Fight Aging!

A couple of pieces on current stem cell politics to point out to you folks today. Firstly, a certain senator continues to hold hearings to denigrate embryonic stem cell research:

Other ethicists and scientists at the hearing touted adult stem cells, which are present in bone marrow, fat and other tissue. Dr. Marc Hedrick, president of MacroPore Biosurgery, talked about the success his company reported recently with transplanting adult stem cells derived from fat tissue into pigs1 that had experienced heart attacks. The transplants improved swines' heart function.

Adult stem cell research is indeed promising, Daley said, but that doesn't mean embryonic stem cell research should be abandoned. Adult stem cells don't have the potential to become as many types of cells as embryonic stem cells do, he said.

Brownback said that while adult stem cell treatments have already treated disease, embryonic stem cells have not yet cured anything.

That's not surprising, Daley said, because researchers have been studying adult stem cells for 50 years, while the first paper on embryonic stem cells was published six years ago. Plus, he said, embryonic stem cell research has been restricted by Bush's policy.

I should note that I see restrictions on federal funding as a tertiary issue at best - efforts to ban theraputic cloning and restrictions at the state level have done far more damage to ongoing research. The potential pool of private and philanthropic funding is something like twice as large as that of government funding in the US - and private funding shies away from legislative threats or uncertainty.

Meanwhile, Proposition 71 continues to gather endorsements. If you're interested in seeing their current ad campaign, you can view the spots at the initiative website. The San Francisco Chronicle says:

But the potential breakthroughs in treatments and possible cures for more than 70 diseases including cancer, diabetes, Alzheimer's, multiple sclerosis and even spinal cord injuries, are, in our view, worth the risk.

The private sector endoses things too, but quietly and with their feet. As Chris Mooney notes:

Advanced Cell Technology is setting up a lab in California because the state is so receptive to embryonic stem cell work (including therapeutic cloning). This is just a small taste of what would happen if Proposition 71 passed in California. The initiative would, quite literally, set off the scientific equivalent of a gold rush.

ACT, you may recall, recently reported the creation of retinal cells from embryonic stem cells. (Here's the obligatory political take on that event from the Daily Kos). I was interested to see the aggressive timeline proposed by the ACT researchers - two years to get to the point of human trials. Very ambitious, and I hope they achieve that goal.

Centers for nanomedical research are coming into being these days as well, illustrative of a healthy and expanding field of science. The new Nano/Bio Interface Center at the University of Pennsylvania is one such example: "As electronics and machines are driven ever smaller, they will inevitably be integrated with biological systems, which will have dramatic technological, biomedical and social implications. The new center will bring together Penn's renowned strengths in nanotechnology and the life sciences." Futurists suggest that advanced nanomedicine of the sort proposed by Robert Freitas will enable healthy life extension beyond that provided by the best regenerative medicine - perhaps 20 or 30 years from now.

Link: http://www.upenn.edu/almanac/volumes/v51/n05/nano_ctr.html

(From HHMI). "Certain brain changes that are common in normal aging are not the beginnings of Alzheimer's disease. Recent research by cognitive aging experts suggests that changes related to Alzheimer's disease appear in distinct regions of the brain and reflect unique pathology compared with changes that occur in older adults without dementia." That scientists can talk in such detail about the condition is a sign of how far both Alzheimer's and brain aging research has come. It is important, however, for us to try and prioritize research that prevents any brain degeneration from taking place - such as intervening in the aging process itself. Neither Alzheimer's nor "normal aging" in the brain are part of a desirable future for anyone.

Link: http://www.hhmi.org/news/buckner4.html

Tufts Daily reports that the first tissue engineering research center has been established at the Tufts Science and Technology Center. Tissue engineering is "an emerging multidisciplinary field involving biology, medicine, and engineering that is likely to revolutionize the ways we improve the health and quality of life for millions of people worldwide by restoring, maintaining, or enhancing tissue and organ function." The article gives a good example of an early practical result: recovery time for a torn anterior cruciate ligament in the knee can be reduced from six months to a year down to a few weeks by growing replacement tissue from bone marrow stem cells. Applying this sort of technology to more vital, complex organs is only a matter of time and funding.

Link: http://www.tuftsdaily.com/vnews/display.v/ART/2004/09/27/4157b31e5a261

The 2nd World Congress on Regenerative Medicine will take place in May 2005; by all accounts the 2003 conference was a great success. As I often mention, the growth of a scientific field can be measured in concrete and conferences. As funding increases to significant levels, research centers are constructed and gatherings become larger, organized and more frequent. By all accounts - and despite political problems relating to embryonic stem cell research and therapeutic cloning - regenerative medicine is doing well. We should all be glad that so much money is going towards improving our prospects for health and longevity ... but much more needs to be done yet.

Link: http://www.regmed.org/

A couple of items appeared at the Longevity Meme in past days covering the discussion of aging as a genetic program of events versus aging as simple unprogrammed decay:

Over at PubMed Steven Austad provides a good argument for considering aging as unprogrammed decay rather than a programmed process in the body. This sort of high level thinking about processes and purpose - like the reliability theory of aging - is an important part of effectively directing the research community. "Aging, except in exceptional cases such as the rapid decay and death of Pacific salmon, is not design but decay. The decay of senescence is not due to natural selection's designing hand, but to its absence. The empirical difference between programed and nonprogramed senescence becomes evident when comparing the stereotypical steps leading to death in salmon contrasted with the lack of such stereotypy in most organisms such as humans and mice."

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On the other side of this debate Valter Longo and Paola Fabrizio have authored a paper suggesting that aspects of aging in mammals may indeed be programmed. "Programmed human aging is just a possibility. We don't know whether it's true yet or not. But if aging is programmed in yeast, and the pathway is very similar, then isn't it possible that humans also die earlier than they have to?" This discussion is still at the level of educated hand-waving - much more work is needed to settle it one way or another. My suspicion is that the genetics and biochemistry will turn out to be more complex than a simple yes or no.

The recent Betterhumans article on Longo's work gives a more comprehensive background to the debate in terms of evolutionary explanations for aging and the ramifications of Longo and Austad's positions. Check it out.

In Darwinism, natural selection happens on the individual level. Organisms better suited to their environment survive and reproduce, and beneficial mutations lead species to change over time.

In Longo's theory, however, the majority of a population dies prematurely to provide nutrients for surviving members, who have genetic mutations that increase their chances of reproducing.

"We're not saying Darwin was wrong," says Longo. "We're just saying that there appear to be some big missing pieces in his theory."

As I've said before, I'm always happy to see new theories of aging - it shows that scientists are working on the problem.

I am always pleased to see essays that expressly refute the zero-sum nonsense that permeates modern political and economic discussions. Life, consisting of economic activity in the broader sense of the word "economic," is not a zero-sum game.

Non-zero-sum situations are an important part of economic activity due to production, marginal utility and value-subjectivity. Most economic situations are non-zero-sum, since valuable goods and services can be created, destroyed, or badly allocated, and any of these will create a net gain or loss.

Here is a piece from Simon Smith of Betterhumans on the non-zero-sum nature of curing aging to help the poor. Some highlights (but read the whole thing!):

Aging takes its toll not only on individuals but also on societies and economies. Billions upon billions of dollars are spent treating age-related diseases and supporting elderly people who are unable to maintain their independence. Nevertheless, many people over 65 still live in poverty.

For this reason alone, the argument that funding antiaging research takes money from the poor always struck me as irritatingly bogus. And it's not the only reason. Certainly, much poverty in the world has little to do with aging and lots to do with economics, bad governance and unequal distribution. But reducing the personal, economic and societal cost of aging and directly alleviating suffering amongst a very large group of people -there are 600 million people 60 years and over today, a number forecast to top one billion by 2025 and reach two billion by 2050 - always seemed to me an unequivocal good. Furthermore, ending aging would free up huge amounts of resources that could be used to address forms of poverty not related to physical and mental degeneration.

Yet increasing funding for the fight against aging continues to be opposed on the grounds that it would be tremendously expensive, take money from the fight against poverty and reflect a selfish attitude of wealthy nations and people. These arguments are based on myths and misunderstandings that have hindered research into ending aging and promoted the false dichotomy that we can't invest both in life extension research and interventions aimed at ameliorating poverty. In fact, ending aging is one of the most effective things we can do to alleviate poverty.

The other, for my money, is an end to all restrictions on free association and trade between willing individuals - the poor are not usually where they are because they want to be. Most current legislation aimed at improving their lot actually hinders their own attempts at self-improvement.

If people didn't need treatment for and weren't incapacitated by aging-related diseases, the money saved and generated would vastly outweigh what was spent on antiaging research, freeing up additional resources to help raise the standard of living for all. Unless we're going to stop people from living past 65 - an abhorrent idea to be sure - then for economic reasons alone it makes sense to fund an end to aging.

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At this point, some might voice another argument of those who oppose funding antiaging research: "Isn't it selfish?" After all, the greatest beneficiaries, at least in the early stages, would almost certainly be the wealthy, and people in wealthy countries.

But in fact, funding life extension research is fundamentally selfless because every human ages. Interestingly, I've never heard the people who criticize antiaging research funding make the same criticisms of research funding for rare diseases, which affect just a small fraction of the population and could therefore be considered far more selfish. Clearly, stopping people suffering from rare diseases is a good thing. So why is it bad to stop people suffering common diseases of aging, and the common disease of aging itself?

Biogerontologist Aubrey de Grey projects a cost of $100 billion over ten years for a solidly organized project to engineer an end to aging. This is a tiny fraction of what is spent over the same period on treating age-related conditions, and a project within the range of the largest funding organizations.

If a cost effective cure for aging were available, all the billions currently directed to repairing and holding off age-related damage could be directed to other, more productive uses. Damage of any sort, whether hurricanes, war, disease or aging, reduces the wealth of individuals and society - it saps resources that could have been used elsewhere to generate more wealth. Prevention and more efficient repair technologies ultimately enrich everyone.

Ever growing numbers of people are able to live past 100, thanks to improvements in medical technology. We can do more, however: "As medicine gets even better, and if people eat right and exercise, experts like Dr. Michael Fossel believe that a 200-year life span is entirely reasonable. ... One major force in increasing the aging process is eliminating diseases like heart disease and cancer. Given the current research on cancer, Fossel said it is to the point that researchers are 'actually getting excited' about a cure." The big questions is "when will we see large gains in healthy life span?" While progress to date is welcome, we need to move beyond incidental life extension towards research that directly attempts to lengthen the healthy human life span.

