to be from other tissue types, including breast and prostate cells, were in fact HeLa cells. It turned out that HeLa cells could float on dust particles in the air and travel on unwashed hands and contaminate other cultures. It became an enormous controversy. In the midst of that, one group of scientists tracked down Henrietta’s relatives to take some samples with hopes that they could use the family’s DNA to make a map of Henrietta’s genes so they could tell which cell cultures were HeLa and which weren’t, to begin straightening out the contamination problem. So a postdoc called Henrietta’s husband one day. But he had a third-grade education and didn’t even know what a cell was. The way he understood the phone call was: “We’ve got your wife. She’s alive in a laboratory. We’ve been doing research on her for the last 25 years. And now we have to test your kids to see if they have cancer.” Which wasn’t what the researcher said at all. The scientists didn’t know that the family didn’t understand. From that point on, though, the family got sucked into this world of research they didn’t understand, and the cells, in a sense, took over their lives.

Q: How did they do that?
A: This was most true for Henrietta’s daughter. Deborah never knew her mother; she was an infant when Henrietta died. She had always wanted to know who her mother was but no one ever talked about Henrietta. So when Deborah found out that this part of her mother was still alive she became desperate to understand what that meant: Did it hurt her mother when scientists injected her cells with viruses and toxins? Had scientists cloned her mother? And could those cells help scientists tell her about her mother, like what her favorite color was and if she liked to dance. Deborah’s brothers, though, didn’t think much about the cells until they found out there was money involved. HeLa cells were the first human biological materials ever bought and sold, which helped launch a multi-billion-dollar industry. When Deborah’s brothers found out that people were selling vials of their mother’s cells, and that the family didn’t get any of the resulting money, they got very angry. Henrietta’s family has lived in poverty most of their lives, and many of them can’t afford health insurance. One of her sons was homeless and living on the streets of Baltimore. So the family launched a campaign to get some of what they felt they were owed financially. It consumed their lives in that way.

Q: What are the lessons from this book?
A: For scientists, one of the lessons is that there are human beings behind every biological sample used in the laboratory. So much of science today revolves around using human biological tissue of some kind. For scientists, cells are often just like tubes or fruit flies—they’re just inanimate tools that are always there in the lab. The people behind those samples often have their own thoughts and feelings about what should happen to their tissues, but they’re usually left out of the equation.

Q: And for the rest of us?
A: The story of HeLa cells and what happened with Henrietta has often been held up as an example of a racist white scientist doing something malicious to a black woman. But that’s not accurate. The real story is much more subtle and complicated. What is very true about science is that there are human beings behind it and sometimes even with the best of intentions things go wrong. One of the things I don’t want people to take from the story is the idea that tissue culture is bad. So much of medicine today depends on tissue culture. HIV tests, many basic drugs, all of our vaccines—we would have none of that if it wasn’t for scientists collecting cells from people and growing them. And the need for these cells is going to get greater, not less. Instead of saying we don’t want that to happen, we just need to look at how it can happen in a way that everyone is OK with.

CONTACT
Rebecca Skloot
http://scienceblogs.com/culturedish/
http://rebeccaskloot.com/about/bio/
email: rebecca [at] rebeccaskloot [dot] com

BEFORE CONSENT
http://en.wikipedia.org/wiki/George_Otto_Gey
http://www.medicalarchives.jhmi.edu/sgml/gey.html
http://www.nytimes.com/2001/11/17/arts/cells-that-save-lives-are-a-mother-s-legacy.html
Cells That Save Lives Are a Mother’s Legacy
by Rebecca Skllot / November 17, 2001

Deborah Lacks closed her eyes as a young cancer researcher opened the door of his floor-to-ceiling freezer. She stood clutching the ragged dictionary she uses to look up words like ”DNA,” ”cell” and ”immortality.” When the icy breeze hit her face, she opened her eyes slowly, and stared into a freezer filled with tiny vials of red liquid. ”O God,” she gasped, ”I can’t believe all this is my mother.” Fifty years ago, when Deborah Lacks was still in diapers, her 30-year-old mother, Henrietta Lacks, lay in a segregated ward of Johns Hopkins Hospital in Baltimore. The resident gynecologist sewed radium to her cervix in an attempt to knock out the cancer that was killing her. But before he finished, and without telling her, he took a small sample of her tumor and sent it downstairs to Dr. George Gey (pronounced guy), head of tissue culture research at Hopkins. Dr. Gey had spent almost 30 years collecting cancerous human cells and trying to make them grow, but until Ms. Lacks came along, they never did. Though Henrietta died a few months after her radium treatments, her cells are still living today.

Henrietta’s cells — named HeLa after the first letters in Henrietta and Lacks — became the first human cells to live indefinitely outside the body. They helped eradicate polio, flew in early space shuttle missions and sat in nuclear test sites around the world. In the 50’s, HeLa cells helped researchers understand the differences between cancerous and normal cells, and quickly became a standard laboratory tool for studying the effects of radiation, growing viruses and testing medications. HeLa is still one of the most widely used cell lines; in fact, this year’s Nobel Prize in Physiology or Medicine was awarded for research in which HeLa cells played a pivotal role. Yet it was not until nearly two decades later — just before magazines like Jet and Emerge started writing stories about a black family whose mother had made important contributions to science without their knowledge — that anyone in Ms. Lacks’s family knew what had happened. Ms. Lacks, 52, doesn’t remember how she heard, but she’ll never forget her reaction: ”I went into shock,” she said. ”Why didn’t they just ask if they could use her cells?”

If the issue of using patient tissue without permission wasn’t a pressing one in the 50’s, informed consent has certainly become a heated topic today. ”In 1951, they wouldn’t have felt like they needed to ask,” said Ruth Faden, executive director of the Johns Hopkins Bioethics Institute. ”It’s a sad commentary on how the biomedical research community thought about research in the 50’s, but it was not at all uncommon for physicians to conduct research on patients without their knowledge or consent.” Today, when patients go in for surgery, they’re usually asked to sign a form saying whether their tissues can be used for research. But, said Lori Andrews, a professor at Chicago-Kent College of Law and co-author of ”Body Bazaar: The Market for Human Tissue in the Biotechnology Age,” that practice doesn’t solve an important problem. ”All of us have blood or tissue on file somewhere,” Ms. Andrews said. ”Today, every drop of blood taken from people, every organ or biopsy removed by a surgeon, is in the pipeline toward research and commercialization. Since the 60’s, every newborn in the U.S. has been tested for genetic disorders, and many of their samples are still on file for use in later research. There are no rules governing who has access to these samples.” Some bioethicists and lawyers want legislation requiring researchers to obtain consent before conducting research on any tissues, including those already in storage. But many research organizations — the American Society for Investigative Pathology, for example, and the College of American Pathologists — have argued that such blanket legislation could seriously damage scientific progress.

Dr. Mark Sobel, senior executive officer of the American Society for Investigative Pathology, agrees that informed consent should be required before new tissues are collected. But to Dr. Sobel, the millions of tissue samples collected before the current shift toward informed consent, like Henrietta Lacks’s cells, are a special case. Scientists conducting research on those samples have no way to contact the donors for permission. ”This is where we want some flexibility,” Dr. Sobel said. ”We want recognition that there’s a way — with policies in place for confidentiality and protecting the patients — that you can still use these very, very, very important resources of human tissue. Otherwise, it’s going to impede medical research.” To Dr. Sobel, using these samples ethically means protecting patient identity and assuring complete anonymity. Dr. Gey tried to do this for Ms. Lacks, but rumors began circulating that HeLa stood for someone named Helen Lane. When a few colleagues of Dr. Gey, who has since died, tried to correct this error, the Lacks family was thrown into a world of science they didn’t understand.

Ever since Ms. Lacks first heard about her mother’s cells, she has been trying to understand how they could be alive decades after her death. So she got a notebook, a dictionary and a science book and began teaching herself about cells, one word at a time. ”A cell,” she wrote, ”is a minute portion of living substance.” She copied one definition after another. ”As long as the cell receives an adequate supply of food,” she wrote, ”it will continue to grow and thrive for the duration of its life cycle.” Not even Dr. Gey ever understood precisely why the life cycle of Ms. Lacks’s cancer cells has continued indefinitely.

Within a few years of learning about HeLa cells, the Lacks family began getting letters from researchers, asking them to donate blood so scientists could find genetic markers to help identify Henrietta’s cells. But Ms. Lacks remembers differently: ”It was a typed letter, stating we need samples of the Lacks family to check her blood cells with theirs, to see if anybody has the same thing that she had,” she said. Ms. Lacks was in her late 20’s and had always worried that she might die at 31, just like her mother. ”I cried and cried,” she recalled. ”I had my two children, they was babies at the time, and I said ‘O God, am I going to make it past 31?’ ” She dodged the researchers at first, because she didn’t want to know whether she had cancer. When she finally decided to take the tests, she thought she’d get a phone call telling her whether she was going to live or die. She never heard back from the researchers and soon had the first of what would become several breakdowns.

Ms. Faden said: ”This could have been a very innocent misunderstanding. But this is why researchers have to be as straightforward as possible, because the expectation is that when a doctor wants to do something to you, it’s for your benefit. Physician-researchers need to make this clear by saying, ‘I’m not doing this to help you, I’m doing it to advance science.’ ” Bobbette Lacks, Henrietta Lacks’s daughter-in-law, says that if researchers had told them about HeLa cells, then informed them of future research, her family would have cooperated. But not now. ”I would never subject my kids to that,” Bobbette Lacks said. This year, the 50th anniversary of Henrietta Lacks’s death, some scientists wanted to honor her contribution. The National Foundation for Cancer Research had invited Deborah Lacks onstage to thank her for her mother’s cells. But the conference had been scheduled for Sept. 13 and was canceled after the terrorist attacks. So for now, Ms. Lacks is back to learning about her mother on her own. Until Ms. Lacks looked into that freezer filled with vials earlier this year, she had only read about her mother’s cells; she had never seen them. Christoph Lengauer, the young cancer researcher who was showing her around his lab at John Hopkins Oncology Center, leaned over a microscope, focused it on a single HeLa cell and projected it onto a monitor. She stared in silence, eyes wide, then sighed. ”I was doing a little bit of studying on that DNA in my books,” she said, patting her purse filled with notes. Now she is in the process of signing up for basic courses at a local community center in Baltimore in the hope that they will lead her toward college. She is not sure what degree she will pursue, but she knows for sure what she will study: science.

ENDLESS SUPPLY
http://www.popsci.com/science/article/2010-01/five-reasons-henrietta-lacks-most-important-woman-medical-history

In 1951, Henrietta Lacks, a poor woman with a middle-school education, made one of the greatest medical contributions ever. Her cells, taken from a cervical-cancer biopsy, became the first immortal human cell line—the cells reproduce infinitely in a lab. Although other immortal lines have since been established, Lacks’s “HeLa” cells are the standard in labs around the world. Together they outweigh 100 Empire State Buildings and could circle the equator three times. This month, PopSci contributor Rebecca Skloot’s book, The Immortal Life of Henrietta Lacks, tells the story behind the woman who revolutionized modern medicine. Here, five reasons we should all thank Henrietta Lacks:
1. Before HeLa cells, scientists spent more time trying to keep cells alive than performing actual research on the cells. An endless supply of HeLa cells freed up time for discovery.
2. In 1952, the worst year of the polio epidemic, HeLa cells were used to test the vaccine that protected millions.
3. Some cells in Lacks’s tissue sample behaved differently than others. Scientists learned to isolate one specific cell, multiply it, and start a cell line. Isolating one cell and keeping it alive is the basic technique for cloning and in-vitro fertilization.
4. A scientist accidentally poured a chemical on a HeLa cell that spread out its tangled chromosomes. Later on, scientists used this technique to determine that humans have 46 chromosomes—23 pairs—not 48, which provided the basis for making several types of genetic diagnoses.
5. It was discovered that Lacks’s cancerous cells used an enzyme called telomerase to repair their DNA, allowing them, and other types of cancer cells, to function when normal cells would have died. Anti-cancer drugs that work against this enzyme are currently in early clinical trials.


HeLa isn’t the only cell line in use today. Thousands have found their way into labs worldwide. Above are some commonly used lines and the number of scientific papers they appear in.

AVAILABLE IN BULK
http://www.atcc.org/
http://www.biocompare.com/ProductListings/18758/HeLa-Cells.html
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CancerCellsInCulture.html
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Media.html#Ham’s_Medium
http://ems3.intellor.com/index.cgi?c=105&t=13&s=corningweb
http://ems3.intellor.com/index.cgi?c=105&t=13&s=corningweb

Hela
http://www.npr.org/templates/story/story.php?storyId=123232331
excerpt from ‘The Immortal Life of Henrietta Lacks’
by Rebecca Skloot / 2010

There’s a photo on my wall of a woman I’ve never met, its left corner torn and patched together with tape. She looks straight into the camera and smiles, hands on hips, dress suit neatly pressed, lips painted deep red. It’s the late 1940s and she hasn’t yet reached the age of thirty. Her light brown skin is smooth, her eyes still young and playful, oblivious to the tumor growing inside her — a tumor that would leave her five children motherless and change the future of medicine. Beneath the photo, a caption says her name is “Henrietta Lacks, Helen Lane or Helen Larson.” No one knows who took that picture, but it’s appeared hundreds of times in magazines and science textbooks, on blogs and laboratory walls. She’s usually identified as Helen Lane, but often she has no name at all. She’s simply called HeLa, the code name given to the world’s first immortal human cells — her cells, cut from her cervix just months before she died. Her real name is Henrietta Lacks.

I’ve spent years staring at that photo, wondering what kind of life she led, what happened to her children, and what she’d think about cells from her cervix living on forever —bought, sold, packaged, and shipped by the trillions to laboratories around the world. I’ve tried to imagine how she’d feel knowing that her cells went up in the first space missions to see what would happen to human cells in zero gravity, or that they helped with some of the most important advances in medicine: the polio vaccine, chemotherapy, cloning, gene mapping, in vitro fertilization. I’m pretty sure that she — like most of us — would be shocked to hear that there are trillions more of her cells growing in laboratories now than there ever were in her body.

There’s no way of knowing exactly how many of Henrietta’s cells are alive today. One scientist estimates that if you could pile all HeLa cells ever grown onto a scale, they’d weigh more than 50 million metric tons — an inconceivable number, given that an individual cell weighs almost nothing. Another scientist calculated that if you could lay all HeLa cells ever grown end-to-end, they’d wrap around the Earth at least three times, spanning more than 350 million feet. In her prime, Henrietta herself stood only a bit over five feet tall.

I first learned about HeLa cells and the woman behind them in 1988, thirty-seven years after her death, when I was sixteen and sitting in a community college biology class. My instructor, Donald Defler, a gnomish balding man, paced at the front of the lecture hall and flipped on an overhead projector. He pointed to two diagrams that appeared on the wall behind him. They were schematics of the cell reproduction cycle, but to me they just looked like a neon-colored mess of arrows, squares, and circles with words I didn’t understand, like “MPF Triggering a Chain Reaction of Protein Activations.”

