Jonathan Rothberg’s Race to Invent the Ultimate Rapid At-Home COVID-19 Test

Jonathan Rothberg’s Race to Invent the Ultimate Rapid At-Home COVID-19 Test

The inventor and entrepreneur prophesies a future in which self-testing has become one more morning ritual between brushing our teeth and putting on a pot of coffee.

On the morning of March 7th, the inventor and entrepreneur Jonathan Rothberg announced, on Twitter, that he’d been thinking through the possibility of “a low cost easy to manufacture home test kit for #Coronavirus.” Attached to the tweet was a photo of a clean-swept desk before an orderly collection of curious desktop appliances, backlit, through a large picture window, by the sun’s reflection in an azure surf. Rothberg lives and works in Connecticut, where his holdings include a biotech incubator, a vineyard, and a full-scale near-replica of Stonehenge, made of Norwegian granite and modified for celestial alignment with his children’s birthdays, but for the moment he was at sea. He, his wife, and three of their five children had just arrived in the Bahamas, where they had planned to take the M/Y Gene Machine, their hundred-and-eighty-foot superyacht, on a spring-break cruise to Atlantis. Fortunately, the ship had been outfitted with Rothberg’s demiurgic propensities in mind. One luxury broker and charter operator told me that Rothberg is venerated, in the small, gossipy world of superyacht owners, as “the mad scientist with his state-of-the-art lab.” The broker continued, “It’s well known in the industry that Rothberg does his best thinking on the ship, where his mind is clear and free of distractions.”

Rothberg’s “best thinking” generates new ideas at a berserk pace, often without regard for immediate feasibility, but his ambitions are warranted by a long history of unlikely successes. At various points in his career he’s considered a return to academia; in each case he has found himself haunted by a practical problem of some personal urgency, and has relapsed into commercial enterprise. At fifty-seven, he presides over seven sibling companies, most of which are organized around the principle of scale: he likes to take existing technologies and make them faster, smaller, cheaper, and more readily available. His portable MRI sells for fifty thousand dollars, his home ultrasound for two thousand. He is most widely known, however, as a pioneer of “next-generation sequencing,” a major advance in the speed with which a genome could be read. The consequences of this breakthrough for personalized health, forensic investigation, and the study of human prehistory, to take only a few examples, have been breathtaking; in 2016, President Barack Obama bestowed upon him the National Medal of Technology and Innovation for his achievement.

Rothberg’s original plan for 2020 had been to use one of his newer companies, Homodeus, to trawl for genetic evidence of “panspermia,” the not entirely disreputable idea that life on earth arrived in the form of ancient space dust. But the problem of coronavirus testing—the need for reliable diagnosis of an unprecedented sweep—was a high-stakes contest of immediate appeal. Rothberg thought the team’s background work in custom enzyme production was well suited to the contrivance of a covid-19 diagnostic that did not rely on cumbersome and expensive machines. In February, Rothberg had been dumbstruck by the U.S. government’s failure to marshal its resources in preparation for a comprehensive clinical-testing regime. He’d assumed that the people in charge would get their act together before long, but he swore to himself that he would face the next pandemic with a simple diagnostic platform of his own devising. By the time he boarded the Gene Machine, he felt that he could not afford to tarry.

The closest thing we have to a gold standard of pathogenic diagnosis is the polymerase chain reaction (PCR) method, which registers even trace amounts of the virus’s nucleic acid. Such “molecular” tests can be calibrated for an unimprovable specificity: false positives are exceedingly rare. (Their sensitivity, or rate of false negatives, is less certain.) The process, however, is embedded in a vast infrastructure: labs depend on complex supply chains for materials and reagents, and samples must be collected and distributed throughout a network of depots for processing. Optimizing this system requires a good deal of centralized coördination and oversight. Other countries rose to the occasion, and were able to use widespread PCR testing to track and manage their outbreaks. But, even if the U.S. government had acted with alacrity and competence, there are limits to what such a system can do. A streamlined operation might be able to complete thousands of tests at once, but trucks can only carry so many samples and move so quickly, and the turnaround time for a result is almost never less than a day.

Rothberg was not alone in his belief that America would continue to fail this test—and that a day’s turnaround could still not guarantee a return to ordinary life. In university labs, small startups, and large life-sciences companies, researchers improvised, drawing upon a variety of techniques to compensate for the lack of national leadership. Rothberg told his core staff not to worry about competitors—he expected that most of them would be focussed on antibody tests, which can only diagnose in retrospect and have often proved untrustworthy, or antigen tests, which register the presence of viral proteins. These can be quick and inexpensive but aren’t generally as accurate as molecular tests, which indicate not the presence of a viral proxy, like a protein, but of the virus itself. Rothberg’s predictions were almost immediately confirmed: a small Massachusetts startup, E25Bio, soon announced that they had raised millions of dollars of venture capital, and anticipated approval for their fifteen-minute at-home antigen test within two months.

Rothberg was committed to the development of a molecular nucleic-acid test as accurate as PCR, as fast and simple as a home pregnancy test, and as inexpensive as an antibody or antigen option. A standard PCR test normally costs about a hundred dollars, though the price is often subsidized; he wanted his available for ten. With such a device, Rothberg wrote on Twitter, “read-out would be in minutes – timer in App – read by camera in your smart phone. No other machines.” Over the next forty-eight hours, Rothberg live-tweeted the creation of a new enterprise, tracing his “thought experiment” with a steady but haphazard accretion of technical detail, earnest self-promotion, and preëmptive networking. He tagged researchers at Yale and the University of Pennsylvania. By the end of the first day, he’d received an e-mail from a “great manufacturer.” On day two, he reported that he’d made “some general progress on the sample collection.” He asked his followers, in a poll, whether they thought he should continue, and, for reasons that were not fully clear, he tagged the Gates Foundation.