Fight Aging!

From The Scientist:

The world's science academies were urged yesterday (August 30) to reinforce their support for an international treaty on cloning that does not outlaw cell nuclear replacement for therapeutic purposes.

The United Nations (UN) General Assembly is expected to revisit the vexed issue of a convention on human cloning this fall, with a vote tentatively scheduled for October 21-22. Ahead of that meeting, the InterAcademy Panel (IAP), an umbrella body for national science academies, recently called on its member groups to step up pressure on their national governments.

Therapeutic cloning, or SCNT, is a vital to developing the most promising regenerative medicine based on stem cell research. Threats to therapeutic cloning in the US - proposed anti-research federal legislation and existing state restrictions - have caused great damage to the availability of private funding over the past few years.

Attempts by the present US administration to obtain an international ban on therapeutic cloning are particularly galling:

Faced with this opposition at home, the anti-research US administration has been pushing for a global ban at the United Nations. We all dodged a bullet when the ban was defeated by 1 vote in November 2003, and further debate delayed until 2005. Unfortunately, the US administration quickly pushed to overturn this vote in December 2003, and two years of delay become one. The ban will be brought up again in 2004.

Now would be an excellent time to support stem cell research by contacting your elected representatives:

I am writing to urge your support for human therapeutic cloning (also known as somatic cell nuclear transfer, or SCNT), a technology vital to embryonic and adult stem cell research, which holds the potential to treat and better understand the deadly and disabling diseases that affect more than 100 million Americans, such as cancer, heart disease, diabetes, Parkinson's, Alzheimer's, multiple sclerosis, spinal cord injury and many others.

The threat of a ban on therapeutic cloning on top of existing legislative restrictions has caused great damage to private funding of stem cell research. Billions of dollars are waiting in the wings to help, but will not be invested in a climate of uncertainty.

Why are US ambassadors to the United Nations continuing to push for a global ban on therapeutic cloning? Why do US senators continue to push back a vote on the therapeutic cloning bill postponed from 2003?

If stem cell research - adult or embryonic - is to obtain significant private funding and thus proceed in any meaningful way, the US government must stop attempting and threatening to ban the most vital technology used in this research.

Reason
Founder, Longevity Meme

You have a voice: use it.

The St. Petersburg Times investigates centenarian and other longevity studies: "By analyzing why the super-old age so well, scientists are gaining valuable information about avoiding the cancers, strokes and heart diseases that ravage younger people and cut short their lives." It turns out to have as much to do with diet and lifestyle as genes - you have a great deal of control over how much damage you are doing to yourself over the years. Since we are talking about diet, calorie restriction should get a mention - it is the only currently proven method of even slightly extending the healthy human life span. For far longer, healthier lives, we must support the future of medical research.

Link: http://www.sptimes.com/2004/08/31/State/Keys_to_long_life_see.shtml

I mentioned the work of Leonid Gavrilov and Natalia Gavrilova last week: here is the full IEEE Spectrum article on the reliability theory of aging. "The problem is that our bodies deteriorate with age. For most of our lives, the risk of death is increasing exponentially, doubling every eight years. So, why do we fall apart, and what can we do about it?" Reliability theory has proven to be very useful in the manufacturing world - it seems that it can be equally useful in the fight to cure aging and greatly extend our healthy life spans. If you want to read more, Leonid Gavrilov has kindly placed an article on his work here at the Longevity Meme.

Link: http://www.spectrum.ieee.org/WEBONLY/publicfeature/sep04/0904age.html

The LEF News is reprinting an article on cancer stem cells and current attempts to build new and better cancer therapies. "The solution would lie in stamping out the highly specialized cells, known as cancer stem cells, that appear to give rise to the cancer in the first place. Such cells are largely impervious to current treatments, enabling them to lurk silently until they repeatedly spawn new tumors, either in the same part or in other parts of the body." At least some types of cancer appear to have identifiable stem cells, and trials are underway for leukemia patients at the University of Kentucky. From the researchers: "It looks fantastic in the lab. In the laboratory we can very effectively kill the tumor without killing the normal stem cells."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1010&Section=DISEASE

A recent news release carried by the Longevity Meme:

https://www.fightaging.org/archives/2004/08/the-adonis-effect/
http://www.sciencedaily.com/print.php?url=/releases/2004/08/040817080650.htm

... taken almost verbatim from a Mayo Clinic original:

http://www.mayoclinic.org/news2004-rst/2384.html

quite badly misrepresents the interpretation of the study to which it refers (1). The story makes it sound as if these results were important for avoiding degenerative age processes:

"Weight gain and bone thinning may seem to be natural complications of aging in humans and mice. Now, Mayo Clinic researchers have discovered a genetic basis for this physical decline."

But that isn't at all what the study shows. I have double-checked with the full text of the study and, as per the news story:

Researchers found that the mutant mice whose TLR4 was silenced had:

Greater bone mineral content at 20 weeks of age compared to normal mice -- and that this relationship increased as both groups aged.

Larger bones at 20-24 weeks of age.

70 percent less body fat than the control group as they grew and aged.

The body fat results, like the bone results, were measured at 6-9, 12-14, and at 20-24 weeks of age, at which point the differences were most pronounced. But 20-24 weeks of age in a mouse is roughly the equivalent of ~12-17 human years. In other words, this study is about the programmed process of development -- not the stochastic process of age-related decay.

Of course, this tells us nothing about their ability to avoid bone loss or weight gain caused by, or even associated with, aging. Indeed, one might well expect that whatever energy-intensive, likely highly mitotic process underlies this result (I'm ignorant of the TLR4 biochemistry), it might well wind up causing premature aging: think of the case of the various growth hormone/IGF1 mutant mice, or CR animals. Their bodies are smaller and scrawnier, and their bones lighter, in youth; but because they don't degenerate with age, they wind up better off in late life -- especially after all of the control animals are dead.

I guess the good news is that researchers and their institutions now want to be seen to be doing aging research.

1. Johnson GB, Riggs BL, Platt JL. A genetic basis for the "Adonis" phenotype of low adiposity and strong bones. FASEB J. 2004 Aug;18(11):1282-4. Epub 2004 Jun 18. PMID: 15208271 [PubMed - in process]

The BBC reports that a United Nations ban on therapeutic cloning - strongly backed by the current US administration and narrowly defeated earlier this year - may be reintroduced as early as next month. Therapeutic cloning is vital to much of the most promising research into regenerative medicine and related potential therapies for age-related conditions. Therapeutic cloning has not been banned in the US (but not for lack of trying, and it is illegal in many states). The only upside to this whole shady business is that "it is clear that if the UN bans all forms of human cloning, the UK, and other countries which currently permit carefully regulated therapeutic cloning, will not sign up to it."

Link: http://news.bbc.co.uk/2/hi/health/3609992.stm

I hadn't previously explored the (possibly overcomplicated) system for online publishing used by the Rejuvenation Research journal, amongst others. What I would like to draw your attention to today is that the full contents of the first issue of Rejuvenation Research are available for free. (Obtaining the PDF format articles is a little slow, however, so be patient).

Good reading for the layman includes "Someone's Knocking on the Laboratory Door," "A New Age for Aging? Ethical Questions, Scientific Insights, and Societal Outcomes" and the interview with Michael West. Take a look and see what you think.

A News-Gazette article hints at some of the research attempting to unravel the peculiarities of bear biochemistry. "They're amazing animals with many possibilities for research that could benefit humans. Bears are the only animals that can go without food and grow. I think they'll have an answer to the aging process." The focus here is on osteoporosis - age-related bone loss - as "sufferers could benefit from a characteristic of ursine chemistry ... that inhibits dissolving of fibroblasts which build bones." Aging and related processes in the body are far from uniform across the animal kingdom - there are even animals that age too slowly for researchers to make a good estimate of life span.

Link: http://www.news-gazette.com/story.cfm?Number=16640

An article at the New York Times demonstrates the current model of retirement to be broken. In a world of lengthening healthy life spans, static retirement ages would cause economic hardship. Attitudes towards older workers (and old age in general) will have to change. This article is a prime example: it assumes that older folk are dependants of the state, incapable of looking after their own interests, work is something that people are forced to do, retirement is a right, and longer life spans are a bad thing. Fortunately, employers and employees are far more pragmatic than writers at the NYT. The culture of entitlement and government meddling will only interfere in progress towards a society of greater and productive longevity.

Link: http://www.nytimes.com/2004/08/29/business/yourmoney/29old.html?ei=5040&en=894fdadb4ae23a8d&ex=1094529600&partner=MOREOVER&pagewanted=print&position=

Since we're on the subject of exercise and natural longevity today, it seems worth reminding everyone that "use it or lose it" applies just as much to the brain as the body. If anything, keeping your brain in good shape is way and far more important than looking after your body: medical technologies to repair the aging brain are likely to lag behind other regenerative medicine. The human brain is a very complex piece of equipment, and consequently presents a greater challenge for researchers. While cures for Alzheimer's and Parkinson's seem likely in the decades ahead, that still leaves an array of fearsome age-related degenerative brain conditions, both known and unknown. You only have the one brain - so take care of it.

Link: http://www.bradenton.com/mld/bradenton/living/9508325.htm

You might recall that I mentioned discussion of a Methuselah Fly prize at the start of the month. It turns out that people have a lot to say on the matter, so the Immortality Institute has devoted a section of their forum to longevity research prizes.

A fair amount of the technical discussion focuses on the suitability of flies for this particular form of research. Other subjects have been nominated - the idea being to find animals that are less costly to maintain and have shorter life spans than mice. Some aspects of fly physiology - such as diapause - have been held up as a bad thing in the context of a competition for the longest-lived flies. Small African fish were one suggestion when the discussion spilled over into usenet.

All in all, it looks like preparation for a new volunteer-run prize for aging science may get underway in the near future.

Research shows - overwhelmingly shows - that a lack of exercise will reduce your healthy life span and raise the risk of suffering all of the most common age-related conditions. "Many of the chronic health conditions we experience as we age come from disuse rather than aging, and exercise can retard the onset of many of those conditions." We are living at the end of an era: real, effective therapies for aging could be as little as a few decades away. Regenerative medicine for age-related damage will help us to get there, starting in a decade or so. It would be a shame to miss the boat because you didn't take a little time and effort to stay in shape now. It's not rocket science, nor is it costly. So get to it!

Link: http://www.azcentral.com/news/articles/0827fountainofyouth-ON.html

Yahoo! News notes that Sirtris Pharmaceuticals - a company founded by David Sinclair to investigate the biochemical processes associated with calorie restriction - has received seed funding from venture firms. Sirtris will focus on the class of enzymes called sirtuins, involved in the regulation of metabolism and aging. "Recently scientists found that the life-extending benefits of calorie restriction do not occur if the animal has been genetically altered to lack sirtuins, indicating these enzymes are crucial to this process." It is good to see more money entering this field of research - Sirtris joins other companies like Elixir and BioMarker in the search for healthy life extension drugs based on calorie restriction.

Link: http://biz.yahoo.com/prnews/040827/nef001_1.html

Research into calorie restriction - the diet choice that has been proven to extend healthy life span as well as confer many health benefits - has so far concluded that it works through changes to the Sir2 gene that increase expression of certain proteins (sirtuins such as SIRT1).

Earlier this week, one researcher group claimed that calorie restriction operates through a mechanism other than tweaking Sir2 - at least in yeast. Betterhumans has another article on this new discovery:

If caloric restriction truly extends lifespan by causing an overexpression of Sir2, then studies suggest that combining caloric restriction with Sir2 overexpression should have no additional effect on lifespan.

Kennedy and colleagues have found, however, that combining caloric restriction with Sir2 overexpression or Fob1 mutation actually increases yeast lifespan.

"Further," say the researchers, "calorie restriction results in a greater lifespan extension in cells lacking both Sir2 and Fob1 than in cells where Sir2 is present."

The findings suggest that a pathway besides Sir2 is responsible for the increased longevity, say the researchers.

Not everyone is sold, however:

"I disagree with the conclusions," says Leonard Guarente of the Massachusetts Institute of Technology in Cambridge, an expert in Sir2 and the molecular basis of aging. "They find a new, ill-defined pathway that can mediate caloric restriction in their strain. This in no way challenges earlier findings that in a different strain, a well-defined pathway including Sir2 does mediate caloric restriction."

Leonard Guarente is one of the founders of Elixir Pharmaceuticals, a company that is is currently licensing one of the new calorie restriction mimetic drugs as a complement to longer term healthy life extension research. As I've probably mentioned before, I like to see scientists arguing - it's usually a sign of progress.

Betterhumans is giving deserved attention to the work of Leonid Gavrilov and Natalia Gavrilova. They have extended reliability theory - developed for use with complex electronic machines in the 1950s - into the realm of the human body and life span: "We are like machines made up of redundant components, many of which are defective right from the start." Machine failure rates and human death rates are very similar in form - which should not be too surprising. Reliability theory predicts no fixed upper limit to life span: "Even small improvements to the processes of early human development - ones that increase the numbers of initially functional elements - could result in ... a significant extension of human life."

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-08-26-3

(From KnightRidder). At the boundary of engineering and medicine, there is a thriving industry engaged in extending healthy life span by building replacement parts for worn organs. In the long run, engineering and biology will merge - into regenerative medicine, tissue engineering and ultimately "wet" nanotechnology. In the meanwhile, we are in the era of artificial hearts, replacement joints, and early stage controlled growth of tissue. We should expect impressive improvements in this field in the years ahead - assuming that regulatory roadblocks are kept to a minimum. "The federal government, research universities, foundations and private companies are betting big bucks on bioengineering."

Link: http://www.realcities.com/mld/krwashington/9495173.htm

A piece at PLoS Biology takes an educational look at the most basic basics of regenerative medicine - the cellular biochemistry that makes it all possible. "The regeneration of lost body parts and injured organs has captured the human imagination since the time of the ancient Greeks ... During the nineteenth century and for most of the twentieth century, regeneration research primarily focused on the phenomenology of regeneration and its cellular basis ... The public has recently exhibited a renewed interest in regeneration research, due in large part to stem cell research, which has provided promising avenues for the field of regenerative medicine." Regenerative medicine will have a large positive influence on quality and length of life in the decades ahead.

