"Biomedical Research and the NIH in the Age of COVID-19" SwatTalk
with Jon Lorsch '90, director of the National Institute of General Medical Sciences
Recorded on Monday, April 6, 2020
Transcript
Jim Sailer:
I want to thank everyone for joining us. My name is Jim Sailer. I'm in the class of 1990. It's a real privilege to be here and to be able to have this discussion with Jon Lorsch, PhD, who's also from the class of 1990 and has been a friend of mine for... It'll be 34 years this September.
Jim Sailer:
I want people to know that this is a recorded session and it will be published on the website. I'm going to explain a little bit the format and how it's going to work.
Jim Sailer:
This is part of a series of SwatTalks. Because this is a series on the COVID virus, COVID-19 in particular. I want to recognize and just acknowledge that we've had... The first is I want to show people that this is part of the series so there's upcoming... I've now shared my screen. You can see some upcoming talks. You see the one tonight here with Jon and then there's a talk next week with David Kaufman who's a MD, who's the head of the translational development at the Bill & Melinda Gates Medical Research Institute up in Boston. David is going to talk about the global health elements of this. And then on April 19, Dean Baker is going to talk about the economic ramifications of all this.
Jim Sailer:
Tonight, we're here to talk about biomedical research in the age of COVID-19 with Jon Lorsch. I do want to acknowledge that this is a very tragic illness for many people. It's touched many of us. It certainly has touched the Swarthmore community.
Jim Sailer:
This is Forrest Compton who's in a long class of '49, part of the greatest generation of World War II veteran. He was an actor for most of his career, lived on Shelter Island where I pulled the story from. He passed away of complications from the COVID-19 virus. As did very sadly from the class of 1991, someone I knew and people from our vintage knew, Anick Jesdanun who was a terrific AP reporter also passed away.
Jim Sailer:
I want to acknowledge that all of us have had people we know or friends or family or extended family affected by this. There may be other Swarthmore alums who have been directly affected by this. We'll just say our best wishes go out to the families and the friends of everyone who is affected.
Jim Sailer:
I also just want to acknowledge that there are many, many Swarthmore alums around the world who are working on this. Specially, thanks to the healthcare workers and the other people who are addressing this directly. We want to thank all of them who are working on the problem in one way or another.
Jim Sailer:
Tonight's session is going to be with Jon Lorsch who's a PhD and he's the director of the National Institute of General Medical Sciences. Jon got his undergraduate degree in the class of '90 at Swarthmore. He got his PhD in biochemistry from Harvard University. He did a postdoc at Stanford. He then became a professor at Johns Hopkins and was a full professor in 2009.
Jim Sailer:
Jon's research specialty is RNA biology. He, then after Johns Hopkins, came and became the director of the National Institute of General Medical Sciences. Jon's going to tell you what that is. It's a very, very influential institute in the United States particularly around the funding basic research, both at the NIH and funding in many, many institutions around the country. Jon will say a little bit more about that in a moment.
Jim Sailer:
And then probably the pinnacle of Jon's career, of course, came last year at Swarthmore when he was given an honorary degree at Swarthmore just last year. If anyone has not seen his talk that he gave at graduation, it's a fantastic talk and one of our classmates wrote me over the weekend, a talk that's very, very apropos in today's environment and for tonight's topic. We're really fortunate to have someone Jon's level in the government with his background and expertise to join us to talk through this situation from the perspective of the NIGMS.
Jim Sailer:
The format is going to be... Jon is about to show some slides for you to give you a little bit of an orientation about the NIGMS and the NIH and then I have a number of questions for Jon and then you can ask questions of Jon. What you'll do is you will... In the chat you can do it or in the Q&A you can do it. Just type them in there. When the general Q&A is over and I will ask the questions and select the questions and pose them to Jon.
Jim Sailer:
One thing that Jon and I did talk about when we were preparing for this yesterday was that Jon's a special... There are different elements of this and the particular angle Jon's going to talk about is research and COVID-19 and that situation, a little bit about the NIH response. Jon is not an MD and he's not a public health physician. Some of the more public health questions, I think, are probably going to be best answered and addressed with David's talk next week.
Jim Sailer:
And then I'm getting a nice reminder from the incoming president of the Alumni Council who says that for people asking questions in the chat, please just indicate your name, your class year, and your Swarthmore affiliation. Thank you, [Bohee 00:06:24], for the reminder.
Jim Sailer:
With all that, I just say, Jon, it's a pleasure to see you and thank you so much for joining us. I'm going to turn it over to you.
Jon Lorsch:
Thank you, Jim. Thanks, everyone, for coming this evening and sharing this discussion. As Jim said I'm going to show a few slides because I'm a recovering academic and it's hard for me not to but I promise, Jim, it wouldn't be more than a few minutes. I'm really just to give you an understanding of the NIH very briefly, a little bit about what NIGMS does, and then we'll have some discussions. Let me just pull that up.
Jon Lorsch:
Here we go. Can you see the slides? Okay, Jim? Good.
Jon Lorsch:
Okay, so let me just give you a brief overview of the NIH and where NIGMS sits in it. It's the National Institutes, plural, of Health and that's because there are 27 institutes and centers actually at the NIH and those are shown here. There's the Office of the Director where Francis Collins, the director of the NIH, operates and underneath Francis and the Office of the Director are these 27 institutes and centers shown here.
Jon Lorsch:
The ones in green have funding authority so that is Congress appropriates money to them. They then can make grants to researchers and institutions across the country. Some of them also, as Jim alluded to, have what we call Intramural Research Programs. There's a lot of research that goes on the NIH campus as well but 85% of the money Congress appropriates goes to academic, small businesses, and other institutions across the country to do research.
