Saturday, January 25, 2014

Why support curiosity driven basic research?

A colleague, recently starting as an assistant professor, with a new laboratory and bright young graduate students, seemed unusually stressed.  I pried, guessing that in the month of January the well of worry for most biomedical scientists is the looming deadline for submission of grant proposals to the National Institutes of Health.  With exacerbation, he said: “The funding line is now less than 10%.  How do I keep my lab open?” 

These days this is a common question, even in elite universities.  Each year tens of thousands biomedical scientists send in a new R01 proposal to the NIH, competing for that small piece of the US budget that has been set aside to fund ‘curiosity-driven’ basic research --- research conducted by independent, often single investigators.  These proposals represent a most remarkable channel for which a small portion of the US budget is allocated: the government allows scientists with a laboratory that houses often only a few students to describe their idea, and then have the peers of those scientists evaluate these ideas and rank them, funding the top 10% or so. 

In contrast to this curiosity-driven basic research is the ‘mission-driven’ research that the government funds, focusing on themes like the Human Genome Project, or the Brain Mapping Project, organized efforts to answer a specific question.  My young friend was facing the existential struggle that is faced by all small, independent laboratories: to research their own questions, rather than the ones that the government dictates.  This struggle has a surprisingly long history.

The day after the bomb

On Tuesday, August 7, 1945, the New York Times printed in giant letters: First atomic bomb dropped on Japan.  Below the headline were reports on speeches made by Truman and Churchill: “New age ushered”, and the report that when the bomb was first tested, it had vaporized a steel tower in the New Mexico desert.  [A small advertisement on page 2 touted a Manhattan bar that had just installed air conditioning, providing a cool relief from the hot NY summer.]

But deep inside the newspaper, in the editorial section, there was a paragraph that more than any other foretold the struggle that was coming.  Not the struggle for liberty and the war against dictators and despots, but the struggle for funding of basic science in the United States.

In its editorial section, the NY Times used the success of the Manhattan project to exemplify the merits of organized, mission-driven research “after the manner of industrial laboratories.”  It used the success of the bomb to lambast university professors that held that “fundamental research is based on curiosity”.  It concluded that the path forward was for the government to state the problem, and then solve it by “team work, by planning, by competent direction and not by a mere desire to satisfy curiosity.”  

The Manhattan project set a shining example.  Why not do the same for other important problems?  Why not a Manhattan project to cure heart disease, or Parkinson’s disease?

The struggle to fund curiosity driven research

Just two weeks before the bomb was exploded a report first commissioned by President Roosevelt but with his untimely death, now sent to President Truman, had expressed a different view, one that championed curiosity driven research.  In that July 1945 report, titled Science, The Endless Frontier, Vannevar Bush had written: “Basic science is performed without thought of practical ends, and basic research is the pacemaker of technological improvement.”

Vannevar Bush, Dean of engineering at MIT from 1932-38, convinced President Roosevelt to form the National Defense Research Committee to coordinate scientific research for national defense, which he served as chairman.  By 1941, NDRC became part of Office of Scientific Research and Development, which coordinated the Manhattan Project.  OSRD, under Bush’s directorship, did something revolutionary: scientists were allowed to be ‘chief investigators’ on projects related to the war effort.  Rather than working in a national lab, or being employed by the government, they would stay at their universities, assemble their own staff, use their own laboratories, and then make periodic reports to committees at OSRD.  James Conant, a member of one of these committees, would later write: “Bush’s invention insured that a great portion of the research on weapons would be carried out by men who were neither civil servants of the federal government nor soldiers.”   This idea fundamentally changed research in the US, de-centralizing it, moving it away from industrial and government labs, and placing it at universities.

In 1944, as the war in Europe neared its end, Bush was called into Roosevelt’s office and there, the President asked him: “What’s going to happen to science after the war?” Bush replied: “It’s going to fall flat on its face.” The President replied: “What are we going to do about it?” 

In November 1944, this question was put down formally in a letter from Roosevelt to Bush and OSRD.  The letter asked four questions: 1) How would the US make its scientific achievements of the war years “known to the world” in order to “stimulate new enterprises, provide jobs, … and make possible great strides for the improvement of the national well-being”? 2) How would medical research be encouraged? 3)How could the government aid private and public research, and how should the two be interrelated? and 4) How could the government discover and develop the talent for scientific research in America’s youth?

Bush believed that advances in fundamental science had paid off spectacularly, resulting in new weapons and new medicines.  “[He] believed that you had to stockpile basic knowledge that could be called upon ultimately for its practical applications, and that without basic knowledge, truly new technologies were unlikely to emerge.”

Bush’s ideas took hold, eventually leading to establishment of the National Science Foundation and the NIH, and the current mechanisms that fund basic science in the US.  But the question persisted: should scientists be allowed to define their own questions in basic science, or should the government organize them into teams that go after mission-driven problems?

From pond scum to the human brain

In 1979, in a Scientific American article, Francis Crick (co-discoverer of DNA) suggested that a fundamental problem in brain sciences was to control a single neuron.  He speculated that if single neurons could be controlled, particularly in the mammalian brain, a critical barrier would be crossed to understand both the function of each region of the brain, and the mechanisms necessary to battle neurological disease.  

Crick did not know it at the time, but basic scientists, doing curiosity-driven research, had already found the key piece of the puzzle in an unlikely place, pond scum.  There, in single cell microbes, there was evidence that light-sensitive proteins regulate the flow of electric charge across the cell membrane (allowing the microbe to respond to light and move its flagella).  Thirty years later, building on these basic, seemingly useless results, Karl Deisseroth put the puzzle pieces together, showing how to use light to control single cells in the primate brain, producing a new field of neuroscience called optogenetics.

In a 2010 article, summarizing the remarkable insights gained by his work, Karl Deisseroth reflected on his findings.  He wrote: "I have occasionally heard colleagues suggest that it would be more efficient to focus tens of thousands of scientists on one massive and urgent project at a time --- for example, Alzheimer’s disease --- rather than pursue more diverse explorations.  Yet the more directed and targeted research becomes, the more likely we are to slow overall progress, and the more certain it is that the distant and untraveled realms of nature, where truly disruptive ideas can arise, will be utterly cut off from our common scientific journey." 

Jonathan R. Cole (2010) The Great American University: its rise to preeminence, its indispensable national role, why it must be protected. PublicAffairs.

Karl Deisseroth (2010) Controlling the brain with light.  Scientific American, November, page 49-55.