Link: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371%2Fjournal.pbio.0020232

I (mostly) left aside commentary on stem cell news for all of six days. Much of the current crop of column inches is not worth bothering with - biased polls, political posturing, talking heads chewing things over and pushing various party lines back and forth. This circus is, however, managing to educate the public about the possibilities of regenerative medicine. Cures for age-related degeneration and resulting longer, healthier lives have become very plausible; the first wave of new, effective regenerative therapies could be as little as ten years away. With these ideas planted, it will become much easier to talk about serious anti-aging research and projects designed to accelerate the rate of progress in this field.

Here are a few of the more worthy odds and ends, starting with the news that Bill Gates is helping to fund the Proposition 71 initiative:

Microsoft chairman Bill Gates has contributed 400-thousand dollars to the campaign backing a California ballot measure that would make billions of dollars available for human embryonic stem cell research and cloning projects.

The Proposition 71 organization has been amassing money and high-power endorsements at an amazing rate. They're up to $12 million already - the count was officially $7 million only ten days ago. At this rate they're going to have millions left over after the November ballot ... to fund appropriate medical research, perhaps?

A few items from Betterhumans in recent days note small steps forward in adult stem cell research. Firstly, work on understanding how to transform bone marrow progenitor cells into bone cells:

A chemical that turns stem cells into bone cells could provide a basis for treating bone-weakening diseases such as osteoporosis, and possibly other diseases involving cell loss such as such as arthritis and Parkinson's.

...

While stem cell therapy is promising, however, there are still challenges hindering its use. One of the biggest challenges to their use is coaxing them to become specialized cells, a process called cellular differentiation. Determining what signals drive stem cells to differentiate into specific mature cells is considered essential for their use.

Osteoporosis is one of the many common age-related conditions we need to beat. It doesn't get the press that cancer and heart disease do, but you really don't want to suffer from it.

Adult stem cells in the pancreas identified:

Researchers at the University of Toronto in Ontario, Canada believe that the cells they have identified could be stem cells capable of generating the insulin-producing beta cells that type 1 diabetics lack. These cells could be transplanted into the pancreas of diabetics to stimulate the production of insulin.

Discussions of stem cell science often overlook just how much work has gone into being able to simply identify stem cells in a reliable way.

Onwards to a very typical example of an article noting that all parties in US politics are lying, exaggerating and spinning on the topic of stem cells. Like most such pieces, it focuses on Federal funding policy when the real problems are elsewhere.

Stem cell research has eclipsed gay marriage as the leading social issue of the presidential campaign. Creative politicking by Democrats and Republicans alike has obscured the truth of what the president's policy does and, just as importantly, what effect it's having on research into treatments for diseases from Alzheimer's to diabetes.

As with so much in emerging science, the answer is not nearly so neat as either campaign would have you believe.

Oh, and the polling - the endless polling. Three short commentaries from Chris Mooney on polls and stem cells:

Pew Research Center survey:

People have heard a lot more about the issue since March of 2002, and when asked whether it's more important to "conduct research" or "protect embryos," 52 percent now say "conduct research." In March 2002 that was only 43 percent.

Poll biases and the biases of those who complain about them:

So in short, even if you bias the question wording very strongly, almost half of Americans now support embryonic stem cell research. Moreover, this is a new development, representing a true sea change in public opinion that has clearly occurred during the past three years.

The popularity of embryonic stem cell research:

The new data show that more people know about stem cell research than ever before, and that apparently as a result, the majority favoring the research has increased from 63 percent (versus 21 percent opposed) to 73 percent (versus 11 percent opposed).

Chris Mooney, as usual, has a bunch of other interesting posts at The Intersection, such as "The Party of Cloning":

I'm also getting very sick of the use of this term, "human cloning," to describe the cloning of embryos for research purposes. I think we should call that what it is: pro-life rhetoric. Plain and simple.

Gina Kolata on Stem Cells:

In summary, then, Kolata's article provides a fascinating overview of the science and the constraints it's facing. I think she downplays the positive results so far--no mention of the success in using mouse embryonic stem cells to create insulin producing pancreatic cells, for example--but there's a hard-headed attempt at realism on her part. We need more of this.

Gearhart and Faden on Stem Cells:

Gearhart and Faden are up front about the problem of uncertainty: "In no cases are cures guaranteed, and even in the most promising areas, reliable cures are years, in some cases as much as five to 10 years, away." They don't go in for faith-based adult stem cell boosterism. They make the very important (and often missed) point about the need for disease-specific embryonic stem cell lines. They expose the piddling amount of money the NIH has invested in this field for what it is.

Adult stem cell research is indeed getting the lions share of public funding - not that this is really all that meaningful in the larger context. Private and philanthropic funding outweigh public funding for medical research, but investors are much less likely to invest while politicians are trying hard to ban essential parts of the technology in question.

Meanwhile, adult stem cell transplants - a whole different branch of stem cell medicine that is closer in concept to bone marrow transplants and blood transfusions than the more debated areas of stem cell research - are getting much more common:

Transplanting stem cells from a healthy woman to her sister with severe rheumatoid arthritis apparently cured the disease, researchers report in the journal Arthritis & Rheumatism.

...

Her morning stiffness disappeared before she was discharged from the hospital and did not recur. Her rheumatoid nodules were completely gone 9 months after transplantation and now one year later the patient is disease-free and is not taking any drugs to suppress her immune system.

Work on regenerating the damage caused by heart disease is making headway too - using both adult and more promising embryonic stem cells:

Scientists back embryonic stem cell research because it appears to give a greater chance of developing regenerative therapies for common age-related conditions. "Stem cells taken from a patient's own muscle or blood failed to make functioning heart cells. Those adult stem cells homed in on damaged heart tissue and latched on, but never got the rhythm the rest of the heart ticked to ... Some of the patients in the study did improve after the therapy .. the [adult] cells may have recruited new blood vessels to the injured area and helped speed the healing." By way of comparison, "the embryonic cells did not just latch onto the wounded heart ... they actually became heart muscle cells that beat in time with the rest of the organ."

Finally, a New York Times piece on the goals and progress of some stem cell researchers:

At three laboratories here, separated by a taxi ride of no more than 10 or 15 minutes, the world of stem cell research can be captured in all its complexity, promise and diversity ...

As you all know, I'm a big fan of research prizes - harnessing the human urge to compete in order to accelerate scientific progress.

If anti-aging and life extension research could break out of its current ghetto, it might be a matter of twenty years or less to obtain the first working therapies. Just look at the fantastic progress made in the Western world in turning AIDS from a mysterious death sentence to a manageable chronic disease - in only 20 years! Look at the results of 30 years of well funded cancer research and advocacy: it seems like not a week goes by these days without some new potential cancer cure announced by a cutting edge biotech company. These are the results that can be achieved with funding, public awareness, advocacy, and hard-working researchers.

If only anti-aging, regenerative and healthy life extension medicine could be taken as seriously. This is why we need an Ansari X Prize for aging. Anti-aging research is the aircraft industry following World War I. It is the tiny private commercial aerospace industry of a decade ago. With an Ansari X Prize for anti-aging research, we would have the chance to turn that all around: publicity, competing researchers, goals that the public could understand, appreciate and cheer for. In short, it would be a fine step forward.

Historically, prizes have inspired somewhere between 16 to 50 times as much investment as is in the purse - a very good deal if you are a philanthropist looking to get the biggest bang for your buck.

One of the important effects of a prize is to gain attention, support and understanding for a particular field or problem. Scientists and futurists also make use of high profile wagers for this purpose:

Jay Olshansky, an epidemiologist at the University of Illinois in Chicago, and Steven Austad, a biology professor at the University of Texas, study gerontology, or the aging process.

A few years ago, the two scientists who are also friends made a bet. Austad stated that he thought it was possible that at least one person born in the year 2000 would still be alive on Jan. 1, 2150. Olshansky thought living to be 150 years old would require almost impossible, "extraordinary conditions."

(The current documented world record for longest living person is 122 years, held by Jeanne Calment, a French woman who died in 1997.)

The stakes of Olshansky's and Austad's bet: $500 million.

Neither scientist has that kind of money. Gerontology doesn't pay that well. Nor can either man, both in their 50s, expect to be around for the bet's conclusion. Instead, Olshansky and Austad each deposited $150 into a trust fund and promised that they or their heirs would contribute an additional $10 annually until 2150.

By their calculations, compounding interest would balloon the total amount of the fund to at least $500 million by 2150. At that time, a panel of notable scientists will determine the winner and award the prize to the victorious bettor's heirs.

"I thank Steve every time I see him for making my future relatives rich," laughs Olshansky.

Olshansky and Austad had other motives for making their bet beyond enriching relatives yet to be born. They both thought the bet would stimulate public interest in gerontology, which is has.

"It has been wildly successful," said Austad. "Both Jay and I have done dozens of interviews, taken inquiries from around the world." Olshansky said the bet was probably what got them an invitation to speak before the President's Council on Bioethics and inspired the Methuselah Mouse Prize, an ongoing effort to extend the life span of lab mice and, in the process, better understand how aging works.

Olshansky, I should note, is a conservative gerontologist - and most likely wrong about the timescale of productive anti-aging research. Unfortunately, public pessimism makes investment in research less likely; it is in danger of being a self-fulfilling prophecy. Biogerontologist Aubrey de Grey has spoken at length on this topic.

However, this wager - like the Methuselah Mouse Prize - accomplishes the all-important goal of drawing public attention towards serious anti-aging research and the prospects for extending the healthy human life span. Large scale research - public or private - does not happen without widespread public support and understanding. Obtaining that support is vitally important.

You can do your part to help - make a donation to the Methuselah Mouse Prize fund!

Growth hormones are a thorny subject, largely due to the actions of the less responsibly portions of the anti-aging marketplace. It's hard to even discuss the topic without getting cut off by spam filters these days. SAGE Crossroads notes a currently fashionable opinion - that any health gains produced by growth hormone therapies come at a cost of shortened life span. This may or may not be the case, but the science of growth hormones is certainly poorly explored and complex. As I've mentioned before, growth hormones are akin to a big red lever on the side of an intricate machine. Pull the lever if you like, but I think that it is a far better idea to wait for scientific understanding to catch up with medical ability.

Link: http://www.sagecrossroads.net/public/news/index.cfm

You might recall all the interest in links between the beneficial effects of calorie restriction and the SIR2 gene. Now, an abstract at PLoS Biology throws an extra wrinkle into the mix. "Kennedy's team has found that the combination of calorie restriction and FOB1 mutation increases life span more than either approach does alone ... If calorie restriction extends life through SIR2, then combining either caloric restriction or SIR2 overexpression with FOB1 mutations should produce the same result. This contradiction raised the possibility that calorie restriction operates through another mechanism, independent of SIR2." While this work studied calorie restriction in yeast, it would seem to indicate that the comparable mechanisms in higher life forms are also a little more complex than was first thought. Stay tuned.

Link: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020308

The New York Times is running an interesting piece on embryonic stem cell research, therapeutic cloning and the goals of researchers in the field. "Another group directed mouse stem cells to grow into nerve cells and tried to use them to treat Parkinson's disease in mice. The nerve cells produced the missing chemical, dopamine, but not enough to cure the disease ... use the cells instead of bone marrow transplants to treat patients with genetic disorders like sickle cell anemia, and inborn disorders of the immune system ... goal in cloning is to understand what goes wrong in a disease like Alzheimer's, Parkinson's or diabetes." This is an energetic, very promising field that would benefit greatly from an end to restrictive legislation and threats of criminalization.

Link: http://www.nytimes.com/2004/08/24/science/24stem.html?ei=5090&en=18f7447019815f0d&ex=1251000000&pagewanted=all

MSNBC reports on yet another study showing that being overweight raises the risk of contracting cancer (as well as almost all other nasty age-related conditions). "With nearly two-thirds of U.S. adults now overweight plus an aging population - cancer is predominantly an older person’s disease - oncologists want more attention to the link." Fat is a complex organ and having to much of it causes subtle long-term damage to your biochemistry and health. So look into a sensible, calorie restricted diet, supplements, regular exercise, a good physician and staying lean - proper long term maintenance of your body is essential if you want to maximize your natural healthy longevity.

Link: http://www.msnbc.msn.com/id/5800296/

Let me direct your attention to an excellent discussion over at the Immortality Institute. The participants pull together aging, DNA, calorie restriction, evolution, telomeres, cancer, mitochondria, stem cells and half a dozen other related topics in a very educational fashion. I won't attempt to pick out the good bits - there are just too many of them. Get thee hence and read!

An interesting press release noting a patent on neural stem cell cultures:

StemCells, Inc. (Nasdaq: STEM) today announced that the ompany has been issued U.S. patent 6,777,233 for work done at the Company overing composition of matter claims for the human neural stem cell.

"This patent further strengthens StemCells' leading position in the human neural stem cell field," said Martin McGlynn, President & CEO of StemCells Inc. "The patent covers human neural stem cell cultures derived from any source, including embryonic as well as fetal, neonatal and adult issue."

Leaving aside my own opposition to state-imposed monopolies of any sort, this looks like a very broad patent. We could look on the bright side and see future patent-related litigation / extortion as a step up from the current political debate over criminalizing this research. At least patents and patent battles mean that the science is moving towards producing commercial therapies.

UPDATE: phosita adds the following after some helpful comments:

Thus, the patent appears to only cover a cell culture capable of enhancing the growth or reproduction of multipotent stem cells and not stem cells in general.

This piece from the Sun Times about the A4M Chicago conference is a perfect example of the sort of nonsense rolled out under the banner of the anti-aging marketplace. If this drumbeat of pills, potions, snake oil and branding is all that the public hears, how will anyone know to support real anti-aging research aimed at extending the healthy human life span? At least a few of the speakers at the conference are reputable (such as Ray Kurzweil and Leonid Gavrilov), but you wouldn't know it from this media coverage - or from looking at the exhibition floor. I commented on this state of affairs and the role that A4M plays in both advancing and harming healthy life extension earlier in the month at Fight Aging!

