As a young man, Stephen Crohn could only watch helplessly as one by one, his friends began dying from a disease which had no name. When his partner, a gymnast called Jerry Green, fell desperately ill in 1978 with what we now know as Aids, Crohn simply assumed he was next. But instead as Green became blind and emaciated as the HIV virus ravaged his body, Crohn remained completely healthy. Over the following decade, dozens of friends and other partners would meet a similar fate. In 1996, an immunologist called Bill Paxton, who worked at the Aaron Diamond Aids Research Center in New York, and had been looking for gay men who were apparently resistant to infection, discovered the reason why. When Paxton tried to infect Crohn's white blood cells with the HIV virus in a test tube, it proved impossible. It transpired that Crohn had a genetic mutation – one which occurs in roughly 1% of the population – which prevents HIV from binding to the surface of his white blood cells. Over the following decade, scientists developed an anti-retroviral drug called maraviroc, which would transform the treatment of HIV by mimicking the effect of this mutation. It has proved crucial in helping to control the virus in infected people. While Crohn died in 2013 at the age of 66, his story left a legacy that has stretched well beyond HIV. Over the past two decades, it has inspired a whole new realm of medical science, where scientists look to identify so-called "outliers" like Crohn, who are either unusually resilient or susceptible to disease, and use them as the basis for discovering new treatments. As a geneticist at the Icahn School of Medicine in New York, Jason Bobe has spent much of the past decade studying people with unusual traits of resilience to illnesses ranging from heart disease to Lyme disease. So when the first wave of Covid-19 struck, his initial instinct was to wonder whether there were people out there who the virus was unable to infect. "It just made me think of Stephen Crohn, and that somebody ought to be looking for these outliers in Covid," he says. Bobe's idea was to try and find entire families where multiple generations had suffered severe cases of Covid-19, but one individual was asymptomatic. "Having a whole family together makes it easier to understand the genetic factors at play, and identify genetic factors behind resilience," he says. In the past, identifying such families might have taken years or even decades, but the modern digital world offers ways of reaching people that were inconceivable at the height of the HIV pandemic. Since June 2020, Bobe has been working with the coordinators of Facebook groups for Covid-19 patients and their relatives such as Survivor Corps to try and identify candidate families. He has also created an online platform, where anyone who has had an asymptomatic case of Covid-19 can complete a survey to assess their suitability for inclusion in a study of Covid-19 resilience. Over the coming months, Bobe hopes to sequence the genomes of people who display signs of resilience to Covid-19, to see whether there are any common mutations that appear to help them evade the virus. If so, this may provide inspiration for antivirals which can protect against both Covid-19, and also future coronavirus outbreaks. There are some clues already. Researchers have identified an association between type O and rhesus negative blood groups, and a lower risk of severe disease. But while scientists have hypothesised that people with certain blood types may naturally have antibodies capable of recognising some aspect of the virus, the precise nature of the link remains unclear. But Bobe is far from the only scientist attempting to tease apart what makes Covid-19 outliers unique. Mayana Zatz, director of the Human Genome Research Centre at the University of São Paulo has identified 100 couples, where one person got Covid-19 but their partner was not infected. Her team is now studying them in the hope of identifying genetic markers of resilience. "The idea is to try and find why some people who are heavily exposed to the virus do not develop Covid-19 and remain serum negative with no antibodies," she says. "We found out that this is apparently relatively common. We received about 1,000 emails of people saying that they were in this situation." Zatz is also analysing the genomes of 12 centenarians who have only been mildly affected by the coronavirus, including one 114-year-old woman in Recife who she believes to be the oldest person in the world to have recovered from Covid-19. While Covid-19 has been particularly deadly to the older generations, elderly people who are remarkably resistant could offer clues for new ways to help the vulnerable survive future pandemics.