“Hammer and Dance”: Prof. Kent Kirshenbaum on the Pandemic (Part 1)

Hammer and Dance

Dr. Kent Kirshenbaum is a Professor of Chemistry at New York University and a co-founder of NYU’s Biomedical Chemistry Institute. His research focuses on molecular pharmacology and bio-organic chemistry, including new technology for detecting specific virus particles. His studies are supported by the National Science Foundation.

I spoke to him while he was driving across the Rocky Mountains en route from New York to his hometown of San Francisco.

F IS FOR FLUNK

THE KING’S NECKTIE: Let me start with the big, broad question. What’s your assessment of how the administration has handled this pandemic?

KENT KIRSHENBAUM: Appalling. Disgraceful. A basic abdication of what needed to be done. And not from a lack of knowledge or resources—just a lack of direction.

TKN: I think everybody understands that a pandemic could happen on anyone’s watch, but how much worse do you think it’s been because of that abdication of leadership?

KK: A lot, lot worse. It wasn’t so easy to say this back in March or even April, but now we can look at other countries and see how they responded. Some have vast public health programs and some do not; some have a lot of resources and some have very few. But there are many examples now of countries that have figured it out, and they provide a very strong object lesson for how we can proceed. The fact that we’re not taking those lessons even today is an indication of how bad this abdication has been.

One indication is this: If you say to some of these countries, “Okay, you instituted contact tracing, you instituted this testing program—how did you guys figure out that would work?” And the answer that you often get is, “We learned it from you. We sent our people to the CDC and they taught us what to do.”

So the fact that the CDC is not doing those things in the US right now is not because we don’t have talented people who have really deep understanding of what needs to be done. It’s because there’s been this lack of direction to implement it.

I’m not an epidemiologist, I’m not a physician, I don’t have any particular expertise in infectious disease. I’m a chemist. I think about developing new pharmaceuticals. So I’m saying all these things from a little bit of a remove. It’s not like I have any particular insight into what is going on at the CDC. I’ve never been there. So I’m looking at it from a very distant perspective.

TKN: I understand that. But this administration and the Republican Party in general have been very dismissive of expertise across the board, and denigrated and attacked people who are experts in all areas, but especially science. Now we’re in the midst of a crisis where we desperately need science. So I’m wondering to what extent do you think this failure—this abdication—is the result of that broader war? 

KK: It’s extremely keyed into that. I don’t think it’s right at the heart because I think right at the heart is that nothing happens unless it addresses Trump’s ego. But the dismissiveness of science is important because it allows policy to be set to be whatever they feel like. Data can be rejiggered, experts don’t need to be listened to. The science is not even an afterthought. It’s just cast aside.

The fact that Trump thinks that he knows more about military affairs than the generals, that he doesn’t feel as though he needs to pay attention to any experts, especially not any scientific experts, that he can redraw a weather map at will—it’s all a manifestation of the same thing. And if you had to put at the top of the list the worst thing that could possibly happen to an administration that doesn’t believe in science, I guess this would be it. A pandemic.

Especially because this thing is not over by any means. We have a lot of work to do to make sure that we can deal with what’s heading our way over the next six to nine months, and that needs to be happening immediately. At this point, we can look around and figure out what to do between now and, let’s say, October to be prepared. That’s enough time; it really is. But you just get the feeling that it’s not going to happen.

FRED WILLIAMSON AND FRED ASTAIRE

KK: Bob, have you heard the expression “hammer and dance”?

TKN: No.

KK: This is something that the infectious disease experts and epidemiologists talk about as far as control of a pandemic.

First you do the hammer, which is you lock everybody down and you figure out the main route of transmission, how are people infecting each other, and you prevent that—whatever it takes. If you have to lock people in their homes, if you have to burn currency—which the Chinese did, by the way, out of some concerns that that may be a route of infection—you do it. It’s draconian. And you need to do it as fast as you possibly can. A week’s delay has huge ramifications. And we’ve seen that those places had early shelter-in-place or stay-at-home policies, that made a huge difference.

That’s the hammer. You put your population through as much as they can possibly handle to reduce the number of people who are infected to as small a number as possible. Then, when they can’t take it anymore, you move on to the dance.

