The idea of people living hundreds of years has about as much credibility today as the idea of the world not being at the center of the universe had in 1540. Intellectually and in terms of our laws, institutions and actions, we are just not ready for radical life extension. I will illustrate this point with a short piece of fiction.
The story of the X pill
A team of distinguished university researchers uses molecular engineering to create a substance X that appears to activate an evolutionary genetic pathway affecting the expression of hundreds of aging-related genes. When tested, the substance doubles the life of laboratory mice and rats. Based on solid theoretical considerations, it appears that X could be the basis for making an anti-aging pill for humans. Extrapolating up from the mice and rats, it appears in theory that people who start taking the X pill on a daily basis in their 40s will double their average life spans. They will, the reasoning goes, continue to age but at a much slower rate. They will still get the diseases and problems of old age but, on the average, much later. At age 110 they should be about as healthy as people are today at 55.
So, the researchers raised venture capital to start up a biotech company to manufacture X pills and sell them to the public. What happened?
1. Everybody including the researchers recognized that the anti-aging effectiveness of the X pill can’t be established for a long-long time. There is no guarantee that X will work in humans as it does in mice and rats. Taking the X pills seems to result in healthier biomarkers and possibly longer telomeres, but this can’t be confirmed until there are 10 years or more of history. And, those factors by themselves do not guarantee longer lives. The new X biotech company is trying the pills on large monkeys, but it will also take 30-40 years to establish that the pills double the average monkey life spans. In 15-20 years it might be noticed that people taking the X pills continue to look younger or have less deadly diseases. But it will take 150 – 200 years to unambiguously establish that most people taking the X pills live twice as long. And this can only happen if data is gathered on the pill-taking cohort for all that time.
2. For the same reason, for a long time it will be impossible to know for sure that taking the pills is safe. How could anybody be sure that some deadly side effect won’t kick in after 5-10 years?
3. The realization soon dawned that the X pills cannot be developed, tested, approved, and sold as a drug. Drugs are approved by the FDA for disease indications and aging is not a disease. The X substance will not cure diseases. Instead, its action is to prevent many diseases from occurring in the first place, and there is no drug category for that. Once this was realized, it became very difficult for the X biotech company to raise additional development capital.
4. The managers of the X biotech company came to realize a horrible truth: because X is a new and strange synthetic chemical, it is possible that the X pills cannot be legally sold for human consumption in the US and most other advanced countries. Fortunately, a graduate school assistant working for X discovered in the literature that members of a rare species of deep-sea urchin have tiny trace amounts of X in them. This fact allows selling X pills as a “natural substance” dietary supplement. Whew! That was a close one!
5. A clinical trial of the X pill is out of the question. If there were such a trial, it would have to last 30 years just to get early indications. Nobody is prepared to pay the hundreds of millions of dollars required for such a trial, particularly the new X biotech company which is running on a shoestring.
6. For the first two reasons listed above, the majority of doctors recommend their patients not to take X pills. They rightfully say that substance X is unproven, unapproved by the FDA and potentially dangerous. They think they are following the basic medical precept “First, do no harm.” For patients who have had an episode of cancer or heart disease, the warnings from the doctors are particularly stern and ominous.
7. Some prominent religious figures start a crusade against taking the X pills. Their point is that “extending human life would go against God’s natural order.” This is a mixed blessing for the X biotech company. On the one hand it gives them press exposure. On the other hand it leads many pious followers to eschew the X pill
8. Big pharmaceutical companies mount a well-funded PR campaign warning people against taking the X pill. They do not want to see large numbers of people taking x pills for good business reasons. They are not afraid that it won’t work; they are afraid that it will work. The ideal pharmaceutical drug from a commercial viewpoint is not a cure for a serious disease, but is a drug that must be taken continuously to prevent or blunt the symptoms or ravages of such a disease, year after year. That is a prerequisite for a blockbuster drug that rakes in $10 billion or more a year. An X pill that results in many fewer cases of disease happening could be commercially disastrous to many big pharma companies. So, they subsidize doctors to write articles and go on TV opposing the X pills.
