This Cancer Breakthrough Has Scientists Cheering—and Crying
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.
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.”
Jonathan Cohn (@citizencohn) is a writer for The Bulwark, and author of Sick (2007) and The Ten Year War (2021).
You may have noticed that sh*t has gotten weird the last few years. The Bulwark was founded to provide analysis and reporting in defense of America’s liberal democracy. That’s it. That’s the mission. The Bulwark was founded in 2019 by Sarah Longwell, Charlie Sykes, and Bill Kristol.