NEW YORK – Precision medicine researchers fear that loss of funding and support from the US National Institutes of Health could hamstring research programs and abandon a generation of early career scientists.
Earlier this month, the NIH sent shockwaves through the medical research community with the announcement that it would cap indirect costs within grants at 15 percent, well below the average of around 28 percent and far under the 50 percent to 60 percent rate commonly received by top research universities. A federal judge issued a temporary restraining order blocking the Trump administration's plan to cap NIH indirect costs.
However, precision medicine researchers remain apprehensive as new directives have rolled out ordering mass layoffs across government, including more than 1,000 positions at NIH. Moreover, according to recent reporting by the New York Times, the administration has also implemented a procedural workaround leading to the abrupt cancellation of 42 out of 47 NIH study section and council meetings to review grants, effectively suspending the issuance of new grants.
Now researchers and administrators are uncertain whether current funding levels will be sustained, new grants will be awarded, or ongoing grants will be renewed. The University of Utah is at risk of losing $43 million in annual funding, said Cornelia Ulrich, executive director of the Comprehensive Cancer Center at the University of Utah's Huntsman Cancer Institute. The institute itself stands to lose $8 million.
"As a cancer center director, I have to figure out what we are going to do if [the NIH indirect costs cap] really materializes," Ulrich said. She cited expenses not directly related to research such as lab benches, freezers, major equipment, heating and cooling, institutional review board members, and grant administrators that would need to be somehow covered within the center's budget. "All of a sudden [the funding] would be significantly less. It creates huge holes in actual research-related reimbursable expenses."
Ulrich leads a group at the Huntsman Cancer Institute that studies the biological mechanisms of cancer, including biomarkers and genetic risk factors. In the NIH-funded ColoCare study, for example, Ulrich and her collaborators are investigating outcomes and analyzing biomarkers in about 5,000 patients with colorectal cancer at five global sites. Their aim is to find ways to tailor therapies to an individual patient's biology and to identify health behaviors that future patients can adopt to improve their outcomes.
"As long as the [NIH] grants come through," the ColoCare study is not in immediate peril, at least until it's due for renewal, Ulrich said. However, she is concerned about a new grant proposal that her team submitted on Jan. 24 to the National Cancer Institute related to cancers affecting younger patients. After discussions with the NCI, her team received approval to submit the application with their proposed budget. However, a week later, the NCI contacted them to request a 20 percent budget reduction, casting uncertainty on their plans for the study, according to Ulrich.
She is also concerned about the cancer center's program to address distance disparity in cancer treatment, which relies on NIH funding. About a third of patients travel more than 150 miles to receive care at the Huntsman Cancer Institute, Ulrich estimated, adding that patients who live in rural areas are 10 percent more likely to die of cancer compared to those from metropolitan areas. Huntsman has invested in a decentralized clinical trial program, which allows patients to access some parts of their care closer to home. She is worried that cuts to NIH indirect funding could mean loss of those services for patients living far away.
Ceding US science leadership
"Biomedical research is a very fragile enterprise," said Ari Melnick, a professor of medicine at Weill Cornell Medical College in New York. "It's not like there are margins to support it." He noted that following World War II, the US assumed world leadership in science, forming a partnership between government and universities to invest in talent and technology. He worries that a diminished NIH will cause the US to fall behind other countries, leaving Americans behind and without early access to cutting-edge cancer care.
Melnick's research into cancer driver mechanisms has been heavily supported by the NIH. In 2023, funded in part by a series of grants from the NCI, he and his collaborators described in Cancer Cell their discovery that inactivating mutations in ARID1A, a subunit of the gene-regulating complex BAF, hasten the progression of follicular lymphoma. ARID1A mutations also induce synthetic lethality to SMARCA2/4 inhibition, they found, a mechanism that can potentially be interrogated by precision medicine approaches in high-risk cancer patients.
"My lab would collapse within a year without [NIH indirect costs] funding," Melnick said. "Each of these research buildings is an intricate machinery unto itself that has all kinds of complicated equipment and installations to make it possible to do high-level research, and maintaining it is incredibly expensive."
Melnick speculated that private donors could step in and help with some of those costs, but, he said, "it's not realistic to think that research will continue here" if the indirect costs cap goes through.
Beyond the impact on individual laboratories and universities, Melnick fears that the US will cede science leadership and that early career researchers will either leave science entirely or emigrate to countries like China, which are investing heavily in science. If the government continues to cut back on investment in research, Melnick believes there will be a "generational loss" within scientific research and that it might not be possible to recover, even with a change in administrations in four years.
Howard McLeod, director for the Center for Precision Medicine and Functional Genomics at Utah Tech University, has similar concerns about the loss of younger researchers but believes that the anti-research political environment could also drain the life sciences sector of senior investigators who may choose to retire rather than continue to struggle in a depleted funding environment. "It's already a difficult task [to conduct cancer research]," McLeod said. "There's a point where people are saying it's just not worth it." And that loss of senior leadership would also mean early career researchers who do choose to stick it out would be without mentors, he noted.