I was a kid who’d failed freshman year at the regular public high school because she never showed up. I’d transferred to an alternative school that offered dream studies instead of biology, so I was taking Defler’s class for high-school credit, which meant that I was sitting in a college lecture hall at sixteen with words like mitosis and kinase inhibitors flying around. I was completely lost. “Do we have to memorize everything on those diagrams?” one student yelled. Yes, Defler said, we had to memorize the diagrams, and yes, they’d be on the test, but that didn’t matter right then. What he wanted us to understand was that cells are amazing things: There are about one hundred trillion of them in our bodies, each so small that several thousand could fit on the period at the end of this sentence. They make up all our tissues — muscle, bone, blood — which in turn make up our organs.

Under the microscope, a cell looks a lot like a fried egg: It has a white (the cytoplasm) that’s full of water and proteins to keep it fed, and a yolk (the nucleus) that holds all the genetic information that makes you you. The cytoplasm buzzes like a New York City street. It’s crammed full of molecules and vessels endlessly shuttling enzymes and sugars from one part of the cell to another, pumping water, nutrients, and oxygen in and out of the cell. All the while, little cytoplasmic factories work 24/7, cranking out sugars, fats, proteins, and energy to keep the whole thing running and feed the nucleus. The nucleus is the brains of the operation; inside every nucleus within each cell in your body, there’s an identical copy of your entire genome. That genome tells cells when to grow and divide and makes sure they do their jobs, whether that’s controlling your heartbeat or helping your brain understand the words on this page.

Defler paced the front of the classroom telling us how mitosis — the process of cell division — makes it possible for embryos to grow into babies, and for our bodies to create new cells for healing wounds or replenishing blood we’ve lost. It was beautiful, he said, like a perfectly choreographed dance. All it takes is one small mistake anywhere in the division process for cells to start growing out of control, he told us. Just one enzyme misfiring, just one wrong protein activation, and you could have cancer. Mitosis goes haywire, which is how it spreads. “We learned that by studying cancer cells in culture,” Defler said. He grinned and spun to face the board, where he wrote two words in enormous print: HENRIETTA LACKS.

Henrietta died in 1951 from a vicious case of cervical cancer, he told us. But before she died, a surgeon took samples of her tumor and put them in a petri dish. Scientists had been trying to keep human cells alive in culture for decades, but they all eventually died. Henrietta’s were different: they reproduced an entire generation every twenty-four hours, and they never stopped. They became the first immortal human cells ever grown in a laboratory. “Henrietta’s cells have now been living outside her body far longer than they ever lived inside it,” Defler said. If we went to almost any cell culture lab in the world and opened its freezers, he told us, we’d probably find millions — if not billions — of Henrietta’s cells in small vials on ice.

Her cells were part of research into the genes that cause cancer and those that suppress it; they helped develop drugs for treating herpes, leukemia, influenza, hemophilia, and Parkinson’s disease; and they’ve been used to study lactose digestion, sexually transmitted diseases, appendicitis, human longevity, mosquito mating, and the negative cellular effects of working in sewers. Their chromosomes and proteins have been studied with such detail and precision that scientists know their every quirk. Like guinea pigs and mice, Henrietta’s cells have become the standard laboratory workhorse. “HeLa cells were one of the most important things that happened to medicine in the last hundred years,” Defler said.

Then, matter-of-factly, almost as an afterthought, he said, “She was a black woman.” He erased her name in one fast swipe and blew the chalk from his hands. Class was over. As the other students filed out of the room, I sat thinking, That’s it? That’s all we get? There has to be more to the story. I followed Defler to his office. “Where was she from?” I asked. “Did she know how important her cells were? Did she have any children?”

“I wish I could tell you,” he said, “but no one knows anything about her.” After class, I ran home and threw myself onto my bed with my biology textbook. I looked up “cell culture” in the index, and there she was, a small parenthetical: “In culture, cancer cells can go on dividing indefinitely, if they have a continual supply of nutrients, and thus are said to be “immortal.” A striking example is a cell line that has been reproducing in culture since 1951. (Cells of this line are called HeLa cells because their original source was a tumor removed from a woman named Henrietta Lacks.)” That was it. I looked up HeLa in my parents’ encyclopedia, then my dictionary: No Henrietta.

The Way of All Flesh, by Adam Curtis

As I graduated from high school and worked my way through college toward a biology degree, HeLa cells were omnipresent. I heard about them in histology, neurology, pathology; I used them in experiments on how neighboring cells communicate. But after Mr. Defler, no one mentioned Henrietta. When I got my first computer in the mid-nineties and started using the Internet, I searched for information about her, but found only confused snippets: most sites said her name was Helen Lane; some said she died in the thirties; others said the forties, fifties, or even sixties. Some said ovarian cancer killed her, others said breast or cervical cancer.

Eventually I tracked down a few magazine articles about her from the seventies. Ebony quoted Henrietta’s husband saying, “All I remember is that she had this disease, and right after she died they called me in the office wanting to get my permission to take a sample of some kind. I decided not to let them.” Jet said the family was angry — angry that Henrietta’s cells were being sold for twenty-five dollars a vial, and angry that articles had been published about the cells without their knowledge. It said, “Pounding in the back of their heads was a gnawing feeling that science and the press had taken advantage of them.”

The articles all ran photos of Henrietta’s family: her oldest son sitting at his dining room table in Baltimore, looking at a genetics textbook. Her middle son in military uniform, smiling and holding a baby. But one picture stood out more than any other: in it, Henrietta’s daughter, Deborah Lacks, is surrounded by family, everyone smiling, arms around each other, eyes bright and excited. Except Deborah. She stands in the foreground looking alone, almost as if someone pasted her into the photo after the fact. She’s twenty-six years old and beautiful, with short brown hair and catlike eyes. But those eyes glare at the camera, hard and serious. The caption said the family had found out just a few months earlier that Henrietta’s cells were still alive, yet at that point she’d been dead for twenty-five years.

All of the stories mentioned that scientists had begun doing research on Henrietta’s children, but the Lackses didn’t seem to know what that research was for. They said they were being tested to see if they had the cancer that killed Henrietta, but according to the reporters, scientists were studying the Lacks family to learn more about Henrietta’s cells. The stories quoted her son Lawrence, who wanted to know if the immortality of his mother’s cells meant that he might live forever too. But one member of the family remained voiceless: Henrietta’s daughter, Deborah.

As I worked my way through graduate school studying writing, I became fixated on the idea of someday telling Henrietta’s story. At one point I even called directory assistance in Baltimore looking for Henrietta’s husband, David Lacks, but he wasn’t listed. I had the idea that I’d write a book that was a biography of both the cells and the woman they came from — someone’s daughter, wife, and mother.

I couldn’t have imagined it then, but that phone call would mark the beginning of a decadelong adventure through scientific laboratories, hospitals, and mental institutions, with a cast of characters that would include Nobel laureates, grocery store clerks, convicted felons, and a professional con artist. While trying to make sense of the history of cell culture and the complicated ethical debate surrounding the use of human tissues in research, I’d be accused of conspiracy and slammed into a wall both physically and metaphorically, and I’d eventually find myself on the receiving end of something that looked a lot like an exorcism. I did eventually meet Deborah, who would turn out to be one of the strongest and most resilient women I’d ever known. We’d form a deep personal bond, and slowly, without realizing it, I’d become a character in her story, and she in mine.

Deborah and I came from very different cultures: I grew up white and agnostic in the Pacific Northwest, my roots half New York Jew and half Midwestern Protestant; Deborah was a deeply religious black Christian from the South. I tended to leave the room when religion came up in conversation because it made me uncomfortable; Deborah’s family tended toward preaching, faith healings, and sometimes voodoo. She grew up in a black neighborhood that was one of the poorest and most dangerous in the country; I grew up in a safe, quiet middle-class neighborhood in a predominantly white city and went to high school with a total of two black students. I was a science journalist who referred to all things supernatural as “woo-woo stuff”; Deborah believed Henrietta’s spirit lived on in her cells, controlling the life of anyone who crossed its paths. Including me.

“How else do you explain why your science teacher knew her real name when everyone else called her Helen Lane?” Deborah would say. “She was trying to get your attention.” This thinking would apply to everything in my life: when I married while writing this book, it was because Henrietta wanted someone to take care of me while I worked. When I divorced, it was because she’d decided he was getting in the way of the book. When an editor who insisted I take the Lacks family out of the book was injured in a mysterious accident, Deborah said that’s what happens when you piss Henrietta off.

The Lackses challenged everything I thought I knew about faith, science, journalism, and race. Ultimately, this book is the result. It’s not only the story of HeLa cells and Henrietta Lacks, but of Henrietta’s family — particularly Deborah — and their lifelong struggle to make peace with the existence of those cells, and the science that made them possible.

SOME JURASSIC PARK SHIT
http://rebeccaskloot.com/the-immortal-life/excerpt/
BY Rebecca Skloot / 2010

Deborah grabbed her bag off the floor, and dumped its contents onto the bed. “This is what I got about my mother,” she said. There were videotapes, a tattered English dictionary, a diary, a genetics textbook, many scientific journal articles, patent records, and unsent greeting cards, including several birthday and Mother’s Day cards she’d bought for Henrietta. While she sorted through the pile, as though she was saying something as everyday as It’s supposed to rain tomorrow, Deborah said, “Scientists do all kinds of experiments and you never know what they doin. I still wonder how many people they got in London walkin around look just like my mother.”

“What?” I said. “Why would there be women in London who look like your mother?” “They did that cloning on my mother over there,” she said, surprised I hadn’t come across that fact in my research. “A reporter came here from England talking about they cloned a sheep. Now you go on the Internet, they got stuff about cloning my mother all over.” She held up an article from the Independent in London and pointed at a circled paragraph: “Henrietta Lacks’s cells thrived. In weight, they now far surpassed the person of their origin and there would probably be more than sufficient to populate a village of Henriettas.” The writer joked that Henrietta should have put ten dollars in the bank in 1951, because if she had, her clones would be rich now. Deborah raised her eyebrows at me like, See? I told you!

I started saying it was just Henrietta’s cells scientists had cloned, not Henrietta herself. But Deborah waved her hand in my face, shushing me like I was talking nonsense, then grabbed a videocassette and held it up for me to see. It said Jurassic Park on the spine. “I saw this movie a bunch of times,” she said. “They talking about the genes and taking them from cells to bring that dinosaur back to life and I’m like, Oh Lord, I got a paper on how they were doin that with my mother’s cells too! “I don’t know what I’d do if I saw one of my mother clones walkin around somewhere.”

Deborah realized Jurassic Park was science fiction, but for her the line between sci-fi and reality had blurred years earlier, when her father got that first call saying Henrietta’s cells were still alive twenty-five years after her death. Deborah knew her mother’s cells had grown like the Blob until there were so many of them they could wrap around the Earth several times. It sounded crazy, but it was true. “You just never know,” Deborah said, fishing two more articles from the pile. One was called Human, Plant Cells Fused: Walking Carrots Next? The other was Man-Animal Cells Bred in Lab. Both were about her mother’s cells, and neither was science fiction. “I don’t know what they did,” Deborah said, “but it all sound like Jurassic Park to me.”


HeLa cells are cultured tumor cells isolated from cancer patient Henrietta Lacks in 1951. It is the first human cell to be kept in culture for long periods of time and is still used today.

CANCER DON’T STOP
http://m.discovermagazine.com/1992/dec/nolongerhuman171
by Lori Oliwenstein / December 1, 1992

Henrietta Lacks achieved a kind of immortality on February 9, 1951. On that day a sample of cancerous cells from her cervix was transferred to a culture dish, doused with nutrients, and left to grow. Lacks, a 30-year-old mother of four from Baltimore, had one of the most aggressive cervical cancers her doctors had ever seen, and the cells culled from her tumor grew avidly, doubling their number each day. Then they escaped. Small spills are always happening in laboratories; what distinguished Lacks’s cells was their ability to survive after they were somehow spilled. They were so hardy that if just one of them fell on a petri dish it would outgrow and overwhelm anything else living on that dish within a month.

Soon Henrietta Lacks’s cells were traveling from lab to lab, either deliberately sent–many cancer researchers had taken to using them in their experiments–or as an unseen contaminant tagging along in another cell line. Some researchers who thought they were looking at something completely different–a line of liver cells, say–ended up studying Henrietta Lacks’s cervical cells by accident. The cells even slipped through the iron curtain and into Russia.

Lacks died in October 1951, but her peripatetic cells lived on. Now some biologists are saying that those cells, called HeLa cells for short, have lost more than their connection to Henrietta Lacks. HeLa cells, these researchers claim, are no longer human at all: they are single-celled microbes–closely related to us, to be sure, but their own distinct species. How so, you ask? HeLa cells are not connected in any way to people, explains evolutionary biologist Leigh Van Valen of the University of Chicago. They have an extremely different ecological niche from us. They don’t mate with humans; they probably don’t even mate with human cells. They act just like a normal microbial species. They are evolving separately from us, and having a separate evolution is really what a species is all about.

The process of evolution is much the same for HeLas as it is for humans, although the former usually reproduce asexually, by cell division. As the cells divide, genetic mutations inevitably occur, and the ones that make the cells better adapted to their ecological niche–the petri dish– are preserved by natural selection. When Henrietta Lacks’s cells first became cancerous, they also acquired the ability to survive indefinitely in a culture medium; that massive genetic transformation made them substantially different from ordinary human cells, and after four decades of evolution they have become more different still. Different strains of HeLa cells, analogous to different races of human beings, have even developed in some of the geographically separated lines.

These little unicellular organisms have crossed oceans, spread their range, got into other cultures and outcompeted them, says Richard Strathmann, a marine biologist at the University of Washington’s Friday Harbor Laboratories who dabbles in evolutionary theory. They’re only different from other single-celled organisms in that a human being gave rise to them. Strathmann and Van Valen (the latter with his colleague Virginia Maiorana) put forth these ideas separately, in two papers in the same issue of the journal Evolutionary Theory, which Van Valen edits. (Both papers, he points out, were independently reviewed before publication.) Van Valen and Maiorana not only declared that HeLa may not be Homo sapiens, they gave the new species a name: Helacyton gartleri–Hela, after the HeLa cells themselves; cyton, from the Greek cytos, meaning cavity or cell; and gartleri after geneticist Stanley Gartler, who was the first to document the cells’ remarkable success.

While Van Valen is willing to name the new species, he is unwilling to suggest which higher taxonomic category it might fall into. Beyond the family name there are problems, he says. Since a HeLa cell can’t survive outside a culture medium, it obviously isn’t a primate in the usual sense. At the same time, says Van Valen, you can’t call it a protist- -a member of the kingdom of all single-celled organisms, which includes bacteria, protozoans, algae, and fungi–since that would mean that the same group had evolved twice, once sometime before 3.5 billion years ago and again today. It’s a fundamental tenet of evolutionary theory that evolution doesn’t repeat itself.

But that’s exactly what has happened, says Strathmann. And to him, HeLa cells are just a particularly aggressive and successful example of an evolutionary transition that has happened numerous times recently. Many cancer cells, in becoming cancerous, undergo the same type of genetic transformation that Henrietta Lacks’s cells did and thereby acquire the potential to be immortal; and many different lines of these cells are now surviving in petri dishes all over the world. All of them, according to Strathmann, have made the huge evolutionary leap from being metazoans– multicellular creatures with organs and tissues–to being single-celled protists. What’s most amazing, he says, is how fast they did it: it took nearly 3 billion years for the first metazoans to evolve after life originated but just a handful of years for HeLa and other cell lines to take exactly the same step in the other direction.

