In an age of masking, compulsive hand sanitizing and plexiglass dividers, it seems inconceivable that for more than 40 years people enthusiastically signed up and were often put on a waiting list to have respiratory viruses, including coronaviruses, dripped into their noses.
They were volunteers at the Common Cold Unit, set up in 1946 by the British governments Medical Research Council. Housed in an abandoned American military field hospital in the English countryside, the Common Cold Units mission was to find a cure for the common cold and by doing so, boost productivity as the battered nation tried to rebuild after World War II.
Every two weeks, 30 participants arrived on the Salisbury Plain, not far from Stonehenge, to enjoy the bucolic setting perhaps do some painting or work on a novel and gamble on getting sick. About a third did. But, according to participant accounts, that didnt stop many of them from returning year after year, some for their honeymoons.
Its hard to overstate the importance of this quirky scientific venture, pitched in ads and newspapers as a cheap and comfortable holiday that was not to be sneezed at. Researchers at the Common Cold Unit discovered that coronaviruses were just one of more than 100 pathogens that cause cold-like symptoms, making a single cure elusive. Scientific orthodoxy previously held that colds were caused by a single organism, and bacterial at that.
Perhaps as significant, the Common Cold Unit established and refined a model for so-called human challenge studies that paved the way for the first Covid-19 human challenge study just completed in Britain, where young, healthy and unvaccinated volunteers were infected while researchers carefully monitored how their bodies responded.
Then, as now, there were those who decried deliberately infecting or challenging healthy volunteers with disease-causing pathogens. It violates the medical principle of do no harm. The tradeoff is a unique opportunity to discover the causes, transmission and progression of an illness, as well as the ability to more rapidly test the effectiveness of proposed treatments.
Its why even detractors pored over research that came out of the Common Cold Unit. There will likely be similarly keen interest when British researchers release data from their Covid challenge study. These kinds of studies can tell you things other kinds of studies cannot.
The key benefit of human challenge studies is that they are controlled everyone gets the same virus, the same amount and they are in the same environment, said Dr. Christopher Chiu, professor of infectious diseases at Imperial College London and chief investigator in Britains Covid challenge study.
We are able to work out what the differences are immunologically between those who get infected and those who are resistant to infection and then figure out which parts of the immune system could be stimulated to provide protection.
The history of human challenge studies dates back well before the Common Cold Unit. Perhaps most famously, Edward Jenner in 1796 inoculated a healthy 8-year-old boy with cowpox derived from a lesion on the hand of a dairymaid. That challenge led to the creation of the first vaccine and eventual eradication of smallpox.
There have also been human challenge studies conducted on prisoners of war and others who had not given their informed consent. Such breaches of scientific integrity led to the Nuremberg Code and Declaration of Helsinki, both drafted to protect human research subjects. But even with ethical frameworks and conventions, human challenge studies today are rare.
In the United States, the regulatory hurdles to conduct challenge studies mean there are precious few, mostly for finding better treatments for malaria, cholera and influenza. Ethicists and regulators are more comfortable approving clinical trials where subjects are given a treatment, say a drug or vaccine, to see if it helps improve a condition volunteers already have, or could prevent them from developing later.
This stance is frustrating for proponents of human challenge trials, who argue that Phase I clinical trials, in which humans are first exposed to a treatment to test its safety, are inherently risky. Moreover, studying people who are already sick or at risk of getting sick doesnt tell you much about why and how they get sick in the first place.
When you get someone who is already sick, they are typically days into the infection, said Dr. Matthew Memoli, director of the Laboratory of Infectious Diseases Clinical Studies Unit at the National Institute of Allergy and Infectious Diseases. A lot of the immunology, a lot of the action, that determines whether you get sick or not happens within the first 24 to 72 hours.
Dr. Memoli has conducted numerous influenza challenge studies and prepared a protocol for a Covid challenge trial that the National Institute of Allergy and Infectious Diseases rejected last year because it felt not enough was known about the virus and there were no effective rescue therapies, according to a statement from the office of the director, Dr. Anthony Fauci.
The consortium formed to run Britains Covid challenge trial, which included scientists who trained at the Common Cold Unit, had access to the British National Health Services robust, real-time data on Covid hospitalizations and deaths. The researchers designing the study said they felt confident that there was little risk to the healthy unvaccinated 18-to-30-year-old volunteers they recruited for the trial. There were no severe adverse events in the 36 people who participated, and they will continue to be monitored over the next year.
The aim of the study was to identify the lowest amount of virus to safely and reliably infect someone, so researchers can later easily test the efficacy of vaccines or antivirals on future challenge trial volunteers. Of course, in doing that, you learn a lot about the actual disease, which indeed we have, said Dr. Andrew Catchpole, chief scientific officer at hVIVO, a British clinical and laboratory services company that partnered with Imperial College London to conduct Britains Covid-19 challenge study.
The volunteers were infected with the original SARS-CoV-2 strain first discovered in Wuhan, China. A Delta strain is being developed to be used in possible later challenge trials. Coronaviruses are not going away and there is going to be continual risk of new highly pathogenic coronaviruses coming along, said Dr. Chiu. We need to understand those immune factors much better so we are better prepared for the next pandemic when it comes.
Dr. Faucis office said the institute has no plans to fund Covid-19 human challenge trials in the future. Many bioethicists support that decision. We dont ask people to sacrifice themselves for the good of society, said Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics. In the U.S., we are very much about protecting individual rights and individual life and health and liberty, while in more communal societies its about the greater good.
But Josh Morrison, co-founder of 1Day Sooner, which advocates on behalf of more than 40,000 would-be human challenge volunteers, argues it should be his and other peoples right to take risks for the greater good. Most people arent going to want to be in a Covid challenge study, and thats totally fine, but they shouldnt project their own choices on other people, he said.
Not that human challenge trial participants arent compensated for their trouble around $6,000 for the Covid-19 challenge volunteers and a free holiday in the country, including lodging, meals and incidental expenses, for those who took part in studies at the Common Cold Unit (which closed in 1990 when its funding was pulled for AIDS research).
But judging from archival and recent interviews with challenge trial participants, the real driver was, and still is, a desire to be of service. The prospect of helping humanity made volunteers feel good, they said, and gave them a sense of agency whether in the dreary aftermath of World War II or now in the uncertain days of a global pandemic.
As one participant in Britains Covid human challenge trial put it: You know the phrase one interesting fact about yourself that strikes terror into everyone? Thats now solved forever. I did something that made a difference.
Kate Murphy is the author of Youre Not Listening: What Youre Missing and Why It Matters.
The Times is committed to publishing a diversity of letters to the editor. Wed like to hear what you think about this or any of our articles. Here are some tips. And heres our email: [email protected].