Feb 8, 2022 - Inside 23andMe

Patients Inspire Therapeutics Scientist

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If there’s a sweet spot between discovery and medicine — between answering the big scientific questions of the day, and administering the small but personal care required of the best physicians — then John Matthews is there.

That has a lot to do with his unique background and experience.

 Born in Malawi to a dad who was an agricultural scientist with a Ph.D., and a mom who worked as a hospital nurse, John grew up curious about both science and medicine. (His parents met in Rhodesia while John’s father was flying in a helicopter over farms and spotted his future wife in a red dress having a picnic among the white of a cotton field.) One of John’s uncles was also a doctor, and John developed a natural affinity toward helping people, even performing first aid on the playground in grade school.

“I learned various solutions to deal with simple problems like how to manage nettle stings or remove grit from the eye, washing grazed knees, bee stings, etc.,” he said. “I was very curious about how the body worked, and why it didn’t.”

Now the senior clinical development fellow on 23andMe’s Therapeutics team, John is still wrestling with those questions. He is both a physician who trained in pulmonary medicine and a scientist with a Ph.D. from the National Heart and Lung Institute at Imperial College in the UK. He worked directly with patients in an intensive care unit at a hospital in London, and after leaving clinical practice he spent years working at companies developing medicines meant to treat people with the kind of serious illness he often attended to on the ward.

And he still draws on his early years as a doctor for inspiration. John points to a handful of patients who he said fundamentally changed him and continue to motivate him. One, in particular, was a dying man with HIV who struggled simply to swallow food. Although there were new anti-retroviral treatments, those treatments didn’t become widely available for patients for another ten years. And those lifesaving drugs weren’t available to help this patient. For John, who cared for this patient as he died, it cemented the need to develop medicines faster.

“It was hard to be in a situation where novel therapeutics were so desperately needed and this patient is a constant reminder of the urgency to find new medicines for severe unmet needs,” John said. 

That’s a central mission for 23andMe’s Therapeutics efforts and part of what drew John to work here.

On a day-to-day basis, John focuses on refining 23andMe drug discovery. Some of that involves developing plans for good clinical practice for such things as safety and data management. But he also brings understanding from those early days on the ward caring for people who were sick or dying. He has been instrumental in 23andMe’s efforts studying rare diseases for instance and explaining the science to patient advocacy groups.

We sat down with John to talk about his career, why he came to 23andMe, and what drives him as a scientist and physician.

You were born in Malawi, can you tell us a little bit about that, and about where you grew up?

John: “My parents were living in Malawi — Dad started working as an entomologist at Imperial College, in 1967 and through a UK government grant was based in the newly independent country Malawi to study cotton pests. Mum was working for a hospital as a nurse and Dad was doing his Ph.D. 

We left when I was almost five. But I went back just before I qualified as a doctor, visiting Zimbabwe and Malawi, working on a project comparing asthma in urban and rural areas. 

I visited the Makoka research station and the house I grew up in. I trekked out to the countryside and with various guides and contacts found the man who had taken care of me as a child. I went back daily for a few days buying fertilizer and new wellington boots for him — feeling guilty the whole time. He can’t speak English but he had a photo of me in his kitchen. I feel bad that (our family) didn’t do enough for him. My effort now is to regularly fund Kiva loans for Malawians (www.kiva.org) and support various efforts in Malawi  — but it always feels like a drop in the ocean.” 

You trained in medicine and practiced for a while. Why did you go into medicine?

John: “My mum was a nurse and my uncle Seamus was a pathologist in Dublin. Between my mum and my uncle “medicine” was referred to a lot. I grew up knowing that medicine was a responsibility to care for anyone in need. When I was at school (aged 7-to-10) kids used to come to me in the playground with injuries – and I learned various solutions to deal with simple problems – like how to manage nettle stings or remove grit from the eye, washing grazed knees, bee stings, etc. I was very curious about how the body worked and why it didn’t.”

You’ve said before that you’re interested in physiology, body metabolism, and aging. Why is that?

John: “I did an extra year at medical school to study physiology. I wanted to go deeper into science. Physiology seemed to be the best way to actually look into how the body worked and it seemed a lot more fun than learning more anatomy or biochemistry. The physiology faculty at my medical school were always the best lecturers. The experiments to make discoveries were also more accessible than imagining what was happening in a chemical reaction. I even took part in human physiology experiments as a subject. 

I was encouraged to study areas with little scientific consensus, such as the control mechanisms of the exercise ventilatory response. I worked in an intensive care unit in London called the Mead ward. It was set up by Professor Ron Bradley, the first full-time intensive care clinician in the UK. He also ran the ICU at St Thomas’ Hospital, London. When I was on the ward, Ron, who had retired, still came in every week to give us tutorials. He had developed a way to estimate cardiac output through his work deriving simple equations that he had developed with quantitative data from human experiments. 

Without going into too much detail, the takeaway for me was that a close physical examination of the patient can give quantitative data on the circulatory state of the patient. The challenge is the ability to capture clinical information and lump or split patients in ways that can help us get to a molecular understanding of disease. 23andMe has pioneered capturing self-report data from the patient, but we haven’t yet mastered capturing the reports of the doctors and nurses that look after them.” 

What are your hopes for the work you are doing?

John: “My hope is to see our work yield significant new medicines in the shortest time frame possible.

I’m also very interested in what 23andMe can do around rare diseases. I hope we can communicate the potential of 23andMe to make genetic findings for a large number of rare diseases for which there is very little known currently. 

We’ve recently finished a paper illustrating that potential. There are more than 7,000 rare diseases. Being able to find a genetic basis for some of these conditions could offer valuable insights into diagnosis and treatment. We have the potential to do that for many conditions if we are able to find enough individuals with these conditions to participate in our research.”  


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