Philip Home—Insulin, Insight, and Internationalism

Philip was born just across the River Mersey from Liverpool in 1948. That was a good time and place from which to observe the revolution of the 1960s—and appreciate The Beatles! He spent his first 18 years there, not always enjoying school, but there were high points. At the age of 6 years, he was awarded a form prize for the year. He chose Patrick Moore's Boys' Book of Space, a riveting account of the unknown and need for further discovery. He traces his passion for science to that early influence. Both parents grew up in Merseyside. His father, son of a banker, served in the navy in the 1939–1946 war and became a tax inspector. His mother, daughter of a baker, was a full-time housewife, looking after Philip and his brother, who became a civil engineer.

At school, the emphasis on sport and languages made for an unhappy few years, but as a senior at Birkenhead School, he was able to enjoy focusing on biology, chemistry, and physics. Biology was then hugely exciting, with lots of new ideas around cell metabolism, control, and biochemistry, approachable even for a schoolboy. On a school trip he was inspired by Fred Sanger, lecturing at Manchester University on his Nobel Prize–winning work on the amino acid sequence of insulin. The decision to study medicine at university was taken on the spur of the moment. Unannounced, a senior school master crashed into a biology class and asked if anyone was thinking of studying medicine at university. With 2 seconds of thought he stuck up his hand, never having considered the decision before or since! He was offered a place at Guy's Hospital Medical School, but a subsequent offer from Corpus Christi College at Oxford University overtook that, and Philip embarked on his undergraduate years at one of the premier academic centers in the U.K.

In the summer between school and university, Philip had his first encounter with the pharmaceutical industry. He worked as a laboratory technician at Evans Medical Supplies in Liverpool. This was mainly quality control work, although he was somewhat astonished that an 18 year old should be asked to check that various medications met their specifications before going out to hospitals. This included diamorphine injections and amphetamine tablets, and he recalls the apparent lack of security in those days. Indeed, this was responsibility at an early age!

Leaving Liverpool in October 1966 for Oxford is associated with an indelible memory as the train pulled out of the station: “Goodbye to all that.” He feels no affection for Merseyside. At the time it must have been all the more poignant because of the death of his mother 2 years earlier. On the positive side was the pleasurable anticipation of a new life. Starting a new era at Oxford, he was surrounded by college medical friends, including David Matthews, who was also destined to become one of the U.K.’s leading diabetologists. Philip and David remain close family friends to this day. He became involved with the undergraduate Scientific Society. At his first society management committee meetings he saw Elizabeth (Liz) Broad and fell in love with the woman who would become his wife. Her circle of friends, based in zoology, provided a broader view of science and opened up a new cycle of learning that continues to this day. He joined the small management committee of the Scientific Society and soon became president. That was followed by becoming president of the Committee of Middle Common Room Presidents (the graduate student representative body).

At Oxford in those days, medical studies consisted of 3 years of science leading to a basic science degree, followed by clinical studies elsewhere. However, after completing the first 3 years, Philip was offered a Medical Research Council scholarship to continue at Oxford and enroll for a doctor of philosophy (DPhil) (PhD equivalent) in his chosen subject of pharmacology. This involved mainly histochemistry to identify peptides that might be important in neurotransmission. Liz was also doing a DPhil, and those extra 3 years in Oxford are remembered with affection. The experience had a profound effect on his subsequent career, which certainly reflected his early experience in pharmacology.

Having completed the DPhil, he resumed his clinical studies with a move to Guy's Hospital. There he found studies relatively easy. The work necessary to come to grips with a new specialty attachment could readily be assimilated in a short time. Diabetes was one such attachment, but it was a fellow student with type 1 diabetes who recommended that he should chose the diabetes “firm” for his first medical attachment. His chief memory of this was having to present to the consultant a person with DIDMOAD (diabetes insipidus, diabetes mellitus, optic atophy, and deafness). Given the person’s lack of hearing and eyesight, this was tough for a green clinical student.

The clinical years at Guy's provided a relaxed environment with opportunities to extend personal interests. The strict Oxford curriculum required some fudges due to the lack of alignment with the practicalities of clinical training at Guy’s. Taking the neurology assessment before actually having done any neurology just had to be carried off. Perhaps this was useful training in carrying uncertain matters off with aplomb! However, his last medical firm introduced me to a new consultant, Professor Harry Keen, one of the doyens of U.K. diabetes. Harry was an inspirational teacher, researcher, and physician. He conducted Saturday morning ward rounds, and Philip made a special effort to attend these sessions, which provided a great basis of knowledge and insight into diabetes.