If this modern-day transition from human being to unicellular blob sounds like far-out fiction to you, you’re not alone. Some biologists consider the survival of HeLa cells a purely artificial phenomenon and argue that evolution in a petri dish has little relevance to evolution in nature. Indeed, Strathmann’s paper was rejected by other journals for just that reason before Van Valen agreed to publish it along with his own. Van Valen and Strathmann, of course, reject that criticism. The perception is that if human beings are manipulating the situation, it’s not natural, says Strathmann. But biomedical researchers are part of nature.

Organisms live in all sorts of odd places, including ones humans have created, adds Van Valen. Parks and cities are environments that we created, and organisms have become adapted to them. Human beings have even created new species before, albeit not from their own flesh. Modern corn, for instance, is a product of selective breeding by generations of farmers, and like HeLa cells, it can’t survive without human help. If HeLa had not been derived from human tissue, Van Valen says, there would be no question about its being a new species.

CONTACT
Leigh Van Valen
http://pondside.uchicago.edu/ecol-evol/people/vanvalen.html
email : leigh [at] uchicago [dot] edu

NEW SPECIES? HELACYTON GARTLERI
http://en.wikipedia.org/wiki/HeLa#Helacyton_gartleri

“Due to their ability to replicate indefinitely, and their non-human number of chromosomes, HeLa was described by Leigh Van Valen as an example of the contemporary creation of a new species, Helacyton gartleri, named after Stanley M. Gartler, whom Van Valen credits with discovering “the remarkable success of this species.” His argument for speciation depends on three points:

  • The chromosomal incompatibility of HeLa cells with humans.
  • The ecological niche of HeLa cells.
  • Their ability to persist and expand well beyond the desires of human cultivators.

It should be noted that this definition has not been followed by others in the scientific community, nor, indeed, has it been widely noted. As far as proposing a new species for HeLa cells, Van Valen proposes in the same paper the new family Helacytidae and the genus Helacyton.[12]Recognition of Van Valen and Maiorana’s names, however, renders Homo and Hominidae paraphyletic because Helacyton gartleri is most closely related to Homo sapiens.

‘LAB WEEDS’
http://en.wikipedia.org/wiki/Stanley_M._Gartler
http://en.wikipedia.org/wiki/Walter_Nelson-Rees
http://www.nature.com/nrc/journal/v2/n4/box/nrc775_BX1.html
http://www.sunypress.edu/p-133-a-conspiracy-of-cells.aspx
http://en.wikipedia.org/wiki/HeLa#Contamination
“Because of their adaptation to growth in tissue culture plates, HeLa cells are sometimes difficult to control. They have proven to be a persistent laboratory “weed” that contaminates other cell cultures in the same laboratory, interfering with biological research and forcing researchers to declare many results invalid. The degree of HeLa cell contamination among other cell types is unknown because few researchers test the identity or purity of already-established cell lines. It has been demonstrated that a substantial fraction of in vitro cell lines — approximately 10%, maybe 20% — are contaminated with HeLa cells. Stanley Gartler in 1967 and Walter Nelson-Rees in 1975 were the first to publish on the contamination of various cell lines by HeLa. Science writer Michael Gold wrote about the HeLa cell contamination problem in his book A Conspiracy of Cells. He describes Nelson-Rees’s identification of this pervasive worldwide problem — affecting even the laboratories of the best physicians, scientists, and researchers, including Jonas Salk — and many, possibly career-ending, efforts to address it. According to Gold, the HeLa contamination problem almost led to a Cold War incident: The USSR and the USA had begun to cooperate in the war on cancer launched by President Richard Nixon only to find that the exchanged cells were contaminated by HeLa. Rather than focus on how to resolve the problem of HeLa cell contamination, many scientists and science writers continue to document this problem as simply a contamination issue — caused not by human error or shortcomings but by the hardiness, proliferating, or overpowering nature of HeLa. Recent data suggest that cross-contaminations are still a major ongoing problem with modern cell cultures.”


Henrietta Lacks rests today in an unmarked grave in the cemetery across the street from her family’s tobacco farm in Virginia. / photo by Rebecca Skloot

RELENTLESS
http://www.jhu.edu/~jhumag/0400web/01.html
by Rebecca Skloot / April 2000

Not long before her death, Henrietta Lacks danced. As the film rolled, her long thin face teased the camera, flashing a seductive grin as she moved, her eyes locked on the lens. She tilted her head back and raised her hands, waving them softly in the air before letting them fall to smooth her curlers. Then the film went blank. Henrietta danced in Turners Station, a small, segregated Baltimore community where she moved in 1943. She had come by train from a plantation town in Virginia, leaving her kin behind, most still picking tobacco long after freedom from slavery. As she sped toward Baltimore, at the age of 23, her husband, David Lacks, waited in their new brick house with a stove that burned gas instead of wood. Henrietta knew she was heading into a more modern world. What she didn’t know was that less than a decade later, after giving birth to her fifth child, her womb would give rise to a new age in medicine.

On February 1, 1951, under the cover of a solitary tree, David Lacks stared through the window of his parked car, watching the rain fall. He and his five children, three still in diapers, sat outside Hopkins Hospital, waiting for Henrietta. A few days earlier, she had found blood spotting her underwear. Now, Howard Jones, a Hopkins physician, found a smooth eggplant-hued tumor glistening under the light on Henrietta’s cervix. He touched its surface, shocked by its supple texture, and Henrietta bled. Jones carefully cut a section of her quarter-sized tumor, sent it to the lab for a diagnosis, and sent Henrietta home with her family. Then came the news: the tumor was malignant.

Henrietta returned to Hopkins eight days later. While David and the children waited under the tree, physicians covered her cervix with radium in an attempt to kill the cancer. But before applying the first treatment, a young resident took one more sample. This one went to George Gey, head of tissue culture research at Hopkins. He and his wife, Margaret, had been searching for a tool for the study of cancer: a line of human cells that would live indefinitely outside the body. If they succeeded, they could observe and test human cells in ways they could never do in humans. Eventually, they could discover the cure for cancer. They were sure of it. After two decades of failure in their laboratory attempts, the Geys turned their attention to cervical cells, at the request of Richard TeLinde, then Hopkins chairman of Gynecology. TeLinde wanted cervical cells for his own research; the Geys wanted any cancer cells they could get. The day George Gey got his hands on Henrietta Lacks’s cells, everything changed. For the Geys, for medicine, and eventually for the Lackses.

Henrietta Lacks’s cells multiplied like nothing anyone had seen. They latched to the sides of test tubes, consumed the medium around them, and within days, the thin film of cells grew thicker and thicker. But Henrietta’s tumor cells took over her body as quickly as they’d taken over test tubes. Within months, tumors appeared on almost every organ, and Henrietta moaned from her bed for the Lord to help her. The day she died, October 4, 1951, George Gey appeared on national television with a vial of Henrietta’s cells. He called them HeLa cells, held them up to the camera, and said, “It is possible that, from a fundamental study such as this, we will be able to learn a way by which cancer can be completely wiped out.” Gey introduced the nation to his hopes for curing cancer while Henrietta’s body lay in the Hopkins morgue, her toenails shining with a fresh coat of red polish. And her family knew nothing of any cells.

As a train carrying Henrietta’s casket rolled back toward Virginia, her cells shocked Gey with their strength. The local undertaker met Henrietta’s body at the station where, less than a decade earlier, she had boarded her train to Baltimore. He buried her in an unmarked grave across the street from her family’s tobacco field, behind the house where her mother was born. But in the Lacks family cemetery, where cattle roam freely when the season’s right, folks today don’t know much about HeLa. They don’t know that soon after Henrietta’s death in 1951, Gey and his colleagues used her cells to grow the polio virus that was ravaging children throughout the world.

“It was Henrietta Lacks’s cells that embraced the polio virus,” says Roland Pattillo, a former fellow of Gey’s, who is now director of gynecologic oncology at Morehouse School of Medicine. “She made it possible to grow the virus so the vaccine could be developed.” That was just the beginning. Gey and his colleagues went on to develop a test, using HeLa cells, to distinguish between the many polio strains, some of which had no effect on the human body. Until researchers knew which strain produced polio’s crippling effects, they couldn’t know what they were fighting. Through Henrietta’s cells, they found their culprit. With this information, Jonas Salk and his colleagues in Pittsburgh created a vaccine, and the National Foundation for Infantile Paralysis established facilities for mass-producing the HeLa cells. They would use them to test the polio vaccine before its use in humans. In the meantime, Gey shared his resources.

Packaged in small tubes tucked in plastic foam containers, with careful instructions for feeding and handling, shipments of Henrietta’s cells went out to Gey’s colleagues around the world. . . to Minnesota, New York, Chile, Russia. . .the list goes on. Researchers welcomed the gifts, allowing HeLa to grow. They used the cells to search for a leukemia cure and the cause of cancer, to study viral growth, protein synthesis, genetic control mechanisms, and the unknown effects of drugs and radiation. And though Henrietta never traveled farther than from Virginia to Baltimore, her cells sat in nuclear test sites from America to Japan and multiplied in a space shuttle far above the Earth. Still, David Lacks and his children hadn’t a clue.

“The [only thing] I heard about it was, she had that cancer,” David Lacks says. “They called me, said come up there because she died. They asked me to let them take samples, and I decided not to let them do it.” But the researchers told Lacks they could use his wife’s cells to study cancer. Something that might strike his family again someday. Their studies might someday help his children and his grandchildren. Lacks was skeptical. But, he thought, if they want to see how my wife’s cancer might affect our children, and get ready to treat them if they get sick, I guess that might be okay. “My cousins said it wouldn’t hurt, so eventually I let them do it. The [doctors said] it was the fastest growing cancer they’d ever known, and they were supposed to tell me about it, to let me know, but I never did hear.”

He didn’t hear, that is, until a hazy day in 1975, 24 years after Henrietta’s death, when his daughter-in-law went to a friend’s house for dinner. In a two-story brown-brick townhouse in Baltimore, five doors down from her home, Barbara Lacks, the wife of Henrietta’s eldest son, Lawrence, sat down for dinner at her friend Jasmine’s house. The two women had been friends for years, but Barbara had never met Jasmine’s sister or brother-in-law, who came all the way from D.C. for dinner. They gathered around the mahogany table, surrounded by plants and soft light, and Jackson, Jasmine’s brother-in-law, looked across the table at Barbara. “You know,” he said, “your name sounds so familiar.” Jackson was a scientist who spent his days in a Washington laboratory. “I think I know what it is. . .I’ve been working with some cells in my lab; they’re from a woman called Henrietta Lacks. Are you related?”

“That’s my mother-in-law,” Barbara whispered, shaking her head. “She’s been dead almost 25 years, what do you mean you’re working with her cells?” Jackson explained. The cells, he told her, had been alive since Henrietta’s death and were all around the world. Actually, by that time, they were standard reference cells–few molecular scientists hadn’t worked with them. Barbara excused herself, thanking him, promising she would be in touch, and ran home to tell her husband what she’d heard. Your mother’s cells, she told him, they’re alive. Lawrence called his father who called his brothers and his sister. They just couldn’t understand. “The question I really had,” says Barbara, “the question I kept asking Jackson was, I wonder why they never mentioned anything to the family. They knew how to contact us.” But, since no one had called in the two decades after Henrietta’s death, instead of continuing to wonder, the Lacks family got on the phone and rang Hopkins themselves. And they did it at an opportune time. Henrietta’s cells, it turned out, had grown out of control. Some scientists thought her relatives were the only people who could help.

Henrietta’s cells were, and still are, some of the strongest cells known to science–they reproduce an entire generation every 24 hours. “If allowed to grow uninhibited,” Howard Jones and his Hopkins colleagues said in 1971, “[HeLa cells] would have taken over the world by this time.” This strength provided a research workhorse to irradiate, poison, and manipulate without inflicting harm; but it also meant research labs were only big enough for one culture: HeLa. Though it took three decades for the Geys to succeed with their efforts to create a human cell line, after their success with HeLa, culturing cells became suspiciously easy. Researchers cultivated tissue samples from their own bodies and the bodies of their families and patients. Most grew successfully. Sure, the samples struggled during the first few weeks, or even months, in culture, but then, suddenly, they flourished. Samples blossomed into full-blown healthy cell lines with the strength of, well, the HeLa cell.

In 1974, a researcher by the name of Walter Nelson-Rees started what everyone called a nasty rumor: HeLa cells, he claimed, had infiltrated the world’s stock of cell cultures. No one wanted to believe him. For almost three decades researchers had done complex experiments on what they thought were breast cells, prostate cells, or placental cells, and suddenly, rumor had it they’d been working with HeLa cells all along. To believe this would be to believe that years of work and millions of dollars had, in essence, been wasted. The truth was, Henrietta’s cells had traveled through the air, on hands, or the tips of pipettes, overpowering any cell cultures they encountered. And researchers had no idea. There was no way to know which cells were growing in the petri dish. And there was no universally accepted test for a cell culture’s identity. To accept or reject the theory that HeLa cells had taken over, researchers wanted more evidence. This required detailed information about the cells’ source. But they knew only the barest facts about Henrietta: She was black, she was a woman, and she was dead.

Though it may have been coincidence, soon after the Lacks children called Hopkins asking about their mother’s cells, letters appeared in their mailboxes. Several Hopkins researchers wondered, the letters said, if the Lacks family would be willing to donate some blood and tissue samples. Soon, a nurse circled Barbara Lacks’s narrow dining room table with needles, blood tubes, and slides, gathering samples from the Lackses. From these donations, researchers would find precious bits of information about Henrietta–like her blood type–that they could use in their attempts to study her cells. “[It was] an elegant piece of work,” Nelson-Rees told a reporter, “by simple Aristotelian class logic and pure applied genetics, you could speculate, to a remarkable extent, as to what Henrietta Lacks’s [genetic makeup] was.” And this is exactly what the researchers did. But if you ask the family, you’ll get a different story. “The doctors tested us to see what was in my mother’s system, was it hereditary,” recalls Henrietta’s son Sonny Lacks. “But that’s all they said. They never got in contact with us again. We contacted them a couple a times, but they said they’d get back at us, then after a while, we just got tired of calling, so everybody just let it go and went back with their lives.” But every now and then, they wonder if they have the gene that killed their mother.

This point of confusion between what the researchers intended to do with the samples and what the participants understood their intentions to be is only one of several elements of the Lackses’ story that points to important ethical questions. Some have yet to find answers. “There are at least two issues that cases like Mrs. Lacks’s raise,” says Ruth Faden, executive director of the Johns Hopkins Bioethics Institute and the Philip Franklin Wagley Professor of Biomedical Ethics. “One is the question of consent, and the other is what, if anything, is morally or legally due to a person if something of commercial value is developed from their cells.”

In terms of informed consent, says Faden, “the Lackses’ story is a sad commentary on how the biomedical research community thought about research in the 1950s. But it was not at all uncommon for physicians to conduct research on patients without their knowledge or consent. That doesn’t make it right. It certainly wasn’t right. It was also unfortunately common.” Since the era when Henrietta walked through the doors of Hopkins, the field of biomedical ethics was born, and with it came regulations about informed consent. Patients now have something like a legal promise that no physician will take samples without permission. It’s the latter issue, the commodification of human body parts, which is still an extremely unsettled area of ethics and law in public policy. And for the Lackses, who don’t all have health insurance or the money to afford it, the issue of commercial value in this case is very unsettled. Unsettled, but with little recourse.

