Robert Gallo, MD, Co-Founder and Director, Institute of Human Virology, University of Maryland School of Medicine
Recorded, June 24, 2020
His session is available for viewing online. This is a transcript of the Q & A:
COVID Webinar Series: Transcript of session with Robert Gallo, MD
Robert Gallo, MD, Co-Founder and Director, Institute of Human Virology, University of Maryland School of Medicine
KRIS REBILLOT: Welcome.
ROBERT GALLO: Thank you for having. It’s a pleasure.
KRIS: How is it going in Maryland?
GALLO: I really don’t know. I don’t follow day-to-day. It’s, you know, not so great in the month preceding, two months preceding, but a bit better now. The county I live in, surprisingly, is one of the worst, if not the worst, Montgomery County, Bethesda, you know, right on the outskirts of NIH, etc. So I don’t even know why it’s so much here. But it’s… you know, the statistics show it’s getting better, so what can I say? But is it great? No. And we got hit very hard with the nursing home, that’s for sure. So that’s what I can tell you.
But I don’t think… yeah, I know we have to, I mean, somebody has to follow the numbers. I don’t… you know, personally, I don’t enjoy following the numbers so much. We got a problem. We have to solve the problem. I’m a little bit obsessive that way, you know, what I focus on, you know, this day with. But if you start following the numbers all over the place, you get so you think you can predict, like I heard yesterday from our friend Tony, that there are some states going up. Yes, we know. And in five weeks, we’ll know if it’s going to be better or not. Well, how about in one week, or how about in 10 weeks? How do you know in five weeks? And better to spend your time on thinking what are you going to do about it? I mean, you know, what the… you know what I’m trying to say.
KRIS: Yes. Talk about the oral polio vaccine.
GALLO: I thought you were going to start talking about the Baltimore Orioles, and they’re not that good, you know, these days. So I said, ‘Oh, god, she’s going to get into that. What do I do?’
Sure, I’m going to talk about it. Do you want to begin with the idea?
GALLO: Why did I get into it?
GALLO: Yeah. Oh, no, we’ll definitely get into what I think it will do, hope it will do, believe strongly it will do if we can get it going. The idea is not new. You know, we like to take a certain pride that we have new ideas. It’s not original. Though, by genetics, there’s a relationship because my closet colleague in this is Konstantin Chumakov, whose father’s picture is, among others, in the hallway as you enter our institute. He’s one of the great virologist, ever. He was Russian. Chumakov came to America as a young man and became Associate Director for Vaccines at FDA. It is his mother, working with his father, who made the first critical observation. Albert Sabin of this oral polio vaccine, who made it, who I used to know quite well, as well as Salk… I kind of bridged that generation… has said in writing that the whole vaccine concept wouldn’t have gotten anywhere without Chumakov. He’s the one who did it in Russia and showed it worked. That was 1950s, early, so 70 years ago. It’s got a history of 70-year use, long time.
And then about 20 years later, his wife… sorry to say, I’m as bad as they were then. She has her own name that she used in science, but, as you know, women weren’t always remembered that well. But it starts with a V, I remember that. She made the observation that, ‘Wow…’ the same year they were vaccinating, they didn’t see the big influenza epidemic that was coming. And there was a 3.8-fold diminution. And that’s a real ‘wow.’ That was better than the influenza vaccine. So they knew there was some kind of heterologous protection. And she coined the term ‘virus interference.’ And a few years later, interferon was discovered. I suspect, do not know, that it was given that name based on what she coined that term. And, indeed, the innate immune system, which we’ll talk about, is highly dependent on one of its key components being interferon, and it’s part of what we’ll come back to and talk about.
So they reported that, and it got reported again in Russia, and again, and then in Singapore. Then the oral measles vaccine did the same thing with other bugs, and would seem to be broadly protective against a wide range of things. Slow realization in time of the science that the RNA sensors in our cells were picking up foreign RNA molecules and instigating this immediate response, within a few hours, not like the adaptive immune system. And it’s an emergency response, as you can imagine and as you know.
It’s a hot area of basic immunology today, one that I do not regard myself as anywhere near expert in, but I’m trying hard to learn as much as I can. As I said, a key component is interferon, the myeloid cells like monocytes, macrophages, but there’s a lot more to it. And this is a chance to learn a lot more and be applicable for future potential epidemics and pandemics, as well as future waves of this.
But I wanted to finish this thought…
KRIS: Is there a clinical trial?
GALLO: Yeah, of course. Yeah, of course, but, you know, you got to… how much time do I have? Because I was, certainly, going to go there.
KRIS: We have 50 minutes left, but there’s a lot I want to talk to you about.
GALLO: Yeah, okay, but… yeah, of course, we’ll get to that. But I did want to say that our… it’s also… we’re not resurrecting a dead concept, also. It’s not a Lazarus phenomenon, to those who know the story of Lazarus. But, rather, you might think of it as a premature infant that we’re trying to develop. Okay? Something like that.
So we’re right… so the idea, it’s important to know how it comes about. We were having a Global Virus Network discussion. That’s 55 centers in about 35 countries. And we influenced Chumakov to be… he’s, you know… though, FDA, he’s got a lab that’s part of the GVN. And I remembered his discussion with me a long time ago about this, and so I raised the question, and nobody paid attention to it. Then I thought, ‘Jesus, this is important.’ So I had a meeting with him after. The idea developed further. And we can talk about what that data is.
