$36,000
$24,768

Meanwhile, in Wisconsin

Stem cell politics in Wisconsin have been heating up of late; anti-research groups and politicians have unfortunately succeeded in banning therapeutic cloning:

Everyone is against human cloning but the real purpose of this bill is to restrict stem cell research, which holds enormous potential for our state as well as the promise of curing juvenile diabetes, spinal cord injuries and Parkinson's disease," said Doyle, also in a prepared statement.

"I do not understand how anyone can, in good conscience, tell a family whose child is suffering from a life-threatening disease that politics is more important than finding a cure."

This criminalization of research is just as idiotic as every other attempt to outlaw therapeutic cloning, a technology presently vital to much of the most important stem cell research. It never ceases to amaze me that such a large number of people are so ready to turn their backs on progress towards regenerative cures for age-related conditions, placing greater value on a few hundred cells than on actual thinking, feeling, suffering and dying human beings.

The Wisconsin governor is a strong supporter of stem cell research and is expected to veto the legislation:

Gov. Jim Doyle invested $2 million in state funds in a company founded by stem cell research pioneer Jamie Thomson on Monday while promising to veto restrictions on the developing science.

Doyle said the $1 million grant and $1 million loan will help startup company Cellular Dynamics International leverage private investments that will eventually turn research discoveries into profitable products.

It is a sad thing that we live in a society in which so much effort must be expended simply to gain the freedom to research better medicine and build steps towards real healthy life extension technologies - how much further could research have advanced if not for these battles? Even after the stem cell wars have ended, it will still be a case of back to the normal mess of regulation and governance that hampers medical research and commercialization in the US. Basic science may be speeding up and producing real results, but the costs - in money, in time, in lives - imposed by the regulatory situation seem only to go from bad to worse.

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Looking To The Future, Medicine and Longevity

A long article in the South African Engineering News Online looks at the near future of medical technology and the effects of advances on human longevity. Conservative but optimistic, it might make a good introductory piece to pass to that healthy life extension skeptic you know (despite the obligatory misguided poverty gap lecture at the end - new technology is always expensive, but always falls in price and improves in quality if allowed the freedom to develop). "Never before has it been as possible to outwit the fiercely-ticking biological clock for longer. ... The good news is [that] the ageing process is much more malleable - susceptible to modification - than used to be thought."

Link: http://www.engineeringnews.co.za/eng/news/thisweek/?show=74392

New Calorie Restriction Gene In Yeast

(From PhysOrg.com). Researchers have discovered more genes related to the mechanisms by which calorie restriction increases longevity: "Deleting Hst2 and Sir2 blocked most of the beneficial effect of caloric restriction. When Hst2 was overexpressed, so the gene was more active than normal, the yeast lived longer than normal. A third gene, Hst1, appears to act when both Sir2 and Hst2 are missing. Sir2 and the newly identified Hst genes account for all of the life-prolonging effects of caloric restriction in yeast." While yeast may or may not be a good place to start, it seems that scientists are on the verge of completely understanding calorie restriction. This bodes well for the prospect of therapies that can produce the same beneficial effects on healthy life span.

Link: http://www.physorg.com/news6877.html

Conversing on Biomarkers and a Definition for Aging

An interesting discussion is presently ongoing over at the Gerontology Research Group email list, covering such topics as workable definitions for aging and the need for biomarkers of aging. I've touched on the topic of biomarkers for aging previously; it's an important issue for the research community. How can you rapidly determine that you have successfully developed an anti-aging technology that works in humans if you cannot tell how advanced the aging process is in any given individual, or if you cannot even agree on a working scientific definition for aging? Obviously you can wait around to count years and deaths, but that reliable fallback is not a good approach for those of us who would like to see working healthy life extension medicine in our lifetimes.

A good excerpt from the GRG conversation has made it's way to the transhumantech group, and is worth reading if you have an interest in the nuts and bolts of the field.

I should mention that, in my view, the Strategies for Engineering Negligible Senescence approach sidesteps many of the requirements for definitions and biomarkers. If researchers jump right on in and work on fixing what we know to be root causes of degeneration, then they can't be going far wrong. You don't need a unified theory of automotive decay to use a toolkit and spare parts to extend the lifespan of your car - the only difference between the human body and a car is the degree of complexity involved. When it comes to repairing the causes of degeneration in people, scientists can measuring the effectiveness of repair strategies on specific modes of age-related damage (mitochondrial mutations, extracellular junk, damaged DNA, etc) in isolation; improvements in repair capabilities in any one area should lead to incremental benefits to patients even while other modes of age-related damage are still taking place unabated. Provided that medical research can reliably identify all causes of age-related degeneration as science moves forward and time advances, researchers should be well set to solve the problem of aging incrementally - without the need for a comprehensive understanding at the outset.

As always, the crucial missing ingredients are significant funds and public support for this sensible, necessary, practical direction in aging research. This is a problem that folks like you and I can help to solve, however, by stepping up to support efforts like the Mprize for longevity research.

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The Tithonus Error Is Alive And Well

Leon Kass is still trying to convince us we should all do nothing to try and prevent age-related suffering and death, this time in the Washington Post. Here, he elists the comprehensively refuted yet still widespread Tithonus Error - the belief that a longer life would mean a greater time spent in increasing depths of decrepitude. All envisaged healthy life extension technologies will accomplish nothing of the sort, of course - they will lead to more healthy, active years. Kass is, as usual, saying whatever he thinks will bring the audience around to his way of thinking, without regard for truth, accuracy or science. His own choice is his own choice, but he and others like him cannot be allowed to dictate access to longevity research and medicine for the rest of us.

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/09/28/AR2005092802119.html

Wired On Regenerating Mice

Wired is running an article on Ellen Heber-Katz's regenerating strain of mice: "Researchers systematically amputated digits and damaged various organs of the mice, including the heart, liver and brain, most of which grew back. ... When cells from the regenerative mice were injected into normal mice, the normal mice adopted the ability to regenerate. And when the special mice bred with normal mice, their offspring inherited souped-up regeneration capabilities. ... If we identified the molecules that allow mice that don't regenerate to regenerate ... and I think we could be close to doing that, then I think the next step is to consider what these molecules would do in individuals." This research was most recently presented at the SENS 2 conference.

Link: http://www.wired.com/news/print/0,1294,68962,00.html

Genetics of Longevity Webcast Transcript Arrives

After long aeons of waiting, the SAGE Crossroads Genetics of Longevity webcast transcript has now arrived - and there was much rejoicing. You'll be hearing a lot about the merits of yeast as a platform for aging research:

It really wasn't a good model for eukaryotic aging at all at the time we started. Yeast is the simplest eukaryote you can work on. And by that I mean, it's a cell that's related to the type of cells we have in our body.

I felt like at the time that even if we didn't learn anything that directly applied to human aging, we would at least set a paradigm for how aging might occur. I think that it's still not entirely clear how related the two species are in terms of aging by any means. But there is accumulating evidence that there are going to be some things that are in common.

Not to mention yeast and sirtuins, the latter being a hot topic elsewhere in aging research (in relation to calorie restriction):

But so - I mean, and this sort of gets back to what you asked - what limits the replicative life span of a yeast cell? We don't completely know the answer. We know that one thing that limits how many times a cell can divide is the accumulation of these extra chromosomal RDNA circles, which some people call ERCs, and SIR2 inhibits that process.

We now think that that's not the whole story, that there are other things going on. So the real question is - one thing that's interesting about these ERCs is that they seem to be specific to yeast. People have looked and there's no evidence that these circles accumulate or cause aging in other organisms. Yet it's very clear in yeast that that's how [SIR2] is acting. So it's a burning question - [SIR2] seems to regulate aging at least in yeast and worms and flies, apparently by different mechanisms. So that's one of the questions, how could such a system have evolved, and is there something else going on that we don't completely understand?

Yeast, like the nematode worm, is a fairly simple organism - this opens up the doors to some methodical approaches that would be unfeasible in more complex life:

In the meantime, the yeast community has gone and made a deletion of every single gene, each in one strain. So there are 5,000 strains now that all have a deletion of each nonessential gene in yeast. What we're doing now is scanning through those, just randomly looking for ones that are long-lived. We're finding that there are a lot of other pathways in addition to [SIR2] that are regulating aging.

As with so much of funded aging research at the moment, the primary focus is the biochemical and genetic processes governing the regulation of metabolism. This is all useful work, but Strategies for Engineered Negligible Senescence it isn't - tinkering with our metabolism is never going to give us radically extended healthy life spans. But back to the topic at hand: as in other laboratories, calorie restriction is a big part of that picture.

The question about how it's activated, I think, gets to the point of calorie restriction or dietary restriction. One of the clues that aging is conserved in different organisms is that if you reduce caloric intake - and that's done in different ways in different organisms. But if you reduce caloric intake, do you extend life span? That works in yeast and flies and mice and monkeys, presumably. And maybe even us.

There is a big question: what is calorie restriction doing? One model that was put forth was that calorie restriction was leading to the activation of [SIR2]. At least in the strains we work in, we think it is a lot more complicated than that, and that [SIR2] may not be the link for calorie restriction. That doesn't mean it is not regulating aging, but we think that there are other pathways that calorie restriction are affecting that are causing aging.

That's just for starters - there's a good deal more, covering telomeres, other prospective aging-related genes and processes, and half a dozen other interesting topics in passing. Go and read the whole thing.

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On Placental Stem Cells

The Pitt Chronicle examines the state of knowledge and use of placental stem cells: "If we could develop efficient methods that would allow amnion-derived cells to differentiate into specific cell types, then placentas would no longer be relegated to the trashcan. Instead, we’d have a useful source of cells for transplantation and regenerative medicine ... Provided that research advances to the point that we can demonstrate these cells' true therapeutic benefit, parents could conceivably choose to bank their child's amniotic epithelial cells in the event they may someday be needed, as is sometimes done now with umbilical cord blood." These cells share many of the same characteristics as embryonic stem cells.

Link: http://www.umc.pitt.edu/media/pcc/sci1_placentas_2005SEP26.html

Cryopreserved Stem Cells Work Fine

A paper from the Journal of Dental Research describes how scientists took frozen - cryopreserved - tissue, extracted stem cells and successfully put them through their paces. "These cryopreserved periodontal ligament stem cells maintained normal periodontal ligament stem cell characteristics ... . Collectively, this study provides valuable evidence demonstrating a practical approach to the preservation of solid-frozen human tissues for subsequent [adult] stem cell isolation and tissue regeneration." This research group has a good history of stem cell research for regenerative dental work. Work on cryopreserved stem cells is of wider interest for those people considering storage of their stem cells for use in later life.

Link: http://jdr.iadrjournals.org/cgi/content/abstract/84/10/907

SENS 2 Report, John Furber

Another of Frank Rummel's reports from the recent Strategies for Engineered Negligible Senescence conference (SENS 2) is up, with a focus on John Furber of Legendary Pharmaceuticals. As his SENS 2 presentation makes clear, Furber is involved in the search for AGE-breakers - drugs or therapies capable of breaking down the detrimental accumulation of advanced glycation end products (AGEs) and crosslinked proteins with age. "Extracellular aging - accumulating molecular damage by glycation, oxidation, and crosslinking of long-lived extracellular proteins, mainly collagen and elastin - is a major cause of several important human aging pathologies." This is an interesting area of study, and perhaps the field of SENS most likely to benefit from traditional approaches to drug discovery and medical research.

Link: http://anti-ageing.us/2005/09/john-furber-sens-2-anti-aging.html

The Muhlestein Challenge Grant Met, and Quickly Too

That was quick - the Methuselah Foundation's $25,000 Muhlestein Family Trust Challenge I mentioned last Sunday has already been met:

To the delight of all volunteers, donors and competitors involved in the Mprize competition, the Stan and Judy Muhlestein Trust $25,000 challenge has ALREADY BEEN MET. This stunning result is due especially to the generosity of David Gore, the newest member of The Three Hundred whose $25,000 donation swept the challenge. Thanks to all involved!

Upon hearing the news Dr. Aubrey de Grey said "this calls for beer all around!".

