The attack on biomedical research — why should anyone care?

By Mark Guyer >>

Starting on its first day in office, the Trump/Musk administration has attacked many of the basic institutions of American society in ways that are illegal, unconstitutional and un-American. Among these has been the National Institutes of Health, the nation’s, and world’s, premier medical research organization.

But why should anyone care about NIH? What is the priority of medical research compared to the legal system, the legislative system, international trade, international alliances, foreign aid and all of the other pillars of our nation’s strength that have already been targeted? I would argue that improving the health of the U.S. population is right up there among the highest priorities. An unhealthy nation is not a strong nation.

While medical research is generally agreed to be valuable and important, the role of the federal government in funding the research has been questioned over and over again. Why should taxpayer dollars be used to support research? Shouldn’t the private sector shoulder the costs? After all, the private sector benefits from the sale of the life-saving products that come from research, so why should it not pay for the research? Two questions repetitively asked are: why does it take so long for the results of research to come to market and why is it so expensive?

I believe it is entirely appropriate for the government to support basic research and I will explain why such research costs as much as it does and why finding ways to prevent and cure disease takes time.

For context, I worked at the NIH for 28 years, retiring about ten years ago. For 26 of those years, I worked at the National Human Genome Research Institute, one of the 27 institutes and centers comprising the NIH. There I helped to manage the NIH’s contributions to the Human Genome Project, eventually becoming the Deputy Director.

The HGP was one of the most astounding scientific achievements since the Second World War. The HGP began in 1990 and was completed in 2003 — ahead of schedule and under-budget, so much for the argument of lower efficiency and wasted expense in governmental supported activities.

But its benefits for human health only began to be realized after its completion. Although slow to emerge, applications of the knowledge obtained are now making an ever-increasing contribution to medical practice. More and more cancer patients, for example, are leading longer disease controlled, or even disease-free, lives. The accomplishments of this international collaborative effort illustrate some key factors in the success of biomedical research that are now being directly threatened by the administration’s actions.

Why is scientific research important to our country?

The understanding that scientific research made a significant contribution to the Allies’ triumph in World War II led to the confidence (1) that further improvement of the country’s scientific capability would contribute mightily in many ways to the further development of the United States, and (2) that the federal government was uniquely positioned to play a crucial role in the post-war development of U.S. scientific capability. This turned out to be true. Focusing only on the health of the U.S. population, government support has been directly responsible for the amazing reduction in the incidence of infectious disease, now increasingly imperiled, the reduction in mortality due to cancer, heart disease and other chronic diseases over the past two decades, the development of biotechnology, millions of jobs, and multi-million dollars of economic benefit. All of these advances, and many others, provide ample proof of the value of biomedical research to our society.

Why should the government fund science? Why shouldn’t that be the purview of private industry?

The biomedical research enterprise in the United States has been a public-private partnership for decades. The government supports upstream basic research, and the private sector supports downstream applied research and product development. But, while knowledge about how biological systems work is critical to, for example, drug development, the private sector will not support the necessary funding for basic research. Basic research does not and is not expected to actually produce useful products, and the results of basic research are usually publicly available. Therefore, the payoffs are too far in the future and are not proprietary to warrant investment by the private sector.

Which biological truths will be the basis for effective new therapies cannot be predicted. Nor can a company predict how long it will take until the information necessary for it to develop a therapy for a particular disease in which it is interested. The private sector cannot plan a business in the face of such uncertainty. But once there is enough basic knowledge, the private sector, driven by profit, will be willing to make the huge investments necessary to develop safe and effective therapies. In other words, the foundational knowledge that basic research forms the crucial foundation that allow the private sector’s applied research and development programs to generate the useful products that lead to healthier lives and increased life spans.

The return on investment of basic research is impressive. One dollar spent by the NIH generates, on average, $2.56 in economic benefit. But that benefit usually comes too slowly to satisfy the short term demands of the private market. Yet it does come, and without it, progress toward disease control would either take very much longer or would not happen. It is up to the federal government to start the process by supporting basic research.

Why does basic research take so much time?

Contrary to popular thought, there are few “eureka” moments in research. Rather, much more often than not, a scientist’s or a scientific team’s activities consist of testing an idea through experiments, then refining, and then re-refining the idea on the basis of the experimental results. Think of a successful research effort as analogous to working your way through a complex maze. The correct path is difficult to find. Decisions need to be made at every step along the way. Some of those decisions are wrong and lead you almost back to square one. You may have to reverse decisions to make a bit of progress, but then you come to the next dead end. In the early stages, you have little idea whether you’re on the right path, but the more you work on it, the closer you get to reaching your goal and exiting the maze. Getting out of the maze usually takes much longer than you thought it would or should.

In the same way, both laboratory and clinical research are iterative, cumulative processes in which incremental advances, obtained on the scale of days, weeks, months or years, lead to the accumulation of enough knowledge to generate new, important insights into how biological systems work and what happens when they do not work properly. While the public announcement of the next “great advance” in the press makes it seem as if the advance came suddenly, almost always it has only come after years of research.

