Seeking better pharmaceuticals: A conversation with Richard J.M. Ross, MD, FRCP
Richard J.M. Ross, MD, FRCP, professor of endocrinology in the department of oncology and metabolism at the University of Sheffield in the United Kingdom, has taken a different career path than most in his field.
As part of his work on replacing cortisol in people with adrenal insufficiency and congenital adrenal hyperplasia, Ross founded the pharmaceutical company Diurnal to develop Chronocort, a steroid used to treat congenital adrenal hyperplasia, as well as Infacort, a novel pediatric hydrocortisone formulation. For his work in developing new therapies, Ross is the recipient of the Outstanding Innovation Award as part of the Endocrine Society’s 2021 Laureate Awards.
Healio spoke with Ross about his career, how the field of endocrinology has changed in recent years, and how changes in practice and the prevention of autoimmune disorders may transform endocrinology in the future.
Healio: What was the defining moment that led you to your field?
Ross: I was appointed as a registrar to the endocrine unit at St Bartholomew’s Hospital, London, in 1983. It was my first experience of academic medicine, and I was enthused and overawed by the excitement and commitment of the group to the discovery of truth in science and its application to patient care. The department head, Professor Michael Besser, was an inspirational leader utterly committed to his patients and clinical research.
Besser cared deeply about his patients and was a fantastic researcher. That’s actually not such a common combination in research. He was old school, drove us hard and in the process trained a generation of clinical academic endocrinologists around the world.
Healio: What area of research in endocrinology most interests you right now and why?
Ross: In endocrinology, most of what we do is balancing people’s hormones to the best of our ability, either replacing their hormones if they are deficient or controlling excess hormone. My research over the last 15 or 20 years has focused very much on optimizing the replacement of endocrine hormones, not insulin, but the other hormones. The last century was often about treating acute disease and curing heart attacks, antibiotics for infection and then replacing hormones. But now, a lot of our care is about chronically maintaining people’s health, living with whatever condition they have. If we can optimize the replacement, then we can give people a healthy life. I’ve been particularly focused on optimizing the replacement of cortisol.
In diabetes, people have focused on trying to replace physiology over the last 20 or 30 years, but it hasn’t hit the rarer conditions. Even in thyroid disease, people have sort of said what we’ve got is good enough. People are beginning to recognize now that there are health consequences to not optimizing hormone replacement.
Healio: Have you ever been fortunate enough to witness or to have been part of medical history in the making?
Ross: In 1985, we used to give human extracted growth hormone to children to help them with their growth. Basically, the postmortem technicians would be paid a shilling for every pituitary they donated. It took a hundred human pituitaries to treat one child for a year, but sadly in 1985, it was discovered that three children in the U.K. and one or two children across the world had developed Creutzfeldt-Jakob dementia because it was transmitted from the cadaveric tissue, so growth hormone was withdrawn in most countries.
I was, at that time, just starting studies with something called growth hormone-releasing hormone, which is a hormone that stimulates the release of growth hormone from the pituitary. That was synthetic, so we could use it because it didn’t come from humans, and we undertook trials very quickly to see whether we could use that to treat growth hormone-deficient children. We found that in a certain population of them, we could. And then we moved on, as biosynthetic growth hormone came available the same year, to doing trials with biosynthetic growth hormone in adults. I was involved in that research and saw that great impact of recombinant DNA technology.
Healio: What do you think will have the greatest influence on your field in the next 10 years?
Ross: We’re going to see a transition, particularly in subjects like endocrinology, to people taking much more responsibility for their own care. In the past, doctors prescribed, and you took. If we’re going to truly physiologically replace people, we need to use artificial intelligence. Continuous glucose monitoring can impact the way that insulin is delivered to provide it being more physiological. We can do the same thing for other conditions like thyroid disease and adrenal insufficiency where we can look at how people feel and understand better how to replace them. That’s going to be become more and more important in how we manage diseases and how people manage their treatment.
Second, in endocrinology, a large part of the diseases we see are autoimmune due to the destruction of glands from antibodies. As we unravel the immune response and understand better why people develop autoimmunity, we should be able to prevent the onset of some of these autoimmune diseases. I don’t know how that’s going to happen, but at we’re beginning to get some real insights. For example, there are these new immune checkpoint inhibitors in the treatment of cancer that cause autoimmunity, and this will lead us through the story of how to prevent autoimmune diseases like Graves’ disease and Addison’s disease.
Healio: What are you currently working on?
Ross: I am currently working on the development of modified-release formulations of hydrocortisone to replace the endogenous circadian rhythm of cortisol. This will allow us to better control diseases such as congenital adrenal hyperplasia, replace cortisol in patients with adrenal insufficiency and control inflammatory disorders where anti-inflammatory glucocorticoid therapy is required. This work is being funded and commercialized by the company Diurnal that I founded and has allowed me to work with an exceptionally talented team of drug developers and experts around the world.