Patient groups are collaborating with medical researchers as never before, creating a new model for progress against long Covid and other diseases – WSJ
FOR EDUCATIONAL PURPOSES
Members of the nascent British Association for the Advancement of Science gathered in Cambridge in 1833 to discuss the state of the field. Science was an increasingly popular pursuit and was helping to expand knowledge about the natural world. Passionate amateurs built telescopes to view the stars. They gathered plant specimens, some of which had never been identified before. They presented their findings at public forums and in private salons. There was a growing sense among participants that something novel was happening. At the meeting, a member suggested that a name be given to these ambitious practitioners. One of the association’s founders, William Whewell, was ready with an answer: scientists.
In the century that followed, science was transformed from a vocation to a profession. To participate, an individual needed years of study, the acquisition of expertise and advanced training. In the modern era, as research addressed increasingly complex questions, amateurs found ever fewer opportunities to contribute, since running experiments required the use of specialized equipment in dedicated labs. Universities became the central venue for the pursuit of science. Professionals directed the studies, evaluated the utility of the projects, gathered the data and analyzed and published the results.
This powerful new model was especially important in the development of the vast, life-transforming enterprise of medical science. Research on cures for a range of deadly diseases was conducted in a more uniform and rigorous way, and scientists could run additional experiments and trials in an effort to replicate others’ results, ensuring the validity of findings. They interpreted data in more objective ways, away from the influence of personal bias and social or political pressure. The emergence of medical expertise advanced what Philip Kitcher, a professor emeritus of philosophy at Columbia University who writes about science and democracy, has called “value-free science,” the idea that scientific progress requires scientists to leave behind their personal commitments and preferences when they enter a lab.
Today, medical researchers still look to the wider society for help. They need patients and families to lobby for more government funding, and they need subjects to fill the clinical trials they organize and to donate blood, tissue and other samples for experimentation. But when it comes to the priorities of medical research and its actual conduct, scientists have usually resisted the idea that amateurs still might have important contributions to make. “Modern science offers a different way of knowing about the world than what came before,” says Bruno Strasser, a professor at the University of Geneva who studies the relationship between science and society. “But the change came at a price.”
Pulitzer Prize-winning WSJ reporter and author Amy Dockser Marcus chronicles the story of a group of activist parents and scientists who join forces to develop a drug to treat a rare disease. The author sat down with Stefanie Ilgenfritz, the Journal’s coverage chief for health and science, to discuss the story and the rise of research led by patients and citizen scientists.In the 1980s, HIV activists pushed the Food and Drug Administration to think differently about the way it went about assessing if a drug was working. They wanted the agency to formally authorize the use of surrogate data markers, data points that indicate patients are benefiting but don’t definitively show they are living longer. The agency agreed and in 1992 initiated the Accelerated Approval Program that has allowed for faster approval of drugs for HIV and other life-threatening conditions.
Breast cancer, disability, and other activists insisted they should have the right to help shape policies surrounding clinical trials, including determining how much risk they were willing to take when trying experimental drugs. As a result of their activism, hospitals and academic centers routinely include community participants as members on institutional review boards that ensure the protection of the rights of people participating in research. Patients serve on various government advisory committees, offering their views on proposed projects or weighing in on some funding decisions.
Yet for many, these gains still fall short of full participation. There is a growing push to make the conduct of medical research itself more democratic. The development of new technologies that raise ethical questions, such as whether gene-edited animals should be released into the wild, has led scientists and scholars to call for giving the public a greater say in what kind of science gets studied and receives public funding. The Covid-19 pandemic has accelerated efforts that were already underway in other diseases to establish collaborations where patients living with a disease and the scientists that study it are both recognized as having expertise and work together as partners to find effective therapies.
After a researcher in China announced in 2018 that he had used the Crispr gene-editing tool to produce the first genetically-modified babies, the World Health Organization and other groups called for members of the public to be engaged in creating policies about how and whether to use the technology to edit DNA in embryos. At the International Society of Stem Cell Research annual meeting last June, scientists wrestled with how to better weigh what sorts of limits people might want to place on scientific research on human embryos and other controversial issues. “A lot of science has been telling the public what we do,” says Amander Clark, the director of the Center for Reproductive Science, Health and Education at UCLA, who spoke at the conference. Dr. Clark said embryo research up to the first 14 days of development has been permitted for decades after careful review and with oversight.
Scientists now have the technology to potentially grow the embryos in the lab for longer periods, she said, which could help scientists better understand how cells in the placenta develop, ways to prevent miscarriages and how to improve outcomes for people undergoing in vitro fertilization. Yet scientists have not pursued such studies with human embryos because of the moral and ethical concerns surrounding the research, she said. In the past, scientists have sometimes approached public engagement as a way of trying to persuade people to agree with them rather than an exchange of different perspectives. Dr. Clark thinks that needs to change: “We need to start listening to the public about what they want. We need to make this more of a two-way street.”
In seeking to advance the search for better therapies, Covid patients have argued that people who live with a disease are experts and should be treated as equal partners with scientists. A group of patients whose Covid symptoms lingered for months or more formed the Patient-Led Research Collaborative. Their survey of more than 3,700 Covid patients around the world identified symptoms that were initially overlooked by the medical community and are now recognized as significant features of the disease such as brain fog and other cognitive dysfunction. They published their study in a peer-reviewed scientific journal, a crucial step in getting clinicians to adopt findings into their practice. Last year, the group announced that a panel of 15 patient researchers, all of whom had lived experience with chronic illnesses, had awarded research grants to nine projects, totaling $4.8 million. They chose projects that patients wanted pursued based on their experience with disease, such as the role of microclots, immune dysfunction and changes in the microbiome in driving long Covid, among other issues.