Going from basic knowledge to product then involves applied research and development. Time is needed to determine whether a potential new therapy reduces risk and improves outcomes. How safe is it to use in humans? Does it have sufficient advantages over existing therapies? What side effects does it have? Coming up with an effective new therapy takes more time than we would like it to, but when all works well, suffering can be eased, death can be prevented and economic benefit can be created.

Why is basic research so expensive?

As we all know, time is money and research success needs adequate, dependable funding. Scientific research is carried out by people who need to earn salaries. The majority of NIH grant funds are, in fact, spent in the personnel category and cover all or part of the salaries of investigators, lab personnel, trainees, and support personnel whose work is needed to achieve the research objectives. Scientific research also requires material resources, such as instruments, reagents, animal care and recruitment of research participants. Funds are needed to acquire and maintain all of these. But taxpayer dollars must be spent carefully. So, an application for an NIH grant requires a detailed budget request with an explanation of all the resources requested to carry out the proposed project and a justification for each. The peer review process includes an item-by-item evaluation of the budget request. The peer reviewers ask what the minimum amount of funding needed is to achieve all of the proposed goals of the research grant and what the effect would be of recommending a lower budget. No one wants to spend more money than necessary to achieve results.

What’s wrong with the actions the administration is taking taking against NIH?

All kinds of things!

1. On-going research programs are being stopped in their tracks. As of March 27, the administration has terminated 300 funded NIH grants. These were all research projects that had been validated at two levels of peer review. The first level was carried out by a committee of experts in the relevant field who assessed the importance of the proposed research question; the rigor and feasibility of the proposed research plan; the expertise of the proposed investigators; the adequacy of the proposed budget; and the appropriateness of the length of time for which support was requested. The second level was carried out by a council of senior advisors who evaluated the quality of the initial review and the priority of the proposed research within the overall portfolio of all the research the Institute is supporting. No NIH grants can be funded without approval at both levels of review, assuring that taxpayer dollars are only spent on the research projects with the most potential to benefit the public.
   
   Yet, the powers-that-be, whoever they are and whose identities I don’t think we know — and who presumably have no scientific expertise themselves nor any judgement about the need for any specific kind of research — have arbitrarily decided to terminate those 300 grants, a number likely to only rise.
2. On-going work is being delayed. In the first ten weeks, $1.5 billion of grant funding has been delayed. The delays include both grants on which work has not yet started and grants in which work is ongoing; NIH grants are typically awarded for 3 to 5 years but are assessed annually to ensure adequate progress before the next year’s money is released. Effective research programs require continuity. At the start of a grant, staff need to be hired, approvals for the use of animals in research and/or for the protection of research participants must be finalized and equipment and reagents need to be purchased. None of that can happen until the award has actually been made because it is risky to make those kinds of commitments just on the basis that an investigator has been told that the grant will be made. As a result, potential staff may be lost to other jobs, the training of students supported by the grant will not begin, or approvals that have been obtained may expire and unnecessarily have to go through the approval process
   again.
   
   In clinical trials, people who have agreed to participate may become sicker and no longer qualify for the trial, or they may withdraw because participation is no longer feasible. For on-going research grants, a delay in the start of the next year may lead to the loss of existing staff who, needing to have a continuing salary, take other jobs. Replacing those staff, even if the grant is restarted, will take time and the new staff will have to be trained. So, the efficiency of the use of grant funds will be compromised. It is also possible that needed reagents will become unavailable, either because unstable molecules will have decayed or specialized animal resources will have aged or even died. For on-going clinical trials, interruption may have a serious negative impact on the validity of the results, as participants may have to forgo the experimental treatment for an unspecified period of time.
3. As mentioned, trained scientists are losing their jobs and training of students has been interrupted. Already, U.S. scientists are leaving to pursue their research abroad. Already, offers of postdoctoral research positions and graduate student acceptance are being withdrawn. Already, people who are considering biomedical research as a profession are being discouraged by the uncertainties created by the threat of further withdrawal of support for scientific research. Pretty soon, the flow of people through the pipeline leading from education to employment will slow down significantly. It will slow down in the United States, that is — production of new scientists will not slow in Europe, China, India and the rest of the world. The United States will fall behind in the competition for innovation and improved health.
   I could go on. The bottom line is that the U.S. biomedical research enterprise is under attack for no stated or good reasons. Development of new therapies is being interfered with and, as a result, many U.S. residents will suffer more than they otherwise would. Why? Because some arbitrary group of unqualified people have decided it would be more “efficient” to cut spending. But will it actually be more efficient? For example, last year, in the United States, the healthcare costs for people with Alzheimer’s Disease were $236 billion. That is five to six times the annual budget for the NIH, which is addressing many more conditions than Alzheimer’s. Research into the causes and prevention of Alzheimer’s is the best, and perhaps the only, way to reduce such costs. Is that worth lower taxes for billionaires? Billionaires are just as likely to suffer from Alzheimer’s as the rest of us — their increased wealth does not save them from that. But research might.

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