Jon Lorsch:
The institute you probably heard of, based on the news, is this one here, the National Institute of Allergy and Infectious Diseases and that's Tony Fauci's institute. He's the director of that institute.
Jon Lorsch:
I'll draw your attention to a couple other things that are important. This one here is the clinical center. It doesn't have funding authority but it does conduct clinical research at the NIH and it's the largest research hospital in the world actually. Some of you may have seen a show called First in Humans that was about all the clinical trials that go on at the clinical center and in fact, there are clinical trials going on there right now to treat COVID-19 that we could maybe touch on a little bit.
Jon Lorsch:
Here's National Institute of General Medical Sciences. That's the institute which I'm the director. Our budget annually is about $3 billion a year. Almost all of that goes to fund a research outside of NIH. We actually don't have an intramural program unlike some of the other institute's that I mentioned.
Jon Lorsch:
What does NIGMS fund? As Jim mentioned, we primarily fund basic research. We also have a very significant training and education portfolio. What do we mean by basic research? This is research to understand how biological systems work and therefore, by understanding how they work we can gain an understanding of what's going on when they don't work. That is when they break down and diseases result. Just as an example of the kinds of things that researchers we fund study.
Jon Lorsch:
This is the famous HeLa cancer cells shown in a micrograph and yellow is the DNA of dividing HeLa cells. Here's one of the DNA and then the sister chromosomes over here and then the colored things are different parts of the apparatus of the cell that are helping to pull these two daughter and parent cell apart during the cell division process. The scientists we support study all of these sorts of processes of cell division, movement of cells, reproduction of cells, etc.
Jon Lorsch:
Another example that I'm very fond of, this has nothing directly to do with the current COVID situation, is regenerative medicine or regeneration. This is an axolotl or Mexican salamander and it's one of the creatures, which there are a number that has really remarkable regenerative properties. This creature can lose one of its limbs, for example, and it can very quickly regenerate and grow back that entire limb.
Jon Lorsch:
Of course, it's obvious that this is not something that humans can do but what's very surprising is they have all the same genes more or less and the same machinery that we have and yet they can grow a severed limb back and we can't. Scientists that we support are trying to understand how these kinds of organisms can do those amazing things with a hope of being able to someday turn it on in us and repair a damaged heart or maybe even eventually a loss of limb.
Jon Lorsch:
And then finally, at a more of a molecular level, we support technology development and structural biology to understand what the machines that make life actually happen look like and how they fit together and how they work together. Again, we can understand how they work, we can understand how they break and then cause disease.
Jon Lorsch:
This is an actual three dimensional picture of another virus, not a coronavirus, but a dengue virus which is not terribly dissimilar from coronavirus. This shows the proteins that are coating the surface of that virus and the really beautiful arrangement of those proteins and this was a technique, the cryo-electron microscopy, which NIGMS has had a significant hand in supporting the development of.
Jon Lorsch:
As I mentioned, we fund a lot of training and education and workforce development across the country. We have the largest training and education portfolio at NIH and more than half of the graduate students that are supported by NIH training grants across the country are supported just by our institute. That's a very significant part of what we do.
Jon Lorsch:
A few areas specifically that we support that are relevant to the current situation and COVID-19, one is infectious disease modeling research. We fund the lion's share of the modeling research that's going on to try to understand how infectious diseases spread and how one might intervene effectively to disrupt the spread and one of the critical parts of that apparatus for us is the Modeling of Infectious Disease Agent Study or MIDAS network which is shown here. And if you're interested, there's a link to that at the bottom, the coordinating center for that group of researchers.
Jon Lorsch:
We also have a few clinical areas that we're responsible for. One that's particularly relevant is understanding sepsis which is a dysregulated and hyperactive immune response to infection. The body normally will respond to a pathogen entering it through the immune system. There's innate and early immune response and then a later one involving the development of antibodies. If that early immune response goes too far, it can become dysregulated and essentially go out of control resulting in this condition, sepsis, which leads to multi-organ failure and can eventually lead to death.
Jon Lorsch:
Actually, over a quarter of million people in the U.S. annually die of sepsis. It's a very serious condition for which we actually have no good therapeutic options currently available. As relevant to COVID-19 because it appears that a considerable amount of the mortality from the disease is the result of sepsis and sepsis like conditions.
Jon Lorsch:
We also fund a lot of technology development. For example, developing new diagnostics for different diseases, developing platforms to make new therapeutics for different diseases. And finally, of particular relevance also is artificial intelligence and machine learning work where computer scientists are approaching biomedical problems including the COVID-19 epidemic right now using artificial intelligence and machine learning approaches and we're very heavily invested in that space as well.
Jon Lorsch:
Just to close a few of the things that we're doing acutely to try to help from the research side to ameliorate the epidemic, we have given supplements or in the process of getting supplements to researchers who were working on a different infectious disease agents in terms of modeling research so they can pivot very rapidly to approach the COVID-19 epidemic using modeling techniques. If you've been watching the news or watching The White House briefings heard a lot of mention of the models, it's these kinds of researchers that are actually doing the groundwork to try to develop better ways to model the outbreaks and to model interventions and what the effects of those interventions might be.
Jon Lorsch:
We're also giving supplements to small businesses that we fund to pivot diagnostics that they were developing for something else into rapid diagnostics for COVID-19 and pivot therapeutics that they were developing for a different indication towards COVID-19. We're targeting this to small businesses because they are poised to move things into the clinic and into the market. They're at the end stage of the development process.
