Science isn’t immune to shutdown

Apr 27, 2020 | Immunology, Research, Transplantation

by Peter Wang

When I started college at UChicago, I thought “This is going to be the best four years of my life! Don’t waste any of it!” I would try out for water polo, make lifelong friends, and jump into research. I wanted to become a doctor in the future and was eager to get my hands dirty.

The spring of my first year, I joined the lab of Maria-Luisa Alegre, MD, PhD. Her lab studies the responses of T-cells, the guardians of the body against foreign invaders, in solid organ transplantation: T-cell tolerance to donor grafts, the impact of infection and inflammation on anti-graft immunity, and interactions between the host immune system against the transplant and microbiota at different body sites.

Roughly 40,000 transplants were performed last year, and over 100,000 people are still on the national transplant waiting list. What the Alegre lab uncovers about the immune mechanisms involved in transplant rejection and tolerance has important implications for the health of these transplant recipients.

My first year as a scientist went by quickly, like when you’re driving somewhere and you lose your sense of time. I found my own groove, balancing chemistry classes in the morning with mouse experiments in the afternoon, not to mention lots and lots of pipetting. I felt I was doing something important, and life couldn’t be better.

Then my life—everybody’s lives—hit a massive speed bump. In March 2020, we were faced with the looming COVID-19 pandemic. My daily routine quickly shifted to life under lockdown: online classes, no labs, stress and anxiety and facing the anti-climactic reality that all I could do to help was to stay indoors. I had so much to look forward to that month; not only exciting experiments, but also a water polo tournament in Des Moines—vanished.

This pandemic has undoubtedly affected the lives of millions of students, small business owners, and brave healthcare workers on the front lines. But I get to give you my perspective, that of the cohort I am joining—scientists—the people best positioned to get us out of this mess.

Scientists in immunology are all motivated by the desire to understand health and disease and improve human health. The more we know about the immune system, the better outcomes we can provide for patients experiencing cancer, organ failure, infection, and allergy.

To advance knowledge, many immunologists utilize unique mouse models. In studying transplantation, Dr. Alegre suggests that “mice are relatively easy to alter genetically, offering the smallest animal model in which it is still possible to transplant an organ (if you are a skilled microsurgeon) and which allows mechanistic investigations into how a given immune gene can lead to graft rejection or graft tolerance. These genes can then become therapeutic targets and improve patient outcomes.”

In the Alegre lab, we use mouse models to study T-cell responses following skin and heart transplantation. Many of our mice are transgenic; like genetically altered fruits or vegetables, our mice have T-cells or tissues engineered to express or lack certain genes and proteins. We use these as donors or recipients of transplanted organs or as sources of transplant-reactive T cells to understand the immune response to the graft.

Because of the limitations in the number of complex surgeries that can be performed in a day, we often plan and perform multiple mouse experiments simultaneously. In her lab, Alegre says that “many of our experiments look at the maintenance phase of transplantation tolerance, 30-60 days after transplantation. Our microsurgeon usually generates a continuous stream of transplanted mice of the various gene backgrounds to have a lineup of experimental mice that have already reached the desired time point.”

Confronted with the necessity to evacuate the lab, we knew there would be few, if any, people left to care for the mice. Soon, universities and labs across the world would ask researchers to wrap up all ongoing experiments and think long and hard about the mice they needed, freeze the embryos of rare and special strains, prioritize the young pups of unique strains, and in many cases, cull the rest.

“The week in which we had to shut down the lab and dramatically reduce our mouse colony was distressing,” Alegre said. “In the span of a week, we erased years of work, prioritized irreplaceable strains and sacrificed all non-essential animals. Mentoring experimental design, methods and data interpretation is obviously much less effective when bench experiments cannot be performed, impacting undergraduate and graduate education.”

Our final in-person lab meeting was heartbreaking. We prioritized our mice: the young and pregnant were spared, with the hopes of ramping up breeding once the lab shutdown is over. Alegre estimates that this crisis has caused a “setback of about a year to be where we were before the lab shutdown. Publication of our findings will be delayed until we can ramp up transplantation and get to the point where we can repeat experiments and generate new data.”

As we adjust to this newfound reality, many at UChicago and the Duchossois Family Institute are confident that our life-saving work will continue, but at a different time and pace. When asked about the future, Alegre expressed that “we scientists are resilient by nature, however we’ll miss the thrill of new discovery and the quiet satisfaction of doing something useful that advances scientific knowledge.” We’ve shifted to lab meetings and journal clubs via Zoom, and I am writing about our work now in a different way—for the public rather than in scientific journals for other researchers. But the sacrifice and isolation in the age of social distancing is one of our important duties as citizens, and saving lives is what I value most.

Peter Wang is a second-year undergraduate student in The College.