With the dance, you loosen things up, but try to keep the fundamental reproductive number, the Rt number, down below one. That’s the metric that describes how many secondary infections a primary infection causes, on average, in a specific area. So an Rt of 1 means one infected person will spread the virus to one other person. An Rt of 2, where one infected person infects two others, is a disaster, because then you’ve got exponential growth. If one person only infects on average, half of another person, then you can expect that overall the numbers will continue to decline week by week, month by month. You’ve got it under control.

So you do the dance, you loosen things up but not too much, pay careful attention through testing to what that Rt number is, and let it hover around one—if you must—and tighten things up again if you need to. And by the way, you can’t get a good handle on Rt if testing is bottle-necked, and Trump is trying to pull funds from CDC for testing. Testing is a problem, because it makes him look bad.

So we’ve screwed this up now twice, Bob. Nationally, we screwed up the hammer, and now we’re screwing up the dance. Yeah, we succeeded—eventually—in getting a lot of people to work from home, stop traveling, numbers came down. But then a bunch of governors thought, “Okay, let’s go back to life as normal. We’re ready.”

Now we’re about to screw things up a third time, because now we’re going to go into fall and then winter and we’re going to get a mix of influenza and COVID-19, and unless we start doing the right stuff it’s going to be an absolute catastrophe. I mean, there’s no sugarcoating it. It’s not guesswork at this point. We’ve got months of experience about whether or not we’re capable of handling things properly in this country, and what the results are if we don’t, and the answer is clear. We are totally incapable of doing the right thing on the national level and hundreds of thousands of people are going to die.

TKN: That is terrifying. So if the leadership isn’t there at national level, how much of the slack can be taken up by the states?

KK: A bit, but nowhere near enough. And there are multiple reasons for that.

Number one, an immediate fast response needs to be coordinated by experts at the federal level. In other words, the CDC. In other words, immediately distributing tests that can be used, immediately providing clear guidance about what can be done.

Two, failure to model good behavior is a huge issue, and I’ve seen that in my drive across the country, different places where people are wearing masks and not. It’s clear that wearing a mask is a crucial part of what we need to do, and we cannot get people like Trump and members of his Cabinet to do that. Pence just now appeared in public in a mask, if I’m not mistaken. I mean, it’s unbelievable.

The third part of the problem is that we really need the federal government to coordinate data collection and dissemination. Different states have these beautiful dashboards. Why doesn’t this exist at the national level? It’s not like there aren’t people at the CDC who understand how to do this. But there’s clearly been an absence of direction…..someone to say, “Yeah, go ahead and put up the website. Load it. Let’s get it out there.”

TKN: In fact it’s been the opposite, right? Those metrics have been suppressed in an attempt to make it look not as bad as it really is.

KK: Absolutely. There’s a lot of talk about data-driven decisions. But if you whip the data into submission and then allow it to drive whatever decisions people have already come to in advance, that’s not data-driven. That’s magical thinking.

And you see it at the state level as well as the federal. You’ve probably heard about this woman down in Florida who was fired for producing numbers regarding positive cases and hospitalizations. The state’s Republican leadership had a plan to open up the economy, and they met with her to say, “We need the numbers to put into this analysis.” They were asking her to cook the numbers, and she refused. So she was fired. They hired an outside vendor who within 24 hours gave them exactly the numbers they needed to justify opening up the economy of Florida.

And we know what happened after that in Florida. There were 9000 positive cases down there yesterday, I believe. I don’t know what the number is today. And that is playing out at the national level as well, in different ways.

NO FLY ZONE

KK: So that’s one role the federal government has, data. The other is restriction.

Why are people getting on planes in places like Arizona or Florida and flying around the country right now? It doesn’t make any sense. Why are carriers like American Airlines saying, “We thought about your health for awhile by blocking out our middle seats, but we’re good now, so we’re going to fly full and refocus on something more important than your health, which is our profits.” I think they got $4 billion in the bailout. Why aren’t they being told that they need to protect the public? So that’s a big part of the reason why I’m in my car right now. I don’t want to be part of that.

