A decade ago Joe DeRisi received a letter from a woman with a picture of herself wrapped in a boa constrictor. “I heard you’re a virus hunter,” the letter began before going on to explain that the snake, which she referred to as “Mr. Larry,” was her service animal. She was terrified that an illness then killing snakes all over the world might carry away Mr. Larry too. “I thought, ‘Wow, that’s crazy,’” recalls DeRisi, a biochemist at the University of California at San Francisco. It actually wasn’t much crazier than a lot of the other problems that landed on his desk. Human beings with illnesses that mystified the global medical establishment often found their way to DeRisi. Snakes, not so much. “I let the letter sit on my desk for maybe a year,” he said. “It was a weird letter.”
One day his curiosity got the best of him. He called a vet he knew and asked, “Is it true that snakes are dying of some mysterious disease?” “Oh yeah,” said the vet, as if everyone knew this, and told DeRisi that zoos everywhere were seeing their snake populations being wiped out. “I then went on YouTube, and typed in ‘Hey, my snake is sick,’” says DeRisi. “And all these videos start popping up, from all over the world.”
DeRisi soon realized that he had stumbled onto a snake pandemic whose origin remained entirely uninvestigated. He ordered up some dead snakes so that he might play around with their genome in the same way that, back in 2003, he’d analyzed human genomes after people were killed by a mysterious new coronavirus that had surfaced in Hong Kong. (SARS, the new virus was being called.)
To work the same magic on snakes that he did on humans — that is, to separate the genetic material that was “python” from everything else, he needed to know the python’s genome. “Who founded the Python Genome Project?” says DeRisi. “No one!”
And so DeRisi took some of his graduate students to the San Francisco aquarium, extracted the blood of one of its snakes, and began what amounted to the Snake Genome project. Once he was done, he was able to take the genetic material of an infected snake, eliminate everything that was “snake,” and thus isolate what wasn’t snake: the virus. “It was actually an ancient ancestor of Ebola,” says DeRisi. “Dinosaurs had this same virus.”
Just before the SARS epidemic, DeRisi had created a new computer chip, which he called the Virochip. It allowed him, in effect, to take the DNA from a sick person and sort the human genetic material from whatever wasn’t human — say a virus. “The game is to separate you from everything else,” he said. In 2003, few knew about DeRisi’s new tool, and it never occurred to the public health authorities to consult him. “We literally had to beg the CDC to send us a sample of the virus,” DeRisi recalls.
Eventually he got his hands on a sample, and presented it to the Virochip. It read SARS as one part cow coronavirus, one part bird coronavirus and one part human coronavirus — in other words, it did not match any known virus. “It was like pieces of a jigsaw puzzle from three different puzzles,” DeRisi says. “They didn’t fit together.” He sequenced the virus’s genome — and that’s what allowed others to figure out that it, like the new coronavirus, had come from a bat. “No one had ever seen bat coronaviruses,” DeRisi says. “They didn’t exist. We should have paid more attention the first time.”
I tell you all this to explain why, on the night of April 11, I found myself driving across the Bay Bridge to see Joe DeRisi. He’s now the co-president of the Chan Zuckerberg Biohub, a nonprofit organization created a few years ago with a $600 million gift from the Facebook Inc. founder Mark Zuckerberg and his physician wife, Priscilla Chan. As a graduate student Chan had heard DeRisi give a single lecture, about the computer chip that could detect and identify all viruses, known and unknown, and it had blown her mind. The Biohub’s stated mission was to eliminate all disease by the end of the 21st century, which sounds audacious but then: Why not? Chan asked herself who in the world might be able to do such a thing and decided that DeRisi was the best hope.
That was an example of a general phenomenon: When a problem feels unsolvable it tends to find its way to DeRisi. Another example occurred at the end of February, when DeRisi’s office phone began to ring. He looked down, didn’t recognize the number and almost didn’t answer. “I thought it was a telemarketer, but I picked it up and it was Gavin Newsom,” says DeRisi of the governor of California. “He asked: ‘What are the three things California could screw up in the coming weeks?’ I said number one was testing. Because if there is no testing there isn’t even the possibility of a solution.” DeRisi thought testing was so important that he would soon forget the other two important things that California might screw up.