9. The big hospital centers that mass-process patients with life-threatening cardiovascular and cancer problems also see their businesses threatened, including cardio surgeons, chemotherapists, radiation therapists, hospital administrators and insurance company executives, people who depend on a steady stream of diseased patients in order to earn from a half-million to more than a million dollars a year. They join the big pharma companies in the anti X pill chorus.
10. The big research-sponsoring establishments like the National Cancer Institute and those who feed in their troughs also have a vested interest in fighting the availability of such a pill. The War on Cancer going back to 1971 has produced marginal results for the hundreds of billions of dollars spent on research. In 2008 the NCI spent $4.83 billion on 5,380 research grants. Until genomics came along, the required basic science platform for discovering what really goes on in cancers was simply not there. Although cancer deaths are down, much of the progress has been due to public health measures like decline in cigarette smoking. Yet, the cancer research establishment is not only going on but is growing. If an X anti-aging pill came along that postpones when most cancers happen by 70 years, imagine what an embarrassment that would be for everyone in the cancer research establishment. Thousands of researchers with their own pet theories about cancer and more thousands working in the cardiovascular, diabetes and neurological disease areas start throwing Olympic-sized swimming pools full of ice water on the X pill idea.
11. As sales of the X-pill increase, the anti X-pill factions decide they have to do something to stop it. They join together in a successful lobbying effort to “regulate” the X pill which means halting its sale and handing rights to future anti-aging drugs to big pharma. People who want to continue taking X pills will have to smuggle them in from Bulgaria. And then they will for-sure not know what they are getting.
This little story brings out several important points about the current reality. Several dietary supplements in the anti-aging firewalls Supplement Regimen are similar to the X-pill in that they theoretically produce healthful and life-extending results, they can demonstrably extend the lives of small animals by 20% to 40%, but what they will do for humans is not yet very clear. Telomerase-activators like cycloastragenol or TA-65 have a significant life-extending potential but what they actually do for humans remains under a cloud of uncertainty. Companies like TA Sciences and Sirtris Pharmaceuticals are facing many of the same problems faced by the fictional X pill company.
There is a major need to prepare the society for the possibility of radical life extension:
1. There is a clear need for educating medical professionals as to progress in developing anti-aging strategies and therapies, and for getting them used to the possibility of radical life extension. The same is true for all concerned parties: lawmakers, institutional administrators, and the public at large.
2. There is a need for a massive shift in government health research funding, away from simply finding chemical and surgical cures for diseases, towards promotion of longevity and disease prevention via public health measures and epigenomic and genomic enhancements of individuals. Public money spent over the years on longevity research is a tiny drop in the bucket compared to money spent of cancer and other disease research, despite the incredible leverage on incidences of the same diseases increased longevity would provide. And significant sums of money need to be set aside for long clinical trials and population studies to help evaluate the effectiveness of emerging anti-aging therapies.
3. Above all, there is a need for a major shift in general perspective regarding life extension FROM more and more doddering, sick, non-functional, non-contributing individuals drawing social security, filling nursing homes, having automobile accidents and driving health care costs ever-higher, TO more and more healthy, creative, fully-functional working individuals in their 70s, 80s, 90s and beyond who are not getting the diseases of old age, and who are more than doing their part to contributing to our society in every way.
Great article! I think you meant to say longer telomeres, not shorter telomeres, in #1 at the beginning.
Steve, of course you are right about longer. I have fixed it. Thanks
Vince
Vince, excellent post!
I have posted this link to my Facebook profile and I strongly encourage other readers to post the link to the various social networking sites they frequent (Facebook, Twitter, blogs, etc.) and/or send it to their friends…one small part of my promotion of anti-aging/longevity/life-extension ideas is directing my friends to your blog, Vince.
This battle against aging and death must be fought on the social/cultural front, to complement the battle on the scientific and technological front.
SingularityFan:
Wow! You have really got what I and this blog are all about. If this were 1000 years ago, your last statement would have deserved to be carved in marble over the portico of some great temple. Today we need to get the message out via every medium available. I think the social networking approach is an excellent one.