But if you want to jump from that all the way to the clinical trial, we are involved as consulting collaborators with trials that are beginning in several different countries right now—some just starting, some already operational for several weeks. We began these discussions in the beginning of February. You know, it’s long time—February, March, April, May, June. And we got a lot of support to begin a trial in the United States, and it was with excitement by your next speaker next week, who, by the way, also cofounded the Institute of Human Virology with me, and also by the director… our director who is on television every day, at NIH, of one institute, very enthusiastic, his associate very enthusiastic. And 14 people form NIH made a site visit, very enthusiastic. And then it all a sudden stopped. They’re going to evaluate all the spike vaccines first.
You know, there doesn’t seem to be a Plan B. Everything is a spike and neutralizing antibodies. That’s obvious. It’s simple. You have the sequence from the Chinese on January 10th. You know, you can sit in your basement if you have enough money and order it. You get the message, put it in the right solution, and you inject it, and you will get the spike protein and you will make antibodies. There are some reasons to be a little skeptical that you might want to have a Plan B, rather than five spikes going forward.
I won’t get into all of that unless you ask me, but I’ll tell you what makes me, you know, wary of not having a Plan B. Yes, this may work. Yes, they should go forward. But I believe strongly there should be a Plan B. Meanwhile, this could have been out months ago.
So the clinical trial that we had involved some important people for studying the innate immune system, as NIH wanted and that they were thrilled by the Cleveland Clinic. It involves other people that are pros in that, and it involved several centers where we’d have enough patient population. And this was set to go. Now, it’s on hold here.
We have another source of funding to do something different. In collaboration with European people, we’re going to deliberately infect people, not with SARS-2, but with the seasonal coronaviruses that cause common cold and separately with influenza. We’re going to get answers fast, and we’re going to hopefully learn something about the mechanisms that correlate with protection within weeks. When does that start? Well, that is developing now funding-wise. This week, next week, we’ll have all the answers to that, and, right now, it’s very positive.
So I think that will happen. And the things in different countries will happen, includes about a half dozen different countries, maybe more now. And we are kind of pushing this still for the trial in the United States, sponsored by where we hoped that it would be sponsored, from NIH. There’s no way that this is something we’re going to, you know, slow down on, that’s for sure.
KRIS: When you mention Plan B, this vaccine could be a Plan B. You hope that it would buy time until the... What would it do?
GALLO: Yeah, you know, first of all… I mean, look, this is completely safe. So there’s been these... I don’t know what the right word is… when you throw something in the air, you don’t really know what you’re fully talking about. ‘Oh, it might get into...’ ‘Oh, it might do this, or it might do that.’ You know, we can come back to the safety in detail in a moment. ‘Oh, are we sure about efficacy?’ ‘Are you sure about efficacy with the adaptive vaccines with the spike?’ But there is a ton of data that this works, I mean a lot of data. Yes, a lot of it came from Russia and elsewhere. But we’re just ignoring it? It works. And so… and if you can give it again and again and again, and you can, you may extend the innate immune response, the emergency response, let’s say, the first responders, you may extend it for several months. We expect two months with one, maybe a little less, maybe a little more. With BCG, by mechanisms they don’t understand called molecular imprinting, they’re getting out to a year. This should be far stronger in its immune stimulation and much simpler. It’s a drop on your tongue.
And Maurice Hilleman was a great vaccinologist at Merck. He gave us the vaccines that you and I take, with the exception of rabies and polio. He was on my board for years, and used to always say, ‘Don’t even begin a vaccine unless you know feasibility.’ Feasibility means I don’t know if it’s… you know, if it’s going to be effective, but it damn well better be inexpensive, easy to give, you know, survive cold chain, have a history… know what you’re doing that it can be done. Nothing is better than the oral polio vaccine for that purpose, with the experience.
When… if you want to go into safety, tell me when and I’ll be glad to tell you what data I’m aware of, after having… beware, but to know such data.
KRIS: So talk about safety. Also, you said it could be a way to kind of get people back to work and get things moving again.
GALLO: Yes, I’m writing something about that right now, Kris. I mean, I hope it gets published. I think it will, but you never know. But that’s something I don’t want to really... as medical scientists, you know, we don’t think so much about that, but then when somebody really tells you the story, if the economy continues to collapse, people suffer in other ways and get sick for other reasons that you’re not thinking about as medical scientists. You’ve got to think about the economy and people getting back to work.
So, sure, my purposes are one, getting people back to work. Two, having an immediate prevention of death, which we could have had months ago. Three, what about the fall season with influenza? And if a new guy comes back resistant to the vaccine, if the vaccine works, if it’s safe, if it’s durable, which I have my doubts about. So you would love to have something like this. And how about for a new pandemic? And let’s say we learned something about the mechanism with real pros that study innate immune system, wouldn’t that be great? Wouldn’t that be really valuable?
To turn to safety, let’s start with all Americans between 1962 and 1997, for those 37 years, took oral polio—a little drop on your tongue. In those days, it was a sugar pill. Many of you listening to this might… well, some of you anyway… probably remember this. It was pretty darn safe. Billions, not millions of people, have received oral polio vaccine by now. The safety record in unvaccinated people is about 1 per 2 million. A complication about 1 to 2 million. That’s pretty safe. But if you’re in a vaccinated population, to the best of my knowledge, in double-checking with Chumakov, he doesn’t know of a single case of anything. And look at all the disease savings and look at here. Look at older people, me. I mean, I don’t want to go back to work until I have an oral polio in my mouth. Okay, so that’s the way I see it.
And then the argument comes, ‘Oh, it might get in the water supply.’ I mean, you know, this one, I have to bite my tongue hard because I tend to not always be in total control of my emotion. And I say, ‘Well, you know… it’s in the water supply. What survives in the United States water supply for the last 150 years?’ I don’t think any virus has survived, but let’s take it at face value. Israelis had oral polio, 6-1/2 million of them, not so long ago, and Chinese, Pakistanis, Indians, many people all over the world. Do we not go to those countries? Do we block them from coming here as visitors or to work? Of course not. So it’s hypocritically inconsistent or you’re just not thinking.
