FIFTEEN YEARS AGO, an up-and-coming oncology researcher in Boston named Catherine Wu had a hunch.
It went something like this: If Wu and her collaborators at the Dana-Farber Cancer Institute could identify some of the genetic mutations inside tumors, they could teach the body’s immune system to recognize tiny fragments of proteins associated with the mutations that sit on cell surfaces. And if the researchers could teach the immune system to identify a tumor based on those fragments, then they could teach the immune system to destroy it too.
Someday, the theory went, scientists might turn this capability into personalized cancer vaccines, genetically tailored to attack a patient’s existing cancer and prevent it from returning.
Science research is filled with these sorts of ambitious ideas. But a hunch is just a hunch. Wu and her team had no way to know if they were right.
And even if their hypothesis proved correct, developing these sorts of personalized cancer vaccines would require many more steps and many more discoveries. In asking the National Institutes of Health to fund their experiments, they were hoping the federal government would place a longshot bet—a $363,000 wager that insights into cancer biology from their studies might someday contribute toward the development of a workable medical treatment.1
The NIH decided to make that bet, as one of about 5,300 standard grants it awarded that year. A decade and a half later, it looks like it has paid off. Big time.
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FIFTEEN YEARS AGO, an up-and-coming oncology researcher in Boston named Catherine Wu had a hunch.
It went something like this: If Wu and her collaborators at the Dana-Farber Cancer Institute could identify some of the genetic mutations inside tumors, they could teach the body’s immune system to recognize tiny fragments of proteins associated with the mutations that sit on cell surfaces. And if the researchers could teach the immune system to identify a tumor based on those fragments, then they could teach the immune system to destroy it too.
Someday, the theory went, scientists might turn this capability into personalized cancer vaccines, genetically tailored to attack a patient’s existing cancer and prevent it from returning.
Science research is filled with these sorts of ambitious ideas. But a hunch is just a hunch. Wu and her team had no way to know if they were right.
And even if their hypothesis proved correct, developing these sorts of personalized cancer vaccines would require many more steps and many more discoveries. In asking the National Institutes of Health to fund their experiments, they were hoping the federal government would place a longshot bet—a $363,000 wager that insights into cancer biology from their studies might someday contribute toward the development of a workable medical treatment.1
The NIH decided to make that bet, as one of about 5,300 standard grants it awarded that year. A decade and a half later, it looks like it has paid off. Big time.
If you’ve read this far, you’re the sort of person who wants to know what’s actually going on—who wants to understand the deeper and wider story beyond the headlines. We make this newsletter for readers like you. See the bigger picture with a Bulwark+ membership:
This past Wednesday, Moderna and Merck announced positive results from a major clinical trial using a cancer vaccine of the kind Wu and her team had envisioned. The target was melanoma, the deadliest form of skin cancer. Using the vaccine in combination with a common cancer drug—rather than relying on the cancer drug alone—significantly reduced the recurrence of melanoma after tumor removal, according to the companies.
Merck and Moderna did not release the actual data, saying they would do so at an upcoming medical meeting. Until that happens, it’s impossible to be sure exactly what their tests show, or how significant the outcome is. But the reported findings from the large trial appear to be consistent with the outcome of a previous, much smaller trial. “This looks like a home run,” Ezekiel Emanuel, an oncologist and vice provost at the University of Pennsylvania, told me in a phone interview.
Emanuel’s reaction was not unusual. Scientists across the country and the world have been buzzing about the news because, if the results hold up, they will be proof of concept for the kind of cancer vaccines researchers have long hoped to create. “This could be revolutionary,” Catharine Young, a biomedical scientist and former Biden administration official who is now a senior fellow at Harvard’s School of Public Health, told me.
Yet behind all the joy there has been concern and even alarm—not about the treatment itself, but about the threat Donald Trump poses to the research ecosystem that made its creation possible.
The Trump administration’s broad attack on America’s scientific enterprise includes cuts and rule changes affecting precisely the sorts of grants that financed the work of Wu and many other scientists whose research laid the scientific foundation for the vaccine’s development.
The administration has also attacked this specific type of vaccine. The Moderna-Merck treatment uses mRNA technology—as did two of the COVID vaccines—and Health and Human Services Secretary Robert F. Kennedy Jr. has singled out mRNA for particular vilification. Last year, he canceled hundreds of millions of dollars in funding for the research and development of mRNA technology, including Moderna’s work on what was supposed to be a new platform for vaccines against influenza.
