The first attempt at an organization called Open Cures was a glimpse into how the future of medical tourism and open biotechnology will interact to work around and ultimately bring down the tall regulatory barriers put in the path of progress. As what can be accomplished in the laboratory becomes ever more advanced beyond what has finally made it into the clinic, there will an increasing pressure to bypass the massively expensive, restrictive, and uncertain process of regulatory approval. That pressure will go hand in hand with the growing ability of small groups to perform their own medical commercialization, using increasingly cheap tools and widespread knowledge, producing a dynamic that will look very similar to the way in which software development became something that anyone could do.
To my eyes this is the only way we're going to see therapies for aging arrive in good time. Attracting research funding requires the outlet of profitable markets at the end of the tunnel. The lack of such a market is one of the reasons why longevity science lacks funding: the FDA will not approve treatments for aging, so what commercial entity will fund early stage development? Thus the future of medicine will be as much about building new channels for the development of - and access to - clinical applications as it will be about the science.
There were two fundamental issues with diving in and doing this. Issue one, which is easy to forget when caught up in the idea, is that I am absolutely not the person to be leading this sort of initiative. Issue two is that despite it being a good, necessary idea, it is still the case that the highest priority in this community now and for the foreseeable future is to channel funds and interest to the SENS Research Foundation. The science needed to build rejuvenation therapies has to happen, and it is still in a comparatively early, formative stage of development: this is where efforts must go until the work is further along, with applications ready for clinical development.
I am going to post the defining essays from the original Open Cures site here to make sure they remain online.
Open Cures: to Speed Clinical Development of Longevity Science
Let me take a moment to talk about why, in this age of biotechnology and accelerating progress, it is even necessary to build an organization to help speed matters along. What is the roadblock that stands in the way of the clinical development of longevity-enhancing biotechnology?
The Biotechnologies of Longevity, Undeveloped
When we look at work on aging and longevity in the laboratory, we can see that more than a dozen ways to use biotechnology to extend the lifespan of mice have been demonstrated over the past decade. About half of those methods appear to lack serious side-effects, delivering only longer lives, lower cancer risk, improved health and vigor, and little else. Similarly, a range of laboratory demonstrations conducted since the turn of the century have reversed specific, measurable biological changes that occur with age in mice: damaged mitochondrial DNA replaced throughout the body, the function of cellular garbage collection mechanisms restored to youthful levels in liver tissue, and so on. We live in an era of rapidly improving biotechnology - and it is delivering the goods, in the laboratory at least.
But there is one common theme to all of these advances: none are undergoing further development for clinical use in healthy humans for the purpose of slowing or reversing degenerative aging, and thereby extending healthy life span. Why is this? You would imagine, given the size of the market for medicine, that a hundred start-up biotech companies would be leaping upon these opportunities, giving rise to an era in which "anti-aging" fakes and frauds finally start to fade away in favor of a market built upon true rejuvenation science. This is not happening, however, as there is a gargantuan roadblock that stands in the way.
The Nature of the Roadblock
In the US, where much of the research most directly relevant to engineered longevity takes place, this roadblock is called the FDA: the Food and Drug Administration. Appointed FDA bureaucrats have absolute control over the commercial deployment of medical technology in the US: only those technologies formally approved by the FDA can be sold for clinical use. Further, the FDA only approves a new medical technology for narrow usage in treating a specific, defined disease in a specific, defined way. Obtaining even this narrow approval is a staggeringly expensive process. For one, that list of diseases changes only very slowly, and an entire industry of lobbyists exists solely to try to add new medical conditions to that list - burning money that would better used for research and development.
Consider sarcopenia, for example, the characteristic age-related loss of muscle mass and strength. Sarcopenia was first named as a distinct condition a decade ago or so, and expensive efforts have been ongoing for some years to convince the FDA to add it to the approved list of diseases. There seems little prospect of this happening any time soon, however, and so the lobbying efforts continue. There are potential therapies for sarcopenia, or at the least the scientific basis for potential therapies that might prove useful in humans, but little to no private funding to further develop these leads - as there is no market on which to sell any resulting treatments. Even if a storybook industrial philanthropist turned up tomorrow to devote his entire net worth to pushing through development of a therapy for sarcopenia, it would still be illegal to offer the resulting medical technology for human use in the US.