That’s my answer to it. And I want to be tempered, but I’m perplexed by the lack of movement here. It’s not true where else we’ve talked to people, I can tell you.
KRIS: You had mentioned something about the current vaccines that are in development for COVID-19, and you have some questions about that. I know work is happening at breakneck speed compared to how it usually goes with vaccine development. Is there a danger in that?
GALLO: Is that true? Do you really believe that?
KRIS: I don’t know. What’s your assessment?
GALLO: I would say if you and I had the right money, as I said before, and you’re sitting at your desk, and January 10th Chinese published the sequence. It’s an acute virus infection. This is not HIV. This is not that complicated. If you know it has an envelope, a spike protein sitting out there that’s needed to attach to cells and you have the sequence of it, and you have money, how long would it take you to make the RNA in mount? And then you would have to do it good laboratory practice and get it into people. It’s six months since we’ve had the sequence, and that’s breakneck speed? Well, we’ve got a lot of vaccine candidates coming forward. And the plan is, as I heard yesterday on those news conferences, we’re going to look at five or six of them, and we’re going to see how one may match the other, or do this better or do that better. Okay?
I’ve seen a tremendous amount of effort for an HIV vaccine go to neutralizing antibodies, and believe me, I was on that side. In fact, the first paper on neutralizing antibodies against HIV was Marjorie Robert Groff and myself in Nature. I think it was 1984 or the beginning of ‘85, a long time ago. And, certainly, we wanted our vaccines to do exactly that, but I’ve never seen in a primate study when we got protection with HIV that had ever correlated with neutralizing antibodies. So it’s not always the answer. But with an acute virus infection, there’s reason, certainly, to go in that direction. I’m not saying I would be against that.
What I don’t like is so much being that with lack of what is the plan if it doesn’t work well. And who is making those decisions? Well, we heard that they’re making a safety committee. ‘They.’ Who are ‘they?’ One or two people, the same ‘they?’ And they’re making the evaluation committee, the same ‘they.’ I don’t like that. I don’t believe that will increase American ingenuity. And I pay a lot of attention to what’s happening abroad, as well. And I don’t think anybody does in our government at all, or very minimally. You know, when we have a Global Virus Network call, we’re talking to everybody, including Chinese, right, including Russians.
So I feel we need a little more, as I said over and over, a Plan B, a little more creativity, a little more thought. And I agree that that would be my first choice. I don’t know if it would be my first, second, third, fourth, fifth, sixth choice, all going forward. And looking at this cross of how one they help with the other one. I mean, it almost looks like desperation to make sure some spike finally does something with a lot of help elsewhere. You know, I… wow. I mean, I don’t know. I’m not happy with it, with that thinking.
And you say is there something that I would be worried about with the spike? Well, there’s evidence in the Chinese literature that if you don’t protect, antibodies do spike, can make pulmonary disease worse. I don’t know how. Is it forming immune complexes? Is it taking it to more tissue sites for infection? I don’t know. I’ve also seen that durability can be a problem. If you look at papers from both China and from Holland, with seasonal coronavirus, for example, less than six months. Then there’s evidence with this guy, not long-lasting.
At the same token, in recent months, we’ve seen evidence that if you’re producing high levels of interferon type I or type II, you not only do better by controlling virus, you reduce inflammation. People forget that interferon also blocks over-activation of CD4 T-cells when it wants to tell the immune system, ‘Okay, you’ve made your antibodies. Now shut up.’ And in addition to that, therapeutically, when you give interferon, it’s done the same thing. That’s part of the innate immune system response.
The next thing I say is… I don’t know if it’s true. It’s real secondhand. I have not verified this whatsoever. But I have heard… you know, we know the bats run around with a lot of coronavirus viruses and they don’t harm the bat. I have heard it’s a strong innate immune system that this keeps in check. But this I do know, that this virus has expended some of its genetic information. And you know viruses don’t like to get rid of any of their genetic information, they don’t have so much to begin with, to try to get away from innate immunity. It must have gone through an evolution period or a period of time when this thing was really… knows to survive, it has to try to minimize this terrible onslaught by innate immunity. That’s one of the things that tickled my thoughts about this and said, ‘You know, that is interesting, and became more quizzical about it.
But it’s the urgency of it all. Yes, I believe right now, it could save life, and that’s… so it’s hard for me to bumble around with it.
KRIS: Where is the science as far as the understanding of this virus and what do we know today that we didn’t know, let’s say, five months ago? Is there anything that’s concerning you that people aren’t paying attention to?
GALLO: Well, with one of my colleagues, Davide Zella, in collaborations with people in North Italy, at the University of Trieste, we tried to follow the sequences and see if they were meaningful. The first observation that we made was that, ‘Boy, it’s mutated a lot more than what they see in China.’ So North Italy, you know, much more mutations, the same as in the United States. So we saw that we have the same thing. I don’t want to call it a problem, but much more mutation. What does that mean? We never found any correlation. That was months ago.