Jon Lorsch:
And finally, I just want to say from the angle of our training and education portfolio which I mentioned is the biggest of NIH, we've been trying to help all of you and people you know who are either trying to learn virtually at home or have someone in their household who is trying to learn virtually at home or trying to teach virtually. We've put out a variety of menus of products that we have funded and we support both for pre-K through 12 teachers and learners and also for older students and teachers of those students, so undergrad through faculty, and the links are here. I'll distribute these slides. I'm happy to give them at Swarthmore so you can find the link. We also have a hashtag if you want to follow the resources that we make available.
Jon Lorsch:
With that, I'm going to turn it back over to Jim to moderate this.
Jim Sailer:
Great. Thank you, Jon. That was a great overview of NIGMS. I think a recurring theme through this is going to be the relevance of basic research and how maybe basic research that was done 10 and 15 years ago is going to advance and accelerate the search for both therapeutics as well as vaccines and other prevention technologies for COVID.
Jim Sailer:
But let me just start with a really basic question for you, Jon, which is what happened? Why is this virus so deadly? Why is it causing such a problem? Why does it spread so fast? We got a lot of viruses that we all have out there that we see. Why has this one been such a problem that has turned the world upside down?
Jon Lorsch:
It's a good question. Part of it definitely comes down to that this is a virus that humans have not seen before. What's thought to have happened is that this virus did what we call an interspecies jump. It went from an animal and most of the coronaviruses have as one of their natural reservoirs is bats. So the thought is, at some point, it went from a bat probably to some intermediate animal that has cells in its airways that are closer to human cells and it evolved in that animal for some time. And then, somehow, either, in a market that was selling wild animals or through contacts in the wild with wild animals or some other means, it then jumped from that intermediate host into humans.
Jon Lorsch:
Because humans have not seen this before, we have no natural immunity to it. It apparently wasn't close enough to another coronavirus that most people have antibodies that could cross react with it and in part because of that and also because of its biology, it is apparently something that rather than causing a common cold in some people at least cause a more serious and often life-threatening condition.
Jim Sailer:
Maybe do you want to say a little bit more, Jon, about the biology of it for those who are not scientists?
Jon Lorsch:
I'm just going to go back to one slide here then to do that because I do have a slide to show the coronavirus a little bit for people. Here's a few pictures of coronaviruses or parts of coronaviruses.
Jon Lorsch:
They're called coronaviruses because here's an electron micrograph from Tony Fauci's institute, NIAID. If you look at a two dimensional projection of these virus particles, you can see they're spherical, they're round, and they have these little spikes on their surface. These spikes turn out to be very important but they look like crowns. Here maybe is a good example. That's why they're called corona which means crown. They look like a crown in these two dimensional projections.
Jon Lorsch:
Now, these spikes are very important for the viruses' biology because they bind to a protein on the surface of the airway cells in our lungs or cells that are in the airways of our lungs called ACE2. ACE2 is an enzyme on the surface of those lung cells which actually has a very important job for us in controlling blood pressure. It's actually an enzyme. It cleaves a very important molecule in blood pressure control but the virus has hijacked that and has learned through the spike proteins how to bind to it.
Jon Lorsch:
This is actually a structure of the spike protein that was again determined by cryo-electron microscopy, that technique I mentioned before, by Jason McLellan who just serendipitously was a graduate student when I was a starting faculty at Johns Hopkins. But within a month or so after the outbreak being recognized, Jason, who's at the University of Texas, was able to determine the structure of the spike proteins and now it's understood better how they interact with this ACE2 on the surface of our cells.
Jon Lorsch:
This is important because A, if you could disrupt that interaction, we might be able to develop a drug that would block the infection and vaccines that you've certainly heard in the news are rapidly under development mostly target this spike protein. The idea is to develop antibodies in our bodies that will recognize these spike proteins and therefore prevent infection.
Jim Sailer:
Jon, let me ask a couple questions that relate to the biology of this. One is from Jennifer Arnold from the class of '92. The question is about how much is known about the different types of the coronavirus are there, different strains and so on, because we are talking about not one virus but a set of viruses, yes?
Jon Lorsch:
Yeah, that's exactly right. The coronavirus is a family of viruses that all share those features. They have some other interesting biology. They have as their genome RNA instead of DNA. We're all used to DNA is the genetic material. Probably you remember from Swarthmore biology, if you took it, that DNA encodes RNA. RNA is the messenger molecule and that then is translated into the proteins that are the machines that do the work. The virus has skipped a step. It uses RNA as its genetic material and then that goes directly into the cell and makes the proteins which then make more virus.
Jon Lorsch:
All of these coronaviruses share that property. They have this RNA as their genome. They have those spike proteins but some of them have been circulating in humans for many, many years, thousands or millions of years, and they just cause the common cold. There are four general known coronaviruses that cause common colds. I think about 30% of the colds we get are caused by one of those four coronaviruses.
Jon Lorsch:
Then there was SARS which you probably remember, Sudden Acute Respiratory Syndrome, a decade ago or so that came around. Again, it started in Asia. That was significantly more deadly than the current one. But it wasn't as transmissible. MERS then came. You may remember that. That was transmitted from camels, talking about the interspecies jump that had similar properties to SARS. That's actually still circulating amongst camels but it's recognized now. So the transmission has been controlled more.
