Ben Neuman, a professor at Texas A&M-Texarkana, was one of the world’s top experts on coronaviruses long before most of us had ever heard of them. He also loves explaining science to non-scientists.
This week he discussed how the U.S. fight against COVID might move forward from here. (Spoiler: Vaccines alone won’t be enough to save us.) And also loads of new scientific breakthroughs.
A couple of months ago, when we last talked, you were feeling discouraged about the U.S. virus response and the general loss of faith in science. Does Joe Biden’s new task force make you feel better?
Yes and no. On the positive side, these are familiar names that I know. They’re people that have worked in public health; they know public health; and they’ve been involved in some way in the COVID response.
On the negative side, I don’t see any actual coronavirus people on there — virologists who study coronavirus in particular. There are certainly a couple that I could recommend to them and that I have tried to recommend. So they don’t have anybody that really knows the virus inside and out. The closest would be Mike Osterholm, director of CIDRAP — the Center for Infectious Disease Research and Policy at the University of Minnesota.
So they’re kind of lopsided. Maybe they just want policy people in place first, and will then reach out and try and figure out what to do, and it does seem to be a decent mix.
Generally, I am hopeful that something will change. But in terms of getting out of all this, at this point the vaccine is going to help but not be enough. We’re going to have to have masks with the vaccine, and those two at the same time are still probably not enough to actually knock this thing out.
We need testing of everybody twice a week — like, every single person, and not just in Texas, every person at least in America, and then we could eventually roll it out to the world. That can be done.
But there’s a lot of organization to do. You need your neighborhood COVID coordinator, and [laughs] I don’t know mine yet.
We also need to have the tools, like the tests. The rapid antigen test is as easy to operate as a pregnancy test: You have to put six little drops from a bottle onto the thing to make it work. I figure most anybody can do that.
The pieces are there. It’s the money behind it, and the organization around it, that I have yet to see coalesce. I suppose we have to wait — until January anyway — for any sort of change there.
Something good could happen before then. I hope it does. I have been waiting and hoping all this time and haven’t seen it.
So until January, I’ll hope. But once we get to January, I expect something new and big — hopefully big enough to get us out of this.
Vaccines won’t be enough? We can’t expect the combination of vaccines and whatever herd immunity we’ve acquired to wipe out COVID?
None of the vaccines gives stronger antibody responses than actually getting the virus, and the response from actually getting the virus seems to wear off in something like three to six months.
Immunity wears off for everybody? Not just in rare cases?
For everybody. On average, the antibodies dropped down faster in people over 65. After three months, something like 30 percent or 40 percent of them are still antibody-positive. For younger people, something like two-thirds still have some remnant of an immune response after three months.
In any age group, there are going to be some people who are not protected. And there so much virus swirling around at the moment that I don’t like the odds. I wish we were doing something big right now, rather than sitting on our hands and waiting and talking about it.
The thing on everyone’s mind right now is the recent good news that Pfizer announced about its vaccine. Can you talk about that? How do they calculate that it’s 90 percent effective?
Nobody knows exactly what that means. They haven’t released the data. You can take a rough guess, though.
If I were designing the study in the simplest possible way, I’d take those 40,000 volunteers and split them into two groups of 20,000: a test group and a control group, so we could compare people who got the vaccine to people who didn’t get it.
The one piece of information we have on the test is that they waited until they had 94 cases somewhere among the 40,000 people. Then they had their analysts take a preliminary peek. It’s basically opening the oven a little bit early to check out the cake. That’s not usually recommended in baking, but it is something that’s done sometimes in vaccine efforts because if the vaccine is not helping, or is making things worse, then you don’t want to keep using it.
The vaccine itself is kind of neat: They have pared the virus down to just 2 percent of its genome. That’s the only thing this vaccine is going to show to your immune system. And your immune system can really only do one thing with it, which is make antibodies.
So they’re cutting out the other side of the immune system. It’s like saying, “We don’t really need T cells. We’re just going to fight virus this one way.” For some people, this is probably going to be an absolute home run. Other people are just not going to be able to do a good job with this little tiny bit of genome.
