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SeXX and Immunity event raises crucial questions for society

Why has it taken the scientific community so long to include sex as a biological variable in research and analysis as a matter of course?
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Photo of Adrianna San Roman describing her research in front of electronic poster monitor.
Adrianna San Roman, a postdoc at the Whitehead Institute, describes her research at the SeXX and Immunity poster session.
Photo: Susan Berthelot
Photo of Linda Griffith standing and addressing a gathering in Stata Center
Professor Linda Griffith (right) addresses SeXX and Immunity event attendees, who include clinicians, researchers, and members of the pharmaceutical industry.
Photo: Daniel Darling

Why are females more likely to survive Covid-19 but at greater risk of developing chronic disease? Historically, why have women and nonbinary people typically been excluded from clinical trials? How do we understand how sex differences affect everyone? What is the interplay between sex chromosomes and sex hormones?

Why has it taken the scientific community so long to include sex as a biological variable in research and analysis as a routine matter of course?

These were a few of the questions prompting lively discussion during the March 2 inaugural event for the SeXX and Immunity series, hosted by MIT’s Department of Biological Engineering; the Ragon Institute of MGH, MIT and Harvard; and MIT’s Center for Gynepathology Research. Sabra Klein of the Johns Hopkins Bloomberg School of Public Health anchored the event with a seminar about sex differences in immune responses to viruses and vaccines, with 180 attendees participating, in person and virtually.

The SeXX and Immunity community brings together basic and translational sciences and academia and industry science to address knowledge gaps head-on. By exploring the impact of female and male biology — both hormones and chromosomes — on normal and pathological immune responses to infection and other immune triggers, SeXX and Immunity participants aim to raise awareness about the crucial importance of considering the differences between male and female biological sex in clinical decision-making, and define specific problems that need attention — then mobilize the entire research community to address them efficiently.

Klein explained how crucial it is to consider the differences between male and female sex in clinical decision-making. However, in recent decades, clinical trials have not always adequately enrolled women or nonbinary people, or analyzed sex-specific differences in the data. This omission has hindered the progress of understanding not only of women’s reproductive health, but both male and female responses to medications, immune disorders, infectious disease, cancer, neurological diseases, and more.

“Females are more likely than males to survive SARS-CoV-2 infection,” Klein explained. She highlighted this and many other findings of her recent work addressing the observed sex differences in the outcomes of Covid-19, adding “The findings were consistent across diverse countries and cultural norm differences.”

Dozens of attendees also attended a post-seminar networking and poster event on the MIT campus, which included an interactive panel discussion about research challenges and funding in sex-based disease research.

During the panel discussion, one attendee asked, “How is it 2022 and we’re just now launching a seminar series looking at sex differences in the immune response? What took so long?”

Panelists explained the historical setting of women of reproductive age getting excluded from clinical trials decades ago, forcing researchers to adopt the assumption that everything could be extrapolated from studying males, and the harm these assumptions have caused.

In a post-event feedback survey, one attendee wrote, “This discussion raises the fundamental questions about the importance of including sex in our research and analysis.”

Another attendee shared that “we have almost no idea how oral contraceptives, or other hormone-modifying medications, impact immune responses! This has to change.”

At the networking event, attendees enjoyed discussions with Klein, poster presenters, other panelists, and each other. One attendee described the atmosphere as “electric,” and another shared that the March 2 event had heightened his interest in this topic from “moderate” to “high.”

Klein is an expert on sex and gender differences in immune responses and susceptibility to infection. She currently has over 130 peer-reviewed publications, authored several book chapters, and edited two books on the broad topics of sex differences in response to infection and treatments for infectious diseases. During the current Covid-19 pandemic, Klein has written commentaries for several journals and been interviewed by several major news media outlets about male-biased disease outcomes.

The SeXX and Immunity series is made possible due to the generous support of the Huiying Memorial Foundation.

Michal “Mikki” Tal is an instructor and team lead at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University and a visiting scientist at MIT Department of Biological Engineering.

Linda Griffith is the School of Engineering Teaching Innovation Professor of Biological and Mechanical Engineering and MacVicar Fellow at MIT, where she directs the Center for Gynepathology Research.

Doug Kwon is a physician scientist and director of clinical operations at the Ragon Institute of MGH, MIT and Harvard. He has a clinical practice in the division of Infectious Diseases at Massachusetts General Hospital.

Katy Bowman is postdoc at the Ragon Institute in the laboratory of Galit Alter. She is studying antibodies and Fc-mediated immune functions in niche compartments across multiple pathogens, including Lyme disease, SARS-CoV-2 infection, and tuberculosis.

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