NIH and my moral compass

A couple of weeks ago I had the opportunity to visit the National Institutes of Health (NIH) in Bethesda, Maryland for the first time in 7.5 years since I completed my postdoctoral research there in 2003.

I will always remember Maryland as a magical place, full of wonderful trails to walk, magnificent trees and forests, and of course the fantastic opportunities of the NIH.

The NIH that I encountered was special because of its independence of grants and the regular political issues surrounding the funding of the laboratory. Perhaps I was naïve, but I don’t think so; for me the NIH was pure science.

Having been invited as a seminar speaker, despite serious concerns a few weeks back about the passing of the budget and the potential lockout of NIH researchers, I found the NIH (or at least those I came into contact with) still populated by outstanding researchers with a very strong commitment to basic research.

I very much understand the idea that the general public wants accountability to the tax dollars that go towards research. However, as important as preclinical research is (now commonly dubbed “translational research”), I’ve been of the opinion for many years that there is absolutely no replacement for basic research. How can we possibly understand what causes cancer cells to proliferate incessantly, when we don’t really understand how a normal cell grows and divides?

I don’t mean to say that clinical trials should be slowed or jeopardized in any way. However, I do think that basic researchers have to stop “going underground” and that it’s time to become unapologetic for the desire to push new frontiers forward.

For a number of years now I’ve been increasingly concerned that science–rather biomedical science–is evolving and diverging into two radically different directions. The first direction is that of clinical science. In this type of research, it matters not what the mechanism of action of a specific drug is, but simply how effective it is. The researchers are concerned with the concentrations of the drug, its mode of delivery, its toxicity, and of course most importantly, its efficacy.

In the second diverging direction of research, the researchers are primarily concerned with basic fundamental studies; figuring out how things actually work. All of the potential applications are therefore left for the future, with the emphasis clearly on understanding the molecular basis and mechanisms by which cells, proteins, and DNA function.

My underlying concern is not that these two realms are showing signs of diverging farther apart, but rather that funding bodies are increasingly expecting researchers to be able to fulfill both of these two spheres simultaneously. This, in my view, is disastrous.

Researchers who specialize on tumor models in mice will not and cannot (in most cases) do the rigorous types of biochemical and cell biological research that are prevalent in the world of the basic researchers. One cannot expect them to have the expertise to be able to carry out high quality, controlled experiments (for the most part) in these areas. On the other hand, these researchers are extremely accomplished at carrying out the preclinical/translational studies that basic researchers are clueless about.

At the same time, funding bodies are putting pressure on basic researchers who do rigorous and exceptional studies at the level of cells, molecules, proteins and nucleotides, to start working in animal models. Zebrafish, fruit flies, worms, mice and even human samples. People such as myself, who have undergone extensive training in biochemistry and cell biology, see this as a huge waste of resources and time. When I need data from animal models, my best bet is to talk to the people–my colleagues–who already work in these animal models and have trained and developed expertise in these systems, and not to try these studies all on my own in an amateur fashion.

So for me it was a great pleasure to give a talk in the presence of biochemists and cell biologists who completely appreciate the value of my own basic research. Perhaps my greatest delight was that after the talk, in the question-and-answer session, no one asked me whether the proteins I work on are up-regulated or down-regulated in cancer cells; the only questions I received were those that related to the fundamental mechanisms that I described.

Thus, my visit to NIH recharged my batteries and once again provided me with a scientific “moral compass”.

About Steve Caplan

I am a Professor of Biochemistry and Molecular Biology at the University of Nebraska Medical Center in Omaha, Nebraska where I mentor a group of students, postdoctoral fellows and researchers working on endocytic protein trafficking. My first lablit novel, "Matter Over Mind," is about a biomedical researcher seeking tenure and struggling to overcome the consequences of growing up with a parent suffering from bipolar disorder. Lablit novel #2, "Welcome Home, Sir," published by Anaphora Literary Press, deals with a hypochondriac principal investigator whose service in the army and post-traumatic stress disorder actually prepare him well for academic, but not personal success. Novel #3, "A Degree of Betrayal," is an academic murder mystery. "Saving One" is my most recent novel set at the National Institutes of Health. Now IN PRESS: Today's Curiosity is Tomorrow's Cure: The Case for Basic Biomedical Research (CRC PRESS, 2021). All views expressed are my own, of course--after all, I hate advertising.
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6 Responses to NIH and my moral compass

  1. Frank says:

    Steve – A heartfelt post, and I heartily agree with your message. So, it seems, does the former chief of Merck. On GenomeWeb there is a report that at the annual meeting of the Pharmaceutical Research and Manufacturers of America, Roy Vagelos

    told the audience that translational research isn’t the proper function of NIH and its money, calling it “the pathway to destruction,” Hobson says. Instead, Vagelos said, the agency should stick to funding basic research.

    It is striking how this theme emerges regularly, whether it be applied versus basic science (Peter Medawar said there is no such distinction, only good or bad science) or translational versus basic science. Reading about the early days of the MRC and the ICRF I noted that there was great concern to make research more scientific. Walter Morley Fletcher, for instance, said back in the 1920s that the problem of cancer had “passed beyond the realms of clinical observation, and clinicians do not possess the requisite education either to add to or even to supervise work which demands highly trained biologists“.

    • Steve Caplan says:

      Frank and Stephen,

      Thanks for the support! As I’m sure you are both well aware, it can be very lonely being a supporter of basic research these days.

      Again, I have no qualms with the preclinical and clinical research being done–it’s all very necessary. But I think (pardon the pun!) that basic science “is getting lost in the translation”.

      Here is a quote from Nobel Laureate Kornberg that I have cited in a recent grant application as my answer to “significance and disease relevance:”

      “Basic mechanistic research is of direct relevance to human health and the overall mission of the NIH. In 1997, Arthur Kornberg, Nobel Laureate in Medicine, discussed X-rays, Penicillin, Polio Vaccine, and Genetic Engineering as four key examples of the essential dependency of applied research on basic research. He commented that: “No matter how counter-intuitive it may seem, basic research has proven over and over to be the lifeline of practical advances in medicine. Without advances, medicine regresses and reverts to witchcraft.”

  2. Stephen says:

    Great stuff, Steve – very nicely and passionately put.

  3. Cath@VWXYNot? says:

    Interesting points, Steve. I know PIs who are engaged in both kinds of research, but always with collaborators who specialise in the areas in which the PIs themselves were not trained.

    There are some grant mechanisms (e.g. DOD) that support two or more collaborating PIs from different disciplines, but not many…

    • Steve Caplan says:


      You are correct that there are more attempts now to draw together collaborative researchers and teams for big projects–yet at the same time, it seems that the reviewing bodies are pushing individual investigators well beyond their expertise. I think it is okay that researchers should be expected to be curious and ‘learn new tricks’, but I also think it’s a waste of time to push basic biochemists and turn them into mouse geneticists. It’s just not cost-effective.

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