Harry Keen’s ward rounds led to Philip’s appointment to the professorial medical unit for his first post after qualifying in medicine. That decision proved to be determinant for the shape of things to come. Harry was already one of the leading stars of U.K. diabetes, and he laid the basis for almost everything, from use of microalbuminuria to insulin pumps. In March 1976, when Philip commenced on the wards, a person with type 1 diabetes was being fitted with an insulin pump. This was the very first one, and the picture of this large cumbersome device, worn as a rucksack, is often shown in lectures on pump technology. This connection of clinical medicine with pharmacology research was a light bulb moment for Philip.

After 3 years of medical jobs, Philip was keen to get back to research, and Harry took him on as a research fellow at Guy’s Hospital to study insulin pharmacokinetics during continuous subcutaneous infusion of insulin. Clinical research is nothing if not exciting, as Philip discovered rapidly. When Harry himself was a test subject, he developed a hemianopia following somatostatin administration. Fortunately this was transient, even though it was, in Philip’s own words, “scaring me stiff.” His resulting article (1) was to be the first of many.

Philip’s next step was every bit as determinant as the experience at Guy’s. He rang Professor George Alberti, purely to ask where he could source somatostatin. A 2-min conversation led to his 1979 move from London to Newcastle upon Tyne in northeast England. Novo Industri funded that first post in Newcastle, enabled by David Owens (then Medical Director of Novo UK) and Lisa Heding (the wonderful head of the Novo research division in Copenhagen). That started a long and fruitful liaison with the company that eventually became Novo Nordisk. He first established the free insulin assay, measuring the concentration of biologically active insulin in plasma, necessary in those days when everyone on insulin had anti-insulin antibodies (2). He also developed a C-peptide assay. Those two assays powered a notable outpouring of research from Newcastle in the 1980s and 1990s. George attracted large numbers of research fellows from around the world. Robert Heine (the Netherlands), Jean-Claude Mbanya (Cameroon), Ayesha Motala (South Africa), Chaicharn Deerochanawong (Thailand), and Romano Nosidini (Italy) were just a few members of this virtual university. Together with George and Massimo Massi-Benedetti (Italy), Philip “reversed” the insulin clamp technique to study the time course of action of the new human insulins (3). This technique was beautifully simple: just inject the insulin and then adjust an intravenous infusion of glucose to keep blood glucose steady. The time profile of the glucose infused was that of the action of the test insulin. As well as permitting detailed study of the pharmacokinetics of shorter- and longer-acting insulins, it provided a tool that in the future would define the characteristics of a myriad of insulin analogs. Insulin pharmacology remains the interest that most excites him.

In collaboration with Novo, Philip led the first multicenter insulin randomized controlled trial (RCT), comparing human and pork insulins (4). His first international presentation was also in Denmark; it was on blood versus urine monitoring. The Steno group, including Christian Binder, Torsten Deckert, Jorn Nerup, and Bruno Hansen and their research fellows, became good colleagues and friends for life. That also led into work on insulin analogs in collaboration with Novo and notably on insulin aspart. One of their clinical development leads then moved to Hoechst and asked Philip to advise on a new basal insulin (1993), insulin glargine, a topic Philip has collaborated on continually for 28 years (5)!

Those early Newcastle years saw George Alberti mold what became the premier U.K. diabetes research center of the era. As well as Philip, he brought to Newcastle Sally Marshall, Mark Walker, Murray Stewart, and myself, with resulting collaborative work that has stretched over 35 years. Philip was closely involved in the many new techniques that were explored, such as the artificial pancreas, needle-free jet injection of insulin (6), metabolic profiling, implanted insulin pumps, intraperitoneal delivery of insulin (7), islet transplantation (8), endothelial dysfunction (9), and information technology systems for diabetes. To say that it was an exciting research environment is an understatement, and Philip was a central figure. He was appointed as National Health Service (NHS) consultant diabetologist senior lecturer in 1986 and promoted to professor in 1993.

Philip first became involved in international standard setting in the 1990s. The European Guidelines on both type 1 and type 2 diabetes were very successful. That, in turn, involved him in International Diabetes Federation (IDF) Europe, which he developed from an amateur enterprise into an organized enterprise with a legal entity in Belgium, a general manager, and recurrent budget funding from industry. IDF Europe then was able to work with WHO Europe on the St. Vincent declaration, a turning point in bringing international political attention to the needs of people with diabetes. That led to Philip becoming vice president of IDF Global, establishing audit initiatives and setting up the Clinical Guidelines Task Force, which developed the globally relevant IDF type 2 diabetes guidelines (10).