Since the development of the HeLa cells, there’s been an explosion of both scientific and commercial interest in the use of human tissues for research purposes, yet research subjects generally see none of the returns. “The amazing thing,” says Faden, “is that here we are, almost 50 years later, the capacity to develop commercial products from human tissues is dramatically greater now than it was then, and we still haven’t figured out how to handle it. . . . In terms of public policy, we’re real clear that you can’t buy and sell organs, that’s illegal. But you can sell blood. You can sell human eggs and sperm. But you can’t sell your kidney. And apparently, you can’t sell your cells, you give those away. So, nothing is very clear, and there are a lot of deep worries about putting price tags on the human body.” This is partially why the United States has recently launched a Presidential Bioethics Advisory Commission to address this and related issues.

To this day, members of the Lacks family feel they’ve been passed over in the story of the HeLa cells. They know their mother’s cells started a medical revolution and are now bought and sold around the world. They’re pretty sure that someone, somewhere, has profited from their mother’s death. They know that someone wasn’t related to Henrietta. And their experience is not well-known. In cases like these, Faden agrees, a good way to begin addressing this problem is through the telling of a story from which everyone can learn. This story starts with Henrietta and the origin of the HeLa cells: They were not from Helen Lane or Helen Larson, as many publications have mistakenly reported, they were from Henrietta Lacks, wife of David, mother of five.

aka HELEN LANE, aka HELEN LARSEN
http://www.oprah.com/world/Excerpt-From-The-Immortal-Life-of-Henrietta-Lacks_1
adapted from ‘The Immortal Life of Henrietta Lacks’ by Rebecca Skloot / 2010

In 1951, at the age of 30, Henrietta Lacks, the descendant of freed slaves, was diagnosed with cervical cancer—a strangely aggressive type, unlike any her doctor had ever seen. He took a small tissue sample without her knowledge or consent. A scientist put that sample into a test tube, and, though Henrietta died eight months later, her cells—known worldwide as HeLa—are still alive today. They became the first immortal human cell line ever grown in culture and one of the most important tools in medicine: Research on HeLa was vital to the development of the polio vaccine, as well as drugs for treating herpes, leukemia, influenza, hemophilia, and Parkinson’s disease; it helped uncover the secrets of cancer and the effects of the atom bomb, and led to important advances like cloning, in vitro fertilization, and gene mapping. Since 2001 alone, five Nobel Prizes have been awarded for research involving HeLa cells.

There’s no way of knowing exactly how many of Henrietta’s cells are alive today. One scientist estimates that if you could pile all the HeLa cells ever grown onto a scale, they’d weigh more than 50 million metric tons—the equivalent of at least 100 Empire State Buildings.

Today, nearly 60 years after Henrietta’s death, her body lies in an unmarked grave in Clover, Virginia. But her cells are still among the most widely used in labs worldwide—bought and sold by the billions. Though those cells have done wonders for science, Henrietta—whose legacy involves the birth of bioethics and the grim history of experimentation on African-Americans—is all but forgotten.

On January 29, 1951, David Lacks sat behind the wheel of his old Buick, watching the rain fall. He was parked under a towering oak tree outside Johns Hopkins Hospital with three of his children—two still in diapers—waiting for their mother, Henrietta. A few minutes earlier she’d jumped out of the car, pulled her jacket over her head, and scurried into the hospital, past the “colored” bathroom, the only one she was allowed to use. In the next building, under an elegant domed copper roof, a ten-and-a-half-foot marble statue of Jesus stood, arms spread wide, holding court over what was once the main entrance of Hopkins. No one in Henrietta’s family ever saw a Hopkins doctor without visiting the Jesus statue, laying flowers at his feet, saying a prayer, and rubbing his big toe for good luck. But that day Henrietta didn’t stop.

She went straight to the waiting room of the gynecology clinic, a wide-open space, empty but for rows of long, straight-backed benches that looked like church pews. “I got a knot on my womb,” she told the receptionist. “The doctor need to have a look.” For more than a year Henrietta had been telling her closest girlfriends that something didn’t feel right. One night after dinner, she sat on her bed with her cousins Margaret and Sadie and told them, “I got a knot inside me.”

“A what?” Sadie asked. “A knot,” she said. “It hurt somethin’ awful—when that man want to get with me, Sweet Jesus aren’t them but some pains.” When sex first started hurting, she thought it had something to do with baby Deborah, who she’d just given birth to a few weeks earlier, or the bad blood David sometimes brought home after nights with other women—the kind doctors treated with shots of penicillin and heavy metals.

About a week after telling her cousins she thought something was wrong, at the age of 29, Henrietta turned up pregnant with Joe, her fifth child. Sadie and Margaret told Henrietta that the pain probably had something to do with a baby after all. But Henrietta still said no. “It was there before the baby,” she told them. “It’s somethin’ else.” They all stopped talking about the knot, and no one told Henrietta’s husband anything about it. Then, four and a half months after baby Joseph was born, Henrietta went to the bathroom and found blood spotting her underwear when it wasn’t her time of the month.

She filled her bathtub, lowered herself into the warm water, and slowly spread her legs. With the door closed to her children, husband, and cousins, Henrietta slid a finger inside herself and rubbed it across her cervix until she found what she somehow knew she’d find: a hard lump, deep inside, as though someone had lodged a marble the size of her pinkie tip just to the left of the opening to her womb.

Henrietta climbed out of the bathtub, dried herself off, and dressed. Then she told her husband, “You better take me to the doctor. I’m bleeding and it ain’t my time.” Her local doctor took one look inside her, saw the lump, and figured it was a sore from syphilis. But the lump tested negative for syphilis, so he told Henrietta she’d better go to the Johns Hopkins gynecology clinic.

The public wards at Hopkins were filled with patients, most of them black and unable to pay their medical bills. David drove Henrietta nearly 20 miles to get there, not because they preferred it, but because it was the only major hospital for miles that treated black patients. This was the era of Jim Crow—when black people showed up at white-only hospitals, the staff was likely to send them away, even if it meant they might die in the parking lot.

When the nurse called Henrietta from the waiting room, she led her through a single door to a colored-only exam room—one in a long row of rooms divided by clear glass walls that let nurses see from one to the next. Henrietta undressed, wrapped herself in a starched white hospital gown, and lay down on a wooden exam table, waiting for Howard Jones, the gynecologist on duty. When Jones walked into the room, Henrietta told him about the lump. Before examining her, he flipped through her chart:

Breathing difficult since childhood due to recurrent throat infections and deviated septum in patient’s nose. Physician recommended surgical repair. Patient declined. Patient had one toothache for nearly five years. Only anxiety is oldest daughter who is epileptic and can’t talk. Happy household. Well nourished, cooperative. Unexplained vaginal bleeding and blood in urine during last two pregnancies; physician recommended sickle cell test. Patient declined. Been with husband since age 14 and has no liking for sexual intercourse. Patient has asymptomatic neurosyphilis but canceled syphilis treatments, said she felt fine. Two months prior to current visit, after delivery of fifth child, patient had significant blood in urine. Tests showed areas of increased cellular activity in the cervix. Physician recommended diagnostics and referred to specialist for ruling out infection or cancer. Patient canceled appointment. It was no surprise that she hadn’t come back all those times for follow-up. For Henrietta, walking into Hopkins was like entering a foreign country where she didn’t speak the language. She knew about harvesting tobacco and butchering a pig, but she’d never heard the words cervix orbiopsy. She didn’t read or write much, and she hadn’t studied science in school. She, like most black patients, only went to Hopkins when she thought she had no choice.

Henrietta lay back on the table, feet pressed hard in stirrups as she stared at the ceiling. And sure enough, Jones found a lump exactly where she’d said he would. If her cervix was a clock’s face, the lump was at 4 o’clock. He’d seen easily a thousand cervical cancer lesions, but never anything like this: shiny and purple (like “grape Jello,” he wrote later), and so delicate it bled at the slightest touch. Jones cut a small sample and sent it to the pathology lab down the hall for a diagnosis. Then he told Henrietta to go home.

Soon after, Howard Jones dictated notes about Henrietta and her diagnosis: “Her history is interesting in that she had a term delivery here at this hospital, September 19, 1950,” he said. “No note is made in the history at that time or at the six weeks’ return visit that there is any abnormality of the cervix.” Yet here she was, three months later, with a full-fledged tumor. Either her doctors had missed it during her last exams—which seemed impossible—or it had grown at a terrifying rate.

Henrietta Lacks was born Loretta Pleasant in Roanoke, Virginia, on August 1, 1920. No one knows how she became Henrietta. A midwife named Fannie delivered her in a small shack on a dead-end road overlooking a train depot, where hundreds of freight cars came and went each day. Henrietta shared that house with her parents and eight older siblings until 1924, when her mother, Eliza Lacks Pleasant, died giving birth to her tenth child.

Henrietta’s father, Johnny Pleasant, was a squat man who hobbled around on a cane he often hit people with. Johnny didn’t have the patience for raising children, so when Eliza died, he took them all back to Clover, Virginia, where his family still farmed the tobacco fields their ancestors had worked as slaves. No one in Clover could take all ten children, so relatives divided them up—one with this cousin, one with that aunt. Henrietta ended up with her grandfather, Tommy Lacks.

Tommy lived in what everyone called the home-house, a four-room wooden cabin that once served as slave quarters, with plank floors, gas lanterns, and water Henrietta hauled up a long hill from the creek. The home-house stood on a hillside where wind whipped through cracks in the walls. The air inside stayed so cool that when relatives died, the family kept their corpses in the front hallway for days so people could visit and pay respects. Then they buried them in the cemetery out back.

Henrietta’s grandfather was already raising another grandchild that one of his daughters left behind after delivering him on the home-house floor. That child’s name was David Lacks, but everyone called him Day, because in the Lacks country drawl, house sounds like hyse, and David sounds like Day. No one could have guessed Henrietta would spend the rest of her life with Day—first as a cousin growing up in their grandfather’s home, then as his wife.

Like most young Lackses, Day didn’t finish school: He stopped in the fourth grade because the family needed him to work the tobacco fields. But Henrietta stayed until the sixth grade. During the school year, after taking care of the garden and livestock each morning, she’d walk two miles—past the white school where children threw rocks and taunted her—to the colored school, a three-room wooden farmhouse hidden under tall shade trees.

At nightfall the Lacks cousins built fires with pieces of old shoes to keep the mosquitoes away, and watched the stars from beneath the big oak tree where they’d hung a rope to swing from. They played tag, ring-around-the-rosy, and hopscotch, and danced around the field singing until Grandpa Tommy yelled for everyone to go to bed.

Henrietta and Day had been sharing a bedroom since she was 4 and he was 9, so what happened next didn’t surprise anyone: They started having children together. Their son Lawrence was born just months after Henrietta’s 14th birthday; his sister, Lucile Elsie Pleasant, came along four years later. They were both born on the floor of the home-house like their father, grandmother, and grandfather before them. People wouldn’t use words like epilepsy, mental retardation, or neurosyphilis to describe Elsie’s condition until years later. To the folks in Clover, she was just simple. Touched.

Henrietta and Day married alone at their preacher’s house on April 10, 1941. She was 20; he was 25. They didn’t go on a honeymoon because there was too much work to do, and no money for travel. Henrietta and Day were lucky if they sold enough tobacco each season to feed the family and plant the next crop. So after their wedding, Day went back to gripping the splintered ends of his old wooden plow as Henrietta followed close behind, pushing a homemade wheelbarrow and dropping tobacco seedlings into holes in the freshly turned red dirt.

A few months later, Day moved north to Turner Station, a small black community outside Baltimore where he’d gotten a job working in a shipyard. Henrietta stayed behind to care for the children and the tobacco until Day made enough money for a house and three tickets north. Soon, with a child on each side, Henrietta boarded a coal-fueled train from the small wooden depot at the end of Clover’s Main Street. She left the tobacco fields of her youth and the hundred-year-old oak tree that shaded her from the sun on so many hot afternoons. At the age of 21, she stared through the train window at rolling hills and wide-open bodies of water for the first time, heading toward a new life. After her visit to Hopkins, Henrietta went back to her usual routine, cleaning and cooking for her husband, their children, and the many cousins she fed each day. Less than a week later, Jones got her biopsy results from the pathology lab: “epidermoid carcinoma of the cervix, Stage I.” Translation: cervical cancer.

Cervical carcinomas are divided into two types: invasive carcinomas, which have penetrated the surface of the cervix, and noninvasive carcinomas, which haven’t. The noninvasive type is sometimes called “sugar-icing carcinoma,” because it grows in a smooth layered sheet across the surface of the cervix, but its official name is carcinoma in situ, which derives from the Latin for “cancer in its original place.”

In 1951 most doctors in the field believed that invasive carcinoma was deadly, and carcinoma in situ wasn’t. So they hardly treated it. But Richard Wesley TeLinde, head of gynecology at Hopkins and one of the top cervical cancer experts in the country, disagreed—he believed carcinoma in situ was simply an early stage of invasive carcinoma that, left untreated, eventually became deadly. So he treated it aggressively, often removing the cervix, uterus, and most of the vagina. He argued that this would drastically reduce cervical cancer deaths, but his critics called it extreme and unnecessary.

TeLinde thought that if he could find a way to grow living samples from normal cervical tissue and both types of cancerous tissue—something never done before—he could compare all three. If he could prove that carcinoma in situ and invasive carcinoma looked and behaved similarly in the laboratory, he could end the debate, showing that he’d been right all along, and doctors who ignored him were killing their patients. So he called George Gey (pronounced “guy”), head of tissue culture research at Hopkins.

Gey and his wife, Margaret, had spent the last three decades working to grow malignant cells outside the body, hoping to use them to find cancer’s cause and cure. But most of the cells died quickly, and the few that survived hardly grew at all. The Geys were determined to grow the first immortal human cells: a continuously dividing line of cells all descended from one original sample, cells that would constantly replenish themselves and never die. They didn’t care what kind of tissue they used, as long as it came from a person.

So when TeLinde offered Gey a supply of cervical cancer tissue in exchange for trying to grow some cells, Gey didn’t hesitate. And TeLinde began collecting samples from any woman who happened to walk into Hopkins with cervical cancer. Including Henrietta.

Jones called Henrietta on February 5, 1951, after getting her biopsy report back from the lab, and told her the tumor was malignant. Henrietta didn’t tell anyone what Jones said, and no one asked. She simply went on with her day as if nothing had happened, which was just like her—no sense upsetting anyone over something she could just deal with herself.

The next morning Henrietta climbed from the Buick outside Hopkins again, telling Day and the children not to worry. “Ain’t nothin’ serious wrong,” she said. “Doctor’s gonna fix me right up.” Henrietta went straight to the admissions desk and told the receptionist she was there for her treatment. Then she signed a form with the words operation permit at the top of the page. It said:

I hereby give consent to the staff of The Johns Hopkins Hospital to perform any operative procedures and under any anaesthetic either local or general that they may deem necessary in the proper surgical care and treatment of: ______________________________.

