It was with much wariness that immunologists traveled to the small town of Skamania, in southern Washington state, last summer. The U.S. seemed to be in a fragile détente with COVID, but it was lost on no one how it would look if the conference turned out to be a superspreader event.
They arrived to a disaster. Not a superspreader event. But a heatwave.
It was fully 110 degrees when they began checking in at ImmunoSkamania, the conference they were attending at a lodge on the north bank of the Columbia River. Cars pulled into the loading zone to unload under the shade of the lodge’s front awning. The shade still felt like a high-grade fever. Over the course of the weekend, the lodge’s fire alarm would go off more than once, but there would not be a fire.
Max Krummel, an Emerson Collective Dial Fellow, dreamt up ImmunoSkamania a few years ago with his colleagues. It was facilitated by the formation of ImmunoX, a cross-disciplinary immunology center at UC San Francisco that Krummel chairs. The center was born in 2018 from a thesis that the usual model of academic science, with principal investigators leading siloed labs, left innovation on the table by disincentivizing collaboration and circumscribing a narrow range of perspectives. ImmunoX links 102 different labs, organizes them into groups, and gives them tools to help researchers share data and experimental designs.
The conference is its echo beyond the UCSF campus. First convened in 2019, it interrogates not simply the science of immunology, but also, one might say, the immunology of science: the system of tools for identification, verification, communication, and preservation of objective truth.
Like all conferences, it began with a dinner. “I’m sorry, I meant to come talk to you earlier!” Krummel said after he spotted a colleague across the banquet hall. “But there’s a thing that happens to your brain in a heatwave. All you can think about is getting someplace not hot.”
It was an apt comment. In 2021, it was hard not to conclude that the system of tools had, in some way, failed: amidst a pandemic, one might hope we would have focused on getting someplace not infectious; instead, people protested isolation, politicized masks, and eschewed vaccinations and boosters. At a time when science delivered a modern miracle—a vaccine after just one year of the worst pandemic in a century—many, many people rejected science. At ImmunoSkamania, attendees were reckoning with the fact that their discipline, like government, education, the media, and other civilizational pillars, had been thrust into the spotlight by the events of the last two years.
So as they grabbed food from buffets, pulled chairs around banquet tables, caught up, and talked shop, the subtext—and often the text—of every conversation was, what has happened to science? And how can we fix it?
After dinner, in remarks opening the conference’s first session, Krummel offered another observation. From the outside, he said, there’s a “cartoon element” to how scientists are seen. The white coat and the beaker. And from the inside, “Sometimes we live in this bubble that is a little bit like a church, the church of knowledge,” he said. “Scientists are—but shouldn’t be—like priests in a kind of priesthood. You get into it and then you only know what goes on in the religion of science. And then when you speak to the public, you can seem to issue commands from a bible only you are allowed to read.”
Sometimes we live in this bubble that is a little bit like a church, the church of knowledge. Scientists are—but shouldn’t be—like priests in a kind of priesthood.
For some time now, Krummel has suspected that there are real shortcomings in how science, as a profession, functions. What began as a series of conversations over beers and lab benches about problems with the machinery of science – things like the glacial pace of the peer review process and the lack of data sharing between labs working on related problems – has led, especially in the context of the racial justice movement of the last two years, to broader efforts to replumb the pipeline for a field that is overwhelmingly White and male.
Over the following few days, the immunologists at Skamania Lodge would talk about emerging cross-disciplinary lines of inquiry. They would analyze the impacts of COVID on their field, not the least of which was, thanks to greater public awareness of immunology, a bigger megaphone to talk about what they do and how they do it. They would discuss models for attracting more diverse talent and mentoring undergrads and graduate students from underrepresented communities.
But ImmunoSkamania 2021 was just the start of a new phase for Krummel and ImmunoX. They plan to pursue wholesale change for their discipline, developing initiatives that will form digital connections that span specialties and result in the construction of whole buildings organized around new, collaborative principles. And maybe, by making science look a bit more like society, they’ll rebuild trust for everyone.
UC San Francisco is in every way a cutting-edge research university. Well, every way except one. “There are these stupidly slow elevators,” Krummel says. “They hold about 25 people and there’s four of them but they’re carrying a thousand people per day.”
Krummel loves those elevators.
“In the morning, there’s these big crowds. On the one hand, it’s super inefficient. Everybody takes a couple extra minutes to get to their workplace. On the other hand, they’re super efficient because they create this temporary community where you bump into each other,” he said. They create opportunities to share ideas and talk through problems.
That’s at the heart of ImmunoX, whose X is the same one that appears in Supreme X Dickies or Jordan X Off White. It’s collaboration, and it’s representative of a sea change that’s taken place over the last several years as researchers have discovered how the immune system interacts with other aspects of our biology. At the intersection of immunology and microbiology are the bacteria that live in our guts and influence our health. At the intersection of immunology and oncology sit new technologies for deploying immune cells against tumors. In fact, the immune system is in collaboration with every organ in the body, in disease but also in health.
