As the coronavirus that causes Covid-19 sweeps across the world, scientists are racing to find vaccines that could stop the virus in its tracks. On Monday, Moderna Therapeutics, a Massachusetts-based company, began the first human clinical trials of its vaccine in Seattle, Washington—skipping the typical phase of trials wherein a new vaccine or medication is tested on animals first. A successful vaccine could be a lifesaver for many. But bioethicists are also concerned about the compressed timeline—and what it means for vaccine development in the future.
Some argue that desperate times call for desperate measures—that the risks of a worsening pandemic outweigh the possibility that the vaccine could adversely affect participants. The call for trial participants put out by the Kaiser Permanente Washington Health Research Institute, where the study will be conducted, pointed out that a vaccine is “urgently needed” because of the large number of people already sick or likely to get sick around the world, and the virus’s ability to spread from person to person. Participants in the study, who must be healthy adults between 18 and 55 years of age, will receive a total of $1,100 for their participation—$100 “for each of the in-person study visits.”
In the United States, some of the pressure to create a vaccine quickly is coming from the top: President Donald Trump has said that a vaccine will be available “in a fairly quick manner”—having misunderstood in a meeting with drug company executives, according to The New York Times, the difference between when a vaccine is ready for initial trials and when it is ready to be offered to the public. He also reportedly offered a German company funding for a vaccine to which the U.S. would have exclusive rights. (The U.S. ambassador to Germany denied that there were plans to keep the vaccine solely for U.S. use.)
Moderna, a biotechnology company, sent its vaccine to the National Institute of Allergy and Infectious Diseases, which will sponsor the trial, on February 24. By early March, Kaiser Permanente had begun recruiting participants for the study, which will last for just over a year. (Moderna declined to comment, telling me that it was no longer commenting on stories involving this vaccine development process, and Kaiser Permanente did not respond by press time; if it does, this story will be updated.)
“There’s a few reasons to think that this is something that we shouldn’t be doing,” Nicholas Evans, an assistant professor in the Department of Philosophy at the University of Massachusetts Lowell, told me. This trial is not just skipping a significant safety step, he said; it’s also skipping the important step of learning, through the animal trial, whether the vaccine will be useful at all. “So this is a pretty big deal.”
Although vaccine developers usually test on animals before humans, there are no laws saying they must. Typically, regulators like the U.S. Food and Drug Administration require proof that a product is safe and is likely to work before it’s tested on humans—and some of that proof can come from trials with mice or other animals.
But in this case, Moderna has gotten approval from the FDA to change up the order. The animal trials began at the same time as the human trial began recruiting participants. One difficulty researchers may face is that standard mice don’t seem to be affected by this virus. As a result, mice that are susceptible to it will need to be bred over the next few weeks.
Conducting the trials simultaneously or reversing the order is a rare but not unheard-of move, Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics, told me. For reasons of safety, efficacy, and ethics, he said, it’s usually better to test on animals before humans. “You have to have good reason to say, ‘We need to go straight to humans or go to humans at this particular point,’” he said.
Kahn worries about people signing up to be in the trial because they think the vaccine could give them immunity before it becomes available to everyone else. In reality, this kind of early trial is just to make sure that the vaccine is not toxic and does indeed provoke some kind of immune response in people. Participants are very unlikely to be fully immunized to the virus over the course of their participation.
Vaccines have different ways of, essentially, tricking the human body into thinking it is facing the real form of a certain disease and getting it to develop immunity without facing the full-blown disease itself. Oftentimes, a weak or dead form of the virus or bacteria is used. This vaccine doesn’t do that. Instead, it relies upon a snippet of genetic code called messenger RNA, or mRNA, which essentially teaches cells how to respond to viruses like SARS-CoV-2 (the name for the virus that causes the disease Covid-19).
The coronavirus looks a little like the sun, with tiny rays extending out. Once the virus is in your body—say, it’s gotten inside your nose—it uses these “rays,” which are actually proteins, as hooks to attach to your cells’ receptors and get comfortable in your body. Moderna’s vaccine is actually a bundle of instructions that would teach cells how to create proteins similar to the virus’s “rays,” in order for your body to learn how to defend against the actual viruses. It’s kind of like a fire drill. This study will test the safety of the vaccine in humans, and it will also see whether the vaccine seems to work. Will the immune system figure out what the instructions are telling it to do, and will it be able to create enough immunity to the virus?