Henrietta printed her name in the blank space. A witness with illegible handwriting signed a line at the bottom of the form, and Henrietta signed another. Then she followed a nurse down a long hallway into the ward for colored women, where Howard Jones and several other white physicians ran more tests than she’d had in her entire life. They checked her urine, her blood, her lungs. They stuck tubes in her bladder and nose.

Henrietta’s tumor was the invasive type, and like hospitals nationwide, Hopkins treated all invasive cervical carcinomas with radium, a white radioactive metal that glows an eerie blue. So the morning of Henrietta’s first treatment, a taxi driver picked up a doctor’s bag filled with thin glass tubes of radium from a clinic across town. The tubes were tucked into individual slots inside small canvas pouches hand-sewn by a local Baltimore woman. One nurse placed the pouches on a stainless steel tray. Another wheeled Henrietta into the small colored-only operating room, with stainless steel tables, huge glaring lights, and an all-white medical staff dressed in white gowns, hats, masks, and gloves.

With Henrietta unconscious on the operating table in the center of the room, her feet in stirrups, the surgeon on duty, Lawrence Wharton Jr., sat on a stool between her legs. He peered inside Henrietta, dilated her cervix, and prepared to treat her tumor. But first—though no one had told Henrietta that TeLinde was collecting samples or asked if she wanted to be a donor—Wharton picked up a sharp knife and shaved two dime-size pieces of tissue from Henrietta’s cervix: one from her tumor, and one from the healthy cervical tissue nearby. Then he placed the samples in a glass dish.

Wharton slipped a tube filled with radium inside Henrietta’s cervix, and sewed it in place. He then sewed a pouch filled with radium to the outer surface of her cervix and packed another against it. He slid several rolls of gauze inside her vagina to help keep the radium in place, then threaded a catheter into her bladder so she could urinate without disturbing the treatment. When Wharton finished, a nurse wheeled Henrietta back into the ward, and a resident took the dish with the samples to Gey’s lab, as he’d done many times before. Gey still got excited at moments like this, but everyone else in his lab saw Henrietta’s sample as something tedious—the latest of what felt like countless samples that scientists and lab technicians had been trying and failing to grow for years. Gey’s 21-year-old assistant, Mary Kubicek, sat eating a tuna salad sandwich at a long stone culture bench that doubled as a break table. She and Margaret and the other women in the Gey lab spent many hours there, all in nearly identical cat’s-eye glasses with fat dark frames and thick lenses, their hair pulled back in tight buns. “I’m putting a new sample in your cubicle,” Gey told Mary.

She pretended not to notice. “Not again,” she thought, and kept eating her sandwich. Mary knew she shouldn’t wait—every moment those cells sat in the dish made it more likely they’d die. But they always died anyway. “Why bother?” she thought. At that point, there were many obstacles to growing cells successfully. For starters, no one knew exactly what nutrients they needed to survive or how best to supply them. But the biggest problem facing cell culture was contamination. Bacteria and a host of other microorganisms could find their way into cultures—from people’s unwashed hands, their breath, and dust particles floating through the air—and destroy them. Margaret Gey had been trained as a surgical nurse, which meant sterility was her specialty—it was key to preventing deadly infections in patients in the operating room.

Margaret patrolled the lab, arms crossed, leaning over technicians’ shoulders as they worked, inspecting glassware for spots or smudges. Mary followed Margaret’s sterilizing rules meticulously to avoid her wrath. Only then did she pick up the pieces of Henrietta’s cervix—forceps in one hand, scalpel in the other—and carefully slice them into one-millimeter squares. She sucked each square into a pipette, and dropped them one at a time onto chicken-blood clots she’d placed at the bottom of dozens of test tubes. She covered each clot with several drops of culture medium, plugged the tubes with rubber stoppers, and wrote “HeLa,” for Henrietta and Lacks, in big black letters on the side of each tube. Then she put them in an incubator.

For the next few days, Mary started each morning with her usual sterilization drill. She’d peer into all the incubating tubes, laughing to herself and thinking, “Nothing’s happening.” “Big surprise.” Then she saw what looked like little rings of fried egg white around the clots at the bottom of each tube. The cells were growing, but Mary didn’t think much of it—other cells had survived for a while in the lab. But Henrietta’s cells weren’t merely surviving—they were growing with mythological intensity. By the next morning, they’d doubled. Mary divided the contents of each tube in two, giving them room to grow, and soon she was dividing them into four tubes, then six. Henrietta’s cells grew to fill as much space as Mary gave them. Still, Gey wasn’t ready to celebrate. “The cells could die any minute,” he told Mary. But they didn’t. The cells kept growing like nothing anyone had seen, doubling their numbers every 24 hours, accumulating by the millions. “Spreading like crabgrass!” Margaret said. As long as they had food and warmth, Henrietta’s cancer cells seemed unstoppable. Soon, George told a few of his closest colleagues that he thought his lab might have grown the first immortal human cells. To which they replied, Can I have some? And George said yes.

the HENRIETTA LACKS FOUNDATION
http://rebeccaskloot.com/book-special-features/henrietta-lacks-foundation/
http://www.flickr.com/photos/42653706@N00/sets/72157623243930457/
http://www.citypaper.com/news/story.asp?id=3426&p=1
The Life After Death of Henrietta Lacks
by Van Smith / 4.17.2002

In the 27 years since the Lacks family serendipitously learned of Henrietta’s unwitting contribution, little has been done to honor her. “Henrietta Lacks Day” is celebrated in Turner Station each year on Feb. 1. In 1996, prompted by Atlanta’s Morehouse College, that city’s mayor proclaimed Oct. 11 Henrietta Lacks Day. The following year, Congress passed a resolution in her memory sponsored by Rep. Robert Ehrlich (R-Md.), whose 2nd District includes Turner Station, and the British Broadcasting Corp. produced a documentary on her remarkable story. Beyond that, however, virtually nothing has been done to celebrate Lacks’ contribution–not even by Hopkins, which gained immeasurable prestige from Gey’s work with her cells.

Lacks-Pullum is bitter about this. “We never knew they took her cells, and people done got filthy rich [from HeLa-based research], but we don’t get a dime,” she says. The family can’t afford a reputable lawyer to press its case for some financial stake in the work. She says she has appealed to Hopkins for help, and “all they do is pat me on my shoulder and put me out the door.”

Hopkins spokesperson Gary Stephenson is quick to point out that Hopkins never sold HeLa, so it didn’t make money from Henrietta’s contribution. Still, he says, “there are people here who would like something done, and I’m hoping that at some point something will be done in a formal way to note her very, very important contribution.” Lacks-Pullum shares those hopes, but she is pessimistic. “Hopkins,” she says, “they don’t care.”

Lost in the acrimony over ethical and financial issues stemming from Henrietta Lacks’ cells, though, is Henrietta Lacks herself. A descendant of slaves and slaveholders, she grew up farming the same land on which her forebears toiled–and that her relatives still farm today. As part of an aspiring black middle class with rural roots, she left her childhood home to join a migration to Baltimore, where Bethlehem Steel was eager to hire hard workers from the country. She was in the midst of realizing an American dream when her life was cut short. And her cells helped realize society’s larger dreams for health and knowledge. As such, she’s been called a hero, a martyr, even a saint. But during her life, as Ehrlich said to his colleagues in Congress, Henrietta Lacks “was known as pleasant and smiling, and always willing the lend a helping hand.” That she did, in more ways than she ever knew.

Trying to find Henrietta Lacks’ grave is a lesson in irony. She is now a world-famous woman, yet her body rests in an unmarked plot in a family burial ground next to her childhood house, now long abandoned and close to falling down. No one, not even her relatives, knows precisely which grave plot is hers.

The search starts in Clover, Va., where Henrietta grew up farming tobacco on her family’s land. It’s a small town of about 200 people in a region southwest of Richmond known as Southside. The first stop–Clover Cemetery, on the outskirts of town–is fruitless; plenty of Lackses but no Henrietta. A quick visit to the post office yields a clue, offered with matter-of-fact bluntness by a man at the copy machine. “What did you say her name was? Henrietta Lacks? Was she black or white?” Hearing the answer, he continues: “The cemeteries you can see from the road, they’re mostly for whites. You got to go back off the road to get to the black cemetery. So go back up that road and make a right on Lacks Town Road. A lot of blacks live up there. You can’t see the cemetery from the road, so you’ll have to ask people. But someone up there should be able to help you.”

Lacks Town is not really a town but a tiny community of relatives living along a one-mile dead-end road. Trailers, shacks, old log homes, and a ranch house or two are surrounded by small plots of farmland, barns, and machinery, with woods filling in the gaps. It’s part of Clover, but Lacks Town clearly has a distinct identity. “They stick together down there,” a local woman from the other side of Clover explains later.

In short order, someone helps me out: Otis Ferrell Jr., a young man, probably in his 30s, who immediately recognizes the proffered name. “Oh, the lady with the cancer cells,” he exclaims. “Yeah, she’s buried up there.” Ferrell points to the top of a hill in a tree-cluttered cow pasture, gesturing toward two downed trees, clearly visible from the road, giant gray hulks lying on their sides next to a large rusty-roofed abandoned building. “That’s where they whupped the slaves,” he says candidly (though falsely, his elders later explain). “And one day the trees just came down. The cemetery is just past them and that old house. Yeah, she’s up there, but the grave’s unmarked. Uncle Clifton knows which one it is.”

Clifton Garrett is Henrietta Lacks’ cousin, now in his 80s. He lives nearby, about a quarter mile down from Lacks Town Road, and he’s burning the leaves in his yard while heating up the barbecue grill. “What, you going to build a memorial?” he retorts when asked if he knows which grave is Henrietta’s, in a tone that suggests it’s high time someone did. As smoke and embers billow around, he says he’s not exactly sure which grave is hers. “I know where her mother is buried,” he says. “She must be close by.”

Garrett gives a poignant tour of the land where Henrietta Lacks is buried. The property, he says, belonged to Tommy Lacks, who, along with his two brothers, was a patriarch of Clover’s African-American Lackses. Tommy was Henrietta’s grandfather, and he cared for her and her siblings after their mother died.

“Henrietta was raised up in that house, and her mother was born in it,” Garrett says as he strolls past the dilapidated building. “It’s called the Old Home House. It was built in slave times. Hadn’t nobody lived in this house in many years. Ain’t nobody to take care of it, and it just started falling down. But back then, they kept everything clean. When we was children, we played together here. There was a henhouse, an icehouse, a corn silo, a stable. But now there’s nothing left of anything.”

It’s hard to say how many ancestors are laid to rest in the burial ground; many of the graves are unmarked, and the sites have long been trampled by cows. “They knocked the rocks away when they came in and cleaned up with a bulldozer,” Garrett explains. “This was a big family,” he continues. “Everybody in this cemetery is related one way or another. When they die, they bring them here because this is the family cemetery.”

Henrietta’s mother, Eliza Pleasant, was buried here in 1924 after she died in Roanoke, Va., giving birth to her 10th child. “I remember when they brought her here,” Garrett says. “I was only about 2 or 3 years old, but I remember it. She had a coffin and they opened it, and a little light in the coffin came on. My memory’s good.”

Eliza’s husband, John Randall Pleasant, worked for the railroad in Roanoke, where Henrietta was born in 1920. When Eliza passed away, John moved their children back to the Old Home House to be raised by their grandfather, Tommy. Eliza’s grave has a headstone: eliza, wife of j.r. pleasant. jul 12, 1886.-oct. 28, 1924. gone but not forgotten. Indentations in the earth indicate five other unmarked graves in two rows behind the headstone. One of them is John’s. One of them is Henrietta’s. Neither Garrett nor any other family members I was able to find in Clover or in Baltimore knows which is which.

Clifton Garrett did know Henrietta, though, and remembers her fondly. “She was just an average child. A nice friendly girl and everything. That’s all I can tell you. We would play out in the yard, go to school.” Going to Clover School, which was for black children and offered instruction through seventh grade, meant a two-mile walk, taking shortcuts through fields, forests, and backyards–and right past Clover Elementary School, then white-only. Garrett still remembers the names of his teachers and the school’s principal, and that the principal’s son was killed during the attack on Pearl Harbor.

“Henrietta helped on the farm until she went up to Baltimore,” Garrett says. That happened in 1943, a short while after her husband moved there for work for Beth Steel. Garrett moved north too, for a job at Beth Steel making nails in the wire mill. “After I got grown, then I went up there. A lot of people from around here did. There were company barracks to stay in, so we used to live in Sparrows Point until we moved to Turner Station. Henrietta’s husband, David, worked on the shipyard. He was a hard worker. And Henrietta, she was a nice lady. Nice as she could be. Very friendly. Very friendly, she was.”

The dredged-up memories lead Garrett to muse aloud, about how some part of his cousin still thrives. “Her cells are still living,” he says, gazing at the ground near her grave. He shakes his head. “She’s dead, but her cells are still living,” he says again, and then is silent.

Gary Lacks, Henrietta’s nephew, cares for his elderly mother, Gladys Lacks, in Lacks Town. Like many in Clover, he’s a religious man, which gives him a unique perspective on his aunt’s story. “I go back to the Book of Genesis when God created man,” he says, his voice quickly rising in a crescendo of fervor. “He created him to live forever, really, but man ate up what God told him he couldn’t eat, and a process of death took over his body. But the possibility was in man that he could live–and if he could live, then his parts could live.” In Gary Lacks’ eyes, his aunt’s immortal cells are realizing God’s original intent for the human race.

Roberta Brooks’ view of Henrietta is more down to earth. “I worked in the field with Henrietta and Tommy and most of the Lacks Town folks when I was young,” recalls Brooks, another relative who lives near Clover. “I used to hang around more at the Old Home House than at my own house. We’d walk six miles to play together. We used to play on the creek, be teenagers together. Singing, playing horseshoes and ball games, shucking corn. There was lots to do. Children today come home and watch TV, but we had everything to do.”

As Brooks’ contemporaries got older, many took jobs in Baltimore. “A bunch of them in Lacks Town were working at Sparrows Point,” she says. “They were good jobs, about the best jobs paying, and they hired you quick there. They’d stay at the barracks, work all week, then return back to Clover for the weekend. And a lot of them stayed–and are living there still.”

Then Brooks touches on a sensitive subject–how Clover’s black Lackses and white Lackses are related. “When you get over in Lacks Town, oh, you don’t know who’s who,” she says. “It’s a big screwed-up thing. All the white Lackses and all the black Lackses, they’re all the same people. We all came up like family together, worked together and everything. And nobody married. Had bunches of children here and there and never married. It’s how it is. It’s a mess. And it’s just so deep, you can’t separate it.” The family history informs Brooks’ perspective on race relations: “That why I say, we’re all just human beings. Not black, not white. Just human beings. So it’s all about respect. That’s it. Respect.”

Gladys Lacks suffered a stroke last year. Her mind and eyes are as clear as day, but she has difficulty communicating. When it comes to the family’s tangled history, though, her two words speak volumes. “Master Ben,” she says, and leaves it at that. Records at the Halifax County courthouse offer further explanation. Ben Lacks and Albert Lacks, who were white (and related, although the African-American Lackses no longer recall how), owned the land Henrietta’s family worked and her descendants work still. When her grandfather, Tommy, married in 1903, he listed his parents as “Albert and Maria.” Tommy’s brother, James Lacks, married twice; the first time, he lists “Ben and Maria” as his parents, but the second time his parents are listed as “Albert and Maria.” Both white Lacks willed land to their black children. Albert’s 1888 will gave 10 acres each “from what is known as the Home Tract” to Tommy, James, and their brother Peter; Ben’s will of 1907 gave more land to Tommy and James.

