11/04/2022

The Quest For New COVID-19 Solutions

17:28 minutes

a simple watercolor painting featuring a 6x4 grid made up of turquoise circles. inside every other circle is a covid virus particle
Credit: Shutterstock

As we head towards our third pandemic winter, the nation still is facing about 2,500 weekly deaths from COVID, and over 3,000 people a day entering the hospital due to the virus. 

Dr. William Haseltine is chair and president of ACCESS Health International, a former professor at Harvard Medical School and Harvard School of Public Health, and the founder of several biotechnology companies, including Human Genome Sciences. 

“This thing knows everything about our immune systems,” Haseltine says. “We have to find new drugs that it has never seen before, and new combinations of those. That’s what’s worked for HIV. That’s what we have to do now—and we’re doing a very poor job of that.”

Haseltine joins Ira to help explore the viral landscape, and where he sees viral research headed—from new vaccines to antiviral drugs and antibody cocktails. 


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Segment Guests

Willam Haseltine

Dr. Willam Haseltine is Chair and President of ACCESS Health International in New York, New York.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

As we head towards our third winter with COVID, this may be a good time to reflect on the paths taken to deal with the pandemic, the development of the vaccines, the distribution, and what may lie ahead. Case in point, Pfizer announced last week that your vaccines may no longer be free next year. Retail price, about 130 bucks per shot.

So what does this all mean? Here to help explore the viral landscape is a scientist who has spent a lifetime researching and battling viruses and who frequently writes about where he sees viral research headed, Dr. William Haseltine, chair and president of ACCESS Health International, former professor of Harvard Med School and Harvard School of Public Health, founder of several biotechnology companies, including Human Genome Sciences. Dr. Haseltine’s writings appear regularly on Forbes Online.

Welcome back to Science Friday.

WILLIAM HASELTINE: Well, thank you. As you said, it’s been 20 years, so I’m happy to be back.

IRA FLATOW: It certainly has. Lots has happened. Let’s talk about some of this stuff. What is there about this disease that the public needs to know, that you spend so much of your time writing about?

WILLIAM HASELTINE: I think the first thing to know about– what it is. And I think most people don’t really have a good grasp of that. It’s a virus, like the flu virus, that’s very well adapted to infecting an adult healthy animal, and then reinfecting them shortly thereafter. And we know that because its natural habitat are bats.

Now, something most people don’t know about bats– they live a long time. They’re about the size of a mouse or a rat, but they can live 20 to 30 years. And these viruses infect them every year, year in and year out, kind of like our colds.

But what does that mean? It means the ecological niche for this virus is an adult healthy person that it infects again and again and again, even if it infected them before. And that means it’s got lots of tools to do that. That’s its niche. We happen to be the new target, the new ecosystem.

IRA FLATOW: So we shouldn’t be surprised, then, about how many times we can get infected?

WILLIAM HASELTINE: No. Just like the flu, it comes back and it changes. This is even more subtle than the flu. It’s bigger. And Science Magazine had it right on the front of its cover, a beautiful issue a couple of weeks ago, calling it an immune saboteur. Not only does it change its code, but it’s got– we’re still counting– and I’m counting up to 35 to 40 different ways– it can jimmy our immune system. So once it gets in, it shuts down your ability to see it until it gets out. And then it doesn’t care what happens to you.

Some of its cousins kill 10% of us. Some of its cousins kill 30% of us. We’re very lucky. This one only kills about 1% of us.

IRA FLATOW: Earlier in the pandemic, there was an idea circulating that, as the virus mutates, it tends to get less severe. Has that been the case here?

WILLIAM HASELTINE: There’s arguments about that. But let me just put an end to that myth. Think about tuberculosis. Think about malaria. Think about what smallpox did when it was rolling on. Did it get, after thousands of years, any less horrible? No. That is not the way pathogens go. They don’t generally get weaker. So that’s a myth. And it’s, I think, a dangerous myth.

What’s the case for this? It’s very hard to tell because the population has changed. There’s tremendous experience of the population now with this, and there is some partial protection.

There’s one other thing I think people should know. Right now, we’re in an era of complacency. I live, amongst other places, in New York City. And the city, it’s as there’s no virus around. There is virus around. But the important thing to know is the vaccine will protect you for about two to three months from infection. It will protect you pretty well for five to seven or eight months from ending up in the hospital or dead. But then, all bets are off.

The idea that there’s perpetual protection from the worst thing this virus can do to you is not right. The latest data that’s coming out says that protection from hospitalization, and even worse, ends, or actually wanes. It just wanes more slowly. And that’s what you would expect for a virus like this that’s got all these tricks– to come back and get you again and again.

So the last thing I like to say that people should know is this thing is around to stay. Unless we’ve learned how to put it to bed, like we’re learning for HIV, to use drugs as well as our immune system to fight it– this thing knows everything about our immune system. It knows how to fight it. We’ve got to find new drugs that it’s never seen before, and combinations of those. That’s what’s worked for HIV. That’s what we have to do now. And we’re doing a very poor job of that.