Link: http://www.mlive.com/news/jacitpat/index.ssf?/base/news-10/109619314953700.xml

The latest SAGE Crossroads webcast features Mike Treder of the Center for Responsible Nanotechnology in a discussion of nanotechnology as it applies to aging and longevity research. In fact the webcast touches on a wide variety of associated topics, with the normal mix of conservatism and forward thinking from all sides. Individual attitudes towards change are certainly interesting to examine. The CRN folks worry about a number of social issues that are, in my opinion, not things we need to worry about at all - but it's good to have people thinking about the future of nanotechnology. Entities like CRN and the Foresight Institute play an important part in the march towards working nanomedicine.

Link: http://www.sagecrossroads.net/public/webcasts/18/

(From Innovations Report). Steven Austad argues that aging is not programmed in most organisms - it is just decay. On the other side of this debate Valter Longo and Paola Fabrizio have authored a paper suggesting that aspects of aging in mammals may indeed be programmed. "Programmed human aging is just a possibility. We don't know whether it's true yet or not. But if aging is programmed in yeast, and the pathway is very similar, then isn't it possible that humans also die earlier than they have to?" This discussion is still at the level of educated hand-waving - much more work is needed to settle it one way or another. My suspicion is that the genetics and biochemistry will turn out to be more complex than a simple yes or no.

Link: http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-34049.html

We've been hearing a lot of late about the use of fat as a better source of adult stem cells (better in comparison to bone marrow, that is, and at the very least more easily harvested). PittsburghLive is printing a great introductory article for those of you interested in this branch of stem cell research. "It is known that there are progenitor cells within fat tissue that have the potential to differentiate, or be induced to become, mature fat cells and other cell types. These stem cells are there to heal the body so they could have many great clinical applications. ... Marra, Rubin and their colleagues are working on several projects to investigate the potential of fat-derived stem cells to aid in bone and nerve repair, as well as soft tissue regeneration."

Link: http://pittsburghlive.com/x/tribune-review/health/s_255438.html

As noted in the latest Longevity Meme Newsletter, and in a press release from the Methuselah Foundation, the $500,000 mark for pledges and cash in hand has been passed! A large thank you to everyone who helped get the Methuselah Mouse Prize for anti-aging research to this point in only a year since the official launch.

"The Methuselah Foundation, creators of the Methuselah Mouse Prize, the world's first scientific prize for research on extending longevity, today announced that it has secured [a total of] $500,000 in funding commitments [as well as] a long term support commitment from an anonymous supporter making his donation in the name of the X PRIZE Foundation, the multi-million-dollar bounty which has successfully encouraged the development of private passenger space travel."

Other sponsoring organizations include the Immortality Institute, the Longevity Meme, Maximum Life Foundation, Advanced Orthomolecular Research and Betterhumans - but I'm sure you are all more familiar with the work of the X Prize Foundation. The Methuselah Foundation and X Prize Foundation founders enjoy a cordial relationship, and I'm pleased to see this sort of publicity resulting from that connection.

There is much more to be done yet, however. Two days ago, I talked about moving beyond incidental life extension:

A continuing slow increase in healthy life span - less than a quarter of a year of life span with each passing year of research at the moment - is not very satisfying for me, however. I'd like to be around to see much more of the future in person, which means that the pace of healthy life extension must pick up in decades ahead. This can only happen if many more researchers and funding agencies focus on intervening in the aging process rather than trying to fix the resulting disease and age-related conditions - a grand vision of prevention rather than cure, if you will.

Scientists like Aubrey de Grey are working to make this redirection of scientific focus happen in their fields - but this is the start of a long process. The roadmap for the science itself is fairly clear, at least. Moving beyond incidental life extension is the only way forward if we want to see real results in our lifetimes.

We have a voice and a vote in the process of redirecting the medical research establishment! We can make our opinions known by donating to causes like the Methuselah Mouse Prize. A dollar in the Methuselah Mouse Prize fund is a dollar that is working to convince scientists to take anti-aging research seriously - and encouraging the medical research community to greatly extend the healthy human life span sooner rather than later.

Research into conditions that are or appear to be accelerated aging - Progeria or Werner syndrome - is a field that has garnered great interest in the past few years. Much of this can be credited to the actions of the founders of the Progeria Research Foundation. A recent reprint from the Life Extension Foundation news gives a fair overview:

Dr. Leslie Gordon of Tufts University School of Medicine was ecstatic the day she heard researchers had found the gene mutation that causes progeria - for an instant.

Then she thought: But that's not a cure.

And it's a cure she's after.

Gordon and her pediatrician husband, Scott Berns, who are the founders and force behind the Massachusetts-based Progeria Research Foundation, have an extra motivation for researching the disease. Their son Sampson, 7, was born with it.

The two started the foundation in 1998 to catalyze the search for a treatment.

"There was nothing going on," she said. Although the disease had long been considered a model for studying aging, no one was doing it because it was so rare, and there was no central repository for blood and tissue samples to facilitate research.

In the century since it was first described, fewer than 100 papers had been written on the subject, she said. And the National Institutes of Health, a prime driver of basic medical research, had no money invested in it.

The discovery of the gene in April 2003 changed that.

"I knew it would make hundreds of doors fly open," said Gordon, who helped recruit and fund the scientists who found the gene.

After discovering the genetic roots of progeria, modern bioinformatics made it the work of less than a year to understand how the condition operates - and to show that it is indeed an acceleration of the aging process. Further research into understanding and curing progeria - and related conditions like Werner syndrome - should also result in important insights for future healthy life extension medicine.

Globes reports on the first steps towards rendering mechanical pacemakers obsolete: "[Israeli researchers] created heart cells out of human fetal stem cells, which he implanted in a pig's heart. The pig previously underwent treatment to artificially slow its heart rate. The implanted tissues partially corrected the resulting defective heart rate by in effect constituting a biological pacemaker." More than half a million people use pacemakers in the US alone. The devices, like most implants, are comparatively short lived and expensive. Replacements based on regenerative medicine and stem cell engineering would be a very big deal - but there is a lot of work to be done to get there.

Link: http://www.globes.co.il/serveen/globes/docview.asp?did=840163&fid=942

Over at PubMed Steven Austad provides a good argument for considering aging as unprogrammed decay rather than a programmed process in the body. This sort of high level thinking about processes and purpose - like the reliability theory of aging - is an important part of effectively directing the research community. "Aging, except in exceptional cases such as the rapid decay and death of Pacific salmon, is not design but decay. The decay of senescence is not due to natural selection's designing hand, but to its absence. The empirical difference between programed and nonprogramed senescence becomes evident when comparing the stereotypical steps leading to death in salmon contrasted with the lack of such stereotypy in most organisms such as humans and mice."

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15379846

In the course of writing entries here and at the Longevity Meme, I comment on a fair amount of medical research that will - hopefully, likely, eventually or maybe - lead to longer, healthier lives for all of us. However, very little of this research is carried out with the intention of achieving this worthy goal. Take the field of regenerative medicine, for example: coupled with a reliable cure for cancer, stem cell based regenerative medicine will greatly extend our healthy life spans. Few - if any - scientists in the field have this goal in mind, however. They are curing Parkinson's, Alzheimer's, osteoporosis or diabetes, or working to create replacement organs to order ... seeking cures for specific (usually age-related) problems, in other words.

Almost all human healthy life extension achieved over the past 150 years or so has been accidental, incidental, or otherwise unrelated to the motivating goals of medical research. It just so happens that if you cure and prevent enough cumulative damage to the body - disease and chronic conditions - average live spans get longer. Nothing mystical going on here.

"Infectious diseases cause chronic inflammation in the blood that, decades later, leads to heart attacks, strokes and cancers - the classic killers of old age ... chronic infections from childhood onward accelerated vascular and other diseases." Suffering chronic disease during childhood - a common state of affairs in past decades - damages your body and thus reduces your chance of a longer, healthier life.

According to the reliability theory of aging, researchers can continue to slowly lengthen healthy life spans through improvements across the board in medical technology for a long while yet. We are not yet close to any mechanical, biological, or complexity-related limits to progress in extending the healthy human life span.

A continuing slow increase in healthy life span - less than a quarter of a year of life span with each passing year of research at the moment - is not very satisfying for me, however. I'd like to be around to see much more of the future in person, which means that the pace of healthy life extension must pick up in decades ahead. This can only happen if many more researchers and funding agencies focus on intervening in the aging process rather than trying to fix the resulting disease and age-related conditions - a grand vision of prevention rather than cure, if you will.

Scientists like Aubrey de Grey are working to make this redirection of scientific focus happen in their fields - but this is the start of a long process. The roadmap for the science itself is fairly clear, at least. Moving beyond incidental life extension is the only way forward if we want to see real results in our lifetimes.

Randall Parker links a number of recent study results in a discussion of lifestyle choices and the rate at which age-related damage accumulates in your body. It's wise to pay attention to what researchers are saying on this topic. Your choices and diligence can make a large difference, even with the comparatively crude medical knowledge and technology available today. You can choose to gain decades of healthy life span and avoid hundreds of thousands of dollars in healthcare costs - or not. The better your health and the longer you live, the greater your chance of benefiting further from healthy life extension medicine in the future - getting closer to what biogerontologist Aubrey de Grey calls "acturial escape velocity."

Link: http://www.futurepundit.com/archives/002365.html

A discussion of Australian therapeutic cloning politics at BioMed Central is a vision of what nearly happened - and still could happen - in the US. Therapeutic cloning is vital to much of the most promising research into stem cell based regenerative medicine, but the Australian research community is prevented from contributing their funding and expertise. If we are to move rapidly towards developing a comprehensive biological repair kit for age-related damage and disease - which is exactly what full control over stem cells, reliable therapeutic cloning and understanding of related cellular mechanisms can eventually provide - then these sorts of anti-research legislative restrictions must be lifted. While we delay, people continue to suffer and die.

Link: http://www.biomedcentral.com/news/20040924/01

It's been a while since I mentioned Proposition 71, the California Stem Cell Research and Cures Initiative. If anything, this proposition is looking even more like it will steamroller through the voting process than it did two months ago. The TV advertising campaign has kicked off and Chris Mooney notes the figures:

Last month, 45 percent of voters said they supported it and 42 said they didn't.

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Now, the Los Angeles Times has done a new poll which finds that 54 percent of voters support the initiative, 32 percent oppose it and 14 percent are uncertain.

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I just watched the ads. I'd encourage everyone to do so, because I'd like to start a discussion about whether people think they're persuasive. My sense is that they are extremely effective--especially the one in which the UCSF diabetes researcher says he's basically certain that a cure will arise from embryonic stem cell research.

The New York Times endorses the proposition too, although I'm not sure that will necessarily influence voters in California one way or the other. Chris Mooney goes on to say that:

If this initiative passes, the embryonic stem cell debate is basically over, no matter who wins the presidency. With the research money that California will provide, embryonic stem cell research will surely either prove its worth or falter.

