Speculation as to the nature of genetic inheritance and which illnesses are genetic in origin predated clinical genetics, as illustrated in the RCP library’s 1815 edition of A philosophical treatise on the hereditary peculiarities of the human race: with notes illustrative of the subject, particularly in gout, scrofula, and madness. The discovery of the molecular structure of DNA in 1953, that humans had 46 chromosomes in 1956, and the sequencing of the human genome in 2001 brought the field out of the realm of speculation and into that of diagnostic pathology.

Victor McKusick

Among the pioneers of the mapping of the human genome and a strong advocate of the Human Genome Project was Victor McKusick (1921–2008) who was widely known as the father of modern medical genetics.

McKusick became interested in genetics while working as a cardiologist; he became fascinated by patients suffering from rare inherited disorders such as Marfan’s syndrome, which often resulted in death due to a rupture of the aorta. He realised that seemingly unconnected symptoms could all be associated with a single abnormal gene and, towards the end of the 1950s, he decided to shift the focus of his career. In an interview in 1957, the year in which he founded the Johns Hopkins division of medical genetics (now the McKusick-Nathans Institute of Genetic Medicine), McKusick said that some of his colleagues ‘thought I was committing professional suicide in leaving cardiology to concentrate on rare and unimportant genetic disorders’.

The unit, along with a similar one in Washington, was the first in the USA. He continued to study, and meticulously catalogue, rare familial disorders and one particular form of dwarfism, suffered by the Amish, is now known as McKusick-Kaufman syndrome. In 1966, he published Mendelian inheritance in man, a catalogue of all best known genes and genetic disorders. The first edition contained 1,500 entries – it has now grown to 12 editions and 20,000 entries and is available only online.

John Edwards

John Edwards (1928–2007) became epidemiology lecturer at the University of Birmingham in 1956, the same year the number of human chromosomes was discovered. One of his talents was with statistics and he applied this to the epidemiology of dislocation of the hip and of neural tube defects in the register of birth malformations. This and his weekly ward rounds at Birmingham Children’s Hospital led him to an interest in genetics.

In 1958, he joined a new unit in population genetics at Oxford directed by Alan Stevenson 1909–1995. When, in 1959, it was discovered that an extra copy of chromosome 21 was the cause of Down’s syndrome, Edwards realised that other syndromes with a similar pattern of multiple minor malformations and learning disability might also be due to an abnormal number of chromosomes. One year later, while at the Children’s Hospital of Philadelphia, Edwards identified an extra copy of chromosome 18 as the cause of what became known as Edwards syndrome. In 1961, he returned to Birmingham where he set up a small cytogenetics laboratory to study Down’s syndrome and to provide a chromosome diagnostic service.

His commitment to patient care led him to develop a new method for obtaining samples for chromosomal analysis. The new skin biopsy – which Edwards practised on his own knees – was considerably less painful than the earlier extraction of samples from bone marrow or the testes.

He was involved in developing computational processes for understanding genetic data, including contributing to Human Gene Mapping Workshops that led to the development of the Human Genome Project. He was also an early advocate for sharing primary research data and openness in human genetics.

Edwards was always interested in genetic susceptibility to common diseases such as diabetes and heart disease. He looked to distinguish the effects of single genes of low penetrance from the combined effects of a multiplicity of genes, which became the subject of his research papers.

The latter particularly intrigued Cedric Carter (1917–1984), who founded the Clinical Genetics Society and co-ran the first genetic counselling clinic in the UK centred at the Hospital for Sick Children (now Great Ormond Street Hospital). He co-pioneered the use of family studies to ascertain recurrence risks in the common congenital malformations and the data form these studies still form the basis of genetic counselling advice today. An observation from this was the ‘Carter effect’ – in which the chances of subsequent children being born with the same genetic condition as their affected sibling or parent are higher if that sibling/parent is of the gender in which the condition is less common.

Sarah Bundey

Sarah Bundey (1936–1998) worked at Cedric Carter’s unit and then with Victor McKusick before going to the University of Birmingham in 1974, where John Edwards, then professor of human genetics, created a position for her. Sarah’s work in Birmingham began as a clinical assistant, then lecturer, senior lecturer and reader before rising to the award of a personal chair from the University of Birmingham. All her posts were part-time, and from these came over 100 papers. She delineated subtypes of cerebral palsy that were most likely to be autosomal recessive neurological syndromes, and performed widely used population studies on retinitis pigmentosa, myotonic dystrophy and fragile X syndrome. Her major contributions also encompassed muscular dystrophy, especially Becker’s muscular dystrophy, ataxia telangiectasia and Wolfram syndrome. Indeed, she was a pioneer in neurogenetics and the genetics of eye diseases, setting up in Birmingham some of the first specialist clinics in the country.

Bundey demanded facts on which to act, hence the establishment of the Birmingham births study, which followed the health of 5,000 babies in different ethnic groups for 5 years and documented the prevalence of genetic disease. She also instituted pioneering work with ethnic minority communities in Birmingham on the understanding of genetics and the provision of appropriate genetic services. One of her legacies is a specialist worker in the clinical genetics unit who works with Asian families.

Bundey was renowned for her honesty and integrity, wisdom and advice, not only with scientific research, but also with complex ethical issues about which she was often consulted behind the scenes. As a member of the RCP’s clinical genetics committee she was the author of some of the planning documents used in the development of national genetics services. The Clinical Genetics Society owes its birth to Bundey, who made the practical arrangements and then became the first secretary.

Bundey’s diagnosis of carcinoma of the breast did not come as a surprise because of her own family history. This was especially poignant as at that time the clinical genetics unit was setting up its services for families with a history of breast cancer.

Karen Reid, library manager

Clinical genetics is the RCP specialty spotlight for February 2017.