Link: http://www.suntimes.com/output/news/cst-nws-aging23.html

TIME Magazine is running an article on calorie restriction and its beneficial effects on health and longevity. The last couple of years of research into calorie restriction has uncovered an array of fascinating biochemistry relating to metabolism, stress, hormones, aging and genetic regulation. The current goal for many scientists is to produce calorie restriction mimetic drugs that replicate the health benefits and extended healthy life span without the need to diet. It's worth noting that the lack of excess body fat in practitioners of calorie restriction could explain some of the health benefits - but given that being overweight greatly increases your risk of suffering age-related disease, that sounds like another good reason to be practicing calorie restriction!

Link: http://www.time.com/time/covers/1101040830/scstarve.html

(From STLtoday.com). Scientists back embryonic stem cell research because it appears to give a greater chance of developing regenerative therapies for common age-related conditions. "Stem cells taken from a
patient's own muscle or blood failed to make functioning heart cells. Those adult stem cells homed in on damaged heart tissue and latched on, but never got the rhythm the rest of the heart ticked to ... Some of the patients in the study did improve after the therapy .. the [adult] cells may have recruited new blood vessels to the injured area and helped speed the healing." By way of comparison, "the embryonic cells did not just latch onto the wounded heart ... they actually became heart muscle cells that beat in time with the rest of the organ."

Link: http://www.stltoday.com/stltoday/emaf.nsf/Popup?ReadForm&db=stltoday%5Cnews%5Cstories.nsf&docid=7BFA440CAADE446886256EF700398283

Randall Parker comments on recent work demonstrating that osteoporosis (age-related bone loss, a serious condition) can be partially prevented in mice through gene silencing:

Mutations in either of two genes prevented much of age-related bone loss and increase in fat.

...

It would be interesting to know whether these mice will live any longer or shorter than wild type mice.

It might then seem logical for life extension advocates to advocate the development of drugs to silence TLR4 (perhaps based on DNA anti-sense technology or RNA interference technology). But keep in mind that TLR4 plays an important role in spurring the immune response to dangerous blood infections.

...

Perhaps this can be finessed somehow. If compounds that could act in place of TLR4 could be found then those compounds could be delivered to patients whose own TLR4 genes have been suppressed by a DNA anti-sense drug. Alternatively, perhaps a drug can be developed that will suppress TLR4's effects on fat cells or bone cells (aside: does TLR4 down-regulate osteoblasts or up-regulate osteoclasts?) without interfering with immune response.

Another possibility is to suppress whatever factors might be up-regulating TLR4 in aging bodies. But my guess is that the most likely factor for the cause of TLR4 expression in old folks is an accumulation of damage that causes an inflammation response. Generally speaking, as people age more of their inflammation and repair genes are activated. Possibly we can selectively suppress subsets of those genes to achieve some slowing of aging. But what we really need to do most of all is to be able to repair all the things that are breaking.

Osteoporosis is one the many nasty conditions that, like Alzheimer's or other forms of senility, was once thought of as being "part of normal aging." I suspect that medical researchers will eventually categorize all age-related degeneration as undesirable conditions of one sort of another, and the sooner the better.

I mentioned another piece on osteoporosis at the Longevity Meme earlier this week. You should read it - it's packed with scary facts about the condition:

Here is a frightening statistic from SAGE Crossroads: "Thanks to thinning skeletons, half of all postmenopausal women and a quarter of men over 50 will fracture a bone." This, like many other unpleasant future realities, is something that we don't like to think about - but sticking our heads in the sand is a bad strategy. It is far better to actively support scientists who are working on therapies for osteoporosis.

I have noted an important point about supplements in at least one previous post:

In any case, most of these near future products would have to be injected to have the desired effect. The human digestive system is very good at breaking down complex compounds - especially those relating to human biochemistry - before they get anywhere near the bloodstream.

This was posted as part of a commentary on resveratrol, a calorie restriction mimetic compound that has been generating some excitement in the old school portions of the healthy life extension community. I talked a little about resveratrol in a recent Longevity Meme Newsletter:

Resveratrol has been in the news recently. It is a supplement found in red wine that triggers some of the same beneficial effects on health and longevity as calorie restriction in animal studies:

...

Does this mean that you should run out and start ordering resveratrol? No, not unless you can afford to throw away that money. Taking resveratrol supplements now is a bet - you are betting that this substance, quick to decay and difficult to keep potent even in laboratories, will still be useful and viable in pill form. The history of the supplement industry shows this to be a bad bet; you are almost certainly going to lose. Many substances backed by wonderful scientific studies have turned out to have little or no effect - for one reason or another - when taken as supplements.

I agree that resveratrol is a step forward for the world of supplements - the discovery certainly demonstrates the power and utility of modern bioinformatics. I plan to take it myself, but only after a vendor steps forward to demonstrate that their resveratrol pills are as effective in studies as laboratory preparations.

Here is a comment from an Immortality Institute thread on resveratrol:

Sinclair and his team at Harvard tested the biological activity of many conventional resveratrol supplements available on the market before the thought of "Longevinex" was ever conceived of. It was in response to Sinclair's findings that existing resveratrol supplements showed no biological activity due to oxidation that health journalist Bill Sardi contacted chemists in the industry to develop a resveratrol supplement which is protected from oxidation. Sinclair has claimed that he has received no compensation from the Longevinex company, and announced on a mailing list that he planned to pursue legal action against Longevinex for using his name to promote their product without his consent. Other than perhaps initially testing(?) the compound for Sardi, Sinclair made it sound as if he had no financial connection with them.

Sinclair found that only research-grade resveratrol produced under hypoxic conditions and sealed under nitrogen during storage were found to have significant biological activity. The compound simply oxidizes rapidly... think of a sliced apple which turns brown after a short time. Longevinex is the first supplement to be produced under a nitrogen environment, and sealed in an air-tight capsule with a nitrogen bubble inside to protect from oxidation. For the same reason, the resveratrol in red wine is quickly oxidized in less than a day after the bottle is opened. Since wine can be purchased in the plastic collapsable bags, some have chosen to supplement with resveratrol in this fashion. However, one would have to drink over 10 glasses of typical red wine per day to get the same amount of resveratrol, if my memory serves; although some red wines contain more resveratrol than others.

Another problem with resveratrol is that it rapidly forms conjugates both in the digestive tract and during the initial pass through the liver. Quercetin can saturate and bind to the same compounds which conjugate with resveratrol, so Longevinex also includes quercetin in the pill. However, it is a small amount, and my guess is that all of the quercetin, plus all of the resveratrol in the pill will become conjugated. A possible solution to this is to take extra quercetin (say 500mg) shortly before taking Longevinex. Two published studies now have found that resveratrol rapidly forms conjugates and is likely not bioavailable. Quercetin is believed to inhibit this conjugation, and quercetin also helps to activate the same gene that resveratrol does, albeit less potently.

Some things to ask yourself about any new supplement backed up by good laboratory work:

• Do the pills deliver the same potency and compound used in the laboratory?
• Will your body break it down before it does anything?
• Has the pill form been demonstrated to have the same (or any) beneficial effects in scientific studies?
• Is spending time, effort and money on this as effective for your future healthy and longevity as putting the same resources towards serious anti-aging research?

In all fairness, that last question is a tough one - but it is something you should think about. I think that we would all benefit from less time spent on pills and more time spent on advanced medicine: telomeres, stem cells, cancer therapies, mitochondria and real anti-aging medicine.

UPDATE 11/25/2006: For more thoughts in the same vein, in the wake of more recent resveratrol science and publicity, you should read one of the more recent posts on the subject.

(From EurekAlert). Modern investigations into accelerated aging disorders (Progeria and Werner's syndrome) are teaching scientists a great deal about the way in which the aging process works. The links between aging, telomeres - the protective caps on the ends of chromosomes that get shorter with each cell division - and cancer have been receiving a lot of attention in recent years. The hurdles overcome during the development of a mouse model for Werner's syndrome demonstrate how far we've come in our ability to manipulate genes and telomeres in living organisms. This field of study is an important one - it could eventually yield therapies to prevent both cancer and aging.

Link: http://www.eurekalert.org/pub_releases/2004-08/uotm-mmo081904.php

The Honolulu Advertiser notes that analysis of a large study performed a few decades ago convincingly links calorie restriction with extended longevity in humans. "There are a lot of people that change eating habits over time. The fact you can see a difference, almost 40 years later, despite the weakness of the measurement tool, suggests this must be a fairly powerful effect." This is as we would expect from the many animal studies, and we will no doubt hear more about this work: "[the link between diet and life span] is one of the great unanswered questions in biogerontology studies and aging research. A study like this just hasn't been done before. And the fact that it supports what we see in the animal studies is important."

Link: http://the.honoluluadvertiser.com/article/2004/Aug/21/ln/ln11a.html

Betterhumans reports on a new study in rats that shows "embryonic stem cells can repair heart tissue and speed recovery after heart attack." This is not too surprising, since effective adult stem cell heart therapies have already been demonstrated. The embryonic stem cell therapy would seem to be superior, however: "The stem cells transformed into heart cells and integrated with the surrounding muscle. Within three weeks, the researchers saw improved heart function and reduced scarring compared to a control group of animals that didn't receive the stem cells. Moreover, the response to stress was superior in the stem cell-treated hearts, and there were no deaths or evidence of abnormal heart rhythms."

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-08-19-2

Here is a frightening statistic from SAGE Crossroads: "Thanks to thinning skeletons, half of all postmenopausal women and a quarter of men over 50 will fracture a bone." This, like many other unpleasant future realities, is something that we don't like to think about - but sticking our heads in the sand is a bad strategy. It is far better to actively support scientists who are working on therapies for osteoporosis. "One recent study found a gene that controls whether cells grow into fat or bone-building cells, whereas another study found a gene that caused both weight gain and bone-thinning in mice. Although the work is in its early stages, drugs aimed at such genes might encourage the maintenance of healthy bones in older people."

Link: http://www.sagecrossroads.net/public/news/index.cfm

When can we expect the first true regenerative medicine to arrive as commercially available products, widely used in hospitals and clinics? Which therapies will be first out of the gate? Getting the science done is just the first step in the long road from laboratory to product. It's a difficult enough process even without the politicians attempting to legislate certain technologies out of existence.

A Houston Chronicle piece mentions some of the conventional wisdom in scientific circles regarding timelines and the first conditions to benefit from stem cell research:

"There has been a lot of inordinate hype," said Terry Devitt, a spokesman for stem cell research at the University of Wisconsin, where the first human embryonic stem cells were isolated in 1998. "Basic science is a slow, expensive, painstaking process. It'll be at least a decade, I think, before stem cell advances make it to the clinic."

...

In any event, most scientists express confidence that embryonic stem cell research will yield fruit. They say the most promising targets are Parkinson's disease, which affects a small and specialized population of brain cells; type 1 diabetes, which is caused by the loss of insulin-producing cells in the pancreas; and spinal cord injuries, where a few crucial nerve cells die.

That the first likely targets are ones in which large benefits can be obtained from the regeneration of comparatively little tissue. This is a good first step. Meanwhile, effective adult stem cell therapies for heart disease, bone regeneration and a few other conditions - those that have already undergone limited human trials and are not subject to the same level of political opposition - are likely to reach the marketplace within the next ten years.

I'll change the topic tomorrow - I couldn't resist mentioning just a few more stem cell politics items. Firstly, a Wired article on changing public opinion:

The number of Americans who approve of embryonic stem cell research has increased from three years ago, while the number who disapprove has fallen by almost half, according to a recent Harris poll released Wednesday.

...

"The results of the poll indicate that journalists and scientists are doing a good job at educating the American people on the potential benefits embryonic stem cells may have. We need the support to explore the potential of these cells," said Jose Cibelli, a stem cell and therapeutic cloning researchers at Michigan State University.

Cibelli forgot to mention the hard working advocates - such as CAMR, Christopher Reeve, Stem Cell Action, or myself for that matter. I wonder how much progress advocates, scientists and journalists have made in generating support and understanding for aging and serious anti-aging research? That's an opinion poll I'd like to see.

Michael Kinsley writes another of his excellent pieces, managing to cut to the core of the debate as always.

As someone with a loved one (myself, as it happens) who has the disease (Parkinson's) for which stem cells hold the most promise, please allow me to say: Thank you so much, Mrs. Bush, for trying to make sure that I don't get too hopeful. While your husband and Sen. John Kerry make a major issue out of who is more optimistic, it is inspiring to have a first lady with the courage to say: Let's be pessimistic! Optimism is unfair!

But talk is cheap. While Laura Bush is destroying hope by the traditional method of spreading gloom and pessimism, her husband is bringing the pessimist's art into the 21st century by actually destroying the objective basis for hope. While she battles rhetorically against false hopes, he works to ensure that there is no hope at all.

Chris Mooney comments on the column, and takes aim at other aspects of current restrictive legislation via a recent interview transcript:

Which panel of ethicists is Bush talking about? I'm not sure. We know he met with Leon Kass and Daniel Callahan, who basically agreed with each other about embryonic stem cell research, and that Bush didn't hear a diversity of views at that meeting. But in any case, why was Bush listening to ethicists to determine whether the existing cell lines were sufficient for federal research? All the leading stem cell scientists at the time could have told him they weren't.

...

The funniest moment of the transcript is when Bush says, "I think my position is very reasonable." Try telling that to the countless Americans who can't understand why it's okay to destroy IVF embryos by throwing them in the trash but not okay to destroy them by extracting their stem cells. I think they will have a hard time understanding why, when you have the same net embryo loss either way, limiting research is "reasonable."

Let me finish up (really this time) by noting once again that Federal funding is not the big issue here - the big issue is that the current administration has been and is still continuing to try and criminalize therapeutic cloning, coupled with restrictions or outright bans on embryonic research at the state level. This creates an environment in which private investment for research is very hard to find and scientists are unwilling to enter the field.

An interesting piece at the International Herald Tribune discusses the effects of growth hormone and body size on longevity. For example, there are "mice that produce growth hormone but cannot respond to it. Called Laron dwarfs, they are fertile and live as much as 50 percent longer than normal mice. The oldest mouse on record, which lived nearly five years, was a Laron dwarf." The science is somewhat up in the air at the moment. Researchers do not yet fully understand how all the hormonal pieces fit together in mice, let alone humans, and a healthy debate is under way. Human hormone therapies are an uncertain proposition at this time, no matter what promoters in the anti-aging marketplace have to say on the matter.