There’s some evidence now that some sequences might be correlated. When they hit the polymerase gene, that, in turn, makes it more mutable because that’s the replication of the virus. And that might be associated with being less virulent. I don’t follow it close enough to be expert to comment to a group like you might have. But the next thing I have seen in... I don’t think it was literature. I think it was in some para scientific newsletter, that some things recently with some mutations look like maybe some things worse, That’s what you’re really looking for, right? I mean, nice to know that it’s going out of business. Yeah, I’d really like to know that. I mean, I don’t know how so many scientists prophesize, ‘Well, we’re going to have wave two, we’re going to have wave three, etc.’ or ‘We’re not going to have any more waves.’ You know, basically, I say, ‘How the hell do I know?’ I mean, it seems reasonable, but what happened… it would have sounded reasonable, also, with SARS… with, you know, SARS-1, but we don’t. So we’re not yet sure about those things.
But the sequence variability is something ongoing that I think needs to be watched, and that’s where places of molecular biology power can make real contributions, I think. And then figuring out the biological correlations to collaborate with some biologists. We know where they are. We know the good ones and who could measure this, that, or the other. I think that bridging is important for the future, to try to make real basic scientific predictions.
So we know a lot more about mutations now, but not yet sure that I can tell you, ‘Yeah, there’s a strain. Let’s call it Strain B, and that’s doing this, that and the other.’ That’s still too early. But I think that might come maybe before summer ends that we’ll have that kind of information.
What can I say? I told you what I thought might be a little new about the spike. I was impressed by this… I think it’s touched paper with the seasonal coronaviruses that came out. Now, I only saw it about maybe two weeks ago. That… you know, that’s less than six months, four or five months or so. That’s really concerning. Yeah. So, I mean, that’s important.
KRIS: You talked about the polio vaccine as a Plan B. In addition to pushing for that polio vaccine to get out there, are there any other things that you think should happen, should be in place as other Plan B?
GALLO: Yeah. Yeah, sure, I do, yes. Actually, I would have made the oral polio Plan A. You know, I would have rushed it out right away, but those days are gone. That’s not going to happen. But, sure, of course, we’d like to see... personally, I’d like to see much more cellular T-cell immunology basic going on in this, and hear from those people what they think are the best stimulants of T-cell immunity.
I would love to hear from an institute that might be... I wonder if there is one that studies aging, and it would be really nice to hear an answer. I actually raised this with Eric, in talking to him. It seems nobody has asked that question. Maybe it’s because the answer is obvious and I’m too dumb to figure it out. But in 1917 and 1918, it was cytokine storm that killed. That’s what we believe today, in addition to all the blood clots. But when they died in 1917, ‘18, they were young. Today, they’re old. There’s got to be a fundamental difference somewhere here, because it’s the old that are dying like flies. The average age in Northern Italy was 81, average. So every time somebody 75 died, you know, you got some older people dying. Now, you can say there are a lot of old people in Northern Italy, and there are, but I think that’s really a telling thing. And I would think that the Buck Institute should figure that out. Not me.
KRIS: I think… well, just to add, we are figuring that out. There’s a lot of work here in collaboration with folks at Gladstone and UCF, and scientists around the world to take a look at the aging immune system, what happens as we age, and then, specifically, some of the drugs that Nevan Krogan’s group found show promise against the virus, they hit some aging pathways. So we’re really drilling down and looking at the responses to those drugs and how we can put that to use.
GALLO: I think it’s terrific. So, yeah, I didn’t know you were, so, therefore, I thought I could joke with you, but you got me. Please inform me. I am a well-qualified candidate.
KRIS: I understand. Me, too, actually. Me too.
GALLO: Well, yeah, you got a way to go.
GALLO: I passed the average age in Italy. You know I’m 83. So this is a worrisome time. Every time I see somebody young coming in my backyard, I run.
KRIS: What are you doing to keep safe? And what do you think about all the hoo-ha in this country about masks, no masks?
GALLO: I wear it… I wear it, certainly, when I go outside, not in my yard, but when I go through a store or things like that, my wife and I both wear masks. She’s almost the same age, a year younger. Yeah, I try to keep a distance when I’m in a drug store or elsewhere, best you can. I mean, Maryland, I don’t know if it’s true everywhere, I mean, the aisles are one ways, and you really don’t get close to anybody. So I feel quite comfortable. Otherwise, I spend... look, it’s the first time I’ve really seen spring since kindergarten, before kindergarten, right? We went to school, all my life, right? Then off to work. And when did we ever see the spring before? You can say, ‘Well, a weekend.’ ‘Yeah, okay, a little bit.’ But, you know, to be outside every day, I’ve really seen my backyard. I talk to all the animals that are there, I get to know them by name. So, you know, it’s different. So that part, I actually, I hate to say it, I’ve come to kind of enjoy, and realize you can do a lot at home. Of course, I can call somebody, and do, and say, ‘How about making a presentation on my veranda with me 20 feet away, listening below my veranda.’ And I do that and we’d have those kinds of discussions. But I do a lot of email and conference calls with different scientists, not just in our institute, but in general. So you find out you really can accomplish a lot at home.
All of us have learned that. My friend at NCI, who is my neighbor, Jeff Schlom, is an immunotherapist. He says he never got more work done in his life than this period. But he also calls people over to his house.
So it’s been different. But I have… the positive side is, also, I have enjoyed seeing flowers open, leaves open, you know, I know what species are gone and declined since I really paid attention, and so on and so forth.
KRIS: Got it.
GALLO: And I’m sure you, too.
KRIS: We have a question for you from one of our viewers. Do you think it is possible to detect characteristics of a new virus that we can predict it will be a pandemic pathogen? How do we stay ahead of this?