We’re only as strong in our responses as our weakest link, and we have some really weak links. I just saw a number this morning, in Arizona they’ve got a 28% positive test rate now. That is soooo bad. Arizona is probably up there with Peru and Brazil and Chile—places where there’s just been a completely incompetent response. A 28% positive test rate?

(NB: Since this interview was conducted, Florida has pulled ahead of Arizona. The Sunshine State has more cases of COVID-19 than Italy, an early epicenter of the virus, and triple the number of China, whose population is 66 times larger. Florida would rank #9 worldwide for COVID cases, were it a sovereign nation.)

So I went on FlightAware and I pulled up the list of flights leaving Phoenix Sky Harbor Airport. Just between 10:00 am and 11:00 am this morning there were ten flights going to California, to Detroit, Philadelphia, Baltimore…. You can see them on the map, they’re going everywhere, and each one of those planes has got people onboard who almost certainly are infectious.

TKN: And these planes are full now. It’s not like when you flew a week or two ago. As you say, now they’re selling middle seats.

KK: That’s why I’m driving now.

TKN: This gets back to your point about Trump’s ego. I would think that even if his only motivation is selfish, he would want to take the steps that would genuinely make things better, rather than thinking that he can hide this or wish it away. Why does he not do that?

KK: it’s hard for me to know, but I’ll try to answer that question by citing his failure to act on other issues—like this latest episode with the bounties that the Russians have offered on American soldiers in Afghanistan. My nephew did two tours there, and I’m so glad he’s come back safe and become a father this past week. I can only imagine how you feel, Bob. This isn’t my area, but I have to imagine that there are experts within the intelligence community, within the defense community, who know that this is unacceptable and something needs to be done. And we’ve done nothing. Why? Is it because we don’t know? No. Is it because there are no experts in the intelligence community and in the military to figure out how to respond? No. They just need somebody to pay attention and say, “This is unacceptable. Do something about it.” They can’t operate on their own.

Why doesn’t Trump just do the right thing? Why won’t he provide a competent public health response? I think it’s just uncomfortable for him. It doesn’t make him look good. He said as much when talking about the testing. If we test more, it’s going to make me look bad.

TKN: But that’s a juvenile attitude because it’s not going to work in the long run.

KK: Right. Your daughter is probably well beyond the stage when, if she didn’t want you to see her do something, she would put her hands over her eyes, you know? Like, “You can’t see me!” No, the fact that you’ve got your hands over your eyes doesn’t make any difference, I can still see what you’re doing. She’s probably figured that out.

TKN: Yes, she has. She’s figured that out a while ago.

KK: One or two more things about the lack of a federal response and not being able to compensate for that at the state level.

Even in a red state like Oklahoma, the public health experts have a good understanding of what to do to keep their citizens safe. So when Trump announced that he was going to hold his rally down there, they asked him not to, and he said “Well, we’re going to do it anyway.” And so the public health authorities came in and put markers down on the ground within the arena to indicate proper social distancing….you know, keep this far apart, stand here, stand here. And the Trump campaign people came into that arena and they pulled all that stuff out. They pulled it out! I mean, it just defies any kind of comprehension.

TKN: I don’t know what to say. It’s a death cult.

KK: Yes, exactly.

ON THE ROAD

TKN: It must be weird to drive across the country in the middle of a pandemic.

KK: Well, there’s some good news and bad news.

The good news is that this is a free country, Bob, and you can go wherever the hell you want. There are no National Guard checkpoints preventing anybody from going wherever they want.

The bad news is, it’s a free country and people can go wherever they want. You’re in the middle of Florida or Arizona, in the middle of a hot zone? Jump in your car, go wherever you want.

TKN: And you’ve had the unique experience of both driving and flying across the country in the space of like two weeks, right?

KK: Yeah. This is kind of interesting because we’re all involved now in this kind of mental calculus that takes place almost minute by minute as we go about our daily lives. “Does this person present a threat to me? Can I touch this object? How much time can I go before I wash my hands after touching that object? How much distance should I give to this pedestrian who’s not wearing a mask?” There are no definitive answers to any of these questions, including something really basic like, “Is it dangerous to get on a plane?” I don’t know.

