This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
American politics has no shortage of ailments. Many do not feel like their voice matters amid the money and influence amassed by corporations and wealthy donors. Many doubt whether elected officials and bureaucrats can or even want to effectively solve problems and respond to citizens' needs. Many feel divided both physically and psychologically, and uncomfortable (if not scared) at the prospect of building new connections across lines of difference.
Strengthening American democracy requires countering these trends. New collaborations between university researchers and community leaders such as elected officials, organizers, and nonprofit directors can help. These collaborations can entail everything from informal exchanges to co-led projects.
But there's a catch. They require that people with diverse forms of knowledge and lived experience, who are often strangers, choose to engage with one another. We know that strangers often remain strangers.
That's why a science of collaboration that centers the inception question is vital: When do diverse individuals choose to work together in the first place? How can we design institutions that encourage beneficial collaborations to arise and thrive? And what outcomes can occur?
How Collaborations Between Researchers and Community Leaders Can Help
First consider the feeling of powerlessness. Individual action becomes more powerful when part of a collective. For ordinary citizens, voting and organizing are arguably the two most impactful forms of collective action, and as it turns out there is substantial research on how to increase turnout and how to build powerful civic associations. Collaborations between researchers familiar with that work and organizers and nonprofit leaders familiar with a community's context can be especially impactful.
For example, in 2019, climate organizers with a nonpartisan group in North Carolina worked with a researcher who studies organizing to figure out how to increase volunteer commitment—that is, how to transform volunteers who only attend meetings into leaders who take responsibility for organizing others. Together, they designed strategies that made sense for the local area. Once implemented, these strategies led to a 161% year-over-year increase in commitment. More concretely, dozens of newly empowered volunteers led events to raise awareness of how climate change was impacting the local community and developed relationships with local officials and business owners, all while coming to see themselves as civic leaders. This experience also fed back into the researcher's work, motivating the design of future studies.
Or consider how researchers and local elected officials can collaborate and respond to novel challenges like the coronavirus. For instance, in March 2020, one county in Upstate New York suddenly had to figure out how to provide vital services like internet and health screenings for residents who could no longer visit shuttered county offices. They turned to a researcher who knew about research on mobile vans. Together, they spoke about the benefits and costs of mobile vans in general, and then segued into a more specific conversation about what routings and services would make sense in this specific locale. Their collaboration entailed a few conversations leading up to the county's decision, and in the end the county received helpful information and the researcher learned about new implementation challenges associated with mobile vans.
In April, legislators in another Upstate New York county realized they needed honest, if biting, feedback from local mayors about their response to the pandemic. They collaborated with researchers familiar with survey methodology. County legislators supplied the goals and historical information about fraught county–city relationships, while researchers supplied evidence-based techniques for conducting interviews in delicate contexts. These interviews ultimately revealed mayors' demand for more up-to-date coronavirus information from the county and also more county-led advocacy at the state level.
To be sure, there are many situations in which elected officials' lack of information is not the main hurdle. Rather, they need an incentive to act. Yet this is another situation in which collaborations between university researchers and community leaders focused on evidence-based, context-appropriate approaches to organizing and voter mobilization could produce needed pressure.
This brings me to the third way in which collaborations between researchers and community leaders can strengthen American democracy. They entail diverse people working to develop a common interest by building new connections across lines of difference. This is a core democratic skill that withers in the absence of practice.
In addition to credibility, we've learned that potential collaborators also care about whether others will be responsive to their goals and constraints, understand their point of view, and will be enjoyable to interact with.
The Science of Collaboration
The previous examples have one thing in common: a collaboration actually took place.
Yet that often does not happen. While there are many reasons why collaborations between diverse people should arise we know far less about when they actually do arise.
This is why a science of collaboration centered on inception is essential. Some studies have already revealed new insights. One thing we've learned is that credibility is important, but often not enough. By credibility, I mean that people are more likely to collaborate when they perceive each other to be trustworthy and have useful information or skills to share. Potential collaborators can signal their credibility by, for instance, identifying shared values and mentioning relevant previous experiences. One study finds that policymakers are more interested in collaborating with researchers who will share findings that are timely and locally relevant—that is, the kind that are most useful to them.
