ONE of the bizarre subplots of President Donald Trump’s illness has been the White House’s unwillingness to explore exactly how he contracted COVID-19. Offers by the Centers for Disease Control and Prevention to investigate the outbreak have been rebuffed, leaving open pressing questions. Who gave the virus to the president, and where did that happen? To whom did he give it, and in what circumstances? Is the disease now sweeping through the White House all from a single source, and if so, who is the source? Twenty years ago it would have been all but impossible to answer those questions, but they can now be answered quickly and cheaply — so quickly and cheaply that I can’t help but wonder why we don’t already have the answers. I sat down with microbiologist Joe DeRisi, a co-president of the Chan Zuckerberg Biohub, who is a pioneer of the use of genomic sequencing both to identify and to track infectious diseases. He has a few thoughts on the subject. Here is a lightly edited transcript of our discussion.
Michael Lewis: When a person is tested for COVID, and their test turns out positive, that’s one piece of information you get — positive or not positive. But there’s other information there. What is that information?
Joe DeRisi: Besides knowing whether you have the virus or not, when you test positive you can also extract the actual sequence of the virus. And what that means is the genetic information that composes all the proteins of that virus.
ML: And what’s the use of that information?
JD: The genetic program of the virus — you might think is set in stone. But it isn’t. The virus is made of RNA, and when it replicates itself, it tends to make errors. From generation to generation, the virus introduces small mutations, errors in its own genetic code. And it does this at about a rate of a new mutation every two to three transmission events.
ML: So you can see it changing as it moves through the population?
JD: That’s right. When a second mutation or error is introduced in that same virus as it’s passed from one person to another, it inherits all those previous mutations. You have a bread crumb trail that links all those viruses together throughout their history.
ML: And with this information, then, you might be able to detect who gave it to whom in a population?
JD: Knowing the sequence of mutations links it to all its past infections. If you have sequences of a bunch of people that were positive, let’s say in an outbreak in a fish packing plant or something like that, you would then be able to know whether those individuals who were sick had the same virus or a different virus. If it was the same virus, then that would imply that they likely transmitted it to each other. If they had a different set of mutations, then you could conclude that there’s no way they could have gotten it from each other at the workplace.
ML: You might be able to keep the fish packing plant open because you could see that it wasn’t inside the place; the thing was being transmitted by people bringing it in from outside.
JD: Correct. This idea of using genomic epidemiology — that is, mapping the mutations inside the genome and using it for public health purposes — is often used to rule out possibilities: We can rule out that this person gave it to that person. Now if it’s an identical genome, the most likely scenario is that they were closely linked in the transmission chain.
ML: The sequencing enables you to see social relationships in the community you might not otherwise see.
For instance, if you see that a woman has it and a guy four doors down the hall from her has it and it’s the same virus, and those two claim to have no relationship, then you might dig further, because the virus is telling you that they came in contact in some way. And it makes me wonder how it might be used in the case of the president right now. If you had the positives from in and around the White House, what do you think you might be able to deduce from them?
JD: If we had all the positive cases from the White House and from members of Congress who were in contact with the White House, and their friends and family, and we sequenced the viral genome from those — not the people, just the viral genome — we could probably create a linkage map that indicates who likely gave it to whom.
ML: How hard is it to do this? Who owns the genome of the virus? Is it an invasion of privacy to sequence the genomes of a virus that comes out of somebody?
JD: The sequencing of your own genome and your own information — we would consider that private health information. But a virus such as COVID-19 is RNA, it’s not even DNA, it’s not part of your genome and no one owns it. You don’t own it. The president doesn’t own it. It’s part of nature. And, in fact, after you clear it from your immune system, you won’t have it in your body anymore. And so, when you sequence just the viral genome, you’re not sequencing any human information. There’s no private health information contained within the virus genome, with the exception of the concept that there’s epidemiological information in there.
ML: Are there any kind of legal impediments to getting the positive samples from in and around the White House and sequencing them?
JD: To my knowledge, there shouldn’t be since we’re not violating protected personal health information. I think that actually sequencing the viral genomes, not just for the president but nationwide, is a good idea because it informs us on strategies we would use to intervene and stop transmission chains where they may be occurring, where you didn’t think they were occurring.
ML: To what extent are we doing it now? What percentage of the positives in this country get sequenced?
JD: A very small amount of the total.
ML: Back to Trump. Explain to me how if Hope Hicks gave it to Donald Trump, how you’d be able to figure that out. If they have an identical virus, if it hasn’t mutated, you couldn’t really tell whether Donald Trump gave it to Hope Hicks or Hope Hicks gave it to Donald Trump, right?