Is Proposition 71 a good plan for long term research results, and how will the law of unintended consequences come back to bite us on this one? Proposition 71 is more than just money - it's a boatload of primed-for-expansion medical research regulation and bureaucracy as well. We shall see whether this short term boost to research funding can outweigh any longer term negative consequences.

Along this line of thinking, here is a piece from the Sacramento Bee earlier in the week:

There's a right way and a wrong way to fund new stem cell research in California. The wrong way is Proposition 71, which would borrow to pay for research grants.

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Establishing an institute for stem cell research would be a fine complement to the state's bold 2000 plan, approved by the Legislature and signed by the governor, to establish four California Institutes of Science and Innovation - $75 million each for facilities and equipment, $25 million each for operations. Each institute was required to match the state's $100 million contribution with $200 million from other sources.

This is the right way to make an investment in cutting-edge research.

The state now has the California Institute for Quantitative Biomedical Research, California Nanosystems Institute, California Institute for Telecommunications and Information Technology and the Center for Information Technology Research in the Interest of Society.

A California Institute for Regenerative Medicine for stem cell research would make a fine fifth institute. But do it right. Go through the normal funding process - and require the same 2-to-1 match from private sources.

Personally, I see the higher path as being a withdrawal of all current and threatened legislative restrictions - allowing private for profit and philanthropic funding to flourish - rather than ever greater government control of the research process ... but wishes and horses and all that.

(From Reuters). A team from Advanced Cell Technology (ACT) have successfully coaxed embryonic stem cells into forming retinal cells. "We believe these new retinal cells could be used to treat blindness and may, in fact, be the one of the very first applications of embryonic stem-cell technology." Degenerative blindness is a fairly common age-related condition, and a number of research projects worldwide are aimed at curing specific root causes. I recently noted an effort using adult stem cells to treat retinitis pigmentosa, for example. ACT is a good example of a private company that has suffered serious funding issues and setbacks due to the threatened therapeutic cloning ban.

Link: http://www.reuters.co.uk/newsArticle.jhtml?type=scienceNews&storyID=6319303§ion=news

ScienceDaily reports on a study demonstrating the large difference that good diet and lifestyle choices have on health and life span. "The researchers found that adhering to a Mediterranean diet was associated with a 23 percent lower risk of all-cause death; moderate alcohol use, a 22 percent lower risk; physical activity, a 37 percent lower risk; and nonsmoking, a 35 percent lower risk. Similar results were observed for death from coronary heart disease, cardiovascular diseases, and cancer. Having all four low risk factors lowered the all-cause death rate by 65 percent." This study was for people in the 70-90 age range, but the lessons apply to us all - better lifestyle choices now greatly reduce the risk of suffering age-related disease later.

Link: http://www.sciencedaily.com/releases/2004/09/040922071339.htm

The MIT Technology Review gives an overview of research into the genetic and biochemical mechanisms of calorie restriction. "For more than a decade, Guarente has been gradually solving the puzzle with the ambitious goal of discovering how to slow the aging process in humans without imposing a thousand-calorie-a-day diet. In 1999, he came to the surprising conclusion that manipulating just one gene, SIR2, could affect longevity." There is competition these days in the field of calorie restriction mimetic drugs - we are probably only a few years away from commercial products that will make a lot of money for whoever develops them. "It's a race now ... both have very big labs working hard. They both have companies working hard, too."

Link: http://www.technologyreview.com/articles/04/10/scanlon1004.asp?p=0

Mitochondria - the powerhouses that provide energy for our cells - are of growing significance in aging research. It was recently convincingly demonstrated that mitochondrial mutations lead to age-related degeneration. Biogerontologist Aubrey de Grey has proposed a strategy for dealing with these mutations as a part of his SENS initiative.

As you might recall from Kip Werking's report on TransVision 2004, biologist Rafal Smigrodski has been working on the tools needed to manipulate mitochondrial DNA. Here is one of the first reports on work he assisted:

Many "classic" mitochondrial diseases have been described that arise from single homoplasmic mutations in mitochondrial DNA (mtDNA). These diseases typically affect nonmitotic tissues (brain, retina, muscle), present with variable phenotypes, can appear sporadically, and are untreatable. Evolving evidence implicates mtDNA abnormalities in diseases such as Alzheimer's, Parkinson's, and type II diabetes, but specific causal mutations for these conditions remain to be defined. Understanding the mtDNA genotype-phenotype relationships and developing specific treatment for mtDNA-based diseases is hampered by inability to manipulate the mitochondrial genome. We present a novel protein transduction technology ("protofection") that allows insertion and expression of the human mitochondrial genome into mitochondria of living cells. With protofection, the mitochondrial genotype can be altered, or exogenous genes can be introduced to be expressed and either retained in mitochondria or be directed to other organelles. Protofection also delivers mtDNA in vivo, opening the way to rational development of mitochondrial gene replacement therapy of mtDNA-based diseases.

This is an important step forward - reliable, low cost manipulation or replacement of mitochondrial genes opens the door to all sorts of new strategies aimed at further understanding and intervening in the aging process.

"The Methuselah Foundation, creators of the Methuselah Mouse Prize, the world's first scientific prize for research on extending longevity, today announced that it has secured [a total of] $500,000 in funding commitments [as well as] a long term support commitment from an anonymous supporter making his donation in the name of the X PRIZE Foundation, the multi-million-dollar bounty which has successfully encouraged the development of private passenger space travel." Many of the Longevity Meme readers have helped reach this milestone, but pledges still need to be converted to cash! As the year ends, consider investing a little money into your future health and longevity by contributing to a research prize for serious anti-aging medicine.

Link: http://www.methuselahfoundation.org/newsflashdetail.asp?News_ID=28

Medical News Today reports on discoveries showing that inflammatory responses could explain how obesity greatly raises the risk of suffering some common age-related conditions. "Circulating mononuclear cells -- the body's monocytes (the largest type of white blood cell) and lymphocytes -- exist in a proinflammatory state in obese persons known to be at increased risk of developing diabetes, heart disease or both." As regular readers will already know, excess weight is bad for your long term health and life span in many different ways. If you want to benefit from new healthy life extension therapies in the decades ahead, you have to stay healthy and save your money for the good stuff.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=13795

A Tech Central Station piece offers some pearls of wisdom: "Far better, surely, for the critics of [embryonic stem cell research] research simply to say forthrightly, 'I oppose this for religious and moral reasons' -- which is clearly their right -- and to forgo the quasi-scientific rationalizations. ... We should 'simultaneously pursue all lines of research to determine the very best sources of these cells.' In other words, instead of arguing about which type is better on the basis of insufficient data, we should pursue research using both, an approach that we find sensible. Competition in medical research, as in commerce, is constructive." Still, the authors fail to identify the damage done by attempts to ban therapeutic cloning.

Link: http://www.techcentralstation.com/092204A.html

On current Alzheimer's study involves trying out gene therapy to boost neural growth:

In Alzheimer's disease, there is a die-off of brain cells involved in memory and cognition. The goal of gene therapy is to boost production of a naturally occurring protein, called nerve growth factor, that prevents cell death and helps neurons grow new connections, said Dr. Zoe Arvanitakis, co-director of the study.

The gene is delivered by a fragment of a harmless virus. The surgeon delivers a few drops, containing about 1 billion viral fragments, deep into the brain. It's hoped the viral fragments will invade brain cells and deliver the gene. The gene then would direct the cells to produce the nerve growth factor.

Gene therapy has been tried for other diseases, including cystic fibrosis, cancer and Parkinson's disease. But many efforts have failed, and no gene therapy has been approved for general use outside of clinical trials.

The Rush trial is the second study of the Alzheimer's gene treatment, called CERE-110. An earlier study of eight patients at the University of California-San Diego found that CERE-110 is generally safe. The Rush study is using a different mechanism to deliver the gene.

If this works, it could prove useful in combination with some way to prevent the ongoing damage mechanisms of Alzheimer's. Randall Parker has the details on just such an attempt (that I also noted recently at the Longevity Meme):

Antibodies injected into a small number of Alzheimer's Disease (AD) patients appear to have stopped the progression of Alzheimer's by attacking the plaques assocated with the disease.

Immunoglobulins which are already being used to treat multiple sclerosis may also be able to help patients with Alzheimer's. This, at least, is the finding of a pilot study on five patients at the University of Bonn. The results are set out in the forthcoming edition of the Journal of Neurology, Neurosurgery and Psychiatry (vol. 75, pp. 1472-1474), which also devotes its editorial to this discovery.

Immunoglobulins contain, among other things, anti-bodies against a protein which is the 'main suspect' thought to trigger off Alzheimer's. After six months of immuno-globulin doses the concentration of this protein in the patients' cerebrospinal fluid was reduced by one third. The patients' cognitive abilities improved slightly.

Studies also show that exercise - mental and physical - reduces the risk of suffering Alzheimer's as well as other common age-related degenerative conditions.

The health benefits of regular walking may include helping prevent mental decline and Alzheimer's disease, research in patients aged 70 and up has found, bolstering evidence that exercise needn't be strenuous to be good for you.

There's plenty of evidence that mental exercise, such as crossword puzzles and reading, may reduce Alzheimer's risks, but previous studies on brain benefits from physical exercise had conflicting results.

The new findings, contained in two studies, clarify how much exercise might be beneficial and are good news for older people who want to avoid mental decline but "don't like doing all that awful, sweaty stuff," said Bill Thies, vice president for medical and scientific affairs of the Alzheimer's Association.

Any effective therapy for Alzheimer's will save a great deal of money - both for individuals and socialized medical systems. While saving money is not high on the list of ethical reasons to save lives, it is what motivates organizations to action:

A new report has found that delaying the onset of new dementia cases by as little as five months could save the [Australian] community more than $1 billion.

As I've said before, preventing or developing cures for neurodegenerative conditions is vital to the process of greatly extending the healthy human life span.

Since today is World Alzheimer's Day, it seems appropriate to take a look at what people are saying about stem cell research and Alzheimer's disease. Chris Mooney has been keeping track, and has a number of posts on the topic:

It's a favorite talking point of the anti-embryonic stem cell research crowd: ES cell transplants will never cure Alzheimer's, they claim. Is it true?

...

Lessons that can be learned from stem cell transplants for Parkinson's and other types of neurodegenerative disease will reveal a great deal about cell signaling and cell environment that could be applied in Alzheimer's.

...

Stem cell transplant therapy doesn't sound like a good bet for Alzheimer's, as scientists fully admit. However, basic research using embryonic stem cells, including from cloned embryos, holds considerable promise for increasing our understanding of the development of the disease, and that in turn could lead to potential cures. So, it's not at all disingenous to talk about Alzheimer's in connection with stem cell research, unless you misleadingly claim that stem cell transplant therapies are going to cure Alzheimer's.

Modern bioinformatics ensures that serious research into any disease tends to improve our overall knowledge of human biochemistry and cellular processes.