You have to move quickly if you want to take part in fundraising events around here! Thanks to these generous folks, and a surprise $125,000 from an anonymous donor, the Mprize for anti-aging research has passed the $1.75 million mark in total pledges. Things are very much on track for the Mprize to do for serious, scientific anti-aging research what the X Prize has accomplished for the private aerospace industry - to wake it up and blaze the way for tangible advances in technology and capabilities.

Have you told your friends about the Mprize and the future of healthy life extension today?

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Socialized Medicine, Broken By Design

Socialized medicine - such as Medicare, or indeed almost any other medical program in the US or Europe - is broken by design, as any the many articles on the costs imposed by increasing life spans make clear. Only in a socialized program does healthy life extension become a problem rather than a wondrous opportunity - oh no, people are living healthily for longer, what will we do? It should be immediately apparent to an observer just how ridiculous and unethical all this faux hand-wringing is. If people live longer, healthier lives, they will be productive earners for longer, capable of saving more and having the choice of the use of more medical technology. More importantly, they will be alive and healthy rather than suffering or dead! The problems only start with programs that disconnect basic financial incentives from consumption by allowing you to spend other people's money.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=31185

The Three Hundred Dinner With Ray Kurzweil and Aubrey de Grey

The Methuselah Foundation has announced the next dinner for The Three Hundred, generous supporters of the Mprize for longevity research, for December in Boston. You can find the announcement here:

The Methuselah Foundation will be hosting a small dinner party. The guests of honor will be Ray Kurzweil and our very own Aubrey de Grey! The event is free of charge.

Here's the catch: you have to be a Three Hundred member to attend.

The Three Hundred is the Mprize's core group of committed givers: those who have pledged $1,000 US per year for 25 years to the cause of finding a cure for the biggest killer of all time: aging. There's plenty of time to become a Three Hundred member... you can sign up anytime here.

If you are looking forward to a future of healthy life extension and working anti-aging medicine, then you should step forward and help to make it happen! The future cannot be taken for granted - it is something that we all build together. The more we do, the faster it comes to pass; $1,000 per year is a the cost of a cup of coffee per day, but it can be put to good use speeding up and invigorating the development of real anti-aging technologies. So what are you waiting for?

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Tissue Engineering A Diabetes Cure

(From EurekAlert). Scientists working on a cure for type 1 diabetes have developed "a 'reversibly immortalized' cell line that can supply large amounts of insulin-producing human beta-cells. ... The resulting cells produced about 40% as much insulin as normal beta-cells and successfully controlled blood sugar levels in diabetic mice for more than 30 weeks. ...
plans to develop a 'universal beta-cell line' are well underway, and Dr. Yoon anticipates that human clinical trials might begin as soon as three to five years from now." This tissue engineering process is clever; it could be applied to age-related medical conditions that result from the failure of comparatively small numbers of specialized cells.

Link: http://www.eurekalert.org/pub_releases/2005-09/rfuo-hbl092505.php

Parkinson's Gene Therapy: Modest Progress

EurekAlert reports on modest progress towards a gene therapy for Parkinson's disease: "One year following treatment, patients exhibited a statistically significant improvement in motor function on the side of their body correlating to the treated part of the brain. ... [this is the] first study to use a viral vector (the non-pathogenic adeno-associated virus, or AAV) for the treatment of an adult neurological disease. In the Neurologix-funded trial, the vector was injected into a specific target site in the brain in order to transfer a gene to treat Parkinson's disease. ... The goal of this research is to determine whether we can 're-set' a specific group of cells that have become overactive, causing the characteristic impaired movements associated with Parkinson's disease."

Link: http://www.eurekalert.org/pub_releases/2005-09/bm-nap092305.php

Boosting The Elderly Immune System

The Life Extension Foundation News is reprinting an article on yet another way to boost a failing, age-damaged immune system: "the researchers also found that [a common anti-AIDS treatment called antiretroviral therapy (ART)] dramatically boosted (up to a factor of 1,000) thymus production of cells from which the immune system makes disease-fighting T-cells. This increase in production even occurred in older people, who tend to produce few new T-cells, the researchers note." A range of other approaches to this same problem have also shown promise. In this new era of gene therapies and immunotherapies (or vaccines) for cancer or Alzheimer's, rejuvenating the aging immune system becomes even more important a goal.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2757&Section=DISEASE

People Who Want To Age And Die

I have nothing against people who want to age, suffer and die - I just think that they haven't given enough thought as to exactly how unpleasant the experience will be. A good example of the type - complete with airy metaphysical nonsense - can be found in this recent Guardian op-ed: "The idea of life extending for 1,000 years is altogether too dreadful to contemplate. Life is possible only because there is an end to it in sight. ... I would be content to live to around 100 ... but not much longer." I'd be willing to wager a great deal of money that the author, if he is lucky enough to be in good health and cheer on his 100th birthday thanks to future anti-aging medicine, will not immediately be reaching for the suicide pills. People who fear change - any change, even positive, wonderful change - more than they fear death are a strange lot.

Link: http://www.guardian.co.uk/Columnists/Column/0,5673,1575825,00.html

The End Result of Anti-Research Politics and Regulation

Comparing the stem cell therapies currently offered in Thailand with stem-cell related products just now coming onto the market in the US is an instructional exercise. For the former we have:

VesCell(tm) is "autologous" adult stem cell therapy. That means we use stem cells taken from your own blood . These stem cells are named "ACPs" (Angiogenic Cell Precursors). ACPs are cells that induce the growth of blood vessels. These cells may also turn into additional types of cells that can benefit heart patients. Similar cells, but probably less effective than ACPs, have successfully been used in dozens of clinical trials all over the world.

Cardiologists and cardiac surgeons are currently using VesCell(tm) to improve the quality of life of patients suffering from ischemic heart disease (or coronary artery disease) cardiomyopathy and congestive heart failure by relieving debilitating symptoms such as severe angina pectoris (severe chest pain) and increasing exercise tolerance.

While for the latter:

Osiris has found a way to take bone from a newly deceased donor for the grafts, while preserving the stem cells. The market for Osteocel potentially could encompass anyone who needs a significant amount of bone regrown -- accident victims, people requiring hip replacements. But Osiris said its ability to supply Osteocel is limited, so it is sticking with the spine operations for now.

The next Osiris product is a drug, not a stem cell product, and the first is simply a better bone transplant technique that happens to involve stem cells. Meanwhile, the commercialization of stem cell therapies for heart disease, the cause of 1/3 of all deaths in the US, is taking place ... but not in the US. This illustrates a part of the damage caused by regulation and anti-research politics; prohibitive cost and time of commercialization on the one hand and reductions in private investment for commercial products on the other. So it is that real regenerative medicine based on the use of stem cells is currently only provided as a commercial service outside the US.

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Regulation, Government, "The Singularity is Near"

I didn't touch on Kurzweil's views on the interactions between overbearing government, regulation, economics and the rate of technological progress - in medicine and elsewhere - in my last post on "The Singularity is Near" (TSiN). They are a challenge for libertarians, even pragmatic libertarians such as myself: Kurzweil says that past evidence of exponential growth in technological capabilities over a period with "extensive regulation in place" is sufficent evidence to suppose that "short of a worldwide totalitarian state, the economic and other forces underlying technical progress will only grow with ongoing advances."

I'm not sold on this idea of economic incentives and the technological imperative as a gel-like mix in a packet - squeeze them down with economic damage, poor governance or regulation (which are all much the same thing) in one part of the world, and off they flow to the regions of least pressure to do their work there. To my eyes, this world doesn't have a constant amount of freedom, nor a constant amount of incentive and imperative - the freedom to research and enact progress is something we must fight for, not take for granted.

Despite exhortations here and there, there is a curious kind of passivity underlying the discussions in TSiN. This is the most dangerous form of futurism, the one that takes the future as a forgone conclusion to be prepared for, rather than something that must be worked on, nurtured and built.

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Use It Or Lose It, Yet Again

(From Science Daily). Most age-related mental decline - at least that not associated with conditions such as Alzheimer's - can be avoided or reversed to some degree: "Mental declines are pathological for about 10 per cent of the general population over the age of 65, and not much can be done at this time to overcome the debilitating cognitive effects of diseases that affect the brain, such as Alzheimer's disease. But for the other 90 per cent of the population, cognitive decline need not be inevitable. ... we found it is never too late to start. With a little effort, even people in their 70s and 80s can see dramatic improvements in their cognitive skills." Science may or may not advance rapidly enough to save you from the consequences of poor health practices - it would be a shame to miss out on the future of healthy life extension medicine because you didn't take care of yourself today.

Link: http://www.sciencedaily.com/releases/2005/09/050916073232.htm

FuturePundit On Research Funding

Randall Parker of FuturePundit comments on the latest figures for medical research funding: "I am not surprised that diagnostics and therapeutic devices [research and development] yielded the best returns. Drug development returns have been declining. Diagnostic devices are taking off in in part because of a shift toward miniaturized devices. Diagnostics are going to follow in the path of computer chips with smaller devices becoming orders of magnitude more powerful and at the same time orders of magnitude cheaper. ... My own take on drug research is that it is becoming yesterday's approach to medical treatments. Most remaining health problems can not be solved with drugs. We need cell therapies and gene therapies much more than new chemical molecule drugs. Most diseases of old age and the very process of aging will be cured by gene and cell therapies and not by drugs."

Link: http://www.futurepundit.com/archives/003004.html

Exceptional Longevity in the United States

Leonid Gavrilov's latest project is entitled "Exceptional Longevity in the United States" and you can find out more from his blog:

The broad long-term objective of this project is to find out why some people manage to survive to extreme old ages (100+ years), and what are the driving forces behind mortality trends at advanced ages (which have important implications for public spending on health care, pensions etc.). This is an important issue not only for demographic forecasts of human mortality and population aging, but also for improving our understanding of the fundamental mechanisms of human aging and longevity.

...

This project is also inspired by unexpected findings from our pilot study of the U.S. centenarians at the Center on Aging supported by NIA and the Society of Actuaries, which suggest that very large differences (2-3 times) in chances of exceptional survival could be linked to such surprisingly "simple" early-life circumstances as person's birth order, birth place (within the United States), and even family socioeconomic background (being raised at farm). This amazing plasticity of exceptional longevity in response to "trivial" early-life living conditions indicate that environmental and behavioral factors should receive much more attention in longevity studies, because even the search for "human longevity genes" could be greatly facilitated when powerful confounding effects of childhood environment are taken into account.

It seems to me that statistical and actuarial assistance to the process of understanding how aging, genetics and metabolism interact will be come less and less relevant as the techniques of biotechnology and bioinformatics continue to improve. Statistical studies allow scientists to narrow the search for genes and biochemical mechanisms that are relevant to the matter at hand - but powerful enough tools will make this process unnecessary.

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p53, Tumor Suppression, Aging

The p53 gene has been the subject of a great deal of scientific attention in past years; it appears to important in many fundamental biochemical processes relating to aging and cancer. As is usual in biochemistry, the closer you look, the more complex things turn out to be: "the p53 gene, the most frequently inactivated gene in human cancer, does not produce only one unique p53 protein as previously thought, but at least six different p53 proteins (isoforms). ... This suggests that, in [some] tumours, p53 activity is being lost by altered isoform expression, rather than by mutation of the p53 gene itself." Meanwhile, research into the mechanisms of Progeria suggests that "hyperactivation of the tumour suppressor p53 may cause accelerated ageing."

Link: http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-49254.html

The State Of Stem Cell Businesses

The Economist paints a gloomy picture of the state of private and venture funding for stem cell research and commercialization: "Just over $1 billion was spent on stem-cell work last year, a mere 1% of global spending on health-care [research and development]. More than four-fifths of that investment came from governments. Venture capital, the traditional engine of biotechnology, is remarkably scarce in stem cells. Only $50m was pumped into the field last year, as private investors look for safer bets in more developed products with larger markets, where regulation and patent protection is more clearly defined. ... there are now roughly 140 stem-cell-related products in development, for various forms of cancer, liver disease and other conditions. But more than four-fifths of these projects are in early-stage development, where many a gleam in a scientist's eye dies."

Link: http://www.economist.com/business/displayStory.cfm?story_id=4427625

Longevity and Economic Growth

Andrew Price pointed me to an interesting paper on mortality (and, by extension, life expectancy) and economic growth, via Bradford Plumer.

