The Quest for a Pandemic Pill-By Matthew Hutson

The Quest for a Pandemic Pill.Can we prepare antivirals to combat the next global crisis?

By Matthew Hutson
April 6, 2020
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With each new virus, we’ve scrambled for a new treatment. Our approach has been “one bug, one drug.” Illustration by Christoph Niemann
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In 1981, a young man visited Cedars-Sinai hospital, in Los Angeles, with shortness of breath and with curious purplish lesions on his skin. After reviewing biopsies and scans, a twenty-eight-year-old medical resident named David Ho found an odd fungal infection in the patient’s lungs and a rare cancer, Kaposi’s sarcoma. These conditions were both associated with immune de!ciency, though nothing in the patient’s history explained why he would be in such a state. He was given antibiotics and discharged; not long after, he died. Over a few months, Ho and his colleagues saw !ve men with similar symptoms. They wrote up the cases and sent them to the Centers for Disease Control—
the !rst report of what became known as aids.
Ho continued to explore the disease. “Some people were very concerned that I was so intrigued by those few cases at the very beginning of my career,” he told me. “ ‘Why would you want to devote your career to an esoteric disease?’ ” Particularly one that seemed mainly to afflict what was considered a fringe population—gay men. But Ho, who had emigrated from Taiwan when he was twelve, speaking no English, had an underdog mentality and would not be dissuaded.

He made several discoveries throughout the nineteen-eighties about H.I.V., the virus that causes aids, and in 1990, at the age of thirty-seven, he moved to New York to become the director of the Aaron
Diamond aids Research Center. A year later, he received a call asking him to 'y back to L.A. to test a very important patient.
There, he con!rmed that Earvin (Magic) Johnson was H.I.V.-positive. The following week, Johnson disclosed his condition and announced that he was retiring from the 0:00 / 32:51


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N.B.A. Ho has cared for him ever since. Johnson later said that he’d never thought aids
would kill him, because Ho had assured him that better medicines were in the pipeline.
In 1994, Ho found that a certain class of drugs could dramatically reduce the viral load in
aids patients. But, within each infected individual, the virus evolved quickly, evading
treatments. One drug was not enough. His team devised the idea of an aids “cocktail”—a
combination of three or four drugs that, acting in concert, could corner the virus. In 1996,
Time named Ho its Man of the Year.

In November, 2002, a novel disease broke out in China: severe acute respiratory
syndrome, caused by a coronavirus called sars-CoV. Ho was asked by China’s top publichealth
officials to advise them. “The most dramatic memory I have is going to Beijing,
arriving in the late afternoon or early evening, and going to the hotel along the biggest
avenue,” he recalled. “If you remember the Tiananmen incidents of many years ago, with
the protester and the tank, that’s the boulevard. It has ten or twelve lanes. There was only
the car that’s driving me and one ambulance for as far as one could see.”
He went on, “That’s when I got interested in coronaviruses, serving as a consultant and
seeing the devastation !rsthand in several cities throughout China.” Back in New York,
Ho began investigating the coronavirus family. Some coronaviruses can produce lethal
diseases, like sars; others are among the causes of the common cold. But, he said, “the
sars epidemic ended in July of 2003. By the next year, there was hardly any interest.
Funding for that area kind of dried up. So we simply dropped it and went on with our
H.I.V. work.” In 2012, another coronavirus, mers-CoV, caused an outbreak in the
Arabian Peninsula; Middle East respiratory syndrome, as it was called, sickened more
than twenty-!ve hundred people and killed more than eight hundred. Ho followed it
with interest, but this outbreak, too, passed quickly. Then, this past December, a disease
with similar symptoms 'ared up in China and, within a month, was linked to another
coronavirus, sars-CoV-2. Ho told me, “My Chinese heritage caused me to focus more
on the news coming out of China in late December and early January. However, the
experience with sars also put a pause on our natural reaction to jump in and get
involved.” His attitude shifted when the story did. “It was the growing magnitude of the
outbreak that told us, ‘Oh, we’d better think about getting into this,’ ” he said.
