For months, grateful people have been sending letters to one man, thanking him for helping bring them out of the isolation and lockdown of the pandemic. He did that by working for 20 years on a molecule that few others thought would make any difference.
Dr. Drew Weissman, together with Hungarian-born scientist Katalin Kariko, spent decades trying to turn messenger RNA, or mRNA—the genetic instructions that tell cells how to build proteins—into a vaccine. Whereas Weissman brought his expertise as an immunologist and interest in vaccine development to the table, Kariko contributed her exhaustive knowledge of RNA, convinced it could be harnessed to revolutionize how diseases are treated. In 2005, Weissman and Kariko found a way to vastly increase the therapeutic potential of mRNA, although their discovery went mostly unnoticed. “Our phones never rang. Nobody cared,” Weissman said. “But we knew the potential and never stopped working on it.”
A native of Lexington, Massachusetts, Weissman pursued a joint medical and scientific degree at the Boston University School of Medicine. In 1991, he went to work under Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. In 1997 he was recruited by the University of Pennsylvania’s medical school, where he was chief of the infectious-diseases division.
Not long after the move to Penn, Weissman ran into Katalin Kariko at the photocopier, where she proceeded to tell him about mRNA and her intention to turn it into a powerful medicine. Weissman wondered if it could also be a way of delivering a foreign viral protein to the dendritic cells that he wanted to target for vaccine development. He asked Kariko if she could synthesize some mRNA for him to try in an experiment.
For seven years they worked on turning mRNA from a biological process into a medical technology, trying everything to push their ideas forward, including securing grants. They also founded a company to turn their technology into a vaccine that could save people’s lives.
More than a year before the pandemic, Dr. Weissman and his colleagues demonstrated that mRNA is key to a robust immune response, because it triggers T follicular helper cells. Those T cells then drive the immune cells that produce virus-fighting antibodies.
After the pandemic started wreaking havoc in the world, this technology was propelled onto the world stage, serving as the backbone for the Pfizer-BioNTech and Moderna COVID vaccines, which use mRNA to teach the body how to recognize and block the coronavirus.
To date, Dr. Drew Weissman has received some of the most prestigious awards in science and medicine, including the Lasker-DeBakey Clinical Medical Research Award. Time Magazine also named him one of its Heroes of the Year.
You’re considered the father of the mRNA vaccine that is currently being used to immunize people against COVID-19. Is that correct?
There wasn’t one father; there were many different elements that were required to make it. Kati Kariko and I developed the mRNA; Pieter Cullis and Ian MacLachlan developed the lipid nanoparticles; Barney Graham and Jason McLellan developed the spike immunogen; and there were many others involved in putting the vaccine together, doing the clinical trials and testing it. Thousands and thousands of researchers had a hand in the making of this vaccine.
What inspired you to develop this technology before COVID came along? There were already good vaccines out there. What motivated you to try for something different?
There are a lot of diseases against which the existing vaccines don’t work well, including HIV, hepatitis C, genital herpes, cancer, allergies, autoimmunity and more. We wanted to develop a better vaccine that would work for them. Additionally, there are many other therapies that can be done with mRNA. Right now we’re doing gene therapy with it, fixing broken genes in sickle cell anemia. That can’t be done with other methods.
How many years ago was this invented?
We and others had been working on it for a long time, doing different animal models and vaccines, but the modified RNA was invented in 2005. Up until COVID no one knew about it. The two big vaccines being used right now, the Pfizer and the Moderna, are the first mRNA vaccines to be approved by the FDA and other organizations. So they’re considered the first mRNA vaccine in humans.
If not for COVID and the pressure that was put on the government to find a weapon against it as soon as possible, how long do you think it would have taken to get FDA approval on something so new?
I would guess around five years.
Donald Trump and his Operation Warp Speed team certainly deserve our thanks for pushing the FDA to approve it as fast as it did.
Yes. He did some good and some bad. He certainly pushed the vaccines, and Operation Warp Speed was a great accomplishment, but he also did some bad things over the course of the pandemic by playing it down and telling people not to take the vaccine.
I guess he’s repented since then, because he recently came out very strongly encouraging people to get vaccinated.