Aging itself as a medical condition is in the same boat. Aging is not a disease, per the FDA - and therefore no-one is legally permitted to treat aging in humans with biotechnology in the US. The present state of the lobbying game, as illustrated by the situation for sarcopenia, is that it will take years and millions of dollars in to carve off one tiny component of aging and have FDA bureaucrats grudgingly allow commercial development to proceed. Thus what comparatively little development of longevity science does take place - such as work on sirtuins and other possible calorie restriction mimetics - sees applications of the underlying research shoehorned into treatments for late-stage diseases of aging, whether it fits or not. Even if successful the resulting therapies will not be legally available for use by healthy or younger people for the purposes of treating aging itself.
The Mirage of Reform
Numerous organizations and advocates (such as FasterCures, for example) have been trying for years to reform the FDA, or at least make it less obstructionist - to try to make it possible for new therapies to emerge without the stifling costs in years and hundreds of millions of dollars, or to emerge at all where they are not recognized by the FDA. These initiatives are all failing: over the course of time that they have been active, and despite the funds and efforts poured into them, the FDA has only become worse, approving fewer and fewer new technologies, and continually raising the bar and the cost for approval. The fundamental incentives that shape the actions of FDA political appointees are these: they suffer very few problems due to medical technologies that are suppressed or denied approval, but take a great risk to their career in approving any new application of medicine or biotechnology. The rest of this undesirable state of affairs unfolds from that basis - bureaucrats will follow their incentives, regardless of the harm it causes.
Meanwhile, the years pass, funds are consumed by political processes rather than being spent on actual research, and we're all getting older - our bodies slowly sabotaged by the processes of aging.
All in all, working with the FDA is not a game that we win by playing. A system so entrenched and badly broken cannot be reformed through existing channels, and efforts to change it by playing within the rules do little but provide the FDA with additional legitimacy. The only way to win here is to refuse to play the game, and take an entirely different approach - which brings us back to Open Cures, which is exactly that: an entirely different approach to the roadblocks put in the path of development by the FDA and its counterparts in other highly regulated countries.
The Rise of Medical Tourism
I'll restate the primary challenge: that it is illegal to commercially offer medical treatments for aging in the US, and based on the lack of progress in effecting change to date, this situation will persist for the foreseeable future - regardless of how much money and effort is expended on lobbying within the system. In turn, that the clinical application of longevity science is forbidden means that there is little to no investment available to develop laboratory demonstrations into therapies. Thus the most promising and advanced biotechnologies shown to extend life or reverse specific biochemical aspects of aging in mice languish unexplored and undeveloped.
Yet if we look beyond America and Europe, we see regions in which clinical development of therapies based on cutting edge science is both possible and less restricted. To pick one example, stem cell therapies that will not be commercially available in the US for years yet have been offered for a number of years by responsible, skilled groups in China, Vietnam, Thailand, and other countries. You might look at Beike Biotech or Vescell, for example. It should make American citizens of a certain age sad that China has become an example of freedom outshining the US in any field of endeavor - not sad for the Chinese, but sad for what has become of medical development in America.
This is a shrinking world we live in. Air fares are cheap, tourism growing, and the internet links together cultures, movements, and businesses ever more efficiently with each passing year. When the cost of travel is low compared to the cost of newly available medical technologies, we see the growth of medical tourism. Clinical development will occur wherever capable institutions exist and local law permits it, and patients will travel from restricted regions like the US to receive treatments that are not available at home.
Medical tourism is a growing business in the US precisely because forbidding and regulating medical development is also a growth concern: medicine is only expensive and unavailable because bureaucrats make it that way. Medical tourism is still a comparatively young industry, however, feeling its way and largely focused on a few major and well-known fields of medicine (such as the early therapeutic uses of stem cell transplants). It is far from the case that people are taking advantage of the full range of cost-savings and possibilities, and this is due in part to all the standard challenges inherent in establishing important business relationships across a great distance.
When you stop to think about it, however, you'll notice that all of these problems are well solved for traditional tourism - even where comparatively large sums of money are involved, such as in the much maligned timeshare business. People comfortably travel great distances and expect to rely on critical services at their destination: this works because intricate, long-standing industries of communication, organization, and education make that possible. It will one day be the same when people routinely travel to obtain medical services from far removed locations.