Ho was just setting up his lab at its new home, at Columbia University. He is friendly
with Jack Ma, the founder of the e-commerce giant Alibaba, who asked how he could
help. In February, Columbia announced that Ma’s foundation had awarded a $2.1-
million grant to Ho and several Columbia colleagues to develop antiviral drugs. This
project was prompted by the covid-19 crisis, but the mission goes beyond it; the
researchers are thinking not only about the current pandemic but about future ones as
well.
What will the next global pathogen be? “If you’d asked me that three or four months ago,
I would have said in'uenza,” Ho told me, with a chuckle of dismay. For scientists, this
isn’t just a thought experiment; it’s the sort of question that shapes years of research. Two
years ago, a team at Johns Hopkins issued a report titled “The Characteristics of
Pandemic Pathogens,” which was based on a literature review, interviews with more than
a hundred and twenty experts, and a meeting devoted to the issue. It grimly considered
the possibilities.
Could bacteria do us in? Outbreaks of plague have wreaked havoc throughout history,
but the development of effective antibiotics in the past century “took bacteria off the
table as a global biological risk for the most part,” Amesh Adalja, a physician at Johns
Hopkins and the report’s project director, told me. Bacteria can evolve, and develop drug
resistance, but usually not quickly. How about fungi? They threaten some species, but
don’t adapt well to warm-blooded hosts (and may have helped encourage the evolution of
warm-bloodedness). Prions? These are responsible for mad-cow disease and its human
variant, but are mostly avoidable by preventing food contamination and refraining from
cannibalism. Protozoa? Malaria has killed perhaps half of all humans who have ever lived.
But protozoa are typically transmitted by vectors such as mosquitoes and 'eas, which are
limited by climate and geography. Viruses, the report concluded, are the real menaces.
Not just any viruses, though. The likeliest candidates are those with a genome of RNA,
which evolve faster than those with DNA. Viruses that spread before symptoms appear
also have a considerable advantage. (The only infectious disease we’ve wiped out,
smallpox, is not contagious during the incubation period.) And the most daunting are
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those transmitted by respiration, rather than by feces or bodily 'uids, which can be
controlled through sanitation. Viruses that can move between animals and humans are
especially hard to manage. All in all, this character sketch gets us pretty close to
identifying two classes of viral assailants: in'uenzas and coronaviruses.
None of our off-the-shelf treatments equip us for such a pandemic. If bacteria invade,
there’s a long list of antibiotics you can try. Between cipro'oxacin and amoxicillin, we can
treat dozens of different types of bacterial infection. For the roughly two hundred
identi!ed viruses that afflict us, there are approved treatments for only ten or so. And the
antiviral drugs that exist tend to have narrow targets. Only a few have been approved for
use against more than one disease. Many drugs that work on one virus don’t work on
others within the same family; antivirals suited for some herpesviruses (such as the one
that causes chicken pox and shingles) aren’t suited for others. Some antivirals can’t even
treat different strains of the same virus.
And so every time a new virus appears we scramble for a new treatment. Our usual
antiviral approach is, as researchers say, “one bug, one drug”; often, it’s no drug. Ho has
spent forty years !ghting the aids epidemic, which has killed thirty million people and
still kills nearly a million a year; he has seen three coronaviruses ambush us in the past
two decades. Like many scientists, he’s tired of being behind the ball. He’d like to see a
penicillin for viruses—one pill, or, anyway, a mere handful—that will eliminate whatever
ails us. He and his colleagues aim to have these next-generation drugs ready in time for
the next pathogen. “We have to be proactive,” he told me. “We must not be in a position
of playing catch-up ever again.”
iruses are quite conniving for things that are not alive. A bacterium is a living cell
that can survive and reproduce on its own. By contrast, a virion, or virus particle,
can do nothing alone; it reproduces only by co-opting the cellular machinery of its host.
Each virion consists of nothing more than a piece of DNA or RNA encased in protein,
sometimes surrounded by a lipid membrane. When it gets itself sucked into a cell, it
manipulates the host into building the proteins necessary for viral replication—in
essence, turning it into a virus factory. Some of the proteins start to work on duplicating
the virus’s genome; others form a new viral coat. Those components get bundled into
entirely new virions, produced by the thousands, which then pop out of the cell and make
their way to other cells, within the same body or in a new one, happy to sail on the winds
of a sneeze.