Impact on the research ecosystem
McLeod said loss of NIH funding wouldn't directly affect the precision medicine work his group is doing at Utah Tech because it is funded primarily through philanthropic grants and clinical partnerships. However, he said those funding cuts would broadly impact the precision medicine research ecosystem. "When part of [the ecosystem] is no longer there or part of it is struggling, it affects everybody," he said. "It doesn't matter whether you are financially in great shape or whether you are 100 percent dependent on NIH funds, you will be affected by this."
As an example, he said he knows of an investigator-initiated clinical trial on tissue-agnostic, biomarker-driven therapies that has already been impacted by the pending NIH indirect costs cap. He declined to specifically identify the trial and the research groups involved but said that the plan initially was to conduct the trial at 10 centers. "Two of those centers have already said they're on hold because they're not sure they can do their part with the finances" to make up for the reduced NIH support, he said.
Tissue-agnostic treatments, a relatively new paradigm in precision medicine, can be given to patients based on the biomarker driving their tumors and not the organ in which their tumors occur. While drugmakers typically pursue tissue-specific drug development, they are starting to embrace tissue-agnostic approaches, and more cancer centers are conducting studies, too. The greater focus on tissue-agnostic trials has been "great for patients," according to McLeod, because often those with rare tumor types or patients who are out of options can receive treatment through such studies as long as they have the biomarker of interest.
McLeod said that the NIH's recent pullback from research funding and reduction in staff comes at an inopportune time. "Precision medicine, broadly, is a field that is making very important advances to deliver better care," he said. "It's exactly the wrong time to throw a spanner in the works. Nearly every day, [precision oncology researchers] are reporting findings that make it easier to care for patients in a safe and effective manner. [The NIH cuts] are an anti-efficiency endeavor in terms of what's happening on the ground."
Thai Ho, director of precision medicine at the Medical University of South Carolina Hollings Cancer Center, said he has a financial cushion that will keep his lab running for six months to a year and won't be directly affected by NIH indirect cost cuts in that time. However, because NIH study section meetings have been canceled, he said, "there's an entire wave of grants that won't get reviewed, and new grants or grant renewals cannot be awarded. This does affect some of my colleagues, and if these labs are dependent on renewals or grants, they will have to scale back their experiments or lay off staff."
Ho is particularly worried about future renewal of the NIH and the US Department of Defense grants that support his work, since this will impact his ability to continue research into areas like cancers with defective DNA repair mechanisms.
On a larger scale, Ho is also concerned about how these cuts will affect progress in precision medicine generally. Ho categorized precision medicine advances into three major categories: immunotherapy, identification of new cancer targets, and replacing chemotherapy with targeted therapy. "These changes in [indirect costs funding] directly impact federally funded research that's different from [the research] pharmaceutical companies do," he said.
For example, the NIH has supported research that focuses on cancer prevention, cancer diagnostics, and repurposing drugs at the end of their patent life. These are areas of study that typically do not interest pharmaceutical companies. Importantly, "most [cancer] drug targets are initially discovered in an academic lab and only later translated in cooperation with pharmaceutical companies," Ho said. "If you slow down research in the basic sciences, this ultimately leads to less drug target discovery."
Bryan Bell, executive medical director of Providence Cancer Institute of Oregon, worries that loss of NIH support for medical research could burden the "already stretched" research infrastructure within Providence Health System and threaten the ability of the Pacific Cancer Research Consortium to conduct trials across the seven-state network.
Among its research activities, the Providence Cancer Institute collaborates with Providence Genomics on biomarker discovery, early cancer detection, and clinical genomics. One of those projects involves a collaboration with Microsoft to develop artificial intelligence-powered digital pathology solutions for cancer detection, biomarker discovery, and clinical trial matching.
For example, researchers at Providence Genomics are developing a foundation model dubbed GigaPath that they hope will accelerate advances in digital pathology and improve patient outcomes. NIH indirect cost cuts will not impact that project directly because the proportion of funding for it from the NIH is "minimal," according to Carlo Bifulco, an investigator on the project and chief medical officer at Providence Genomics.
However, Bell sees those cuts as a risk for the cancer center and the healthcare system. Bell said Providence's NIH funding is "modest" compared to large universities that receive hundreds of millions of dollars. "Nevertheless, these cuts to facility and administrative costs are an important component of grants to organizations like Providence," Bell said.
The cuts are affecting Providence at a time when healthcare, in general and particularly on the West Coast and in Oregon, is undergoing unprecedented financial disruption, Bell noted. "The weakening of the NIH threatens to delay the development of new therapies, which limit access to clinical trials in some of our ministries, as a Catholic, not-for-profit health system committed to serving all, especially the poor and vulnerable," Bell said.