“All of them hooked up together. They’re kin,” says William Morton, Peter Lacks’ grandson. Morton lives near Clover, having moved back after several decades in Baltimore, working at Sparrows Point (“Practically all of these fellows around here worked on the Point,” he says) and later for Morgan State University. Although records do not indicate Peter’s parentage, Morton says his grandfather “got land because he was kin to the owners.” Among Clover’s Lackses, he says, echoing his cousin Roberta Brooks, “that’s just the way it is.”

In Deborah Lacks-Pullum’s estimation, her parent’s middle-class aspirations in coming to Baltimore were realized. “We weren’t poor,” she says. “We were living comfortably.” Henrietta held down the home on New Pittsburgh Avenue in Turner Station while her husband, David, earned decent wages at the shipyard. Folks from Clover, in town to start jobs on the Point, would stay over until they could find their own housing. Before he came to Baltimore, David Lacks “was the hardest working man in Clover, working 15 acres by himself,” Lacks-Pullum says. Once here, he and Henrietta enjoyed a sterling reputation in the community as gracious, generous people.

“The door was always open for new arrivals from Clover,” says Barbara Wyche, a Morgan State lecturer who has dedicated much time and effort to studying Henrietta Lacks. The link to the family’s Virginia roots stayed strong, Wyche says–“Henrietta went home every summer and farmed.” It’s still strong: Deborah Lacks-Pullum frequently visits relatives in Clover.

After Henrietta died, David Lacks raised the children–Lawrence, Elsie (who died at the age of 15, a few years after Henrietta passed away), David Jr., Deborah, and Zakariyya–by himself, just as Henrietta’s grandfather had done after his wife died. They remained a happy family, though they missed their mother.

The news that Henrietta’s cells had been taken and used for research without their knowledge, though, cast a cloud over the family. David Lacks, Henrietta’s husband, doesn’t even like to talk about it. “He’s tired of talking–it’s the same thing, over and over,” she says. By default, Lacks-Pullum has become the family spokesperson when it comes to Henrietta–and she herself is getting weary. “I’m just tired of my family getting walked over,” she says. “It hurts.”

Recognition has been slow in coming, but the future holds some promise. Rebecca Skloot, a Pittsburgh-based science writer, has spent the last three years researching and writing a comprehensive book, HeLa: The Immortal Cells of Henrietta Lacks, that’s due to be published by Times Books next year. And Charlene Gilbert, a Washington, D.C.-based filmmaker, is hard at work on a documentary titled Colored Bodies: Henrietta Lacks and the HeLa Cells.

Back in Clover, Gary Lacks is roaming the Old Home House, trying to avoid the holes in the floorboards. He’s explaining how the house and the family burial ground have fallen into disrepair. “There’s no one to keep it up,” he says. “People only think about it when they come up here to bury someone, then they forget about it until the next time. They let the cows come in, and the cows keep it clean, keep the bushes down.”

It wouldn’t take much money to save the Old Home House, he says, and even less to keep up the cemetery, find Henrietta’s grave, give it a headstone. But people don’t have much money in Lacks Town. He hopes that with the attention generated by the book and the film–and with all the millions of dollars at Johns Hopkins’ disposal–resources will become available to give his aunt’s final resting place the honor it deserves. He’s hopeful, but he isn’t holding his breath.

LIVING TO 1000
http://en.wikipedia.org/wiki/Aubrey_de_Grey
http://news.bbc.co.uk/2/hi/uk_news/4003063.stm
‘We will be able to live to 1,000’
BY Dr Aubrey de Grey  /  University of Cambridge  /  3 December, 2004

Life expectancy is increasing in the developed world. But Cambridge University geneticist Aubrey de Grey believes it will soon extend dramatically to 1,000. Here, he explains why. Ageing is a physical phenomenon happening to our bodies, so at some point in the future, as medicine becomes more and more powerful, we will inevitably be able to address ageing just as effectively as we address many diseases today. I claim that we are close to that point because of the SENS (Strategies for Engineered Negligible Senescence) project to prevent and cure ageing. It is not just an idea: it’s a very detailed plan to repair all the types of molecular and cellular damage that happen to us over time. And each method to do this is either already working in a preliminary form (in clinical trials) or is based on technologies that already exist and just need to be combined.

This means that all parts of the project should be fully working in mice within just 10 years and we might take only another 10 years to get them all working in humans. When we get these therapies, we will no longer all get frail and decrepit and dependent as we get older, and eventually succumb to the innumerable ghastly progressive diseases of old age. We will still die, of course – from crossing the road carelessly, being bitten by snakes, catching a new flu variant etcetera – but not in the drawn-out way in which most of us die at present.

So, will this happen in time for some people alive today? Probably. Since these therapies repair accumulated damage, they are applicable to people in middle age or older who have a fair amount of that damage. I think the first person to live to 1,000 might be 60 already. It is very complicated, because ageing is. There are seven major types of molecular and cellular damage that eventually become bad for us – including cells being lost without replacement and mutations in our chromosomes. Each of these things is potentially fixable by technology that either already exists or is in active development.

‘Youthful not frail’
The length of life will be much more variable than now, when most people die at a narrow range of ages (65 to 90 or so), because people won’t be getting frailer as time passes. The average age will be in the region of a few thousand years. These numbers are guesses, of course, but they’re guided by the rate at which the young die these days. If you are a reasonably risk-aware teenager today in an affluent, non-violent neighbourhood, you have a risk of dying in the next year of well under one in 1,000, which means that if you stayed that way forever you would have a 50/50 chance of living to over 1,000. And remember, none of that time would be lived in frailty and debility and dependence – you would be youthful, both physically and mentally, right up to the day you mis-time the speed of that oncoming lorry.

Should we cure ageing?
Curing ageing will change society in innumerable ways. Some people are so scared of this that they think we should accept ageing as it is. I think that is diabolical – it says we should deny people the right to life. The right to choose to live or to die is the most fundamental right there is; conversely, the duty to give others that opportunity to the best of our ability is the most fundamental duty there is. There is no difference between saving lives and extending lives, because in both cases we are giving people the chance of more life. To say that we shouldn’t cure ageing is ageism, saying that old people are unworthy of medical care.

Playing God?
People also say we will get terribly bored but I say we will have the resources to improve everyone’s ability to get the most out of life. People with a good education and the time to use it never get bored today and can’t imagine ever running out of new things they’d like to do. And finally some people are worried that it would mean playing God and going against nature. But it’s unnatural for us to accept the world as we find it. Ever since we invented fire and the wheel, we’ve been demonstrating both our ability and our inherent desire to fix things that we don’t like about ourselves and our environment. We would be going against that most fundamental aspect of what it is to be human if we decided that something so horrible as everyone getting frail and decrepit and dependent was something we should live with forever. If changing our world is playing God, it is just one more way in which God made us in His image.

CONTACT
Aubrey de Grey
http://www.sens.org/index.php?pagename=mj_about_who_founders#adg
http://www.ted.com/speakers/aubrey_de_grey.html
email : aubrey [at] sens [dot] org

LONGEVITY ESCAPE VELOCITY
http://www.edge.org/3rd_culture/degrey07/degrey07_index.html
Bootstrapping Our Way To An Ageless Future
BY Aubrey de Grey / 2007

An important fact is that the therapies we develop in a decade or so in mice, and those that may come only a decade or two later for humans, will not be perfect. Other things being equal, there will be a residual accumulation of damage within our bodies, however frequently and thoroughly we apply these therapies, and we will eventually experience age-related decline and death just as now, only at a greater age. Probably not all that much greater either—probably only 30-50 years older than today. But other things won’t be equal, and I’m going to explain why not—and why, as you may already know from other sources, I expect many people alive today to live to 1000 years of age and to avoid age-related health problems even at that age. I’ll start by describing why it’s unrealistic to expect these therapies to be perfect.

Evolution didn’t leave notes
The body is a machine, and that’s both why it ages and why it can in principle be maintained. I have made a comparison with vintage cars, which are kept fully functional even 100 years after they were built, using the same maintenance technologies that kept them going 50 years ago when they were already far older than they were ever designed to be. More complex machines can also be kept going indefinitely, though the expense and expertise involved may mean that this never happens in practice because replacing the machine is a reasonable alternative. This sounds very much like a reason to suppose that the therapies we develop to stave off aging for a few decades will indeed be enough to stave it off indefinitely.

But actually that’s overoptimistic. All we can reliably infer from a comparison with man-made machines is that a truly comprehensive panel of therapies, which truly repairs everything that goes wrong with us as a result of aging, is possible in principle—not that it is foreseeable. And in fact we can see that actually one thing about them is very unlike maintenance of a man-made machine: these therapies strive to minimally alter metabolism itself, and target only the initially inert side-effects of metabolism, whereas machine maintenance may involve adding extra things to the machinery itself (to the fuel or the oil of a car, for example). We can get away with this sort of invasive maintenance of man-made machines because we (well, some of us!) know how they work right down to the last detail, so we can be adequately sure that our intervention won’t have unforeseen side-effects. With the body—even the body of a mouse—we are still profoundly ignorant of the details, so we have to sidestep our ignorance by interfering as little as possible.

What that means for efficacy of therapies is that, as we fix more and more aspects of aging, you can bet that new aspects will be unmasked. These new things will not be fatal at a currently normal age, because if they were, we’d know about them already. But they’ll be fatal eventually, unless we work out how to fix them too. Even within each existing category, there are some subcategories that will be easier to fix than others. For example, there are lots of chemically distinct cross-links responsible for stiffening our arteries; some of them may be broken with ALT-711 and related molecules, but others will surely need more sophisticated agents that have not yet been developed. Another example: obviating mitochondrial DNA by putting modified copies of it into the cell’s chromosomes requires gene therapy, and thus far we have no gene therapy delivery system (“vector”) that can safely get into all cells, so for the foreseeable future we’ll probably only be able to protect a subset of cells from mtDNA mutations. Much better vectors will be needed if we are to reach all cells.

In practice, therefore, therapies that rejuvenate 60-year-olds by 20 years will not work so well the second time around. When the therapies are applied for the first time, the people receiving them will have 60 years of “easy” damage (the types that the therapies can remove) and also 60 years of “difficult” damage. But by the time beneficiaries of these therapies have returned to biologically 60 (which, let’s presume, will happen when they’re chronologically about 80), the damage their bodies contain will consist of 20 years of “easy” damage and 80 years of “difficult” damage. Thus, the therapies will only rejuvenate them by a much smaller amount, say ten years. So they’ll have to come back sooner for the third treatment, but that will benefit them even less… and very soon, just like Achilles catching up with the tortoise in Zeno’s paradox, aging will get the better of them. An extremely counterintuitive fact is that, even though it will be much harder to double a middle-aged human’s remaining lifespan than a middle-aged mouse’s, multiplying that remaining lifespan by much larger factors—ten or 30, say—will be much easier in humans than in mice.

The two-speed pace of technology
I’m now going to switch briefly from science to the history of science, or more precisely the history of technology. It was well before recorded history that people began to take an interest in the possibility of flying: indeed, this may be a desire almost as ancient as the desire to live forever. Yet, with the notable but sadly unreproduced exception of Daedalus and Icarus, no success in this area was achieved until about a century ago. (If we count balloons then we must double that, but really only airships—balloons that can control their direction of travel reasonably well—should be counted, and they only emerged at around the same time as the aircraft.) Throughout the previous few centuries, engineers from Leonardo on devised ways to achieve controlled powered flight, and we must presume that they believed their designs to be only a few decades (at most) from realisation. But they were wrong.

Ever since the Wright brothers flew at Kitty Hawk, however, things have been curiously different. Having mastered the basics, aviation engineers seem to have progressed to ever greater heights (literally as well as metaphorically!) at an almost serenely smooth pace. To pick a representative selection of milestones: Lindbergh flew the Atlantic 24 years after the first powered flight occurred, the first commercial jetliner (the Comet) debuted 22 years after that, and the first supersonic airliner (Concorde) followed after a further 20 years.
This stark contrast between fundamental breakthroughs and incremental refinements of those breakthroughs is, I would contend, typical of the history of technological fields. Further, I would argue that it’s not surprising: both psychologically and scientifically, bigger advances are harder to estimate the difficulty of.

I mention all this, of course, because of what it tells us about the likely future progress of life extension therapies. Just as people were wrong for centuries about how hard it is to fly but eventually cracked it, we’ve been wrong since time immemorial about how hard aging is to combat but we’ll eventually crack it too. But just as people have been pretty reliably correct about how to make better and better aircraft once they had the first one, we can expect to be pretty reliably correct about how to repair the damage of aging more and more comprehensively once we can do it a little. That’s not to say it’ll be easy, though. It’ll take time, just as it took time to get from the Wright Flyer to Concorde. And that is why, if you want to live to 1000, you can count yourself lucky that you’re a human and not a mouse. Let me take you through the scenario, step by step.

Suppose we develop Robust Mouse Rejuvenation in 2016, and we take a few dozen two-year-old mice and duly treble their one-year remaining lifespans. That will mean that, rather than dying in 2017 as they otherwise would, they’ll die in 2019. Well, maybe not—in particular, not if we can develop better therapies by 2018 that re-treble their remaining lifespan (which will by now be down to one year again). But remember, they’ll be harder to repair the second time: their overall damage level may be the same as before they received the first therapies, but a higher proportion of that damage will be of types that those first therapies can’t fix. So we’ll only be able to achieve that re-trebling if the therapies we have available by 2018 are considerably more powerful than those that we had in 2016. And to be honest, the chance that we’ll improve the relevant therapies that much in only two years is really pretty slim. In fact, the likely amount of progress in just two years is so small that it might as well be considered zero. Thus, our murine heroes will indeed die in 2019 (or 2020 at best), despite our best efforts.

But now, suppose we develop Robust Human Rejuvenation in 2031, and we take a few dozen 60-year-old humans and duly double their 30-year remaining lifespans. By the time they come back in (say) 2051, biologically 60 again but chronologically 80, they’ll need better therapies, just as the mice did in 2018. But luckily for them, we’ll have had not two but twenty years to improve the therapies. And 20 years is a very respectable period of time in technology—long enough, in fact, that we will with very high probability have succeeded in developing sufficient improvements to the 2031 therapies so that those 80-year-olds can indeed be restored from biologically 60 to biologically 40, or even a little younger, despite their enrichment (relative to 2031) in harder-to-repair types of damage. So unlike the mice, these humans will have just as many years (20 or more) of youth before they need third-generation treatments as they did before the second. And so on…

Longevity Escape Velocity
The key conclusion of the logic I’ve set out above is that there is a threshold rate of biomedical progress that will allow us to stave off aging indefinitely, and that that rate is implausible for mice but entirely plausible for humans. If we can make rejuvenation therapies work well enough to give us time to make then work better, that will give us enough additional time to make them work better still, which will … you get the idea. This will allow us to escape age-related decline indefinitely, however old we become in purely chronological terms. I think the term “longevity escape velocity” (LEV) sums that up pretty well.