The fact that viruses have so few moving parts is one reason they are so hard to destroy
without carpet-bombing the host organism. “They’re basically evolutionarily optimized
to be minimalists, so there aren’t a lot of targets,” David Baker, a biochemist at the
Howard Hughes Medical Institute, told me. The strategies employed against bacterial
diseases are generally useless when it comes to viruses. Some antibiotics, including
penicillin, interfere with proteins that form the cell walls of bacteria, causing the germs to
burst open and die. (Viruses don’t have cell walls.) Other antibiotics interfere with
bacterial ribosomes—tiny intracellular structures that manufacture proteins—or mess
with an enzyme crucial to a bacterium’s metabolism. (Viruses have neither.) When a
strain of virus does have an obvious vulnerability, there’s no guarantee that another strain
will share it—an obstacle for crafting generalist antivirals. And viruses tend to mutate
quickly and readily acquire drug resistance, as Ho found with H.I.V.
The most valuable weapon against viruses remains the vaccine—but vaccines (at least the
kinds we’ve formulated so far) tend to work against only speci!c, identi!ed viruses, and
have to be taken before infection. Since they’re not effective for everyone, moreover, we’d
want antivirals for acute treatment even if we had a vaccine in hand. And fast-mutating
viruses, like in'uenza, present a moving target, which is why, by the time a new batch of
'u vaccine is manufactured every year, it’s already outdated, powerless to !ght much of
what comes along. These limitations typically apply to antibody therapies as well: they
tend to be speci!c to a single, already encountered virus, and can’t be stockpiled for use
against new ones. That’s why Ho and his colleagues, like researchers elsewhere, are
looking for molecular vulnerabilities in virus families, and ways to exploit them.
The earliest antivirals were discovered by means of empirical observation, and almost
through happenstance. The !rst antiviral drug that came on the market, in the early
nineteen-sixties, was a repurposed anti-cancer drug put to use as a topical treatment for a
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herpes infection that attacked the cornea. Another early drug, ribavirin, was developed in
the nineteen-seventies, and worked against several DNA and RNA viruses, including
those that cause pneumonia and hemorrhagic fever. The same decade also saw the
development of acyclovir, which Ho called a “true breakthrough”; it inhibits the
reproduction of a variety of herpesviruses. A series of advances came in the nineteeneighties,
in response to H.I.V. One history of antivirals, published in 1988, decried the
toxicity and low efficacy of earlier drugs: “Two decades ago, antiviral therapy fell
somewhere between cancer chemotherapeutic principles and folk medicine.” Today, with
advances in genomic analysis and computer modelling, researchers hope to !nd drugs
that are both stronger and broader in their effects. Different researchers are targeting
viruses at different points, like generals probing for weak spots along an advancing front.
ne afternoon in March, I was set to visit the lab of Alejandro Chavez, a frank and
fast-talking pathologist and cell biologist at Columbia who is collaborating with
Ho. (Their lab buildings are kitty-corner.) A few hours before our appointment, though,
I got a message: the university had barred visitors. All nonessential employees had been
sent home. Ho and Chavez could carry on with their work, since they were researching
sars-CoV-2, the virus that causes covid-19, but I wouldn’t be allowed in. When I asked
if Chavez would give me a virtual tour of the lab by FaceTime, he was skeptical. “It’s not
gonna be that exciting, man,” he warned me. “You know what biology looks like. It’s like
moving clear 'uids from one thing to another. It’s not gonna blow your mind.” The lab,
sparsely peopled, contained a dozen PCR machines—DNA-ampli!ers, each about the
size of a toaster oven—and shelves cluttered with supplies and glassware. Debbie Hong, a
graduate student, was hunched over a lab bench, holding a pipette.
“It’s not like the movies, with lasers and lights and, like, crazy cells in green,” Chavez said
as he panned his iPhone around his lab. “It’s all pretty benign-looking.”
