An interesting exchange of views on longevity research is taking place on the GRG mailing list, as I noted when I posted some of Robert Bradbury's thoughts on the matter a few days ago.

Derya Unatmaz is the researcher behind the Biosingularity blog, and a good illustration of the younger generation of scientists: optimistic, realistic and thoughtful on the topic of longevity research and healthy life extension. You might recall that Unatmaz was interviewed by Attila Chordash of Pimm earlier this year:

I am going to be blunt and say that it is nonsense that we have to make an argument for life! ... Treating or controlling indefinitely all chronic deadly human diseases should be achievable within the next 25-30 years ... I anticipate continuous body regeneration soon after that within the next 40 years.

Here is a mail to the GRG list from Unatmaz, reproduced with permission:

I fully agree that there is no biological reason why human life can not be extended indefinitely and at some point in future (hopefully near one) in my opinion it is almost a certainty this will be achieved.

The point that I disagree with (if I understood correctly) is that the current biological research somehow can be directed, made less wasteful and if the money were to be spent "wisely" we can then achieve the above goal much quicker.

Research by its nature, especially in biological sciences because of enormous complexity, is very wasteful. This is simply because we have not yet identified all the components of the system we are studying, let alone have the capability to put it together from it's individual pieces. I think this is a common mistake made, especially by non-biologists, that the scientists working on biological systems can be more efficient by working on the right solutions and if there was a top down approach on defining the areas to research then we can figure out the solution to aging pretty quickly. This far far from the reality.

It is true that having more money available is critical and advances surely will move much quicker with more funding available, especially nowadays with declining federal support. However, amount of information generated reaches a plateau at some point no matter how much more money is available and you simply start to increase the waste to productive knowledge ratio. Why is that? Because we are still trying to figure out how the system works, and solving difficult problems depend on development of future technologies, which we don't really know where they will come from. There is also limited pool of talent that can work on these problems. For example, as Robert B. pointed out, we would have needed trillions of dollars to sequence all the genomes we have sequenced now if we attempted this just 15 years ago, that would not be the best way to spend your money. You have to let the technology mature and cost come down to reasonable levels before you can ramp up with such advance!

In addition, you simply cannot predict a priori where the major breakthroughs will come from. If they were so obvious, they wouldn't be breakthrough in the first place. Somebody makes a discovery studying fruit fly basic RNA regulation mechanism then that discovery just opens up a whole new frontier of technologies and capabilities (such as RNA interference). Somebody tries to understand how viruses work, then that allows ways to deliver genes into cells using viruses as hosts (retroviral vectors for gene therapy). I can go an with these examples ad nauseam.

My point is this: if you have a lot of money to spend and you want to make a difference in aging research, the best way is still the way NIH grant system works, i.e. distribute your money based on scientific merit to the best scientists and labs you can find who are working in related areas. Don't limit your focus narrowly, they could be working on yeast, worms, turtles, or humans, you or I simply don't know where the next discovery will come from and how it will impact human longevity.

You give out 100 grants to 100 scientists with million dollar each, if 10 of these generate a breakthrough that would be considered spectacular success in research. You can of course look at it as wasting 90-95% of your money, but that's the price you pay to make the major technological discoveries that will leapfrog us forward. What one has to be careful is not to spend too much on brute force approaches in areas where the technology is still not mature (as I gave the sequencing example above). Once you have cost effective ways to look at millions of parameters parallel, as information and other technologies co-advance, then it becomes highly cost effective way of discovery based science, where you look for things without preconceived hypothesis. That's risky science but the payoff can be very big. This can be a especially good area for private funding since even NIH grants are too much dependent on hypothesis and directed research.

Howard Hughes Institute is a great example. Only the best of the best scientists become HHMI investigators. They spend 300-400 million dollars a year, no strings attached, scientists decide what they want to do. In the end you have several breakthroughs every year from HHMI researchers that become the locomotive of biological research. Directed research decided especially by people who are not on the bench doing the science is a bad idea and a great way to waste your money, in my opinion. There is of course merit to highly focused and directed research and that is in development of already identified products. But then that's why we have a whole profit-driven industry for that.... my two cents.

As I see it, this is a perspective on the knowledge problem, but I think it conflates the following:

• an attribute fundamental to research: risk based on lack of specific knowledge
• issues of investment: risk of investing poorly based on having less knowledge of the field than those who work in it
• an attribute of central control of resources: the inability to plan

Scientific research is no more inherently risky or unplannable than starting a company; both are forms of research for those doing the work. Will business plan X work to bring in money; will understanding and intervening in biomechanism A help slow or repair aging. It's much the same thing - and so investment is just as open to planning, risk management and the setting of goals.

The real problem with massive expenditures on research that come from government - as opposed to massive expenditures on research that are sourced from private funds - is an utter lack of accountability for results at all levels of the process. Where there is no accountability, there are no real goals, and thus progress is incidental and slow - relying as it does on individual drive and goodwill rather than more pressing economic incentives.

This is another fundamental difference between the Strategies for Engineered Negligible Senescence and the mainstream of gerontology - for the most part, the mainstream relies on government funding, has not set goals, has no accountability for progress, and hence has no pressure to produce. You can throw as much money as you like into a system with no incentives, but you're not going to get much out it. The NIH is like NASA, or any other huge, unaccountable arm of government - a huge and wasteful sinkhole for resources and talent that could have been achieving great progress if held accountable for their work and inventivized to set a path towards definitive goals.

Technorati tags: aging, economics, gerontology, life extension, research

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