Malcolm Andrew Ferguson-Smith was born in Glasgow in 1931, the son of the distinguished physician and dermatologist John Ferguson-Smith. He graduated in medicine from Glasgow University in 1955 and held House Physician and House Surgeon posts at the Western Infirmary, Glasgow, 1955-1956, and was Senior House Officer and Registrar in Pathology, 1956-1958. While undertaking postgraduate training in pathology he was introduced to research on sex chromatin under Bernard Lennox. Their buccal smear surveys revealed for the first time the high frequency of Klinefelter's Syndrome among subfertile males and those with learning difficulties. Unsuccessful efforts to undertake chromosome analysis in these patients during 1957-1958 led to Ferguson-Smith continuing his research in the USA, with appointment as Fellow in Medicine at the School of Medicine, Johns Hopkins University, Baltimore, in 1959. Ferguson-Smith remained at Johns Hopkins, working on chromosomes with Victor Almon McKusick, for nearly three years. Here he established the first human chromosome diagnostic laboratory in the USA and undertook cytogenetic research into the Turner Syndrome and true hermaphroditism.
Ferguson-Smith returned to the Department of Genetics (headed by Guido Pontecorvo) at Glasgow University in 1961. He was appointed successively Lecturer, Senior Lecturer and Reader, becoming the first Burton Professor of Medical Genetics in 1973. His duties included teaching genetics to medical students and the establishment of a Regional Genetics Service for a population of three million in the West of Scotland. The clinical cytogenetics service provided opportunities for contributing to the human gene map using familial chromosome polymorphisms, deletion mapping, in situ hybridisation and chromosome sorting by flow cytometry. His work on mapping the Y-linked sex determinant in XX males led to the isolation of the mammalian sex determining gene twenty-five years later. The work on translocations in pachytene, gene mapping through chromosome deletion and by in situ hybridisation proved to be the first descriptions in the human genetics literature. He also participated extensively in all eleven international Human Gene Mapping Workshops from 1973 to 1991. During this period he published on many other aspects of human meiosis, clinical genetics, antenatal diagnosis and human chromosome mapping.
In 1987 Ferguson-Smith was appointed Professor and Head of the Department of Pathology at Cambridge University and Director of the East Anglia Regional Genetics Service. He led research on gene isolation, fluorescence in situ hybridisation (FISH) techniques, reverse chromosome painting and studies in karyotype evolution using chromosome sorting and cross-species chromosome painting. He retired as Head of Pathology in 1998 and he and his team moved to the Cambridge University Department of Veterinary Medicine. In 2002 he established the Cambridge Resource Centre for Comparative Genomics, with Wellcome Trust support. The Centre produced and distributed chromosome-specific DNA from over 120 species of animals, birds and fish to scientists throughout the world for research in biology, evolution, gene mapping and cancer. This data led to many collaborative studies and allowed cross-species comparisons to be made and homologies between species mapped, so allowing detailed studies of relationships between species and research into genomic evolution. The cross-species chromosome homology maps generated by these studies were made available in a database (www.chromhome.org). An important aspect of the research of the Ferguson-Smith laboratory at the Vet School was on the evolution of vertebrate sex determination and their discovery and characterisation of the unique ten sex chromosome system of the platypus.
Ferguson-Smith's expertise as a medical geneticist was called on in a number of other capacities. In 1969 he was approached by the British Olympic Committee to administer the tests for competitors for the 1970 Edinburgh Commonwealth Games. He declined, arguing that the method of testing (the sex chromatin or buccal smear test) would be more likely unfairly to exclude women athletes than detect cheats. The buccal smear test was challenged again in the 1980s and in 1991 the International Amateur Athletic Federation set up a Working Group on Gender Verification. Ferguson-Smith served on this Working Group which called for an end to genetics-based gender verification and its replacement with a health test for all athletes. It met with gradual success until in 1999 the IOC abandoned genetics based testing for the Sydney Olympics. In 1998 Ferguson-Smith was appointed as the scientist member of Lord Phillips' Committee reviewing the UK Government's original Bovine Spongiform Encephalopathy Inquiry. The Phillips Committee considered the emergence of BSE and new variant CJD and the action taken in response to it, reporting in 2000.
Ferguson-Smith has received many honours including election to the Fellowship of the Royal Society of Edinburgh in 1978 and the Royal Society of London in 1983, the Royal College of Obstetricians and Gynaecologists in 1993 and the Academy of Medical Sciences in 1998.