Chavez’s antiviral research focusses on a particular type of protein involved in viral
reproduction—a scissoring enzyme known as a protease. In normal cells, ribosomes read
instructions encoded in RNA and make a batch of some speci!ed protein. When a virus
like sars-CoV-2 presents itself to a ribosome, the intruder’s instructions are followed—
making the particular proteins that the virus requires in order to replicate. But the
ribosome delivers the batch of proteins all linked together in a long chain, a
“polyprotein.” So both cells and viruses then slice up these polyproteins into the smaller
pieces they need. It’s a little like what happens at a newspaper-printing plant, when a
huge roll of paper spins through the press and then gets sliced up into individual
broadsheets.
Cells and viruses both use proteases to do the slicing; for Chavez’s team, the challenge is
to identify new compounds that will inhibit viral proteases without interfering with a
human cell’s proteases. He’s planning to test about sixteen thousand drugs, taken mainly
from three “libraries” of compounds, many of which have already been tested for safety in
humans. “If you have some information on toxicity, it’s very helpful to advance the
compound faster,” Chavez said, referring to the process of pharmaceutical development.
Each library—a case !lled with thousands of chemicals—is packed in dry ice and
shipped from facilities elsewhere straight to the laboratory door.
In standard “high-throughput screening,” you might take a plate with three hundred and
eighty-four wells, each three millimetres wide, and introduce into each well a tiny sample
of the same viral protein—in this case, a particular protease—but a different drug
candidate. It’s as if you were testing three hundred-odd insecticides against one kind of
pest. But Chavez has devised a method that lets him study more than one viral protein at
a time. In each well, he will place about twenty coronavirus proteases, plus about forty
proteases from H.I.V., West Nile, dengue, Zika, and so on. “I can do as many as I want,”
he said. “Why would I stop at coronavirus?” In effect, he’s testing an array of insecticides
against a menagerie of pests—aphids, weevils, Japanese beetles—at once.
The innovation came naturally to Chavez. “My background was in building new
technologies,” he said. “And so I was, like, ‘Oh, I think I have a clever trick. Let’s play
around with it.’ ” He and Debbie Hong tried it. “We were, like, ‘Holy crap, there might
be something here.’ And this is the opportune time to really apply it full scale.” The
approach could speed the identi!cation of chemicals with broad effects—ones that work
against an array of viral proteases, not just one. (The main protease used by the new
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coronavirus, researchers say, is similar to one used in picornaviruses, a family that includes
poliovirus, the hepatitis-A virus, and the human rhinovirus.)
Chavez estimates that his multiplex project could take one or more years. “But if, at the
end of that process, I could have a compound that I know works not only against the
current strains but also on a lot of the future ones, that would be very useful to prevent
this sort of event down the road,” he said. “Because it’s not a matter of if it’s gonna
happen again—it’s simply a matter of when it’s gonna happen again.”
o replicate, viruses need to chop things up; they also need to glue things together.
Proteases do the chopping. Another class of proteins, called polymerases, do the
gluing. Interfere with the polymerases and you interfere with the assembly of the viral
genome.
DNA and RNA molecules are strings of smaller molecules called nucleotides. A good
way to stop polymerases from functioning, it turns out, is to supply decoy versions of
these nucleotides. A virus is tricked into integrating these building blocks into its own
genetic sequence. These nucleotide “analogues” are faulty parts; once they’ve been added
to a chain of viral RNA, they effectively bring things to a halt. It’s as if you’d been
assembling a toy train from a pile of cars and someone slipped in a car with no hitch on
the back, ending the sequence prematurely. Human cells are generally good at detecting
and avoiding such defective parts; viruses are more easily duped.
One pioneer in developing such polymerase inhibitors is Mark Denison, the director of
the Division of Pediatric Infectious Diseases at Vanderbilt, who—remote learning being
the new way of things—spent an hour and a half on the phone talking me through a
PowerPoint presentation. Denison began studying viruses in 1984, working with Stanley
Perlman, a microbiologist now at the University of Iowa. “I couldn’t spell ‘molecular
biology,’ I couldn’t spell ‘pipette,’ ” Denison recalled, but Perlman took a chance on him.
“I didn’t really understand how difficult the problem is, which is a good thing.” He
persisted, with his wife occasionally nudging him back to the lab. “Ultimately, I started
seeing the incredible, terrible beauty of viruses, and how unique their replication patterns
were and how much we had to understand about them.”