Link: http://www.iht.com/articles/534574.html

A press release from Yahoo! News describes some new aging science. Andrzej Bartke, respected in the field, says, "The theory of aging developed by Drs. Bowen and Atwood is striking in its novelty ... The authors use this new and different way of looking at endocrine changes that accompany aging to suggest novel therapeutic interventions." This work is apparently in the context of Alzheimer's treatment and early drug trials at Voyager Pharmaceuticals - we shall see where it all goes in due course. An outgrowth in the number of theories of aging (such as the reliability theory of Leonid Gavrilov) is fine in my book: It shows that scientists are working on the problem.

Link: http://biz.yahoo.com/prnews/040818/lnw001_1.html

As reported at ScienceDaily, researchers have uncovered the genetic basis for age-related bone thinning and weight gain. Their work shows that "laboratory mice without this gene function have 70 percent less body fat and exhibit the dense bones and lean bodies of young mice." Osteoporosis - age-related bone loss - is a concern for many people in the healthy life extension community, especially those practicing calorie restriction. The prospect of a genetic therapy for this condition - at some point in the future, past many more experimental, regulatory and commercial hurdles - is an exciting one. Controlling the amount of body fat should also greatly reduce the risk of suffering other age-related conditions.

Link: http://www.sciencedaily.com/releases/2004/08/040817080650.htm

Ronald Bailey comments on the Methuselah Mouse Prize for anti-aging research over at Reason Online. "The aim of the Methuselah Mouse Prize is not just to tempt scientists to get involved with anti-aging research. It's also a public relations stunt aiming to capture the public's imagination. De Grey believes that the public will demand more research into finding effective anti-aging treatments once they are convinced that it's possible to significantly retard aging in a mammal." As regular readers know by now, I see the Methuselah Mouse Prize as one of the most important initiatives currently underway - if you donate today you'll still be in time to get free promotional Mouse gear!

Link: http://www.reason.com/rb/rb081804.shtml

Polling yesterday and stem cell politics earlier in the week - so now some political analysis before I drop the subject for more constructive topics. As a reminder (since no-one out there seems to be talking about it), here is why embryonic stem cell research is important:

1) The aim of stem cell research is to produce a biological repair kit, tools that will allow age- and illness-damaged tissue to be repaired or replaced. These tools, coupled with effective cancer therapies, will greatly extend our healthy life spans and bring cures for all the most common degenerative diseases.

2) It is probably the case that scientists would eventually make as much progress using only adult stem cells - several extra intervening steps would be required, but it is conceptually possible. It is widely agreed that progress towards a full biological repair kit would be much faster due to embryonic stem cell research.

3) Time matters a great deal - more than 100,000 lives are lost worldwide each and every day precisely because we don't have a biological repair kit complete with therapies for the most common age-related conditions. There simply is no sane counterargument to this point. Speed is of the essence.

Chris Mooney has been commenting on the latest tactics used by opponents of embryonic stem cell research and therapeutic cloning in political circles. Some quotes:

I don't condone all of the Democrats' political tactics, and have condemned many of them here. But let's face it, all of this is typical politics, and the GOP has no record for honesty on embryonic stem cell research.

Conservatives exaggerate the potential benefits of adult stem cell research at least as much as Democrats exaggerate the potential benefits of embyronic stem cell research--probably far more. And if Democrats have misrepresented Bush's policy, it's also worth pointing out that that policy itself relied on a misrepresentation of the number of available lines. Finally, both sides have and will continue to use polling to their advantage. There are no saints here.

...

John Leo, a conservative columnist, echoes all the same tropes that we've heard so often lately: Democrats are being dishonest about an embryonic stem cell research "ban"; they're promising the moon; they're hyping Alzheimer's cures; they're ignoring adult stem cells, yada yada. Interestingly, few of these arguments really arose in full force until after Ron Reagan delivered his Democratic National Convention speech--they are, clearly, the arguments of a conservative movement on the defensive.

But let me add a few additional comments. Leo gets pretty dishonest (or perhaps just uninformed) on the money front ... Actually, everything I've heard suggests that most pharaceutical/biotechs are scared to move into this field because of the politics. Granted, there are exceptions like Geron and Advanced Cell Technology. On the "state governments" front, meanwhile, I'm not aware that money is "pouring in"--the California intiative has not passed yet. So what state is Leo talking about--New Jersey perhaps? Frankly, I don't think he knows what he's talking about.

...

Finally, Leo speaks of the "anti-religious thread of the Democratic stem cell campaign." This is, of course, too funny for words. If you oppose the moral views of religious conservatives then you're anti-religious? Once again, it seems that those accusing the Democrats of spin and dishonesty on embryonic stem cell research have no particular high ground, and in fact, need to look in the mirror.

A piece at Wired today offers some more thoughts on this topic:

United States presidential nominee Sen. John Kerry (D-Massachusetts) is in favor of cloning.

It's a true statement, and shocking, if you don't know that there are two different types of cloning. Both use the same technique, but with different goals. Therapeutic cloning is the process of creating an embryo and extracting stem cells before they've become specific cell types while the embryo is smaller than the period at the end of this sentence. The other kind of cloning is the stuff of Raelian mythology -- reproductive cloning resulting in cloned babies.

...

Kerry is not alone in his support for therapeutic cloning. The National Academy of Sciences (the body put in place to advise the federal government on matters of science and policy), the American Medical Association, and the American Association for the Advancement of Science all support therapeutic cloning.

But the yuck factor associated with cloning could hurt Kerry if his campaign isn't proactive about explaining what exactly the science involves.

"The Republicans are trying to link Kerry to the word 'cloning,'" said Michael West, CEO of Advanced Cell Technology, a company that has created early cloned embryos in hopes of developing medical treatments. "My honest reaction to all this is simply shame. The United Kingdom had a rational (although sometimes heated) debate about (embryonic stem) cells and the use of cloning in medicine, and came out with careful guidelines to allow potentially lifesaving research to move forward. In the U.S., we are using this area of medical research as a political football, trying to win one for the Gipper."

The winner-takes-all politics of a modern representative democracy lead to these wasteful, dishonest battles over every bone of contention. There are better ways of doing things - such as decentralized, pluralist societies, even that imperfect example of the type envisaged by the Founders of the US - but don't hold your breath waiting for those in power to stop the march towards increasing centralization and control.

The International Herald Tribune has published a good article on calorie restriction, a diet demonstrated to extend life span in mammals and at the very least produce impressive health benefits in humans. "Scientists, who are still uncovering exactly how the process works, believe the effects of caloric restriction are an evolutionary response to allow creatures to survive during adversity and live long enough to reproduce when conditions improve. Guarente recently reported that caloric restriction triggers a release of stored fat, which may tell the body 'it's time to hunker down for survival.' In addition, he suggests that caloric restriction may spur the body to become more efficient at using nutrients." We should be seeing more results from the CALERIE study next year - hopefully as good as the first set.

Link: http://www.iht.com/articles/534207.html

I briefly noted recent Proposition 71 polling a few days ago as an item of interest. Here are some more polls on embryonic stem cell research (as well as cloning and other science topics) that I noticed in a post at Cyborg Democracy:

"There is a type of medical research that involves using special cells, called stem cells, that are obtained from human embryos. These human embryo stem cells are then used to generate new cells and tissue that could help treat or cure many diseases. I am now going to read you two statements about this type of research.

"Statement A: Those OPPOSED to this type of research say that it crosses an ethical line by using cells from potentially viable human embryos, when this research can be done on animals or by using other types of cells.

"Statement B: Those IN FAVOR of this research say that it could lead to breakthrough cures for many diseases, such as cancer, Alzheimer's, Parkinson's, and spinal cord injuries, and this research uses only embryos that otherwise would be discarded.

"Who do you agree with more: those opposed or those in favor?"

Agree more with those opposed	22%
Agree more with those in favor	71%
Depends (vol.)	2%
Not sure	5%

There are others as well; a nice cross section of public opinion on the topic.

CORDIS reports on calls from German politicians for an European Union wide ban on therapeutic cloning, a technology vital to the most promising branches of stem cell research. Criminalization of this research - threatened and actual - has caused great harm to progress towards cures for age-related and other degenerative conditions. Private funding is scared away and scientists move into other areas of research rather than risk their careers. Meanwhile, more than 100,000 people die each and every day precisely because we have not yet developed a regenerative toolkit for common medical conditions. How long will you allow this state of affairs to continue? You have a voice: use it.

Link: http://dbs.cordis.lu/cgi-bin/srchidadb?CALLER=NHP_EN_NEWS&ACTION=D&SESSION=&RCN=EN_RCN_ID:22470

I'm not a supporter of NASA, or any facet of big government for that matter. NASA is waste incarnate like all government agencies, while philanthropy and the free market seem to be doing a much more efficient job of turning low cost space travel into reality. That said, this Wired article on current NASA ventures into medical research is interesting:

"We plan to use adult stem cells derived from the astronauts' blood and to put that in a zero-G-microgravity-simulating bioreactor," said McGuckin. "Using the right cocktail of stimuli, we can instruct the cells to grow into not only blood, but also the liver or part of the muscles, for example, to regenerate the damaged tissue. The long-term goal would be (to be) able to take those bioreactors on a space flight to regenerate tissue for the astronauts."

Growing body parts on demand has been the Holy Grail of tissue engineering experts all around the world. The main challenge so far has been growing tissue in three dimensions. Because of gravity's effects, cells grown in a flat dish have a sheet-like appearance, behave like individual cells and fail to form the associations that lead to the growth of tissues or organs.

I can't say that the rigors of space travel had occurred to me as a likely near term pressure for funding of regenerative medicine - as opposed to, say, more than 100,000 deaths each and every day and the hundreds of millions who currently suffer the crippling effects of degenerative conditions.

As I note at the Longevity Meme, we're making progress in three-dimensional tissue engineering using biodegradable scaffolds here at the bottom of the gravity well - microgravity experiments are no doubt helpful, but by no means essential.

Wired reports on NASA plans to invest in cutting edge medical research. Methods of preventing cancer come first, and "if the astronauts' immunity to radiation cannot be significantly enhanced, then the next step, according to the team, is to grow replacement tissue. They'll begin their research by combining umbilical blood and bone-marrow stem cells with tissues from adults to grow new body tissue in a zero-microgravity environment that mimics conditions in the womb." The article speculates on whether microgravity offers a better environment for tissue engineering of replacement organs - although I should note that work with biodegradable scaffolds here at the bottom of the gravity well has been proceeding apace.

Link: http://www.wired.com/news/space/0,2697,64577,00.html?tw=wn_tophead_2

MSNBC is carrying a three part article on fat and its influence on long term health and longevity. In a nutshell, fat turns out to be a surprisingly complex part of the body: "Increasingly, researchers believe that the biochemistry of fat holds clues both to its tenacity and to the diseases associated with obesity, including heart disease, diabetes and even certain cancers." The weight of scientific evidence strongly links excess weight (and thus excess fat) to all of the most common - and terrible - age-related conditions. If you are even modestly overweight younger in life, you are significantly raising your risk of suffering cancer, diabetes, Alzheimer's and other degenerative conditions as you age.

Link: http://www.msnbc.msn.com/id/5709350/site/newsweek/

If you haven't yet taken a look at the non-profit Immortality Institute, you certainly should do so. The forums have become something of a watering hole for many of the volunteers and younger organizations relating to healthy life extension - you'll find conversations about starting a Methuselah Fly Prize to complement the Methuselah Mouse Prize for anti-aging research, or TransVision 2004, for example. Go and browse - it's a friendly community and you'll find useful information and many points of view. As a reminder, the community-created book, "The Scientific Conquest of Death," is due out later this year. The last of the editing is wrapped up and it should be on the way to the printers at this time.

Link: http://www.imminst.org

Randall Parker comments on the use of genetic screening to uncover compounds that affect longevity via the metabolism. "Some researchers have been comparing the pattern of gene expression found in mice on CR diets with the patterns of gene expression found in mice given a variety of drugs. Some already used drugs may induce a metabolic state that will extend life expectancy by the same mechanism that CR diets extend life expectancy." Several threads of research underway at the moment are extending our knowledge of the ways in which metabolism and the aging process interact and are controlled. This can only be a good thing - it brings us closer to early therapies that can effectively extend healthy life spans.

Link: http://www.futurepundit.com/archives/002290.html

Some initial polls on Proposition 71 (the California Stem Cell Research and Cures Initiative) have surfaced:

If the November election were held now, 45 percent of likely voters would support Proposition 71, compared with 42 percent opposing it and 13 percent undecided, according to Field Poll results released today. It's the first Field Poll conducted on voters' attitudes toward the proposition.

The sharp division of opinion stems partly from voters' tendency to see the fight over Prop. 71 as a mirror of the larger U.S. presidential race, which is similarly marked by firmly held opinions with little wiggle room, said Mark DiCamillo, a veteran analyst for the Field Poll.

In the poll, pro-John Kerry Democrats support the stem cell initiative by a more than 2-to-1 ratio, while pro-George W. Bush Republicans are 2-to-1 in opposition, DiCamillo said.

There are also age, gender and educational divides, with voters younger than 40, women and college graduates likelier to support Prop. 71 than men and high school graduates. Forty-eight percent of women would vote yes on Prop. 71, while 36 percent would vote no; 48 percent of men would vote no and 43 percent yes.

...

"I thought the margin in favor of stem cell research would be a little higher. ... It's quite clear that it is highly contested at this point," said stem cell researcher Dr. Irving Weissman, a Stanford pathology professor who started a firm, Stem Cells Inc.

Fiona Hutton, a spokeswoman for the Yes on 71 campaign, said that "given the state's economic climate, this (poll result) is a good starting point for our campaign. We know that Americans overwhelmingly support stem cell research and believe in its potential to cure some of the most debilitating diseases and injuries.

"And as we educate voters about the positive impact of Prop. 71 in reducing California's crippling health care costs and improving and strengthening the economy," Hutton added, "we are confident support for the measure will continue to grow."

The Proposition 71 organization has a large pool of funds ($7 million at last count) and hasn't started in on serious advertising yet. We shall see how this turns out - if you want to make a difference, the initiative is asking for your help.