In addition to credibility, we've learned that potential collaborators also care about whether others will be responsive to their goals and constraints, understand their point of view, and will be enjoyable to interact with. For instance, potential collaborators can explicitly acknowledge that they know the other person is busy, or start with a question rather than a statement to indicate being interested. One study finds that busy nonprofit leaders are more likely to collaborate with researchers who explicitly state that (a) they are interested in learning about the leaders' expertise, and (b) they will efficiently share what they know. Another study underscores that potential collaborators need to feel like they know how to interact—that is, to feel like they have a "script" for what's appropriate to say during the interaction.
We're also learning that institutions (such as matchmaking organizations) can reduce uncertainty about credibility and relationality, and also help collaborations start off on the right foot. They are a critical avenue for connecting strangers. For instance, brokers can use techniques that increase the likelihood that diverse people feel comfortable sharing what they know, raising concerns, and being responsive to others.
A science of collaboration that centers the inception question is helpful on two levels. First, it provides an evidence base for how to effectively connect diverse people to work together. Second, when applied to university researchers and community leaders, it can produce collaborations that strengthen American democracy. Moreover, these collaborations are easily implemented, especially when informal and beginning as a conversation or two (as in the mobile vans example).
Existing research on the science of collaboration has already yielded actionable insights, yet we still have much to learn. For instance, we need to better understand the latent demand. Interviews that ask a wide variety of community leaders and researchers who have not previously collaborated to talk about why doing so might be helpful would be enlightening. They could also be a useful antidote to the narrative of conflict that often permeates discussions about the role of science in American politics.
In addition, we need to learn more about the downstream consequences of these collaborations, such as whether new networks arise that include colleagues of the initial collaborators. Here, it would be helpful to study the work of brokers – how they introduce people to each other, how much they follow up, and the impact of those decisions.
Ultimately, expanding the evidence base of the science of collaboration, and then directly applying what we learn, will provide important new and actionable avenues for strengthening American democracy.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]
In November 2020, messenger RNA catapulted into the public consciousness when the first COVID-19 vaccines were authorized for emergency use. Around the same time, an equally groundbreaking yet relatively unheralded application of mRNA technology was taking place at a London hospital.
Over the past two decades, there's been increasing interest in harnessing mRNA — molecules present in all of our cells that act like digital tape recorders, copying instructions from DNA in the cell nucleus and carrying them to the protein-making structures — to create a whole new class of therapeutics.
Scientists realized that artificial mRNA, designed in the lab, could be used to instruct our cells to produce certain antibodies, turning our bodies into vaccine-making factories, or to recognize and attack tumors. More recently, researchers recognized that mRNA could also be used to make another groundbreaking technology far more accessible to more patients: gene editing. The gene-editing tool CRISPR has generated plenty of hype for its potential to cure inherited diseases. But delivering CRISPR to the body is complicated and costly.
"Most gene editing involves taking cells out of the patient, treating them and then giving them back, which is an extremely expensive process," explains Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the COVID-19 vaccines.
But last November, a Massachusetts-based biotech company called Intellia Therapeutics showed it was possible to use mRNA to make the CRISPR system inside the body, eliminating the need to extract cells out of the body and edit them in a lab. Just as mRNA can instruct our cells to produce antibodies against a viral infection, it can also teach them to produce the two molecular components that make up CRISPR — a guide molecule and a cutting protein — to snip out a problem gene.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies."
In Intellia's London-based clinical trial, the company applied this for the first time in a patient with a rare inherited liver disease known as hereditary transthyretin amyloidosis with polyneuropathy. The disease causes a toxic protein to build up in a person's organs and is typically fatal. In a company press release, Intellia's president and CEO John Leonard swiftly declared that its mRNA-based CRISPR therapy could usher in a "new era of potential genome editing cures."
Weissman predicts that turning CRISPR into an affordable therapy will become the next major frontier for mRNA over the coming decade. His lab is currently working on an mRNA-based CRISPR treatment for sickle cell disease. More than 300,000 babies are born with sickle cell every year, mainly in lower income nations.
"There is a FDA-approved cure, but it involves taking the bone marrow out of the person, and then giving it back which is prohibitively expensive," he says. It also requires a patient to have a matched bone marrow done. "We give an intravenous injection of mRNA lipid nanoparticles that target CRISPR to the bone marrow stem cells in the patient, which is easy, and much less expensive."
Meanwhile, the overwhelming success of the COVID-19 vaccines has focused attention on other ways of using mRNA to bolster the immune system against threats ranging from other infectious diseases to cancer.