GALLO: I think… I got it… yeah, you know, again, you’re not going to stay far ahead of it and there will always be danger of a pandemic. If you look at the last… the last 150 years, they’ve almost all been RNA viruses and they come about every 30 years, if you think about it—the flu of 1879, the flu of 1917, polio of 1950s, early AIDS of 1980s, earlier, and now this. And in-between, some epidemics like SARS and MERS, and some other things as well. In the midst of all of that was the great smallpox, which goes on and on and on until conquered. So we’re always going to face that and we’re not going to... I don’t care what somebody does. They can sequence every DNA on earth. I mean, I knew there was the Virome Project, they were sequencing everything. And then I saw a television program where they were in Africa, and there was an antelope, native antelope shot for food, and they were taking feces and saliva and blood and muscle, and with rapture and holiness they were sending it to Cambridge, as well as to Harvard, Cambridge, England and Harvard for sequencing. And I thought to myself, ‘You know… I don’t know how many viruses have ever come from an antelope to man, but if we’re going to spend money doing that, you better start biopsying my hamburger.’ At least I’m eating that. You know, it gets a little silly. So I don’t think that… I wouldn’t put too much there.
I like what we’re doing with the Global Virus Network, virus centers of excellence as far and wide as you can, reporting on everything to a whole entire global group, and not bothering with government. We can all be together, whether Russian or Chinese, and the Russians have contact with Iranians. So I got to be a little careful with that. But, by the way, the Iranians are starting an OPV trial of 130,000 people, and we’re going to be aware of the data. I mean, you know, again, I want to be careful of that one, so… but, you know, it’s… now, I had a senior moment. I lost the track of the main point I wanted to make.
KRIS: You were talking about epidemiology and efforts to find...
GALLO: Yeah, yeah, predicting, predicting. I’ll tell you what I... the answer to that question, I think, is yes. I mean, if you did find the virus and a new disease coming, you could start making some reasonable predictions. Look, if it was a coronavirus, you have quite a bit of experience now, MERS epidemic, SARS epidemic, SARS-2 pandemic. So let’s say another coronavirus comes in from bats and causes disease. I mean, you’re going to get a little worried, right? I mean, for sure. We would have to be really stupid not to take that really seriously.
But if I looked more broadly... I mean, my… in my career, I can’t... I mean, nobody really told me this or taught me this. It might be wrong thinking, but it’s worked for me, anyway. I tend to think of starting with a disease or starting with the virus. If you know the tropism of a virus, what cells it’s going to go after, and if you understand the strategy today in molecular biology, the strategy for its replication, and you know a little bit about the immune response to it, you can kind of predict the disease, and maybe even how rapidly it can move and spread. Conversely, if I see a disease and I think it’s a viral origin, I start with thinking with… let’s say it’s a central nervous system disease, let’s say starting to appear with increased frequency, let’s say the country in Egypt, or something, I’d start thinking of what are the classes of viruses I can go to the Global Virus Network that target this central nervous system disease? Which experts do we have in that? What class did they fall in? Who are the best in the world on that? And what do we make, the kind of virus this should be? And it’s replicating very slowly, it looks like, from the epidemiology. What would that tell us? You know, and move like that. So there are things we can do at a basic level, but we always need it combined with public health experts, epidemiology people.
KRIS: Is there a reason to expect pandemics more or less often than every 30 years?
GALLO: Well, I’ve often dreamed of being God, but it didn’t work. What do I know about that? I mean, if somebody gives you an answer to that, you know, they are being hyper speculative. I can be hyper speculative, too. We don’t know the answer to that.
KRIS: Got it.
GALLO: We do know... if I was talking to the public, and I’m not. I am talking to you guys.
KRIS: Well, you’re talking to... there’s public listening to you now.
GALLO: Hmm. Well, I have one word for what I always say when… think change. One word, ‘change.’ Change of virus? Yeah, polio. It used to be probably a Coxsackie enterovirus that was in your gut and doing nothing. But it became neurotropic. Not good news. Or society change. Think about it. Refrigeration and air conditioning. Legionnaires’ disease. The forest is smaller in my backyard. I live next to Congressional Forest. Lovely area, with a river going by. However, the deer have less room. They’re in my backyard. The deer have ticks, Lyme disease. The crows in my backyard carry West Nile these days, because of global warming, right? Other things like insects came a little further north, like Zika. Change. Warming. Or the Romans opening up a new port in the Eastern Mediterranean. New epidemics came to Western Europe and to the Eastern Mediterranean. Columbus came to America. He gave a gift to the Indians, tuberculosis, smallpox. The Indians returned the favor with syphilis brought back to Europe.
So what happened with HIV? You know what happened? It used to be in the rainforest and limited. And then the colonial powers left. People came to the big cities. Kinshasa. Prostitution went up because poverty went up. It became more common. And how did it become global, we think? What changed after World War II? Travel, tourism, money, availability. The sexual promiscuity came on strong. And the insanity of global intravenous drug abuse. But that explains the spread of HIV. Change in society.
So every time, that’s the way you have to think about it. So will there be another? Of course, there will be another epidemic or a pandemic. The questioner knows that, and I’m sure maybe better than I do. But I could never say it will be more or less frequent. I can say if we keep making more changes... I don’t know what happens if, let’s say, the Amazon rainforest continues to get less and less, and global warming continues, and more mosquitoes move further north. We can certainly predict Zika moving up further north, as it gets warmer, as the mosquitoes migrate. Another change is boats, ships, whatever you call them, going all around for with cruises, right? So you had much more norovirus epidemics, not pandemics. But, also, rats, mice, they travel. So do mosquitoes on airplanes and boats. Airplanes are another big way things are spreading.
So would you anticipate that there will be more? Yes. If I’m a betting man? Yes. Would I expect it a little more frequently? Well, if you look at the last 50 years, they seem to be more frequent. And the way we’re becoming a smaller globe, yes, I expect it. But I sure don’t know it.
