Scientists point to biological-sex barriers hindering medical research

Medical research that could improve patient outcomes and change how diseases are treated is being hampered by a lack of research tools that address key aspects of biological sex, two UVA Health experts say.

Doctors and scientists are increasingly appreciating the importance of biological sex, both in developing new treatments and in understanding the basic cellular processes essential to good health. For example, sex chromosomes are known to play an important role in a wide range of diseases, from heart problems to Alzheimer’s disease.

But UVA Health’s Bradley D. Gelfand, PhD, and Jayakrishna Ambati, MD, argue in a new Science paper that protein-based research resources are not keeping pace with this evolving understanding. Current approaches, Gelfand and Ambati say, simply don’t provide scientists with adequate clues to sex-specific discoveries that could have huge benefits. And that means a treasure trove of medical breakthroughs remains undiscovered.

“We know so much about the consequences of being male or female for many disease states,” said Gelfand of UVA’s Center for Advanced Visual Sciences (CAVS). “What we haven’t quite come to grips with yet is why sex plays such an important role in human health. We hope that by drawing attention to this blind spot in the research community, new tools and approaches will be developed.

Sex in health and disease

Gelfand and Ambati note that there has been tremendous progress in including women in medical research, from basic laboratory research to clinical trials testing new treatments. The National Institutes of Health, the European Commission and the Canadian Institutes of Health Research are urging scientists to consider the potential role of sex. But protein-based research, in particular, still has a clear blind spot when it comes to sex, Gelfand and Ambati say.

This is because important genetic research resources have not been refined to distinguish sex chromosome effects. Normally, men, you may recall, have an X and a Y chromosome, while women have two X chromosomes. These chromosomes contain our genetic blueprints—the operating instructions for our cells. The genes in our chromosomes produce cellular proteins that are instrumental in carrying out these operating instructions and can play an important role in disease.

Scientists know a great deal in general about the function and effects of proteins produced by genes. But existing research resources often do not make critical distinctions about sex chromosome-specific proteins. For example, protein databases may falsely report the presence of Y chromosome proteins in tissues that do not have a Y chromosome.

By not taking gender into account, these critical research resources are woefully incomplete and often misleading, Gelfand and Ambati say. Improving them could have huge benefits for medical research – and for patients. For example, doctors may be able to fight certain diseases in women by introducing a Y chromosome gene into tissues that lack it. Conversely, silencing a disease-causing Y chromosomal gene in males can provide protection against male-predisposed disease processes.

“With currently available research tools unable to distinguish between X and Y genetic components, we simply don’t know what we don’t know,” Gelfand said. “Improving our ability to measure them could be the key to better and more personalized care.”

Ambati added, “Resources and high-fidelity reagents related to sex chromosomes are critical to advancing scientifically accurate conclusions about sex-based differences.”

Published article

Gelfand and Ambati’s paper was published in the prestigious journal Science. The entire piece in perspective is available to read for free.

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