Denison has been studying polymerases and nucleotide analogues for the past thirty
years, and he points out that coming up with these decoys is especially challenging when
dealing with coronaviruses. Unlike other viruses, coronaviruses are excellent proofreaders
when it comes to reproducing their genome. Another small protein sits on top of the
polymerase, checking its work as it goes down the RNA chain. “It’s like an autocorrect on
your phone, if it worked well,” he said. Coronavirus genomes, which are about three times
the size of the average RNA virus’s, “are the biggest and baddest,” Denison said.
Still, he !gured that there was a way to elude the proofreaders. In 2012, he cold-called
Gilead, a pharmaceutical company with a specialty in antivirals, asking to try its
hepatitis-C drug sofosbuvir. He recounted, “They said, ‘Well, no, you can’t. That’s our
multibillion-dollar drug. We don’t know you.’ ” But they were open to collaboration, and
sent Denison’s lab a selection of other compounds. Denison and his team got to work
testing them on a coronavirus called mouse-hepatitis virus, which is safe to work with
because it doesn’t infect people. “To our shock, basically, the very !rst one we tried had
activity against our model virus,” he told me. “And I thought we made a mistake, and
then it worked again. So I wrote them back and said, ‘Umm, this looks like it works.’
They said, ‘Here’s sixty chemical modi!cations of that same drug.’ So we tested all sixty,
and every single one was more active than the original compound. But one of them was
really good. And they said, ‘Well, then, here’s the one we want you to work with.’ ” It
turned out that this drug, called remdesivir, had been developed, without notable success,
for use against Ebola.
This research helped Denison and his longtime collaborator Ralph Baric, a virologist at
the University of North Carolina, land a large N.I.H. grant, in 2014, to study coronavirus
drugs. Denison and Baric have been particularly excited about a small-molecule drug
known as NHC. (It’s technically a nucleoside analogue—nucleosides lack the
phosphorus group that nucleotides have.) This one also sneaks into a growing RNA
chain, but, instead of halting construction immediately, it introduces mutations in
subsequent copies. Denison says that NHC checks all the boxes: it inhibits multiple
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coronaviruses (including sars-CoV-2), has a high barrier to resistance, and protects mice
that have been given the drug even before infection. Unlike remdesivir, which has to be
infused intravenously, it can be taken orally, as a pill—an easier and cheaper way of
administering a drug. (To be sure, neither NHC nor remdesivir has yet been shown to
work in clinical trials.)
“Most people do extensive testing on one drug, then see if it works more broadly,”
Denison said. “We took the opposite approach, which was: we don’t even want to work
with a compound unless it works against every coronavirus we test, because we aren’t even
worried about sars and mers as much as we are about the one that we don’t know about
that’s going to come along.”
he usual goal with antivirals is to interfere with the virus, not the host. But some
researchers have taken a seemingly counterintuitive approach, seeking to change
the host environment in a way that makes it less congenial to viruses. With “hosttargeted
antivirals,” the aim is to disrupt certain processes in the human cells which are
used for viral replication but—with luck—not for much else. Shirit Einav, a Stanford
virologist who completed medical school in Israel before doing a residency in Boston, is
one enthusiast of this strategy. Frustrated that some of her hepatitis-C patients were
beyond the help of available treatments, she turned to research, spending !ve years
looking for a way to target hepatitis C and studying a drug that looked promising. She
became discouraged when she realized how narrow-bore it was. It worked against one
strain of the virus but proved useless against others, and resistance to it quickly
developed. “In the end, I realized how limited the scalability of this approach is,” she said.
“That was actually how I then transitioned to the host-targeted approach.”
Host-targeted drugs, she believes, could have a broader application than other antiviral
drugs. No matter which speci!c virus invades them, human cells have the same basic
machinery. The challenge is typically to !nd a dosage high enough to bother the virus
but not so high that it harms the host. It helps that our cells feature redundancy: if you
interfere with one cellular protein that viruses depend on, the cell often has a backup for
itself.
