Imagine a world where therapies are made available only to the males in the society. A new twist to an Atwoodian dystopia? In 2019, Gilead’s drug for preventing HIV was approved exclusively for males by the FDA, not for any nefarious reason, but because the female population was excluded from its clinical trials. This could have stemmed from a historical bias which linked HIV exclusively to men. As a result, there was no evidence that the drug worked or was safe for women! The assumption, that sex has no effect on the efficacy of therapeutics, hangs like a shadow over most clinical studies; however, the light doesn’t seem to get brighter.
It is now clear that mortality rates from COVID-19 skews to the male population, despite their under-representation in the front-line healthcare workforce. This is likely due to immunosuppression by testosterone which makes males less equipped to fight a coronavirus invasion. Years before COVID struck fear in the hearts of the elderly, another ‘pandemic’ had stealthily started spreading among the teenage population of the world. With smartphones and lightning-fast internet, young minds had unknowingly offered themselves up to the grand ‘social media experiment’ ushering in a decade of plummeting mental well-being. According to the UK’s NHS, girls are prescribed more than 2/3rdof all antidepressants and are five times more likely to be hospitalized due to self-harm than boys. Can such stark differences be waved away in the name of social conditioning? Simone de Beauvoir’s claim that one is not born as but rather becomes a woman or Gloria Steinem’s tirade against researching sex-differences might have been politically expedient but fall short when tackling real health issues of real people. What biological principles underlie such differences and how can we exploit these differences to improve our global well-being?
I spoke to neuroscientist and medical doctor, Antonella Santuccione Chadha, the CEO and co-founder of the Women’s Brain Project (WBP) who has fought back against a casual dismissal of sex differences in neuroscience, pointing out that this denial closes the door on precision medicine (see our YouTube channel for full version of the interview). The Women’s Brain Project grew out of lakeside chats in Switzerland among three friends about the importance of sex differences in Alzheimer’s disease. The WBP, now consisting of a diverse group of scientists, science communicators, and artists from all over the world, is leading the charge toward addressing mental health issues that overwhelmingly affect women.
But are male and female brains really that different? Although they are more similar than different, according to Antonella, the differences get amplified under the backdrop of disease. Antonella thinks it is essential to “understand these differences to make better medicines” and prevent unfortunate instances where drugs had to be withdrawn from the market due to their adverse effects on women. She adds that a more holistic approach using precision medicine, which seeks to incorporate data from different sexes, races, and ethnicities, can prevent such large-scale wastage of resources. She pointed out that the ‘default human model’ assumed in most clinical trials, doesn’t exist, and biases are introduced in datasets by a failure to diversify these trials. Antonella made this very clear in her recent TEDx talk– trials for drugs approved by the FDA between 2015-2017 consisted of 43% women and only 5% of all participants were African-American. She expressed concern that a perceived ‘sameness’ can come in the way of high-resolution healthcare, which is why WBP is working on training artificial intelligence (AI) to parse through large data sets on diseased brains to identify features that might be unique to each sex. Since AI is as good as the data fed into it, Antonella stressed on the importance of collecting datasets from diverse populations if we are to recognize these ‘digital biomarkers’. She pointed to studies where AI, fed with x-ray images from only male patients, had a hard time predicting lung diseases in females and vice-versa but did better when trained on datasets from both male and female patients. Clearly, there is a lot to be done.
The Women’s Brain Project has already initiated academic collaborations to hunt down structural differences in cognitively impaired male and female brains. Recognizing the limited reach of academic research, WBP has organized the International Forum on Women’s Brain and Mental Disease to bring together regulators from around the globe, including the US FDA, to discuss how to tackle sex and gender issues in drug development. Antonella thinks that sex differences need to be considered at the very source of the data – the laboratory. I was surprised to learn that the lack of female representation isn’t just a problem with human clinical trials – females are also under-represented in lab mice used to test new drugs!
But how long is the path toward precision medicine? We are currently at 1.5/10 according to Antonella, which though scary, presents a unique opportunity for young researchers to be at the frontiers of discovery in the coming decade.
We can develop a sustainable healthcare system through precision medicine only when the word ‘differences’ is replaced by the term ‘characteristics’.
While she continues to fight against neurodegenerative diseases like Alzheimer’s, Antonella thinks we can do more to prevent such tragic outcomes. WBP has launched the ‘Be Brain Powerful’ campaign, which is a platform to educate the public on the importance of caring for mental hygiene and encourage healthy choices for our brains. In her words – “we are the owners of our brains and as much as you have to train your muscles you have to train your brain” – and who would disagree?
In this world of constant mental distractions, how do you make your brain powerful?
Reading helps, as does learning another language or playing musical instruments, thinks Antonella. She also suggests ample physical exercise and a healthy diet. Then Antonella raised perhaps the most relevant point – “one of the key factors to stay mentally fit is to be socially engaged”. In the backdrop of a year of intermittent lockdowns and social isolation, her call for more social interaction and a need for purpose in life rings louder than ever.
Science went through a dark phase when ideological application of pseudoscience tried to highlight differences between groups to maintain the hegemony of the powerful. This has made research into ‘differences’ between the sexes a minefield, exposing the sciences to the dangers of ideological corruption once again. As Antonella keeps saying – we can develop a sustainable healthcare system through precision medicine only when “the word ‘differences’ is replaced by the term ‘characteristics’.”
With Antonella’s boundless optimism for the future, we are perhaps not too far from a day when our doctors will prescribe customized medicines in the same way we order our favorite sandwich.
Club SciWri congratulates Antonella on receiving the World Sustainability Award for the year 2020 and the Italian National Prize Medicina Italia. To know more about Antonella please visit her webpage.
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Author:
Saurja Dasgupta is originally from Kolkata, India. He obtained his Ph.D. at the University of Chicago, where he studied the structure, function, and evolution of catalytic RNA. He is currently doing his postdoctoral research at Massachusetts General Hospital, Boston, where he is trying to understand the biochemical milieu that could have given birth to life on earth (and elsewhere) and reconstruct primitive cells. One of his scientific dreams is to observe the spontaneous emergence of Darwinian evolution in a chemical system. When not thinking about science, Saurja pursues his love for the written word through poetry and song-writing (and meditating on Leonard Cohen’s music). His other passions are trying to make science easier to understand, and fighting unreason and pseudoscientific thinking with a mixture of calm compassion and swashbuckling spirit.Editors:
Illustrator:
Sohini Dutta is currently pursuing her PhD in neuroscience at Kent State University, USA where she studies the underlying neural circuit of fear memory and how dysfunction can result in development of anxiety disorders. Her dream is to contribute to the development of effective precision medicine for treatment of anxiety disorders. She enjoys talking about science with a broader audience and hopes to bridge the knowledge gap between researchers and the public. She loves doodling , hiking, travelling, photography and playing with and petting dogs.
The contents of Club SciWri are the copyright of Ph.D. Career Support Group for STEM PhDs (A US Non-Profit 501(c)3, PhDCSG is an initiative of the alumni of the Indian Institute of Science, Bangalore. The primary aim of this group is to build a NETWORK among scientists, engineers, and entrepreneurs).
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