Scott, John Martin (1940–2012), biochemist, was born on 20 May 1940 in Dublin, the son of Martin Scott, an engineering inspector in local government, and Clare Scott (née Doran), who was a nurse before her marriage. He had one sister, and grew up in Churchtown, Co. Dublin, but attended Garbally College, Ballinasloe, Co. Galway, probably his father's old school.
In 1962 John graduated with a B.Sc. in biochemistry from UCD, and then moved to TCD to work for a Ph.D. He took up a junior lectureship in TCD in 1965, and from 1966 to 1968 had his first sabbatical period in the USA as National Institutes of Health (NIH) international post-doctoral fellow in the University of California, at Berkeley. He had three further sabbatical periods during his career, two in the USA and one in London.
Shortly after returning from his first sabbatical, Scott became friends with Donald Weir (regius professor of physic in TCD from 1977). Weir credited Scott with showing him, in a tremendously fruitful collaboration over thirty years from 1969, how biochemistry can elucidate the problems encountered in clinical medicine. The two men quickly established a research group of scientists and clinicians, with specialisms in nutrition and biochemistry, a group which gained the reputation of being able to move with equal commitment between laboratory bench and bedside. Scott was appointed to a personal chair in experimental nutrition in TCD in 1978.
His main focus throughout his career was on folates, a group of compounds with shared structure and equivalent biological activities, that collectively make up one of the B vitamins essential to health. Folates are derived naturally from food sources such as green leafy vegetables. The synthetically produced, commercially available precursor molecule, folic acid, is an important source of folate. Scott's early work was on the role of polyglutamate forms of folates in microbial and mammalian cells. This work gave an understanding of how folates are retained in cells and how excretion and breakdown of folate molecules occur. With Weir he also carried out research on the form of megaloblastic anaemia caused by deficiency of folate or the closely associated vitamin, B12. Together Scott and Weir and their group elucidated the general biochemical mechanism of the classical demyelination of the spinal cord and clinical neuropathy seen in vitamin B12 deficiency, but not in folate deficiency.
Researchers had recognised since the 1960s that a maternal micronutrient deficiency (most likely of folates) in pregnancy could cause neural tube defects (NTDs) in the foetus. NTDs include spina bifida and anencephaly, and cause high infant mortality or serious lifelong disabilities. Up to the 1970s, Ireland's rate of such NTDs was one of the highest recorded in Europe; with nearly eight babies out of 1,000 born with NTDs. In the early 1990s two important clinical trials (an international trial coordinated by the UK Medical Research Council (1991) and a Hungarian trial (1992)) demonstrated conclusively that maternal supplementation with folic acid before and during early pregnancy would greatly reduce the risk of having an NTD affected pregnancy.
Years before that result was published, Scott and Weir's team, in collaboration with the Health Research Board and Dublin maternity hospitals, had made substantial contributions to the subject by organising the collection (1986–90) of more than 56,000 blood samples from Irish women in early pregnancy. Most women at the time in Ireland did not take nutritional supplements and there was little or no fortification of foods, so, crucially, these data reflect a baseline situation. Using this biobank, bloods from eighty-four mothers who had delivered babies with NTDs were identified, and the team was able to demonstrate that affected mothers had lower folates in red blood cells than non-affected mothers, and that having a red blood cell folate concentration above a specified concentration was greatly protective against having an NTD affected pregnancy. The work was published in a significant and forthright paper 'Folate levels and neural tube defects. Implications for prevention' in the Journal of the American Medical Association (1995). The paper, which has been cited over 500 times, had immediate and lasting impact. Twenty years later, it formed the basis for a World Health Organization guideline: 'Optimal thresholds for serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects' (WHO 2015).