Jon Lorsch:
This new virus then emerged from against some unknown sources, probably started in bats moved to another animal. There's some thinking it might have been something called a pangolin, which is an armored anteater. The closest, most similar virus that has been found at least the last time I saw it a few weeks ago was from a pangolin. There are certainly many, many more coronaviruses that are out there unfortunately that we have not encountered yet.
Jim Sailer:
Thank you. That's very helpful. We have another. This is from... Professor Ted Abel, class of '85, has a question for you. He says, "Do you think there are non-human species that might be impacted severely by COVID-19, but would studying the mechanisms by which the animals that are less impacted by the virus, if there's some that are more impacted, some are less impacted, could that be of therapeutic importance?" is Ted's question.
Jon Lorsch:
It certainly could be. For instance, if you understood why one animal was much less seriously affected than another, you could gain some insights into the pathogenesis within humans. Whether that's useful or not would depend on the mechanism of why that's the case. It could be that spike protein just doesn't bind very well to the surface of the cells in that species whereas it does in us. That information may be less useful. But if there's something about the hyperactive immune response after infection that's different, maybe that would be useful. I think that's interesting.
Jon Lorsch:
It has been studied to an extent already. I did see a paper not long ago from a Chinese group that looked at infectivity in ferrets, cats, and dogs. This was not a peer reviewed paper yet. It was a preprint. But dogs apparently are resistant to the virus, whereas cats and ferrets... That actually maps with the similarity of the cells in the airways that I was talking about before.
Jim Sailer:
Does that mean that it can jump from the cat, ferret to human from human to... Back and forth? Does that make it more dangerous?
Jon Lorsch:
That could be a concern. The extent of that would not be clear, but you may remember some controversy a few years ago about what were called gain of function studies of influenza in ferrets and they use ferrets because they're actually susceptible also to influenza and can propagate the virus in a laboratory setting.
Jim Sailer:
The last I'm going to... We have a bunch of questions, Jon, around this but there's some other elements I want to cover that I think will be of general interest. The last one is just a nice, simple but really significant question that we're all wondering, from [Norman Sarachek 00:27:40] was a class of 1960 and the question is, why is this coronavirus so transmissible from person to person compared with other coronaviruses?
Jon Lorsch:
That's a great question. The reasons for one virus being more transmissible than another can be multiple and are not entirely clear yet. We're at the very early stages of understanding the biology of this virus. Remember that 30% of the common cold is caused by other coronaviruses and they are also quite infectious and transmissible they just don't cause nearly as serious disease as this does.
Jon Lorsch:
It can have to do with how well the virus, that spike protein, binds to ACE2, that receptor protein, on the human airway cells. That can be one reason for the transmissibility. It can be more physical things like how well the virus survives in the air or on surfaces. If it dies very quickly, it's not going to be as transmissible. There are lots of different factors that can go into that and we don't fully understand them yet.
Jim Sailer:
Thanks, Jon. I want to move on to a topic. The federal government, of course, has enormous resources and the U.S. government is the most important funder and coordinator of work in the world, I think, in terms of devoted to medical research and basic research, scientific research, and a lot of public health things. We see these different federal organizations, the NIH, there's Health and Human Services, there's the Centers for Disease Control and the Food and Drug Administration. I wondered if you could just talk about the different roles of those institutions in the response to something like COVID-19.
Jon Lorsch:
Yeah, that's a good question. NIH's role is entirely research. So we are a research agency. As I mentioned, we fund research. Research is conducted on the NIH campus. That's NIH's role. We do not make public health recommendations. We do not get involved in regulatory issues directly. We're supporting the research and trying to understand how things work and translate that into some kind of an outcome.
Jon Lorsch:
The Centers for Disease Control is a public health organization, an agency. They're the ones trying to understand how to intervene and to make the specific recommendations for what interventions should be done at a public health level. They're the ones tracking the actual spread of the virus and using that information, again, to inform public health decisions.
Jon Lorsch:
The FDA is a regulatory agency. It's responsible for ensuring that either diagnostics or devices or therapeutics are safe and are actually effective. That's what their role is. That's sort of the chain of division of happenings. Of course, there are other agencies in there with different parts of that same process.
Jim Sailer:
I'll say this part that's one of the things that Anthony Fauci, we mentioned before, is very prominent and actually is a peer of Jon's. They both had institutes at the National Institutes of Health and his day job is overseeing the research portfolio, both intramural and extramural, that NIAID funds. But because he is so experienced, he's seen so many different infectious disease issues come up, he's so well spoken and known, he's taken a role in a way speaking about issues of public health quite prominently which you might think is part of the CDC role in a way really too. But his day job, his bailiwick, so to speak, is about research.
Jim Sailer:
Lots of questions coming through but I know you wanted to talk a little bit about some of the vaccines that are under development with support from NIH. Could you tell us a little bit about that?
Jon Lorsch:
Going back to what you said about Tony Fauci and NIAID, that's one of the things that NIAID focuses quite a lot on is research to understand how vaccines can be better developed and then to put that into actual action, to develop vaccines. On the NIH campus, they run something called the Vaccine Research Center, which has been set up to rapidly respond to these kinds of outbreak situations to, as quickly as possible, go from the isolation of a virus to the production of an experimental vaccine, to the testing of that experimental vaccine to see if it is safe and effective.
Jon Lorsch:
They did that with Ebola, you may remember a few years ago and it was really remarkable when this virus was first isolated in China December-ish. They got the sequence and in partnership with a company called Moderna in Cambridge, Massachusetts, they very rapidly were able to produce an experimental vaccine which is now in trials in humans for safety. It's what's called phase one trials for safety.