IRA FLATOW: What do you mean we’re doing a very poor job of that? Please tell us what you’re talking about.

WILLIAM HASELTINE: Well, you can count on your one hand the number of drugs we have. And those aren’t really great drugs. As somebody who’s worked on developing HIV drugs, both the theory and the practice, we now have super drugs. We now have a drug that you can get injected once every two months and you won’t get infected. And you’ve got the virus, HIV, it won’t make you sick. We’re on the brink of having a shot that’ll do that every six months.

We are so far away from that for this disease. For example, Paxlovid. Paxlovid doesn’t stop you from getting infected. Paxlovid does have an impact on keeping you out of the hospital, but only about 50%. We’d like it to wipe out the virus completely.

I had COVID last May. And I took Paxlovid for– and I mention Paxlovid because it’s our best drug– I took Paxlovid for 10 days, and I was virus-positive for 15. So is that a good viral drug that’s wiping it out? No.

Yes, it’s an important drug to have, and I urge everybody who gets infected to take it because it does reduce your chance of ending up in the hospital. But it is not the powerful drug that we want.

IRA FLATOW: Why don’t we have that powerful drug like we have with HIV?

WILLIAM HASELTINE: Well, it’s taken us 40 years to get where we are. I think we can do it in five or six years if we really put our mind to it. But developing drugs is a complicated business. I’ve been at it for a long time. And the way I liken it to is like saying we’ve got to fix my Ferrari by throwing a wrench into the engine. OK, it’s a complicated machine. There is a small chance it will get better. There’s a lot bigger chance it’ll mess something up that I don’t know about yet. So drug development is tough, and you’ve really got to have a lot of knowledge.

Now, there’s one or two little pieces of the SARS-COV-2 virus that we know well enough to begin to do really rational drug design. One of them is how it puts a cap on. Because it’s a completely differently way from most other viruses and cells. But it gives us a great juicy target, and we know every atom involved in that process. And so we can start to make drugs. But we know very little.

This thing has a giant replication machine. It’s got many moving parts. You can probably mess it up a lot of different ways. We only have one way to mess it up, which is screwing up its polymerase a little bit. Not working as well as we’d like. And so we just need a lot more research on this. We have the tools now. And thank goodness. We have so much better tools than we had at the outset of HIV that it’s just incomparable how much more we could do in the time we could do it. But we’ve got to do it now.

IRA FLATOW: Who’s the “we” we’re talking about here? Is it drug companies, the NIH? I mean, is there money–

WILLIAM HASELTINE: I mean, it’s really not the drug companies yet.

IRA FLATOW: No.

WILLIAM HASELTINE: Drug companies are able to take something that academics have shown will work and then turn it into a drug. We need the companies. And actually, we need the companies to work more closely together.

What really worked for HIV? First of all, money. The United States was willing to spend $2 billion to $3 billion a year on HIV research. Second, the collaboration– a very tight collaboration– between academia and business.

In fact, I remember working with Dr. Fauci to create a special series of grants in which the federal government would give an academic laboratory money provided they had an industrial partner which would develop their drug. That’s the kind of programs that really work. We have a couple of those, but we need to expand them.

IRA FLATOW: We don’t even give money now for preparing our society for the next attack of a virus, right?

WILLIAM HASELTINE: You’re getting into a series of politics and other questions, but it is the case– and I’ve been working on health policy for a long time now, too– that there are great reports– the Commonwealth Fund just did a really important d on the need for a powerful national public health service. We don’t have it. It’s all Balkanized. And that is a Commonwealth Fund report. My friend Peggy Hamburg chaired it. She was former head of the FDA. It’s a great report. It shows you what we should do. Will we do it?

The same thing– the National Academy of Medicine did a wonderful report on how we have to integrate our health care services across the nation to help people who are underserved, and talked about the way we deliver health care now. A beautiful report. It tells us a clear idea of where to go. It’s now up to us, as American citizens, to make sure that our politicians follow the directions we need them to follow.

But you know as well as I do that this country is in a difficult spot right now.

IRA FLATOW: Yeah. And you’ve written– just moving on a bit– that new research published in Science Translational Medicine suggests an mRNA vaccine that targets both the SARS-COV-2 spike protein as well as something called the nucleocapsid protein may offer stronger and broader protection than current spike-only vaccines. This research opens the possibility that one vaccine may protect against current and future variants.

I’m asking– is it possible to create a universal COVID vaccine?

WILLIAM HASELTINE: Well, thank you for asking, Ira. That’s a topic really very close to my heart. And I do think it’s possible.

Let me just tell you what I was working on just before we started talking. It’s a great paper, a wonderful group. Dr. Saphire, in La Jolla, has done some very beautiful work on developing antibodies, cocktails of antibodies, that neutralize two really important viruses. One everybody knows about, Ebola. And she’s developed drugs that will probably work against this new Sudan strain. Very exciting.