Analyzing a variety of cross-national and sub-national data, we argue that high adult mortality reduces economic growth by shortening time horizons. Higher adult mortality is associated with increased levels of risky behavior, higher fertility, and lower investment in physical and human capital. Furthermore, the feedback effect from economic prosperity to better health care implies that mortality could be the source of a poverty trap.

I think that there are other factors at work in the African regions that are the focus of their paper, such as rapacious governance, absence of the rule of law, and so forth. Life expectancy and mortality in the economic boom times of the 18th century in Europe weren't much better than the worst of Africa today, after all. The basic concept is a good one, however, and we should turn it around and ask ourselves how much more economic growth could we experience if healthy life spans were greatly extended? I think it to be eminently sensible to view short-termism in the management of public companies, to pick one example, as a function of our life spans. Short-termism would still exist if we lived twice as long, but there is every reason to think that it would be lengthier short-termism, with less of the sacrifice of long term gains.

What long-term and potentially very profitable opportunities do we set aside because aging and death require us to hasten everything along - and because aging and death destroy more value than all the natural and man-made disasters worldwide each year? Now there is something to think on.

Technorati tags: economics, life extension

A Florida Stem Cell Initiative?

Wired reports on efforts to create a California Proposition 71-like stem cell research initiative in Florida: "Embryonic stem-cell research advocates in Florida have drafted a ballot initiative that would put $200 million toward the science over the next 10 years, citing frustration with lack of interest in the promising field among federal and state agencies. Floridians for Stem Cell Research and Cures, an organization formed to promote the new measure, must collect 600,000 petition signatures to get the measure on the Nov. 7, 2006, statewide ballot. The Florida Supreme Court must also approve the measure before it appears on the ballot. ... they'll keep the effort simple, small and straightforward, hoping to avoid the red tape that has plagued Proposition 71 in California."

Link: http://www.wired.com/news/print/0,1294,68940,00.html

Royal Society On Personalized Medicine

I've mentioned personalized medicine a number of times in the past: it's a promising part of the future of medicine for many reasons. Present day treatment is all too often a hit-and-miss affair, as we understand all too little about the large variance in effectiveness of therapies between individuals. The Royal Society has issued a lengthy report on timelines for the development of the underlying medical technologies. "The Society concludes that personalised medicines also known as pharmacogenetics have a promising future. However, it will be another 15 to 20 years before their use is widespread because of the many gaps in our understanding of how genetics relates to the causes of disease."

Link: http://www.royalsoc.ac.uk/news.asp?id=3781

Closer To An Alzheimer's Gene Therapy

Medical News Today has news of progress in Alzheimer's gene therapy research: "What we are showing is a proof of principle that stopping the synthesis of a protein that is necessary for the formation of the telltale plaques reverses the progression of the disease, and more importantly, the cognitive function of these mice, which had already been impaired, has now recovered ... Within a month of treatment, mice that had already suffered memory deficits could learn and remember how to find their way through a water maze ... It appears that these mice can come back from a very severe level of disease progression. This is a very important finding because humans are usually diagnosed when the disease has already progressed relatively far."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=30923

The State Of Research Funding

(From MSNBC). $100 billion a year may seem like a lot of money for medical research, but it's a drop in the bucket of medical expenditures in general - and the present regulatory environment ensures that a great deal of that money is wasted on needless hoop-jumping exercises. "The imbalance between late-stage and early-stage research is growing, the authors wrote, and is due partly to lengthy clinical trials required for new drug approval and partly to pure marketing. Companies often run costly studies to show their drugs work better than competitors' drugs." Which is disingenuous - companies are forced to run ever more costly and unnecessary studies by risk-averse and unaccountable government regulatory bodies. The best way to reduce the cost of medicine is to remove government regulation, thereby increasing the economic reward for greater research funding, and allowing that research funding to achieve results more effectively.

Link: http://www.msnbc.msn.com/id/9407342/

Reading "The Singularity is Near"

I have been working my way through Ray Kurzweil's "The Singularity is Near" (TSiN) over the past few days, having been the fortunate recipient of a review copy. The book might alternatively be titled "The Modern Futurist Consensus: a Review" or "Damien Broderick's The Spike: the Extended Remix." Those of us who have haunted transhumanist enclaves in the past few years (or more) are unlikely find new ideas here, but the book serves a most useful purpose in bringing the best and brightest of transhumanist, futurist themes and thinking all together under one roof, in a popularist manner, with a unifying, easily-marketed theme. It's been done before - by the aforementioned Damien Broderick, amongst others - but not quite as comprehensively. This sort of book is something of a necessary precursor to wider advocacy and education in today's culture; a pleasant irony, given the subject matter, and one could debate where in the present S-curve in the evolution of futurist thought TSiN fits.

My own two cents thrown into the ring say that the class of future portrayed in TSiN is something of a foregone conclusion. It's quite likely that we'll all be wildly, humorously wrong about the details of implementation, culture and usage, but - barring existential catastrophe or disaster - the technological capabilities discussed in TSiN will come to pass. The human brain will be reverse engineered, simulated and improved upon. The same goes for the human body; radical life extension is one desirable outcome of this engineering process. We will merge with our machines as nanotechnology and molecular manufacturing become mature technologies. Recursively self-improving general artificial intelligence will develop, and then life will really get interesting very quickly. And so forth ... the question is not whether these things will happen, but rather when they will happen - and more importantly, are we going to be alive and in good health to see this wondrous future?

As you might guess, my criticisms of TSiN center around the timeline predictions for development of new technologies, the acceleration of the rate of discovery, and the management of complexity. I made a stab at discussing this last item recently in connection with Arnold Kling's comments on TSiN (which are well worth reading, by the way):

Progress towards general (and/or strong) artificial intelligence (AI) - a grail for many transhumanists and other futurists - has been slower than we'd like. The level of difficulty has been consistently underestimated in the past, and I see this as one part of a larger underestimation of any form of complexity management. You may recall seeing this idea put forward in a variety of 1990s writing on the topic of nanotechnology; the production of millions of nanorobots wasn't thought to be as hard as the process of controlling and managing those nanorobots in a useful fashion - strategies for information processing are as much the key to future medical technologies as nanoscale and molecular manufacturing. Complexity is hard, both to manage and estimate in advance.

Now replace "nanorobot" with "human cell" and that's where we are today with biotechnology. Biological systems - such as your body, or even just a small piece of it - are immensely complex. The reason researchers can make meaningful progress today with medical technology such as gene therapies and stem cell research is that they are, effectively, tweaking settings on existing machinery that largely handles the complexity management itself. Our grasp of how things work - based on our ability to process information and build the tools required to gather information and effect change - is now adequate for this task, just as it is almost adequate to guide existing biological machinery to build replacement tissue and organs in a useful, controlled manner. But it seems to me to be a very large leap - in terms of managing complexity - to go from where we are today to reach the point of, for example, replacing biochemically complex systems within the body with artificial substitutes. Or reverse-engineering the brain, that sort of thing.

Kurzweil's commentary on types of complexity in TSiN is a good read - and one of the better explanations for the layman I've seen - but it seems a little disconnected from the actual business of dealing with complexity in ways that matter. My take on it all is that science is largely the process of discovering keys to complexity; by this I mean finding algorithms, recipies or methodologies that enable us humans to understand and manage complexity that would otherwise be beyond us. To take an applied example, manipulating stem cells through comparatively simple procedures enables scientists to perform tasks - the regeneration of age-related tissue damage - that they cannot even monitor in detail, let alone control. A simpler and more abstract example would be the mathematics and physics of atoms, comparatively simple equations that we can use to describe very complex collections of objects and behaviors.

We humans are in the process of building tools that enable us to create or meaningfully interact with ever-greater complexity, and computers are at the heart of it, but this process is one in which our individual, unaided capacities for complexity management are not increasing. Humans are still humans as of this decade, and the keys we utilize have to be useable at our level. I view the speeding of progress as part and parcel of building a larger capacity for discovering and utilizing the keys to complexity. This, as Kurzweil makes the case in TSiN, is a process that is growing exponentially, and we are moving out of the timespan in which exponential growth appears more linear.

There is one important area of complexity management in which we seem to be making little headway, however: the organization of humans in business and research. For all that we can now accomplish with faster computers and enormous leaps in telecommunications, we don't seem to have made significant inroads in getting large numbers of humans to cooperate efficiently. As Arnold Kling points out, that the excessive use of Who Moved My Cheese? is even in the running as something to try is not a good sign. I've been involved in more technological attempts to improve efficiency in large organizations, and the state of the art is not pretty - nor especially effective in the grand scheme of things.

I am prepared to go out on a limb here, as I have done before, and say that business and research cycles that involve standard-issue humans are incompressible beneath a certain duration - they cannot be made to happen much faster than is possible today:

I'm dubious about large reductions in the length of business or research cycles through technology while humans are still in the loop. You can certainly make the process cheaper and better, meaning that more attempts at a given business or research model will operate in parallel, but there is a point past which the length of the business cycle cannot be easily compressed. That point is very much a function of the human element: meetings, fundraising, decisions, organizational friction, and so forth - all very time-consuming and proven very resistant to improvements in the time taken.

This is not to say that they cannot be made cheaper. But cheaper doesn't equate to faster business and research cycles; rather, it means that any given problem will be tackled by many more parallel attempts. The professionals are joined by skilled amateurs, the priesthood dissolves, and everyone with a will to work gets in on the action. In this sort of a market, any given problem (what business model works, how does this disease process kill people, what does this biochemical signal do) is more likely to be solved in a single cycle of innovation. Biotechnology is not too many years away from this state of affairs, a repetition of what is currently taking place in the software development industry. If matters become cheap enough, people will be willing to risk ventures and research on incomplete solutions, on untested business models, and thus shortcut the existing cycle - but all to many forms of development are not vulnerable to this sort of shortcut. The answers cannot always be guessed or jumped to on the basis of incomplete work.

Back in the deep end, expensive projects mean conservative funding organizations, which means organizational matters proceed at a slow pace. This is a defining characteristic of our time: we have blindingly fast rates of research and technological advances once the money is on the table, but the cycles of business, fundraising and research are still chained to the old human timetable. I regard this incompressibility of the business or research cycle - the fact that a given iota of progress cannot be accomplished as fast as technology allows because of human organizational factors, and there is a certain minimum length of time taken to accomplish this iota of progress - as a form of limit on exponential growth, one we are now hitting up against.

Kurzweil's Singularity is a Vingean slow burn across a decade, driven by recursively self-improving AI, enhanced human intelligence and the merger of the two. Interestingly, Kurzweil employs much the same arguments against a hard takeoff scenario - in which these processes of self-improvement in AI occur in a matter of hours or days - as I am employing against his proposed timescale: complexity must be managed and there are limits as to how fast this can happen. But artificial intelligence, or improved human intelligence, most likely through machine enhancement, is at the heart of the process. Intelligence can be thought of as the capacity for dealing with complexity; if we improve this capacity, then all the old limits we worked within can be pushed outwards. We don't need to search for keys to complexity if we can manage the complexity directly. Once the process of intelligence enhancement begins in earnest, then we can start to talk about compressing business cycles that existed due to the limits of present day human workers, individually and collectively.

Until we start pushing these limits, we're still stuck with the slow human organizational friction, limits on complexity management, and a limit on exponential growth. Couple this with slow progress towards both organizational efficiency and the development of general artificial intelligence, and this is why I believe that Kurzweil is optimistic by at least a decade or two.

So how does this all fold into healthy life extension? Well, physical immortality is one obvious product of singularity-level nanotechnology, biotechnology and complexity management. There are no known barriers in physics to the construction of nanomedical systems capable of simultaneously managing, repairing - or replacing - every cell in our bodies. Even something as complex as the sum of all your cells can in principle be kept in the best possible shape for as long as you like - "all" it takes is knowledge, the future tools of nanoscale engineering and powerful enough computers. But when do we get there? This is the question, and it is one that shapes the actions of futurists and transhumanists. There are many who believe that the best sort of activism and advocacy for the future - even for healthy life extension - is in the area of artificial intelligence, because making self-improving intelligence arrive earlier will lead to all other currently pressing problems, such as age-related degeneration and death, being rendered trivial in the mid to long term. Obviously, I'm not in that camp: I'm sufficiently dubious about Kurzweil-like timescales - based on my views as set forth above - to think that we need to be tackling the problem of aging first.