I’m happy he did that.
Do you think that because it was approved in record time we might not know enough to celebrate quite yet, or do you think we do have enough data?
The mRNA vaccines are incredibly effective and safe. They’ve been given to a billion people. No vaccine has ever been given to that many people. They were also tested in more people than any other vaccine ever developed. So while they were developed quickly, no shortcuts were taken. All of the testing was done appropriately. I’ve said that if we had taken five years to develop it, people would have screamed at us for going too slowly and allowing people to die. I don’t think we could have won on this one.
Can you explain how the mRNA vaccine is different from the old vaccines that we’re accustomed to?
It’s actually different from most other vaccines, including some that are being used for the coronavirus. The Chinese vaccines are inactivated, so those are like the standard influenza vaccines where you first grow the virus and then kill it. The J&J and AstraZeneca are adenovirus vaccines; those are viral vectors. That means that they put part of the coronavirus—the spike protein—inside an adenovirus, which is a standard cold virus, to serve as a delivery vehicle. It works well, but not as well as the mRNA. There’s also something called a protein subunit vaccine, which isn’t available in the US but has been approved elsewhere, where they take a purified spike protein and mix it with an adjuvant [immune stimulator] to immunize people. There are also DNA vaccines that haven’t been approved yet, as well as many others that people are working on. They’re all different technologies and platforms, but they all do the same thing: they stimulate an immune response against COVID-19 to protect people.
But the mRNA vaccine is different because it isn’t delivering the actual virus to the vaccinated. Is that correct?
It only delivers the spike protein, but then again, the adenovirus vaccine only delivers the spike protein and the adenovirus carrier, and the subunit vaccine only delivers the spike protein with adjuvant. So it isn’t that much different; it just uses mRNA to deliver the antigen instead of something else.
You were watching the attack of the coronavirus together with the rest of the world. At what point did you say, “I think I have the vaccine to fight it”?
In November 2019 I started to hear about a new pneumonia in Wuhan, China. I have friends who work in the Wuhan Virology Institute, and they were telling me about these infections. They themselves were scared and the Chinese government wasn’t saying how scary it really was. We knew it was a problem, so we immediately started working on an mRNA vaccine, because we knew it would be ideal. We could make it very quickly, it’s very potent and it’s also very safe.
Is there any evidence that getting the vaccination can expose a person to harm from COVID rather than offer protection?
There is no data at all that the mRNA vaccines cause harm. The only adverse effects we’ve seen—other than feeling lousy and the sore arm—are that two in a million people get an anaphylactoid reaction, and one in 100,000 young men develop mild myocarditis. But if you look at the numbers—and most people don’t—the COVID-19 infection causes myocarditis at a rate that is 30 times higher than the vaccine. So, yes, the vaccine does cause myocarditis in very rare cases, but it’s at one-30th the rate of the actual infection.
I spoke to Dr. Fauci and to Dr. Ben Carson about the response of the Trump administration. There’s been an ongoing debate about the vaccines, with some scientists saying that they were embraced too strongly at a cost to therapeutics. What’s your take on that?
The pharmaceutical companies moved very quickly to make these vaccines. The US government gave some of them a lot of money, but it also gave a lot of money to develop therapeutics, which resulted in monoclonal antibodies and now two pills that can be taken orally. All of these were developed incredibly quickly, and the US, EU and other governments all helped it to happen. So I don’t think that any resources were held back.
I wonder what your thoughts are right now as the world suffers from the omicron variant as well as numerous breakthrough infections. Will we ever see an end to this virus?
I think that COVID-19 is going to turn into a seasonal virus, similar to influenza. But I can’t imagine that it will ever disappear. The important thing at the moment is that we have to get the entire world vaccinated, and at a level that will turn this from a pandemic into just another seasonal flu-like virus.
Everyone talks about following the science, but there are so many opinions out there right now. One theory is that the virus is trying to outsmart the vaccine and is therefore mutating and infecting people who have already been vaccinated. I understand from what you just said that you believe the biggest issue right now is those who are unvaccinated. What’s your perspective on that?