Within the European Association for the Study of Diabetes, Philip became secretary of the Pump and Transplantation Study Group and secretary of its Postgrad Education Committee. Later, he served on the European Association for the Study of Diabetes Council for 3 years. In the U.K., he became involved with a national specialist manpower planning and data initiative, later becoming committee chairman of the Royal College of Physicians Diabetes and Endocrinology Specialist Committee. Involvement with a national evidence-based guideline resulted in interaction with the newly established National Institute Clinical Excellence (NICE) organization. He was appointed clinical lead on type 2 and type 1 diabetes guideline committees during NICE’s initial 10 years of influential function (11). He also joined the new NICE Technology Appraisals Committee as one of the three physician representatives. This group of health economists, epidemiologists, heads of patient associations, and NHS managers was tasked with developing new processes. That 3-year appointment turned into 9 years, and he became vice chair of the committee. He chaired the historic final NICE Appraisal Committee meeting for approval of statins for wider use in the NHS.

Philip had close involvement with another hugely significant group of drugs. In the late 1990s he advised Glaxo Wellcome (as it was named then) on troglitazone and gave evidence to a U.S. Food and Drug Administration Advisory Committee on behalf of their U.S. partners. He also chaired the steering committee of the rosiglitazone cardiovascular outcomes study (from 2000). When the Nissen bombshell landed, a data analysis suggesting an increased risk of myocardial infarction during rosiglitazone therapy, he was centrally involved in the drama. At a needle session of the 2007 American Diabetes Association Annual Scientific Sessions, Philip spoke immediately after Steve Nissen to three packed halls. He was able to introduce critical thought into a flawed data analysis and to introduce the results of an emergency but formal interim analysis of rosiglitazone’s safety RCT (12). Of course the argument was won, and eventually the U.S. Food and Drug Administration withdrew its restrictions on rosiglitazone. Although the thiazolidinediones were ultimately shown to have other problems, the matter of setting right an erroneous analysis was critically important. Given the tendency for use of big data to guide decisions on individual patients, this is a parable for our time.

The heading for this section is the title of one of Philip’s tongue-in-cheek but thoughtful articles in the Journal of the Royal College of Physicians (13). His long experience of editing journals and reviewing papers began in 1979, when George Alberti, as editor in chief of Diabetologia, asked him to be an assistant editor. A whole new avenue of professional activity opened up. He learned rapidly from the comments of high-quality reviewers on high-quality papers, and that guided further development of critical thought. Subsequently he became an associate editor of Diabetologia. Jay Skyler then asked him to join the editorial board of Diabetes Care (1984), following parallel studies in Newcastle and Miami with Jay on continuous subcutaneous insulin infusion compared with multiple subcutaneous injections of insulin (14). In 1988, he took over from John Ireland as editor of Diabetic Medicine, having previously been deputy editor. The relentless pressure of being editor was helped by an excellent editorial assistant—his wife Liz. He edited every paper published himself to guarantee quality and ensured that Diabetic Medicine focused on studies of human diabetes. Now, in 2021, Philip has just completed a second term on the Diabetes Care editorial board, again stemming from a research collaboration, this time with Matt Riddle concerning insulin glargine developments. He continues to be active in reviewing papers and was pleased to be recognized as one of Diabetes Care’s top 10 reviewers recently. A complete list of the personal papers that Philip authored is available in his online curriculum vitae (15).

That first meeting with Liz at the Oxford Scientific Society set the scene for life. Philip and Liz married in 1971. They have two children, who both followed their parents to Oxford. That in itself is no mean achievement; entry to Oxford is intensely competitive and based on outstanding academic success. Doubtlessly this reflects a great environment at home, as well as genetics! Their daughter trained in medicine and now works as a family doctor. Their son is now professor of quantum physics at ETH Zurich. Four grandchildren are a major focus of life these days. Half the family lives in Switzerland with fluency in four languages, perhaps making up for Philip’s original language skills aversion!

At home the garden and family have always filled any time left over from erratic work schedules and international traveling. Gardening is a particular source of pleasure, and lecturing widely has provided opportunity for Philip, with Liz, to vacation around the world. He has a justified claim to know America better than most Americans, and the same goes for Australia and Australians!

Philip’s career in diabetes has spanned a time of unprecedented advance. In 1979, when he moved to Newcastle, type 1 diabetes was managed with two injections per day of soluble and intermediate-acting insulins. That was effectively two shots in the dark, as the only indications of appropriate dosing were urine testing and hypoglycemia. From moving the time of intermediate insulin to bedtime, home monitoring of blood glucose, and use of biosynthetic insulins, insulin analogs, insulin pumps, and ultimately closed-loop pump systems, Philip has been a central player. He has worked on guidelines for diabetes care and formal testing of therapies by RCT, both of which were unheard of in 1979. That is quite a career.

Acknowledgments. I am grateful to Philip for provision of information and photographs. Insights from sharing an office with Philip from 1984 to 2006 have contributed to this portrait. Apologies are due to the many collaborators and coauthors whom it has not been possible to acknowledge.