Normally, if you have a little bit bigger piece, like in most of other vaccines, there’s more of a chance that something is going to work. And generally, as long as you can get some part of your immune system fired up, there is a path to protection.
So I think this approach will have high variance — a high ceiling but low floor. But it’s neat that it’s come out and gotten this far.
And you saw the news today about the Russian vaccine? They announced that they are 92 percent effective.
What is the Russian vaccine? Do we know anything about it?
Oh, yeah! This is actually the vaccine for which we have the clearest and most complete set of data — paradoxical as that may seem. They’ve done the most tests, and they’ve done them the best, weirdly enough.
It’s a combination of an adenovirus vaccine that they made in China and an adenovirus vaccine that Johnson & Johnson are making over here. So it’s just a shell from this thing that causes something like a common cold or a sore throat. They’re throwing away almost all the virus — they don’t need that part — they’re just packing the vaccine full of one gene, the spike gene. That’s around 13 percent of the entire virus’s coding capacity.
That’s significantly more than the 2 percent with the Pfizer vaccine. So you have a little more leeway in how your body chooses to make an immune response. That will probably protect more people because the immune responses won’t be as concentrated on this one spot.
We have yet to see which is a better approach, Pfizer’s or the Russian vaccine. I don’t think the difference between 90 percent and 92 percent is big enough that we ought to read anything into it. And the Russian results are just as preliminary as Pfizer’s, just as cake-not-quite-done-yet. They both need to shut the oven now and finish the bake.
With these announcements, are you seeing the kind of detail that you expect from a scientific study?
There’s no scientific detail here. These are PR-based announcements. I think each group is trying to get out in front of the other.
I like it that the Russian vaccine just ended up being 2 percent better. If it feels like a war of very, very small details for hearts and minds around the world.
I think you’ve probably got a couple of vaccines that work roughly equivalently. That’s fine: We can protect more people if we have more vaccines in more places. I like that.
How can we non-scientists tell the difference between shaky science and solid science? What basic advice do you give regular people — to you mom or to your cousins?
[Laughs.] They don’t always listen to all the things I say. When you’re at home, you’re part of a family. You’re not the expert.
What I do is, I try to see how deep I can dig into the claim. There are so many layers to good science: They will tell you exactly how they did the experiment, exactly all the ingredients that you would need to reproduce this recipe at home. They’ll show you all the data points, not just, like, a bar graph that sums up 100 data points. They will have larger sample sizes — more people or cells or whatever is being studied.
After that, the regular public can fall back on the the second trick that I use, which is, “Okay, says who?” You have a quick little Google, and you try to see, “All right, what is this person who’s telling me this thing? Is there a reasonable chance that they probably know what they’re talking about?”
The thing with science is, we all have our fields, and our fields are fairly narrowly defined. Generally, if you’re a scientist, you’ll be pretty good in your field, and it’s going to be pretty rocky when you get even just a little bit off the path.
So consider someone like me, who studies coronaviruses. Even within coronaviruses, there are areas where I am much stronger than other areas. When we get to other viruses, I am at least a step slower than I am in the coronaviruses. And when we get something to something beyond — like RNA viruses that are related to coronaviruses, my opinion is not that much more informed than anybody else’s.
So you look for people that are working inside an area where they seem to know something, where they maybe have a job already. For example, it may seem that a medical doctor would know everything about the human body, but even medical doctors have their specialties. And frankly, we’re all much better off when we stay in our specialties. That’s when you’re getting expert advice, or at least informed advice. When we’re outside our specialties, it’s mostly just talking.
I still like it when you tell me about the latest coronavirus science news, even if it’s not quite your field. I know how closely you’re following it. What’s the latest? What excites you?
What isn’t the latest news? This has been a heck of a week.
The Regeneron antibody therapy is really neat. To make that thing, they bred a mouse so that they took out its immune system — all the genes that make its antibodies — and they put in all the ones that make human antibodies. So they’ve got a mouse that makes human antibodies. That’s really good because if you put mouse antibodies into a human, they’re going to be recognized as foreign and then not going to do their job.