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Enthusiasm for Radical Life Extension, Always a Welcome Sight

I thought I'd point out a blog essay on radical life extension that I stumbled across earlier today. The author is somewhat out of shape on the science and who is doing what, but can't be faulted for enthusiasm - the community could certainly do with more people with this sort of mindset. Advocacy is powered as much by enthusiasm as by anything else, after all. Some choice quotes, which I have hyperlinked for reference purposes:

The life extension field is haunted by pessimists who are hung up on the Greek myth of Tiphonius who asked the Gods for eternal life, but was doomed to become decrepid because he forgot to specify eternal youth. I would argue that one of the main goals of medicine is to help people live as healthy as possible for as long as possible. Getting the impaired, repaired

...

It seems that curing the diseases of old age is now more of an engineering problem than a scientific mystery. The Methuselah M-prize has been started by the people who got private industry into space with the Ansuri X-prize. The M-prize goes to the people who get mice to live significantly longer, in ways that may be applied to people.

If you can just survive to the next medical breakthrough technology, you might be able to survive a few years more, until the next little development, which might give you even more years. This way, if you're very lucky you may get climb a sort of "stairway to heaven" and leapfrog from one medical engineering discovery to the next. Imagine what the medical technology of 2150 might be able to do for us?

...

When talking about immortality its fascinating that some people get angry when you propose living forever. The audience for the panel were split between the "dyers" or "terminators" and the people who believed that life is worth living. One correspondent spoke to me about about living longer being a selfish use of Earth's limited resources. This ignores the fact that RIGHT NOW Paul and the many people who agree with him, are making selfish use of Earth's limited resources, and by the same argument that condemns old people to die in the future, they are condemning themselves to die right now. I asked himl if he was offering to suicide to give up his use of Earth's resources right now, but he declined. They've decided on a particular number that is "natural", and not only have they decided to die at that age, but they insist that EVERYBODY should be forced to go without whatever medical treatment might become available, and commit suicide at their favourite number. The dyers, with my correspondent as their spokesperson decided that most of them would like to die at age eight-five, which is about a ten year extension of the average life expectancy of seventy-five. This requires life extension technology not yet available. What right does anybody have to tell other people to commit suicide?

American writer Ronald Bailey wrote about the emotional battle between the pessimists and the optimists: "Future generations will look back at the beginning of the 21st century and marvel that intelligent people actually tried to stop biomedical progress just to protect their cramped and limited vision of human nature."

The hoary old Malthusian arguments (professions of faith, really) on the topic of resources and overpopulation just never seem to go away, no matter how well refuted or disproven. Longer, healthier lives will not lead to any challenge greater than that imposed on us by the ongoing tide of death and suffering that is aging. Challenges can be overcome - and far greater ones have been in the past century - but only if we are alive and healthy, capable of action.

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Fundraising For The Mprize

A great many generous folks have helped raise funds for the Mprize for anti-aging research over the past two years; here's an article on the efforts of the youngest volunteer to date: "When eight year old Avianna asks potential donors to help, they all realize that Avianna is not doing it for herself. Her approach is logical: 'Aging is bad, and it can be repaired in our lifetime.' She has caused her neighbors to consider a future in which increasing years of life doesn't have to mean becoming old and frail. Avianna's efforts have exceeded even her own optimistic expectations, resulting in $3000 of donations in just a few short weeks. Said Avianna, 'I want to help peole live longer so that they can help with the problems of the world more.'" The more people willing to help meet the Muhlestein Family Trust Challenge, the better.

Link: http://www.mprize.org/index.php?pagename=newsdetaildisplay&ID=081

Fetal Stem Cells, Spinal Injuries

From Wired, news of another step towards regenerative medicine capable of repairing damage to the spine. "Injections of human [fetal] stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again. ... But the new work went an extra step, suggesting the connections that the stem cells form to help bridge the damaged spinal cord are key to recovery. Surprisingly, they didn't just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin." Embryonic stem cells have also shown promise for repairing spinal injuries and paralysis.

Link: http://www.wired.com/news/print/0,1294,68913,00.html

Nanotechnology, Healthy Life Extension

The folk at Responsible Nanotechnology have added their own thoughts to biomedical gerontologist Aubrey de Grey's recent article on the intersection of nanomedicine and the Strategies for Engineered Negligible Senescence. How do the future of medical nanotechnology and the future of real, working anti-aging medicine overlap? Read the post here:

Of course, if CRN is right about how quickly molecular manufacturing can be developed (and probably will, once militaries and corporations start racing for it), then it will arrive long before anyone has a chance to become 200 or even 150 years old. That's the good news.

The bad news is that in different people, each aging process happens at different rates. If a thirty-year research cycle is enough to keep the average person alive, a fraction will die for lack of the breakthrough in less than 20 years. After several such cycles, the fractions add up, and by this model, most of the population would still have to expect to die of old age sooner or later. (This isn't covered in the article, but I emailed my analysis to de Grey, and he confirmed it as a concern.)

On the third hand, I expect that--if regulation allows--molecular manufacturing should allow a far shorter research cycle than 30 years. With the ability to build custom-designed diagnostic and treatment hardware on the fly for pennies per device, it should be possible for a research group to test and evaluate hundreds of treatments per year, benefiting almost instant feedback--which should make such a rapid testing cycle safer than today's medicine, if it's done responsibly.

I'm dubious about large reductions in the length of business or research cycles through technology while humans are still in the loop. You can certainly make the process cheaper and better, meaning that more attempts at a given business or research model will operate in parallel, but there is a point past which the length of the business cycle cannot be easily compressed. That point is very much a function of the human element: meetings, fundraising, decisions, organizational friction, and so forth - all very time-consuming and proven very resistant to improvements in the time taken. Regulations don't help either - if you want to slow progress, ensure that the end results are not as reliable or effective as they could be, and make the product more expensive, you can't do better than regulation. It has always puzzled me as to why CRN see ever larger regulatory structures as the way to go, but to each their own.

The Responsible Nanotechnology post ends on a gratifyingly sensible note, however:

The implications of extended healthspan are not as scary as most people assume. Birth rate has a much higher potential effect on the population than death rate. End-stage medical care takes more resources than simply staying alive and healthy. That's not to say there are no reasons for concern, but I don't think it should be assumed that trying to slow aging is irresponsible or destructive, as some have claimed. In any case, molecular manufacturing will pose far larger and more urgent problems than a population of healthy hundred-year-olds.

You can find an excellent Max More article on why overpopulation is unlikely in world of far longer life spans at the Longevity Meme.

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Revisiting Voyager Pharmaceuticals

I mentioned Voyager Pharmaceuticals in 2004 in the context of another new theory of aging. Here, JS Online presents a good article on both this theory of aging and the forthcoming trials for a related - and as yet unproven - Alzheimer's therapy. "In their paper published last year in the journal Gerontology, Atwood and co-author Richard Bowen titled the idea 'Living and Dying for Sex.' Simply stated, they say hormones that regulate sexual reproduction early in life can act in a harmful manner later in life, generally when people reach their 40s. That happens because in an attempt to maintain reproduction, the hormones futilely stimulate cells in the body to divide, resulting in cell damage and disease." It's unclear as to how much of age-related degeneration could be due to this mechanism, but it's clearly worth further investigation.

Link: http://www.jsonline.com/alive/news/sep05/356670.asp

The Merits Of Killifish

If you recall the discussions last year on creating a Methuselah Fly Prize to run alongside the Methuselah Mouse Prize, then you'll probably already know the significance of killifish in aging research. From Practical Fishkeeping: "Scientists are using killifish from the Nothobranchius genus to study the effects of aging.... Nothobranchius can be used to test the effects of aging at a pace comparable to that seen with other model organisms such as the fruit fly, Drosophila. ... Because they live fast and die young, they make good subjects for studying the effects of aging upon vertebrate cells." The cost and length of mouse experiments in healthy life extension science is an obstacle: for some types of experiment, flies and fish provide much cheaper, faster alternatives.

Link: http://www.practicalfishkeeping.co.uk/pfk/pages/item.php?news=727

Towards A Practical Alzheimer's Vaccine

Medical News Today reports on progress towards an Alzheimer's vaccine therapy in Austria: "The Vienna-based company Affiris is now reporting that it has succeeded in significantly reducing Alzheimer plaques by at least two-thirds in pre-clinical models by means of an innovative vaccine ... the Affiris approach not only avoids an autoimmune disease, but also offers the advantage of targeting simultaneously both the plaques and the soluble beta-amyloid fraction. Therefore, whether the soluble or plaque forms - or both - are responsible for causing the disease is not ultimately crucial for the vaccine's success." The company is aiming for human trials in 2006; the next few years should definitively show whether removing amyloid is a viable strategy for an Alzheimer's cure.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=30802

Tracking Stem Cell Recipients

The BBC reports on a follow-up study of some of the first recipients of stem cell transplants: "Blood cancer patients who had stem-cell transplants are virtually as healthy as their peers 10 years later ... This study looked at patients who had received haematopoietic cell transplants (HCTs) to replace diseased blood-forming cells produced in the bone marrow. All of the patients received their transplants between March 1987 and March 1990. Most of them had been treated for these two conditions. After 10 years, researchers compared their health with that of 137 healthy people, most of whom were siblings of the patients." The absence of obvious, serious problems connected with this form of therapy is good news - hopefully this will continue to be the case as much larger groups of patients are studied: "More than 45,000 people receive stem-cell transplants across the world each year."

Link: http://news.bbc.co.uk/2/hi/health/4251972.stm

Mprize: Meet the Mark and Judy Muhlestein Family Trust Challenge

Good news from the Methuselah Foundation, organizers of the Methuselah Mouse Prize, or Mprize, for anti-aging research:

The recent SENS II conference was a huge success and The Mprize one of its beneficiaries. Mark Muhlestein saw the possibility of building on the amazing research presented and accelerating the day when real anti-aging therapies are available by supporting the Mprize and has committed to $25,000 with an offer that expires Jan 1, 2006. From the date of conference end until then, ALL incoming donations will be matched 1:2 (ie. a dollar donated is matched by two from the Muhlestein commitment) until there are no more funds available. We're confident we can help ensure that this generous offer is taken full advantage of! Join us and let's get every penny of research incentive!

Our community has three months to meet this generous challenge grant and push the Mprize further towards the $2 million mark. If you've been thinking about donating to the Mprize to help grow support for the science of healthy life extension and accelerate progress towards real anti-aging medicine, then now is the time! Ultimately, we are responsible for the way in which the future turns out; if we want our future to be one of longer, healthier lives and effective medicines capable of reversing age-related degeneration, then we have to step up and help to make it happen. Sitting on the sidelines and hoping is not going to cut it - the future doesn't make itself, and the past is replete with examples of advances still possible yet never accomplished. We don't want healthy life extension to be left on the sidelines when progress is so clearly possible with greater public support and research funding; if you feel that way too, then donate!

Even just a few dollars makes a big difference in the long term; research prizes like the Mprize are a very efficient way of making your support count. The Ansari X Prize led to competitors raising 16 research dollars for every prize dollar - other prizes have been even more effective. One-time donations are very welcome, but if you can spare a few dollars a day then please consider joining the ranks of The Three Hundred:

For the price of a cup of coffee per day, would you like to join a select group of humanitarians who will be remembered for their vision and saving millions of lives?

Modern medical science continues to show us that the aging process may no longer be the intractable problem it has been perceived to be for every generation preceding ours. There is a present need to move faster towards a previously unattainable goal: the control of aging. This need for more rapid medical progess is only magnified by the current profound lack of funding for aging research. Funding springs, at root, from widespread public awareness of advances and possibilities in aging research. Educating the public is an essential step in moving philanthropists and governments to allocate more resources to the study of aging. The problems caused by aging leave us poor in body, spirit, and finances. We must step forward to tackle them!