KRIS: It sounds like the vaccines that the young people are getting either for mumps, measles, rubella, might be keeping them resistant to COVID-19. Do you think that’s a possibility? Do you have any insight about why there some young people who are having pretty serious reactions to this disease?
GALLO: Yeah, but very few young people have serious reaction. At one time, Bob Redfield, CDC Director, a friend of mine, and my former colleague, he didn’t think anybody under 30. He was really… you know, we were talking about experimenting with SARS-2, itself, going into young volunteers. And then quickly, I got a call from him, ‘Oh, Jesus. Forget about it. You know, just got so-and-so, and so-and-so data coming in.’ But, nonetheless, come on, when the average age in Northern Italy, where there’s a tremendous epidemic, is 81, that tells the whole story. And, I mean… well, how did Italy get hit so hard? We know that the first virus that entered Italy is from Frankfurt, Germany, the airport, undoubtedly. But Italy’s fashion industry around Milan is a tremendous number of Chinese people learning fashion there. I heard it’s like 220,000 people. That’s big for Northern Italy, right? And they… a lot, went home for the New Year, and then came back. I suppose that had something to do with things starting, and really pushing there.
KRIS: Do you think the fact that young people get regular vaccinations…
KRIS: …do you think that…
KRIS: …do you think that could be behind some of the…
GALLO: Yeah, it could, but I don’t want to… it’s a hazard if I say yeah, because then they’ll say, ‘Oh, look, he’s using data that doesn’t exist.’ So I can’t say. But would it make sense? Yes. Could. And we don’t know how long this thing lasts. So… but if somebody got vaccinated, let’s say, a six year old, or a 10 year old, it might give them a year of protection, maybe longer. If you believe the BCG molecular imprinting, maybe it can last significantly longer. But I don’t want to claim that. But it’s not irrational. The thought has, of course, occurred to us, but we’ve never said any... we don’t bring it up at all, because we just don’t know, and I don’t have the statistics.
Well, yes, this is hard. They don’t get infected with this virus very much, but when they get infected they don’t get disease much. That’s another thing we don’t control, right? So that could be the reason. Not that they were protected, but that they got infected and they blew it away. Maybe because they have a much better innate immune system at that age, right?
KRIS: So that brings me to a question about where we are with testing for this disease, both who has it and also antibody testing. People are looking at antibody testing as that it will be really valuable. Do you think we’re going to get there and will it be valuable?
GALLO: Well, first of all, yes, I do believe it would be valuable. Yes, I think we will get there. I think we’re already there. I think there are good tests now coming into play. It took a long time. Bob Redfield took the blame. If you know the story, you know, it’s a little sad. I mean, the CDC apparently had a pretty good test, and then they were informed this is the… let’s call it for the sake of simplicity… I don’t know what it was…. it’s a reagent, let’s say, nutrient broth. That screwed the test up a lot.
You know, my colleagues and I developed a blood test for HIV, both the first and the second generation test. And people would say, ‘Well, gee, that was really fast, and really good, and very specific, and all that.’ Yeah, but there were some things better about it. We could relatively safely mass produce the virus. We were not afraid of it. We just didn’t use glassware and needles. So we had a lot of material to work with. And then we collaborated with people in Frederick, Maryland that had these enormous vats. So we have loads of virus to work with. That’s one. And number… so we didn’t have all these fears of things. Number two, is that the antibodies, the HIV proteins, we had… did not cross-react with the retroviruses, the human retroviruses that we had discovered just before. Known as HTLV-1 and HTLV-2. Those viruses are human retroviruses. One can cause serious disease. But it didn’t cause us any problem with testing, because there’s no significant cross reaction.
Whereas with this SARS-2 problem, there is cross reaction with the seasonal coronaviruses, for example, some, creating a little problem. So one of the key things in people are there, now I’m sure, with the focus on the segments of viral proteins that don’t cross react, to find those epitopes and really produce them and really make better tests. And I think that’s probably developed. You know, I keep saying probably, because I don’t have it in hand. I’m not sure what company. You’ll ask me specifics. I know a lot of people are working in that line. And I know that tests are getting better.
KRIS: Do you think that they will be a key factor in tracking this thing?
GALLO: Yes. Well, what worries me more... I was about the finish… is the false negatives. I mean, that’s really scary, because you could say, ‘Well, those people didn’t make antibodies.’ Well, maybe they did, and the antibodies have already gone away. Hmm. What I was worried about before. The spike antibodies. Maybe they’re gone. Because that’s a strong antigen, and, you know, they’re gone. I mean, so that is one... they say, ‘Well, those people didn’t make antibodies.’ Well, are we sure of that? Did we look early? Have we followed people from early, and see how long the antibodies last? That’s being done now. I suspect these things are not lasting a long time. And that’s a worry, both for the immunity to the people, for the idea of a herd immunity, and certainly for a vaccine.
KRIS: I listened to parts of the hearings yesterday, and when they were talking about vaccine safety, there was some comment about a concern that if somebody had a low response to the vaccine that they could actually get a worse case of COVID-19 if they happen to be infected. Are there concerns… or what’s happening with that?
GALLO: There are reports in the literature from China at the very beginning of exactly that. That’s... look, if you talk to outstanding world leaders in corona virology… we have some in America. I haven’t talked with them, Baric [?] in Carolina, for example. But… Ab Osterhaus from Holland, now in Hannover, Germany, or Johan Neyts in Leuven, Belgium, you know, they insist on animal model testing, and they’re working with several animal models that they developed. Yesterday, I heard it said in that same hearing, we just developed animal models. Well, we didn’t. They were developed earlier in Europe. I don’t know who ‘we’ is. But, you know, that gets sometimes a little much. But they worry about that a lot, those virologists, that we could get some kind of enhancing antibodies that really don’t simply enhance, they may be making immune complexes, they may be distributing the virus differently, one Chinese paper said they got worse pulmonary disease. I don’t think the mechanisms are understood yet. And I don’t think everybody has crossed that bridge to accept that. But, certainly, there are papers reporting something like that. And, certainly, the European continental colleagues that I talk with on those telephone calls that I told you about push for these animal models being carefully looked at before rushing to vaccines in men.