I like the Eli Lilly approval, too. That treatment is just a single antibody. Once again, it attacks the virus at this little tiny part, which happens to be the same part that they’re trying to vaccinate against in just about every vaccine that we’ve got out there.
The tiny part they’re all attacking — is that the coronavirus spike?
It’s a little tiny piece of the spike. We’re aiming for the Achilles’ heel — a little teeny-weeny Achilles. [Laughs.]
Why is that spot special?
The spike is a three-pronged battle club of a thing. It kind of looks like a little tree. At the top, there are these three little modules that will open up and sort of stand up, and then lock back down. The spike can have one, two or three open at a time. And until they open up, the spike can’t actually stick to anything meaningfully: It can’t find the right cell that it’s going to enter.
They’re trying to do two things with the antibodies. One is, put an antibody on there that keeps the spike locked down so it can’t reach up and grab anything. The other is, just stick the antibody to that one little tiny bit of surface at the very top of the spike where the spike would attach to something else.
The problem is, it’s difficult to target this site because it’s made of little tiny loops of protein from lots of different parts of the protein. The normal way that antibodies get made is, you sort of stretch out a little piece of the protein and you say, “Okay, I’m going to make an antibody from 17 to 34, and it’s going to be great.”
But with this one, 17 may be on the surface, 34 is buried way down in the interior and you have to make a thing called a conformational antibody. We don’t need to go into that. But it’s harder to do. If the immune system were just randomly rolling dice the way it does, it’s less likely to come up with that particular combination.
That’s vaccine making: trying to get the immune system to do this difficult thing that it’s not likely to do otherwise.
That’s very cool. Okay, so back to new science: What else are you excited about?
A really neat paper just came out in Cell and just came to my attention. (I think the pre-print was out a month ago.) The virus is using a thing called a lysosome to get out of infected cells so it can go infect new ones.
You say, “Okay, ‘lysosome.’ That’s a science word. Who cares?”
A lysosome is a little chamber inside a cell. It’s like the stomach of a cell; they break down whatever goes in there. It is full of acid and enzymes whose job is to chop up things like coronavirus. A lot of viruses get into cells through the lysosomes. But they try and get out just before the lysosome snaps down and destroys them.
This coronavirus is finding a way to deacidify the thing. The viruses are poking enough holes in the lysosome that all the acid leaks out; they’re shutting down all the proteins that would be chopping them up. And then they take a joyride in the empty lysosome: They’re loading it up with hundreds of viruses and using it as a car to get out of the cell.
Knowing that is really cool. It is not what I expected to happen. Usually if something goes into the lysosome, nothing but tiny shredded bits comes out.
Does that offer potential therapies? Or is it just exciting to understand how this virus works?
That’s a good question. Drugs like hydroxychloroquine stop the lysosomes from having a low pH; they sort of turn it into a neutral pH. Normally we use those because on the way in, the viruses sense the drop in pH, and that drop is like a timer that tells the virus when to get out before it hits the digestive pits — like the Sarlacc pit, basically.
But if the virus is exiting through the lysosome, that suggests that in addition to maybe messing with the timer, hydroxychloroquine is also probably hurting things in another way. It’s playing right into the virus’s hands, doing the thing that the virus would otherwise have to work harder to do. That’s probably one reason why hydroxychloroquine didn’t work out particularly well.
So no, knowing about the lysosomes doesn’t directly lead to a therapy, but it kind of explains why another therapy didn’t work.
Any other new science?
We’ve learned that there are two populations of cells that seem to really go after this virus; they get really, really stimulated when the virus is there, and when they are turned on, they seem to do a good job at knocking back the virus. They’re two kinds of what we call “helper T cells.”
Now, normally in this world, there are two kinds of helper T cells: Type One and Type Two. But these are neither of those. These are Type 17, Th17. One of these we’ve only just learned about. The other one is still so new that you don’t find it much in most textbooks.
We don’t understand fully what these things do, but they seem to be the major driver in immunity against this virus. So the virus is teaching us how the immune system probably always worked — it’s just easy to see here, because it’s the big component.