I am confident that the wider community can meet this challenge grant and in the process increase public support - and improve the funding environment - for serious anti-aging research: now get out there and prove me right.

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On Stem Cell Line Mutation Rates

Randall Parker shares his thoughts on mutation rates in embryonic - and adult - stem cell lines at FuturePundit: "These results suggest that existing embryonic stem cell lines are going to have limited utility in the development of therapies. Lots of research can still be conducted on these stem cell lines. But I'd be very reluctant to have any of these mutated embryonic stem cells injected into yours truly. Also, years will go by before these stem cells can get massaged into useful forms for therapies and they will accumulate even more mutations in that time. Stem cell lines created just when they are needed (whether embryonic or slightly more differentiated adult stem cell lines) would reduce the risk of mutations. However, even 'just in time' stem cell lines would need extensive genetic testing because whichever cell would be used for the starter nucleus might contain mutations that put the resulting stem cell line at heightened risk of creating a cancer."

Link: http://www.futurepundit.com/archives/002995.html

Protofection At SENS 2

Kevin Perrott of Health Extension reports on biologist Rafal Smigrodzki's presentation on mitochondrial protofection at SENS 2: "It has become apparent that more than 90% of our [mitochondrial DNA] is mutated by adult life. He proposes that the mutation burden of mitochondria, although specific species may comprise less than 3% each, together combine to cause age related disease and point an even sharper finger at mitochondrial degneration as the main culprit in the aging process. ... If wholesale mitochondrial gene therapy becomes available AND [mutational damage to mitochondrial DNA] indeed turns out to be critical to the aging process, it is possible that this may be one of the most significant discoveries yet in biogerontology."

Link: http://www.healthextension.net/archives/2005/09/sens_ii_rafal_s.html

1000 Years Of Healthy Life Extension Explained

Aging researcher Tom Kirkwood has described biomedical gerontologist Aubrey de Grey's comments on the plausible results of accelerating healthy life extension technologies as "nonsense." Kirkwood, like many other mainstream gerontologists, doesn't buy into the idea that we can make real inroads into the treatment and reversal of age-related damage in next few decades. This, sadly, is a self-fulfilling prophecy - if everyone thinks that way, then it certainly won't happen, regardless of whether it is possible or not. Here is one of de Grey's comments from a BBC article:

I think the first person to live to 1,000 might be 60 already.

de Grey has a short and explanatory response to Kirkwood published in SAGE KE. Fortunately for those without subscriptions, it has also found its way to the Transhumantech list:

In your August 18th issue, Kirkwood [1] describes my recent claim [2] that the first person to live to 1000 could be 60 already as "laughable" and "arrant nonsense." I derive it as follows:

...

Arguable? Certainly. Laughable? MIT Technology Review's $20,000 "SENS Challenge" says not [8]. The longer that prize goes unclaimed, the hollower the skeptics' ex cathedra scoffing will ring.

Go and read the whole thing; I think you'll find it an excellent short justification for devoting high levels of funding to serious anti-aging research.

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ACT Raises More Funding

From Mass High Tech, welcome news that Advanced Cell Technology has raised another $17 million in venture funding. "The proceeds of the financing are expected to be used by the company for general corporate purposes and to accelerate its research and development of human embryonic stem cell technology and stem cell therapies with particular emphasis on retinal, dermal and hemangioblast cell lines." ACT has been something of a bellwether for private funding of stem cell based regenerative medicine - this news indicates an upturn in the funding environment is well under way for this vital branch of medical science. Good news for those people looking towards a future of effective therapies for common age-related conditions.

Link: http://www.masshightech.com/displayarticledetail.asp?Art_ID=69677

Sonia Arrison On Longevity Research

Sonia Arrison - who, incidentally, will be speaking at the forthcoming Immortality Institute Life Extension Conference - opines on the state of healthy life extension research in this op-ed at TechNewsWorld: "Society's long-held view of aging probably left us years behind in research ... Fortunately, those days are over, and numerous scientists are working on finding ways to extend human life by fighting aging. ... a disease is defined as "condition in which the functioning of the body or a part of the body is interfered with or damaged." Cell damage involved in the process of aging clearly fits under this definition. Since that's the case, one might wonder why the very same agency sports a Web page titled "Healthy Aging." That's like saying "Healthy Disease" or "Healthy Cancer." The explanation for this logical inconsistency lies in our low-tech past, which we are quickly leaving behind."

Link: http://www.technewsworld.com/story/46165.html

Immortality Institute's Life Extension Conference, November 5th 2005

The Immortality Institute's Life Extension Conference is coming up in Atlanta on November 5th 2005. The Institute represents one of the more dynamic offshoots of transhumanist culture in recent years; the conference promises to be a worthwhile event. The film Exploring Life Extension will get its first public airing - it will be interesting to see how Bruce Klein and the rest of the film crew distill hundreds of hours of interviews with members of the healthy life extension community into the essence of what we stand for and aim to achieve.

The Immortality Institute's science documentary, Exploring Life Extension, aims to create a realistic impression of the modern scientific pursuit of Life Extension. The documentary includes interviews with authors from the Immortality Institute's book, The Scientific Conquest of Death, plus more than 80 other individuals working to advance life extension.

The conference speakers include biomedical gerontologist Aubrey de Grey, biologist Michael Rose, Max More of the Extropy Institute, as well as representatives from the transhumanist end of the general artificial intelligence and cryonics communities. For those of you in the Eastern and Central US who have not yet had a chance to meet Aubrey de Grey, the driving force behind the Strategies for Engineered Negligible Senescence, this is a golden opportunity.

You can register directly from the conference page, just scroll down for the form.

The Immortality Institute founder, Bruce Klein, is a strong advocate of pushing out the boundaries in public discussion of healthy life extension. The Institute has a provocative name and step-right-to-the-end-goal mission statement, and quite deliberately so. I've pointed out the benefits of this sort of strategy in the past: provided you are discussing scientifically sound propositions, your wider community has little to lose and much to gain over the long term. Physical immortality - in the sense of vulnerable agelessness - is sound science; we know of no obstacles beyond our own considerable lack of understanding and capabilities when it comes to our cells, medical technology and related fields.

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Human Embryonic Stem Cell Therapy Trials Coming Soon

A great piece from Ronald Bailey at Reason Online focuses on the work of Korean stem cell researcher Woo Suk Hwang, who, it seems, is only just getting warmed up.

In accepting the award, Hwang said that his research could ameliorate the health problems that accompany aging, such as failing memories, muscle wasting, cancers, and immune system declines. With stem cell therapies "these might become conditions of the past," declared Hwang. He added that cloned stem cell lines from patients who suffer from chronic debilitating diseases will help researchers identify what goes wrong and point toward cures for diseases such as Alzheimer's, Parkinson's and diabetes. Hwang noted that with cloned stem cells we would be "treating our bodies with our own perfectly matched cells," thus avoiding the problem of immune rejection that bedevils conventional organ and tissue transplants.

...

Before his presentation, I talked briefly with Hwang and asked him when we might see therapies derived from human embryonic stem cells. Hwang smiled and told me that he expected to start transplanting cells derived from cloned stem cells into patients by the end of next year. He expects that the first patients will be a person with a spinal cord injury and another with Parkinson's disease. He will treat them with cloned cells that will be perfectly matched to those specific patients. Of course, lots can go wrong with the early development of biomedical treatments, and Hwang might be a tad overoptimistic. However, considering his results so far, Hwang may actually succeed in using human embryonic stem cells as a treatment. "I promise that our medical researchers are working non-stop," concluded Hwang.

This is what you can accomplish when you have the freedom to pursue your research - scientists elsewhere in the world are still at the stage of demonstrating successful embryonic stem cell therapies in animal subjects. Yet winning this freedom was a long and arduous process even in comparatively pro-science South Korea. Just imagine where medical research could be by now if not slowed, held back or blocked by unneeded regulations and anti-research legislation. As another scientist notes:

Speaking afterwards, Hwang's American collaborator, Gerald Schatten from the University of Pittsburgh, agreed that cloning lines of diseased stem cells instead of relying on animal research could "vastly accelerate" research on many diseases. However, Schatten noted that creating such cloned human stem cell lines in his home state of Pennsylvania is a felony. "It's amazing, said Schatten, "that we criminalize this work. Imagine if instead of one lab in Korea there were a dozen, or even a hundred labs, fighting to make sure we all live longer and healthier lives."

Unfortunately, we can only imagine this scenario today, because anti-research groups and hostile politicians have reduced the mighty river of medical research to a mere stream in most countries. It continues to mystify me that so many people are so eager to see therapies for age-related diseases blocked.

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Embryonic Stem Cell Heart Therapy

Express India reports on animal trials of regenerative medicine for the heart based on the use of embryonic stem cells. "An important aspect of their study was that the embryonic stem cells used in the research were not completely undifferentiated. They had been guided or coaxed into developing into heart cells before they were transplanted in the sheep. ... They are not fully differentiated. They will complete their maturation and their differentiation in vivo, once grafted into the heart ... I think that overall the (scientific) community has recognised the limitations of adult stem cells with regard to plasticity. If you really want to make cardiac cells you probably have to rely on embryonic stem cells." Adult stem cell therapies probably work via other means, as recent studies demonstrate.

Link: http://www.expressindia.com/print.php?newsid=54720

Cancer Vaccine Progress

(From Science Daily). Cancer is one of the biggest obstacles to healthy life extension amongst the common age-related conditions. The good news is that development of cancer vaccines - a form of immunotherapy that reprograms the immune system to attack cancer cells - is progressing nicely: "A team from the University of Pennsylvania School of Medicine has shown that by using [a cancer vaccine] they can cure mice with established breast tumors. ... We found that we can stop the tumor from growing out to 100 days, at which time we stopped measuring since this is a long time for experiments of this type. The tumors stopped growing or went completely away." The wider field of immune therapy is moving forward at a similar pace, as progress towards vaccines for Alzheimer's demonstrates.

Link: http://www.sciencedaily.com/releases/2005/09/050915004756.htm

Nanomedical Innovation Revisited

You might recall a clever delivery mechanism for cancer drugs based on the latest in nanoscale engineering: here we have another delivery mechanism for cancer therapies crafted using a completely different branch of nanotechnology. It's equally clever, however: "The vehicles look nothing like delivery trucks, though that is their function once inside the body. Instead, these so-called nanoparticles, which are assembled from three short pieces of ribonucleic acid, resemble miniature triangles. The microscopic particles possess both the right size to gain entry into cells and also the right structure to carry other therapeutic strands of RNA inside with them, where they are able to halt viral growth or cancer's progress." Advanced, low-cost biotechnology will give rise to a whole new generation of ingenuity and experimentation - we are seeing but the smallest first step.

Link: http://news.uns.purdue.edu/UNS/html4ever/2005/050914.Guo.nanoparticles.html

Aubrey de Grey On Aging, Cancer Research

From Casey Research, we have biomedical gerontologist Aubrey de Grey on the parallels between cancer research and real anti-aging research: "Once we realize that combating aging is an engineering problem, no different in essence from maintaining a car, many things become clearer. First, it's actually wrong to focus single-mindedly on preempting the accumulation of damage: we should prevent what we can, sure, but we should also strive to repair damage that has already occurred. ... Just how likely does success at a given venture, within a given time frame, have to be to justify trying? ... [Radical life extension is] pretty big benefit, and one worth fighting a war for, even if we think it'll only be in time for our kids and not for ourselves. More than that: just as the War on Cancer continues unabated (and with intense public support) today, despite the slowness of progress, so a war on aging, once started, will continue until it's won."

Link: http://www.caseyresearch.com/displayArchiveArticleWwnk.php?id=172

A Reminder That the Post-Kass Bioethics Council Will Be Just As Obnoxious

In the midst of William Saletan's latest at Slate, we find a timely reminder that the President's Council on Bioethics will be just as hostile to freedom of research and efforts to extend the healthy human life span post-Kass as it was when Leon Kass pronounced his desire to mandate aging and death for the masses from his position as chair.

The debate over today's topic, aging, breaks down along similar lines. The younger, more liberal faction wants to talk about allocation of resources. We spend too much money on sickness and not enough on prevention, they argue. Too much on keeping old Americans alive for two more months, and not enough on protecting African babies from AIDS. Too much on doctors, and not enough on safe air and water.