(From Reuters). Slowly but surely, money is heading into the field of personalized medicine: "This study will look at whether pharmacogenetics, the designing of drug treatments based on a person's genetic make-up, is a scientifically achievable aim, be it five, 10 or 25 years from now." Like the ability to identify, manipulate and use stem cells, personalized medicine will allow for broad advances in the capabilities and effectiveness of medical technology. Our genetic differences are large, speaking from a medical standpoint: "Some treatments work in only abut 30-50 percent of patients." You can find a little more on the topic in a post at Fight Aging! from earlier in the year.

Link: http://www.reuters.co.uk/newsArticle.jhtml?type=healthNews&storyID=6274053§ion=news

The Toronto Star notes that today is World Alzheimer's Day: "People are much more aware of it and prepared to talk about it. We are now where we were with cancer 30 years ago." In actual fact, I believe that the medical community is further ahead than that - Alzheimer's research has been a high priority for a decade now and bioinformatics allows scientists to move much faster than in previous decades. As early regenerative medicine extends our healthy life spans, it becomes ever more vital to prevent and cure neurodegenerative conditions. The brain is in a class of its own; other organs can be replaced or repaired using comparatively crude future medicine, but damage to the brain must be repaired in situ.

Link: http://www.thestar.com/NASApp/cs/ContentServer?pagename=thestar/Layout/Article_Type1&c=Article&cid=1095718215837

In the latest Longevity Meme newsletter, I wrote about "the problem with immortality."

The problem with immortality is really a problem with people, and it extends to any discussion of the topic. As soon as you mention immortality outside of a religious context you are in danger of being lumped in with the vocal wingnut and oddball fringe. Sadly, these are the people who tend to make the most noise outside of theological circles - vendors of magnetic rings, self-proclaimed mystics and the like.

From where I stand, the problem is the same as that suffered by anti-aging science and medicine - a confusion of alternate meanings, many of which are colloquial or specific to certain groups or professions.

...

In scientific, rational circles - such as the cryonics community or Immortality Institute forums - the term "physical immortality" is often used to denote "vulnerable agelessness," or freedom from the degenerative effects of aging. For many people, this accurately describes the ultimate goal of medical science: prevent or cure all disease, disability and degeneration, thus allowing people to live in perfect health for as long as they desire.

...

So what can we do - what should we do - when the wingnuts, frauds and a collision of definitions have rendered it hard to discuss a sensible topic in public?

What do you think about immortality, the varied meanings of the word and its use in rational conversation?

The latest SAGE Crossroads article takes a look at the future of medical nanotechnology: "If doctors could intervene at the nanoscale, they might be able to fix the body's aging systems from the bottom up, without leaving a trace that a patient once suffered from Parkinson's disease, osteoporosis, or macular degeneration." There is, as usual at SAGE Crossroads, a little too much focus on legislative matters and potential doom and gloom, but the promise of nanomedicine in both the short and long term is very clear. As our materials science advances, we can gain ever more precise control over the tiny machines that make up our bodies. Where regenerative medicine leaves off in the fight to cure aging, nanomedicine will pick up the slack.

Link: http://www.sagecrossroads.net/public/news/show_article.cfm?articleID=81

From the International Herald-Tribune, some interesting commentary on California Proposition 71 - the proposal to fund $3 billion in embryonic stem cell research over the next decade. "We are on the edge of one of the great watershed medical discoveries in history. We have more than 50 percent of the biotech capacity in the United States and more than most other countries. We can run a substitute national program." In many ways this initiative has become a repudiation of current US policies on therapeutic cloning and embryonic stem cell research. If the public opinion polls and initiative funding numbers are any indication, this proposition is very likely to pass.

Link: http://www.iht.com/articles/539654.html

Reuters reports on yet another study showing just how good exercise and calorie restriction are for your health. In this case, they are shown to dramatically reduce risk factors for diabetes: "Men who restricted their calorie intake not only lost a significant amount of weight and had a nearly six percent reduction in body fat, but their insulin concentrations were also reduced by 40 percent on the glucose tolerance test." This isn't rocket science - it's just good preventative maintenance for what is, in essence, a complex machine. If you want to be healthy and active (and alive!) to benefit from the healthy life extension medicine of the future, then you have to take care of your body in the here and now.

Link: http://www.reuters.com/printerFriendlyPopup.jhtml?type=healthNews&storyID=6256119

USA Today aptly illustrates a number of problems relating to the way in which people think about medical research. Gene therapy is offered up as a technology hyped as offering cures for age-related conditions (amongst others), but is now perceived as having "gone nowhere" because commercial results have not been achieved within a decade. This is nonsense - the field of gene therapy is still healthy, active and in development. Media-driven expectations of instant gratification present a problem for stem cell research as well, but: "I can find no example where over the long term we have not moved ahead for research for cures of major diseases." We can certainly hope so.

Link: http://www.usatoday.com/tech/science/genetics/2004-09-16-stemcells_x.htm

Mike Treder of the Center for Responsible Nanotechnology (CRN) has posted a report after recording a webcast for SAGE Crossroads on aging science and nanotechnology.

Joining me as a guest on the program (which will be shown as a webcast on September 27) was Dr. Robert Best, director of the genetics division at the University of South Carolina School of Medicine. Bob spoke about progress being made in the field and on the opportunities for nanotechnology to hasten the detection and curing of diseases. We disagreed about the likelihood that molecular manufacturing will be developed in the near future (he was skeptical), and about the need to address this as an issue in current policy discussions.

Morton Kondracke, who moderates the program, also asked us to talk about the potential for using nanotechnology to substantially extend the human healthspan and even to change us as humans. We had a discussion about the philosophical objections to this that sometimes are raised by bioconservatives.

Condensing complex topics into a sound bite format -- even a 60-minute program -- is a difficult challenge. It's probably impossible to adequately cover all that needs to be said, but I think I represented CRN's positions effectively. You can see for yourself beginning September 27, and then let me know what you think.

The other founder of CRN, Chris Phoenix, has contributed an article on nanotechnology and extending the healthy human life span to the Longevity Meme - it's well worth reading.

While a human study on the beneficial effects of calorie restriction is underway, researchers are still working with primate subjects in order to better understanding the processes involved. The University of Maryland Diamondback takes a look at a decade-long study of calorie restriction in rhesus monkies: "So far, the rhesus monkeys' calorie-restriction diet has produced results similar to those of the rodent study." In other words, better health and a slowdown in the measurable degeneration associated with aging. The human studies to date are producing equally good results, although the comparatively long human life span (still too short for my liking!) makes it much harder to find definitive data.

Link: http://www.inform.umd.edu/News/Diamondback/archives/2004/09/16/news7.html

Life expectancy for humans has doubled over the last 150 years as a result of progress in medical science. Medical News Today reports on a new study that links specific advances to the historical increase in average healthy life span. "Infectious diseases cause chronic inflammation in the blood that, decades later, leads to heart attacks, strokes and cancers – the classic killers of old age ... chronic infections from childhood onward accelerated vascular and other diseases." Suffering chronic disease during childhood - a common state of affairs in past decades - damages your body and thus reduces your chance of a longer, healthier life. This makes perfect sense if you consider the reliability theory of aging.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=13624

Some details are now up for the second Strategies for Engineered Negligible Senescence conference:

The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of a true cure for human aging by tackling it as an engineering problem: enumerating the accumulating molecular and cellular changes that eventually kill us, and identifying ways to repair -- reverse -- those changes, rather than merely to slow down their further accumulation.

Over 35 illustrious speakers are already confirmed. The provisional schedule for the conference is here.

SENS 2 will therefore continue and extend the superlative quality of the inaugural SENS conference held in 2003. The calibre of that meeting can be seen from the list of abstracts, the online audio recordings of the talks, and most of all from the proceedings volume, which was published as volume 1019 of the prestigious Annals of the New York Academy of Sciences. We anticipate that the proceedings of SENS 2 will also be published there.

I am particularly interested in the work that is being done on overcoming mitochondrial mutations - see Kip Werking's report from TransVision 2004 for a little on the work of Rafal Smigrodzki in this field, for example.

Next, Rafal Smigrodski, from the underrepresented private sector, gave his presentation titled "How to buy new mitochondria for your old body." Smigrodski described how his company is preparing a treatment to repair broken mitochondria. They have developed a method to deliver genetic cargo to mitochondria that is superior to traditional virotherapy. By marketing the treatment to those with a rare genetic defect in their mitochondria, Smigrodski hopes to jump the gap between therapy and enhancement and prepare the way for age retardation therapies within a couple of decades. I felt that much of his presentation was too good to be true; only time will tell.

Aubrey de Grey gave another presentation after Smigrodski titled "Removing toxic aggregates that our cells can't break down." He did not share the latter's optimism in obtaining FDA approval or bringing to market a treatment for a disease which afflicts less than one hundred people in the United States. Much like the speaker before him, de Grey was concerned with mitochondria, the power plants in each one of our cells which possess their own DNA. According to de Grey, these energy generating organelles create waste that is typically treated by the lysosomes. Sometimes, however, the lysosomes fail and the waste simply accumulates within the cell. This waste has been shown to be related to aging. Many researchers are now working upon a gene therapy to correct this defect in mitochondria and slow aging.

I notice this posted at the Anti-Aging Medicine and Science Blog. It's an account of recent discoveries relating to the intersection of Sir2, calorie restriction, metabolism and aging.

The discovery that Sir2p requires NAD for its activity immediately suggested a link between SIR2 activity and caloric restriction. This link was strengthened by the observation that life span extension by caloric restriction requires Sir2 protein. Caloric restriction is likely to reduce the carbon flow through glycolysis and result in more free cytoplasmic NAD. SIR2 could act as a sensor of NAD levels within the nucleus. Under conditions of caloric restriction, NAD levels are high, SIR2 is activated, and the rate of aging is decreased.

Scientists are in the middle of a good old fashioned research story here - the outcome is likely to have a strong positive impact on our future health and longevity. In the meanwhile, you should certainly investigate calorie restriction if you haven't already done so.

A line from this Pacific News Service article: "Progress is just not fast enough for the 47,000 people who have died of Parkinson's disease, or the 150,000 who have succumbed to Alzheimer's disease, since Bush's decision on August 9, 2001. This is worse than a World Trade Center collapse every month." While the article confuses the effects of public funding decisions with the effects of actual attempts to ban research, these figures provide a reminder not visible elsewhere in the public debate over embryonic stem cell research. Thousands of people die each and every day from age-related conditions that stem cell based regenerative medicine will most likely one day cure. The sooner that day arrives, the more lives will be saved - any and all delays have a terrible cost.