The practicality of mRNA vaccines – relatively small quantities are required to induce an antibody response – coupled with their adaptable design, mean companies like Moderna are now targeting pathogens like Zika, chikungunya and cytomegalovirus, or CMV, which previously considered commercially unviable for vaccine developers. This is because outbreaks have been relatively sporadic, and these viruses mainly affect people in low-income nations who can't afford to pay premium prices for a vaccine. But mRNA technology means that jabs could be produced on a flexible basis, when required, at relatively low cost.
Other scientists suggest that mRNA could even provide a means of developing a universal influenza vaccine, a goal that's long been the Holy Grail for vaccinologists around the world.
"The mRNA technology allows you to pick out bits of the virus that you want to induce immunity to," says Michael Mulqueen, vice president of business development at eTheRNA, a Belgium-based biotech that's developing mRNA-based vaccines for malaria and HIV, as well as various forms of cancer. "This means you can get the immune system primed to the bits of the virus that don't vary so much between strains. So you could actually have a single vaccine that protects against a whole raft of different variants of the same virus, offering more universal coverage."
Before mRNA became synonymous with vaccines, its biggest potential was for cancer treatments. BioNTech, the German biotech company that collaborated with Pfizer to develop the first authorized COVID-19 vaccine, was initially founded to utilize mRNA for personalized cancer treatments, and the company remains interested in cancers ranging from melanoma to breast cancer.
One of the major hurdles in treating cancer has been the fact that tumors can look very different from one person to the next. It's why conventional approaches, such as chemotherapy or radiation, don't work for every patient. But weaponizing mRNA against cancer primes the immune cells with the tumor's specific genetic sequence, training the patient's body to attack their own unique type of cancer.
"It means you're able to think about personalizing cancer treatments down to specific subgroups of patients," says Mulqueen. "For example, eTheRNA are developing a renal cell carcinoma treatment which will be targeted at around 20% of these patients, who have specific tumor types. We're hoping to take that to human trials next year, but the challenge is trying to identify the right patients for the treatment at an early stage."
Repairing Damaged mRNA
While hopes are high that mRNA could usher in new cancer treatments and make CRISPR more accessible, a growing number of companies are also exploring an alternative to gene editing, known as RNA editing.
In genetic disorders, the mRNA in certain cells is impaired due to a rogue gene defect, and so the body ceases to produce a particular vital protein. Instead of permanently deleting the problem gene with CRISPR, the idea behind RNA editing is to inject small pieces of synthetic mRNA to repair the existing mRNA. Scientists think this approach will allow normal protein production to resume.
Over the past few years, this approach has gathered momentum, as some researchers have recognized that it holds certain key advantages over CRISPR. Companies from Belgium to Japan are now looking at RNA editing to treat all kinds of disorders, from Huntingdon's disease, to amyotrophic lateral sclerosis, or ALS, and certain types of cancer.
"With RNA editing, you don't need to make any changes to the DNA," explains Daniel de Boer, CEO of Dutch biotech ProQR, which is looking to treat rare genetic disorders that cause blindness. "Changes to the DNA are permanent, so if something goes wrong, that may not be desirable. With RNA editing, it's a temporary change, so we dose patients with our drugs once or twice a year."
Last month, ProQR reported a landmark case study, in which a patient with a rare form of blindness called Leber congenital amaurosis, which affects the retina at the back of the eye, recovered vision after three months of treatment.
"We have seen that this RNA therapy restores vision in people that were completely blind for a year or so," says de Boer. "They were able to see again, to read again. We think there are a large number of other genetic diseases we could go after with this technology. There are thousands of different mutations that can lead to blindness, and we think this technology can target approximately 25% of them."
Ultimately, there's likely to be a role for both RNA editing and CRISPR, depending on the disease. "I think CRISPR is ideally suited for illnesses where you would like to permanently correct a genetic defect," says Joshua Rosenthal of the Marine Biology Laboratory in Chicago. "Whereas RNA editing could be used to treat things like pain, where you might want to reset a neural circuit temporarily over a shorter period of time."
Much of this research has been accelerated by the COVID-19 pandemic, which has played a major role in bringing mRNA to the forefront of people's minds as a therapeutic.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies," says Mulqueen. "In the future, I would not be surprised if many of the top pharma products are mRNA derived."
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.