Vince
I fear, based on history, your vision will only come to pass as the naysayers die off and we slowly inherit the Earth.
So in the meantime, I am not that concerned in-so-as-far my freedom to access bioagents in an affordable manner is not restricted by regulation (like Senator McCain’s recent legislation).
In my view, the most serious threat will come from the religious fundamentalists. They simply deny any validity to science and the scientific method.
http://www.nytimes.com/2006/12/12/science/12turt.html?_r=1
Dr. Christopher J. Raxworthy, the associate curator of herpetology at the American Museum of Natural History, says the liver, lungs and kidneys of a centenarian turtle are virtually indistinguishable from those of its teenage counterpart, a Ponce de Leonic quality that has inspired investigators to begin examining the turtle genome for novel longevity genes.
“Turtles don’t really die of old age,†Dr. Raxworthy said. In fact, if turtles didn’t get eaten, crushed by an automobile or fall prey to a disease, he said, they might just live indefinitely
Machine Ghost
Yeah, we will probably inherit the earth. In the interim I have the personal temerity to think we might make the transition a bit easier by preparing the ground for it now.
And I am also not too concerned about immediate restrictions. Finally, yes the religious fundamentalists are bound to pick up extraordinary longevity as an issue to crusade against. I don’t think any of us will get burned at the stake but we might well get singed by the heat.
Vince
Hi Res
Interesting about the centenarian turtle. I will look at the link, Lobsters also don’t age and just keep going. There seems to be some evidence that when species don’t have competitors, they evolve to have longer and longer lifespans. I think that is happening with humans now. Finally, today’s post – MicroRNAs in cancers and aging, and back-to-the nematode – discusses the advantages of learning about longevity from other short-lived species.
Vince
Hi Vince
See this pdf
http://www.ese.u-psud.fr/epc/conservation/Publi/abstractr/AE_CHA99a.pdf
It was known that the squirrels never get cancer.. Told to me by a geneticist
Res
(jtereting about the European Turtles, I suspect they must keep their telomeres the same lengths by expressing telomerase. Otherwise, cell division would shorten them. The author also reminds us that cell senescence can come about through other mechanisims besides too-short telomeres.
As to squirrels and cancer, Lots of blog posts on that at http://www.google.com/search?pz=1&cf=all&ned=us&hl=en&q=squirrels+cancer&btnmeta%3Dsearch%3Dsearch=Search+the+Web work by Vera Gorbunova
http://www.rochester.edu/College/BIO/professors/gorbunova.html who appears to have written many papers on aging mechanisms.
Vince
Related to religious fundamentalism, here’s a brief article on the decline of religious belief in general of younger Americans, the so-called “millennial generation” (never heard of that term before) consisting of 18-29 year olds.
http://www.cnn.com/2010/US/02/17/report.millennials.faith/index.html
I think and hope that this encouraging trend will continue.
Seems like a free flow of information, leading to more accessible and a higher general level of education, will naturally marginalize fundamentalism without a direct and violent confrontation with progressive ideas.
We live at the edge of an incredible period of human history. I fully support any individual’s right to live as long as they choose to live. Nanotechnology, advanced biotechnology, and various emerging technologies will give us the option of choosing our lifespan. I, too, fear the potential backlash of the short-sighted and power hungry organizations that have too long controlled society. Alas, we must live and live well by our own future focused terms and philosophy. Let those that must “die to make room for the next generation” do so. I choose to live and experience the future.
Matthew
Well said!
Vince
Thank you. Please consider contributing to my Anti-Aging Discoveries Forum. It will be live within the next day. I really appreciate the in depth discussions here.
SingularityFan:
I agree that there is cause for optimism with respect to younger Americans. Thank goodness! A lot of the issue has to do with education and socio-economic status, where low education and poverty being highly correlated with fervent religiosity. Nonetheless rabid fundamentalism, general ignorance and a political climate of strong partisanship combined with poverty and difficult economic times can still constitute a fundamental threat to peace, freedom and progress. The rise of Hitler provides a good example.