I felt okay about flying from San Francisco to New York, but that was several weeks ago. I got a brand new N95 mask, I wore swim goggles, which was weird for me because it blocked my vision. I like to sit in a window seat, stare out the window the entire ride, which I did, but I could only barely make out Lake Michigan and that was about it.

TKN: Why did you feel like swim goggles were a good idea?

KK: The tissue in the eyes can be a major route of transmission. It’s not just into the lungs. So if you’re incubating your eyes with some kind of aerosol, it potentially could be a major route of transmission. So yeah, swim goggles. I picked that up very early on from a friend who does research in biology….

Oh, right now I’m driving by Dugway Proving Ground in Utah.

TKN: Yeah, I know Dugway. I spent a few weeks there in training.  

KK: So you must know all about how not to get contaminated.

(NB: Dugway, in the remote high desert of Utah, was a longtime chemical warfare testing site for the US Army. Although no longer used for that purpose, live chemical munitions remain randomly scattered about the installation, most of which consists of open land.)

TKN: It’s funny. I don’t know what the schedule is now, but back in my day, the final phase of the Ranger course took place there. I was there in the winter and it was miserable, but the interesting part was that we had to carry protective masks—gas masks—while we were training. That’s the only phase of the course where you had to have them, because we never knew when we were going to come across some old unexploded chemical ordinance. I got frostbite there, but I don’t think I got any chemical contamination.

Yeah, Dugway. What a terrible place that is. (laughs)

 KK: (laughs) Yeah. I’m happy to be moving through at like 80 miles an hour.

JUST THE VAX, MA’AM

TKN: Let me ask you about the vaccine, which many people of course are pinning all their hopes on. What you think the odds are of a vaccine, and if so, on what timeline?

KK: I’m really astounded by the response of biomedical researchers in so many different ways. The extent of cooperation, the pace of discovery, the sharing of information—it’s been phenomenal.

At the beginning of this year, before the pandemic hit, I was leading an advanced biochemistry class at NYU. And I said, “Look, there’s this disease in China and I think it might give us some stuff to talk about during the course of the semester.” And it was only a few weeks later that I was able to tell the class, “Well, actually they already have a vaccine candidate and they’ve already begun Phase One trials on it.” So the pace is really extraordinary. All of these things that I thought would take a lot longer are actually going blazingly fast.

What’s going on in laboratories around the country, both in academic labs and in corporate ones, I think is truly impressive and it does make me optimistic. If you had said, “There’s going to be a new respiratory infectious disease, a retrovirus, what do you think would be an optimistic timeframe for vaccine development? I would have said, if we’re really lucky, maybe two to three years. But now Fauci and other people are saying maybe by the beginning of 2021 we could have the vaccine for distribution. It’s unbelievably fast, and a lot of things have to go right for that to happen.

But we’re still talking about months at best until it becomes available. So that means we have to do what we can now as far as nonpharmaceutical intervention, NPI. That means public health, that means mask-wearing, that means travel restrictions, all those things. It’s still quite a way to the beginning of 2021, and at the rate that people in this country are dying, it’s going to be continuing tragedy.

TKN: It’s hard to believe that a country that screwed up the hammer and dance in the way you described can get its act together to produce the vaccine that fast.

KK: Well, the good news is that there’s a profit incentive here! So there are individual scientists working at individual companies who’ve done this before very successfully and who are ready to do it again. They are unbelievably motivated, and they are doing everything right. They’re doing a remarkable job.

I have a friend at Regeneron Pharmaceuticals, one of the big movers in antibody-based therapeutics, so I’ve got some insight into what that company has been able to do as far as quickly transitioning their technology to respond to COVID-19, which is of course caused by the SARS-CoV-2 virus. The good news is that they have made antibodies against coronaviruses before, they know how to do this, and there’s a phenomenal scientist named George Yancopoulos who’s the chief scientific officer, the guy is brilliant and nobody’s going to get in their way, at least as far as what they can do within the company.

As far as therapeutics, I’m most interested right now in antibody-based therapeutics. We can produce antibodies, manufacture them, and administer them as a therapeutic. And there’s now I think 110 different antibody therapeutic candidates that are in different stages of development, including some that are very far along. Essentially we could have these therapeutics and begin producing them for distribution three to four months from now.