KRIS: So when a vaccine or vaccines become available, what needs to happen for you to feel comfortable getting a dose yourself or having your loved ones get a dose of a vaccine?
GALLO: Watching what happens with other people, and listening, and talking to my GVN colleagues that I trust. And… I mean, you know, I… let’s see what happens when they first have the... you got a lot of volunteers. I don’t expect any toxicity. But when they talk about toxicity, they’re talking about acute toxicity from the vaccine, per se. This takes time to determine what the toxicity is, like things you’re talking about. That will take a year or two. I don’t know. I don’t know.
KRIS: Do you think there’s some hope that we could have a vaccine by the winter? Do you think that’s reasonable? If you had a window of when you think a safe, effective vaccine could be available, what’s your take on that?
GALLO: Well, I think we’ve got to promise, make a promise, they won’t do it on the nightly television stuff, the government people. We have to promise we will say vaccine candidate. Once again, you have a vaccine when you have a vaccine. That takes time to evaluate. So if you’re saying by winter, we’re going to know all this, of course not. And, you know… and that will already be… since it was first announced that it would be 5 months or 11 months, that will already be about that time, way past five, and it will be then.
We could know acute toxicity, right? We’ll know that. We might even get some efficacy data by late fall. That’s possible. But we won’t know the full impact of safety and durability and future health, the second waves, etc., before one and a half years, maybe. From when? Maybe even from now. From the time you have it, probably another year, is my best guess.
KRIS: What about our relationship with the World Health Organization? How important are they in all of this?
GALLO: Well, I mean, I have pros and cons about... you know, we need WHO, and we need to be part of it. So let me just make that as the conclusion. I mean, they have good people. If they have an unknown, like HIV, the experience wasn’t great. Because when it’s an unknown, they don’t know who to call, right? And they sometimes have directors, general directors… I don’t want to go through past history with negativism. But they’ve had a past director that didn’t think we should do anything with HIV. Met with me privately. You remember, I said that I had discovered the first retrovirus, that’s HTLV 1. It causes leukemia. It’s endemic in certain countries. Not in America and Europe, but in Japan, for example. This man was from Japan. And he said, ‘Bob, you and I know it’s much more important, the HTLV than HIV.’ I almost dropped because HIV was going like that. HTLV is an ancient virus, and, you know, it is where it is. We know where it is. It’s important. For the people in endemic areas, it’s very important. And if you get a blood transfusion from the wrong person, it’s going to be very important for you, or have a partner that’s the wrong person, it’s going to be important for you. But it’s so much more difficult to transmit. It was such a less urgent problem. So is that WHO in general? No, but it can happen, right? So they have to be, by very nature, political, because they represent all the nations. So it’s a very sensitive position for them. I don’t envy it. But we must be part of it, and we must be supportive of it. The last thing we need in a global epidemic, i.e., pandemic, is to be nationalistic and to be with ourselves only.
That’s why I love the GVN, you know, because I know I get total story, not just what is in the interest of one person, or in the interest of the president, or this, that, and the other. You know what I mean? You’re talking everybody.
KRIS: If someone is taking a daily antiviral, like Valtrex, which is used for herpes, could it provide some protection?
GALLO: I understand. Of course, they’re desperate. But antivirals, what does it mean? You’ve got to be specific. Viruses differ like you and I differ, just as much. You know, I mean, they’re different, one from another. You can’t throw one thing for this to that or the other. And so… but that doesn’t mean that Valtrex wouldn’t be helpful. I cannot say that. I can only say, I don’t know. But you certainly can’t say because it worked for this, it should work for that. That’s… no way, right?
When do you think antiviral efficacy and real effect first happened, historically? When do you think it was? I’m asking Kristine Rebillot.
KRIS: I do not know.
GALLO: Well, I want to tell you something I believe is historical. I believe the first time a systemic… the words are important… serious virus disease was shown objectively... so those are the important words that I emphasized… to be treatable was in 1985. It was in my lab and it was principally by Sam Broder. We made a visit to Burroughs Wellcome at the invitation of Duke University. We went there first. Sam Broder decided to come with me. He was a clinical guy, doing clinical research. And he talked with a guy named David Berry at Burroughs Wellcome. They had a shelf-load of compounds that were made for cancer just sitting there, realizing that they could be polymerase inhibitors, and that reverse transcriptase is a DNA polymerase, Broder wanted to push testing them. I was a little scared because I said, ‘If people with this disease... you’re going to end up killing them with this drugs, I’m afraid.’ But we published the first paper, I forget, it might have been Lancet, on in vitro studies. So we showed you could inhibit the enzyme of HIV, reverse transcriptase, better than the DNA polymerases of human cells, which we happen to be working on in my lab at the time, also. And then in vitro, you could block HIV with AZT without so much toxicity to the cell.