WebMD aptly illustrates the problems facing newcomers to the field of healthy life extension: faced with the noise generated by the anti-aging marketplace, how do you find out which claims are legitimate and which of the legitimate claims are useful? How can you distinguish reputable scientists and doctors from the quacks and adventurous marketeers? It took me several years of being a customer and advocate to sort it all out in my own mind - it certainly isn't as easy as counting red flags, but that can help you avoid the worst traps. Be skeptical, do your research, and remember that there are no simple solutions. Hopefully the materials at the Longevity Meme will give you a head start on the process.

Link: http://my.webmd.com/content/article/92/101875.htm

Anders Sandberg has more on TransVision 2004:

Perhaps the most major theme of the conference (in the sense of reporting real progress) was fixing ageing. Aubrey de Grey's initial speech laid out the plan and showed some recent progress on fixing mitochondrial mutations by moving the genes to the nucleus. That was followed by another talks sketching a possible way of finding enzymes that break down lysozomal gunk using bioremediation as an inspiration: since graveyards are not overflowing with the substances the body cannot break down, there must be bacteria that can do it. These can be isolated, and the relevant enzymes gathered. Very elegant, but rather early to tell how useful it will be.

As for elegance, Rafal Smigrodzki had an even more exciting approach: using protofection, a new form of gene therapy, mitochondrial DNA can be replaced. This is promising as a treatment of mitochondrial disease, but of course also against some aspects of ageing. And if the method was as powerful as he implied, it may be a great vehicle for gene therapy too. Which makes the other approaches more plausible as treatments too, since most seem to rely on the presence of suitable genes rather than small molecules. João Pedro de Magalhães has built a database of genes involved or implied in ageing. The network is tangled, but it is not that impossible to start to deal with using the powerful tools of modern genomics and proteomics.

You can find Aubrey de Grey's PowerPoint presentation from the conference in his collection of presentation materials.

The New Zealand Herald reports on genetic research that lays the groundwork for ambitious future medicine - regrowing lost limbs, suppressing cancers, repairing the damage caused by neurodegenerative conditions such as Parkinson's, and increasing resistance to common diseases. "Starfish can regenerate limbs. We are highly similar to starfish [compared to flies or plants]. We will come to understand aging, cancer and the regeneration of limbs." Knowledge is at the root of all modern medical progress - especially in areas like regenerative medicine, where we seek to manipulate existing cellular processes. The more we learn, the closer we come to cures for age-related conditions and the aging process itself.

Link: http://www.nzherald.co.nz/storydisplay.cfm?storyID=3584086&thesection=news&thesubsection=general

Chris Mooney's latest article (in PDF format here) is an overview of stem cell research and politics, including Proposition 71 and "scientific secession" in California. "This November, Californians will vote on a stem-cell ballot initiative that could trigger a far bigger influx of scientific talent while simultaneously providing the closest thing to a popular referendum on the Bush policy." It's a good read, especially if you want to catch up on how this whole situation came about, but falls into the same trap as most other political analysis at the moment - it focuses on the comparatively minor issue of Federal funding while ignoring the impact of threatened criminalization of therapeutic cloning and hostile legislation at the state level.

Link: http://www.chriscmooney.com/PDF/CellBlock.pdf

Medical News Today notes that the second issue of the Journal of Gerontology dedicated to anti-aging medicine is out. As I've noted before, mainstream gerontologists are not happy with the anti-aging marketplace. I see fault in both sides: the major players in the marketplace need to stop associating with fraudulent and borderline fraudulent ventures, while conservative gerontologists need to wake up and see that an effective therapy for aging could be developed in a matter of decades with the right level of funding. Claiming that real anti-aging medicine is impossible or far in the future is a self-fulfilling prophecy - one that we do not want to see come to pass.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=11943

Well, the stem cell research news has been flowing thick and fast the past week or so - some nice science results have been announced. On the other side of the honest worker/parasite on society divide, the political debate seems to have energized itself to the point of disconnection from reality. So perhaps we should start with a reminder as to why we should support all stem cell research, adult and embryonic:

1) The aim of stem cell research is to produce a biological repair kit, tools that will allow age- and illness-damaged tissue to be repaired or replaced. These tools, coupled with effective cancer therapies, will greatly extend our healthy life spans and bring cures for all the most common degenerative diseases.

2) It is probably the case that scientists would eventually make as much progress using only adult stem cells - several extra intervening steps would be required, but it is conceptually possible. It is widely agreed that progress towards a full biological repair kit would be much faster due to embryonic stem cell research.

3) Time matters a great deal - more than 100,000 lives are lost worldwide each and every day precisely because we don't have a biological repair kit complete with therapies for the most common age-related conditions. There simply is no sane counterargument to this point. Speed is of the essence.

On with the research news, starting with this interesting fact: cancers have stem cells too.

Researchers have discovered cells that continually replenish leukemia tumors. Killing these infinitely renewing cells could be key to halting the disease.

...

The promise of this line of research can only be realized, Weissman said, by studying adult stem cells as well as embryonic stem cells, which are controversial because an early embryo is destroyed when researchers remove stem cells from it. While in this study volunteers could provide samples, that won't be the case for all types of disease. An alternative is to take the stem cells from embryos that carry a genetic defect for specific diseases.

"There are whole areas of tissues you can't get at, but which human embryonic stem cells almost certainly will develop daily," Weissman said.

Scientists at the Reproductive Genetics Institute, a private clinic in Chicago, are also studying stem cells to discover the origins of disease. They have isolated 12 new stem-cell lines from genetically flawed human embryos, providing stem cells that will specifically develop seven diseases, including two forms of muscular dystrophy, thalassemia, Fanconi anemia, fragile X syndrome, Marfan syndrome and a type of neurofibromatosis. Couples undergoing in vitro fertilization donated the embryos after the clinic performed prenatal genetic screening.

Continuing progess towards growing bone with adult stem cells:

A single type of primitive stem cell transplanted from donor mice gave rise to both blood-forming and bone-forming cells in recipient mice. This finding, by investigators at St. Jude Children's Research Hospital, appears in the Aug. 10 issue of the Proceedings of the National Academy of Sciences (PNAS).

The discovery suggests that this primitive cell could one day be the basis of new medical treatments to replace bone that has been lost to disease or injury, the researchers say.

As I noted at the Longevity Meme, the recent approval of a specific embryonic stem cell research project (including therapeutic cloning) in the UK has led to some interesting commentary from Peter Singer:

We think research using adult stem cells should be encouraged, but it's too early to know whether human adult or embryonic cells will prove superior for treating patients ... Although Canadians support therapeutic cloning, Ottawa won't likely reopen its new reproductive law. Then, when patients elsewhere are successfully treated using therapeutic cloning, Canadians will beg Parliament to change our law -- too late.

Personally, I think it's nuts that medical progress towards working regenerative medicine has been so held up and slowed by politicians and the regulatory impulse that the approval of a single therapeutic cloning research project aimed at curing diabetes makes world news.

Diabetes, by the way, has already been cured in mice using embryonic stem cell therapies, as has Parkinson's. There is no doubt at all that this UK project will result in a working cure for diabetes in humans - it's just a matter of time, money and hard work. Here is an interview with the scientist in charge, Austin Smith:

Professor Austin Smith, 42, is the director of Edinburgh University's Institute for Stem Cell Research, which is recognized as a world leader in this promising new area of science. Stem cells, taken from embryos, are the basic building blocks from which tissues and organs grow. These pluripotent cells, whose development potential hasn't been fixed, have the potential to revolutionize medicine by offering ways of repairing diseased and damaged body tissues.

William Saletan has written a rather shady sort of article on stem cell politics and research - characteristic of political debates. I think that Chris Mooney does a good job of picking it apart, so I won't attempt to go one better:

The latest piece from Slate's William Saletan, on embryonic stem cell research, really gets my goat. I know Saletan (vaguely at least) and have nothing against him, but I'm afraid he's gone overboard in searching for something contrary to say on the question of embryonic stem cell research.

...

The person whose wisdom really sticks out for me on the "hype" issue is Nobel Laureate David Baltimore, who spoke at a 2004 Biotech Industry Organization conference I attended last June in San Francisco. "Hype is only a matter of time" when it comes to embryonic stem cell research, Baltimore explained. In other words, we're at the point now where scientists known enough about embryonic stem cells to know that if they just continue with basic research, the cures are going to come. How long that's going to take is unclear; there may be many unexpected challenges along the way; and some projected cures might not materialize. But scientists wouldn't be so committed to this field if they didn't have strong grounds for that commitment. Saletan thinks he's being wise in denouncing the Democrats' "religious" commitment to the idea of cures, and calling John Kerry a "faith healer," yet the promise of embryonic stem cell research has a firm scientific basis.

...

Is Saletan suggesting that the economics don't support investing in embryonic stem cell research? If so, that's just nuts. If you do a cost benefit analysis of embryonic stem cell research, as the California ballot initiative has done, you find that the research could easily pay for itself in terms of reduce healthcare costs down the road. Bring on the cost benefit analysis! Bring on the economics!

...

Then Saletan makes the predictable Alzheimer's point--denouncing the "fairy tale" that embryonic stem cell transplant therapies could be used to treat Alzheimer's. Again, Saletan just doesn't get it. As I have explained with respect to Alzheimer's, embryonic stem cell research isn't just about therapies. From the standpoint of basic research and learning more about the disease--knowledge that could eventually lead to cures of a non-transplant nature--embryonic stem cell research does have significant promise in the Alzheimer's area. That's why proponents keep on bringing up Alzheimer's; that's why the Alzheimer's Association, California Council, supports the California stem cell ballot initiative.

Cynthia Tucker's latest:

I've never understood a set of religious principles that attach so much importance to unfeeling, unseeing blastocysts and so little to actual living, suffering human beings -- children with diabetes, or middle-aged adults enduring the body's breakdown through Parkinson's, or adolescents condemned to a wheelchair because of a car or diving accident. And I certainly don't understand a 21st-century superpower that devotes billions to building smart bombs to destroy life efficiently but refuses to fund the research that could save or enhance the lives of millions of its citizens.

No wonder Mrs. Bush didn't have anything more persuasive to say about her husband's position on stem cell research. It is a ludicrous policy for which there is no enlightened defense.

This is actually a good example of the disconnect between the political debate over stem cell research and the real world. The public funding issue is not a problem at all in my eyes. Federal funding accounts for perhaps 30-40% of medical research in the US, meaning that there would be no shortage of private money if the research community were left alone to get on with things. The big problems for stem cell research - and especially embryonic stem cell research, but also any research involving therapeutic cloning - are varying degrees of criminalization at the state level and the ongoing attempts by the US administration to ban therapeutic cloning at home and at the United Nations.

This constant threat - the US has been a single delayed Senate vote away from a full ban on therapeutic cloning for some time now - has the effect of scaring away private investment and younger scientists from the field. We can see the results now; countries with much smaller medical research establishments are slowly getting the work done ... but we are now five years behind the point that could have been reached. Five more years of 100,000 preventable deaths each and every day. Think about that for a while.

The Canadian Globe and Mail is running a piece by Peter Singer and Abdallah Daar on the recent approval of regulated embryonic stem cell research in the UK. Canada currently forbids this research, as do many other countries worldwide: "We think research using adult stem cells should be encouraged, but it's too early to know whether human adult or embryonic cells will prove superior for treating patients ... Although Canadians support therapeutic cloning, Ottawa won't likely reopen its new reproductive law. Then, when patients elsewhere are successfully treated using therapeutic cloning, Canadians will beg Parliament to change our law -- too late." The enforced slow speed of progress has terrible consequences.

Link: http://www.theglobeandmail.com/servlet/ArticleNews/TPStory/LAC/20040812/COSTEM12/TPComment/TopStories

EurekAlert reports that SIRT1, a protein linked to the mechanism by which calorie restriction extends healthy life span, can also delay degeneration of neural tissue. This presents a range of future options: "Scientists report in the Aug. 13 issue of Science that their findings might open the door to new ways to treat a wide range of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), various kinds of neuropathy, and multiple sclerosis ... Scientists previously found evidence that this process of axonal degeneration may be an active self-destructive process that the neuron activates under certain conditions. Increased activation of SIRT1 appears to block some or all of those self-destructive processes."

Link: http://www.eurekalert.org/pub_releases/2004-08/wuso-lpm081104.php

Kip Werking (author of "The Posthuman Condition," the Haldane award paper for 2004) was kind enough to send over a long report of his time at TransVision 2004. I'm excerpting and commenting on the parts pertaining to healthy life extension and related scientific research:

After these less memorable lectures, everyone walks further north to another pub for the award ceremony. I walk next to de Grey and sit next to him at the banquet. We are both receiving one of the two awards that evening: I win the Haldane Award for Best Undergraduate Paper and he wins the H.G. Wells Award for Outstanding Transhumanist Contributions. We both grab beers at the pub and chat about aging. I ask him to explain once again his skepticism towards the benefit of caloric restriction in humans. De Grey maintains that the life extension benefit of CR correlates well with the lifespan of the species. Humans, however, are one of the mammalian species that live the longest. So, on de Grey's view - which is a small minority amongst the gerontological community - caloric restriction might expand the human lifespan by one or two years at most. More importantly, any CR mimetic that researchers might develop in the future will suffer from the exact same limitation because it will use the same genetic mechanism. He intends to present a more rigorous account of this idea. I tell Aubrey, "I hope to God you are wrong."

Aubrey de Grey's views on calorie restriction are fairly well known and debated within the community. My view on the subject is that research into calorie restriction is likely to shed light on important genetic and biochemical mechanisms relating to metabolism and aging. All knowledge in these areas is very important - the more we learn, the sooner we can craft truly effective therapies to extend the healthy human life span.

De Grey presents an alternative proposal for saving human beings from the disease of aging (and not the diseases of aging - like most transhumanists, he would characterize aging itself as a disease). He calls this effort ENS or Engineering Negligible Senescence. According to de Grey, one would only need to cure seven things in order to provide negligible senescence. Having read Olshansky describe how decreasing the likelihood of one disease killing a person only increases the likelihood of another, so that the aging retardation approach of targeting specific diseases suffers from diminishing returns, I had my own reservations about the sufficiency of these seven problems. When I confronted de Grey about them he admitted that others remain. He maintained, however, that these other problems would be easier to fix and not as deleterious to our health. Even if they are sufficient, I marveled at his optimism - his list includes curing heart disease and cancer. Nevertheless, de Grey asserts that, with $100 million per year for ten years, he can do it. Of course, he would not have to cure every problem that afflicts humans; all he needs to do is give us enough life extension to reach the point at which medicine is adding more time to life expectancy than aging and disease are - a point which de Grey calls "escape velocity."

