John Quackenbush , 2025-04-23 08:30:00
I have been doing biomedical research for than 30 years, since earning a Ph.D. in theoretical physics. I’ve published more than 340 papers that have garnered more than 100,000 citations. I was elected to the National Academy of Medicine because of my unique contributions. I don’t mean to sound boastful, but I know what I’m doing.
Throughout my career, my only agenda has been to improve health for everyone by understanding how our unique biology — including differences by sex — affects disease.
Yet somehow, that is now considered a dangerous ideological goal.
In 2024, my colleagues and I submitted four grant proposals to the National Institutes of Health. All of them were innovative approaches to dealing with large biological data to address fundamental questions in human health. Two of these laid out plans to extend work on our most exciting and consequential research projects.
One proposal involved refining and applying cutting-edge big data analytics to understand how sex and aging work together with other factors to alter regulatory processes and affect disease as we grow older. Another proposed developing new methods to map cancer evolution with a particular emphasis on understanding sex-specific truths — like the fact that men are at higher risk for colon cancer but respond better to chemotherapy.
My colleagues and I submitted these proposals in November after months of work preparing them. Then we waited. And waited.
Earlier this month, I was told that the review panel (“study section”) that had been slated to evaluate the first grant had been permanently disbanded, the program I had applied to had been terminated, and my application was unlikely to be reassigned. The second grant remains in limbo at an NIH paralyzed by mass layoffs, rampant delays in review timelines, and increasing scrutiny of projects that touch on subjects the Trump administration considers off-limits. I suspect that both grants were caught up because they used words like “sex” and “female” and laid out plans to study differences between men and women. I find it ironic that an administration that insists there are only two biological sexes seemingly wants us to pretend there are no differences between them.
This news is devastating for my research team, but even worse is knowing that we are far from alone.
Many of my colleagues and their work are falling victim to a nationwide, indiscriminate destruction of university-based biomedical research, fueled by the apparent rationale that some words and ideas fail an ill-posed and completely nonscientific test of orthodoxy.
The damage will not be easy to repair. I am particularly pained to think about the students and postdocs across the country who learn by apprenticing with teams like mine — and then go on to produce the next generation of biomedical breakthroughs. I’ve mentored dozens of trainees of all ages, helping them forge successful careers dedicated to improving health by advancing science. Now, that path to a scientific career is in tatters. If the NIH continues to stall, reject, and terminate grants, we are in danger of losing an entire generation of scientists and the life-changing discoveries they would have made.
There is other collateral damage as well. Consider the implications of my two grants falling into this senseless limbo:
For decades, my group and I have developed groundbreaking methods for inferring and comparing gene regulatory networks to understand cancers, pulmonary disease, and other serious illnesses. A tool we developed recently, PHOENIX, uses a unique machine learning implementation based on biological constraints to predict future states of the 25,000 genes in the human genome. It was recognized by the National Cancer Institute as one of the most important advances of 2024.
PHOENIX and the nearly 20 other freely available, open-source methods we have developed have been downloaded tens of thousands of times. Without the funding requested in my stalled grants, we will not be able to advance this work or even maintain it.
At best, new methods and potentially lifesaving developments will be delayed significantly while I search for alternative funding and try to overcome the substantial expertise I will lose if I have to lay off members of my team and stop accepting new trainees. At worst, the new tools we have been working on will never be completed. Beyond my own work, this loss will prevent others from using our methods to drive breakthroughs we can’t imagine today.
The clock is winding down, and I have no idea whether NIH will give me time to use unspent funds to keep the lights on until I can secure new funding — I hear that “no cost extensions” are being terminated for most projects. If grant reviews are consolidated and the NIH budget is cut, my work may well not be reviewed by those who fully understand it. And private foundations that might support our innovations are going to be flooded by unprecedented requests from scietists who facing the same challenges.
Being a successful scientist requires a thick skin and the ability to respond to critiques from one’s peers. I relish thoughtful critiques; reasoned and evidence-based debate makes my work stronger. But what is happening here is not a rational process — it is death by word search.
It is hard to build things and easy to break them. Rebuilding them will be harder still. Let’s stop the destruction before it’s too late.
John Quackenbush, Ph.D., is Henry Pickering Walcott professor of computational biology and bioinformatics and chair of the Department of Biostatistics at Harvard T.H. Chan School of Public Health.
