More than a dozen people showed up in November, 2007, at the National Institutes of Health (NIH) lab run by Christopher Austin. The parents of children dying from the lethal cholesterol metabolism disorder, Niemann-Pick disease type C (NPC), gathered alongside scientists and doctors looking for a treatment. They wanted to work together to find effective drugs and get them into clinical trials within a few years, accelerating the typical timeline for drug development. They hoped to find a compound that might extend the lives of children with the rare disease, who typically died by age 19.
In terms of the science, the meeting was a success. Dr. Austin’s lab had built a robotics system that rivaled ones found at pharmaceutical companies, enabling the rapid screening of drug libraries. By the end of the meeting, he agreed to use the robots to test thousands of different drugs on skin cells that one of the doctors collected during a study of children with NPC disease. Once they generated a list of promising drugs that got the cholesterol stuck in the cells moving again, the parents and researchers would all meet together to winnow down the candidates and figure out which ones to push forward.
But the partnership established that day was not only focused on advancing the science. Members of the collaboration had also embarked on a remarkable social experiment, one with implications extending far beyond NPC disease. They were testing the idea that professional scientists and citizen scientists, each with valued and essential expertise, can work together as equal partners to identify and then help develop potential treatments for diseases, particularly those that may be overlooked by pharmaceutical companies or biotechs because they are less common.
During the meeting, Dr. Austin highlighted some of the potential obstacles that might arise during scientific experiments. Sometimes a drug that seems promising in an animal doesn’t work in a person, he explained, or has an unexpected, deleterious side effect and must be abandoned. Later, he realized that he should have talked about the threats to the social experiment they were running too. It wasn’t simply that parents of seriously ill children with a fatal disease and scientists used to doing basic research in the lab might have different agendas, he said. His main worry was, “They have different belief systems.”Bridging such a divide is a challenge. Scientists and patients may be reluctant to raise disagreements, afraid that the collaboration might stop before it even gets started. Many patients feel fortunate to even get the attention of scientists, Dr. Austin pointed out, or “don’t feel they know the vernacular well enough to bargain intelligently.” Even so, one of the key things Dr. Austin learned from his work in the NPC collaborative: : “We needed a constitution.”
In recent years, patients, particularly those with rare or lethal diseases, have decided they were no longer willing to leave science to the scientists. Many realized that pharmaceutical companies were not developing new treatments for their conditions, often because the market was simply too small to justify the resources and investment required to identify, test, and get novel drugs approved. Even if the companies were willing to try, studies indicated that the time from a promising idea in a lab to market approval was closing in on seventeen years, far too long to help current patients. Researchers often pursued scientific questions that reflected their own interests rather than those of the patients they set out to help.
In pursuit of answers, patients started gathering and analyzing their own medical data. They used the internet to find one another, and joined other like-minded patients or families in chat groups and organized communities springing up on Facebook. They found scientists to work with them and launched collaborations like the one that started in Dr. Austin’s NIH lab.
Only then did they realize that the rules and frameworks that traditionally guide scientific research and partnerships didn’t seem to apply.
For over half a century, the focus in medical research had been on discovery launched by an individual investigator and experiments inside a lab. The system of research ethics, which evolved over decades, was set up in order to protect vulnerable people from scientists, doctors, and investigators, all groups that traditionally wield more power and more information than patients or families. There was no established system of rules when families and patients started to drive science.
On the list of leads that the scientists and parents in the NPC collaboration drew up to test, some of the compounds were ones that parents could buy on their own and try on the children, without the scientists’ approval. There was disagreement over who should decide how soon experimental drugs that were promising in animals but whose toxic effects were not fully understood should be tried in humans. The parents wanted to prioritize what they saw as in the best interest of their own children, without harming others in the group. The scientists felt a moral obligation to the broader community, especially to patients who hadn’t even been born. When the scientists emphasized that the only valid form of research was the gathering of data to benefit future, not current, patients, some of the parents objected. They didn’t have a way to assess and resolve their differences.
Partnerships between citizen scientists and professional scientists—like the one launched in Dr. Austin’s lab—are becoming increasingly common. In order to truly flourish, they need written agreements, drawn up by all the members of the collaboration, establishing how to address the challenges that arise when patients are viewed as creators of scientific knowledge, not simply research subjects.
Some attempts to move such a compact forward have already been launched. A group of scientists and researchers met in London to try to hammer out a version of a new social contract that could address the ethics of patient-led research. The creators of the proposal recognized that both citizen researchers and scientists have responsibilities toward society, and toward one another, to produce work that could benefit everyone. It is not enough for scientists to tell patients and families that they don’t produce rigorous science; professional scientists have an obligation to help citizen scientists do better work, these researchers argued in a paper they published in the Journal of Medical Ethics in 2015. Under the terms of the contract they devised, parents may fund, launch, and drive scientific projects to save the lives of their own children, but the experiments should be designed and data collected in ways that can also benefit the wider community.
In February, members of the Patient-Led Research Collaborative, a group of patients who have Long Covid and are also researchers, discussed their own version of the social compact. They created a set of scorecards designed to define, from the patient perspective, what one patient researcher on the webinar referred to as “a new baseline of acceptable collaboration.” In service of that goal, the scorecards measured a variety of different areas where citizen scientists and professional scientists often come into friction, particularly areas that have traditionally been exclusively in the domain of professional scientists, such as devising hypotheses, designing studies, analyzing data, and publishing papers.
The scorecards, developed in partnership with the Council of Medical Specialty Societies, can be viewed in some ways as an attempt to write the opening declaration of a future constitution, establishing that patients’ expertise about their own bodies and conditions must drive science. “Our intention is to create a shared language between groups,” said Hannah Wei, a co-founder of the collaborative.
Susannah Fox, a member of the advisory committee for the Patient-Led Research Collaborative and former chief technology officer of the U.S. Department of Health and Human Services, said the scorecards are useful for constructing partnerships involving any kind of research related to patients, not only those with Long Covid. “Scientists and patients have not historically had a common set of principles or even a way of expressing what those could be,” she said, adding that the scorecards help fill the gap. “I don’t think this is the constitution,” Ms. Fox said. “But the scorecards are a tool for a partnership to move towards its own constitution.”
Over the course of more than a decade, the NPC collaboration that got underway in Dr. Austin’s lab changed direction and shape. Working together, the scientists—professionals and citizens alike—identified a promising compound called cyclodextrin, tested it in clinical trials, recorded data, and authored scientific papers. They engaged directly with the Food and Drug Administration at every step of the process. They are still hoping to get FDA approval for the compound, although there is no guarantee they will succeed. Dr. Austin hopes that everything they did will also help inform others pursuing science together to craft a constitution. “Writing it down is worth doing,” he said.