Vince
Matthew,
Please post the address of your new anti-aging discovery forum here as soon as it is up.
Vince
Hello Vince,
What’s the rule that things always take much longer to finish than was planned? Anyway, my forum is up and running. Only a couple topics right now but I am certainly open to any and all ideas for topics as your readers might enjoy.
http://www.future-of-anti-aging.com/Anti-aging-discoveries-forum.html
Thanks and keep up the great work!
Peace and long life,
Matthew
One of my favorite researchers (and there are many great ones out there), is Aubrey De Grey. Recently, he coined the term “The Methuselarity”, meaning the point in history when humans have the choice to live significantly longer lives.
The Singularity is now a popular term for when our exponentially growing technologies allow us to merge with machines and also to radically extend our lives. The key distinction is that Dr. De Grey believes that radical life extension should be possible without nanotechnological implants, etc.
Deep understanding of the biological functions along with genetic engineering, tissue engineering, etc. should allow for what he calls “Robust Human Rejuvenation” treatments.
For example, a person at 60 could get a treatment that makes them 20 years younger biologically. They would then have another 20 years before they were biologically 60 again and so on.
The exciting thing here is that technology of all sorts will continue their exponential curves so that each successive treatment would be even more effective than the last so that the biological years gained would increase each time. So in the case of the 60 year old, they may actually get to a point where their biological age could be a point of choosing such as going back to age 20 after decades of treatments.
I found his new thinking encouraging and a valuable alternate route from those who might find “becoming Borg” unappealing. I, for one, might still consider neural implants to help me learn and function faster.
For those of you who want to see a lecture by Dr. Aubrey De Grey on the differences between The Singularity and The Methuselarity can find it here:
http://vimeo.com/7339349
Those who prefer text can find some excellent articles here:
http://www.fightaging.org/archives/2009/09/the-methuselarity.php
Matthew
Matthew
Thank you for your comments and for posting links to the Aubrey de Grey video and information I agree with Aubrey about some things and disagree with him about others. I agree that it is a possibility that continuing research and practical progress in anti-aging approaches may lead us to the point where we reach an aging “escape velocity.” I certainly hope so.
I disagree that aging is explainable simply in terms of accumulation of damage, a central truth in Aubrey’s view of aging. This might have been a good explanation for aging in 1990, but too much is known now about lifelong epigenetic changes and changes in stem cell markers and differentiation capabilities to support credance to this simplistic view. I have elsewhere argued that aging is a very complex program involving systematic changes in epigenetic features and the expression profiles of thousands of genes. Why would mice die in two years and bats that look like winged mice live for 20 years? They are exposed to more or less the same biological damage as the result of living, but their aging programs are different. Aubrey is fun to listen to, however and he does have some other interesting and innovative things to say.
Vince
I do agree that some of his theory of aging is far too simple. Perhaps he uses this reductionist angle to make the fight against aging seem more achievable in our lifetime.
(I do think that the perfect storm of technologies should give us those breakthroughs within a few decades rather than centuries.)
I totally agree with you that aging is very complex and probably different in each individual as well based on our lifestyles, diet, environment, DNA, etc.
What I really like about him is his focus on fixing the damage we do understand now. He is quite entertaining though and has value in his role as a Pied Piper of Human Rejuvenation. He often makes the case that scientists in general are too cautious about direct anti-aging research. They gingerly pick at different aspects of aging but few are truly working towards viable solutions that will give us the option to live hundreds of years if we so choose. I am sure there is a fear factor involved. Extending human life to 150 or 200 or whatever would come across as sheer lunacy to most and terribly selfish to those who think we don’t have the right to live longer than “nature” intended.
I am not sure if you follow the scientists at The Singularity Institute but they seem focused on the global, big picture, problems. I love their sponsoring the X-Prizes and also their 10 to the 9th programs. The later being challenges specific to “what can you do to improve the lives of one billion people.” The next century should be a fascinating one. I hope I am around for most of it.
