The Scientific Institution is Biased Against Shortcuts to the Production of Practical Technology

Technology is the application of scientific knowledge. The scientific culture and scientific process as it is practiced today embodies a strong bias against any sort of shortcut towards the production of technology, however. If it seems plausible at a lesser level of understanding of a system that you could achieve some beneficial application, then the peer pressure in the scientific community is always to hold off and work instead towards a full understanding. This situation is not uncommon in medicine: many discoveries are serendipitous, but to try to turn demonstrated positive results in the laboratory into positive results in the clinic will be opposed at every turn until the underlying mechanisms can be fully explained.

The bias against action and towards understanding as the primary goal is baked into every level of the research establishment and surrounding institutions. The scientific method has researchers moving eternally towards greater understanding. It has nothing to say about what you do with that understanding, however. Application to produce technology is where you step from the Platonic ideal and into the messy real work of engineering: the art of creating meaningful solutions in the absence of full understanding. This boundary between knowledge and technology produces all sorts of cultural friction, and I think it is fair to say that scientists who depart to be engineers are not treated as well as they might be by their former peers. There is little disapproval in the world quite like that of pure scientists directed towards one of their own who steps away to start a technology business.

At root there are very good reasons for this bias: the scientific method is required for progress, yet it is constantly under attack from opportunists and fallible human nature: wishful thinking, the desire to find progress where there is none, the desire for short-term gain over long-term gain, and so forth. If shortcuts are not treated as heresy, then there will be all too many research programs led astray, and development predicated on false results, and in the worst cases outright fraud. This happens even with the scientific culture of disapproval, but far less so than it otherwise might.

While the core of the scientific method is centuries old, to some degree this strong bias against early attempts at practical application is a phenomenon of modern times. In the institution of medical research everything that moves beyond early stage exploration must be explicable to the standards of the day, but matters were not always so rigorous. There any number of grandfathered treatments available today that are not sufficiently well understood at the level of molecular biology to get into clinical trials if they were discovered today. Regulation as it stands today in the US states that you shall only treat named conditions, and you shall present a full understanding of how you are doing it. Since everything else is actually outright forbidden, you end up with a situation in which all funding and effort - even back down the chain to supposedly unconnected free-ranging fundamental research - is focused on the molecular biology of late stage disease and the proximate causes thereof. For most researchers that's the only work with a future if you want to contribute to something that might actually end up approved for clinical use.

So these influential edifices of thought, and all the funding that is influenced by them, say that any approach in research that specifically aims to circumvent our lack of knowledge in some areas is simply Not The Done Thing. Yet there are many lines of research in which it is clearly plausible that great benefits could be derived by doing just this, and - as currently constructed - the walls that the scientific institution is forced to erect for its own defense exclude all of this good, solid work that might lead to better therapies. As one example you might look at leukocyte/granulocyte transfer therapies for cancer. These came to prominence on the basis of very promising results in animal studies, but have not seen significantly funding or much work on human studies precisely because researchers cannot yet present a full accounting of how these treatments work. Without that, you won't see much movement.

In this context we of course come to the Strategies for Engineered Negligible Senescence (SENS). This is not just a proposal for the shortest path to the best results when treating aging, a research plan to create rejuvenation in the old and prevent all age-related frailty and disease, it is also a critique of the scientific community and its way of doing business. The present system is broken by virtue of the fact that its members have gone too far in building defenses against failure modes in the scientific method. They now systematically marginalize useful endeavors aimed at the production of meaningful results in absence of complete knowledge of the biological systems involved. Application of partial knowledge can be good engineering, and is viable, necessary, and needed in medicine, where every delay costs lives. The past shows that the engineering approach can be perfectly workable, as many drugs in use today were brought into use through exactly this sort of methodology, and their full mechanisms are in fact still not understood.