You can read a fairly concise explanation of the escape velocity concept in a review at PLoS Biology, and you should certainly read Aubrey de Grey's SENS website. I should point out that heart disease is already close to being dealt with - early stage adult stem cell therapies are proving very effective in trials. The hurdles remaining are largely regulatory and commercial. As for cancer - the US National Cancer Institute aims to render cancer a controllable chronic illness by 2015. A lot of money and talent is being thrown at that problem.

"Now that I am here, I must take the opportunity to thank at least two people for whom I feel a great deal of gratitude. I do not intend these remarks to be at the expense of others, such as our keynote speakers. First of all, I would like to thank Nick Bostrom, who fights for and defends us in the ivory tower, against people such as Leon Kass. Nick, moreso than any other philosopher I know, takes an uncompromisingly transhumanist position against these bio-conservatives."

Bostrom seemed surprised by my remarks but I had to mention him. His In Defense of Posthuman Dignity (forthcoming in Bioethics) and The Fable of the Dragon Tyrant (forthcoming in Journal of Medical Ethics) impressed me greatly and showed how absurd reactionary ethicists can be.

If you have not yet encountered the exceptionally clever Fable of the Dragon-Tyrant, then you must do so this very instant. Get thee hence and read!

"Second I would wish to thank Aubrey de Grey, who is fighting hard every day to save each of us from death and help us to live forever. I would also like to say one other thing. I am very happy to see so many people, from such diverse nationalities and various political positions, all united together under the celebration of transhumanism. I thank you for that, and I thank you for this."

...

Now Ronald Bailey gave his address at the pub. The bulk of his talk dissected the arguments that prominent bioethicist Daniel Callahan made in a recent issue of Gerontology. These arguments can be summarized as the charges that life is bad that further life would be useless and that life extension would exacerbate the problems of war, poverty, Medicare, Social Security, and so on. For example, Callahan argues that further life would not bring further vitality, but more golf. At this point Aubrey de Grey spoke up. "Why pick on golf?" Against the former, I also love Bailey's quip that "just because Callahan is bored with life" we should not conclude that we will all become so. His other arguments are mistaken upon many grounds, not the least of which is the testimony of history, during which life expectancy has doubled. Callahan also seems to commit the common fallacy of thinking that because people are older, they must be decrepit. Finally, he does injustice to important moral considerations (when, exactly, would he insist that a person die?).

I noted Ronald Bailey's report on TV2004 at the Longevity Meme yesterday, and a shorter version of his address can be found at Reason Online.

After More's presentation, I stayed in the same auditorium for the discussion on aging. This began with Joao Pedro de Magalhaes, from Harvard Medical School, giving his presentation titled "The genetic network of human ageing: a system-level approach." Earlier, Magalhaes had explained his skepticism towards caloric restriction to me. He mentioned how there is no study of caloric restriction in primates or humans, but that ongoing studies suggest that the severe diet increases the risk of infection. In his presentation, Magalhaes explained how his approach to aging differed from de Grey's by comparing the rates of aging of various species instead of younger and older organisms. This is novel strategy that I remembered from Steven Austad's excellent book Why We Age: What Science Is Discovering about the Body's Journey Through Life; later I learned that Austad has invited Magalhães to work in his lab. During his presentation, Magalhães showed how the rate of aging can be measured as the doubling time of the mortality rate. The doubling time for humans is quite large. Magalhães also presented his online genetic database of genes related to human aging. He linked each of these genes together in an impressive graphic according to how they influence each other. Like a bald child with cancer looking at an array of oncogenes, I marveled to look upon the network of genetic defects that would sentence me to death.

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.

Yes indeed, mitochrondria are hot at the moment. They are important to so many mechanisms in the body that it is almost a given that good new possibilities for medicine are going to materialize if enough scientists work at it. The truly interesting connection is to the aging process, however - just how important this connection is will become clear within four or five years at the outside, I predict.

Some calorie restriction related news: Details and registration information for the 3rd Annual CR Society Conference have been announced.

The third CR Society Conference will be held at The Howard Johnson Riverfront Hotel in Charleston South Carolina (click here for map and directions).

The Conference will run from Thursday November 4 through Sunday November 7, 2004. There will be a welcoming reception/registration on Wednesday Nov. 3 afternoon/evening - exact time and place to be announced.

The conference promises to be science-oriented - CR Society members have been building bridges with the research community for a number of years now.

A great deal of exciting progress in the science of calorie restriction has been made over the past year. Researchers are much closer to understanding exactly how calorie restriction extends healthy life span and provides resistance against age-related degenerative conditions, how genetic changes influence metabolism and the aging process, and how to replicate the effects with calorie restriction mimetic drugs.

Ronald Bailey of Reason Online reports on his time at TransVision 2004: "[TransVision 2004] attracted some 125 philosophers, scientific researchers, and techno-visionaries to Toronto last weekend to think about, discuss, and promote the ways in which technology will transform human lives ... Probably the most immediate goal of these transhumanists is promoting research that will radically increase healthy human lifespans." The scientific focus at the cutting edge these days seems to be on mitochondrial damage and what to do about it. From the sounds of it, we should be hearing much more about new techniques for repairing, moving or replacing mitochondrial DNA - with the aim of slowing the aging process - within a few years.

Link: http://www.reason.com/rb/rb081104.shtml

Another way in which modern bioinformatics speeds useful research: A map of the genetic changes caused by calorie restriction is allowing researchers to screen for candidate drugs that will reproduce the beneficial effects of CR without the dieting. Many research groups, public and private, are working to develop meaningful calorie restriction mimetics. The increased healthy life span and resistance to age-related diseases observed in animal studies - and the impressive human studies to date - are very compelling. It is increasingly the case that genetic knowledge can be quickly turned into trial therapies - this research work is now far faster than the process of satisfying organizational and regulatory requirements.

Link: http://www.jhsph.edu/Press_Room/Press_Releases/PR_2004/Kensler_caloricrestriction.html

One of my roundup posts on the politics of stem cell research over at Fight Aging! has generated a fair number of posts. It's a reproduction in miniature of the larger abortion-tinged embryonic stem cell research debate as visitors from Instapundit interact with the regular Fight Aging! crowd. While experience teaches us that people are not going to see eye to eye on these issues, it is always helpful and instructive to see where the other guy is coming from. From where I stand, the moral value of a hundred cell embryo - a tiny sphere with no capacity to feel or think - is no different from that of any other clump of a hundred cells, but many people feel otherwise. So jump on in and have your say.

Link: https://www.fightaging.org/archives/000196.php

How do scientists discover longevity-related genes? An article from Betterhumans explains how looking for genes affected by environmental stress can uncover mechanisms relating to longevity. "Using a gene-screening technique to find genes regulated by heat, oxidants and starvation, researcher Seymour Benzer and colleagues at the California Institute of Technology in Pasadena, California found 13 candidate longevity genes and tweaked two to increase the lifespan of fruit flies." This sort of work probably has similar potential to that on calorie restriction mimetic drugs. Even if it doesn't, there is no such thing as useless knowledge in biochemistry - everything we learn helps to illuminate other parts of the puzzle.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2004-08-09-3

One of my earlier roundup posts on stem cell politics is generating a fair number of comments: visitors from Instapundit and elsewhere are debating embryonic stem cell research with Fight Aging! regulars.

Looking at the abortion debate teaches us that people are not going to see eye to eye on these issues, but it is always helpful and instructive to see where the other guy is coming from. To be clear on my position, I see the moral value of a hundred cell embryo - a tiny sphere with no capacity to feel or think - as no different from that of any other clump of a hundred cells not involved in vital brain functions in a living being. Needless to say, many people feel otherwise.

So jump on in and have your say in the discussion.

UPDATE: Glenn Reynolds has posted a short summary of his opinions on embryonic stem cell research, just for the record.

The battle between mainstream gerontologists and the anti-aging marketplace has escalated into lawsuits for defamation, it seems. This may mean all sorts of things - a higher profile for anti-aging science and medicine in the public eye or possibly an admission from both sides that anti-aging science (intervening in the aging process) and anti-aging medicine (treating age-related conditions) are two different things nowadays. Perhaps conservative gerontologists will stop issuing self-fulfilling pessimistic prophecies on the likelihood of a cure for aging, and perhaps organizations like A4M will stop encouraging the fraudulent fringe in the marketplace. We can hope. It seems to me that both sides could stand to improve on their methodologies.

Link: https://www.fightaging.org/archives/000202.php

A4M appears to be suing some conservative gerontologists for defamation:

They've been called quacks and embarrassments to the scientific community, doctors who use "pseudo-scientific mumbo jumbo" to persuade people to give them their money.

Now, they're fighting back.

The American Academy of Anti-Aging Medicine and its Chicago founders, Drs. Robert Goldman and Ronald Klatz, are suing professors from the University of Illinois-Chicago and Harvard University, alleging they have trashed their reputations in an effort to discredit their anti-aging works.

S. Jay Olshansky and Thomas Perls are the targets of the $150 million lawsuit filed last week in Cook County Circuit Court.

Goldman and Klatz say Olshansky and Perls are on "a witchhunt" and making "false statements" about their academy. They also say that while at an Australian conference this year, Olshansky presented the group with a mock award -- "The Silver Fleece" -- which was a bottle of oil with a "Snake Oil" label.

Told of the lawsuit by the Chicago Sun-Times, UIC's Olshansky made no apologies for his mockery.

"There is no evidence to show there is anything that will slow, modify, reverse or stop the aging process," Olshansky said. "Anyone who says otherwise doesn't have the evidence to support it."

This should be interesting. As you may recall, I have my issues with both sides of this fight. I see A4M as being too closely entangled with the fraudulent, study-picking, disreputable side of the anti-aging marketplace. I view conservative gerontologists like Olshansky as propagating an irresponsible, self-fulfulling pessimistic view of the possibilities offered by serious anti-aging research. Both sides are damaging the potential for progress just as much as they are helping things along.

You can see more on this topic and why the two sides are fighting in the first place at the Longevity Meme:

The war over the meaning of "anti-aging" is being fought over money and the perception of legitimacy. It is this perception of legitimacy that determines funding for scientific research and revenues for businesses. Scientists feel, quite rightly, that the noise and nonsense coming from the anti-aging marketplace is damaging the prospects for serious, scientific anti-aging research. If everyone knows that anti-aging means high-priced cream from Revlon marketed to the gullible and brand-aware, no scientist is going to get funding for a serious proposal in aging research that uses the word "anti-aging." Worse than that, people start to assume that real efforts to reverse aging must be impossible - and large scale science requires public support and understanding.

Businesses in the "anti-aging" marketplace make money from the aura of legitimacy whether or not their products perform as advertised, and so a lot of effort is expended to create and maintain this perception of legitimacy. Those businesspeople with working, accurately marketed products carry out their own fight against opportunists, frauds and "marketeers" - businesses that are damaging the market and diluting the brand. Ironically, this is much the same argument used against the more legitimate businesses by scientists.

One can hope that at the very least this lawsuit will manage to get the two sides to agree that they are talking about very different things when they say "anti-aging":

For the scientific community, anti-aging research refers exclusively to slowing, preventing, or reversing the aging process. There is, as of 2004, no medical technology that allows this to be done - although the jury is still out on calorie restriction in humans. Nor is there any currently available method (short of waiting for people to die) to accurately measure the effects of an alleged anti-aging therapy.

In the medical and more reputable business community, anti-aging medicine means early detection, prevention, and reversal of age-related diseases. This is quite different from tackling the aging process itself, and a wide array of strategies and therapies are currently available. Calorie restriction, for example, is a demonstrated way to lower risk for a wide range of age-related degenerative conditions.

The wider business community - including a great many fraudulent and frivolous ventures - views "anti-aging" as a valuable brand and a demonstrated way to increase sales. At the worse end of the scale, this leads to snake oil salesmen, "anti-aging" cremes that may or may not make your skin look younger, and infomercials that tout the "anti-aging" benefits of exercise machines. Broadly, and very charitably, we can look at these varied definitions of anti-aging as meaning "to look and feel younger in some way" - which has no bearing on how long you live or how healthy you actually are.

Some onlookers may find it ironic that, putting the merits of their chosen methodologies to one side, the founders of A4M are far more invested in seeing working anti-aging medicine become a reality than most conservative gerontologists.

The Coalition for the Advancement of Medical Research reprints an overview of the funding and legislative situation for embryonic stem cell research. It reinforces some of my own points: it is the threat of criminalization at the state and Federal level that is damaging research, not limitations on public funding. "Drs. Bob and Larry Goldstein both said uncertainty surrounding the politics of stem cell research is making young scientists wary about entering the field ... It shouldn't be a surprise that there are so few applications, because people are nervous about pursuing this. What if they make this illegal next year?" If you support regenerative medicine, now is certainly the time to stand up and say so.

Link: http://www.camradvocacy.org/fastaction/news.asp?id=1058

Newsday.com reports that the California Republicans have voted to oppose Proposition 71, the California Stem Cell Research and Cures Initiative that aims to provide $3 billion for regulated embryonic stem cell research in that state over the next ten years. The GOP opposes therapeutic cloning in medical research and the expansion of the state budget (or at least, to be realistic about these things, expansion of the budget for a purpose they object to). There are supporters of stem cell research within the California GOP, but they did not prevail at the three day state convention. We shall see what all this means for the field of regenerative medicine come November.

Link: http://www.newsday.com/news/nationworld/nation/wire/sns-ap-stem-cell-proposition,0,1372161.story?coll=sns-ap-nation-headlines

(From the BBC). The Kerry camp in the US presidential election is following the lead of various advocacy groups in marking the third anniversary of restrictions placed on federal funding of stem cell research by the current administration. This is absolutely the wrong focus - these restrictions have been nowhere near as damaging to progress as ongoing efforts to ban therapeutic cloning and restrictions imposed at the state level. Private sources account for approximately two thirds of all medical research, and these funds have been scared away by uncertainty over bans on vital technology over the past few years. One rule of politics seems to be that debates drift away from reality and fact as they grow - very unfortunate.