Link: http://news.pacificnews.org/news/view_article.html?article_id=2eda5bc0063003fc1eee40520dec0f95

Betterhumans reports that "a new antibody treatment for Alzheimer's has apparently halted its progression in a small human trial." The trial had only five participants, so we should not draw conclusions from such a small sample. "While cognitive function improved marginally in four patients, their condition didn't worsen, which might have been expected after six months. Visual tasks improved in three of the patients and stayed the same in the other two." This work builds on previous research in mice showing that antibodies can clear the buildup of beta amyloid plaques in the brain. This is a promising step towards a much-needed therapy, but there is a way to go yet.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-09-16-3

USA Today takes a look at the state of stem cell research politics in the US, finding that all sides are guilty of hyperbole and outright lies. No surprise there. While embryonic stem cell research "represents a breakthrough in terms of medical therapy that has been unprecedented since antibiotics and anesthesia," commercially available therapies are still some years - or even a decade or two - away. Opponents use the uncertainty inherent in research in their fight to suppress freedom of science for ideological reasons. But as Irving Weissman says, "If you have to prove ahead of time that something has to work before you will fund it, then stop funding all NIH research. Medical research is about discovery."

Link: http://www.usatoday.com/news/politicselections/nation/president/2004-09-16-stem-cells_x.htm

I received an e-mail from Eric Geislinger the other day containing some musings on a direction for embryonic stem cell research. You may recall the finding that embryonic stem cells from a growing fetus cross over into the mother's body, differentiate and become specialized cells - literally performing a form of stem cell therapy on the mother. Here is what Eric had to say:

Personally, I don't think this will affect the ethical arguments a whit, but it does bring up something I suggested years ago - large, periodic injections with genetically identical embryonic stem cells. Do you know of anyone trying out what seems to be a pretty obvious experiment? Or am I missing something? I wrote a similar question to [biogerontologist Aubrey de Grey] a while ago and received the following:

Aubrey wrote:

As for large, periodic injections with genetically identical embryonic stem cells: well, the basic technical problem with stem cell therapy is not the amount of cell division, so "large" is probably not needed. The problem is getting them to differentiate along the desired pathway after injection. To *some* extent they respond to local cues from the tissue they're in, and just do what's needed, but by and large they need a bit more instruction than that. Some of this differentiation can be done in the lab, prior to injection. Basically stem cell work is at the point where we just need to do a lot of "fishing" -- trying lots of different things and seeing what works.

At this point he had to go off to some conferences and we haven't really gotten back to the conversation. While he didn't completely poo-hoo the idea, it didn't seem like he was very interested in it either. I don't get it. It *may* not be as difficult as folks are thinking. What we have here is a bunch of older women with some nice young cells incorporated into their bodies - not even the same sex, let alone genetically identical - and they're perking along doing their various (liver, thyroid, etc) little cell jobs. Seems important.

I think the differentiation problem is the wrong problem. For the last hundred years researchers have been more concerned with the diseases of aging rather than aging itself. I think a similar thing is happening with stem cells. Everybody has their own particular favorite organ or disease that they're working on and this wonderful new tool comes along (stem cells) so they're bashing their brains out trying to figure out how to use them to grow a new liver (or whatever). The Bianchi work indicates that this may not be necessary. The fact that the cells get enough clues from their surroundings to at least sometimes differentiate properly is all you need for a "proof of concept." And this was with cells that weren't even identical and were probably being attacked to some extent and were just the result of "leakage" in the first place.

Why not take an animal that can be cloned (like a rat), create a nice batch of ESCs, and just infuse the critter on a regular basis? It seems like, to at least some degree, you're going to create a chimera that's part young rat and part old rat. Unless someone like Michael West is working on this, everybody else seems too specialized to care.

What am I missing?

It seems like an experiment that should be performed in mice. There's certainly nothing to lose by trying! The current first generation of adult stem cell therapies have essentially come about through a educated trial and error process - finding out where injections of appropriately treated stem cells can assist the process of regeneration.

From Betterhumans, news of research suggesting that adult stem cells can be used to regenerate the damage caused by certain kinds of degenerative blindness. "Stem cells, injected into the eyes of mice with a model of retinitis pigmentosa, lead to the development of blood vessels. Some stem cells were found to incorporate into the vasculature of the retina while others took up residence very close to blood vessels. This provided a protective effect, rescuing and stabilizing the retinal vessels when they would otherwise degenerate." As scientists experiment with adult stem cells - an uncontroversial and thus well supported field - we can expect to see more of these sorts of potential therapies come to light.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-09-15-2

EurekAlert reports on a good example of research into practical regenerative medicine: "By combining stem cell science with orthopedic surgery, a team of researchers at the University of British Columbia and Vancouver Coastal Health Research Institute aims to reduce the 10 per cent failure rate in hip replacements and make repeat replacements and other joint repairs obsolete within 10-15 years." This may sound prosaic compared to some work in stem cell research, but improvements in the reliability, effectiveness and economics of treating age-related joint failure are a big deal. The future of medicine is composed of thousands of advances like this one; by supporting research, we help to ensure our own future health and longevity.

Link: http://www.eurekalert.org/pub_releases/2004-09/uobc-ura091404.php

This Sacramento Bee article discusses an economic study by the Proposition 71 organization (the California Stem Cell Research and Cures Initiative). Such studies - extrapolations and educated guesswork, really - should always be taken with a large pinch of salt, but some of the underlying data should give you pause for thought. In particular, the economic cost of disease: medical services over a lifetime can top a million dollars, nearly all of that due to common, chronic age-related conditions in later life. Diabetes and cardiovascular disease are expensive propositions, for example. Good insurance is key, but far better to support medical research into real preventation and reliable cures!

Link: http://www.sacbee.com/content/politics/ca/election/story/10747356p-11665736c.html

An article from earlier this year at KurzweilAI.net does an excellent job of illustrating the advances that are driving the increasing rate of progress in medical research.

The parts for a DNA synthesizer can now be purchased for approximately $10,000. By 2010 a single person will be able to sequence or synthesize 10^10 bases a day. Within a decade a single person could sequence or synthesize all the DNA describing all the people on the planet many times over in an eight-hour day or sequence his or her own DNA within seconds.

...

Indeed, the continuing costs of sequencing (expendables such as reagents) have fallen exponentially over the time period covered by Figure 1.5 Lander et al., state in Nature that by 2000 the total costs of sequencing had fallen by a factor of 100 in ten years, with costs falling by a factor of 2 approximately every eighteen months.6 With the caveat that there are only limited data to date, it does appear that the total cost of sequencing and synthesis are falling exponentially.

...

Despite the fantastic nature of these numbers, there is no physical reason why sequencing an individual human genome should take longer than a few minutes.

The article as a whole is a doom and gloom effort relating to safety - but plenty of people are thinking hard about ensuring the safety of biotechnology (and nanotechnology). We should be celebrating the advances that will herald a new level of scientific understanding of the human body - and therapies to cure or prevent age-related diseases.

This is worth mentioning:

Germany should maintain its ban on reproductive cloning and the penalties for violating the law should be more clearly defined in the future, the country's National Ethics Council said on Monday.

The Council, appointed by Chancellor Gerhard Schroeder in 2001, also recommended that the country's prohibition of therapeutic cloning be maintained for the moment, but this was more of a political than an ethical recommendation.

...

Currently, German law only allows research with human embryonic stem cell lines that are imported from overseas and were created before January 1, 2002. Every research project is peer-reviewed by a national authority, the Robert Koch Institute, and has to be considered "high ranking" in order to get approval. This leaves German stem cell scientists wanting a generally more positive climate for their research.

This sort of situation, in which an entire promising field of medical research is legislated out of existence, almost happened in the US in 2003. It still could happen, since a ban on therapeutic cloning is still pending in the US senate. This ongoing threat - part of a wider atmosphere of legislative uncertainty - has caused great harm to private research funding.

Therapeutic cloning is vital to much of the most promising stem cell research and many of the best near future regenerative therapies. If we wish to live longer, healthier lives with the help of advances in medical science, then we must stand up to support freedom of research.

The Salt Lake Tribune takes a look at calorie restriction, the CR Society and the ongoing CALERIE study sponsored by the National Institute on Aging. You may recall that the first results from that study were announced earlier in the year, and very impressive they were too. Now that scientists have a better handle on the genetics and biochemistry of calorie restriction, a fair amount of time and effort is going towards uncovering drugs to mimic beneficial effects on health and life span (but without the dieting). Companies like Elixir and BioMarker - amongst others - are racing to develop and commercialize some form of calorie restriction mimetic. We should expect interesting progress in this field over the next few years.

Link: http://www.sltrib.com/healthscience/ci_2412133

The latest SAGE Crossroads weekly article discusses mitochondria, our cellular powerhouses: "Recent studies have implicated unchecked mitochondrial decay in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), obesity, diabetes, and aging itself ... some studies have suggested that one of our most popular all-purpose panaceas--exercise--acts in part by slowing and perhaps suspending the mitochondrial countdown." Repairing, replacing or moving mitochondrial DNA is on biogerontologist Aubrey de Grey's engineering list. If, for example, we could move mitochondrial DNA into the comparatively well-protected cell nucleus, we would be in much better shape to resist ongoing damage.

Link: http://www.sagecrossroads.net/public/news/show_article.cfm?articleID=79

As previously noted at Fight Aging!,, the National Cancer Institute has announced a nanotechnology initiative. "Nanotechnology has the potential to radically increase our options for prevention, diagnosis, and treatment of cancer ... Nanotechnology supports and expands the scientific advances in genomics and proteomics and builds on our understanding of the molecular underpinnings of cancer. These are the pillars which will support progress in cancer." Basic cancer research - understanding how our cells and bodies function at the molecular level - will also support the fight to cure aging. The more we know, the more we can do. You can find out more about the NCI initiative at their new website.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1050&Section=DISEASE

The folks over at Marginal Revolution are discussing cryonics, a topic on which I have my own comments to make:

Death is not a topic that people like to think about, and that is just as true of healthy life extension advocates as anyone else. We have to recognise, however, that the future of healthy life extension (regenerative medicine, stem cell therapies, understanding the biochemical processes of aging, and nanomedicine, to name a few fields) will not arrive soon enough to benefit everyone. Many people are too old, or suffer from other conditions that will kill them before cures can be developed. This is an unpleasant reality that we must face.

Do we just write these people off and forge ahead regardless? Of course not. Instead, we turn to the science and business of cryonics, a serious effort to solve this problem that has been underway since the early 1970s.

Cryonics is the only option for life extension open to many older and seriously ill people: those who cannot wait for the promised therapies of the next few decades. It is the science of placing humans and animals into a low-temperature, biologically unchanging state immediately after clinical death, with the expectation that advances in medical technology may eventually enable full restoration to life and health. A small industry of cryonics providers exists to freeze your body on death, in the hopes that future scientists (most likely using nanotechnology and nanomedicine) will be able to revive and repair you.