Jon Lorsch:
They also look in the phase one to see if it produces the kind of immune response that you would predict would be protective. That will take a few weeks to months and then once that's done, they can move into the next phase where they actually start to see does it really work in the wild, so to speak, in actual subjects who might be exposed.
Jon Lorsch:
That's one vaccine. There are a number of others in the pipeline, both in the U.S. and other countries particularly China as well and in Europe. I'm pretty confident that within 18 months there will probably be a safe and effective vaccine. But it does take time to actually show that the vaccine works, to show that it's safe, and importantly, to show that it doesn't actually make getting the condition worse because there have been examples. For instance, a dengue vaccine where it can actually make it worse if you get the virus. That's why it's so important to do the research rather than just give it to everybody.
Jim Sailer:
A lot of questions coming through. One about vaccines in particular, and this is from [Suma McGourty 00:34:41] from our class, the class of '90, and she's asking if the newer RNA based vaccines might be more effective than the traditional, whole weakened virus vaccines against COVID-19 and then the follow on is whether all the vaccines have similar development timeframes regardless of what type they are?
Jon Lorsch:
That's a great question. The historic vaccines were often either what are called attenuated viruses or a close cousin virus like the original cowpox that milkmaids would get and was protective against. Smallpox was a relative virus that you know could provide some protection against the virus that you were trying to stop. That then lead to the idea of if you kill the virus as where you take the actual virus, you kill it, but its proteins would still be there and when injected cause an immune response. Those kinds of vaccines are still used today.
Jon Lorsch:
These new RNA-based vaccines take a piece of RNA basically from the virus. Remember I mentioned that the genome of these viruses is RNA not DNA and in this case, it encodes the spike protein and they put it in a less harmful virus or actually a delivery system that can get it into your immune cells directly and from there, it makes this protein which your immune cells display and hopefully produces an immune response that gives you protective antibodies.
Jon Lorsch:
That is in theory, as the question alluded to, could be faster than the traditional routes and maybe safer than traditional routes because you can go from a sequence to a vaccine very quickly just using a platform where you plug in the RNA and go. That's basically what Moderna and NIAID had done here. If this works I think it'll be very important in our ability to respond quickly with vaccines to viruses.
Jim Sailer:
Good. Thank you, Jon. Another question is coming. I'm going to shift a little bit because you talked in the beginning, and when we talked yesterday, you spoke to me a lot about modeling and there's some things that are known. There's not a lot that's known. We have a question from Charlie Sussman in the class of 2005. He says that with respect to the modeling the virus and the spread, what are the biggest challenges for COVID-19? And what sort of uncertainty standard errors might we expect in the projections?
Jon Lorsch:
As you expect from Swarthmore, these are excellent questions. That really is the question with modeling. What I like to tell people is the reason we support research on infectious disease modeling is because we don't really know how to do it that well unfortunately and therefore, we still have to do a lot of research to try to improve the methods. To compare it to, say, modeling of the weather and making predictions of the weather, we're still back in the 19th century probably in terms of infectious disease modeling relative to where weather prediction was.
Jon Lorsch:
If you look at the models that came out over the last few weeks for instance in the U.K., there was really a 100 fold difference in the outcomes from different models and that obviously has tremendous implications for the public health response. In the U.S., are 20,000 people likely to die or is it two million? That's a huge difference and has big implications for your response. What one needs to have is a very robust group of different people trying different approaches and hope that the models start to converge on answers that makes sense.
Jon Lorsch:
The other issue of course is the output of the model can only be as good as the data that are modeled used as the substrate for the modeling, so to speak. Our data is incomplete in most places in terms of how many people are infected, how many asymptomatic people there are, what's the rate of spread. That's becoming... What's the infectivity? That's becoming a little clearer. But there are lots of, to quote a wise man, both known unknowns and unknown unknowns here which makes the modeling even more difficult.
Jon Lorsch:
Again, this is an active area of research. It's full but it's very important to remember that the modeling we're doing here is not like predicting the weather yet.
Jim Sailer:
Right. Let me go on to another topic here. This is from someone named David Ruby.
Jon Lorsch:
Never heard of him.
Jim Sailer:
Should we expect of a COVID vaccine to be on the same level of efficacy like the seasonal flu vaccine? Or are there going to be multiple vaccines a rolling wave of vaccines that takes years before we have a universal cure? I think it's a good question because this idea that there's a vaccine under development and once people get it, the problem is solved. People have that hope. But I'm not sure that's the case. Do you have any thoughts on that?
Jon Lorsch:
It's a great question again and I wish I could answer it. The real answer is I don't know. The hope would be this vaccine might actually be better than a flu vaccine in the seasonal drift that the flu does which means we need a new vaccine every year, won't be as big a situation at least that's what Tony Fauci suggested to me. We hope that's true.
Jon Lorsch:
The flu vaccine is not, to be honest, a great vaccine. In a good year, it's sort of 60, maybe even 70% effective. Many years, it's less than that. If I'm being optimistic, I'd say this might be a better vaccine for a variety of biological reasons than the flu but we have to wait and see. It's a great question.
Jim Sailer:
We have a question from a current Swarthmore student, Jon. Her name is Emma and she's a junior at Swarthmore. She's double majoring in engineering and French. If you could answer in French, it would be appreciated. The question is how is artificial intelligence being utilized in treated or managing COVID-19 in the pandemic?