TKN: And by therapeutic, do you mean for treating someone who already has the virus, not a prophylactic?

KK: Yes. Treating somebody who’s already in the hospital. It’s not clear whether or not it would work prophylactically, but these things are going to be so insanely expensive, so probably only certain people will be able to contemplate taking them that way.

TKN: And to what extent is that sort of research domestic to the US and how much is international and requires global cooperation?

KK: It’s all international. Everybody’s doing their part. The Chinese are doing their part. The Australians, the Germans, the US, the University of Oxford—everybody’s coming through in ways that are truly magnificent. The extent of cooperation by individual scientists, not by the federal government, has been amazing. Unfortunately, the federal government, one misstep after another, pulling out of the WHO, trying to strongarm a German company into supporting their vaccine research on the condition that it’s distributed in the United States first. Really stupid things like that.

TKN: Well, that’s why I bring it up, and maybe it’s spurious, but I’ve heard it suggested that all that maneuvering could backfire on the United States and we could be shut out of a vaccine that’s developed overseas because we’ve been so uncooperative. Which would serve us right, but it’s an awful thought.

KK: Yeah, I could, I could easily see that. If you really want look hard for a silver lining, with regard to the failure to control the spread of infection in this country, here’s the silver lining, Bob:

In order to do a good job of testing a vaccine, you need populations who are at risk and who are capable of getting sick. If your public health system has done a good job of tamping down infection, there’s no reservoir of virus in your population, and there’s no way to test whether or not a vaccine is doing anything. So in order to test these vaccines, they’re going to have to go to places like Brazil, India, and you know what, it’s going to be fantastic to test these vaccines here in the US! We’ve got such a massive problem that it should be quite straightforward to run these clinical trials and compare the incidence rate of vaccinated versus unvaccinated individuals.

TKN: We’re number one! We’re number one!

KK: Yeah. And this is not some theoretical kind of thing: this has actually been a huge impediment for vaccine development in the past. They have developed vaccine candidates for viral pathogens, and they were like, “Well, where are we going to test it?” But in the meantime they had actually done a good job of controlling the infection and it became really difficult to do the actual testing of the vaccine. I think that’s happened on more than one occasion. But not a problem for us!

Maybe we’ll be able to make some kind of accommodation with a vaccine developer in Germany, like, “Hey, you can come to the US and test your vaccine, if you don’t mind sharing a few doses with us.”

The international aspect is terrible in terms of how it reflects on the US. Right now I’m looking for a way to go to Italy, and it’s basically impossible, because Americans are banned from entry. The US is on the pariah list. They’re talking about a year before even Canada’s going to open up the border to us.

TKN: As a friend of mine pointed out, it’s a perfect irony to the Muslim ban that started this administration.

KK: A perfect irony. There are plenty of other countries that are being permitted travel to Italy. Some of them make sense: much of Europe, Canada, New Zealand, Japan. Uruguay! Serbia. Rwanda! I would have better chance of getting into Rome as a Rwandan citizen right now than as a US citizen.

***********

In part two of this conversation, to be published later this week, Prof. Kirshenbaum discusses what we can do ahead of a vaccine, the problems we can expect if and when it arrives, the deadly risks of a government that is contemptuous of science, and the future of pandemics.

Dr. Kent Kirshenbaum is a Professor of Chemistry at New York University and a co-founder of NYU’s Biomedical Chemistry Institute, where he conducts research in Molecular Pharmacology and Bio-Organic Chemistry. Current projects include developing synthetic mimics of proteins in order to discover a new family of drug molecules, and establishing a new technology for detecting specific virus particles. His studies are supported by the National Science Foundation. A recipient of a NSF CAREER Award, Kirshenbaum received his PhD in Pharmaceutical Chemistry from the University of California at San Francisco and conducted his post-doctoral training in protein chemistry at Caltech. He is an inveterate bicycle enthusiast, and enjoys studying the interface between chemistry and cuisine. He serves on the Scientific Advisory Board for the Good Food Institute.

 

 

 

One thought on ““Hammer and Dance”: Prof. Kent Kirshenbaum on the Pandemic (Part 1)

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s