Kennedy’s animus toward mRNA vaccines, which is based on wild, unsupported conspiracy theories tying COVID shots to harm and death, has so far not led him to meddle with mRNA funding outside of the context of infectious disease. But scientists say his hostility is bound to have—and is already having—a chilling effect on research into mRNA for other purposes, including cancer. The same goes for the broader cuts the administration has made to research funding, despite claims from officials and their allies that truly important experiments into diseases like cancer haven’t taken a hit.
The backstory of the melanoma vaccine is in many ways a perfect case study in what’s at stake. It illustrates vividly how medical breakthroughs depend on generous, sustained support of basic research that the private sector will never provide on its own—and on freedom from interference from politicians, especially those like Kennedy who routinely traffic in scientific nonsense.
WU’S RESEARCH IS JUST ONE PIECE of that story, which arguably starts in the late twentieth century when scientists like James Allison and Steven Rosenberg developed a sophisticated understanding of how the immune system interacts with cancer cells.
These findings increased interest in so-called immunotherapy, which seeks to fight cancer by getting immune cells to recognize, swarm, and kill tumors that might otherwise grow unchecked. That’s different from surgery, radiation, and chemotherapy, which generally attack or remove cancer cells more directly—and frequently do so with brutal side effects, because they damage or kill so many healthy cells too.
Today immunotherapy takes many forms, including medications like a drug called Keytruda that now treats multiple kinds of cancer. Keytruda acts directly on immune cells by removing the biological equivalent of brakes that stop them from attacking certain tumors. With Keytruda, the brakes come off, the immune cells go to work and—in the best of cases—eliminate tumors altogether. Treatments like that help to explain why the five-year relative cancer survival rate for all cancers has reached 70 percent, up from 49 percent in the 1970s, according to the American Cancer Society.
But even with drugs like Keytruda, some tumors escape total destruction. One reason is that sometimes the cancerous cells remain difficult for the immune system to recognize or to attack. Scientists over the past two decades have spent a lot of time trying to figure out how to make cancer cells more visible—and, then, more vulnerable—which in turn has required learning a lot more about the genetic mutations that turn healthy cells into cancer.
A number of key advances have made that possible. Among them were the completion of the Human Genome Project (which provides a comprehensive map of human DNA) and then the Cancer Genome Atlas (which provides information about the mutations in different kinds of tumors). Technical leaps in DNA sequencing and computational algorithms have made it possible for researchers to pinpoint the genetic structure of tumors far more quickly than before.
These and other related developments rest on a foundation of federal research funding from agencies like the National Science Foundation, the Defense Advanced Research Projects Agency, and—especially—the NIH, which includes the National Cancer Institute. The same goes for the NIH-funded experiments from researchers like Wu, which zeroed in on protein fragments called “neoantigens” that appear on the surface of cancer cells and give the immune system a target to find.
“My specific entry into personalized medicine came from the desire to use what was then a very new technology, genomic sequencing, as a way to systematically find mutations,” Wu told me in a phone interview, making sure to mention she is just one of several scientists whose work contributed to cancer vaccine development. “Then we used prediction algorithms that could help us find these neoantigens that could then become good targets for vaccines.”
Even that list of projects and innovation comes nowhere close to capturing the ways this new breakthrough was fueled by federal research funding—which, as Johns Hopkins University biomedical engineer Jeff Coller pointed out, traces back to America’s determination to maintain scientific supremacy during the Cold War.
“Science always builds upon itself, and so from a federal funding standpoint, you really have to continue to support research because you never know where the breakthroughs are going to come from,” said Coller, who also specializes in mRNA research. “I could give you a lineage of how [the new cancer vaccines] got to where they are, but it’s really all of the infrastructure of biomedical science and science in general that this country has championed since World War II.”
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FEDERAL RESEARCH FUNDING was also critical to the development of mRNA technology, which was another essential step in the development of a workable vaccine for cancer—and, now, its most potentially controversial piece.
With mRNA, scientists can feed human cells the genetic code to manufacture those neoantigens, so that the immune system can learn to recognize and react to them quickly when they appear on tumors. And the process can be rapid by medical standards—it’s possible to produce a vaccine for a patient within weeks, Coller said—which is essential in cancer treatments when tumors can appear, grow, and become lethal with such speed.