Now consider this: there is no technical barrier to, for example, clinical development of a way to replace all damaged mitochondrial DNA in humans - the basic technology has existed, demonstrated in mice, for six years. The work is published, fairly well known in the small part of the field where it matters, and were it made into a therapy there would be tens of thousands lining up to pay for it. Yet in countries where it is both possible and legal to move ahead with that commercial development, and where there is already an established, albeit nascent, medical tourism industry, that development has not yet happened. Why is this?
A Material Role for Open Biotechnology Movements
When it comes to the passage of information, we do not live in a frictionless world. Scientists and medical development groups in widely separated regions do not in fact necessarily have good insight into the work of their far-removed peers, or even know that the work exists in the first place. They are separated by distance, culture, and language - far less so than in the past, thanks to the internet, but separated nonetheless.
The effects this has on a given field of research and development are a matter of degree: smaller fields are more affected than the larger ones, as more researchers, more funding, and more public interest means more transmission of information. Aging research and longevity science is not a very large field, as it happens, at least not in comparison to stem cell medicine or cancer research - and you can see the difference that makes in cooperation and organization across national boundaries in the resulting levels of medical tourism. The relationships for development and transmission of knowledge that exist for stem cell research, to pick one example, dwarf those developed for longevity research. Thus you don't see clinical projects outside the US and Europe that are analogous in scope and ambition to those that presently take place in the field of stem cell medicine.
But all is not doom and gloom: I do not expect the gaps in the transmission of knowledge to last. Institutions and cultural forces will arise to close these communication gaps, and they will arise from present-day open biotechnology movements. These movements are still young and small, but very similar in aims and ethos to the open software engineering cultures that first formed in the 1970s in the US: information and designs are freely shared, there is an emphasis on moving the ability to produce significant products out of the ivory tower and large institutions, and the result is a massive body of work that greatly lowers the barriers to entry for hobbyists and professionals alike. Software development, once an arcane art practiced only within large organizations and universities, became possible as a garage industry, and then as a hobbyist activity - which in time gave rise to a vast breadth of knowledge and practice, a staggering pace of innovation, and a community of developers that has grown in size and sophistication by leaps and bounds.
The last 40 years in the culture of developing software is a snapshot that will be repeated for the next 40 years in the development of biotechnology. Costs of equipment and processes will fall, garage developers and hobbyists will come to greatly outnumber institutional professionals, and the pace of innovation will accelerate dramatically. On the way to that end result, open biotechnology movements (such as the DIYbio groups) will play an important role in bridging the communication gaps that exist between life science professionals and clinical developers in different parts of the world.
How will this happen? Consider that in software development today, there are no secrets and no specialty so small that it doesn't have a hundred skilled observers in the broader open community - watching, talking, and tinkering on their own time. When an important new advance arrives, it will be echoed around the world, dissected, analyzed, and evaluated. The best new strategies rise to the top very rapidly indeed exactly because the community is very large. Unfortunately, this state of affairs is not yet realized for biotechnology and the life sciences, but that is only because the open community of demi-professionals and hobbyists is still comparatively small. It won't remain small for many more years, however, and as the community grows, it will become increasingly unlikely that any promising biotechnologies will remain buried in scientific papers, undeveloped.
So in short, it is my conjecture that the present scientific demonstrations that might possibly be applied to extend life or reverse aspects of aging in healthy humans go undeveloped because they haven't been brought out into the open by a community of thousands: they haven't been discussed, picked over, buffed up, and presented far and wide in overseas regions where provision of clinical therapies for aging is not illegal. This process would happen as a matter of course given a much larger open development community associated with the biotechnology industry, but until that community arrives, a helping hand is needed.
Information and Relationships: the Role of Open Cures
And here we come to the point of the exercise: the reason for Open Cures. The high-level goal of the Open Cures initiative is to produce the communication, examination of research, and relationship building in longevity science that would naturally emerge from a larger open biotechnology community - but which is nowhere in evidence today, and will not arrive on its own for a long time yet.
The foundational items on the Open Cures to-do list are as follows:
- Establish a repository of how-to documentation for longevity-enhancing biotechnologies demonstrated on mice in the lab, with sufficient detail and explanation to make it comprehensible and useful for garage biotech groups, DIYbio practictioners, and overseas developers.