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Where Chavez and Denison are targeting viral proteins, then, Einav focusses on host
proteins—in particular, a class of enzymes that are co-opted by viruses to shuttle
themselves inside invaded cells. A few years ago, she discovered two cellular enzymes
required for viral infection and found that, in mice, two drugs that impair these enzymes
reduced dengue and Ebola viral loads. In lab-grown cell cultures, they slowed the
replication not only of dengue but also of other pathogens in the Flaviviridae family, such
as West Nile and Zika. Einav’s collaborators are now testing these drugs on the new
coronavirus. She’s hopeful, given that they’ve also shown promise against the virus that
causes sars. But she notes that they didn’t work for DNA viruses. An in!nitely broadspectrum
antiviral, she acknowledged, may be out of the question: “I don’t think it’s one
for all, but it might be one for many.”
Other host-directed drugs are being tested for use against sars-CoV-2. A pancreatitis
drug, camostat mesylate, inhibits a cellular enzyme that helps some viruses dock with
cells, and was shown last month to work against the new coronavirus, at least in cell
cultures. And, because the same enzyme is enlisted by other coronaviruses, like the ones
that cause sars and mers, there’s hope that the drug might be effective against a range of
these viruses. Chavez told me that if Einav’s compounds work in patients—always a big
if—“I think it could be a jackpot. These are all interesting ideas. I think you really want a
multipronged approach.”
t a moment like this, the urgency of such research is self-evident. But the market
has not encouraged the development of drugs for use in acute infections. The big
investment has been in drugs for chronic viral diseases, such as aids and hepatitis B. “If
you start looking at acute viral infections”—which hit suddenly and kill you or pass on
through—“it’s pretty gloomy,” Einav said of the !nancial prospects that pharmaceutical
companies see. David Baker, of the Howard Hughes Medical Institute, noted that,
although cancer drugs are also expensive to develop and bring to market, “there will
always be people dying of cancer.” But pandemics arrive infrequently and don’t
necessarily stay for long—characteristics that make them a commercial liability. “It’s one
of those cases where a traditional market economy doesn’t work so well,” Adalja, of Johns
Hopkins, said. “Suppose you made a sars antiviral in 2003,” after its 2002-03 run. “You
would not have had a return on investment, because sars was gone.”
In 2014, Timothy Sheahan, a microbiologist now at the University of North Carolina
and a collaborator of Denison’s, joined a group at GlaxoSmithKline working on broadspectrum
antivirals for respiratory infections. A year later, the project was shut down. “I
gained insight into how pharma works and how hard it is to develop drugs that not only
work but are safe,” he said. (He noted that many drugs that seem safe in animal models
prove otherwise in human trials.) “Twenty years ago, most if not all Big Pharma
companies probably had some antiviral-drug program. Now there aren’t many.” Jason
McLellan, a molecular biologist at the University of Texas at Austin, pointed out that, of
the six human coronaviruses known before the Wuhan outbreak, the two that caused
sars and mers killed only a few thousand people combined, and the four others cause a
common cold. “I’m not sure you can fault companies for not doing a bunch of drug
development on coronavirus,” he said. Denison’s sense of the need for basic,
noncommercial research makes him voluble in his gratitude to the N.I.H. “They’ve
supported me doing this work for about thirty years,” he said. “And so I think this
demonstrates the critical importance of doing fundamental research on every known
human-virus family and understanding their mechanisms and their unique targets,
because you just don’t know which family it’s going to come out of next.” All these
researchers agreed on the importance of developing multiple broad-spectrum antivirals;
all recognized that the private sector was unlikely to be a mainstay of support.
Last month, the Bill & Melinda Gates Foundation, Wellcome, and Mastercard pledged a
hundred and twenty-!ve million dollars to the covid-19 Therapeutics Accelerator to
help researchers, regulators, and manufacturers overcome some of the market
impediments to drug development. Creating a new antiviral will cost much more than
that, but funding from foundations, along with public institutions, can ease certain pain
points—for instance, by making it possible to solicit compounds for a pandemic-drug
library of candidates for screening. I asked Trevor Mundel, the Gates Foundation’s
president of global health, how we might prepare for the next global contagion. Let’s say
we had a drug that worked against a broad spectrum of coronaviruses, and maybe other
viruses, too. Would we manufacture and stockpile billions of doses, just in case? Who
would pay for that? He said that, if drugs with clear broad-spectrum potential came
along, governments likely wouldn’t need much convincing. At a minimum, countries
might make tens of millions of doses available for health-care workers and other critical
employees. But in the absence of truly broad-spectrum antivirals we might need twenty
drugs that act on different components of infection. Then we’d need to stockpile all
twenty.