The virus is mutating because two years ago it was in bats, and only in bats. Then it made the jump to humans, so all of the mutations we’ve seen are the virus learning how to better infect humans. And the virus is going to keep mutating. The fear is that in the future it will mutate to avoid the vaccine in the way that influenza does. We can’t stop that, but if enough people are vaccinated the spread will slow down, the amount of disease will slow down, and the world will be able to return to normal and see cases of COVID only in the wintertime, around the same time we see flu.
It seems that the mRNA vaccine hasn’t been able to stop the omicron variant.
What we’re seeing is that vaccinated people can still get infected. They’re about 75% protected from infection, but even if they are infected the illness is much milder and they don’t get as sick. They aren’t ending up in the hospital and dying the way unvaccinated people are.
I just read that France has discovered a new variant. Should we be concerned that it will be even deadlier than anything we’ve seen, or is that overreacting to this kind of news?
I wouldn’t overreact because new mutations appear all the time and all over the place. When those mutations grow more efficiently, like omicron, then it spreads. I work with people who sequence viruses all the time. They’re constantly finding new mutations, but they don’t matter unless they can spread better.
Israel is a country that really embraced vaccination, and they are now in the midst of distributing a fourth dose of the vaccine. Where do you stand on the number of doses a person should receive?
I look at it based purely on the data. After Israel gave people a booster shot they saw that after around six months the levels of antibodies in their blood dropped, so they said that they need another booster. That’s the best we’ve got right now.
Are scientists watching Israel very carefully because such a high percentage of its citizens have been vaccinated? Has Israel become sort of like the world’s laboratory?
Certainly. We rely on the data coming out of Israel on vaccine effectiveness and the need for boosters.
Looking back, a lot of people unfortunately died from this virus and some are still dying. What would you like to see happen at this point?
Obviously, the first thing I want is for the pandemic to be over, but that’s going to require vaccinating the entire world. I’ve been spending a lot of time helping Third-World as well as lower- and middle-income countries make their own vaccine so they won’t have to rely on rich pharmaceutical companies giving them some whenever they feel like it. Right now, only 3% of the African population is vaccinated, which is terrible. Asia is better. South America is a little bit better, but they’re also still in bad shape. We have a lot of work to do in order to vaccinate everyone. Once we do that, we can move to the next project.
There have been three coronavirus epidemics in the last 20 years: MERS, SARS and COVID-19. I would bet anything that we’re going to have more, so in the summer of 2020 we started working on a vaccine that would prevent any bat coronavirus from infecting humans. I think this is important and needs to be fast-tracked and given to people prophylactically.
How far along is that effort? Is it really going to happen, or is there only hope that it will?
We have money from the NIH and we’re working on it. We’ve been talking with BioNTech, and they’re interested in doing the clinical trials, so I think it will happen.
This might be more of a value question than a scientific one, but I’m sure it’s something that’s already been posed to you. Why not vaccinate people in Africa and other impoverished places before we start giving third and fourth shots to people in the more developed countries?
I completely agree. We should do that. Unfortunately, the pharmaceutical companies determine who gets the drugs sold to them, and the rich countries aren’t willing to forfeit theirs in order to give them to others.
But wouldn’t their citizens be better protected if people in Africa and Asia were also vaccinated at least once or twice?
You’re asking a politician to take the long view, and they don’t. People say, “I want my booster now.” They don’t think, If we vaccinate the world, COVID will be gone.
So from a purely scientific perspective, it would be better to first vaccinate the world before giving out boosters.
Yes. I think we need to do that.
I think that what confuses laypeople is that while the vaccine doesn’t afford complete protection against omicron, if more people were vaccinated there would be better protection overall.
Well, we are protected from omicron, we just aren’t completely protected. To me, that’s what’s most important.
Do you fear that the mutations in a year or two will be more severe than the original SARS-CoV-2?
I don’t think that will happen. What I expect is a bit of a complicated scientific thing referred to as fitness. When a virus mutates to avoid an antibody response from a vaccine, it has to change its proteins. When that happens, they don’t work as well and the virus loses its pathogenicity rather than becoming worse.
So we’ll see a weaker and less potent threat as it keeps mutating.
That’s my guess. It already looks like omicron is weaker than delta. ●
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