- Establish a network of relationships with the open biotechnology community, overseas developers, and the movers and shakers who are building the medical tourism industry rooted in the US.
That might not seem like much, but we stand at a fulcrum point in the growth of three large movements: regulation of medicine, medical tourism, and open biotechnology, all driven in their changes by accelerating technological progress in computing and biotechnology. The initial Open Cures projects are a lever for that fulcrum, a foundation for the construction of lasting bridges between researchers who discover and demonstrate the biotechnologies of engineered longevity and overseas development groups who can translate that science into new medicine for clinical use.
The bottom line is that the groundwork for a range of potentially life-extending therapies exists already, and the development groups legally able and capable of turning this science into therapies exist already: something must be done to bring these two sides together, and ensure that they build further ties for future development. If this were a better world, therapies built upon replacement of mitochondrial DNA would already be emerging, today, for example - there is no technical reason why that could not have been the case. That this has not happened is a challenge of people and organization: regulation, relationships, fundraising, the transmission of knowledge and experience.
My vision for the future of Open Cures is a long-term process of growth in establishing a self-sustaining community around the process of rescuing longevity science from its current fate: discovered and published, yet unheralded and undeveloped for use. This is analogous to the long-term vision of the SENS Foundation, which is as much about the development of a culture and community of longevity research as it is about the development of true rejuvenation biotechnology capable of repairing the biochemical damage of aging. When the scientific research of SENS is complete in its first phase, perhaps twenty years from now, we want to be living in a world in which potential biotechnologies of longevity are routinely and eagerly developed into clinical applications, no matter where they were initially researched, and no matter what destructive games the regulators and bureaucrats have found to play.
Making this happen is as much a project as researching the technologies in the first place, and just as necessary: it is also a project that we can all help with, even those of us who are not and never will be life scientists. So take a look at Open Cures, and consider how you might be able to help make the future a better place for progress in medical science and longer, healthier lives.
Longevity Science Needs Documentation
We all express the symptoms of a fatal, inherited degenerative condition called aging-or so the joke goes. It's a dark joke, but there's truth to be found in it, as is often the case in black humor. Unfortunately, all too few people think of themselves as patients suffering aging, and fewer still would call themselves patient advocates, agitating for research leading towards therapies and cures for aging. This is a sorry state of affairs: given that our time is limited and ticking away, the tasks upon the table should always include some consideration of aging. What can we do about it? How can we engineer a research community, funding and support to make real progress within our lifetimes? If you don't spend at least some of your time on this issue, then you're fiddling while Rome burns. Time is the most precious thing we have, and we live on the cusp of technologies that will allow us to gain more of it-but those advances in medicine won't happen soon enough unless we work at it.
Working on progress in longevity science doesn't have to mean working in a laboratory. Much of what I have done to help matters along takes the form of written advocacy at Fight Aging! and elsewhere: sharing events, passing on news, putting scientific publications in context, explaining where we stand in research and development, encouraging fundraising, and so on. In effect this is a sort of loose documentation of the existence of the community of people interested in engineered longevity, and a way to provide direction and grounding to newcomers: how to become involved, how to benefit from becoming involved, and how to help advance the science of human longevity.
My latest effort, the volunteer initiative Open Cures, is more explicitly a documentation project in its early stages: an effort to clearly and extensively document the range of longevity-enhancing biotechnologies demonstrated in the laboratory over the past decade. A body of documentation is a necessary foundation for later phases of the Open Cures roadmap, but will also help broaden the community of people who are both aware of this work and understand what it might be used to achieve.
Not everyone agrees that this is useful, however. One of the challenging attitudes I've encountered of late is the idea that documentation of longevity science in this manner is largely worthless-that time and funds spent trying to make science clear to developers and laypeople should go towards other, more direct activities like further research. This sort of criticism is, I think, symptomatic of a failure to understand the necessary role of documentation in the broader scope of technological progress. This article, then, is an answer of sorts: what is the role of documentation, and why is it important enough to need dedicated organizations that do it well?