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Mundel, a former pharmaceutical executive trained in mathematics, highlighted two
basic challenges when it comes to preparing antivirals for pandemics. “One rate-limiting
factor is manufacturing. People !nd that a boring subject, but if you don’t get
manufacturing right you can end up with nothing,” he said. “The other thing that is, of
course, rate-limiting is clinical studies. And you saw how chaotic that can be with Ebola,
and initially in China”—he was referring to the covid-19 pandemic. “There were a lot of
studies being done that were not well designed or controlled. And we start to see that in
other places as well: everybody’s jumping in with an observational study.”
A better platform for doing clinical studies would insure better data, but geography
stands in the way. Because pandemics move 'uidly across borders, ongoing studies like
Gilead’s remdesivir trials in China risk running short on patients if an outbreak is
contained in one location while 'aring elsewhere. “You’ve got to have a global clinical
study where you can shift around where you’re getting patients from,” Mundel told me.
“And nobody has ever had that kind of clinical study that’s been global and could pull
from different geographies as things pop up. So that’s what we’re trying to put in place.”
Meanwhile, the World Health Organization has launched a multi-arm trial across many
countries, with room to add more arms and countries. It’s called the Solidarity Trial.
n my call with David Ho, he led me on a FaceTime tour of his spartan office and
sprawling lab spaces. Hanging in an atrium was a two-story tapestry depicting a
double helix, which he’s had for twenty-!ve years. It was made by a man who helped
design Ho’s previous lab space and who later died of aids. Down a hallway, Ho pointed
through a window to a high-containment facility with PCR machines, centrifuges,
incubators, and microscopes. Venturing inside this area requires head-to-toe protective
gear.
Another room housed the lab’s most expensive machines, including one that makes cells
'uoresce and one with a sign warning “caution laser in use.” (Chavez’s disclaimer
notwithstanding, green cells and lasers aren’t just for movies.) The main lab was big and
open, with the capacity for seventy-!ve researchers. That day, it was nearly empty. The
“nonessential” people who had been sent home included aids researchers.
As he walked back to his office, the deserted corridors reminded me of Ho’s description
of the empty boulevard in Beijing. Now at his desk, Ho re'ected on negligence and
hubris. “We as a society dropped the ball after sars,” he said. “Just because the virus went
away, we naïvely thought, Well, you know, goodbye, coronaviruses.” There’s no reason, Ho
said, to think that it will ever be possible to bid such a farewell: “This is the third
coronavirus outbreak in two decades.” There is, undoubtedly, a fourth somewhere on the
horizon, if a different RNA virus doesn’t encircle the world !rst. There is no way to
predict what disease it will cause—it won’t be sars, or mers, or covid-19—but certain
things will be the same. Masks will come out, streets will empty, fear will take hold. One
thing might be different, if Ho and others like him have their way: there might be a
therapeutic arsenal already in place.
“This one is teaching us the lesson that we should persist and come up with permanent
solutions,” he said. “We need to persist until we !nd a broader solution. An outbreak due
to this virus or some other viruses will surely come back.” ♦
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A Guide to the Coronavirus
How to practice social distancing, from responding to a sick housemate to the pros and cons of ordering food.
How the coronavirus behaves inside of a patient.
Can survivors help cure the disease and rescue the economy?
What it means to contain and mitigate the coronavirus outbreak.
The success of Hong Kong and Singapore in stemming the spread holds lessons for how to contain it in the United States.
The coronavirus is likely to spread for more than a year before avaccine is widely available.
With each new virus, we've scrambled for a new treatment. Can we prepare antivirals to combat the next global crisis?
How pandemics have propelled public-health innovations, pre!gured revolutions, and redrawn maps..
What to read, watch, cook, and listen to under coronavirus quarantine.
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Published in the print edition of the April 13, 2020, issue, with the headline “Attack Mode.”
Matthew Hutson, a science writer living in New York City, is the author of “The 7 Laws of Magical Thinking.”

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