Matthew:
I do agree about what you say about the perfect storm of technologies. Have you seen any of earlier posts in Giuliano’s law having to do with improvements in anti-aging interventions? See http://anti-agingfirewalls.com/2009/03/29/factors-that-drive-giuliano%e2%80%99s-law/
i have possibly not focused enough on the Singularity Institute since most of my blog work has been hard-science oriented. I will give their website another look, though.
And I do think Aubrey adds color, texture, questioning and charisma to the aging science field. And those are very positive qualities.
Vince
The movie Transcendent Man is coming soon from Ray Kurzweil and others. The X Prize folks and the Singularity Institute are connected and involved in many projects.
I love the 10 to the 9th Projects that they are exploring. In essence, these projects are trying to focus on what might benefit a billion or more people. (This is what 10 to the 9th means.)
I know many of these various scientists are connected in some way to these various movements. I hope they make progress faster than society has the opportunity to limit them. I guess I am somewhat pessimistic when it comes to what the government will allow the public to access. We have some great progress now but it will be years before most see the benefits.
Matthew:
I want to pick up on one of your key points which is “We have some great progress now but it will be years before most see the benefits.” Possibly but not necessarily true in my perception. Specifically, connected with both the mTOR amd SIRT1 pathways, life practical life extension technologies that could add 10-12 years to us humans seem tantilizingly around the corner yet so far away in terms of widespread practice.
We have plenty of good research programs that spawn yet more-research, but other than for a few outside-the-mainstream groups like the Singularity Institute, there is no mission-oriented R&D specifically oriented to life extension. That kind of R&D does not fit into our existing paradigms. As pointed out in the blog entry, there are major societal barriers to getting anything like an X-pill out there in the market.
Perhaps our best hope lies in the development of drugs for age-related diseases that in fact extend lifespans. In other words, using the cover of the existing drug development paradigm to develop anti-aging drigs. Sirtris Pharmaceuticals is a good-case example. According to their website “Sirtris is focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, such as Type 2 Diabetes. Our research focus is on modulating the sirtuins, a recently discovered class of enzymes involved in the aging process.” If they succeed, and I think they will, they will have developed one or more anti-aging drugs. Meanwhile, many of us including many sirtuin researchers have been taking resveratrol for years now.
Vince
Hi Vince,
Thank you as always for your excellent work. I find it very encouraging. It reminds me that there is real scientific progress being made.
Did you see that TA-65, the telomerase activating chemical, got awarded a patent recently? Apparently, the staff has been taking it for four years now with measured improvements in telomere length and various improvements in health markers. Unfortunately, the cost is a substantial barrier for most people. Testing and the various supplements would exceed $1,000 per month.
I have been following Sirtris’s work for some time. I am excited by the potential for resveratrol and the drugs that might be developed from that molecular base. It is my understanding that Sirtris Pharmaceutical is working on formulas that are thousands of times more potent than straight resveratrol.
I agree with you that our society really lacks the focused R & D needed specifically for life extension drugs and therapies. Progress is being made of course but it seems many of the efforts are focused on specific diseases “associated with the aging process.” Not a bad thing but it is different than a blatant focus on creating life extension drugs and therapies. Maybe it is just my perception or maybe researchers want to deflect attention or criticism for going after the holy grail of extended life.
It seems timid to me but I fully acknowledge that the potential backlash from various groups or governments. Abortion is legal and look how many nuts are out there threatening and killing doctors. What might happen if we get serious and effective life extension clinics out there? Some nut is going to think we are going against nature by wanting to live longer. Hopefully my fear about that is unfounded. But I have to think there will be a great gap between those who can live to say, 150 years or more and those who still think that 70 or 80 years is a burden on society. Your X Pill article identifies these issues.
I noticed on a recent article that the company Cenegetics is mentioned. What do you think of them and their program? Like the TA-65 compounds, it remains a rich man’s game. No way I can afford several thousand per month for life extension therapy, at least at this point in my life. Also, the hormone HGH and others that are probably given would cause me some concern. As a testicular cancer survivor, I am always somewhat worried that some supplements or hormone replacement therapies might be dangerous for me.
Hi Matthew
First of all, thanks for your thanks.