“That’s really the advance here,” Coller explained. “We can go and sequence a patient’s tumor, design an mRNA specific for them and only them, inject it into their body . . . and then have their own immune system essentially attack the tumor and lead to a remission.”
Figuring out how to make mRNA work in this way was its own endeavor with a long backstory. The timing worked out so that scientists had figured out how to use the technology shortly before COVID appeared on the scene, which is why companies that had been developing it—like Moderna—were able to produce vaccines so rapidly.2
Now, as a deeply reported article from STAT details, companies are using that same technology and capability to produce cancer vaccines, starting with melanoma. But those firms’ work also traces back to federally funded research studies, not to mention the massive investment in COVID vaccines during Operation Warp Speed.
“If it hadn’t been for Operation Warp Speed, we would not be able to do that—we would not be able to manufacture these personalized cancer treatments at scale,” Coller told me.
OPERATION WARP SPEED was back in Trump’s first term, when his administration still supported vaccination and mostly left the medical research enterprise alone. Things are rather different today.
Grants from the NIH are down, though it can be hard to tell that from the budget numbers because Congress ignored Trump’s request and kept the agency’s funding stable. The problem is that NIH hasn’t been spending all of that money. There are several reasons for the bottleneck, including new scrutiny of grant applications for words and subjects (like “diversity”) that trigger administration political sensitivities, delayed processing of grants (because of downsizing and loss of expertise across the Department of Health and Human Services), and a shift to multi-year grants (which has the effect of reducing annual grant awards).
“On paper, it’s been allocated by Congress and they’re spending it,” Coller explained. “But what they’re doing is they’re paying forward grants in multiple-year increments, and what that essentially does is reduces the overall pool of grants by about 40 to 60 percent. . . . It’s affecting almost every single researcher.”
And there may be more interference to come. The administration has proposed changing the process for grant approval, so that awards would require some kind of signoff from political officials. This would represent a major departure from the heavy reliance on intensive peer review, meaning applications go through layers of scrutiny by actual experts in the field. The process is not always ideal and it can certainly be cumbersome. But it also made possible all of the research that led to the new cancer vaccines, among many other groundbreaking innovations.3
“This is the first time that we are seeing this level of interference at the decision-making process in terms of what science should be funded going forward and what shouldn’t,” said Young, who also hosts a podcast about women in science called Alpha. “That alone should be sending up a lot of red flags.”
This is on top of Kennedy’s ongoing crusade against mRNA technology. Targeting vaccines is bound to have an effect on cancer research, if only because insights from one can so frequently help the other. The proof is in what’s happened already: The discoveries and improvements arising from years of working toward a cancer vaccine have made it easier for companies like Moderna to produce COVID vaccines quickly—and, now, knowledge from that exercise is guiding development of the cancer shots.
And while it’s likely that companies like Moderna and Merck will continue to invest in mRNA cancer vaccines, because the science is now so solid and the sales opportunities so vast, they are unlikely to provide the kind of support for underlying scientific research that the federal government has. They aren’t going to underwrite labs or researchers at the scale the federal government has historically, and they aren’t going to change the perception—already affecting decisions by scientists considering where to do their work—that America is no longer a place where robust support of research is a given.4
“When you get what is essentially misinformation coming from the leader of HHS, when it’s antithetical to the scientific method, it sends a chill to the entire industry as well,” Coller said. “It says this is a government that’s not going to have scientific rigor, that is not going to base its judgments in fact. That changes the narrative of these companies to say, well, we won’t invest our money into the United States. We’ll move our technologies offshore because other countries have not done that.”
Even a figure like Emanuel, an NIH veteran who has frequently criticized the grant-review process and called for reforms, has said the Trump administration’s approach seems “moronic.” He invoked a sports analogy to capture its likely impact.
“This is research, and especially at the frontier, the number of shots on goal matter,” Emanuel said. “Not every shot is going to work. There ought to be a high failure rate because it means you’re taking a lot of shots—you’re chasing a lot of ideas—some of which will pan out and some of which won’t.”
Nobody knows that better than Wu, who remembers what federal funding meant for her projects and her career, going all the way back to that 2011 investigator grant.
“Federal funding is just hugely important to academic medicine, to all of the foundational biology,” Wu told me. “I’m greatly indebted and appreciative of the resources that have been there, and … it’s not just the work. It’s our entire ecosystem, where we help to train the next generation of investigators and to carry forth the biomedical mission.”