The Challenge of Complex Ideas
Most important topics relating to the future of advanced technological development are very complex: engineered human longevity, strong artificial intelligence, molecular manufacturing, and so forth. Even the general concepts (such as "why is this important?", "why is this plausible?", or "why should I support it?") are made up of many moving parts and conditional arguments that the broader public generally hasn't heard or thought about yet. Thus we advocates can't just jump in and start persuading people that life extension is a great idea: instead, when it comes time to try to explain why this goal is important-and how best to proceed with research and development-we must first walk through a whole squadron of supporting concepts that are unfamiliar to the audience. Each must be explained, and only then can they be assembled into the final persuasive conclusion.
In the area of healthy life extension and biotechnologies to repair aging, an array of foundational ideas might include the following:
- This is a time of radical progress in biotechnology, far more so than even just a decade ago
- Scientists can extend life in a score of different ways in laboratory animals
- But you don't see the results of this work in the clinic because the FDA is needlessly obstructive
- Aging is just damage, and that damage is well enough understood for work on practical repair biotechnologies to proceed
- A large-scale research program could plausibly produce decades of life extension by 2040
- Any effective longevity therapy will give people more time of life and health to wait for even better new therapies
- Overpopulation is a myth, and longer lives won't greatly increase population in any case
- Ethical objections to engineered longevity are all weak in comparison to the massive and ongoing harm caused by aging
Each of these is no small thing in and of itself, and worthy of longer treatment. So presenting all of the concepts that lead up to thinking about rejuvenation biotechnologies is time-consuming, hard to do well, and requires a willing and interested audience. Unfortunately few people in the broader public are in fact willing put in the effort to follow you, me, or anyone else with a complicated idea all the way from square one to the end point. That takes time and attention-both of which are precious commodities, hard to obtain at the best of times. Thus the ideas that do gain traction in our culture are those that can be successfully communicated in a short period of time, because they build directly upon what is already known.
The Example of Hotmail
The recent past provides many good examples of ideas that could be quickly communicated to the public at large, and as a result rapidly gained interest and support. Hotmail is one such example: when the company was founded in 1996, it was the first service to offer email over the web. The founders were petrified that they would be beaten to the punch because the idea was absolutely obvious in hindsight: take email, take websites, and merge the two. Anyone in the internet-using world could easily grasp that concept, and the service took off like wildfire when it launched.
But let's stop to think about that for a moment. Both email and the way in which most people experience the web are in and of themselves very complicated concepts. Imagine that some visionary fellow gave you the task of explaining to the public an email service used via a web site in 1970: you would be right back to having to explain many foundational, unfamiliar concepts to an audience unwilling to give you sufficient time and attention. What is a network? How do ordinary people connect to or even use a network? What is a web browser? How does an ecosystem of websites and hosting services arise? Why would I need email, or some sort of patchwork visual information service? And so forth.
Nonetheless, in 1996 Hotmail was an idea that could be conveyed and understood in a single sentence. "Email via a website." When we consider this and other similar examples, we see that there must be an ongoing process by which complex, unfamiliar, and challenging ideas become simple, familiar, and easily communicated ideas.
Layers of Knowledge, Attention, and Expertise
You might envisage the broad field of longevity science as a series of concentric circles. The innermost circle is made up of a small number of people who pay a great deal of attention to the field, and who possess the most knowledge and expertise: researchers who work on cutting edge science, for example. The outermost circle consists of a large number of people who pay just a little attention to the field, and who possess the least knowledge and expertise-such as casual advocates and interested members of the public. The progression of circles from innermost to outermost reflects an increasing number of people, but lesser expertise and attention. I'd loosely categorize the circles from inner to outer as follows:
- Cutting edge researchers
- Other researchers, postgraduates, and scientists in related fields
- Dedicated patient advocates
- Medical technology developers, funding sources
- Physicians, clinicians and medical technicians
- Interested members of the public
In this model of human endeavor, knowledge flows outward while funds and newly participating members of the community flow inward-or at least, that is the ideal. In practice, managing this flow of knowledge is a big and thorny problem: many of the most important movements in technology over the last few decades have focused on how to best move knowledge from inner circles to outer circles. Consider the open science movements, fights over closed journal business models, and the many efforts to try to adopt open source practices in the scientific community, to consider but a few examples.