The trouble is that the study of immunology, in the institutional setting, is not designed for collaboration. “At UCSF, as everywhere, it’s been very disjointed,” said Vincent Chan, ImmunoX’s chief strategist, who started developing the organization with Krummel and their colleagues in the mid-2010s. “Not all immunologists sit in the Department of Microbiology and Immunology. They sit all over the place. They’re in dermatology, they’re in surgery, they’re in pediatrics, neuroimmunology. And they’re working on different diseases, so that wealth of information they are gathering from their specific fields isn’t really cross-fertilizing within the rest of the immunology community.”
What if doing better science isn’t just about making sure scientists have more opportunities to work together—what if it’s also about who is doing the science in the first place?
But right now there’s a unique opportunity: UCSF is building a new science building, and the ImmunoX team has been afforded the opportunity to provide input into the process. Their advice has been: build something modern and cutting-edge, but be sure to include the equivalent of those elevators.
Of course, this doesn’t have to be elevators. Part of it is about the structure of the science facilities themselves. ImmunoX has developed two collaborative models that envision physical space that is constructed with them in mind. They fund CoLabs, a type of communal laboratory in which technologies developed by one research team are shared for use by others in their own experiments; and CoProjects, in which teams from different disciplines work together on what Chan calls “human-centered science.” Together they would, for example, allow scientists to develop one common protocol to take biopsies from patients in separate studies of cancer and auto-immune diseases in such a way that the discoveries of one disease could be applied as solutions to the other. By consolidating what would once have been two separate research projects, scientists get—at risk of sounding ghoulish—more bang for their biopsy, and new opportunities to find, say, links between brain tumors and neuro-degeneration.
But there also needs to be in-between spaces, like those elevators, that are outside the bounds of professional workspace. Being in the elevator—as opposed to the lab or the department lounge—is how you find what Krummel calls the “weird relationships” that lead to breakthroughs.
The new building is on track to be completed by 2026, which aligns with the 10th anniversary of the earliest conversations that led to ImmunoX. Ten years since Krummel and his colleagues started to think about how to short-circuit one of the least fortunate quirks of scientists: their tendency to go for the myth of the ‘Great Individual.’ That’s not really how you discover stuff, Krummel says. Real discovery doesn’t come from bestowing lab fiefdoms on individual scientists—it requires input from other people. People who are different from you and who see different messages in the data. And the way you form bonds with people who are different from you—the way you build the ability to work together, trust, that indefinable shorthand—that’s the kind of thing that really only comes from chatting while waiting in line for a beat and then getting stuck in a small car for a five-story ride.
But that begs a question: what if doing better science isn’t just about making sure scientists have more opportunities to work together—what if it’s also about who is doing the science in the first place?
Oscar Aguilar Alfaro arrived at UCSF in January 2018 to do post-doctoral training focused on natural killer cells, which control the spread of viruses and can be useful in fighting cancer. Originally from El Salvador, Aguilar and his family left during the country’s civil war and settled in Canada, where he grew up and went on to earn a PhD in immunology, at the University of Toronto. In neither the United States nor Canada did Aguilar encounter many scientists who looked like him. But in his transition from Canadian academia to American academia, he observed differences that impacted the paths of Latin American students who, like him, had fallen in love with science at a young age. In the U.S., the cost of school was so much higher that it amplified the barriers scientists of color faced. On the other hand, his colleagues in the U.S. struck him as more open to acknowledging the lack of diversity and having real conversations about it.
In 2020, those conversations came suddenly to the fore. After the murder of George Floyd, scientists affiliated with ImmunoX began to talk about the need to do something—something tangible. Aguilar and others put together a proposal to help train and create opportunities for the next generation of immunologists. “We know that education is really transformative,” he says. “I know that myself. I’m a first-gen refugee. I know how my education and PhD have really opened up doors, not only for myself, but also for my family and my community.”
The proposal led to ImmunoDiverse, an advocacy group within ImmunoX focused on racial equity. ImmunoDiverse hosts an allyship program to help scientists learn about and discuss bias barriers, and puts on an annual colloquium that shines a light on the work of peers from communities underrepresented in the field. Aguilar heads up Outreach, the largest portion of ImmunoDiverse’s work. It’s all about fostering the next generation of scientists. Through a variety of programs, students from high school and up through every level of higher education are brought to UCSF to train. “And not only to train,” Aguilar says, “but to give them a really meaningful experience, making sure they feel welcome in the field of science.”
Welcome. That’s where the hard work lies. The pipeline into immunology—like many of the sciences—is broken. The demographics of the field of immunology are mostly old and male and White, and tenure is an ossification device. And how can someone feel welcome if they don’t feel that their work is valued, that they can have mentors who care about and understand them, that they have peers who look like them? And this takes hard work and time. “Some of the successes that we’ll see are going to happen five years from now, when we track where these students go,” Aguilar says.