JD: In this hypothetical situation, if Hope Hicks and the president’s viral genome were identical, then all you could conclude is that they’re as closely related as two viruses can be, and they either likely transmitted it to each other, or there was no more than one extra person between them.
ML: Now, if the president had one extra mutation on top of all the mutations that were in Hope Hicks’s viral genome, you would know that he was downstream of Hope Hicks. And you could sequence them in time — Hope Hicks first, then the president. In the other situation, it might be the president first and then Hope Hicks if they’re identical and you wouldn’t know which direction the virus went.
JD: Yes, exactly.
ML: If you had whatever the passel of positives end up being — 100 people from rallies, from Rose Garden ceremonies and so on — would it allow you to figure out the conditions in which it was transmitted?
JD: If you were able to sequence as many of the positives as you could, you’d likely be able to link the transmission events to particular environments. A closed office. A rally. A Rose Garden event. From a public health standpoint, you could identify which of those environments need intervention.
ML: So you might be able to show that nothing happened in the Rose Garden, but it all happened on Air Force One.
JD: Correct. It could have happened on the plane, it could have happened in a limousine. Those are the kinds of connections and contact tracing combined with the genomic epidemiology that would really be a precision-mapping tool for knowing the situations in which the virus is transmitted, and how you intervene to stop it.
ML: I understand that maybe we don’t have the firepower or the energy to do this for the whole country — but we have this unbelievably high-profile event. It seems strange to me that we’re not using the technology to figure out what happened.
JD: If there was an armed assailant who somehow hopped the fence at the White House and went in through an open window and roamed the halls freely, you can guarantee that somebody in the Secret Service would lose their job.
ML: There would be a videotape of the guy running around and no one would think: “Oh, don’t consult the videotape.” And the analogy of the genomic sequencing is sort of like — it’s a version of the videotape. It can describe what happened.
JD: The security tapes could tell you who might have assisted the assailant, who opened the window and let that person in. In the same way, the genomic sequencing can tell you who was at the scene, who might have transmitted the virus to whom and who could not have been at the scene. So I find it really striking that not only does there not appear to be any use of the genomic sequencing to understand how this occurred, but they’re not even doing basic contact tracing.
ML: In what way do you think it’s more than just academic interest?
JD: The use of the sequencing to understand how a virus flows is certainly more than academic, and in this case it can help us understand the situations that lead the virus to spread. These are the ones we need to interrupt and stop.
ML: I’m trying to think if there has been another outbreak like this where you would have had such a detailed record of exactly where these people had been during the period in which they became infected. It’s almost like a stage play, where they’re moving from scene to scene. It’s all on camera or at least recorded somewhere.
JD: I can’t think of any better case in which to use the technology because you know where everybody was at every single moment. Plus, this has endangered the security of the president of the United States and should be taken with the utmost seriousness.
ML: So why wouldn’t somebody want to know how the armed assailant got through a window? Can you imagine any reasons why? It’s perplexing to me because it seems so obvious.
JD: I am just as perplexed as you are.
ML: When you did your genomic contact-tracing study in San Francisco’s Mission, I remember thinking: Who wouldn’t want this information? And then I looked at the information and thought: Well, if I was the guy down the hall having an affair with the married woman at the other end of the hall and I didn’t want anybody to know about that and we both had COVID, I certainly wouldn’t want that social relationship exposed. And that’s what the genomic sequencing does: It exposes social relationships that might not have been in plain sight. And so I wonder if that’s at the bottom of the kind of squeamishness about this.
JD: Hard to know.
ML: If I sent you to Washington to do it, how long would it take you if everybody cooperated?
JD: If everybody cooperated, if we had all the samples in one place, it would take a couple of days to get it done.
ML: And at the end of that, what would we have?
JD: We would have a map of the viruses, the sequence of the viruses, that we would then put on a family tree to understand which viruses are related to which people. And it’s unknown what the result would be because we haven’t done the experiment, but one might expect to see that if the president’s viral strain and other people that are at the Rose Garden or other meetings were the same, you could conclude with reasonable confidence that there was a very close transmission chain among them. Likewise, if the viral family tree says all these strains are very different, you can rule out that they transmitted the virus to each other.
ML: Could you find out if the president picked it up himself in, say, Minnesota? How possible would it be to track that event?
JD: It depends on how many of the viral genomes are getting sequenced from all those different places in states where he’s been. If he had been, for example, here in California, there’s a good chance that many of those viruses would’ve been sequenced because we’re doing a lot of sequencing here. But some states aren’t doing it at all, so it really depends on where that virus was picked up for us to be able to have any reasonable idea of where it was last.
ML: Just like a database of fingerprints.
JD: Yep. It’s a bread crumb trail and you don’t know where it goes. If no one’s laying down the bread crumbs, then there’s no trail to follow.