We’ve been trying a lot of immunotherapies to kind of knock out the Type Two helper T cells and cheer on the Type One helper T cells, but it turns out that none of those have worked very well. Now we’ve kind of got an explanation: “Oh, yeah, neither one of those was actually the target.” That’s the good side of it.
The bad side of it is, we’ve also got really nice data about people’s T cells from, I think, six months after they were infected. It turns out that both of the ones that we see prominently during an infection are gone then, and the T cells that are left are making signals that would absolutely stamp down any attempt to make those useful T cells appear again. They’re driving the immune system in a different direction.
So I don’t know that we can count on a T cell response the second time a person gets infected. And those second infections have been rolling out all over the place. There was a paper from Mexico a couple weeks ago with, like 285 second infections; I believe they had PCR-confirmed all of those, which is crazy.
We’re seeing now average time to reinfection is somewhere around two-and-a-half to three months, which is really not great. So in terms of vaccination, what are we gonna have to to protect people who have been sick and have recovered?
The immunity window is small. You can’t really tell how small until you get reinfected, and nobody wants that.
We also know that the virus is sometimes worse the second time, and sometimes not as bad. On average, based on the limited data we have so far, the severity is pretty much as severe as the first time.
Understanding this is very interesting for biologists, but there aren’t a lot a lot of obvious ways to change it yet.
How’s the pandemic affecting you personally?
We’ve had infections in the family. Every family is probably gonna get touched at some point. There are just so many cases around here.
You read about achievements in reducing the infection rates, generally outside Texas, and that makes me feel a little bit better. But then I go into Walmart, where maybe a third of the people are wearing masks, and that makes me feel really bad.
I’m feel like I’m giving the right advice to people, but a lot of people would not like to hear that advice. I’m not sure what else to do, except to keep trying.
Was anyone in your family seriously sick?
They’re seriously sick. One hospitalization. And one person had blood oxygen levels down in the 75th percentile, which is not what you want. But both pulled through. It could easily have gone the other way. I’m very glad that it didn’t.
We’ve even had cases of people around me who have this sort of persistent COVID-19. It lasts for month after month. It’s really terrible for that person because you just quarantine for what seems like forever. They’re expecting this to be over — just an acute illness that goes up, goes down and then you’re fine. But for some people, it is not working out that way. And we don’t really have an explanation.
You’re saying that they’ve stayed COVID-positive for more than two weeks? The infection just lasts?
It just lasts.
So they’re still sick, and they’re still infectious?
Presumably still infectious, yeah. Not particularly sick, but very virus-positive — virus-positive by the least sensitive tests. What do you do?
I don’t think we’ve seen anything quite like this in medicine. And I don’t think anybody’s quite set up for how to deal with this.
Anything else you want us to be thinking about here in Houston?
I would say, don’t read too much into any anti-vaccine stuff that you hear. All the vaccines that have gotten into Phase Three testing which is all the ones in Operation Warp Speed plus several in China and around the world all of these have all published very nice complete safety profiles. It looks like the worst that most people experience a sore arm where they inject the thing. And that’s really not bad. That’s the lowest baseline for negative effects of a vaccine.
These things are still erring very much on the side of being safe. They may not be as effective as they could be, but they sure as heck aren’t going to do anything bad to you.
I would take one. I’ve read the papers, looked at it, and yeah, any of the ones that are through Phase Two right now seem to be generating some immunity, don’t seem to be causing serious side effects. And frankly, those are the two things that you need right now for an effective vaccine.
The common cold is a coronavirus. Could all this research stop the common cold?
The common cold is 40 or so different viruses, each of which has separate causes and cures, and are mostly unrelated to each other. You can knock out maybe somewhere between 5 and 25 percent of the common cold by attacking other human coronaviruses that we know about. Then you have to go after the rhinoviruses, the metapneumoviruses, the pneumoviruses, etc.
So stopping that one coronavirus’s spike protein won’t knock out my sniffles?
No. Antibodies against coronavirus do not seem to do anything against the others. They’re so diverse. It’s just minimal similarity between any two of these.
But if they can make a vaccine for SARS-COV-2, they can make a vaccine for any of those things. This would provide the road map. And then we could start building roads.
