“People in My Lab Are Scared”

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.

Being awarded my first-ever federal grant was both frustrating and exhilarating.

I wrote a bunch of grant proposals that didn’t get funded, so I finally decided to move into a new area, studying the basal ganglia — a very old part of the brain involved in decision-making — and designed experiments that nobody had done before. Suddenly everybody was excited about what I was doing. The process taught me to take bigger risks and branch out into new directions. Since then, federal grants have been a key source of support for my lab — or were up until recently, when the federal government terminated all of my grants awarded by the National Institutes of Health [NIH]. 

My lab studies how animals choose what to do next — how you use information about your past, your current goals, and your sensory environment to choose the next action. We study the basal ganglia because many human neuropsychiatric disorders that affect decision-making, including Parkinson’s disease and drug addiction, arise from changes in this brain area. The basal ganglia are highly conserved across vertebrates, which means we can study them using mouse models of human disease. Through this work, we’ve discovered many classes of basal ganglia neurons and connections that link intention to action. We’re particularly interested in dopamine signaling, which is underactive in people with Parkinson’s disease and overactive in people with addiction. 

We’re also studying thyroid hormone signaling, which is something that caught my attention during medical school. I remember learning that people with too much thyroid hormone are often hyperactive, sleep less, and take more risks. Conversely, people with too little thyroid hormone can appear depressed, become withdrawn, and tend not to engage in activities. This made me wonder why and how thyroid hormone interacts with the brain to alter behavior. 

My lab discovered a pathway by which thyroid hormone rewires the brain in mice. We found that this pathway acts on the brain and body by connecting the controls for metabolism and exploratory behavior. We also analyzed existing data from the Centers for Disease Control and Prevention to link thyroid hormone in humans to employment, mortality, and income level. Now, we’re trying to develop drugs that manipulate thyroid signaling in the brain and may have potential for treating depression. We’re also exploring the connection between thyroid hormone and stroke recovery. This work is a great example of what can happen when you ask a simple question and do basic research studies. It has opened up a huge amount of unexpected science that is highly relevant to human health. 

What I like about studying the brain is that we can move from knowing nothing to making fundamental discoveries incredibly quickly. We can ask a question and, six months to a year later, be making new discoveries and opening totally unknown areas of research. There aren’t too many fields in science where that’s true. 

My grant terminations are having a huge impact on my research. We’ve had to find ways to cut expenses as rapidly as possible. We’ve dramatically decreased the size of our mouse colony. We’ve changed the way we use lab materials. We’ve reduced the number of lab technicians and support staff. We’ve decided to not do certain experiments. 

In the past, federal funding allowed us to pursue new areas, but we can’t do that anymore. There are whole classes of experiments that we’ve had to shut down. This means that progress is going to slow down on existing projects, and we will not start new projects. For example, I think we’re close to making important discoveries about how thyroid signaling impacts stroke and neurodegenerative diseases, but the research would require federal support, so we probably won’t be able to do it. 

People in my lab are scared. They’re spending less time and mental effort on their research, because they’re so worried about their own futures. That’s been painful to watch. And the visa situation has made things far worse. Graduate students and postdocs here on visas are terrified. They don’t know day-to-day whether they’re in compliance or in violation of federal law. They don’t know whether they could be stopped and deported. They don’t know whether they will have a job a month from now. 

There’s so much uncertainty. I’m worried about having to fire people and make the lab smaller. These are highly talented scientists who have dedicated years or decades of their lives to pursuing science and medicine, and now they may suddenly find themselves out of a job. The lab is like a living organism, and the knowledge base, the know-how, is not in my head — it’s in that collective body. If I have to trim my lab, I can’t simply reboot it at a later time. By not having continuity, we will lose the knowledge of how to do certain techniques and how to interpret data, and we’ll have to reinvent all of that downstream. 

I also have people who are coming to the end of their graduate school training or postdoctoral work and are ready to move on to the next stage, but there aren’t any openings or opportunities available for them. I honestly have no idea what they’re going to do. I’m afraid that a whole generation of researchers will leave academic science. It’s just as bad for people coming into the pipeline, and I don’t think international students or postdocs are going to choose to come to Harvard. 

Scientific research in the United States is basically going to stall, and when it starts up again, it will be at a slower pace. That’s not only because of the funding cuts to Harvard but also because of broader threats to reduce NIH funding. There won’t be enough money to do the studies that need to be done. I think we’re going to see a slowdown in the development of new drugs; a slowdown in what we’re learning about disease mechanisms; and a slowdown in advancing our basic understanding of how the brain and body work and of what it means to be human.

Bernardo Sabatini is the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS and codirector of the Kempner Institute for the Study of Natural and Artificial Intelligence.