One feature of LEV that’s worth pointing out is that we can accumulate lead-time. What I mean is that if we have a period in which we improve the therapies faster than we need to, that will allow us to have a subsequent period in which we don’t improve them so fast. It’s only the average rate of improvement, starting from the arrival of the first therapies that give us just 20 or 30 extra years, that needs to stay above the LEV threshold.

In case you’re having trouble assimilating all this, let me describe it in terms of the physical state of the body. Throughout this book, I’ve been discussing aging as the accumulation of molecular and cellular “damage” of various types, and I’ve highlighted the fact that a modest quantity of damage is no problem—metabolism just works around it, in the same way that a household only needs to put out the garbage once a week, not every hour. In those terms, the attainment and maintenance of escape velocity simply means that our best therapies must improve fast enough to outweigh the progressive shift in the composition of our aging damage to more repair-resistant forms, as the forms that are easier to repair are progressively eliminated by our therapies. If we can do this, the total amount of damage in each category can be kept permanently below the level that initiates functional decline.

Another, perhaps simpler, way of looking at this is to consider the analogy with literal escape velocity, i.e. the overcoming of gravity. Suppose you’re at the top of a cliff and you jump off. Your remaining life expectancy is short—and it gets shorter as you descend to the rocks below. This is exactly the same as with aging: the older you get, the less remaining time you can expect to live. The situation with the periodic arrival of ever better rejuvenation therapies is then a bit like jumping off a cliff with a jet-pack on your back. Initially the jetpack is turned off, but as you fall, you turn it on and it gives you a boost, slowing your fall. As you fall further, you turn up the power on the jetpack, and eventually you start to pull out of the dive and even start shooting upwards. And the further up you go, the easier it is to go even further.

The political and social significance of discussing LEV
I’ve had a fairly difficult time convincing my colleagues in biogerontology of the feasibility of the various SENS components, but in general I’ve been successful once I’ve been given enough time to go through the details. When it comes to LEV, on the other hand, the reception to my proposals can best be described as blank incomprehension. This is not too surprising, in hindsight, because the LEV concept is even further distant from the sort of scientific thinking that my colleagues normally do than my other ideas are: it’s not only an area of science that’s distant from mainstream gerontology, it’s not even science at all in the strict sense, but rather the history of technology. But I regard that as no excuse. The fact is, the history of technology is evidence, just like any other evidence, and scientists have no right to ignore it.

Another big reason for my colleagues’ resistance to the LEV concept is, of course, that if I’m seen to be right that achievement of LEV is foreseeable, they can no longer go around saying that they’re working on postponing aging by a decade or two but no more. There is an intense fear within the senior gerontology community of being seen as having anything to do with radical life extension, with all the uncertainties that it will surely herald. They want nothing to do with such talk. You might think that my reaction to this would be to focus on the short term: to avoid antagonising my colleagues with the LEV concept and its implications of four-digit lifespans, in favour of increased emphasis on the fine details of getting the SENS strands to work in a first-generation form. But this is not an option for me, for one very simple and incontrovertible reason: I’m in this business to save lives. In order to maximise the number of lives saved—healthy years added to people’s lives, if you’d prefer a more precise measure—I need to address the whole picture. And that means ensuring that the general public appreciate the importance of this work enough to motivate its funding.

Now, your first thought may be: hang on, if indefinite life extension is so unpalatable, wouldn’t funding be attracted more easily by keeping quiet about it? Well, no—and for a pretty good reason. The world’s richest man, Bill Gates, set up a foundation a few years ago whose primary mission is to address health issues in the developing world. This is a massively valuable humanitarian effort, which I wholeheartedly support, even though it doesn’t directly help SENS at all. I’m not the only person who supports it, either: in 2006 the world’s second richest man, Warren Buffett, committed a large proportion of his fortune to be donated in annual increments to the Gates Foundation.

The eagerness of extremely wealthy individuals to contribute to world health is, in more general terms, an enormous boost for SENS. This is mainly because a rising tide raises all boats: once it has become acceptable (even meritorious) among that community to be seen as a large-scale health philanthropist, those with “only” a billion or two to their name will be keener to join the trend than if it is seen as a crazy way to spend your hard-earned money. But there’s a catch. That logic only works if the moral status of SENS is seen to compare with that of the efforts that are now being funded so well. And that’s where LEV makes all the difference. SENS therapies will be expensive to develop and expensive to administer, at least at first. Let’s consider how the prospect of spending all that money might be received if the ultimate benefit would be only to add a couple of decades to the lives of people who are already living longer than most in the developing world, after which those people would suffer the same duration of functional decline that they do now.

It’s not exactly the world’s most morally imperative action, is it?
Indeed, I would go so far as to say that, if I were in control of a few billion dollars, I would be quite hesitant to spend it on such a marginal improvement in the overall quality and quantity of life of those who are already doing better in that respect than most, when the alternative exists of making a similar or greater improvement to the quality and quantity of life of the world’s less fortunate inhabitants.

The LEV concept doesn’t make much difference in the short term to who would benefit from these therapies, of course: it will necessarily be those who currently die of aging, so in the first instance it will predominantly be those in wealthy nations. But there is a very widespread appreciation in the industrialised world—an appreciation that, I feel, extends to the wealthy sectors of society—that progress in the long term relies on aiming high, and in particular that the moral imperative to help those at the rear of the field to catch up is balanced by the moral imperative to maximise the average rate of progress across the whole population, which initially means helping those who are already ahead. The fact that SENS is likely to lead to LEV means that developing SENS gives a huge boost to the quality and quantity of life of whomever receives it: so huge, in fact, that there is no problem justifying it in comparison the alternative uses to which a similar sum of money might be put. The fact that lifespan is extended indefinitely rather than by only a couple of decades is only part of the difference that LEV makes, of course: arguably an even more important difference in terms of the benefit that SENS gives is that the whole of that life will be youthful, right up until a beneficiary mistimes the speed of an oncoming truck. The average quality of life, therefore, will rise much more than if all that was in prospect were a shift from (say) 7:1 to 9:1 in the ratio of healthy life to frail life.

Quantifying longevity escape velocity more precisely
I hope I have closed down the remaining escape routes that might still have remained for those still seeking ways to defend a rejection of the SENS agenda. I have shown that SENS can be functionally equivalent to a way to eliminate aging completely, even though in actual therapeutic terms it will only be able to postpone aging by a finite amount at any given moment in time. I’ve also shown that this makes it morally just as desirable—imperative, even—as the many efforts into which a large amount of private philanthropic funding is already being injected.

I’m not complacent though: I know that people are quite ingenious when it comes to finding ways to avoid combating aging. Thus, in order to keep a few steps ahead, I have recently embarked on a collaboration with a stupendous programmer and futurist named Chris Phoenix, in which we are determining the precise degree of healthy life extension that one can expect from a given rate of progress in improving the SENS therapies. This is leading to a series of publications highlighting a variety of scenarios, but the short answer is that no wool has been pulled over your eyes above: the rate of progress we need to achieve starts out at roughly a doubling of the efficacy of the SENS therapies every 40 years and actually declines thereafter. By “doubling of efficacy” I mean a halving of the amount of damage that still cannot be repaired.

So there you have it. We will almost certainly take centuries to reach the level of control over aging that we have over the aging of vintage cars—totally comprehensive, indefinite maintenance of full function—but because longevity escape velocity is not very fast, we will probably achieve something functionally equivalent within only a few decades from now, at the point where we have therapies giving middle-aged people 30 extra years of youthful life. I think we can call that the fountain of youth, don’t you?

SENS (Strategies for Engineered Negligible Senescence)
http://www.sens.org/
http://www.methuselahfoundation.org/
http://www.mfoundation.org/
http://us.cnn.com/video/?/video/international/2009/11/30/vs.clinic.immortality.cnn
http://www.longevitymeme.org/topics/strategies_for_engineered_negligible_senescence.cfm

DONATE OR COMPETE
https://www.mfoundation.org/index.php?pagename=mj_donations_donate
http://www.mfoundation.org/?pagename=mj_mprize_how
http://www.mfoundation.org/index.php?pagename=mj_mprize_overview

The Mprize competition is an exciting and viable mid-term strategy to deliver on the Methuselah Foundation’s mission of extending healthy human life. It directly accelerates the development of revolutionary new life extension therapies by awarding two cash prizes: one to the research team that breaks the world record for the oldest-ever mouse; and one to the team that develops the most successful late-onset rejuvenation. Previous winners have already proven that healthy life can be extended; each new winner pushes the outer limits of healthy life back even further…and each new winner takes us even further.

Why Mice?
Because of the mouse’s availability, size, low cost, ease of handling, and strong genetic similarity to humans, there is no other experimental animal that offers such a wide variety of uses to science and medicine. Mice are widely considered to be the prime model of inherited human disease and studies have shown that mice share 99% of their genes with humans. The similarities between sections of human and mouse DNA allow researchers working with mouse genes to make incredibly accurate predictions about the location and function of their human counterparts. To this point, mice have been the mainstay of laboratory research on human illness, and they will continue to be essential players in future studies.

NAKED MOLE RATS
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=2774
http://www.fightaging.org/archives/2008/01/naked-molerats-and-negligible-senescence.php

Naked mole-rats live in captivity for more than 28.3 years, approximately 9 times longer than similar-sized mice. They maintain body composition from 2 to 24 years, and show only slight age-related changes in all physiological and morphological characteristics studied to date. Surprisingly breeding females show no decline in fertility even when well into their third decade of life. Moreover, these animals have never been observed to develop any spontaneous neoplasm. As such they do not show the typical age-associated acceleration in mortality risk that characterizes every other known mammalian species and may therefore be the first reported mammal showing negligible senescence over the majority of their long lifespan. Clearly physiological and biochemical processes in this species have evolved to dramatically extend healthy lifespan. The challenge that lies ahead is to understand what these mechanisms are.

AGELESS ANIMALS
http://www.agelessanimals.org/

NEGLIGIBLE SENESCENCE
http://www.smart-publications.com/articles/MOM-guerin.php
Learning From Ageless Animals: An Interview with John Guerin
By David Jay Brown

John Guerin is the founder and director of the AgelessAnimals Project—also known as the Centenarian Species and Rockfish Project. This long-range research project involves investigators at fourteen universities around the world who study animals that don’t seem to age.

There are certain species of rockfish, whales, turtles, and other animals that are known to live for hundreds of years without showing any signs of aging—a phenomenon known to biogerontologists as “negligible senescence.” No one knows for sure how long these animals can live for, but we know that they can live for over two hundred years without showing any observed increase in mortality or any decrease in reproductive capacity due to age. Striking examples are a 109 year old female rockfish that was captured in the wild while swimming around with fertilized eggs, and a hundred-plus year old male whale that was harpooned while it was having sex. The purpose of the AgelessAnimals Project is to understand why these animals don’t seem to age and then to apply that understanding to human longevity.

Guerin is an experienced project manager, who conceived of the AgelessAnimals project and orchestrates all of the studies. The two principal advisors to this project are Dr. Leonard Hayflick and Dr. Aubrey de Grey, both of whom were also interviewed for the Mavericks of Medicine collection. Dr. Hayflick, discoverer of the “Hayflick limit” of cellular senescence, states that “Guerin’s project is not only unique, but probes an area of almost total neglect in biogerontology, yet an area with more promise to deliver valuable data than, perhaps, any other.”

When I asked Dr. de Grey about the importance of studying ageless animals he said, “All organisms with organs that rely on the indefinite survival of individual non-dividing cells (such as neurons in the brain) should age, though some, including humans, age very slowly. Some species do even better—we cannot yet measure their rate of aging at all—and studying them may well reveal ways to slow our own aging.”

In addition to coordinating and orchestrating the AgelessAnimals project, Guerin lectures regularly on the subject of ageless animals. To find out more about Guerin’s work and the AgelessAnimals Project visit their Web site: www. agelessanimals.org. John Guerin seemed eager and excited to discuss his project with me. We spoke about some of the latest research that’s going on with long-lived animals, why this type of research has been neglected for so long, and how studying ageless animals might help us to understand the aging process better and extend the human lifespan.

Q: What inspired the AgelessAnimals Project?
John Guerin: Back in 1995, I began looking into biotech, biogerontology, and the studies of aging. I read many different books, articles, and scientific papers. The turning point came when I read Dr. Leonard Hayflick’s book How and Why We Age. Dr. Hayflick had a chapter called “Some Animals Age, Some Do Not,” and I thought, wow, now that’s interesting. I’d heard rumors and old wive’s tales about how some animals live for an extraordinarily long time, but this was the first time that I had come across that information from a scientific source. So I started doing some research on long-lived animals, and I found out that there’s very little known. On my web site, I have some references available.

I met Dr. Hayflick at a Gerontological Society of America meeting in November of 1995, and I told him about my project management background. I said I’d like to join whoever is working in this area, and I asked him who is. His answer was, “Nobody is, but they should be.” So I tried to get something going on my own. I did a lot of research on different animals. I spent about a year looking at koi—the fancy Japanese carp—and it’s very likely that they do live quite a long time, at least over fifty years. They were reputed to live over two hundred years, but the readings were based on scales, and those are not accurate. So they didn’t turn out to be a good candidate to study.

Then in 1997, I got some data from the Alaska Fish and Game. There’s a chart at the bottom of my Web page with a rockfish on it that shows ages for different rockfish that were caught off the coast of Alaska, and the range is between twelve and 107 years. Now, that’s a randomly caught sampling—it wasn’t like they were trying to get older individuals.

Those were the ones that fishermen caught and were going to people’s dinner tables that evening. So when I realized that individuals at those ages were available, I became very interested. We got samples from the Alaska Fish and Game in 1997. I say “we” because by then I had a couple of researchers at Oregon State University and the Linus Pauling Institute interested in looking at the rockfish. So the Alaska Fish and Game sent us five older rockfish. After we aged them, it turned out that the the youngest rockfish that they sent us was 79 years old, and the oldest was a 109 year old female that still had eggs.

Q: Isn’t that extraordinary?
John Guerin: Yeah, and kind of sad. It’s like, how long would this fish have lived if it wasn’t caught? It didn’t die of old age. It was fertile and still going strong in the ocean at 109 when they caught it. So that helped us to focus the project on rockfish. We have had one study on turtles. Whales are a very fascinating subject too, because they’re warm-blooded mammals like we are, and they’ve now been documented to be over two hundred years of age.

Q: What is the goal of the AgelessAnimals Project?
John Guerin: Quite simply, the goal is to understand the genetic and biochemical processes that long-lived animals use to retard aging. These long-lived animals have what’s technically called “negligible senescence,” as defined by Caleb Finch at the University of Southern California in Longevity, Senescence, and the Genome (1995).

Q: What is negligible senescence?
John Guerin: Basically, this refers to an animal species that doesn’t show any significant signs of aging as it grows older. Unlike humans and most other mammals, there’s no decrease in reproduction after maturity.

There’s also no notable increase in mortality rate with age, but that’s a little harder to prove. I’ve been talking with a statistician and he’s asking, how do you know? To do a study of this type would take a couple of hundred years to complete. But compared to us there’s no noted increase in mortality rate. I mean, if you are ninety years old, you’re much more likely to die next year then you are if you’re only twenty years old. But we don’t seem to see any increase in mortality with rockfish and several of these other animals over time.

