U.S. scientists raced to develop a rubella vaccine ahead of an epidemic expected in 1970.
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In 1964, an unprecedented epidemic of rubella (German measles) swept the United States. The virus responsible is about twice as contagious as the novel coronavirus spreading around the world today seems to be; rubella infected some 12.5 million people, an estimated one in 15 people in the United States. Like the novel coronavirus responsible for the current pandemic, the virus that causes rubella usually produced mild disease—in the case of rubella, typically fever and a rash. In about one-third of people, it caused no symptoms at all. Although the coronavirus does kill some people, especially the elderly, rubella caused by far the most damage to fetuses, especially when a woman contracted the disease in early pregnancy. During the mid-1960s epidemic, some 20,000 U.S. babies were born with serious birth defects including blindness, deafness, heart defects, and intellectual disabilities. (There’s no evidence so far that this new coronavirus infects or hurts fetuses, but it’s an open question.)
In 1964, working in his Wistar Institute laboratory, Stanley Plotkin invented the rubella vaccine—the “R” in MMR—that’s now used the world over. Since then, he has worked extensively on the development and application of other vaccines, including ones for anthrax, polio, and rabies. He also coinvented the rotavirus vaccine that’s part of today’s childhood vaccine schedule.
Science reached Plotkin, now 87, at his home outside Philadelphia, where he consults for vaccine companies. In recent weeks, he has been advising six of them on the development of novel coronavirus vaccines. This interview has been edited for brevity and clarity.
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Q: You lived through another pandemic that had devastating consequences in the United States and around the world. Tell me about it.
A: The infection was very widespread. The difference is that it was “only” pregnant women who were [primarily] affected. It wasn’t the general worries that you have with the current situation—although of course their husbands were also concerned. That being said, the panic among women either pregnant or wanting to be pregnant was considerable. I was able to calculate that in Philadelphia, 1% of all pregnancies were affected.
Q: Were you impacted as a young parent yourself?
A: I had one son who was a little over 1 year of age. And my wife was not pregnant. So, I had no personal concerns at that point. But I was running a research lab that became, in effect, a kind of unofficial diagnostic lab. And sitting with those women and trying to explain what the issues were, what the risks were, was eye-opening. There were women who decided to go on [with their pregnancies]. There were women who decided to terminate the pregnancy. But one thing that was common to all of them was the anguish.
Q: So, if rubella frequently didn’t cause symptoms, it must have been very unsettling for pregnant women. What measures did public health authorities take?
A: There really wasn’t much that you could tell them except to keep away from people who had evidence of rubella infection, primarily a rash. Otherwise one didn’t know who could be subclinically [having no symptoms] infected. That was part of the fear, that women could not know who was potentially a risk for them.
Stanley Plotkin is consulting with multiple companies trying to develop a coronavirus vaccine.
Stanley Plotkin
Q: Can you connect the dots to what’s happening today?
A: There are similarities. Obviously, if somebody has a fever one should not be in contact with that person. And we think we know that there are asymptomatic infections with [the novel coronavirus] particularly in young people or children. That’s why authorities are talking about social distance, not having touching contact. Today, as was the case with rubella, one did not absolutely know who might be infected.
Q: But there was no kind of social shutdown remotely like today’s?
A: There were warnings. There were lots of warnings to women. But there was nothing like what’s happening today.
Q: Before the rubella vaccine was licensed in 1969, rubella was cyclical, coming in outbreaks every 4 to 6 years. Should we expect that with the novel coronavirus?
A: That is the $64,000 question. I really have no firm answer to that. We all hope—and I underline hope—that the [novel] coronavirus will not persist in the population in some mild form that could pop up again and again. Bear in mind that there are three or four [different] respiratory coronaviruses that were isolated years ago and which are still circulating, and which cause fortunately mild respiratory infections. They are not going away. And we just don’t know about this coronavirus. That’s why the effort to develop a vaccine in the shortest possible time is so important. Because obviously if next winter [it] returns, we must have a vaccine by that time.
Q: How did the race for a rubella vaccine in the mid-1960s differ from today’s race for a coronavirus vaccine?
A: There were intense efforts and intense competition to develop a [rubella] vaccine. But remember that at that time there were not as many major vaccine companies as there are now with the advent of Indian and Chinese companies. At that time there were only a handful of major players, like Merck and [the company that is today called] GlaxoSmithKline.
Q: Your rubella vaccine was better than its competitors—it produced higher levels of antibodies and had fewer side effects—but here in the United States, it got sidelined and failed to win government approval for 10 years because of politics. Does politics always invade any vaccine race?
A: You have to say yes.
Q: What cautionary tale does the rubella story tell for politics invading today’s coronavirus vaccine race?
A: There are at least 40 vaccine candidates being developed in various companies and biotechs not only in the United States, but elsewhere in the world. The choice of which one is licensed should be made on objective criteria and perhaps not only one should be licensed. There may be advantages to having more than one anticoronavirus vaccine because if—and it’s a big if—one needs millions of doses, asking a single manufacturer to produce enough for the world is unlikely. One is going to need multiple manufacturers and if there are multiple effective vaccines so much the better. I am not arguing for the selection of a single coronavirus vaccine unless there are difficulties with others.
Q: Can you speak broadly about the different approaches—so-called platforms—being used by these dozens of companies to develop a vaccine? And how that differs from the 1960s?
A: [In the ’60s rubella vaccine race] it was live weakened virus only. Today we have so many different candidates: RNA vaccines, DNA vaccines, single protein vaccines, multiple protein vaccines. It could be there are multiple vaccines that will give both safety and efficacy. So, the good thing is that you have now multiple roads to get to the same point.
Q: Besides technology, do we have other advantages now that we didn’t have in the 1960s?
A: CEPI [the Coalition for Epidemic Preparedness] is leading the pack in the way of financing and helping to develop multiple vaccines [against the novel coronavirus]. They are financially supporting six projects right now. And that’s the kind of thing that was needed [in the ’60s] and is now fortunately in place, so that it’s not only commercial companies that are developing vaccines but an organization that can be creative.
Going back to the rubella experience, it took at least 5 years before a vaccine was on the market. And we cannot afford to have that kind of delay when you have an emergency such as this one. So, the prospect that we have of getting a coronavirus vaccine by next year, which I think is a reasonable hope, is a big difference. And the idea that we are more ready than we were, perhaps not ideally, but more ready than we were for an emergency that requires vaccine development is a positive point here.
Q: What else should we know from your decades of vaccine development experience?
A: One needs to prepare now—and I’m assuming that there will be a vaccine or multiple vaccines—for the production of large numbers of doses. Because that’s not something that you can do on your laboratory bench. We need to have companies ready to go into superaction and that needs to be done now.