Link: http://news.bbc.co.uk/2/hi/americas/3546418.stm

Yesterday, I pointed you towards the work of Aubrey de Grey and Joao Pedro de Magalhaes. Today, I'll ask you to think about regenerative medicine and nanomedicine - two broad fields presently in their infancy that could have profound effects on your healthy life span.

Regenerative medicine - especially that based on the use of stem cells - is essentially aimed at controlling existing cellular processes to promote healing that would not otherwise have occurred. Implanting (or reimplanting) adult stem cells that release biochemical signals encouraging new healthy tissue growth is regenerative medicine. This can presently be accomplished. Engineering large masses of tissue - including, researchers hope, entire organs complete with the proper blood vessel structure - via therapeutic cloning of a patient's own cells is also regenerative medicine. We will most likely see this happen within a decade.

Regenerative medicine is, in essence, the path to a toolkit that allows damaged tissue in the body to be replaced, repaired or regrown. How long would your car last without replacement parts? How long will it last with access to replacement parts? That is the sort of difference that regenerative medicine could make to the healthy human life span.

Regenerative medicine will grow and become ever more effective as researchers understand more about human genetics and biochemistry. We are barely at the start of this process, yet we can already effectively treat heart disease in human trials using adult stem cells, and have cured the equivalent of Parkinson's and diabetes in mice using embryonic stem cells.

(As an aside, I should note that regenerative medicine cannot protect us from cancer - which appears to result from a different sort of age-related process. Even if the effects of disease and age-related conditions will be repaired with regenerative medicine, our vulnerability to cancer will still increase with time. The threat of cancer must be dealt with in other ways. Fortunately a great deal of progress has been made towards transforming cancer into a chronic, survivable condition).

Nanomedicine is simply the "wet" applications of nanotechnology, the science of manipulating matter and creating machines on a scale of nanometers - the same size scale as cells, bacteria and viruses. It is natural that we would turn newfound expertise in nanoscale manufacturing to medical applications.

The first applications of nanotechnology to medicine are diagnostic in nature. Control of fluids in microarrays, sophisticated genetic tests embedded in silicon chips and similar marvels have enabled great advances in the sophistication and capabilities of diagnostic medicine. Diagnostics are not a sideshow - preventation is always far better than a cure, and diagnostic advances shift the balance of medicine towards identification of risks and use of appropriate prevention strategies. Early diagnosis is already the difference between surviving and dying from cancer, for example.

Early nanomedicine is already looking to merge with regenerative medicine - through reprogramming cellular processes via the use of nanoscale devices. This may turn out to be very much more efficient, and thus less costly, than current methodologies.

More advanced nanotechnology offers some impressive future visions and opportunities to greatly extend our healthy life spans. Scientists are investigating how to use medical nanorobots to carry oxygen in blood, fight infections and repair damaged DNA - all many times more efficiently than our existing biological mechanisms can manage. These advances are probably no more than a few decades away; researchers can already construct fairly complex nanoscale structures - efficient mass production is the goal that takes time to reach.

As you can see, a great deal of medical research currently taking place could have a large impact on the future of our health and longevity. You owe it to yourself to be aware of this - it greatly affects your plans for the future. Beyond that, remember that we get the future that we work towards and call for. Nothing is set in stone. If you want to ensure that regenerative medicine and nanomedicine are used to extend the healthy human life span - and there is no certainty that this will happen - then you have to speak out!

What does real anti-aging science look like? What are the plausible aims and areas of research? How much do we know about the aging process, what can we reasonably extrapolate from this, and what is the best way forward to find a cure for aging? If you have not yet read the material provided by biogerontologist Aubrey de Grey at the Strategies for Engineered Negligible Senescence (SENS) website, then now is the time to do so. Aimed at a wide audience, the site explains why a cure for aging is plausible and how - with sufficient funding - we could attain it within a few decades. You should certainly also take some time to read about Joao Pedro de Magalhaes' work on aging and genetics at senescence.info.

Link: http://www.sens.org

On Monday August 9th, the Coalition for the Advancement of Medical Research will mark the third anniversary of restrictions on Federal funding for embryonic stem cell research. "In letters to be sent on Aug. 9 to every candidate seeking federal elected office, CAMR will ask if they agree with Nancy Reagan that President Bush should lift the current restrictions on federal funding of stem cell research and instead allow full funding of all embryonic stem cell research done on left-over donated fertilized eggs, which would otherwise be destroyed." My feeling is that the issue of Federal funding is secondary to the ongoing threat to criminalize therapeutic cloning - a vital technology for stem cell research - since this scares away private funding.

Link: http://releases.usnewswire.com/GetRelease.asp?id=101-08072004

I am declaring this to be "Read Up On Serious Anti-Aging Science Weekend." Far too many people have formed their opinions on medical research, legislation, extending healthy longevity and the prospects for the future without having looked at what reputable, forward-looking scientists have to say on the matter. Far too many people have not looked beyond the limited, old school world of pills and supplements. Far too many people have not seen that all objections to greatly extending the healthy human life span have been debunked for decades.

This weekend, take a few minutes to read and browse - you may be surprised to find out just how close we could be to a cure for aging and how determined researchers are to achieve this goal.

Aubrey de Grey's Strategies for Engineered Negligible Senescence:

SENS is a detailed plan for curing human aging. SENS is an engineering project, in the same way that medicine is a branch of engineering. The key to SENS is the appreciation that aging is best viewed as a set of progressive changes in body composition at the molecular and cellular level, caused as side-effects of essential metabolic processes. These changes are therefore best thought of as an accumulation of "damage", which becomes pathogenic above a certain threshold of abundance.

Why cure aging?

Because saving lives is the most valuable thing anyone can spend their time doing, and since over 100,000 people die every single day of causes that young people essentially never die of, you'll save more lives by helping to cure aging than in any other way.

What to fix in order to cure aging

The relevance of these dates is that they are all over 20 years ago. The fact that we have not discovered another major category of even potentially pathogenic damage accumulating with age in two decades, despite so tremendous an improvement in our analytical techniques over that period, strongly suggests that no more are to be found -- at least, none that would kill us in a presently normal lifetime.

How soon could we cure aging?

Most of my colleagues absolutely refuse to answer this question, because they feel that no answer can be scientifically defended and hence that to provide an answer is to misuse their exalted status as scientists. I agree with that stance in all areas of science that are not medically relevant, but not in medical areas: I feel that those with the best information have a duty to state their best-guess timeframe.

Obstacles within the scientific community:

There are three main reasons why most mainstream gerontologists remain so conspicuously absent from the growing band of vocal advocates of the SENS approach to curing aging. They are all understandable, but given the importance of the problem and the key role that senior specialists play in determining public opinion and hence public policy, I feel that none of them is a legitimate excuse.

Joao Pedro de Magalhaes' senescence.info:

Aging is directly or indirectly the major cause of suffering, disease, and death in Western civilization. Gerontology is the science that studies the aging process aiming to prevent age-related degeneration, preserve health, and prolong life. In a sense, aging is the ultimate challenge to human quality of life and gerontology the most ambitious scientific endeavour. The highest goal of gerontological research is to make aging optional, to cure aging. With that goal in mind, senescence.info offers a scientific approach to the biology of human aging and the possible routes, the long, hard, dusty routes, to success.

Should we cure aging?

Aging fosters sickness and disability, increases human suffering, and makes us more likely to die. Yet there are a number of possible objections to the endeavour of curing aging. Most of these are unfounded myths, easy to disprove. This essay draws on my own lectures on the subject and attempts to answer the most commonly raised questions and concerns about a possible cure for aging.

The grandparents of tomorrow:

Imagine that your grandmother looks like a teenager, plays soccer, parties at the clubs all night, and works as a venture capitalist. Or imagine your grandfather teaching you the latest high-tech computer software in his office, which you hate to visit because of the loud heavy metal music. Such a scenario is hard to envision because we are taught to accept aging and the resulting suffering and death as an immutable fact of life. We cannot picture our grandparents in better physical shape than we are. Nonetheless, aging may soon become nothing more than a scary bedtime story, perhaps one your grandfather will tell your grandson after a day of white-water rafting together.

Turning back the clock:

By the year 2030, we will have (1) developed a complete model of all human cells types, obviating the need for many laboratory experiments (by doing computer simulations instead); (2) lowered the cost of doing a complete genomic sequence for an human individual to less then $1,000 each; and (3) catalogued all the genes involved in aging. Therefore, human clinical trials to extend life span could already be underway by this date."

Small Times examines the ongoing convergence of nanotechnology and biology - the wellspring of future nanomedicine and resulting healthy life extension. Hot topics today center around reprogramming existing cellular mechnanisms to do new and useful things: Regenerative medicine based on stem cell research is an early step forward in this process. "The better we get at hijacking, and even designing, biological systems, the broader the impact of the nano-bio convergence." The groundwork of today will make possible the medical nanorobots of tomorrow, tools that could be used to greatly extend the healthy human life span. As they say, "Biology is the nanotechnology that works."

Link: http://www.smalltimes.com/document_display.cfm?section_id=76&document_id=8188

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. I discussed this at the time of the Singapore conference:

But back to conferences. 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.

I have my own opinions on A4M, of course. Having spoken to the folks in charge, I think their hearts are in the right place - but their methodologies leave something to be desired:

I would be the first to admit that I have my issues with A4M - such as their focus on old school technologies, and the fact that they allow the modern equivelant of pill and potion merchants to exhibit at their conferences. Although these folks do pay the bills so that reputable scientists can speak in the scientific portions of these events, I think A4M could certainly be putting much more effort into ensuring that the worst, borderline fraudulent and outright fraudulent offenders in the anti-aging marketplace are not allowed in.

A4M, in my opinion, is currently hurting the advance of serious anti-aging research as much as it is helping it. (I'll happily say the same and worse about mainstream gerontology organizations - they are as much a roadblock as they are responsible enablers of research). Fortunately, A4M shows signs of shaping up and becoming a much more positive influence overall; we shall see how that goes.

It does occur to me that much of this "shaping up" is the result of reputable aging and anti-aging researchers and advocates attempting to steer A4M and the as much of the rest of the anti-aging marketplace back to the path of righteousness (as it were). The yearly Singapore conference benefits from a local organizer who is very pro-reputable-science and has sufficient reputation within the scientific community to attract good science to the conference. The Chicago event lacks this benefit, and so there are fewer reputable speakers in the program - Ray Kurzweil and Leonid Gavrilov are amongst them, however.

There are some real borderline cases in the exhibition, as is usual. Reclaiming A4M as a net positive force for the future of real anti-aging medicine looks to be a lot of work - but worth trying, given their influence.

Science Blog talks about resveratrol in the context of calorie restriction, extended longevity, and the underlying biochemistry of it all. There are definite signs of complexities that researchers don't yet understand: "Sirtuins don't extend life when coupled with real caloric restriction. In fact, when flies on a low-calorie diet ate resveratrol and fisetin, they didn't live any longer than average flies. Another surprising discovery was the fact that flies feasting on sirtuins didn't have problems reproducing -- a negative side effect of caloric restriction." More research is needed - and perhaps a more ambitious research direction. We're still spending far too much time on old school methods that just don't measure up to what is possible.

Link: http://www.scienceblog.com/community/article3524.html

Proposition 71 on the California state ballot - to fund regulated embryonic stem cell research to the tune of $300 million a year for ten years - is looking about as certain to pass as these things get.

Oakland billionaires Marion and Herbert Sandler contributed $1 million to the campaign supporting a November bond measure in California that would make $3 billion available for stem-cell research.

The Sandlers are prominent Democratic donors, as are most of the big donors to a campaign that has amassed more than $8 million this year. Opponents of the proposition, which include the Roman Catholic Church, have not reported a single contribution.

The Sandlers made their contribution Friday, according to campaign finance records made available Wednesday. The gift came three days after the son of former President Reagan delivered a prime-time speech endorsing stem-cell research at the Democratic Convention in Boston.

Reading between the lines, and looking at the timing (November presidential elections, November California state budget), this initiative has become something of a referendum on stem cell research in general over the past few months. One can imagine that many of these donors see strong California support for the research as a hedge against continuing restrictions at the Federal level and in other states.

A Scarabee article discusses recent history in the search for calorie restriction mimetics - drugs that will replicate at least some of the beneficial effects of calorie restriction on health and longevity without the need to reduce calorie intake. The relationship between metabolism, food intake, controlling genes and proteins is a complex one. As scientists understand our basic biochemistry, we can expect to see new and better preventative health strategies emerge. I am of the opinion that the real anti-aging technologies of the future are not going to be found in pills, but calorie restriction mimetics are driving important research into aging.

Link: http://scarabee.co.uk/news/news_uk_02.php

The Christian Science Monitor is running a piece on healthy life extension, the anti-aging marketplace and more serious science. There is some interest in the psychology that is pushing interest in extending healthy life spans: "They were raised in the post-World War II era of a booming economy, grew up watching the wonders of science fiction, and were told they lived in a world where everything was going to be possible. And then they're faced with death. That makes them angry." Most of those quoted are pessimistic on developing working anti-aging therapies - this is a self-fulfilling prophecy. Even progress in regenerative medicine, cancer and Alzheimer's research could together significantly extend healthy life spans.

Link: http://www.csmonitor.com/2004/0805/p14s02-stct.html

Journalist Ronald Bailey will be speaking at TransVision 2004 later this week, alongside many other luminaries. A shorter version of his remarks is at Reason Online, touching on longevity, serious attempts to extend the healthy human life span, and the bioethicists who oppose these projects. "Biomedical researchers understand more with each passing year about the processes that cause the increasing physical and mental debilities that we define as aging. Aging is no more or less 'natural' than cholera, smallpox, diabetes, arteriosclerosis, or any disease that cuts short human lives." Ronald Bailey has a talent for highlighting the ridiculous, unethical nature of opposition to healthy life extension - it is well worth reading.

Link: http://www.reason.com/rb/rb080404.shtml

InfoAging presents a carefully conservative take on aging and longevity research. Given this, it is interesting to see the way in which this organization presents the ongoing dispute between mainstream gerontologists and factions in the anti-aging marketplace: the focus in their eyes is very much on calls for increased aging research funding from some of the most conservative gerontologists. To quote Leonard Hayflick (who believes - in contrast to folks like Aubrey de Grey - that aging cannot be cured): "Most physicians believe that the greatest risk factor for age-associated disease is the fundamental aging process. Yet research on this - the greatest risk factor for all of the leading causes of death - is virtually ignored."