Q: Why do you think these animals can live for so long without showing any signs of aging?
John Guerin: The purpose of the project is to understand why, and how to apply it to extending the health and lifespan of humans. My background is in business project management; I have a project management professional certification. I’m not a bioresearcher, a biochemist, or a biogerontologist—but I’m the one who organizes it all, and gets everyone involved. I get the researchers the samples and all that.

Actually, I thought I had a better idea about why these animals have negligible senescence when I started this project ten years ago. But it’s hard to say. Back then we didn’t know whales lived that long. That whales can live for over two hundred years was just discovered in the last five years. Up until then we thought that humans lived longer than any other mammal. So why certain animals would live much longer than others, and much longer than we do as a matter of fact—pretty much double what we’ve known humans to live—we don’t understand.

There are some people who think that this can’t be so, that this would violate the evolutionary theory of senescence, because nature doesn’t select for longevity. But that’s not necessarily true, because what’s commonly seen is that there’s just such a high mortality rate in nature.

Even for humans, probably before two thousand years ago, we didn’t live very long. We were hunted by tigers and wild animals, and traits of longevity, presumably, weren’t selected for. But if these animals, like the rockfish, can be 109 years old and still be reproductive, nature is going to allow those genes to keep contributing to the gene pool, so that it won’t select against longevity.

Q: So we don’t know if these animals are simply aging more slowly or not at all? Since we have haven’t found any rockfish or whales that live for three or four hundred years, that might suggest that there is a certain limit on how long they can live.
John Guerin: Well, we just do not know. We honestly do not know. It really is unfortunate that there is so little known in this field. Ecologists have never thought of this in the terms that gerontologists are now thinking of it in. To give you an idea, let’s say you have a sample of a species, and you see they live to twenty years. That’s the oldest you sample out of several hundred. Then that’s their maximum longevity. That’s really the basis of their thinking in most cases. Mice, as you probably well know, don’t live for more than a couple years, even in the best laboratory environment, with all the best nutrients and all the best food. They don’t live very long. They just can’t. They’ll start having all sorts of age-related pathological functions, and they’ll die of old age.

But this other group of organisms, those that possess what Finch termed “negligible senescence,” they don’t seem to be showing the classical signs of aging that we’re used to. So, who is to say the longest they could live? As an example, in Finch’s book that was published in 1990, at that time the longest lived whale was—I believe it was a Blue Whale—something like 108 years old. That’s like, okay, well that’s not so startling. Humans live longer than that. We’re mammals. They’re mammals. We live longer. Then a study was done on bowhead whales, and they found that out of forty whales sampled, four of them were over a hundred years old, and one of them was over two hundred years old. And they didn’t die of old age either—they were harpooned. I have a reference on the web site.

Q: How might studying ageless animals help us to understand human aging better?
John Guerin: By understanding how other animals are naturally able to live a lot longer than we are, we can ask: What is genetically different? What is biochemically different? There are two major problems with studying long-lived animals. One is that nobody knows what causes aging. If you’re able to say what causes aging, that’d be really easy then to target that same factor in animals that are living a very long time—whales, rockfish, sturgeon, lobsters, and several other animals—and then you could study it. If you looked on our web site you’ve seen that we did studies in everything from lisosones to microarrays to telomere-telomerase activity, because you just don’t know. That’s one problem. The other is that these animals live so long that you have to ask: How do you do an experiment? Let’s say we think a certain gene’s involved in aging, so we were going to do a knockout. Then instead of living two hundred years a rockfish lives seventy-five years.

Q: Wouldn’t it take quite awhile to run the experiment?
John Guerin: Yeah, it would be somebody else finishing it up, and it certainly wouldn’t be of much practical benefit. So the direction we’re taking in the project is we’re looking at the difference between long-lived rockfish and short-lived rockfish. The other thing is basically identifying genetic differences, and going at it that way, because there’s no practical way you could run an experiment that would go on for decades.

At first rockfish just seemed to be a good model, or a handily available model. They’re commercially caught, go on the dinner table, and we were able to get lots of samples of them. Then, of course, the news about whales came out, which is very intriguing, and there are lots of other animals that are either known or suspected to live a very long time. But the really intriguing thing about rockfish is that in the same genus—which is sebastes—there are rockfish that have not been noted more than about twelve to twenty years maximum longevity, and these are essentially cousins. They are rockfish, and some of these at least have been caught in thousands of samples, so it’s not just an aberration of a small sample size.

One of the key issues people have raised to me at meetings is that you have to have something to compare these long-lived animals to in order to try and understand why they’re successfully retarding aging. So what better model can you have than another species within the same genus that don’t live a very long time? In all the meetings I’ve gone to I haven’t had anybody come up and say, oh here’s another species that has a really diverse longevity. There is one kind of similar one—the naked mole rat. It’s just in the last few years that it’s gotten more publicity. It’s a rodent, and most rodents—like mice and rats—live maybe two to five years maximum. The naked mole rat has been documented to live at least into its twenties. So it’s on quite another order of magnitude different than other rodents. The bat is another exception that lives way longer than other mammals, and birds, of course, are their own interesting exception.

So that’s our focus, which is almost out of necessity, because how do you design an experiment to test for longevity when you’ve got such long-lived animals? Whatever tests we’re going to do to the long-lived rockfish in the future, like a micro-array, we want to do with the short-lived ones too.

Q: Could you talk about some of the principal investigators for the Ageless Animal project, and can you summarize some of the latest research that’s going on with long-lived animals?
John Guerin: There’s fourteen principal investigators at fourteen different universities. There are some co-PIs involved as well, such as Dr. Judd Aiken at the University of Wisconsin, Madison. He’s very well-known and respected in the field. He does mitochondrial mutation studies, and this could be one of the more important areas because of what we know about free radical damage. The oxidative theory seems to be of the more important theories of aging, so I’m encouraged, even though at this point he hasn’t gotten results yet. His lab is working on amplifying the primers. So that could be a very important study. I think the microarray study is an important one too.

Dr. Ana Maria Cuervo, who’s at Albert Einstein College of Medicine in New York City, did the most complete study. Her study was on lisosomes and proteolytic activity, and she actually has done more than is on the web site. She added some more tests that she didn’t have available a couple of years ago, and she told me about a month ago that she was getting her manuscript ready to publish. So that would be the most extensive study. Also, there’s Glenn Gerhard, M.D., who was at Dartmouth and then he took a full-time research position at a research institute in Pennsylvania. He did a SOD (superoxide dismutase) study and then also the microarray study.

Q: Why do you think that the study of long-lived animals has been neglected for so long?
John: I have thought about it, and partly I have to say I don’t understand why. I think that’s why somebody like me would get involved, because I have a project management background and I can see the big picture. There’s more than one reason I can see as to why people in the field wouldn’t have gotten involved. It’s risky to put your career on the line to look at animals that haven’t been studied very well and that there’s no cultures available of. Whereas with other species strains are easily available. For instance, with any mouse you want you could get a strain, and you could have it under the identical conditions you need.

But this hasn’t been done with any of these long-lived animals. For me, the biggest question really is: Why hasn’t the National Institute of Aging taken a lead? This is a perfect opportunity for government to get involved, where there is no profit motive. This is basic research that we’re doing with these animals, and basic research doesn’t necessarily have a pay-back. Now, let’s say we find something like we did with the SOD study. We had a very interesting finding that SOD went up with age in rockfish, and as you may be aware, SOD is the strongest antioxidant in our bodies, and in most animals. So that it goes up with age is a very intriguing finding. That’s something we hope to look into more, but in general all of the things we’ve done are just basic science. We’re just laying the groundwork.

Q: Has anybody done any studies to see if whale cells, rockfish cells, or turtle cells reach a Hayflick limit in the number of times that they can divide? Are their telomeres growing shorter with each cell division?
John Guerin: In terms of the Hayflick limit, you very well may be aware that most gerontologists don’t consider that to be a limitation of aging. At some point, maybe about ten years ago, it was a much bigger topic. Nowadays, telomeres and telomerase is much more of a cancer issue, because most cancer cells keep producing that enzyme that allows cells to keep dividing.

Q: When I interviewed Dr. Michael Fossel for this collection he thought differently.
John Guerin: I would have to say that the majority of gerontologists don’t believe it that way. I remember at a meeting a couple of years ago, somebody just making an offhand remark that we used to think telomerase and telomeres were important. I think if you do a survey you would find that that the majority of gerontologists don’t believe it that way. The telomerase limit and the Hayflick limit don’t seem to necessarily be what it once was thought to be, because even older people have continued replication of the cells that do divide. There’s a bunch of reasons that it doesn’t seem as important now as at one point when they thought it was.

Q: Yes, I understand that, but I’m still curious. Do you know if these animals that have negligible senescence, if their cells reach a Hayflick limit? Is there a limit to how many times the cells from these animals can divide?
John Guerin: We have fourteen studies—twelve in the U.S. and two in Europe. One of the European studies is in Germany by someone named Guido Krupp, who looked at telomerase levels in nine different rockfish. He looked at three samples—one of heart, one of liver, and one of brain—all the way from teenage years up to a 93 year old rockfish. All of the three tissues showed expression of telomerase, and there was no age-dependent change of expression of telomerase in the tissues. There was individual differences. Some were higher and some were lower. One of the higher levels of telomerase was found in the 93 year old, but the primary finding was that there was no trend. As far as whales go, the only other person I know outside our group and Caleb Finch at USC, who actually is studying these long-lived animals is a guy at the University of Texas in Dallas named Jerry Shay. He got some samples of bowhead whale, and he’s basically doing these cell replications to see how many replications he gets out of them.

Apparently, it’s pretty hard to get the samples, because they had to go through the Canadian government, and it was quite an ordeal. Jerry Shay is the only one I know of who’s done bowhead whale studies. But in this one study four of the whales out of forty were documented to be over a hundred years old, and one of them was over two hundred years old. And that’s without doctors. Although this was not in the paper, we know that at least one of those hundred-plus year old male whales was reproductive, because when he was harpooned he was caught in the act.

Q: Wait a minute. This hundred-plus year old whale was harpooned while it was having sex?
John Guerin: Yes, and it was over a hundred. There were three that were between a hundred and two hundred. One was 211 years old. When I talked to the researcher, who is an ecologist, I said, “Gerontologists want to know, how do you know that the whales weren’t about to keel over, that they were on their last leg?” And then he has an example like this. I’m like, were they reproductive? And he goes, well, one of the males sure was.

LOBSTERS IMMORTAL?
http://www.npr.org/templates/story/story.php?storyId=11382976
http://animals.howstuffworks.com/marine-life/400-pound-lobster.htm/
Big Lobsters and Eternal Life

Decline is an accepted part of old age for most people, even for those still searching for the fountain of youth. We expect the same in our pets and in the flies that buzz around us, albeit at a different rate. So why are lobsters different? A study conducted in 1998 showed that lobsters maintain telomerase activation late in life. But before we explain that, let’s talk briefly about cell division.

Telomeres are like caps or sheathes that encase the ends of chromosomes. When cells divide, telomeres get shorter. When telomeres get to a certain length, they can no longer protect chromosomes and the chromosomes start to suffer damage. The number of cell divisions before damage sets in is called the Hayflick limit. Telomerase is an enzyme that adds length to telomeres, extending their life span. In humans, telomerase is abundant in embryonic stem cells and then declines later in life. This is actually a good thing because when cells re-activate telomerase after reaching the Hayflick limit, they become cancerous (in other words, they don’t die when they’re supposed to). The downside is that cells with short telomeres weaken and die, so we eventually die, too.

In humans, telomerase levels decline later in life and are only found in some types of tissue, but in lobsters, telomerase is found in all types of tissue. That likely accounts for lobsters’ ability to grow throughout their lives. And because lobsters’ skeletons are on the outside and the molting process allows them to periodically shed their exoskeletons in favor of a new, larger one, their constant growth isn’t a problem. With a steady, evenly distributed supply of telomerase, lobsters don’t approach the Hayflick limit, which means that their cells stay pristine, young and dividing.

The dual role of telomerase in keeping cells healthy and in cancer growth means that it’s an important area of research for both anti-aging and cancer treatments. Further study of lobsters may teach us more about their longevity, how long they can actually live and what that knowledge may mean for human health. Scientists are also studying a variety of other animals that are long-lived. Like lobsters, many types of turtles don’t show compromised immunity or physical breakdown because of age. They also become more fertile with age and usually die because of a predator or malady unrelated to age.

A bird known as Leach’s storm petrel fits into a human hand yet lives more than 30 years. They’re also the only known animal in which telomeres grow longer with age. Related animal species with vastly different life spans are also a point of interest. Conventional mice live only three years, but naked mole rats can live for 28. Other animals being studied include whales, bats, rockfish, zebrafish and clams, the oldest of which, a quahog clam, lived to be 220 years old. In many of these animals, the rate of telomere deterioration corresponds with their lifespan. The longer the telomeres last, the longer the animals live. Studying these creatures may tell us much about human aging and lead to treatments for aging-related diseases. Exciting research is being conducted on many fronts — on the molecular and genetic levels and regarding lifestyle, diet and habitat. If one day humans discover an important new treatment for cancer, it may be due to one of these creatures — or to a 200-pound lobster living peacefully in a tank at Boston University.

CONTACT
Jelle Atema
http://people.bu.edu/atema/
http://www.bu.edu/biology/people/faculty/atema/
email : atema [at] bu [dot] edu

FOREVER
http://www.kuro5hin.org/story/2004/12/20/184723/82
http://metafilter.com/88971/Nobody-Home
“For the past 21 years, across the limitless expanse of the North Pacific, a lonely whale has been singing, calling for a response. There has been none, and there never will. Picked up first in 1989 by NOAA hydrophones, the call is clearly a whale, but different than all other known species. Different enough that no other whale has responded in all this time. Hypotheses vary, but the mental image is definitely haunting.”

ALONE AT 52 HERTZ
http://www.pmel.noaa.gov/vents/acoustics/whales/sounds/whalewav/ak52_10x.wav
http://www.pmel.noaa.gov/vents/acoustics/whales/sounds/sounds_52blue.html
http://www.newscientist.com/article/dn6764-lonely-whales-song-remains-a-mystery.html
Lonely whale’s song remains a mystery
BY Jon Copley / 10 December 2004

Marine biologist Mary Ann Daher of Woods Hole Oceanographic Institution in Massachusetts, US, and her colleagues used signals recorded by the US navy’s submarine-tracking hydrophones to trace the movements of whales in the north Pacific. The partially declassified records show that a lone whale singing at around 52 hertz has cruised the ocean every autumn and winter since 1992. Its calls do not match those of any known species, although they are clearly those of a baleen whale, a group that includes blue, fin and humpback whales.

Blue whales typically call at frequencies between 15 and 20 hertz. They use some higher frequencies, but not 52 hertz, Daher says. Fin whales make pulsed sounds at around 20 hertz, while humpbacks sing at much higher frequencies. The tracks of the lone whale do not match the migration patterns of any other species, either. Over the years the calls have deepened slightly, perhaps because the whale has aged, but its voice is still recognisable. Daher doubts that the whale belongs to a new species, although no similar call has been found anywhere else, despite careful monitoring.

CONTACT
Mary Ann Daher
http://www.whoi.edu/profile/mdaher/
email : mdaher [at] whoi [dot] edu