Viral DARPA

29 APR 2020

Britain is perfectly placed to replicate the DARPA miracle, but it will need to embody the qualities that have made the agency exceptional.

They’re pretty prescient at DARPA. When the American defence research agency published its list of the 23 greatest mathematical challenges, it included the development of “an information theory for virus evolution”. That was 13 years ago.

The inclusion may seem surprising. You might have thought the war on viruses would be fought by medics rather than mathematicians. But in fact, the structure of viruses, and the way they spread, have a symmetry and subtlety that are particularly suited to mathematical insight.

If you were to invent a self-replicating machine, you’d be hard-pressed to beat viruses for lethal efficiency. There are 1031 viruses on Earth—many kinds of which are swirling around you as you read this. Unlike most organisms, they rely on the infrastructure and raw materials of other life forms to replicate themselves, in the same way as computer viruses rely on existing software to spread. In the case of COVID-19, the genetic information is just 30,000 base pairs. That’s 7 kB of data, the equivalent of about a hundred lines of computer code. The human genome, by contrast, is 3 GB. So if man is a two-hour feature film, COVID-19 is 0.02 seconds of subliminal messaging.

The COVID-19 virus consists of little more than its own construction manual, in the form of a strand of RNA, and a container to protect it and interact with the host, called a capsid. One of the early mysteries about viruses was how such a short RNA program could code for and assemble its own container.

In a triumph of mathematical insight into biology, scientists discovered the answer. Through a mixture of imaging, geometry and group theory, they deduced that only a few protein building blocks are coded for, but they are used repeatedly in a symmetric fashion. Remarkably, they self-assemble into an icosahedron, or regular 20-sided solid, which forms the capsid. They achieve this feat by forming a combination of flat pieces, called hexamers, and curved pieces, called pentamers. For an analogy, picture how the surface of a football is made of alternating hexagons and pentagons. More recently, mathematicians at the universities of York and Leeds found that this order reflects how the genomic material is organized inside, providing potential targets for antiviral therapies.

Since publishing its 23 mathematical challenges, DARPA has put its money where its mouth is. It now has at least three research programmes contributing to the war on viruses: Prophecy, which aims to predict viral spread; Preempt, which aims to prevent it; and Intercept, which seeks alternative treatments. Given the nature of high-risk, high-reward research, it’s impossible to say if these programmes will succeed. Yet DARPA’s track record indicates how transformative the results could be.

The Advanced Research Projects Agency, as DARPA was originally known, was founded in 1958 in response to the Soviet Union’s launch of Sputnik. Since then, it has racked up an extraordinary litany of breakthroughs: GPS, drones, the internet, RISC computing and stealth technology among them.

In its Spring Budget this year, the Government committed to developing a DARPA of its own. To which one might respond: what took you so long? Britain’s history of scientific discovery and military innovation is second to none. Quite simply, no country in the world is better placed to replicate the DARPA miracle.

Yet many governments and businesses have tried to emulate DARPA’s success, with mixed to poor results. If Britain is to be the exception, it will need to identify and embody the qualities that have made DARPA exceptional. Since its inception, the London Institute has been involved in three DARPA projects. Indeed, DARPA was the first agency to fund it. As a result, the Institute has got to know how DARPA works, and seen how it benefits from three core virtues.

First, DARPA is supremely ambitious. It tackles fundamental problems at the fringes of our ability. This is rare. While working at Bell Labs, information theory pioneer Richard Hamming asked his colleagues to name the most important problems in their fields. Later, he asked them what they were actually working on. To his surprise, the two sets of answers didn’t overlap. Yet as he pointed out, “If you don’t work on important problems, it’s unlikely you’ll do important work.” The trouble is, if you tackle the toughest problems, there’s a likelihood of failure, and agencies are wary of funding research that is likely to fail. Scientists often avoid it because modern publication metrics tend to give equal credit for leaps and incremental advances. DARPA’s appetite for risk makes it a singular instigator of moonshot innovation.

Second, DARPA takes a “special forces” approach to research. When creating its Delta Force in the 1970s, America emulated the SAS. Now it’s time for Britain to call in the favour and learn something from the Yanks. DARPA keeps its teams small and agile, led by a confident programme manager who is also an experienced practitioner. Projects operate to a tight deadline of three to five years, which ensures a sense of urgency. As new sub-problems emerge, people may be taken off the programme, and others brought in. Researchers, known as “performers”, don’t apply for positions; they are tapped on the shoulder. They don’t work at DARPA labs. Rather, they do their research from the universities, research institutes and corporations where they’re based, but meet their team and managers regularly to assess progress. Everything is geared towards simplicity and efficiency.

Third, DARPA possesses extraordinary convening power. Put another way, it can pretty much get any scientist it wants. Identifying talent is one thing, but the hard part is convening it. Like in a heist movie, you want to bring together a crack team as fast as possible, with all the requisite skills for breaking into the vault. DARPA’s brand magnetism means its shoulder-tap is compelling. Thanks to its operational autonomy, it is free of the indecision and in-fighting that plague other government agencies. It circumvents the bureaucracy that can slow the progress of research, whether by bypassing open calls for detailed proposals or dispensing with progress reports. The result is a virtuous circle that makes working for DARPA an irresistible prospect.

At present, the country’s focus is on minimizing the deaths and economic collapse caused by COVID-19. This battle is being carried out by medics, biologists and our nation’s leaders. When we have converted retreat into advance, we shall continue to fight the war. In this longer game, mathematical scientists and the nascent British DARPA will play a vital role.