Ironically, a figure like Krummel in some way exemplifies the reasons systemic issues persist. The traditional model of academic science has worked pretty well for him. He earned his Ph.D. at the world’s foremost public university, UC Berkeley, where his thesis project under principal investigator James P. Allison was the primary underpinning for the 2018 Nobel Prize in Physiology or Medicine, awarded for research on manipulating immune cells to fight cancer. Krummel’s career has taken him to Australia and France, and now he’s a full professor at UCSF, another venerated research university.
But something crystallized for Krummel when the Nobel was awarded: the yawning gap between the perception of science and the practice of science. “Allison was the single human representative of that Nobel Prize, but the actual aha! moments came at my lab bench, and happened because [Allison], and me, and a lot of other folks began to see the connections between what we were doing,” Krummel says. Science advances as a series of linked events perpetrated by a whole bunch of actors, as offhand comments and snippets of conversation from a cacophony of voices that, at the right time, harmonize into a new discovery.
And while it is a good in and of itself to open more opportunities to more people, there are also pragmatic arguments for improving representation in that cacophony. To see this, you don’t have to look beyond ImmunoX’s efforts to create data sharing infrastructure, says Casey Beppler, a PhD candidate in Krummel’s lab on the trainee leadership team for IgEquity, a sister organization to ImmunoDiverse that focuses on gender equity. The reason ImmunoX made this a priority is that in science, the tiniest of differences—like, say, the speed at which two different teams thaw out the same kinds of tissue samples before studying them—can lead to radically different experimental data. So just imagine, Beppler says, the new and powerful data that would arise from the different experiments and protocols that might be dreamt up by people with a wider variety of lived experiences.
Science advances as a series of linked events perpetrated by a whole bunch of actors, as offhand comments and snippets of conversation from a cacophony of voices that, at the right time, harmonize into a new discovery.
There are already strong signs that Krummel’s approach is working. When the pandemic hit, everything but COVID was put on hold—literally, because only COVID research was considered essential. So ImmunoX jumped on the need to build an understanding of the virus and the resulting disease. Working with others in the UCSF community, it launched two projects built on the CoLabs infrastructure, convening scientists from different disciplines to conduct a variety of experiments using common sets of tissue samples and observations from COVID patients. They’ve produced a steady drumbeat of important learnings about how COVID short-circuits the immune system to debilitate patients with the most severe cases. Perhaps the most interesting, and most characteristic of ImmunoX, is an exploration of how immunotherapy techniques like those from Krummel’s Nobel-winning research can be deployed against COVID. “An immunotherapy for a pandemic would be a breakthrough" in how we drug a pandemic respiratory infection, he told the UCSF news service last year.
And work on cancer continues. This year, a paper that Krummel calls an “enormous re-imagining of cancer immunity” was published in the journal Cell. Through their cross-collaborative model, researchers at ImmunoX discovered that across patients, immune systems fighting cancer take on one of 12 fundamental forms, what the researchers called “archetypes.” “If you say that a given cancer is one thing, then you’re trying to find one drug,” Krummel explains. But if you understand that these archetypes mean that a given patient’s body may be trying to fight that cancer in one of 12 different ways—essentially meaning that one cancer actually represents 12 different diseases—it allows you to take a more sophisticated approach to finding the right drug for them.
This potential for this type of breakthrough has always been at the heart of the ImmunoX project – a cross-disciplinary community of scientists who are unraveling the mysteries of the immune system, while democratizing the culture around scientific discovery in the process.
Having different people from different walks of life that know how to problem solve differently gets our teams to problem solve more efficiently.
That was part of the goal of ImmunoSkamania, too: to welcome all scientists, across disciplines and personal backgrounds, into the conversations that drive discovery. Because if everyone is part of the conversation internally, it’ll lead to powerful new findings and also help break down some of the barriers to communicating them externally, to the public. And it’s a goal Krummel and his colleagues hope to share more broadly: If it can work for a bunch of immunologists on the West Coast, why not try it everywhere? ImmunoX recently started a nonprofit, Solving for Science, to spread its model to other fields and other institutions.
And if the results of this approach are not and will not always be the kind published in journals, they will be breakthroughs nonetheless. Aguilar thinks back to when ImmunoX first began, shortly after he got to UCSF. There were just a handful of colleagues of color doing much of the heavy lifting on initiatives to improve representation. Now there are 14 scientists of color in his group, supported by a formidable allyship group, and many more have come in as paid interns and post-baccalaureate students recruited by ImmunoDiverse’s outreach efforts.
And with that kind of change comes a flywheel effect, in which diverse researchers enroll diverse subjects in immunology studies, leading to breakthroughs that benefit everyone, and diverse funders begin doling out research dollars to a more representative set of investigators. Aguilar puts it this way: “Having different people from different walks of life that know how to problem solve differently gets our teams to problem solve more efficiently.”
It becomes apparent that ImmunoX is, itself, one big science experiment. An experiment on science. And results are starting to come in.