In another highly influential paper, published in the Lancet in 1996, Scott and his team published results showing that the bio-availability of naturally occurring folates was rather poor, compared to the uptake of the synthetic vitamin (folic acid). They demonstrated that the protective red blood cell folate concentration noted earlier, which was well above levels that resulted in clinical deficiency, could not easily be reached by eating dietary folates but only with supplements and fortified foods. Scott also demonstrated that an ongoing intake of small amounts of folic acid, such as the amount that could be added to fortified foods, would, over time, allow a protective blood concentration to be achieved. The work provided support for calls to add folic acid to foodstuffs, particularly to fortify bread, so that the cohort of women of childbearing age who might fall pregnant unexpectedly would be at least somewhat less at risk of an NTD pregnancy. Campaigns led in due course to the mandatory fortification of foods with folic acid in the USA, Canada and over seventy other countries worldwide.
Scott's team engaged with collaborators in the National Institutes of Health (NIH) in the United States to study the role of folic acid in NTDs. With these collaborators, he worked on strategies to establish the level of supplementation, whether taken voluntarily and individually, or in fortified food, which seemed likely to be optimal in preventing NTDs. He and his team also researched the possible positive or negative implications of treating whole populations with supplementary folic acid. His collaborative work in TCD and in associated institutions such as St James's Hospital and the University of Ulster, examining the risks and benefits of increasing folic acid consumption in various populations and for many health outcomes, led to scores of publications, presentations, applications for research funding and clinical trials. Even for someone unacquainted with the field, the titles of the team's publications, appearing every few months in the 1990s, convey the scope of their studies, as well as the sense of excitement, urgency and enthusiasm for discovery which characterised this period of Scott's career.
Scott served on the UK's Department of Health Expert Advisory Group, which in 1992 unanimously recommended food fortification, and was a member of the Irish Food Safety Authority, but was disappointed that the UK and Ireland continued to refuse to fortify food. Scott's team also worked to disprove several of the concerns which opponents of fortification put forward to justify their position: published papers on pregnancy complications, cardiac problems and the development of cancers broadly found no increased risks due to folate supplementation. Research showed that the incidence of NTDs was unchanged in countries where voluntary supplementation was recommended, compared with the USA and Canada, where there were indeed fewer affected pregnancies thanks to mandatory fortification of flour. Overall, a very great deal of credit for the worldwide understanding of the requirement for folic acid to prevent NTDs must go to the work of researchers from Trinity's Schools of Biochemistry and Medicine, led for thirty years by John Scott.
Largely in collaboration with colleagues in the NIH, Scott and his team looked at possible genetic differences between women which might lead to less successful metabolism of nutrients such as the folates and other B vitamins, and towards the end of his career, he examined the influence of genetic makeup on whether or not individuals experienced changes to blood pressure after riboflavin therapy. Even after retirement age, Scott continued his research and collaborated on major work to examine the role in pregnancy and otherwise of vitamin B12; the group reported in 2009 that maternal blood status of vitamin B12 is likely to be an important additional factor in causing maternal risk for having an NTD affected pregnancy. He was also interested in orofacial clefts, and was involved in the collection in Ireland of a biobank of DNA from patients with clefts, which was used with other internationally collected samples to confirm the involvement of previously unidentified genes. The study was published in Nature Genetics in 2010.
Alongside an internationally recognised research career, Scott was also involved in the administration of his discipline, serving on national, European and American scientific committees. He was elected to fellowship of TCD in 1973 and was a member of the RIA from 1984. Serving as bursar of TCD (1977–80), at a time of considerable change and development in the college, he was also a member of the board of St James's Hospital for more than twenty years. Scott received many awards in recognition of his outstanding contributions to science, medicine and human welfare, such as the degree of Doctor of Science (1981) by TCD and honorary degrees from the University of Ulster and from University San Pablo, Madrid. He received the TCD Provost's Award for Outstanding Contribution to Teaching and Learning, and was the first non-American to receive the Lederle Award from the American Society of Nutritional Science. In honour of Scott's achievements, TCD in 2016 established three John Scott fellowships for Ph.D. students to research in biochemistry.
On 6 July 1966 Scott and Isabel Finnegan were married in Dublin; they had a son and a daughter. His wife predeceased him in 2010, and John Scott suffered increasingly poor health for the last couple of years of his life. He died on 29 December 2012 in St Luke's Hospital, Rathgar, Dublin.