By Desmond J. Smith
April 11, 2013 | Guest Commentary | Some three decades ago, I was lucky enough to be elected to a research fellowship in molecular biology at Trinity College, Cambridge in the UK. My first (and only) social occasion in this role was to dine at High Table, in which the fellows enjoy their food in a magnificent 17th Century hall elevated on a dais above the students. Seated next to me was one Ian Glynn, a distinguished physiologist and now Professor Emeritus.
Trying to sound profound, I asked Professor Glynn in the dimly lit ambience what he thought was the most important problem confronting modern neuroscience. Glynn replied that we needed new technologies to record many neurons in parallel. It did not take much imagination to realize that what would be illuminatory with many neurons would be revelatory for the whole brain.
In April 2013, President Obama announced the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative. Although not spelled out in so many words, the main goal is to develop new technologies to record the activities of all neurons in the brain in parallel. We know this because several scientific magazine articles have revealed its history, which started with a select group of like-minded individuals who lobbied the government for ear-marked funding for their plan. The project is to be spearheaded by Cori Bargmann (Rockefeller) and William Newsome (Stanford), two Howard Hughes Medical Institute Investigators with impeccable research credentials.
Other scientists, however, are up in arms about the initiative. They argue that this is pork-barrel science, with special interest groups pushing their personal agenda with the lawmakers. Critics also say the project is premature. The technical platforms do not yet exist, and there are no strategies to ensure there would be useful insights from current technologies if innovations fail. Last but not least, there are no clear milestones to judge success or failure.
As is so typical of historical inference, both proponents and opponents of the BRAIN initiative use the Human Genome Project (HGP) to support their cause. Despite its eventual and undeniable success, there were many prominent critics of the HGP in its infancy. The HGP was seen by some as premature and unrealistic, a politically constructed boondoggle to further the careers of participating scientists while suffocating traditional principal investigator, hypothesis-driven research. (An amusing interactive poll at Wired.com convincingly shows just how similar the complaints about the two big biology projects are, even though separated by nearly 25 years.)
In retrospect, if genomic technologies had been allowed to mature, perhaps we could have had the sequences for a tenth of the cost with only minimal delay. Nevertheless, inspired by the spirit of the HGP, other large projects have been pursued. But whether the “Decade of the Brain,” the “War on Cancer,” the HAPMAP and ENCODE projects have provided much value for money remains unclear. Just as the unique triumph of World War II has been used to support other, more unfortunate adventures, perhaps the success of the HGP—leaving aside the somewhat dubious 140:1 economic benefit touted by the President—is an unreliable exemplar for subsequent projects.
North and South
On balance, I think it is difficult to argue against the long-term goals of the BRAIN Initiative. Hence, I tend towards support of the project, even with its manifold uncertainties. But without a more open evaluation process, how can we be certain that the money wouldn't be better spent on some equally worthy goal, such as curing dengue fever, constructing a DNA-based quantum computer or finding genes for humor? I don't know and neither do you, because other large scale proposals were not evaluated as part of an open and rational discussion. This opacity leads to twinges of professional jealousy and suspicion of careerism on both sides of the debate.
In fact, we can think of two career states: North Career and South Career. North Career is an isolated hermit state, reminiscent of the traditional scientist, while the South is gregarious and persuasive. To be successful in modern science, it is increasingly necessary to follow the South Career path.
But what are the end limits of unregulated lobbying efforts to advance pet projects? Simply put, rather than promoting the best science, politically connected and persuasive individuals will gain the greatest leverage for their own research. In conferences and meetings, we have all seen prominent scientists canvassing top NIH officials to promote their particular brand of science. It is forbidden for grant applicants to approach study section members about their proposals, and I am not sure why similar regulations could not apply to senior NIH officials. Indeed, I would like to propose the BRIAN (Balanced Research Investigation Advocacy Network) Initiative, which would allow competing large-scale investigative opportunities to be evaluated against each other by the funding agencies in transparent and collaborative fashion.
Architects like to say that no new buildings would ever be constructed if clients knew the real costs at the outset. The intense discussion over the BRAIN project may thus be a measure of its worth. After all, no truly innovative initiative could avoid such debate. As the BRAIN initiative commences, I lift a glass in honor of Professor Glynn and hope that this particular venture will indeed yield revelation and not obfuscation.
Desmond J. Smith is a Professor in the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA. He can be reached at: DSmith@mednet.ucla.edu