Jon Lorsch:
Yeah, that's an excellent question. There are a variety of ways that the system, we and others, are trying to employ artificial intelligence and machine learning and other approaches you can imagine is in terms of infectious disease modeling. What most of the model is trying to do is what we call first principles. They come up with different variables they think are going to be important like the rate of spread, the infectivity, mortality, these kinds of things and then they try to fit that to a mathematical model that is based on all those variables and those functions.
Jon Lorsch:
One, however, take a less first principles approach and just say here's a whole bunch of data for real, what's really happening, and let artificial intelligence start to connect the dots and find patterns within the data that a human may not be able to see and we may not even understand what's happening but that may lead to a better predictive model in the long run than us trying to think we understand what's happening. That's one thing.
Jon Lorsch:
There's also more and more papers being published, reams of data coming out, and having machines basically, again, look at everything that's out there and try to make connections, find correlations may lead us to understand things that just with our brains alone we will not be able to make and those can be economic inputs coupled with mortality rates, coupled with intervention effects, etc. But I think when you have a huge amount of data, you need something beyond just our brains to try to put it together.
Jim Sailer:
Thank you. Jon, we've had a number of questions about what happens post infection. Paul Krauss from the class of '96 is one of the people. There's been a number of questions that come through about will people test positively maybe they've had it, that negative, then it's positive again and is this reliable? What does it mean... Are people reacquiring the virus? Do we think is it a different strain? Any idea... Do we know yet what's going on with that?
Jon Lorsch:
There have been some anecdotal reports of people who had negative tests then coming back later and having a positive test. I think that's led to some speculation that perhaps you're not immune once you get the virus. Francis Collins is talking about this a lot. My take on it from talking to people like Francis and looking at the literature that I was able to see is that those are really not very convincing anecdotes when you look at the person who may have had a false negative test, for example, the first time and then the second time it was a true positive. It could be that it was not actually as clear when they were infected versus when they were cleared, etc.
Jon Lorsch:
Best guess from everything I'm hearing at this point is that if you are infected and recover, you are very likely to be immune but again, this is still an active area of research. So we'll have to wait but that's what I'm hearing for sure.
Jim Sailer:
Thank you. There's a couple of questions come in and I had one as well. I wonder, Jon, if you could talk about what is it like in the room where it happened? You're the top echelon at the NIH. We had a question from Connie Bowen, the class of '16, about how sort of intraorganization communication works and so on. We can see you're actually working at home if I'm not mistaken, like many of us. You're not going into the office all the time. How is it working at a massive institution like the NIH on the frontlines in terms of dealing with this? Tell us how that's being coordinated and managed.
Jon Lorsch:
Yeah, that's a great question. We are all at home except for Tony of course. You see him not at home. The same as you, since the 13th, we've all been teleworking except for essential people who are working in the clinical center, for example. We have probably four or five calls a week at the leadership level, the institute center, director, and Francis Collins is office level for briefings about the latest of what's happening and really importantly, over the last couple of weeks, there's been a massive ramp up in our research response to this.
Jon Lorsch:
We've been working very hard on a number of new initiatives in addition to the things that have already started to come out to address every aspect of this epidemic and also the exit strategy which was related to the previous question. Once we do start to see the cases going down and mortality going down, how do we get out of the whole telework situation that we're in and go back and so that's one of the very active areas of research and modeling is going to play an important role.
Jon Lorsch:
Dr. Collins does a fantastic job with his staff organizing this. Although there are a lot of institutes and centers that I mentioned, we are very collegial and work very well together. It's been really heartening to see everyone pitching in and working together and the ideas that are coming forward, I think, very soon are going to be launched as major research initiatives.
Jon Lorsch:
We also work across the government with, for instance, the National Science Foundation, the Department of Energy. We're meeting just the next couple days and importantly, the Office of Science and Technology Policy in The White House has been very engaged and catalytic regard as well.
Jon Lorsch:
At the research level, I think a lot is happening and I think it's going to make a difference.
Jim Sailer:
Just to follow up on that, Margot Hillman from the class of '78, is asking, what's the impact of the response to the COVID-19 and actually just being able to do research because of the social distancing and so on and so forth? Is that affecting how the actual research is happening?
Jon Lorsch:
Oh, huge, huge. I still have a lab, a small lab and everyone in my lab is teleworking even though we're bench scientists and that's true pretty much at every institution across the country at this point. Lab research, except for research that's directly related to COVID-19, has basically halted and everyone else is trying to find things to do that are productive that they can do from home.
Jon Lorsch:
Again, the research community has been really remarkable in their response to this. Everything from opening centers up, for instance, for cryoelectron microscopy that I mentioned. Those centers that we fund across the country have made themselves completely available to COVID-19 research and they're dedicating themselves to that right now.
Jon Lorsch:
To a story I heard about Stony Brook University, the chemistry department got the recipe for making hand sanitizer because it was a critical shortage in their hospital and a bunch of postdocs and grad students made an assembly line and were making four liter bottles of hand sanitizer and bringing them to the hospital. There are, amongst all of the tragedy and depressing news, these beacons that really shine which is good to see.
Jim Sailer:
That's a great story. We've had a couple of questions. Daniella from the class of 2014 and Paul, I think, from the class of 2005 asking about how do you see this changing the research landscape, the strategic priorities at your institute, is there going to be more of a focus in terms of funding infectious disease research because of this? Is it going to change how the NIH works or coordinates? Any early thoughts on that?
Jon Lorsch:
It's a great question. NIAID, Tony Fauci's institute, is the second biggest institute in terms of budget after the National Cancer Institute. I think that already speaks to the priority of infectious disease for the NIH and for Congress.