Link: http://www.infoaging.org/feat32.html

I really had to take issue with this part of a recent post by Chris Mooney:

Applebaum also notes the following:

Stem cell research is not, in fact, either illegal or unfunded: The federal budget in 2003 included $24.8 million for human embryonic stem cell research -- up from zero in 2000. Private funding of stem cell research, which is unlimited, runs into the tens and possibly hundreds of millions of dollars.

This, too, is revealing, although not in the way Applebaum seems to think. First, note that she can't put a figure on the amount of private funding that embryonic stem cell research is receiving. Neither could I when I tried to research the question recently. Nobody seemed to know. And that's precisely the point: We pay for science with taxpayer money so that we can have standards, accountability, fixed and transparent budgets, ethical regulations, and so on. That's why you can't leave research to the private sector. You won't know what the hell is going on.

Note also that Applebaum estimates that private funding is probably higher than federal funding in the U.S. That's striking: I'm told that in most biomedical fields NIH is the real go-to source for money, not the private sector. So this essentially shows just how differently embryonic stem cell research is being treated.

Hostility towards private research is something of a knee-jerk reaction for some people - but it makes no sense. It's the reaction of a control freak, of someone who is upset that things happen outside his or her sphere of influence. That the world turns without you is a fact of life and not a good reason to advocate centralized control. In addition, the complaints Mooney makes about the private sector apply just as well to publicly funded research. If anything, government efforts are far less accountable for failure, waste, ethics and safety than private initiatives, as even a brief perusal of recent history will demonstrate.

Medical research funding is approximately 30-40% public, 50-60% private for-profit and 10% philanthropic according to my research on the subject - it didn't take long to dig that up from studies on Fortune 500 research spending and NIH budget commentary.

The best way to ensure that funding for serious anti-aging research happens is to speak out - sound like someone who will spend money on working anti-aging medicine. Venture capitalists and entrepreneurs hear that sort of thing; you can see the results in the field of regenerative medicine right now. Businessmen listen carefully for the demand for cures, and are working hard to make the products that you and I want.

In a centralized system we'd still be waiting in line for bread, never mind cheering on the advent of cures for Parkinson's, paralysis, diabetes, cancer, and many other age-related conditions.

You'll recall I mentioned a few days ago that the Democrats have positioned themselves as the party of stem cell science. Timothy Noah has an article up at Slate today that looks at this from a wonkish point of view - for those of you who are interested in that sort of thing.

The Democrats' eagerness to discuss stem cells is strikingly different from their attitude before Aug. 9, 2001.

...

According to the Kerry campaign's polling, fully 69 percent of voters currently support stem-cell research, and a majority say they support it "strongly." It is no longer necessary - or even advisable - for Democrats to whisper their support for stem-cell research.

...

If you search the entire Bush-Cheney campaign Web site, you'll find only four instances where the phrase "stem cell" comes up. It's a subject Bush wants to avoid at least as much as Kerry wants to emphasize it. That's why Democrats will keep saying "stem cell, stem cell, stem cell" over and over until Election Day.

Chris Mooney has been keeping up his stream of posts on recent stem cell politics:

More on August 9:

Come to think of it, it's a safe bet that we can probably expect some political activity (and not just heavy drinking) on the anniversary of Bush's stem cell decision. So far I've only heard a little bit about what may be in the works, but I would bet that more's on the way. If I were John Kerry and wanted to make embryonic stem cell research a campaign issue, for example, I highly doubt that I'd allow this date to go by unnoticed and un-remarked upon.

A Steamroller in California

The state ballot initiative to pump unprecedented billions into stem cell research has raised more $ 7 million. The opposition has (so far) raised zero. The founder of eBay and his wife have donated a million on their own. It's still early, but it looks like the embryonic stem cell research backers may simply squash the opposition. If so, governor Schwarzenegger might think about hitching himself to the campaign--and then basking in the glory of being a beneficent science patron come November.

Stem Cells and the "Soul"

"Limiting research to adult stem cells is like asking the government to develop an Air Force only using prop airplanes and ignoring the existence of jets."

CORDIS provides an example of modern research into nanomedicine in the public sector: "A new EU-funded Integrated Project, with a total budget of 26 million euro has become the largest ever project to deal with nanotechnologies. It seeks to develop a new generation of nano-biotechnological devices with therapeutic applications in the field of tissue engineering." You can find more technical details at the CellPROM website - it's fascinating, advanced, forward-looking stuff. These are the sorts of fundamental technological capabilities required for progress towards greatly extending the healthy human life span through nanomedicine.

Link: http://dbs.cordis.lu/cgi-bin/srchidadb?CALLER=NHP_EN_NEWS&ACTION=D&SESSION=&RCN=EN_RCN_ID:22409

The business world and private research community is forging ahead in the broad field of regenerative medicine, based both on stem cell research and other technologies. This press release and others like it show that at least some venture capital is flowing - the potential revenue that will result form from cures for diabetes, Parkinson's, Alzheimer's and other age-related conditions are too large to pass up, even in this currently hostile legislative environment. "It is very exciting to bring this work to a region that is already leading the way in regenerative medicine and tissue engineering. We want to build on Pittsburgh's reputation as a global leader in these areas, ultimately saving lives."

Link: http://biz.yahoo.com/prnews/040802/clm035_1.html

Posters at the Immortality Institute forums are debating the case for a Methuselah Fly Prize as a complement to the Methuselah Mouse Prize for anti-aging research:

Considering the differences between the fruit fly and the mouse, the length of the investigation can be dramatically shortened for two reasons:

1. You don't have to wait years to see the results of alterations in the animal genome because the fly's lifespan is measured in weeks instead of years.

2. You can literally run hundreds of thousands of experiments in parallel because of the size and ease of maintenance of flies.

So rather than the comparison of 25 years pledge for mouse versus 15 years for the fly is should be more like 5 years only for the fly.

The other difference to point out - and this is a terrific marketing tool - is that the interactivity that can be created between the research lab, the donors and other participating and interested parties by reporting on the progress of the fly experiments on a daily or weekly basis via the web, because the experiment is over in a period of weeks rather than years.

With the experiment only needing to run for 6 - 12 months instead of years, the entire experimental investment is substantially reduced. Meaning that a prize of, say, $300k would actually be attractive to the smaller research group based on the monetary incentive alone.

The economic and timescale arguments for running a prize for fly longevity are good ones. You can get more done with less in comparison to mouse studies - even a few hundred thousand dollars would get some traction and attention within the scientific community, I suspect. You can still get a great deal of very valid science done - flies and humans are more alike than you might think when it comes to genes and biochemistry. Many of the current investigations into the genetics of aging and calorie restriction mimetics started off with fly studies.

Where the potential for a Methuselah Fly Prize falls down, I think, is on the publicity angle. I am very dubious that you could get the public as interested in flies as they are in cute, fuzzy, long-lived mice. One Yoda - with pictures - is worth a thousand press releases when it comes to attracting support for healthy life extension research.

So I suspect a Methuselah Fly Prize would do well if funded off the bat to the tune of $100,000 or $1 million - but I don't see the same fundraising methodologies used by the Methuselah Mouse Prize administrators to build funds from scratch working in this case. Not that I'm discouraging anyone from trying. If you want to launch a Methuselah Fly Prize, then I wish you the best of luck in proving me wrong about the way in which the public thinks about these things!

Boston.com casts a critical eye on Elixir Pharmaceuticals and its progress towards stability and real anti-aging drugs. Elixir is suffering some of the growing pains of any younger medical research company, and is apparently refocusing to reach a reliable revenue stream more quickly. "In a sense, every company must at some point surrender some of its promise as it moves toward a real product. But for Elixir, a company founded to continue the centuries-long quest for an antidote to aging, that transition has been much more pronounced." According the the article, Elixir will license one of the new calorie restriction mimetics in order to come closer to profitability.

Link: http://www.boston.com/business/technology/biotechnology/articles/2004/08/02/unfocused_elixir_seeks_new_life?pg=full

ScienceBlog reports on efforts to create genetic tweaks to prevent obesity. In this study, mice with ramped up metabolisms that burn fat at a higher rate not only stay thinner, but also live longer: "despite their svelte appearance, beta/beta mice actually eat more food and are no more active than their genetically normal littermates ... the white adipose tissue, which is normally reserved for fat storage, had actually been converted into fat burning cells in beta/beta mice." You may recall that scientists recently overturned the common wisdom on metabolism and longevity - mice with more active metabolisms have been shown to live longer, possibly due to a lower rate of free radical creation.

Link: http://www.scienceblog.com/community/article3473.html

While meandering the web, as I often do on Sundays, I came across a promising article from Harry Moody, one of the many bioethics-oriented folks affiliated with the International Longevity Center. You might recall his appearance in a SAGE Crossroads debate over whether to define aging as a disease. It's interesting - and pleasing - to watch the conservative rump of gerontology start to come around as real anti-aging science becomes ever more plausible:

When I began to prepare to write this article, I was clear and confident about my direction. Anti-aging technologies, I was sure, are a snare and a delusion--an appeal to vanity, to narcissism and denial of reality. Instead of techno-utopian delusions, I would argue for a more "ecological" vision of life where youth and age are both accepted as part of the natural life cycle. It is a line of thought I have held for many years, and what is more comfortable than familiar opinions?

But the more I thought about my skepticism and hostility to life-extension technology, the more uneasy I became. Gradually, as I reflected on my uneasiness, I found it more and more difficult to rationalize my strong rejection of life extension.

In this piece, Moody summarizes the for and against arguments as he sees them. His emphasis is on anti-aging medicine rather than anti-aging science, as mainstream, conservative gerontology is in the midst of what can only be described as a feud with the anti-aging marketplace over legitimacy, definitions and public understanding what is possible. As I've said before, both sides are as much in the wrong as they are in the right.

Diversion of scarce resources.

Diverting scarce biomedical resources to anti-aging research is wasteful, since the odds of success are remote and the consequences for society are problematic. Funding should go instead for more conventional research to ameliorate age-related diseases, as the National Institute on Aging contends.

Counterargument: A tradeoff decision isn't ours to make. Funding for anti-aging research mainly comes from private corporations, not government anyway. The situation is comparable to cloning: Research will go on either here or overseas, whatever we think. Tradeoffs will be decided in the marketplace, not at the policy level. Moreover, anti-aging research will have benefits in ameliorating age-related diseases. It is impossible to separate anti-aging research from other forms of geriatric medicine.

...

Virtues of aging.

Aging, death, and finitude are essential conditions for human flourishing. Working within limits is what artists do in the act of creativity. To live without limits would not provide a basis for the human virtues that give life its creative meaning.

Counterargument: Life extension is not immortality and doesn't do away with the finitude of existence. Life extension may even make the threat of "premature" death more poignant. Acts of artistic creation entail limits imposed by social convention (e.g., the form of a sonnet or a symphony). So too, extended life may require different new conventions. By analogy, instead of a short lyric poem, we aim for a longer epic poem. The extension of life will open greater possibilities for human expression and fulfillment on a larger scale. Why then should we be afraid of life extension?

Moody is still in the group of gerontologists who believe - unlike Aubrey de Grey and his supporters in the field - that radical life extension is either impossible or still far in the future. Both are self-fulfilling prophecies when held by those in charge of funding, since they won't fund what they believe to be a waste of time. Moody does recognize that the mainstream gerontological response to serious anti-aging research is lacking, however:

Indeed, within mainstream gerontology, anti-aging medicine is widely viewed with hostility and skepticism (an incipient form of "gerontological correctness"?). But we are entitled to wonder: Are the arguments against anti-aging medicine valid, or are the opponents of anti-aging medicine (including me) simply gerontological Luddites?

The response of mainstream gerontology to anti-aging medicine reminds me of an old joke about the man who borrows a pot from his neighbor and doesn't return it. Eventually the neighbor asks for his pot back. The one who borrowed it says nothing at first, then blurts out, "First, I never borrowed a pot from you. Anyway, I returned it last week. And besides, that pot was no good to begin with." What is it that bothers us about the technology of life extension? Is it perhaps the fear that it might--just might--work?

...

Here one cannot escape the memory of Lord Kelvin, who proudly declared that radioactivity must be a hoax, or the case of the French physicists who proclaimed that heavier-than-air flight was impossible--just a few years before the Wright brothers took off into the air at Kitty Hawk. Again, we come back to the question, Do we believe that life extension technology doesn't work, or that it can't work, or that it shouldn't work?

Overall, the article in not indicative of a large change in attitude. If the conservative scientists and funding administrators are slowly seeing the light, however, then we're getting somewhere. It is becoming harder and harder for these people to continue to ignore demonstrations of radical life extension in animals, working regenerative medicine, progress in understanding the causes of aging, and other steps towards real anti-aging medicine.

Myrtle Beach Online has a good piece on aging research and the remaining mysteries of the aging process. After an overview of current progress and what we know about aging, it's quite clear that the underlying biochemistry is very complex. There is a long way to go yet, but researchers are optimistic: "Sinclair says that research on aging is 50 years ahead of where he expected it to be when he began his work a decade ago. There's even a feeling among scientists, he says, that a Nobel Prize may be awaiting someone who finally cracks the molecular code that controls aging." Bioinformatics has dramatically accelerated aging research, just as it has for all other fields of medicine - greater funding is needed.

Link: http://www.myrtlebeachonline.com/mld/myrtlebeachonline/news/nation/9296013.htm

The latest Longevity Meme article is up - George Dvorsky's "Bio-Luddite Nation," a revision and reprint generously donated by the folks over at Betterhumans. "As the prospect of radical extension of the healthy human life span becomes more real with each passing year, prominent bio-Luddites have gone on the offensive to convince immortal wannabes that death is where it's at. They speak in a flowery and comforting tone, proclaiming that death defines our species and endows our lives with meaning, purpose and social stability." This article serves as a reminder of the dangers posed to the future of medical research, healthy and longevity by people like Leon Kass.

Link: http://www.longevitymeme.org/articles/viewarticle.cfm?page=1&article_id=20