The older, more conservative faction wants to get beyond questions of allocation. Even if we can afford to extend life spans, should we? Where does it end? What's the point of living once you've had your education, raised your kids, and finished your labors? What if you can't think straight, recognize your family, or remember who you were? How many of your parts can we replace before your body no longer feels like it's yours? Maybe life should be finite even if doesn't have to be. Life is "not an absolute good," the council's gentlest speaker, Alfonso Gomez-Lobo, advises his colleagues. "There are moments in which we just have to open ourselves to the fact that we have to let go."

The conservatives worry that extended life will become pointless and empty - an escalator to nowhere, as council member Bill Hurlbut puts it. They fear the loss of limits. Life-extending procedures "are going to become easier to do and relatively less burdensome," says Kass. If "there's no such thing as enough," the obligation to prolong life will become "limitless," defying the principle of "the life cycle, the accepting of limits."

Philosophical nonsense on one hand, economic nonsense - the same old tired refrain of centralized control of resources and imposed equality, the one sure path to poverty and pain for all - on the other, united in opposition to research that could prevent the suffering and death of billions in the decades ahead. Can you imagine the uproar if these people were talking about suppressing cancer research or diabetes research? Bioethics has become a business of self-justification through the creation of problems where none exist, and thus has been harnessed by those groups who are opposed to progress and change. The Bioethics Council is just as much the rubber stamp for anti-research politics as it has been. It's a sorry end for once-admired medical ethics.

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Aubrey de Grey's SAGE Crossroads Trading Card

Biomedical gerontologist Aubrey de Grey is now one of the SAGE Experts honored with a trading card at SAGE Crossroads. I recall being sorry to see that he wasn't included in the first batch put up online, but there he is now, large as life. You can send the cards to friends via email - pick from a list of 50 gerontologists and other researchers in the field - so I'm sure you folks will be having fun with that feature. Yes, it's gimmicky, but I think it could serve as a good educational and introductory tool for certain demographics, such as younger students or journalists. It's certainly the case that public understanding of - and familiarity with - the names and deeds of aging and longevity research could be greatly improved.

While you're over there, feel free to pester the SAGE Crossroads staff on getting the transcript uploaded for the Genetics of Longevity webcast ... we've been waiting a while for that one.

UPDATE: I find myself in the set of demographics that would benefit from perusing the cards - so I think we'll have to add "advocates and pundits" to the list. It's quite helpful to frame the past few years of reading around the field by looking at sets of micro-CVs of the people involved.

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More On Tengion's Tissue Engineering

MSNBC looks at tissue engineering company Tengion, who have been in the press since receiving significant venture funding. "Tengion plans to use the proceeds from the private stock sale to further the development of its lead products, which are organs and tissues derived from a patient's cells that can be used to replace a patient's diseased or impaired organ or tissue. The company's most advanced product - not yet tested in humans - is an autologous pediatric bladder. In biology, autologous refers to cells, tissues or proteins that are taken from the individual being treated and reimplanted in order to augment, repair or replace specific organs or tissues. ... Tengion's goal is to use regenerative medicine to enable people with organ and tissue failure to lead healthier lives without donor transplants or the side effects of current therapies."

Link: http://msnbc.msn.com/id/9307801/

Kirkwood On Genetics And Aging

From Science Daily, a fairly content-light piece on researcher Tom Kirkwood's views on aging, evolution and genetics: "there is no single gene for aging. Throughout time, Humans have used energy to get food, produce offspring and survive danger - not to repair and maintain cells. So the maintenance system in the body slowly breaks down. ... But genetic factors do exist. 'Approximately 25 percent of how a person ages is inherited from parents. Stress, environment, nutrition, lifestyle and immunity play an additional role. Great variation between individuals can be seen in organisms such as round worms - and in humans.'" A much better summary of Kirkwood's views can be found in an EMBO Reports article from earlier this year.

Link: http://www.sciencedaily.com/releases/2005/09/050912125002.htm

Fighting The Wrong War On Cancer?

A long, very interesting article at Fortune looks at efforts to defeat cancer and finds them wanting: "virtually all these experts offered testimony that, when taken together, describes a dysfunctional "cancer culture" - a groupthink that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs; that fosters isolated (and redundant) problem solving instead of cooperation; and rewards academic achievement and publication over all else." Cancer research perhaps has more in common with the current sorry state of aging research than might be thought - I don't think the author correctly identifies the nature of the problem, but his piece echoes major concerns regarding the efficiency of medical research from other sources.

Link: http://www.fortune.com/fortune/print/0,15935,598425,00.html

Cancer Stem Cells In The Brain

As we now know, at least some cancers are created and sustained by errant stem cells. Cancer itself is an age-related condition, the end result of malfunctions in our complex cellular mechanisms - these malfunctions become ever more likely as we accumulate genetic damage over time. Researchers have been broadening their investigations, as Reuters notes: "Continued research into the biology of adult stem cells will aid in the understanding of how cancers originate and develop and may lead to possible new therapies for treating aggressive, currently incurable brain tumors ... This could help explain why these tumors are so hard to cure. Surgery and radiation therapy my remove the tumor, but the cancer could be replenishing itself from the stem cells."

Link: http://today.reuters.co.uk/news/newsArticle.aspx?type=scienceNews&storyID=2005-08-15T211339Z_01_HO576394_RTRIDST_0_SCIENCE-CANCER-BRAIN-DC.XML

Kevin Perrott on SENS 2

Mprize volunteer and healthy life extension advocate Kevin Perrott has posted his initial impressions of the SENS 2 conference at Health Extension:

Over the next little while as the buzz and exhilaration fades I will attempt to post both images and approved video clips from some of the more intriguing sessions although I will be hard pressed to pick and choose which those might be as indeed, the quality of the presentations was quite high and their very diversity makes it difficult to rate them. Still, there were a few which stood above the others in their descriptive capacity which was able to bring a crystal clear clarity and support and indeed vindication to the idea that rejuvenating aging tissues via replacement or removal of damage is happening.

Now.

Not in some far-off bad (or good) science-fiction novel... but TODAY.

A great deal of promising science relevant to repairing Aubrey de Grey's seven classes of age-related damage is taking place - but almost all of it is only incidentally relevant, drops in the ocean of general biomedical research that will lead to inadvertant healthy life extension. More support, funding and infrastructure must be directed towards a deliberate effort to reverse the causes of age-related degeneration if we are to see success in our lifetimes:

Making gains in SENS science in unrelated bits and pieces is likely to be a slow path for progress towards meaningful healthy life extension, however. Curing any one age-related condition is a wonderful thing for sufferers, but it will not increase healthy life span for anyone else - nor will it lead directly to therapies that can extend healthy life span without further investment and work. It would be much more cost-effective to directly address the root cause of aging and age-related disease.

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The Near Future of Stem Cell Science

A recent News-Medical.net article captures, I feel, the zeitgeist of stem cell science:

"Once we have found the factors by which body cells can be re-programmed into stem cells, then therapeutic cloning might become superfluous," said Hans R. Scholer, director of the Max Planck Institute for Molecular Biomedicine in Munster, Germany, at an international scientific symposium on stem cell research in Kobe, Japan.

...

"The fact that cell biology is becoming increasingly combined with molecular biology is a major step forward."

While first generation stem cell therapies - transplants, in effect, founded on well-educated guesswork and careful experimentation ahead of an understanding of the mechanisms involved - are on their way from laboratories and successful trials to the wider marketplace, the forward edge of research is now very much focused on understanding and controlling stem cell behavior and biochemistry ... right down there at the molecular level. As Scholer notes, knowing what makes a stem cell a stem cell is high on the priority list - being able to turn normal cells into stem cells on demand would solve a great many logistical problems for regenerative medicine aimed at repairing age-related conditions.

Fighting aging through advanced medical technology will be more than just a matter of brewing up stem cells and setting them to work, however. For example, one problem that cannot be solved with an infinite supply of your own stem cells is the effect of accumulated DNA damage, occuring in both cell nuclei and power-generating mitochrondria. This damage is happening to your stem cells as well as your other tissues, degrading their efficiency at best and creating cancer stem cells at worst.

The longer and harder you look, the more complex our cellular biochemistry becomes. It makes developing the technologies of radical life extension seem like a daunting task, to say the least. But it is important to remember that it this worthy goal is no more daunting nor difficult than curing cancer: the key is funding and public support for the science of healthy life extension.

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More Brain Stem Cell Research

The Life Extension Foundation News reports on further progress for brain stem cells. Researchers "have been able to get mouse brain cells to duplicate in a lab dish for the first time, increasing the odds that they may one day be able to do the same with human cells. ... their cell culture method offers the promise of producing a limitless supply of a person's own brain cells to treat illnesses ranging from Parkinson's and Alzheimer's disease to epilepsy. ... We've isolated for the first time what appears to be the true candidate stem cell. Thave been other candidates, but in this case we used a special microscope that allows us to watch living cells over long periods of time ... so we've actually witnessed the stem cell give rise to new neurons. Possibly, a different method may come up to identify the mother of all stem cells, but we're confident this is it."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2681&Section=AGING

New Stem Cell Institute At Cambridge

It seems appropriate that as the second SENS conference is wrapping up, Cambridge University has announced a new Institute for Stem Cell Biology: "Prof Smith, currently director of the MRC Centre of Development in Stem Cell Biology at Edinburgh University, will initially share his time between Cambridge and Edinburgh before moving with his lab to Cambridge next August. His research will focus in particular on embryonic stem cells, determining how stem cells maintain themselves, and how they become specialised into the different cell types of the body." The degree to which a field of science is prospering can be measured in conferences held and concrete poured - stem cell research is doing fairly well, it seems, despite political hostility and stifling regulation.

Link: http://www.cambridge-news.co.uk/news/city/2005/09/10/6ad3334a-fbf1-4df1-aa52-321a546dc1bc.lpf

Wrapping Up the Science at SENS 2

As reported by Frank Rummel, the second Strategies for Engineered Negligible Senescence conference (SENS 2) held this week is wrapping up - all bar the traditional dinner and punting, that is. Rummel is coming back with goodies for those of us watching online:

In retrospect, I've made new friends and learned much about ageing research and SENS. I've got some ideas for how I can promote the curing of aging, but there is much work to be done.

When I get home, I'm going to store the interviews I've gathered along with one complete Powerpoint presentation video that I captured in the Internet Archive for posterity. I'll keep you posted.

I have it on good authority that some of the Mprize volunteers and other interested folks will be bringing back multimedia as well.

In an earlier post, Rummel comments on the largely missing mainstream media:

The Longevity Meme reported an article about SENS 2 in Guardian Unlimited this morning and I spoke with a film crew (http://www.arte-tv.com/) that was reporting for German and French language TV yesterday. Other than that, big J journalism was absent from SENS 2. One can only conjecture the underlying causes of the failure of media to pick up on the importance of this historic event.

It has to be said that I'm also surprised. Admittedly, yes, it's a hard science conference, but when you have Korean stem cell researcher Hwang Woo Suk, Michael West of Advanced Cell Technology and many others of equal note - such as Ellen Heber-Katz and Amit Patel - all coming to the same Cambridge conference on advancing a cure for aging, it is suprising to me that only the Guardian turned up to see what was going on. Thankfully the economic barrier to entry for journalism has fallen to the point at which there really is no excuse for any event of note to go uncovered. Thanks go to Frank Rummel for spending the time and resources to get the job done.

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Grants, But Not

The Sacramento Bee reports on progress, sort of, for the California Institute for Regenerative Medicine: the first grants have been declared, but "the money comes in the form of an 'IOU' because bond sales to pay for the research are tied up in litigation. Robert Klein, chairman of the California Institute for Regenerative Medicine governing board, said the grantees are encouraged to begin their programs now if they have the money, with the promise of reimbursement later. The award winners, not surprisingly, include research heavies such as UCLA, Stanford University, UC San Diego and UC San Francisco." The wasteful battle over funding embryonic stem cell research and stalling of actual money awards looks to continue into next year at the current rate - par for the course for public programs.