“I think we need to change the narrative of expertise,” says Lisa McCorkell, who has long Covid and is a co-founder of the research collaborative. “Patients are living with the condition day in and day out and have done their own research. We are not going to find answers that will work for patients unless we are listening to patients and value that experience.”
Helen Burstin, a doctor who is CEO of the Council of Medical Specialty Societies and is collaborating with the patient-led research group, says that patients who want to produce scientific knowledge need access to the same resources that sustain professional scientists, including the opportunity to seek federal research funding. True democracy in science allows patients and scientists to work side-by-side as partners. “They need institutional support from the research community to support them,” says Dr. Burstin.
Scientists do not always want to work with patients or advocates in the early stages of a project, says Christopher Austin, the former head of the National Center for Advancing Translational Sciences, who helped to create a collaborative including families whose children have the rare and fatal cholesterol metabolism disorder Niemann-Pick disease type C (known as NPC) and scientists studying the disease. “Conventional wisdom is that patients impede the process,” said Dr. Austin.
He put forth the objections that scientists often make: Patients do not have familiarity with science or scientific terms and concepts. They don’t know the regulatory rules or fully appreciate the risks involved with trying experimental compounds. “Science demands a level of rigor and skepticism and a tolerance for failure that is difficult in the best of circumstances for scientists who really get devoted to what they do,” Dr. Austin said. “The concern was if a patient was involved or a parent, it might not matter what the data showed. They would find it difficult to admit that the data were not promising because of wishful thinking.”
The NPC collaborative, drawing from both researcher and family-generated information, pushed forward development of the drug cyclodextrin for the potential treatment of the disorder. A clinical trial of cyclodextrin failed in 2018, but the families and scientists continued to gather data. A company bought the rights to the drug in 2021 and is now trying to develop it.
During the cyclodextrin project, Dr. Austin said that the families brought connections to the scientific community that were important. They knew the researchers in the field better than anyone and got them to join the collaborative. Many of the parents immersed themselves in the scientific literature, acquiring an understanding of the disease that was sophisticated and advanced. They kept detailed records of their loved ones’ experiences living with the disease, and at critical moments generated new ideas for experiments, additional funding, and regulatory and public attention that helped advance science. Most of all, Dr. Austin said, “They have a sense of urgency, a sense of focus and staying on task to get to a therapeutic outcome.”
In any democratic arrangement, there is a struggle to balance the right of people to have a say with the recognition that in any given matter, there will always be some people who possess greater qualifications or technical training. When a plane hits turbulence during a flight, no one stops to ask the passengers to weigh in on how to safely navigate a way through, said Dr. Strasser, the historian of science. “You trust the pilot,” he said. “Science communication has mainly been trying to get people to trust the pilot.”
The strategy backfired during the Covid pandemic, Dr. Strasser said, when public officials and scientists were not always forthright about the uncertainties and limitations surrounding their understanding of a new disease and the way additional scientific information might change their views as well as their policy recommendations. “There is a long way to go to create a culture where people understand enough about the scientific process to know when they can trust the pilot and when they have to beg to disagree,” said Dr. Strasser.
At a webinar in January, co-founders of the Patient-Led Research Collaborative announced that they had created scorecards to help patients, scientific collaborators and funders better measure and assess how well they work together and ways to improve their partnerships. The project grew out of their frustration that long Covid patients’ priorities were not always taken into account when important choices were made about what drug to study, what trial to design, what research to fund. Even after the patient researchers published their paper, scientists often approached the group for help only after forming their own hypotheses. Or they asked the patients to help recruit others to join studies without first soliciting the viewpoints of the very people who lived with the disease.
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The patient researchers drew from these experiences to encourage collaborations that were more open and inclusive. When discussing the integration of patients into the research process, the ideal collaboration on the scorecard was one where research goals are based on patient priorities, trials are devised alongside patients, patients are recognized as experts in their own condition, and patients and scientists together analyze the data and write and publish their findings. “We should be on equal ground,” said Hannah Wei, a co-founder of the research collaborative.
The government has an important role in helping to make medical science more democratic. The FDA already regularly advises scientists who are trying to advance clinical trials. The agency could also task knowledgeable staff members to address questions and provide feedback on patient-led proposed studies. In a journal sponsored by the Citizen Science Association, scholars published papers last year on how to open up biomedical research to patient researchers, including calling for the establishment of a special pathway at the FDA to evaluate citizen science research. The National Center for Advancing Translational Sciences, which is part of the National Institutes of Health, has tried to help by creating online resources for patients to set up patient registries, collect data and find researchers with whom to partner. “We consider patients as researchers,” says Dr. Joni Rutter, the current director of the center.
Dr. Kitcher, the Columbia University professor, said that enabling more widespread participation will not only result in richer science but could lead to a more robust democracy in general. “I think the core of democracy is learning to live together,” he said. “Democracy requires a very deep level of citizens constantly trying to understand one another’s problems. So does science.”
Ms. Dockser Marcus is a staff reporter for The Wall Street Journal. This essay is adapted from her new book, “We the Scientists: How a Daring Team of Parents and Doctors Forged a New Path for Medicine,” which will be published on Feb. 14 by Riverhead Books.
Corrections & Amplifications
Joni Rutter is the director of the National Center for Advancing Translational Sciences, An earlier version of this essay incorrectly spelled her first name as Jodi. (Corrected on Feb. 10)
Appeared in the February 11, 2023, print edition as ‘Making Medical Science More Democratic’.