“This Will Have a Negative Effect on the Entire Drug-Development Enterprise”

The federal government has terminated numerous federally funded grants and contracts to Harvard and is scaling back investments in scientific and medical research across the country. In this series, Harvard Medical School scientists discuss how these actions are affecting their research and their labs.

Essentially, my lab operates as an early stage drug-discovery unit.

We do pharmacology, which means we test large libraries of chemical compounds to find ones that are promising enough for companies to pursue. People often ask why it’s necessary for early stage research on drug development to happen at a place like Harvard Medical School instead of at a pharmaceutical company like Pfizer or Merck. It’s a good question.

Currently, Big Pharma gets most of its drug candidates from small biotech companies, and biotech companies get them from basic research labs at universities that are largely supported by federal funding. Biotech and pharmaceutical companies don’t have the freedom that we have in academia to test risky strategies. My lab can take the time to figure out if an approach is worth pursuing or not — and sometimes it’s not. That’s part of our goal: to triage what initially looks promising and identify approaches that we can pass along to companies to develop into drugs.

We were three years into an eight-year NIH grant that was recently canceled. The goal of our project was to use basic discoveries about pain-signaling neurons to develop new, nonopioid approaches to treating pain. We also have a parallel project on epilepsy.

The way I explain our research is that the brain works by electricity, which is generated by pores in the membranes of neurons called ion channels. Normal brain function — including normal pain signaling — requires dozens of different kinds of ion channels to work in concert. However, neurons in the human brain have evolved to be right on the edge of being too excitable, which means they have a propensity for going over the edge into hyperexcitability. When this happens, it can result in conditions like chronic pain and epilepsy. The hyperexcitability of neurons stems from subtle changes in how their ion channels work, which is what we study. We believe the most rational way to address these conditions is to develop drugs that target the specific ion channels involved.

We have known for a long time that pain signaling is from the electrical activity of a specialized population of neurons. Through federally funded basic research, researchers in my field have learned a huge amount about the properties of pain neurons, including finding the ion channels that make them unique. We now have the foundation of biological knowledge needed to develop drugs that inhibit pain without addiction, and I want to be part of doing that. I think my lab has something important to contribute. Our research into developing nonopioid pain drugs is incredibly promising; we’ve been testing several exciting new approaches. Before our funding was canceled, we were making great progress. Now we’re trying to figure out how we can keep doing our work.

The federal grant system has been an amazing success story for the United States.

In college, I originally intended to study philosophy, but once I realized that you could scientifically study how the mind works, I switched to neurobiology. I had no real career plans after I graduated. I thought maybe I’d support myself by working as a welder and try to write a comic novel. I never considered a career in scientific research. But I ended up getting a job as a lab tech at Boston Children’s Hospital. The lab was studying the electrical system of the heart to develop pacemakers for kids, which was the start of my interest in ion channels.

When I learned about science as an undergraduate, it seemed like something that was only done by geniuses who won Nobel Prizes for having brilliant ideas. I knew I wasn’t a genius, and I didn’t think I was likely to have brilliant ideas, so it never occurred to me that I could be a scientist. What I discovered working in that cardiology lab was that day-to-day research was really fun. I realized that a lot of science is incremental and is done by normal people.

What I love about my research is being able to combine neurobiology and pharmacology. I’ve always been fascinated by the fact that almost all drugs we use in neuroscience were developed before we had the slightest idea why they worked. For example, antiepileptic drugs were discovered by trial-and-error testing in animal models. It’s only recently that we have started to understand the basic biology of these systems well enough to understand why drugs work. I’m excited by the idea of using this knowledge to develop better drugs. A top-down approach to drug development can and has worked, but I think a bottom-up approach that builds on basic research will allow us to improve and accelerate drug discovery.

The federal grant system has been an amazing success story for the United States. It’s an engine for technological advancement and it’s a partnership between the government and research labs. At a medical school, most scientists use federal funds to work on research that will benefit taxpayers. People may not realize how competitive it is to get federal research grants. In my field, the funded projects typically represent only 7 percent of the total projects deemed to be scientifically valuable. Only the very best, most promising projects are funded, which reflects that tax dollars are being used in a really impactful, targeted way to improve health care.

The reduction in federal research funding is potentially devastating. The entire U.S. biotech and pharmaceutical industry relies on training graduate students and postdoctoral researchers in academic labs. For example, all four people in my lab are ultimately interested in careers in drug development at biotech or pharmaceutical companies. They joined my lab because it provides them with an opportunity to collaborate with medicinal chemists, pharmacologists, and other labs and gain the experience they’ll need to succeed in industry. So beyond the effects on basic research — which are terrible — this will have a negative effect on the entire drug-development enterprise. The United States has been far ahead of any other country in biotech and pharma, and it’s because of the foundation of federal support to train scientists at research universities.

I’m also concerned about the disruption of funding, because research takes a long time. The work in my lab is built on a large base of knowledge, and the techniques are highly specialized, so it is time-consuming to train new people. It’s no accident that academia has evolved so that people spend five years as PhD students and another four or five years as postdocs; that’s how long it takes to master the science. Most projects take years, so continuity is key. Having a five- or eight-year grant is phenomenally effective for making progress on research — and disrupting that continuity is a huge problem.

Bruce Bean is the Robert Winthrop Professor of Neurobiology in the Blavatnik Institute at HMS.