Thursday, August 29, 2013

Misguided choices? How the NIH decides to prioritize research areas is a strange and mysterious process.

This week’s SCIENCE magazine notes that the NIH is committing $17M to a program to evaluate the role of extracellular RNA (exRNA). Obviously a variety of RNA types including miRNA, siRNA, piRNA, lncRNAs as well as conventional messenger RNAs play key roles within mammalian cells. In certain lower organisms like nematodes there is good evidence for cell-to cell transfer of functional siRNA. However, in mammals the exRNA story is very muddy indeed. While cells shed various RNAs enclosed in membranous structures called exosomes, there is no evidence that this material has any function whatsoever (cells shed lots of stuff, most of which is just debris). So how did exRNA get to be a NIH funding priority? What will be the contribution to human health?

This is somewhat reminiscent of the recent commitment of $100M federal funds to the “Brain Activity Map’.  The initial energy and organization for this concept came from non-neuroscientists and from private groups such as the Kavli Foundation. So how did the BAM get to be an NIH priority? (

These episodes illustrate the byzantine process by which funding priorities are set at the NIH and presumably at other federal funding agencies. The usual process is that NIH staffers seek advice from certain scientists about future funding needs. The scientists consulted are often ones who have devoted a lot of time to service on NIH study sections (grant review groups) and who are therefore well known to the staffers. No doubt the consultants are good scientists, however they may not be representative of their fields and they certainly will have their own interests to pursue. It is well known in the academic community that the surest way to get a research grant is to be involved in writing the RFP (Request for Proposals) in that area. Thus funding priority decisions are made in a very murky and nontransparent manner somewhat similar to the old-style politics of ‘smoke filled rooms’.

Surely in this age of near instantaneous communication there must be a better way to set funding priorities. For example, why not let the NIH convene panels of experts in various areas and give them a day or so to make some initial recommendations for new areas to fund. The recommendations, as well as the names of the panel members, could be posted on the internet and the larger scientific community allowed to comment. At some point a decision would need to be made by NIH staff, but at least broader input would be achieved. Additionally, the entire scientific community, not just a few ‘insiders’, would know that an area of research was under consideration for increased funding. Its time for a little sunlight to penetrate the darkness of NIH prioritizations. 

Thursday, August 8, 2013

Ageing, Human Enhancement and the Economy: Work and Sex at 120.

Today’s NY Times published an opinion piece by the columnist Charles Blow that discussed the prospects for radical increases in human lifespan and possible implications for society (1). This was partly driven by the recent online publication of a report (2) from the Pew Foundation that surveyed American’s attitudes toward old age and the possible radical extension of life. Interestingly most people did not express interest in living much beyond 90 or so, what would be considered a ripe old age, but nothing exceptional.  In his article Mr. Blow briefly mentioned some of the economic, ethical and societal problems associated with advanced old age. Many of the on-line comments appended to the Blow article expressed concern about increasing the number of frail, sickly elderly people.
In my view this column and most of the comments have it all wrong. They visualize increasing numbers of decrepit elders acting as a drain on society. They fail to anticipate the accelerating wave of ‘human enhancement’ technology that will allow people to live far longer but also to be healthier, stronger and smarter in their advanced years than most middle-aged humans are today.  Gene therapy, stem cell technology, advanced neuropharmacology, physical and mental prostheses, all of these are converging to allow a re-engineering of the human organism.  Clearly there are key issues about who will be able to access these advances and what impact they will have on our economy and society. Will it be only the very rich or will many people be able to enjoy the benefits of human enhancement? What will be the effects on our economy and our social structures? By the way, the finding of the Pew Foundation that most people do not want to live much beyond current lifespans will likely go out the window as people start to see smart, vigorous, sexually active 120 year-olds!
To me the most worrisome prospect is that advances in human enhancement will be arriving on the scene just as another technological wave is cresting. Ever-smarter and more capable machines (think IBM’s Watson coupled with a very sophisticated robot) will be doing more and more of the work of the economy.  Thus we may see large numbers of very healthy, vigorous people who make no contribution to the production of goods or services. How will society deal with this?
These interesting themes regarding ageing, technology and the economy will be developed at length in future blogs on this site.

Tuesday, August 6, 2013

Scientific Reproducibility, Hype, and the Glut of Ph.D.s

There is an interesting conjunction of articles in this week’s NATURE.  One opinion piece from an idealistic young graduate student deplores that fact that scientists must promote their work as being medically, economically or socially relevant, to an extent verging on ‘hype’ (1). In the same issue a news feature reports that the NIH is considering verification rules for some of the research it supports partially because of many comments from the pharmaceutical industry that much academic research cannot be reproduced (2). Finally, the issue contains an obituary of the Nobel prize winning physicist Kenneth Wilson (3).

Here is what relates these three articles- two are examples and one a counter example of the consequences of the overexpansion of contemporary science. Scientists oversell the pragmatic ramifications of their work largely because funding agencies require them to do so. For example, all biomedical investigators must deal with the NIH requirement for explaining the ‘significance’ of projected research as well as with the agency’s current emphasis on ‘translational’ research.  Other funding entities in the US have similar stipulations and the situation may be even worse in Canada and the UK where there is increasing emphasis on the commercial ramifications of research. However, as has been shown by many historians of science, the greatest impacts often flow from unfettered basic research rather than from work intended to address specific medical or technical problems. The career of Prof. Wilson is a good example of this. After being hired by Cornell in 1963 he did not publish a paper until 1969. Then in 1971 he published theoretical work that revolutionized areas of physics ranging from sub-atomic particles to fluid mechanics, thus earning himself the Nobel. Today it is hard to imagine anyone lasting for six years in an academic position without multiple publications (preferably ‘translational’ ones!).

Delving further, why are the funding agencies so insistent on research that claims to have immediate pragmatic ‘significance’. The reason is that the agencies must drum up political support for their enormous budgets, and it’s much easier to sell a Senator or Congressman on curing say prostate cancer than on elucidating some obscure molecular interaction. While society should generously support fundamental scientific research, both for its own sake and for its long term practical benefits, the level of support must be ‘right-sized’ to the state of the economy and the level of development of science itself. If maintaining public support for science means a constant process of overselling its short-term payoff, then perhaps the bloated science establishment needs some trimming.

One of the major problems, however, is that universities have used the relatively generous science budgets of the last few decades to train an enormous cohort of Ph.D.s who now must struggle for research funding. The current rather obscene degree of ultra-competition drives investigators to publish results prematurely leading to increasing concerns about reproducibility. As discussed previously on this blog (4) curtailing the production of Ph.D.s would be immensely helpful in obtaining the right balance between reasonable levels of publically supported science funding and the size of the scientific work force. Fewer, better quality Ph.D.s may actually produce a greater amount of high quality science than hordes of ill-trained Ph.D.s, many from 3rd rate institutions.