She’s just recently published one on another nasty critter out there called Lassa. And she’s got a cocktail, three antibodies, that you know exactly atom to atom which ones it touches, and can lock the thing up and probably stop that, too. So I think we can do this. There are cocktails now of monoclonal antibodies that are very broadly neutralizing. They neutralize not only SARS-COV-2, but SARS-COV-1 and MERS, and some of these crazy bat viruses. You can do this.

Now, they’re also beginning to use that knowledge to design vaccines. Is it possible to design vaccines? Well, let me talk a little bit about some of the mRNA vaccines.

We’re really excited that RNA can now be used directly as a vaccine because it’s really simple to make, a totally chemical process, and it’s really fast and flexible. But the way it’s currently being used with these modified nucleotides– you stick it in, the RNA lasts a couple of days– the protein is there for no more than two to three days– and then your immune system can’t see it anymore.

There’s now something called self-amplifying messenger-RNA, really exciting. You put a little bit of the RNA, and it makes a lot of the RNA. You don’t put it in the muscle. You put it in the layer of the skin where most of your immune system can see it. And that is giving very, very good results. The antibodies last for up to a month. Your body gets to see it. And you can add lots of different proteins very, very easily, including what you mentioned, the nucleocapsid.

And when you do that, you get some broad reactions that can react all the way across most of the SARS variants– in fact, all of them that I know about– the MERS, as well as SARS-1. So I think there’s some good things coming both with the vaccines and with monoclonal antibody cocktails, and hopefully, eventually, for small-molecule drugs. It’s not impossible to put this thing behind us. It’s just hard.

IRA FLATOW: This is Science Friday, from WNYC Studios.

In case you just joined us, we’re talking with Dr. William Haseltine about the future of the COVID pandemic and lessons learned.

You’ve worked with many different viruses, as we’re talking about. And many people, as you say, know of your work with HIV. And I’m wondering what you can tell us, what we can learn from those other viruses, about living with COVID.

WILLIAM HASELTINE: Well, we live with flu. And we’ve lived with flu all our lives. I’ve been in bed for 5-10 days, five times from the flu. I’ve lived with flu. I haven’t liked it, but I’ve lived with it. I get my flu shots and, most years, they work and some years they don’t. But the difference between this and flu is this is a worse virus. It’s much more lethal. It’s already killing, on average every year, a lot more people than the flu does. It’s not seasonal. It doesn’t come along only in the winter. It comes along fall, spring, summer, and winter. So it’s not seasonal like flu, which makes it nastier. And it affects many more organs.

So yeah, we can live with it. But right now we’re living in sort of a lull. And the average is about 500-600 people a day are dying. What would we do if an airplane fell out of the sky and killed 500-600 people every day? We wouldn’t like it, right? But that’s what’s actually happening right now. And it’s not seasonal. It’s been a pretty constant drumbeat.

And so, yeah, we can live with it. Hopefully, it won’t get worse. The real nightmare for somebody like me, who thinks about what these viruses can do, is I know that, with some very subtle change, this could move from killing 1% of us to 20% to 30% or more. We don’t know that’s not going to happen.

So the reason you hear people like me say, we’ve really got to control this as much as possible, it’s to reduce that possibility. The more viruses that are out there in humans, the more they get into our animal environment, the more likely it is that something worse will happen– not better– worse.

And I can give you enough examples to curl your hair about how viruses get worse– one of the questions you asked me at the very beginning. We know how it happens. We know it can happen. And we’re just praying it won’t happen now.

I would say something else to think about, and why we really have to pay attention to this. This is happening to us not because we’re moving into new ecosystems, but because we are a new ecosystem. When I was born, there might have been 2 billion people in the world. There are 8 billion today. That’s a lot more people. There are 5 billion single airplane flights, with people taking flights, a year. We move around a lot.

Think of us as bats congregated together in a cave. When you’re on one of those cramped airplanes, that’s like being in a bat cave. And these viruses are taking advantage of a brand new ecosystem. We’re great food for viruses, and we’ve got to be able to protect ourselves.

IRA FLATOW: Dr. Haseltine, you’ve given us a lot to think about, both scary and hopeful.

WILLIAM HASELTINE: In the end, I have more hope. And the reason I do what I do is I think that there’s a lot of hope. There’s a lot of great people out there that I work with. And we have really great scientists and great people working on this.

IRA FLATOW: So would it be fair to say you’re more hopeful than fearful?

WILLIAM HASELTINE: Yes. Cautiously optimistic that we can do better.

IRA FLATOW: Thank you very much for taking time to be with us today.

WILLIAM HASELTINE: You’re welcome. Thank you.

IRA FLATOW: Dr. William Haseltine, chair and president of ACCESS Health International.

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