“Did you see that TA-65, the telomerase activating chemical, got awarded a patent recently? Apparently, the staff has been taking it for four years now with measured improvements in telomere length and various improvements in health markers. Unfortunately, the cost is a substantial barrier for most people. Testing and the various supplements would exceed $1,000 per month.”
I have long knew about the patent – it gives what the substance is away, and have been following them. In terms of published research on TA-65, as far as I know there is only one published paper which does not sustain most of the claims made by the company. As to health markers in the staff, I have not been following that.
“I have been following Sirtris’s work for some time. I am excited by the potential for resveratrol and the drugs that might be developed from that molecular base. It is my understanding that Sirtris Pharmaceutical is working on formulas that are thousands of times more potent than straight resveratrol.
“I have been following Sirtris’s work for some time. I am excited by the potential for resveratrol and the drugs that might be developed from that molecular base. It is my understanding that Sirtris Pharmaceutical is working on formulas that are thousands of times more potent than straight resveratrol.”
That is my understanding too. However it is not at all clear to me that a drug 1000 times as potent will have 1000, 100, 10 or even 2 times the biological impact, or that it will not be toxic. Imagine drinking 1000 cups of coffee. Those things require extensive testing and Sirtris has some of the substances in the clinical trial pipeline now.
“I agree with you that our society really lacks the focused R & D needed specifically for life extension drugs and therapies. Progress is being made of course but it seems many of the efforts are focused on specific diseases “associated with the aging process.†Not a bad thing but it is different than a blatant focus on creating life extension drugs and therapies. Maybe it is just my perception or maybe researchers want to deflect attention or criticism for going after the holy grail of extended life.”
Yes, but I think the issue lies more with the research fund-providers and our institutional structures than with the researchers themselves. Aging is not seen as a disease and therefore anti-aging is not explicitely funded. Aging is seen as inevitable and anti-aging research as snake oil. So congress will fund research into aging but not anti-aging. The problem is one of public perception.
“It seems timid to me but I fully acknowledge that the potential backlash from various groups or governments. Abortion is legal and look how many nuts are out there threatening and killing doctors. What might happen if we get serious and effective life extension clinics out there? Some nut is going to think we are going against nature by wanting to live longer. Hopefully my fear about that is unfounded. But I have to think there will be a great gap between those who can live to say, 150 years or more and those who still think that 70 or 80 years is a burden on society. Your X Pill article identifies these issues.”
In my view, you are right-on with these concerns
“I noticed on a recent article that the company Cenegetics is mentioned. What do you think of them and their program? Like the TA-65 compounds, it remains a rich man’s game. No way I can afford several thousand per month for life extension therapy, at least at this point in my life. Also, the hormone HGH and others that are probably given would cause me some concern. As a testicular cancer survivor, I am always somewhat worried that some supplements or hormone replacement therapies might be dangerous for me.”
As to Cenegetics, I don’t know much about it. It appears to be a different kind of beast – a for-profit health management network for older people. I don’t know how science-based their practice is but the material on their web site suggests that the substance of what they offer is reasonable – counseling on exercise, nutrition, supplements, weight management, etc. – all material publically available for people willing to go out and find it. I guess there is a lot of economic value-added by having this advice given by a doctor in an impressive office wearing a white coat.
As to the affordability issue, the problem is that life and healthspan extension is following the medical model. TA-65 is a proprietary substance priced like an expensive drug. Sirtris is developing proprietary drugs that will no-doubt be expensive. Cenegetics appears to be functioning as an elite specialized medical practice.
I don’t think maximizing healthspan with aging, the low-hanging fruit, needs to be that complex or expensive. Exercise. Consume avocados, hot sauce, blueberries and wallnuts, keep mentally active, take certain supplements, etc. Have you seen my treatise ANTI-AGING FIREWALLS THE SCIENCE AND TECHNOLOGY OF LONGEVITY at http://www.vincegiuliano.name/Antiagingfirewalls.htm ? There, I suggest a “lifestyle firewall†and a “dietary supplement firewall†that are designed to protect against the progress of aging according to 14 of the most classical theories of aging.
Vince
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