Jon Lorsch:
In terms of changing priorities, I think it may change our thinking and focus even more in terms of how we can become as nimble as possible to respond to a crisis. I don't think it'll change it in terms of priorities like basic science versus translational science or political science because every single thing that's happening scientifically now, vaccines and therapeutics, small molecule therapeutics, diagnostics, modeling, is built on the basic science that the institute's and NIGMS and other institutes are fund.
Jon Lorsch:
You could not make a vaccine, the RNA vaccines we're talking about, without years and years of basic science that laid the foundation. I don't think that will change. But I think we may become more administratively nimble in terms of how we can very rapidly respond to something like this.
Jim Sailer:
I have a number of questions, Jon, about the future. One of them from Bohee of the class '01. She said, "Well, I've read the COVID-19 antibodies. They may last only six months. There could be a second wave of the virus in September. Are people going to get sick again?" Do you have any sense of what you think the future, the next six months, one year is going to hold? Or if there are signposts or markers where when X happens, we'll know something either really good or really bad is going to happen?
Jon Lorsch:
I wish I could answer that question and there are many people much smarter than me trying to figure that out. Again, I think that goes to this exit strategy research problem that we're very actively working on. How do we get out of this? How do we minimize any potential reoccurrence? There's a lot of research questions there still. Again, the data I've heard so far don't suggest that you will rapidly become not immune anymore but we'll have to wait and see exactly how that behaves.
Jon Lorsch:
Again, I anticipate that with all the work going on there will be a vaccine within the next 18 months or so. That's my prediction, as much as I'm willing to make a prediction and at that point. The situation will become a lot clearer. I think with much more rapid diagnostics with diagnostics that are based on antibody, detections that called serology instead of based on detecting the viral RNA will help us a lot in understanding who's already been infected, is immune, how many people were infected, but never knew it because it was subclinical. Things like that. If we could get very rapid tests on the order of... Something you could even do at home that would dramatically change the equation.
Jon Lorsch:
All those things are in progress and if we can get to happen fast enough, any future wave, I think, would be a different situation than what we're in now, but again, we just don't know yet.
Jim Sailer:
Any sense of when we're going to have the sufficient testing capacity?
Jon Lorsch:
I don't know the answer to that. I think it's ramping up a lot but again, we need different kinds of tests as well and those are in development and starting to come out. But I think that serological tests based on antibodies instead of just being based on detecting the virus is going to be very important for our exit strategy and preventing recurrence.
Jim Sailer:
Something that was a question here is a good one, something I don't understand, from our class, [Greg Smirin 00:54:43]. We're reading about in South Korea and other places, Germany, they're testing, testing, testing, testing, tests. They got lots of tests. What do they have that we don't? Do they have a technology? Is it materials? Is there any reason why we can't just license their test and do it here? Or what's stopping our ability to test when there are places that are doing thousands of them at a time?
Jon Lorsch:
Yeah, there were some countries, South Korea, in particular, that really focused a lot on testing and I think that was a good strategy. I'm not involved in the supply chain in that level of public health so that may be a better question for next week's speaker. But again, I do agree that testing is critical, both the RNA based or the nucleic acid based test, PCR tests, that have been used so far, but really getting to the serological test, I think, is going to be critical for having a different ability to control things in the fall setting.
Jim Sailer:
Serologic test means what for?
Jon Lorsch:
Antibodies. The test that you're hearing about now is mostly one where look to see if you can find the viral RNA. Do you have virus actively in your body? This is using the polymerase chain reaction that many people probably heard about. But since you've been infected once your body has had time to respond and has developed antibodies, you can make tests to look for those antibodies. I think that's going to be really important because that'll tell you who has the antibodies and is therefore immune. But it'll also allow you to figure out how many people were infected again and never really knew it because they didn't get very sick. We don't know that. That denominator is still not very clear how many people are subclinical or asymptomatic.
Jim Sailer:
Jon, I had a number of questions a little bit around epidemiology and public health and other factors. One question is, do you think that a fruitful area of research has to do looking in the way different communities, whether it's socioeconomic, communities of color, so on and so forth, are affected by this? Is that a fruitful area of research and something we need to know more about? We've had a couple questions.
Jon Lorsch:
Oh, it's critical. Not just fruitful, it's critical. My good friend, Eliseo Perez-Stable, the Director of the National Institute of Minority Disparities and he's certainly been working on some rapid research responses in this area.
Jon Lorsch:
I just read a very [inaudible 00:57:39] statistic just today that said that, if I recall, 15% of cases in the U.S. so far have been in African Americans but they comprise 40% of the fatalities at this point. That's a huge disparity. The percent infected versus the outcome. The reasons for that need research. Certainly, that could be because of disparities in health care but we need to know that it's absolutely critical and we won't actually get a good handle on this virus and containing it until we have some understanding of that so we can intervene appropriately.
Jim Sailer:
We've had a couple of questions, Jon, about... Are we seeing more? Are we seeing more of these big pandemic kind of infections than in the past? Is climate change having something to do with it? Is it the way we're able to move around the world having to do with it? Or are we just more focused on it today and in fact, we're not seeing anything really that different than what's been in the past?
Jon Lorsch:
It is important to recognize that there have always been pandemics of various diseases, influenza 1918, 1919, 1957, etc. Not to belittle what's happening now, but of course, the Black Death in Europe killed a third of the population. This is historically, throughout history, been part of the struggle of humanity against microorganisms.
Jon Lorsch:
It is certainly if you look at coronaviruses. That has been something that starkly over the last decade or so. We have seen now three serious emergent coronaviruses. Why are we suddenly seeing these? Why is Ebola arisen the way it has?