The practice of cryonics is an ongoing medical experiment with an unknown chance of success. Responsible cryonicists understand that cryonic suspension is an educated gamble. The chances are certainly better than zero, however, and as one wag noted, "the control group in this experiment isn't doing so well." By this, he was referring to the vast number of people who are cremated, buried or otherwise interred. The chances of any plausible future science restoring them is zero. Cryonic suspension is, after all, only the second worst thing that can happen to you.

Tyler Cowen points out the Robin Hanson paper on why cryonics remains an unpopular option and comments:

Alas, I am a cryonics pessimist and I have yet to sign up for the extant services. (It is an interesting exercise to sit down and calculate how much resurrection would be worth to you, your implicit probability expectation, and your value for the modest yearly fee; many people have to fudge the numbers to justify their absolute dismissal of the idea.) But I also am pretty sure that most people, including prospective donors, reject the idea for the wrong reasons.

If you are interested in learning more about cryonics, the Alcor website is a good place to start. The Alcor staff go over the basics, the facts and the myths in a very helpful, open and straightforward manner.

UPDATE: Here is another long, good post on cryonics and the rational choice to sign up.

Unbiased discussion of stem cell research (embryonic and adult) is something we certainly need to see more often at the moment. Here, the Wisconsin Technology Network prints comments from an influential scientist in the field: "There are still some fundamental reasons why embryonic stem cells, as well as stem cells taken from adults, are needed for research breakthroughs in the next decade." Some anti-research factions are trying to portray adult stem cell research as sufficient for the future of regenerative medicine. While some very promising first generation therapies use adult stem cells, embryonic stem cell research is essential to the long term goal of developing a regenerative repair kit for human beings.

Link: http://www.wistechnology.com/article.php?id=1176

Yesterday's post at the Longevity Meme on research into great feats of bacterial DNA repair probable bears a few further references. The DNA Repair Special Interest Group is one of the NIH special interest groups:

The DNA Repair Interest Group is concerned with all forms of DNA damage and repair. As a major defense against environmental damage to cells DNA repair is present in all organisms examined including bacteria, yeast, drosophila, fish, amphibians, rodents and humans. The members of the DNA Repair Interest Group perform research in areas including DNA repair enzymology and fine structure, mutagenesis, gene and cell cycle regulation, protein structure, and human disease.

Amongst other material, you'll find a basic information on DNA repair mechanisms and how DNA repair fits into the bigger picture of cancer and aging:

Biogerontologist Aubrey de Grey has his own take on this topic in the context of developing a cure for aging - be sure to read it after perusing the DNA Repair SIG site.

There are two types of accumulating change that happen to our chromosomes as we age: mutations and epimutations. Mutations are changes to the DNA sequence, and epimutations are changes to the "decorations" of that DNA which control its propensity to be decoded into proteins. Luckily, we don't need to deal with these two phenomena separately, because we can obviate them both in the same way.

This is another of the areas of aging in which evolution has done the really hard work for us. We have an enormous amount of DNA, and the job of keeping it intact and functional is incredibly complicated. But evolution had to do it, so it has developed the necessary sophistication for us. We're particularly lucky in one way: evolution (since the emergence of vertebrates, anyway) has had one DNA maintenance problem that is far bigger than all the others, and that is to stop organisms from dying of cancer. Cancer can kill us even if one cell gets the wrong mutations (or epimutations), whereas any loss of function in any genes that have nothing to do with cancer are harmless unless and until they have happened to a lot of the cells in a given tissue. So, all those genes get a free ride -- they are already maintained far better than we need them to be in anything like a normal lifetime.

This means that we don't actually need to fix chromosomal mutations at all in order to stop them from killing us: all we need to do is develop a really really good cure for cancer.

The Life Extension Foundation News reprints an interesting breakdown of the current set of drugs for age-related conditions in human trials or awaiting FDA approval. It gives a good view of research and regulatory priorities: "123 medicines would treat heart disease and stroke and 395 would assist cancer patients ... 22 new medications being developed against Alzheimer's ... 14 new drugs being developed for Parkinson's disease and 53 for diabetes. Eighteen of the proposed new compounds would treat osteoporosis." The cancer research establishment is enormous, the result of thirty years of deliberate intent, education and strong public support. This is a model we should emulate for the future of serious research into a cure for the aging process.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1042&Section=AGING

As reported by Medical News Today, there is a growing level of interest in the process of obtaining adult stem cells from fat tissue. "Research has indicated [fat]-derived stem cells can be coaxed into bone, nerve, cartilage and endothelial cells." Reliably identifying and isolating stem cells from fat will provide a better source of adult stem cells for some of the regenerative therapies currently in human and laboratory trials. Obtaining stem cells from fat tissue is much less onerous and invasive than working with bone marrow stem cells; fat-extracting techniques (like liposuction) are more quickly and easily performed. This seems like a good step forward.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=13146

The Senior Journal notes the launch of another study on longevity - what factors, genetic or otherwise, enable some people to live longer than others? "We will be looking for genetic risks for cancer, heart disease, stroke, Alzheimer's disease, diabetes—all the major risks—as well as asking about personal habits, looking at medical histories, and doing clinical tests." Personally, I think that researchers should be spending more time focusing on realistic prospects for reversing aging while continuing to examine the current state of affairs. That they don't is a function of the conservative funding environment - more public support for and understanding of serious anti-aging research is needed.

Link: http://www.seniorjournal.com/NEWS/Aging/4-09-11LiveLonger.htm

A NASA publication discusses the investigation of DNA repair in the humble Halobacterium: "We have completely fragmented their DNA. I mean we have completely destroyed it by bombarding it with [radiation]. And they can reassemble their entire chromosome and put it back into working order within several hours." Damage to DNA - especially mitochondrial DNA - is associated with aging, and possibly a cause of age-related degeneration. While the NASA study is focused on repairing radiation damage incurred during space travel, knowledge relating to DNA repair could be turned to other tasks as well. A reliable DNA repair kit for humans would likely go a long way towards extending our healthy life spans.

Link: http://science.nasa.gov/headlines/y2004/10sep_radmicrobe.htm?list687582

Knowledge drives the current speed of advance in medical science - knowledge of the way in which our bodies actually work. Without specific knowledge of underlying mechanisms, all investigations are trial and error, poking around in the dark.

The first step in the modern investigation of the body was to understand and categorize our genes. Now, the focus is on using these results to understand and categorize the biochemisty and biomechanics of cells - which will lead to a full comprehension of disease, cancer and aging.

With this in mind, here an article on the topic. Firstly, "Cracking the Cellular Code":

In the past few years, biologists have churned out the entire genetic sequence of dozens of organisms, including humans, dogs, mosquitoes, rats, and bacteria. But these strings of genes amount to the most basic molecular parts list, not much more helpful to deciphering how the genes combine to run a living cell than an array of microchips and wires would be for assembling a computer.

...

"One of the exciting outcomes of this kind of work," Young says, "is that we have the potential to understand why mutations in key human regulators cause disease."

You may recall my comments on the American Academy of Anti-Aging Medicine (A4M) sponsored conference in Singapore:

A fair number of folks in the scientific aging research community don't like A4M. If you ask them why, the A4M conferences are singled out as a cause. Scientists don't like the fact that the less reputable "anti-aging" business community - i.e. pills, potions, and adventurous marketing alongside potentially serious ventures - attend these conferences. It's taint by association. If you look at the structure of the 2004 Singapore conference, it's divided between the scientific or medical speakers and workshops and the wider community of exhibitors from the "anti-aging" marketplace.

And on the recent conference in Chicago:

The A4M Chicago conference later this month is, like the recent Singapore event, is very much a collision between the best and worst that business, activism and science has to offer on the topic of intervening in the aging process.

Now we have more of the same in London. The enthusiasm of the A4M founders for extending the healthy human life span is admirable, but in the process of becoming poster boys and promoters by proxy for skin cream and exercise machines, this message gets lost. People look at "anti-aging medicine" and see scams and nonsense, a state of affairs that is entirely the fault of elements within the marketplace:

About 40% of the individuals sampled believe that anti aging products are basically "hogwash", while another 36.4% are "curious but sceptical." Only 3.41% say that they like such products a lot but more than 20% say that they can "work sometimes".

This state of affairs is causing great harm to the prospects for real, serious, scientific anti-aging research, which - like all major fields of research - requires widespread public support and understanding to obtain sufficient funding for progress.

Ben Bova, science fiction author and columnist, takes a look at calorie restriction as a part of his latest outing at the Naples Daily News. "For several years now, biologists have known that certain organisms can extend their life spans significantly — more than 50 percent, in some cases — by severely restricting their intake of food." Given the latest research results, it seems very likely that calorie restriction works to extend life span in humans as well - if not to the same extent. Meanwhile, scientists are closing in on an understanding of the mechanisms by which calorie restriction improves health and extends life span. I expect to see fairly reliable calorie restriction mimetics appearing in the drug pipeline within the next five years.

Link: http://www.naplesnews.com/npdn/pe_columnists/article/0,2071,NPDN_14960_3159801,00.html

A piece in the Guardian notes that biogerontologist Aubrey de Grey will be speaking at at the current Anti-Ageing Conference in London: "Dr de Grey will warn them, in his speech today, that they may have misused the term anti-ageing. He said that physicians and suppliers of anti-ageing medicine were selling things that were perfectly legitimate within their own scope but the use of the phrase gave the impression that it could do more." This, I think, is too generous to some of the junk that gets promoted at this sort of event - especially considering the damage the "anti-aging" industry is doing to the prospects for serious anti-aging research aimed at extending the healthy human life span. If industry members want to become scientifically respectable, then they have to clean up their act.

Link: http://www.guardian.co.uk/uk_news/story/0,3604,1302126,00.html

A very much overhyped - but still interesting - piece of science appears in the New Zealand Herald. Many lower forms of life have the ability to extend their lives in a sort of low-activity state, but this particular parasite is impressive: "The genes allow worms in the possum's small intestine to live for up to a year - while the same worms live outside in the soil for only a matter of days if they do not 'switch on' the longevity genes." Similar genes occur in humans, but that certainly doesn't mean the work has any relevance to our health and longevity. From the researcher in charge: "If you are putting money into this, from a commercial angle a lotto ticket would be a better idea." Still, a grant has been provided for further study.

Link: http://www.nzherald.co.nz/storydisplay.cfm?reportID=53009&storyID=3590426

A cure - or at the very least a family of reliable therapies - for cancer is a vital stepping stone in the path towards greatly extended healthy life spans. This piece from ScienceDaily is a good example of the sort of research taking place at the moment: a focus on basic mechanisms and uncovering better ways to interfere with cancer growth or correct faulty cellular processes that lead to cancer formation. The science of bioinformatics (advances in computing and automation) has greatly increased the speed at which biochemical processes can be investigated and understood. New information leads to new avenues of investigation and potential treatments, and the pace is continuing to pick up.