Still, the mainstream of the aging research community will continue to spend billions on efforts that have no greater expectation of practical utility than the sirtuin research of the past decade. They are working towards a full understanding of the overlap of metabolism and aging as a primary objective. This in and of itself is a fine thing if knowledge is the desired end result, but I object to its presentation as a sensible path toward therapies to extend healthy life to any significant degree in the near future. This is just not plausible for the drug development approach to altering metabolism: the best that might be done here in the next couple of decades is to gently slow the progress of aging. Researchers involved tend to think that adding five years of healthy life by 2030 is an ambitious goal. If that five years is all that happens, and when it does it certainly won't be five years for those people already old when treatments arrive, then what a waste of opportunity that would be.

No, we want to see work on rejuvenation, on ways to reverse aging by repairing its causes - work after the SENS model that has a clear plan to produce results in absence of a full understanding of metabolism throughout aging. What is needed is a comprehensive list of damage that distinguishes old tissues from young tissues. This exists, and given this list there is no great need to fully understand how the damage interacts and progresses in intricate detail: researchers just need to periodically repair it. In this environment drawing more researchers to work on SENS repair biotechnologies is a bootstrapping process of attention and funding and results, just like the disruption of any industry by new technologies and new approaches. Things like clearance of senescent cells seem like one of the areas of research that will eventually get grudging attention by virtue of the fact that it will work far more effectively than anything the mainstream is producing with their drugs and their messing with the operation of metabolism in the late stages of disease. If you are trying to make a damaged engine work slightly better when damaged, rather than trying to address the damage itself, why would you expect good results?

The replacement of the present mainstream culture of aging research by SENS-like research focused on periodic repair of the causes of aging to achieve rejuvenation will proceed gradually and through the demonstration of effectiveness. There is a lot of of replacing to be done, however. It's a long road yet, and conservative institutions will continue to support work that does nothing but add knowledge of the fine details of metabolism long after rejuvenation research is much more of a going concern, I'd imagine. Groups like Google's Calico venture do not fund SENS because they are run by exemplars of the current institutions of medical science, who have worked their entire careers in the world of full knowledge as a requirement and where the primary strategy is a struggle to alter metabolism in the late stages of age-related disease, people who live and breath the drug pipeline and FDA dictates. Why should it be any surprise that what they are going to do is simply a continuation of existing programs of aging research? Calico will fund SENS at the same time that other institutions of the mainstream are doing so as a matter of course, which is to say when the disruption has come full circle and when people talk about aging research they usually mean the SENS approach of repair of primary causes.

Comments

Bravo Reason - this really needs to be said and talked about more. I keep wondering whether in medicine today "First, do no harm" is becoming "First, do nothing."

Posted by: Mark Bruce at January 7th, 2015 8:35 PM

Is the SENS foundation guilty of this bias against shortcuts too?

Moderna Therapeutics was handed another $450 million of venture capital money yesterday to keep developing their mRNA as a therapeutic technology. I was wondering why the SENS foundation doesn't just order mRNA (with the Mitochondria surface targeting introns and exons) for all 13 protein encoding mitochondrial genes, and treat 60 or so mice over two years with an injected cocktail of this, then examine the muscle fibres for evidence of cells using alternative oxidation pathways.

Yes if it doesn't work this experiment won't tell you where it went wrong. But if it does work it would be a powerful in-vivo demonstration that mitochondrial DNA damage is a cause of aging. There may also be some lifespan and healthspan benefits in the mice.

Posted by: Jim at January 7th, 2015 9:25 PM

"Researchers involved tend to think that adding five years of healthy life by 2030 is an ambitious goal."

Actually, life expentancy is currently growing by around 2.5 years per decade (at least here in Spain, but probably also in the rest of the developed world).

Posted by: Antonio at January 8th, 2015 1:45 AM

@Reason: Ah, ok, healthy life extension but not total life extension.

Posted by: Antonio at January 8th, 2015 7:20 AM

Let as a paradigm be neural nets in programming. Neural nets are essentially black boxes: you educated them using multiple examples, and they return positive results, but there is no theory or algorithm visible to base their judgement on, except that they work well. Frankly, most people don't understand how most technology works anyway - to say it is magic to them is not far off the mark.

Posted by: Brad Arnold at January 8th, 2015 11:51 PM

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