Let me advance a definition for the purposes of this article: documentation is the name given to explanations and tutorials produced by the members of one circle that are intended for the next outermost circle. For example, review papers written by scientists present an overview of progress in one area of research rather than new data or results. These review papers are a form of documentation for the next outermost circle of researchers-scientists in other fields, or postgraduates, or other academics with less experience in the topic at hand.
To take another example, what I do at Fight Aging! is a form of documentation by this definition: ongoing efforts to explain the ins and outs of longevity science to people who are less familiar with the field, and who have less time to devote to understanding the work of researchers. Academic publicity services at the major universities also perform a similar task, producing explanations for the outer circles of doctors, interested members of the public, and the like.
Documentation thus moves raggedly and through many hands, as each circle learns from the inward circles and then in turn explains its knowledge, understanding, and work to the outer circles. That there are so many layers involved goes a long way towards explaining how science so often becomes garbled and misinterpreted on the way from researchers to the interested public. The process works over time, however, as the example of Hotmail well illustrates. The level of knowledge in the outer circles does increase, and the efforts of people involved in producing documentation make it easier for new ideas to gain traction.
Researchers, Like Most Communities, Document Poorly and Reluctantly
Anyone who spends time working in a technical field eventually forms a cynical attitude towards documentation: it is never what it might be, and the next innermost circle never does a good enough job of explaining themselves. This is simply the way of the world: most people in a given circle spend the majority of their time and effort in communicating with each other, not with the members of the next outermost circle. In the sciences, researchers write papers for one another as a part of the business of research, and this publishing of results is not intended to educate anyone other than peers at a similar level of expertise in the same field.
The process of producing documentation for outer circles is nonetheless very important, despite being undertaken by only a minority in any field. It is only through documentation that there can exist a roadway of information to connect researchers who produce new science with developers who build clinical applications of that science. If documentation is lacking, then so is the pace of development: developers work on what they know, what can be understood, and what can be sold to their investors. Ultimately, that knowledge must come from efforts made by researchers to explain their work.
Across the years I've spent following work on longevity-related research as an interested observer, I've seen a score of techniques demonstrated to significantly extend healthy life in mice, or reverse a narrowly specific manifestation of the damage of aging. Many of these results are languishing undeveloped, as the FDA forbids clinical application of biotechnologies for the treatment of aging. There is little writing on these research results, and no good sources other than the original papers-most of which are behind journal paywalls. What hope is there for the proper transmission of knowledge to the circle of clinical developers when the researchers have no incentive to explain their work, due to the FDA roadblock, and no other group seems to be picking up the slack? Potentially viable medical technologies are lying fallow, buried in the output of the scientific community, and left unexplained for the rest of us.
The Solution: Produce Documentation to Take up the Slack
Addressing the challenges of documentation and transmission of knowledge is an area in where a volunteer organization like Open Cures can make a real difference to the future of longevity science-and for a comparatively small amount of effort and money.
The flow of knowledge from the research community is vital, but as described above there exists a clearly identifiable gap in that process: science that might lead to therapies for aging exists in many different forms, but there is little to no documentation of it. Thus there is little in the way of a roadway to systematically bring this knowledge out to the circles of life science students, entrepreneurs, clinical developers, and other interested parties. Those groups, in turn, have nothing to work with when it comes to educating the medical community and public at large. This, in a nutshell, is the problem. The US may be closed to development of longevity-enhancing biotechnologies by regulatory fiat, but much of the rest of the developed world remains open for business in this field-if the developers in those countries knew more about the work that has taken place and presently lies largely buried.
The irony of the situation is that documentation isn't expensive in the grand scheme of things, and certainly not in comparison to scientific research or clinical development. It doesn't require more than a few weeks of part-time work for a life scientist, a graphic artist, and an editor to produce a long document that explains exactly how to replicate a demonstrated research result in longevity science-a way to extend life in mice, for example. That document will explain the research in plain English, at length, and in a way clearly comprehensible to people who are not cutting edge scientists: exactly what is needed open the door to a far wider audience for that research.
So in conclusion, documentation is important: it's not just words, but rather a vital structural flow of information from one part of the larger community to another, necessary to sustain progress in any complex field. We would all do well to remember this-and to see that building this documentation is an activity in which we can all pitch in to help.