Jon Lorsch:
I think the questioners' thoughts were certainly things that are potential factors. Climate affects encroachments in habitats that previously humans had little contact with, the sale and slaughtering of wild animals in larger scale that has happened in the past, and of course, travel. If travel was only by ships, at least the things are slower not necessarily worse but not as rapid. Air travel, etc., has... And the population density cities, very densely populated cities, high rise buildings, those things allow for spread.
Jon Lorsch:
Complex whether we are releasing a major acceleration or not I think again is a research question, but when you look at coronaviruses, it does appear that way.
Jim Sailer:
We have a bunch more questions. I'm going to just ask one more from the group. We recognize we're about at an hour and we have a big group but we thank you for your time here, Jon. I've seen two or three, including Karen Saravanos from the class of '88 asks, is there international cooperation in the research space? Is there any coordination or cooperation, things like that? How does that happen if it does happen?
Jon Lorsch:
Absolutely. I think that science has historically always been a very collaborative and international operation that continues. It's made easier, of course, by this thing where we can have conferences very easily online with people on the other side of the planet.
Jon Lorsch:
One exciting development that I've been watching which may be one of the points of light that come out of this very dark period has been preprints. There has been a movement in science to rather than waiting till the entire peer review process happens which can take many months to even a year or more to publish in a journal to make your results public.
Jon Lorsch:
People are putting it on these bio archives and other servers a preprint version. It said, "This has not been peer reviewed. This is just our draft." But there are now thousands and thousands of those in just a few weeks related to COVID-19 and the virus and a lot of very important information has been shared.
Jon Lorsch:
The downside of it is there are probably a lot of things in there that are wrong because they haven't been peer reviewed but I think it's probably outweighed by the upside which is a lot of information is getting out much, much faster than it would have otherwise. So I'm excited to see that.
Jim Sailer:
Certainly, it's another advantage of the journals that are online is that you don't need to wait for the quarterly whatever to publish. Let me finish up here by asking, Jon, you're seeing a lot, we're all seeing so much noise out there on TV and papers, the internet, Twitter has lots of people telling us what to do all the time. What is something that you wish people would fundamentally understand about this situation and what we're going through? Is there anything that you think maybe isn't getting through? Or is a message that should be amplified a lot louder about what people should really know and understand?
Jon Lorsch:
Let me start with the positive, Jim. I am very confident that science is going to address this problem over the next months and that we really will see science coming to the rescue. I really think that's true.
Jon Lorsch:
It's going to take a while. It's going to take months for that to take place. Hopefully, there'll be some more incremental advances. Maybe there'll be some antiviral drugs that show promise and can help critically ill patients or other things. Certainly, there can be rapid diagnostics coming online soon.
Jon Lorsch:
The more negative answer to that, like people understand, is there is a lot we don't know and that's really important to remember. This is a totally new virus. We had not seen it before December of last year. We are working very quickly to understand it, to understand its biology, to understand the spread, and the various impacts. But there's a lot of research work that needs to be done in a very short period of time.
Jon Lorsch:
I would just caution people when they do read things on Twitter, in the media, or anywhere, do remember there's a lot we don't understand. A good example is a report says, "If you get the virus, you're not immune you can get it again." Don't take that as the final answer until you really have seen some concrete evidence that that's true published in journals and respected scientific authorities saying that they do believe that.
Jim Sailer:
I'll just say that one of the things that you and I talked about yesterday as we're preparing for this is that anybody who says with a great degree of certainty, they know what's going to happen in the next three, six, nine, 12 months is probably something to take with a huge grain of salt, I think.
Jon Lorsch:
True, true.
Jon Lorsch:
Hs Jon, we have answered as many questions as we can. We have many more in the Q&A that you could stay and look at and maybe type some responses if you wanted, but I want to thank everybody. We've had upwards of 270 people join us for this which is a fantastic turnout.
Jon Lorsch:
Most importantly though, I want to thank you and your colleagues at NIGMS. I think this particular situation that we're dealing with now is just one example of why basic research is so important to fund and to develop and you don't always know where it's going to go.
Jon Lorsch:
But how many times have we heard in the last two weeks, three weeks, two months about something being developed for one thing that might have a role in helping us with this and your institute, it has a budget of, I think, $2.9 billion. That's an annual budget. Most of that, the vast majority is given out to research centers around the United States to do basic research. It's unbelievably important. I'll say this, anyway, which is that if you think about spending trillion dollars on this recovery effort, I would rather spend extra billion dollars, more billions of dollars, in this basic research and scientific endeavor.
Jon Lorsch:
The fact that we have really serious scientists and senior officials who are very, very carefully watching what happens and trying to make decisions in the public interest is incredibly important. You're one of a number of Swarthmore alumni who are taking a prominent role. I think the deputy director of the CDC is a Swarthmore alum as well and I just want to say thank you for taking some of your valuable time. I know you're extremely busy to join us tonight and answer these fantastic questions from the Swarthmore alumni.
Jon Lorsch:
I'll give you the last word, Jon.
Jon Lorsch:
Thank you, Jim. I could not have said it better myself. Thank you so much for setting this up. It was a lot of fun.
Jim Sailer:
All right. Very good. Nice to see all our classmates from '90-
Jon Lorsch:
Thank you, everybody.
Jim Sailer:
And the other classes.
Jon Lorsch:
Stay safe, everybody.
Jim Sailer:
All right. Be well. Thank you, everyone.
Jon Lorsch:
Bye-bye.