He then watched the entire country screw up testing. By the second week of March it was clear that the absence of federal leadership, combined with the fragmented nature of the American health-care system, meant that tests for the coronavirus either were not available or were not processed by labs in anything like a useful period of time. He read stories of patients waiting 10 days for test results. “We heard that sending tests even to the CDC was taking days, not hours,” says DeRisi.
Absent fast tests, the hospitals were being forced to treat anyone who rolled into the parking lot with coronavirus-like symptoms as if the patient had the virus, when more often than not, the patient did not. Beds in the coronavirus wing were being taken by people who didn’t need them; nurses and doctors were running through scarce protective gear they needed for actual coronavirus cases. But the biggest problem of having no tests was not knowing where the virus was, and where it was not. Without fast tests you could not isolate the people who needed to be isolated, or free up the people who didn’t.
On March 12, DeRisi decided to turn the Biohub into a coronavirus testing lab. He enlisted the help of 200 University of California at San Francisco graduate students, and persuaded Newsom to issue an executive order that would allow the Biohub to operate under U.S. regulations, rather than the more stringent California ones, which prevented people not specifically trained to work in a clinical lab from doing so.
His student army organized themselves into squads kept separate from one another — so that if one person contracted the virus it would incapacitate only one squad and not the entire army. Each squad had its hierarchy, and people learned the jobs of the people immediately above them, so that they could replace them if necessary. “We built in battlefield promotions,” says DeRisi. They looked into what was going on in the various markets, all tight, for the stuff you needed to run tests — the plastic jugs of chemical reagent, for example. They designed the lab around the supplies they were sure they’d have access to.
The equipment — well, that was its own story. American medicine is littered with machines designed for testing. But they lay idle because the companies that made them were failing to supply the reagents they needed to work. UCSF itself had a machine, called the Panther, capable of processing 1,400 tests a day, but it was just sitting there unused for this very reason. “Big clinical testing machines are designed on the razor/razor blade model,” says DeRisi. “You can’t use them without their razors.” His graduate students either built the machines they needed themselves or grabbed wherever they could find that might be adapted. “Here is the frightening aspect of the global supply chain,” says DeRisi. “When there is a surge in demand, inventory goes to zero.”
Eight days after the 200 volunteers started building the new UCSF testing lab, the Biohub was up and running. Since March 20, it’s been able to process 2,500 tests a day, at no cost. Quest Diagnostics, one of the biggest diagnostic labs in the country, was saying that if you sent them a test, it would take them a week to get back to you with an answer, along with their bill. In just one day more than it took Quest to process a single test, DeRisi built an entire lab that could process 2,500 of them. A day. For free. Any given test it could process inside of three hours. DeRisi was pretty sure his lab was bigger than any lab in the country that was faster than his, and faster than any lab that was bigger.
It was also different, in an important way. The commercial labs are set up to take in the samples and spit out a simple answer: positive or negative. They aren’t set up, as the Biohub is, to sequence the genome of every positive specimen and look for variations among them. As it moves through the population, the virus replicates and, as DeRisi says, “every time you replicate something there is a chance of an error.” He’s already found tiny differences from one coronavirus genome to the next — not so great that it changes the essential nature of the virus but noticeable nevertheless.
Those tiny disparities can paint a picture of how the virus has traveled and how widely it has spread. It’s a bit like a game of telephone. A group of people sit in a circle. A person starts the game by whispering a little story into the ear of the person to his right, who then repeats it to the person on her right, as best as she can. As the story travels around the circle, tiny flaws get introduced. If you knew the flaws — both the number and the nature — you could make good guesses about the number of people playing the game, and also where they were sitting in relation to one another. That’s exactly the sort of information we’re all now starving for: How is the virus spreading, and how many people have had it.
The lab is a single room the size of half a basketball court organized into stations, and staffed by graduate students, in white coats and masks, working in shifts of roughly 60 people, around the clock. DeRisi walks me around and introduces me. The masked people are from everywhere in the world, and the only obvious pattern is that, when asked where they are from, the Americans answer with a city or a state, and the non-Americans with a country: China, Taiwan, Colorado, Tanzania, Lithuania, Florida, Canada, Phoenix, Belgium. None of them are doctors; they’re research scientists, many with PhDs; exactly zero of them have ever done the jobs they’re doing now. “It’s different from a regular research lab where people just do what they want and come and go as they please,” says DeRisi. “It’s more like a factory. A production line.”