Link: http://www.sacbee.com/content/politics/story/13543609p-14383968c.html

First Press From SENS 2

The Guardian reports on the Second Strategies for Negligible Engineered Senescence (SENS) Conference and the work of biomedical gerontologist Aubrey de Grey: At a conference at Queen's College, Cambridge, this week, Aubrey de Grey, a 41-year-old Cambridge computer scientist, told a research audience that there was no reason why people should not live to 1,000. It sounds like science fiction, but for all that Dr de Grey has been dismissed as a crank, his papers continue to be published in peer-reviewed journals and scientists continue to flock to his meetings. The editor of the MIT Technology Review has gone so far as to offer a [$20,000] prize to any gerontologist who could put together a serious argument refuting his claims. So far there have been no takers." Don't forget that you can help advance serious anti-aging science by donating to the Mprize for longevity research.

Link: http://www.guardian.co.uk/print/0,3858,5282378-103690,00.html

Your Stem Cells Or Someone Else's?

An interesting view on the near future of stem cell transplant therapies from Medical News Today: "Tricking the body's immune system into ignoring stem cells will be the key to successful stem cell transplants ... Our recent experiments suggest that we could use regulatory cells to stop the immune system responding to foreign transplants, whilst leaving the rest of the immune system intact ... Cloning stem cells using a patient's own cells is another option for preventing the rejection of stem cell transplants. ... However, the cost and intricate nature of this procedure means that it may not prove to be a practical option for widespread use." This is from someone working on the immune system of course; it seems to me that the majority of recent successful trials and studies have used the patient's own stem cells.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=30395

Finding Heart Stem Cells

Adult stem cells are everywhere in the body - the difficulty lies in identifying and isolating them for therapeutic use. The promising nature of first generation stem cell transplant therapies means that new sources of adult stem cells can only be a good thing. In this short Washington Post article, we hear of new progress: "Japanese researchers have discovered stem cells in human heart tissue ... [the researchers] were able to culture stem cells from the samples that developed into different types of cells, including heart muscle cells, blood cells and neurons, the report said. Injections of the cells into a mouse that had suffered an embolism helped the animal regenerate damaged heart muscle and blood vessels. Similar tests are planned on dogs and pigs before conducting clinical tests on humans as early as next spring."

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/09/08/AR2005090801940.html

Leon Kass Departs the Bioethics Council

Given my considerable disapproval of the positions put forward by Leon Kass, not to mention my thoughts on the President's Council on Bioethics and, indeed, bioethics in general, it seems both worth noting and no news at all that Leon Kass has departed the Council. As Ronald Bailey notes over at Hit and Run, it will continue to be business as usual in a council that more or less reflects the reprehensible views of its former chair.

The bottom line: Pellegrino's appointment as chairman of the President's Bioethics Council will, if anything, increase that body's opposition to a lot of biotechnological progress.

Amongst that biotechnological progress is the quest for longer, healthier lives. People like Kass want to use government power to ensure that you and I suffer and die by outlawing the research and use of healthy life extension technologies. That's murder in my book, however you choose to try and justify it, and we must fight to ensure that these despicable ideas gain no more ground.

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Stem Cell Pluripotency Fully Decoded?

Good news from EurekAlert: "Once an embryo is a few days old, the stem cells start to differentiate into particular tissue types, and pluripotency is forever lost. But if stem cells are extracted, researches can keep them in this pluripotent state indefinitely, preserving them as a kind of cellular blank slate. The therapeutic goal then is to take these blank slates and coax them into, say, liver or brain tissue. But in order to guide them out of pluripotency with efficiency, we need to know what keeps them there to begin with. ... We've uncovered a key part of the wiring diagram for these cells and can now see how this is accomplished." Oct4, Sox2, and Nanog proteins are the master regulators. "These findings provide the foundation for learning how to modify the circuitry of embryonic stem cells to repair damaged or diseased cells or to make cells for regenerative medicine."

Link: http://www.eurekalert.org/pub_releases/2005-09/wifb-rdk090705.php

Conservatism In Aging Research

From Penn State Live, a good example of conservatism in aging research: "As far as maximum lifespan goes, we suspect it's around 125 years. There's no evidence that humans can live any longer than that. ... I don't suspect that we'll see maximum lifespan increasing beyond 125." This is a "magic number" - and an example of magical thinking, if you ask me. Laboratories around the world are teeming with life-extended flies, mice and worms, we can make the strong case for describing and repairing the causes of aging, and rapid progress is being made in our understanding of human biochemistry and genetics - the cogs of the complex machine that is the human body. Yet the aging research mainstream insists that we will never make any meaningful progress in healthy life extension. This, not to put too fine a point on it, is utter nonsense.

Link: http://live.psu.edu/story/13373

VesCell / TheraVitae: Interesting To Note

It is interesting to note that TheraVitae is now pushing their VesCell brand of adult stem cell therapy for heart disease - with the procedures performed in Thailand - quite aggressively in the US. They've recruited Amit Patel, a researcher in the field involved in US trials of stem cell heart therapies, and are conducting a slick advertising campaign. This seems to me to be a step forward; private capital is now confident enough in stem cell medicine to be funding and marketing medical tourism to Asia in the US. From their website:

VesCell(tm) is "autologous" adult stem cell therapy. That means we use stem cells taken from your own blood . These stem cells are named "ACPs" (Angiogenic Cell Precursors). ACPs are cells that induce the growth of blood vessels. These cells may also turn into additional types of cells that can benefit heart patients. Similar cells, but probably less effective than ACPs, have successfully been used in dozens of clinical trials all over the world.

Cardiologists and cardiac surgeons are currently using VesCell(tm) to improve the quality of life of patients suffering from ischemic heart disease (or coronary artery disease) cardiomyopathy and congestive heart failure by relieving debilitating symptoms such as severe angina pectoris (severe chest pain) and increasing exercise tolerance.

Overseas visits for stem cell therapies - that will not be approved in the US in the forseeable future - have been taking place for some time now, but I don't recall the groups involved making waves to this extent in the past. Which is a pity, as the deployment of working therapies outside the US is one of the few remaining things that can temporarily speed up the regulatory morass inside the US.

It will be interesting to see how this plays out; medical tourism will grow rapidly if the most impressive new therapies are increasingly deployed outside the US. If companies like TheraVitae turn a profit providing this service, then there will certainly be more providers next year and the year after - it might be the first step in a chain of events that finally succeeds in reining in the FDA and the risk-averse regulatory culture that is blocking and slowing progress in the US. We can hope.

As to whether VesCell is a viable stem cell therapy, we shall see - but trials of comparable therapies and stem cell technologies have been successful and increasingly promising for years now. Given the choice between trying stem cell therapies oversees or the comparatively crude medical technologies generally available in the US, I know where I'd be heading if I had heart disease.

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Aubrey de Grey On Aging, Nanomedicine

In case you haven't seen biomedical gerontologist Aubrey de Grey's views on nanomedicine, here he is in Always On: "I think the first therapies, the 30-year-conferring ones, will probably not involve nanotech at all ... But as I've explained, the problems to be solved will get progressively harder as time goes by, and we can't afford to slow down - if any of those seven types of damage reaches pathogenic levels, it's game over. I think it's quite likely that pure biotechnology will come up against some brick walls by the time we get out to ages like 200 or 250. At that time, we'll need machinery that's fundamentally different from enzymes and vaccines and such like, let alone pharmaceuticals: machinery that we can control as precisely as we control computers. Nanomedicine will need to be at the heart of all medicine by then, but especially at the heart of life extension medicine."

Link: http://www.alwayson-network.com/comments.php?id=11895_0_35_0_C

Stem Cells, Science And Politics

Every change in our knowledge of embryonic stem cells is spun by the anti-research camp these days, it seems, but this is important science for the future of medicine. Ronald Bailey at Reason Online dives into the politicized mess to extract a sensible summary: "New research shows that human embryonic stem cells acquire mutations and other genetic changes over time as they grow and divide ... the new Johns Hopkins research will become a part of a standard quality control regimen that identifies and isolates genetically normal stem cells that can be safely used in therapies. ... Stem cell lines, like any other drugs, will have expiration dates. This is not the death knell of embryonic stem research as some opponents might fondly hope, it's just another problem to be solved."

Link: http://www.reason.com/rb/rb090705.shtml

Blogging From SENS 2

Frank Rummel of Anti-Aging Medicine & Science is blogging from the SENS 2 Conference in Cambridge, England. First post in the series is here:

SENS 2 is about to begin and already I'm overflowing with interesting information and news. Currently Aubrey de Grey is making his opening remarks. And the first speaker is up...

Kevin Perrott of Health Extension and a number of other blog-enabled folks are also in attendance, so I'm hoping we'll see more in the way of reports and commentary once they have the time and connectivity.

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Nanomedicine In The Near Term

Forbes looks at the near future of medicine, dominated by nanotechnologies for detection and manipulation and our increasing knowledge of genetics and cellular biochemistry. This is all part and parcel of the dawn of personalized medicine; it's a truism that almost any condition can be successfully treated or averted if caught early enough. "Molecular imaging agents could speed the advent of a new era of personalized medicine, in which therapies are tailored to patients' individual gene maps and doctors can monitor the treatments' impacts on a molecular scale. ... We are trying to revolutionize the way we look at the body ... In the future we will look at unique molecular beacons that signal disease."

Link: http://www.forbes.com/forbes/2005/0919/107_print.html

Improving Stem Cell Technology

Medical News Today reports on an advance illustrative of the pace of progress in the well funded portions of regenerative medicine: "researchers have developed a new purification procedure that gives direct access to muscle stem cells. These cells can both repair and contribute to the progenitor cell population of damaged muscles ... 20,000 purified muscle stem cells were as efficient as one million cultured cells in muscle fibre repair, when grafted in dystrophic mouse muscles ... this higher regenerative capacity reflects these cells' ability to more effectively colonise grafted muscle. Cultured cells undergo modifications that make them less efficient, probably partly because they tend to differentiate too quickly, losing their ability to regenerate damaged cells."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=30179

Peer At Every Study For Signs Of Calorie Restriction

Via the transhumantech list, comments on life span experiments in mice and unintentional calorie restriction. This is a helpful reminder in light of the recent vitamin E study on aging accelerated mice. Read it here:

There is one thing that I learned during my time as a research fellow in neurodegenerative disease: almost all medication tried in mice increased their lifespan: levodopa, pergolide, eldepryl, you name it. The thing is that all this sort of medication causes some nausea and thus anorexia, and if mice eat less, they live longer. Vitamine E in high dosages can also induce nausea.

...

ANY calorie restriction typically extends lifespan dramatically so if the animals don't eat you get bad data unless you've identically restricted your controls.

This is why the calorie restriction community is justifiably skeptical of a great many animal studies. The effects of calorie restriction on life span in mammals are very much proven, but all too many experimenters fail to control properly for these effects.

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Another One From The Pro-Death, Pro-Aging Contingent

I ran across a particularly egregious pro-death, pro-aging op-ed just a few days ago and thought I would share it.

People who live a healthy lifestyle should be rewarded with a long life. Millionaires who can afford the costs of Klotho gene therapy should not have an advantage over the common man. Each person has a certain period of time to make his or her contributions to the world and for that period of time is granted the use of Earth's resources. To fester in a realm of impoverishment is not the key to the success of the human race.

One of the purposes of science is to make life more enjoyable by reducing the pains of cancers and diseases, but prolonging life doesn't necessarily make it more enjoyable. We aren't meant to be Methuselahs. I'm with Billy Joel on this one. Only the good die young.

Where to start with something as outrightly ridiculous as that? I do think that the editorial as a whole serves as a good, albeit exaggerated, example of a certain class of knee-jerk reaction to healthy life extension, but beyond that it's the response of someone who fears change and inequality more than personal pain, suffering and death. There are far too many people like that in the world, and we must win them over as a part of broadening support for longer, healthier lives; both change and inequality exist regardless of fear, and neither is necessarily a bad thing. Malthusian fears are nothing more than fears, for example - human ingenuity has risen to best greater challenges in past decades.

It seems self-evident to me that the challenges of an ageless, disease-free world would be trivial compared to the challenges posed by this ongoing plague of suffering and death that claims tens of millions of lives every year - but, sadly, not everyone thinks that way. Mistaken Malthusian ideas on overpopulation and resource depletion, repopularized again and again despite continual proof to the contrary, cast a long shadow yet, as do the politics of envy and spite.