Now, that was the end of it for me. Broder did this in my lab, because he didn’t have a, you know, virus laboratory. And so we set it up for him with our culture systems. But then he wanted to go right to the clinic. I said, ‘Oh, here’s where I say, thank you for much.’ I was afraid… I really was afraid that we were going to really cause harm. He made a major impact with a major paper, he and Bobby Yarchoan, who is still at NCI, National Cancer Institute, where this was done. And that showed virus going down, immune system coming back, objectively, patients doing temporarily better. It wasn’t the answer, but it was the beginning of the beginning. And it brought the pharmaceutical industry, and by 10 years, you had all the anti HIV therapy you needed, and it got better and better and better. That’s the story.
So now you want to just take any drug that we use for HIV and dump it on here? It doesn’t work quite like that. You’ve got to have a specific… why do we have antiviral therapy at all? Why didn’t we have it earlier? Because, you know, viruses don’t have a… they’re not alive. They’re… I mean, they use us to replicate with a few genes of their own. So you have to have a clear understanding of the molecular biology of their cycle of replication. That came from molecular biology, from basic research, the kind of things that are done at your place.
So by 1984, 1985, we had the ability to see the stages of HIV replication in detail. We knew it in our lab very, very well, and almost completely. I mean, most of the things that are targeted today were know then. And so you could much more laser-sharp attack. And that’s changed the whole world that you could now have somebody ask the question, ‘Well, you know, antiviral therapy.’ Well, we can… that was just for animal studies at the time. I remember doing reverse transcriptase inhibitors for my studies in mouse leukemia, but you would be doing that for humans.
So that’s the answer in can give. I can’t say no, but I sure can’t yes. And the toxic side effects, be really careful.
KRIS: Talk about the Global Virus Network. What is it doing in relationship to COVID-19?
GALLO: I’ll do my best. But to close the other, I just wanted to say, we should have more drugs than Remdesivir, which you get out the hospital a few days earlier, and that’s what was talked about yesterday, after six months and a lot of money. I mean, come on, we’ve got the world working on this. This is a disappointment so far. So… and I wish that question came up in the hearings.
So for the GVN, it was a concept that came to me out of what happened in HIV. I used to hear from the last Jonathan Mann of WHO, this was the fastest pace in the history of medicine. From a mysterious, unknown disease, where you couldn’t find anything, you know, and blah, blah, blah, becoming a global pandemic, etc., etc., to having the gene sequences, the blood tests, the cause, blah, blah, blah, everything you wanted. And then I thought, ‘We could have really done better.’ And the things that happened in laboratories happened by change, because… CDC would have had some responsibility, but they didn’t know about retroviruses. NIH, well, it was the cancer institute. That was the infectious diseases where our friend, Tony is? You know, they have nothing to do with retrovirology, minimal, almost nothing.
So, you know, we… I only got involved by chance, as anybody else that was in that early period. I happened to hear a lecture from James Kern at CDC, who was the town crier, he really made people aware. And he made a talk at NIH, and he said, ‘Where are the virologist?’ And I… you know, there were like six patients in New York, and I said, ‘Well, you know, we’re not going to change fields from…’ I was working in cancer before that, so I had two careers. You know, then AIDS came. But he came a second time about a month or two later, and when he brought up the new statistics, I said, ‘He’s right. And we work in T-cells and we know how to grow T-cells, and this damn thing sounds like the viruses that we knew that were retroviruses.’ Okay. So, you know, blood, sex, mother-to-child was transmitting it. Targeting CD4 T-cells. That sounded like a relative of HTLV-1. The irony is it was a retrovirus, but it’s not a brother of HTLV-1, it’s a cousin.
So that idea spawned in me that we really need to be sure there are enough virologists, particularly when I was told by people at the Karolinska Institute in Sweden that they, too, hadn’t seen a new virologist, a young man training, or woman, training in virology, the youngest one was 55 years old. And I said, ‘This is all left to chance. So we need to get a group of people that are the best experts we can find to cover every virus that’s a danger to man, and have centers of excellence connected as best we can.’
The President is Christian Brechot. We recruited him a few years ago. He used to be President of Pasteur Institute. And it’s working. I mean, we have a course in the summer, we have a meeting every year, that I don’t know what we’re going to do this year for the course or for the other part, but we got to work something out. And we’re making more young people aware of virology for all these years that this is formed, since 2011.
And its goal? Train more virologists. Be available to be advisers to the public. Speak forthrightly when asked questions by Kristine Rebillot, and to the Buck Institute. No political pulling punches. Tell what you really believe. Advise public when they… public health people when they ask. Try to survive without governments by begging for money from the Buck Institute, etc. You know, I’m a terrible joker like that. You know, those are two things, we have to hustle for getting a little money. But it’s working.
And we, also, other than training virology, giving advice. We do have things to respond. You wanted about the pandemic, and yes… the polio vaccine came out of those discussion. And we’re doing other things, in serology and helping, and really trying to work to hear the latest in people in the GVN that are developing drugs, and really developing drugs, and really doing the work that’s developing animal models. And we’re making those things available as fast as we can. And we hear everything that China knows from China directly. Okay?
KRIS: Is there a final message?
GALLO: I can be serious and close with a little like I’ve been doing. Get more than one source of your information. It is not always just coming from the nightly news. Keep that in mind. It’s important. Look more broadly. Look to your fellow scientists in your own region and your medical health region in your own region for opinions, first-hand opinions, and through the medical centers, and to the institutes. I mean, that generally, not as patronizing this institute. Don’t just rely on you think, ‘Oh, that’s somebody that knows…’ that’s not exactly true. You’ve got to have more than one source of information. I think that’s important.
Be aware of the Global Virus Network. We would not be unresponsive, and we do have information flow from a broad board.
And the other side is support the Buck Institute, and make them work faster and harder because I’m 83 years old, you know, and that’s… it goes faster and faster, and we want them to understand the intricacies of the aging process in immunology.
KRIS: Thank you.