There’s another hitch here: Moderna has never brought a product to market.
A company that did have “a long track record of bringing drugs to the market,” Evans said, would have more credibility when asserting that this vaccine needs to be fast-tracked despite not having completed animal trials yet.
Both Evans and Kahn stressed the need for explaining clearly the potential risks to the study participants. The call for volunteers from Kaiser Permanente notes that this vaccine has not been tested on humans before. But it doesn’t mention that it hasn’t been tested on animals, either.
“I think that’s a huge issue,” Evans said. The consent form that participants sign before enrolling in the trial hasn’t been released, but he and Kahn agreed that truly informed consent is a fundamental part of conducting human testing—especially in a fast-tracked process. “We need to understand, as best we can, the risk that people are being asked to expose themselves to,” Kahn said.
And there’s also the issue of paying participants. In general, while researchers may compensate participants for the expenses of being in a study—for instance, for transportation costs—“it should only offset the cost that the individual bears by their participation,” Kahn said. “You’re not supposed to pay people to accept risk.” In the research community, the question of how much to pay participants can be a tricky one. It’s a way of making sure that participants don’t drop out of the trial, Kahn said. “The number gets set in a way that isn’t overly enticing somebody to participate, like, ‘Wow, I could pay my rent with this money,’ or something.”
Several other companies are racing to find effective vaccines. Novavax, a Maryland-based company, is also working on a vaccine that doesn’t use dead or weakened viruses. Instead, its vaccine is a recombinant nanoparticle—basically, a fake version of the virus that hooks into the cell in the same way as SARS-CoV-2, giving the cells practice at warding off a harmless facsimile of the virus. The company has made similar vaccines for other respiratory viruses, like the flu, and other coronaviruses, including SARS and MERS. The other coronavirus vaccines have made it through animal testing before, although they weren’t brought to market because of a lack of demand, the company says. The flu vaccine will soon undergo human testing.
Dr. Gregory Glenn, president of research and development at Novavax, said the company plans to begin human testing of the SARS-CoV-2 vaccine in May or June, with results expected by the end of the summer. They are currently testing several different vaccine possibilities in animal trials now.* Normally, it takes several years to get a license, but this pandemic may mean an accelerated timeline. “Usually you do phase one, phase two, phase three—that often takes, you know, six to eight years,” he told me, pausing. “This can’t.”
Glenn hadn’t heard the news about Moderna, he told me. “That’s kind of remarkable,” he said. “That shows the FDA’s flexible.” If the regulatory agency is changing its mind about how it’s typically done things, he said, that could be good news for vaccine makers.
But Evans isn’t so sure. The Trump administration has largely failed to act during this pandemic, he said, “but at the same time, we’re seeing the shredding of regulations and regulatory norms as part of their response to this outbreak. That’s a really dangerous proposition.” Evans said, “I am concerned about what it means for this particular trial, but I’m also concerned about what it means for all future trials. I think that could be really bad for science, and that could be really bad for the people involved in this trial.”
Evans is particularly worried that fast-tracking human trials and potentially exposing people to risk could become fodder for the anti-vaccine movement. (Trump, now a vocal supporter of the coronavirus vaccine, has a long history of anti-vaccine statements himself.) If the study participants experience adverse side effects from new vaccines that haven’t been thoroughly tested, others might be less likely to trust vaccines in general. Even if the study goes well, Evans said, anti-vaccine advocates could use the rushed process in this case to argue that the entire vaccine industry is unsafe and poorly regulated. Broad swaths of the population refusing to give their kids the polio or measles vaccine could have devastating consequences. Evans urges caution. “I think that everyone is very panicked, and I think that we are running a real risk of creating more problems, years in the future,” he said.
These trials, which normally take years to conduct, are only the beginning for creating an effective new vaccine. The next step would be getting them approved by the FDA and producing them on a large scale. But how vaccine makers conduct themselves in this health emergency could have ripple effects for years to come.
*This piece has been corrected. Novavax will be starting human trials, not animal trials, for their SARS-CoV-2 vaccine this summer—the animal trials are already underway.