Link: http://www.sciencedaily.com/releases/2004/09/040909075807.htm

Some good points are raised in a lecture at Yale:

Paul Berg, a professor of cancer research and biochemistry at Stanford University, made it clear from the start of his lecture last night which side of the stem cell debate he supports.

"How could any administration with any conscience at all prohibit the possibility of saving lives just because the technology offends them?"

...

He said in recent years scientists have feared the government may forbid certain lines of biomedical research altogether. Several bills have already passed through Congress and are sitting in the Senate that propose to make stem cell research a criminal offense.

"I am astonished that so many people are unaware that pending in our government is a law that says you will go to jail if you try to clone a stem cell," Berg said. "Biotechnology and certain valuable lines of biomedical research are at increasing risk."

In attacking the ethical dilemma of stem cell research, Berg drew a comparison to Dick Cheney's reformed stance on gay marriage. He said as soon as someone has a close friend or relative suffering from a disease that could benefit from stem cell research, his previous ideology goes out the window.

"I have no problem with the political system providing for the oversight of the application of new knowledge, but what we're seeing here is a big effort to prevent the acquisition of this knowledge altogether," he said.

...

"Political power is being used to prevent research that there is broad consensus could be highly beneficial," he said. "And thus science is being threatened."

As I have said before, these pending anti-research bills are the real source of damage to research: they scare away private funding and deter researchers from entering the field. If you oppose government restrictions on research, now is a good time to speak up and be heard.

Biogerontologist Aubrey de Grey is featured in an article at The Australian. "Ultimately, we could extend life indefinitely because these processes do not simply slow down the damage which causes ageing, but repair it." He predicts that with the right level of funding (and it would be a large project, on the order of $100 million per year), we could develop the technology to greatly slow or prevent age-related degeneration in mice in a decade. This sort of timeline can be given because the path forward is clear: No new pathways for the accumulation of age-related damage have been discovered in the last 20 years, which "strongly suggests that no more are to be found -- at least, none that would kill us in a presently normal lifetime."

Link: http://www.theaustralian.news.com.au/common/story_page/0,5744,10709848%255E421,00.html

Terry Grossman is doing the rounds to talk about his new book "Fantastic Voyage: Live Long Enough to Live Forever." "In our new book, Ray Kurzweil and I make the scientific case that immortality is within our grasp. We explain how to slow down aging and disease processes to such a degree that you can remain in good health until the more radical life extending and life-enhancing technologies - now in the research and testing pipeline - become available." I'm less optimistic about the future of healthy life extension medicine and the ability of present day techniques to affect the aging process. This is why I believe that we must all get involved to ensure that serious anti-aging research is funded in time for us to benefit from it.

Link: http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20040908005616&newsLang=en

The latest weekly article at SAGE Crossroads (entited "Deja Vu") examines similarities between the political debate over in vitro fertilization (IVF) in the 1970s and the present debate over embryonic stem cell research.

The debates then and now aren't perfectly parallel, but how society at first recoiled from and then embraced IVF foreshadowed the negative reaction to stem cells--and might well portend the outcome of the controversy. Today, IVF raises few eyebrows.

Funnily enough, Leon Kass (of the President's Council on Bioethics) was strongly opposed to IVF until its acceptance was more or less a given:

Even Kass, a leading opponent of the technology in its early days, changed his stance after the 1978 birth of Louise Brown, the first "test tube baby." He recognized the joy IVF could confer by blessing infertile couples with children. Still, he remains apprehensive about the broader implications of assisted reproduction and its associated innovations. "If anybody thinks that the controversies that were started by IVF have been settled and gone away," he says, "they should rethink."

Unfortunately, Kass hasn't yet come round to endorsing embryonic stem cell research for the purpose of curing fatal diseases yet. Working around infertility is apparently more important in his hierarchy of values than healing people who are dying from their conditions.

Still, Kass - and, one hopes, the Bioethics Council - are becoming irrelevant in the face of public support and scientific progress. No-one listens to what he has to say about IVF anymore, after all. Politicians can certainly continue to hinder progress towards regenerative medicine based on embryonic stem cell research, but they can't stop it now. That said, speed is of the essence - tens of thousands of people continue to die each and every day from conditions that will be curable in a matter of years.

Here is a little poll data from PR Newswire for you to mull over: "In 2001, a Harris Poll reported
that a 3-to-1 majority of Americans believed that stem cell research should be
allowed. Three years later, a new Harris Poll finds that this majority
supporting stem cell research has increased to more than 6-to-1." If nothing else this promises to make life interesting for US politicians should they continue to attempt a ban on therapeutic cloning. For those who follow these things more closely, you can find links to more polling data at Fight Aging! Personally, I look forward to seeing the day when serious anti-aging research enjoys the same level of public understanding, debate and support.

Link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/09-07-2004/0002245361&EDATE=

The Gazette at John Hopkins University provides insight into how research into calorie restriction moves forward: "Calorie restriction has intrigued scientists for decades because it increases the life span of almost every species studied." Genetic screening allows scientists to establish a profile of changes caused by calorie restriction. This profile can then be compared with those produced by various compounds to try and narrow down the field of candidate drugs and drug targets in the body. "Our findings could be used to take a rational approach to designing drugs that mimic beneficial aspects of calorie restriction." Calorie restriction mimetics are a hot topic in medical research at the moment.

Link: http://www.jhu.edu/~gazette/2004/07sep04/07mimic.html

A thought-provoking post from Scott McClatchey to the CR Society mailing list:

Dean Pomerleau and I have separately calculated that each excess calorie costs about 30 seconds of lifespan. Indeed, each calorie (excess or not) hastens aging and shortens the expected life span by this amount. Here are some derivative calculations.

Given the above and the Harris Benedict formula for Basal Energy Expenditure, for a 40-year-old man, each extra pound of weight costs 0.2 years of life span. Since this comes in terms of earlier aging, this results in perhaps 0.15 years of lost wages. Thus, if your earnings are $100,000, each extra pound of weight costs $15,000. Ouch! (n.b., the figure of 100,000 was used as a round figure, to make extension of these calculations more simple).

More precisely for varying ages, it costs 2 days of lifespan in order to carry one excess pound for one year. In dollar terms, this extra pounds costs about $400 /(pound*yr).

Stated another way, those who are over the minimum optimal weight pay a tremendous dollar cost for the privilege of being overweight!! Can anyone
afford NOT to practice CR???

These figures should all be taken as ballpark averages across a large sample, as the 30 second per calorie number is extrapolated from data in mouse studies (as I recall). Then there is the matter of quantifying the minimum calorie intake or weight above which you start counting deductions in life span - but you get the general idea.

The point of the exercise is to act as a reminder: rigorous scientific evidence shows that even average calorie intake and average weight carries a sizeable cost in dollars, health and life span. The real cost of a shorter life span, to my mind at least, is the prospect of missing out on advances in medical science and radical healthy life extension in decades to come. Calorie restriction is a way to reach a little further forward into the future, a stepping stone to better technologies.

A nice long piece at Medical News Today discusses movement towards controlling stem cells to treat osteoporosis (age-related bone loss, or "brittle bone disease"). The ability to quickly discover compounds that cause stem cells to differentiate into specific types of mature cell - bone cells in this case - is one of the great benefits of bioinformatics. Advances in computing, automation and miniaturization mean that hundreds of thousands of compounds can be screened in the time it once took to check a dozen outcomes. This allows scientists to skip directly to the answer, as it were - new biochemistry is being uncovered in a year of work where it would once have taken a decade or more.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=12975

Medical News Today notes that more than one billion people are expected to be over the age of 60 by 2025, double the present number. The challenge we face: how soon can the scientific and business communities research and commercialize regenerative therapies for age-related degenerative conditions? How soon can we develop and manufacture ways to intervene in the aging process so as to prevent damage and disease from occurring in the first place? This is a race against time to save - and improve - a billion lives over the next few decades. Each year of delay is accompanied by fifty million deaths and untold suffering for hundreds of millions of afflicted people.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=12976

A recent press release of survey results demonstrates, quite nicely I think, how the anti-aging marketplace is damaging the prospects for real anti-aging research (such as that advocated by Aubrey de Grey in his Strategies for Engineered Negligible Senescence):

Excerpts from this study: About 40% of the individuals sampled believe that anti aging products are basically "hogwash", while another 36.4% are "curious but sceptical." Only 3.41% say that they like such products a lot but more than 20% say that they can "work sometimes".

Serious research requires serious money; hundreds of millions of dollars a year over decades. Public and private funding at that level only happens in an environment of strong public support, understanding and demand. Look at the fight to cure cancer or Alzheimer's, for example. Here we see that the opportunistic anti-aging marketeers have managed to create an environment in which 70% of people are either justifiably skeptical or think it's all nonsense - which a good deal of it is. These attitudes are then applied to any attempt to lengthen the healthy human life span, legitimate or otherwise. This is not good at all for the prospects of a serious large scale effort to develop medical interventions for the aging process.

Comments worthy of note from an Australian scientist who is working with embryonic stem cells:

Breakthrough treatments for multiple sclerosis (MS) may be just five years away, an Australian leader in stem cell research said in Christchurch yesterday.

Professor Alan Trounson, director of Australia's main centre for stem cell research at Monash University, was speaking about advances in stem cell therapies.

Speaking at the Christchurch School of Medicine and Health Sciences open day, Professor Trounson said that animal trials of an MS therapy had proved so successful he believed hospital trials were likely "really soon".

Researchers had found that primitive nerve cells, grown from stem cells in the lab, could reduce symptoms of an MS-type illness when injected into mice.

The cells had been able to pass into the rodent's brain where they matured into myelin-producing cells. Myelin is an important protective coating around nerve cells that is stripped away in MS sufferers, causing messages to become scrambled.

"Using these cells to reverse conditions like MS I think is highly probable in the next five years, perhaps even less," he said.

Multiple sclerosis is not on my normal research watch list, but I thought it interesting that Alan Trounson is giving such an enthusiastic timeline for this work. Unfortunately, it isn't too clear from the articles as to whether the prospective MS therapy relies on adult stem cells or - as for Alan Trounson's other work - uses embryonic stem cells.

The Chicago Sun-Times reports that advances in tissue engineering and artificial organs are making xenotransplantation - use of animal organs to replace failing human organs - less interesting. "Ten years ago, everybody thought it would come about. Enthusiasm has waned." Overcoming immune system rejection and other barriers has - like more or less everything to do with medical research - proven to be more difficult than first thought. Meanwhile, stem cell research and materials science advances seem likely to lead to the first artificial organs grown from patient tissue in a decade or so. This is a brute force method of extending healthy life span - in the long run we should eliminate the root causes of age-related damage.