The graduate students were still getting used to the idea that some actual human is out there on the edge of a hospital bed, waiting to hear what they’ve found. One scientist tells me she has a version of a recurring dream she used to have when she worked as a cocktail waitress. “I used to have these terror dreams that we’d have 100 people need a cocktail at the same time for happy hour,” she says. “Now I have the same dream about thousands of people needing test results at once.”
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But this isn’t a dream. It’s the problem consuming American society at every level, even if it isn’t always put that way. Every question about when the country reopens is actually a question of when testing will be good enough to allow it to reopen. Every question about the virus itself — how lethal it is, how many people have it without knowing they have it — can only be answered by more testing. In mid-March, when DeRisi got started, the entire state of California was generating test results for only about 2,000 people a day — with tens of thousands of tests backed up in commercial labs. DeRisi knows he can help close this gap, doubling or even tripling his lab’s capacity to 6,000 a day from 2,500. In a sane world, the Biohub would be doing just that. Instead, it is receiving only about 200 tests each day.
Two things interfere with DeRisi’s ability to solve the nation’s biggest problem. The first is that U.S. hospitals are either contractually obliged or habitually inclined to send tests to the for-profit labs, and the for-profit labs aren’t moving fast enough. The tests that arrive each morning and evening at the Biohub’s nonprofit lab come from the UCSF hospital down the street or public health clinics in surrounding counties. These clinics are places of last resort for people without health insurance, but they now offer the fastest and most reliable coronavirus tests.
But the bigger problem is the scarcity of testing kits, for both rich and poor. Actually that’s not quite right. If you roll into a hospital parking lot with a dry cough and a fever and ask to be tested and they say, “Sorry, we have no testing kits,” what they likely mean is “We have no nasal swabs.” The long translucent sticks that can be inserted deep into the nasal passage, and offer the only reliable, safe method to obtain a sample of the virus, were manufactured in just two factories. One, in Northern Italy, was crippled by the virus, and other countries moved faster than the U.S. to soak up the nasal swabs on the market. “It’s the one thing if I could go back in time and change I would,” says DeRisi. “I wish I had bought 100,000 swabs. It was not on my radar. It was not a thing I thought would be a limiting factor in life.”
When he said this, he was leaning back in a chair in a room down the hall from his new lab, filled with a dozen exhausted volunteers. Like DeRisi, the students were mostly infectious disease researchers, and so I took it as an opportunity to ask actual experts a bunch of seemingly relevant questions.
“What comes first, a treatment or a vaccine?” I ask.
Every one of them thought a treatment. “Coronavirus vaccines are tricky,” says DeRisi. “We still don’t have one for the common cold.”
“How many of you are worried about getting the virus yourself?” I ask. They were all in their 20s and, I assumed, more or less immortal. Every hand in the room went up. Some already knew a person their age who had died from it.
“It’s starting to knock off people who matter to us personally,” one says.
More to the point: None of them knew why some people walked around never knowing they had the virus, while other people were killed by it. The knowledge simply didn’t exist.
“It feels like a roll of the dice,” another of the young scientists adds. “But it’s a nasty roll of the dice.”
Maybe hoping to cheer everyone up, DeRisi pointed out just how much worse the situation could be. “If the virus had a higher fatality rate we might be looking at societal collapse,” says DeRisi. “What if it was worse in kids? Would I be here? Or would I be looking for a cabin somewhere?”
“It’s disturbing how much no one knows about this,” I say, at length.
“Welcome to science,” says DeRisi. “You don’t have to scratch too much below the surface here to realize you have reached the limit of knowledge.”
In the last week or so, word’s spread that the absence of nasal swabs is screwing up Joe DeRisi’s ability to save us from ourselves. The day after my visit he had a phone call from a UCSF donor. A big shot. “I know a guy who has some swabs,” the donor said. DeRisi was dubious: He’d already searched high and low, at every level of business and government, for the swabs. “I said, Really, you know a guy? Prove it.” The big shot said that he would have his friend overnight 5,000 swabs.
The next day DeRisi went to the UPS Store, and grabbed the package. “I pop open the box and there’s 5,000 of something in there,” he says. “They clearly didn’t just fall off the back of a truck. And they kind of looked like swabs.” But they weren’t packaged, or sterile, so they clearly weren’t medical supplies of any kind. DeRisi picked one up and studied it. It looked familiar. Then he realized: eyelash brushes. Someone had actually bought eyelash brushes, relabeled them as medical swabs, and was now selling them at a huge profit. The free market at work.
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