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The State Of Alzheimer's Research

The Life Extension Foundation reprints a review of the state of research into Alzheimer's disease: "Now, another half a dozen drugs and therapies are poised to go into trials. Yet another 300 drugs are at various stages of development, and geneticists are also at last homing in on the genes implicated in the disease. And in what promises to be the biggest development so far, a new vaccine designed to prevent the onset of Alzheimer's is due to go into human clinical trials, probably in the UK, within the next few weeks." This diversity of progress results from a mere 15 years of high levels of funding; imagine what could be done in the fields of aging and serious anti-aging research if they received the level of funding they deserve.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2674&Section=AGING

Free Radicals And Vitamin E

An interesting experiment is reported by EurekAlert: a form of mice suffering from accelerated aging benefit greatly from vitamin E supplementation. The researchers suggest these results "are in line with the free radical theory of aging." The more products of free radical reactions seen in the mitochrondria of these mice, the less capable those mitochondria were - and we already know that mitochondrial decline is strongly linked with degenerative aging. This is similarly the case for mitochondria in the brain: "Moreover, brain mitochondrial enzymatic activities were linearly related to mice success in the tests of neuromuscular function and of exploratory and cognitive activity and to the maximal mice life span." The caution here is the accelerated aging - the vitamin E is making up for protective mechanisms these mice lack, and this may or may not increase our understanding of normal aging.

Link: http://www.eurekalert.org/pub_releases/2005-09/aps-hdo083105.php

Towards A Real Artifical Kidney

Medical News Today reports on progress in shrinking down replacements for dialysis technology: "Researchers have developed a human nephron filter (HNF) that would eventually make possible a continuously functioning, wearable or implantable artificial kidney. ... In the ideal RRT device, this technology would be used to mimic the function of natural kidneys, continuously operating, and based on individual patient needs. No dialysis solution would be used in the device. Operating 12 hours a day, seven days a week, the filtration rate of the HNF is double that of conventional hemodialysis administered three times a week." Nanoscale engineering is making a great many interesting concepts possible in the world of prosthetic replacement parts.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=30109

The Aging Enigma

The Harvard Magazine looks at aging research: "Is aging necessary? Are the wrinkles and gray hair, weakening muscles, neurodegeneration, reduced cardiovascular function, and increased risk of cancer that afflict organisms toward the end of their lives inevitable? Or are these age-related changes part of a genetic program that can be altered?" The article is a review of the conservative gerontological position on aging and where we are in our attempts to understand and manipulate the aging process - all metabolic or genetic investigation and tinkering, in other words, with no mention of SENS-like work to repair and reverse the damage of aging. This absence is very much part of the problem when it comes to making meaningful, rapid progress towards healthy life extension.

Link: http://www.harvard-magazine.com/on-line/090548.html

A Commencement of Tagging

In a fashionably late adopter manner, I have finally acquiesced to the power inherent in self-organizing, distributed taxonomies. Moving forward, I will be tagging my posts the Technorati way; it will be interesting to see how it affects traffic, accessibility and the reach of the Fight Aging! message, if at all. If you'd like to know how people come to find Fight Aging!, the hierarchy of referrers runs something like this:

This rather content-light post is the beneficiary of a recursive, self-referential tag, but I'll be trying to tag future posts a little more helpfully.

Technorati tags:

Upsets at Alcor

Alcor, the largest cryonics provider, has not experienced the best of luck with staff in the past. As their latest newsletter makes clear, it looks like the poor luck is still ongoing:

Alcor's President and CEO, Joe Waynick, has decided to leave Alcor and pursue other interests. We received his resignation effective August 28, 2005. Joe has been President and CEO for nearly two years. He will continue to be an Alcor member. We wish Joe the best in going forward.

...

Second, on another matter, we have learned that a substantial sum of money is missing from Alcor. We suspected that a former employee misappropriated approximately $180,000. Last week, the police arrested former Alcor bookkeeper, Tim Reeves. While Mr. Reeves has yet to be tried on these charges and is innocent until proven guilty, the police have informed us that he has confessed to most of the theft. We are cooperating with the Scottsdale prosecutor assigned to this matter, and we will keep you informed as the case progresses. We are also working with the police and a private investigator to recover the funds.

The embezzlement is unfortunate, but managing the aftermath seems to be in hand and it will probably have no negative effect on the organization's capacity to serve existing customers - thanks to the dedication of present staff and volunteers. The embezzler (or embezzlers) were stealing vital resources needed to support individuals in cryonic suspension who are in no position to protect themselves, a notably despicable action in a world filled with despicable actions.

I'm sorry to see Joe Waynick move on: I have long said that a more professional, business-oriented hand on the wheel would help Alcor make the jump to the next level. In order to provide cryonics services to a greater number of people, Alcor simply has to grow, become more professional, diversify their technologies into other profitable outlets - doing all the things that any business must do as it moves forward to greater success. To my eyes, Waynick brought a necessary mindset to the job; I hope that his replacement will be looking to the same future, as it seems that Alcor still has a way to go.

Common Sense On Wealth And Longevity

Plain common sense on the relationships between wealth, health and longevity is, sadly, hard to find in the mainstream media. Here is some from the Financial Times: "The older segment of the population does consume a high share of resources simply because of the higher probability of disease and death with advancing age. But this does not hold for the individual patient: for the same condition, older patients use less healthcare than younger ones. The highest costs occur in the 12 to 18 months prior to death, and this is true at any age. What is expensive is the cost of dying, not the cost of ageing. ... Put simply; health, plus longevity, generates wealth." Live healthily for longer and you can work and save for longer. Mandatory retirement forced by law is deeply unethical, as are wealth transfer schemes like social security.

Link: http://news.ft.com/cms/s/365c78b4-1b4e-11da-a117-00000e2511c8.html

Research Prizes For Better Science

The Mprize for anti-aging research gets a good mention in a recent PLoS Biology article on research prizes. Personally, I believe you'll be hard pressed to do better than harnessing the engine that is human competitive instinct - but not everyone thinks that way, it seems: "It is not so much that legitimate ageing researchers do not want to be seen as actively seeking a prize, as it is that a research strategy built on the goal of winning the prize would be way too high a risk. When I heard about [the M Prize] we were in the midst of our ovary transplant mouse studies and it crossed my mind momentarily that maybe we'd be in the running. ... If we were to ever win this prize (hypothetically), it would be by default rather than by inspiration; that is, we would claim the prize (since why not?) but that would not have been the driving force." To me that simply sounds like the Mprize fund needs to grow some more - so donate!

Link: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030288

Supercentenarians And Skeptics

The BBC looks at those people who reach extreme old age and the longevity research that seeks to understand why. It's a reminder that most gerontologists - and journalists - are deeply skeptical of the ability of advancing science to improve human capabilities. From Tom Kirkwood: "It's a bit like the world record for the mile," says Mr Kirkwood. "Once it was thought that no one could run a mile in under four minutes. ... The current world record can always be broken, but it's highly unlikely we'll see anyone run the mile in two minutes." But there is a way to do it - it's called an automobile. Gerontologists are failing to account for the future of medical technology, and by their pronouncements are suppressing public support for research that could lead to greatly extended healthy life spans.

Link: http://news.bbc.co.uk/2/hi/uk_news/magazine/4207850.stm

Reviewing Fat Stem Cell Research

The use of adult stem cells from adipose tissue (fat, in other words) is a growing field within regenerative medicine, as EurekAlert reports. "Findings suggest that adipose-derived stem cells can be used to repair or regenerate new blood vessels, cardiac muscle, nerves, bones and other tissue, potentially helping heart attack victims, patients with brain and spinal cord injuries and people with osteoporosis. The work to be presented reflects a growing number of researchers who believe that adipose tissue (fat) will be a practical and appealing source of stem cells for regenerative therapies of the future. ... Five years ago we were seen as mavericks. Now there is a sense of validation and growing enthusiasm from an increasing number of international researchers who view adipose tissue as a potentially valuable source of therapeutic cells."

Link: http://www.eurekalert.org/pub_releases/2005-09/uovh-asc090205.php

Talking Klotho at the Immortality Institute

A good discussion is underway in the Immortality Insitute forums on the topic of the recent klotho research. Michael Rae suggests that this was yet another experiment in which life span was not measured against the proper control groups - something that has bedeviled much research in mice in the past, and that calorie restriction groups have spent a fair amount of time and energy discussing.

All that the extra klotho dose did was move the 2 transgenics closer to - and in no case fully! - the average and maximum lifespan expected of mice that aren't genetically disfavored or in poor husbandry conditions. In the case of the females, the effect is nearly negligible; since the data were never formally reported, I'm guessing that the difference was statistically nonsignificant, as I suggest it was also "clinically" and scientifically.

Of course, a zillion things - melatonin, cysteine, hydroxylamine, alpha-tocopherol, ethoxyquin, 2-mercaptoethylamine, etc etc - do this. This tells us something about how antioxidants can counter the abuse of poor animal husbandry or bad genes, but it doesn't tell us anything about basically healthy animals - and even less about aging per se.

Michael goes on to make a point I agree with wholeheartedly:

What is needed is interventions which directly target aging damage.

Klotho is not that, even if the experimental conclusions are validated - slowing aging via metabolic tweaks is not the way to radical life extension.

Supercentenarian Research Foundation

The Supercentenarian Research Foundation (SRF) is opening its doors online. The SRF "is being formed as an international 501(c)(3) organization to accept tax deductible donations that will be utilized to fund research into the biology of aging. The initial focus will be on supercentenarians, their siblings, and offspring, but successively younger age groups will also be investigated. Before research into methods of intervening in aging are conducted, diagnosis of the causes and effects of aging as exhibited in supercentenarians will be studied in order to determine 1) why they live longer than most, and 2) what limits their life span. Consideration will be given to all reasonable theories of aging to answer these questions, but none will be adopted a priori."

Link: http://www.supercentenarian-research-foundation.org/

Reminder: SENS2 Next Week

The Second Strategies for Engineered Negligible Senescence (SENS) Conference kicks off on the 7th of this month in Cambridge, England: a gathering of scientists talking seriously about how to halt and reverse degenerative aging. Judging from the flurry of last minute registrations and media inquiries, it's going to be a packed, interesting event - very much the place to be this month. This year's SENS Lecture will be given by Michael West, CEO of Advanced Cell Technology, and Woo Suk Hwang is amongst the well known scientists in the field of regenerative medicine to be giving a presentation - the conference program contains a number of other luminaries. Healthy life extension is moving up in the world!

Link: http://www.sens.org/sens2/

Height and Longevity

I just noticed an interesting post from John Hawks on correlations between height and longevity:

Findings based on millions of deaths suggest that shorter, smaller bodies have lower death rates and fewer diet-related chronic diseases, especially past middle age. Shorter people also appear to have longer average lifespans. The authors suggest that the differences in longevity between the sexes is due to their height differences because men average about 8.0% taller than women and have a 7.9% lower life expectancy at birth. Animal experiments also show that smaller animals within the same species generally live longer.

...

The authors also suggest that the added longevity due to caloric restriction in experimental animals may actually be a reflection of small body size, rather than of caloric restriction per se. Their preferred explanation is called the "entropy theory" of aging, which essentially is the argument that the bigger you are, the more things can go wrong.

The calorie restriction connection doesn't jump out at me as plausible now that we know more about the underlying biochemistry - it seems more likely to me that it's the other way around. A lower calorie intake over a lifetime leads to a smaller body size as a side-effect, while health and longevity benefits stem from metabolic and gene expression changes due to that lower calorie intake.

Looking to the future: as scientists aquire ever better tools and knowledge of genetics and cellular biochemistry - and the cost of using the tools and acquiring the knowledge falls - these sorts of speculations on statistical correlations will seem quaint. The time between noticing a correlation and understanding the precise biological mechanisms that cause it will become shorter than the time taken to write and publish a scientific paper on the correlation itself ... and that will be that. Suddenly it will be sheer laziness to talk about a correlation of biological traits without knowing why it exists - and medical science will be the better for it.