Link: http://www.suntimes.com/output/news/cst-nws-pig05.html

Something for you to look over at your leisure: the National Cancer Institute maintains a large and informative website on nanotechnology and its role in the future of cancer research. A cure for cancer is an important milestone in the road to radical life extension, as the immediate future of regenerative medical technologies (such as those based on stem cells) will lead to repairs for age-related damage that do not reduce the ever-increasing risk of cancer.

As I have noted before, the first applications of nanotechnology to medicine are diagnostic in nature. Improvements in nanoscale manufacturing have led to powerful applications in this field. The NCI website notes:

NCI programs conducted over the past five years have supported research on novel nanodevices that may detect and pinpoint the location of cancer at its earliest stages, deliver anticancer drugs specifically to malignant cells, and determine in real-time if these drugs are effective in killing malignant cells.

We envision that nanotechnology will change the very foundations of cancer diagnosis, treatment and prevention.

For current day cancer treatment, early detection makes the different between life and death. Most cancers can already be dealt with if caught very early on.

For those of you who like such things, there is a webcast on September 13th:

The National Cancer Institute (NCI), part of the National Institutes of Health, hosts a media briefing on the formal announcement of its $144.3 million, five-year integrated initiative to develop and apply nanotechnology to cancer prevention, detection, diagnosis and treatment. Nanotechnology, the development and engineering of devices so small that they are measured on a molecular scale, has already demonstrated promising results in cancer research and treatment.

The NCI has invited experts from both the oncology and nanotechnology disciplines to brief reporters on the science, the issues, and the potential of the new NCI initiative.

(From the Milwaukee Channel). Researchers have announced a potential breakthrough in Alzheimer's research - the discovery of a protein that may halt progression of the condition. Like many advances, this stems from lateral thinking when faced with a research problem. In this case, scientists were struggling to create a mouse version of the disease. "I said to myself, everybody is trying to kill neurons in mice to create the Alzheimer's pathology. And here we have a mouse that has amyloid deposition and plaques yet no neurons are dying. Let's try to figure out why these mice aren't getting the disease." It remains to be seen as to whether this new work will translate to humans, but it looks promising.

Link: http://www.themilwaukeechannel.com/health/3702618/detail.html

A collection of articles at Science Magazine examine aging as a collection of disparate processes: "Though we tend to speak of aging as a generic condition, its most devastating manifestations -- things like the deterioration of bones, joints, and neurons -- seem maddeningly specific to particular organs and tissues." Beating age-related degeneration through regenerative medicine - rather than preventing the root causes of the aging process - will require us to be able to repair many different types of damage to all our organs. It's a big job, which is why the level of funding and rate of progress are very important. Given the important recent research on the topic, you may find the article "What Can Progeroid Syndromes Tell Us About Human Aging?" interesting.

Link: http://www.sciencemag.org/sciext/aging2004/

(From Betterhumans). Researchers claim to have identified adult skin stem cells capable of differentiating into all kinds of skin tissue - at least in mice. "We've identified cells within skin that bear all the characteristics of true stem cells - the ability for self renewal and the multipotency required to differentiate into all lineages of epidermis and hair." This raises the possibility of a regenerative cure for baldness based on stem cell medicine - something I mentioned briefly earlier this year. More importantly, the ability to manipulate and use multipotent skin stem cells should bring a welcome boost to regenerative medicine for a variety of serious injuries and conditions.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-09-02-4

We humans are downright irrational beings - witness the fact that the possibility of a cure for baldness arising from stem cell based regenerative medicine garners just as much interest as a cure for heart disease using the same technology.

I think that the Onion had it right in its satirical treatment of the topic.

"I've always said I don't believe in that Frankenstein-type research, but lately I've been thinking that there might be something to it," said Tell, a 43-year-old father of two and victim of male-pattern baldness. "If there are people out there who could truly benefit from that stem-cell stuff, who are we to deny them?"

The shift in thinking occurred just three days after Tell received a haircut that revealed a large, bare patch at the crown of his head. The bare patch accompanies the recently converted stem-cell-research advocate's receding hairline, of which he has long been aware.

I'm not one to tell other people what they should be thinking, but fixing the fatal conditions before the vanity issues sounds like the better way forward to me. Still, if vanity is what it takes to get people to understand and support stem cell research...

Randall Parker has more on the most recent work on mice and their adult skin stem cells - and what that means for hair regrowth in humans.

CNN reports that Singapore has banned reproductive cloning but continues to permit regulated therapeutic cloning research, a position similar to that of the UK government. The Singapore administration has been moving towards development of their state as a biotechnology hub: "To draw scientists and biotech funds into its 40,000-sq-meter (430,600-sq-ft) Biopolis park, Singapore is offering a mix of tax breaks, grants and other incentives worth $1.3 billion -- and one of the world's most relaxed legal climates for research." It is unfortunate that we now live in a world in which scientists require permission to proceed from politicians - delays in medical research impact all of us.

Link: http://www.cnn.com/2004/TECH/science/09/02/singapore.cloning.reut/index.html

The cover story for Chemical and Engineering News provides a good overview of some of the more recent aging science - and what we could to to slow or halt the aging process. The bulk of the article focuses on scientific research stemming from calorie restriction: investigations into the genetic and biochemical mechanisms by which CR extends healthy life span and reduces the risk of suffering age-related degenerative conditions. Work on telomeres - the protective caps at the ends of our chromosomes that serve a number of important functions - also gets a mention, as does research into how we lose our ability to heal ourselves as we age. "A decline in Notch signaling in [stem cells] may be a general mechanism underlying the diminished regenerative properties of aged tissues."

Link: http://pubs.acs.org/cen/coverstory/8234/8234aging.html

Long time readers will be aware of my opinions on Leon Kass:

If you want to take the interview at face value, Leon Kass is a mystic. He is a modern alchemist. The alchemists of old stood atop what little knowledge of chemistry they had and built a speculative religion of hermetic magic, transient wishes, celestial signs and hidden gold. Leon Kass stands atop what little biotechnology we have today (and seems to have a good grasp thereof), building his own structures of fanciful thought, equally disconnected from the real world.

On the President's Council on Bioethics:

It has recently become very clear the President's Council on Bioethics is nothing more than a rubber stamp intended to justify bans on stem cell medicine, therapeutic cloning and other new medical technologies that anti-abortion groups dislike. Research in these new fields is vital to the development of working regenerative medicine, a field that promises near term cures for a wide array of age-related conditions.

And on bioethics in general for that matter:

Once upon a time, a discipline called "medical ethics" existed and was held in high regard. Medical ethics addressed the subjects of triage and best use of sparse resources in medicine: who to save when you cannot save everyone? New advances in medicine were welcomed and enthusiastically funded, because new and better medical technology meant improvements in health, lifespan and the ability to save more lives.

Somewhere along the way, overstressed, under funded medical ethics - a discipline whose members welcomed new medicines, new therapies and better ways to treat disease - became fat, well-funded "bioethics." Bioethics is concerned with slowing down the advance of medical science with deep philosophical and ethical questions that can only be answered by means of large salaries, hundred million dollar buildings, and political interventions.

In short, medical ethics lost its way and become corrupted by power.

Given all that, I thought I should point you to this update on the Council from Chris Mooney, since we haven't heard anything from that direction for a while.

One of the chief ways in which the council was undermined, of course, was that Bush announced his position on "therapeutic" cloning before the group's report had even come out. Similarly on stem cell research: Bush set the policy, then convened his bieothics council. No wonder the group hasn't had much influence--the president himself doesn't seem to take it seriously.

My position on the council stems from my opposition to regulatory and legislative restrictions on medical research; the Bioethics council was simply a facilitator - a rubber stamp. Kass, Fukuyama and others are welcome to hold their pro-death views and oppose healthy life extension research, but they are not welcome to force the consequences of those views onto the rest of us.

A couple of articles from the Ludwig von Mises Institute that you might find interesting:

100 Years of Medical Robbery:

In the days of its founding [the American Medical Association] was much more open--at its conferences and in its publications--about its real goal: building a government-enforced monopoly for the purpose of dramatically increasing physician incomes. It eventually succeeded, becoming the most formidable labor union on the face of the earth.

Real Medical Freedom:

Economic constraints, like the force of gravity, always return. The question is, in what form? Free-market forces which are the source of the highest standard of living on the planet, or government budget constraints? The latter has not only hurt the quality of care in Canada but, in the end, failed to control costs. Says Canada's Fraser Institute, "Canadian taxpayers are paying for a world-class health care system, while getting service that ranges from mediocre to terrible. Even a decent performance in Canada is an unimpressive performance overall."

Enforced single-provider regulation and oversight is always a bad thing - freedom to compete and real consumer choice are the only recipe for better service and better products in any given industry. As US politicians shift ever closer towards socialized medicine, research investment will decline and quality of service will fall off.

Research matters to you and I. It matters greatly, and here is why: The level of investment in appropriate medical research determines the speed with which cures for age-related conditions and life-extending therapies can be developed and brought to market. Private investment - 60-70% of all medical research funding - is only deployed where profits can be made. Regulation makes it harder for new businesses to profit, as existing companies buy protection through government-enforced cartels, monopolies and imposition of large costs for new businesses. It's no coincidence that most of the world's medical research occurs in the least regulated regions, where there is at least some freedom to compete and innovate.

The length of your life and your future health depends on the medical research taking place today. This research is in turn greatly impacted by freedom or the absence thereof.

The Coalition for the Advancement of Medical Research is reprinting an article on German criminalization of embryonic stem cell research. Similar restrictive legislation for the related (and important) technology of therapeutic cloning is still possible in the US. The current situation in Germany clearly demonstrates the end results: "The restrictions ... leave scientists there with only one legal option for producing embryonic stem cells for research: leaving the country. For those who remain in Germany, even collaborating with international colleagues on new lines could leave them at risk of prosecution." Slowing the pace of stem cell research has real, ugly consequences for our future health and longevity.

Link: http://www.camradvocacy.org/fastaction/news.asp?id=1121

The MIT Technology Review cuts through the fog to examine the true state of stem cell research. How close are we to cures for age-related conditions and working regenerative medicine based on this research? The scientist interviewed here suggests a decades-long timeline, although others estimate the first therapies are more like ten years away. The adult versus embryonic stem cell debate is also examined: "The public has been misled by the partisan tug of war over the notion that, given more study, adult stem cells could accomplish the same regenerative feats as their embryonic counterparts ... studies of embryonic stem cells yield important information for the understanding of adult stem cells, and vice versa. But overall, embryonic stem cells still appear to hold the advantage."

Link: http://www.technologyreview.com/articles/04/08/wo_asbrand083104.asp