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Introduction/Overview

John Alexander MacWilliam, a physiologist at the University of Aberdeen in the late nineteenth and early twentieth centuries, was a pioneer in the field of cardiac electrophysiology. He performed groundbreaking research in the study of the human and mammalian heart. He spent many years studying ventricular fibrillation, and was the first person to propose that ventricular fibrillation was the most common cause of sudden death - and that fibrillation could be terminated by a series of induction shocks to the heart. He was the first to accurately describe the condition of arrhythmia (irregular heartbeat), and he suggested transthoracic pacing to treat transient asystole (cardiac arrest). Although his work was recognised with honour in his lifetime, it was not until many decades later that it laid the foundations for very significant developments in the understanding and treatment of life-threatening heart conditions, such as in the cardiac pacemaker. He was appointed Regius professor of Physiology at the University of Aberdeen at the age of 29 in 1886, and remained in that post for 41 years until his retirement in 1927.

Background

MacWilliam was born 31.8.1857 at Kiltarlity, Inverness-shire in Scotland, where his father was farmer at Culmill farm. His parents were William McWilliam (b.1814) and his wife Isabella Cumming (b.1816) who had moved from the parish of Inveravon on Speyside to the farm at Culmill. His mother Isabella Cumming was the daughter of John and Helen Cumming, founders of the Cardhu whisky distillery on Speyside.

John Alexander had two siblings. His elder brother, William Lewis McWilliam, was born at Kiltarlity in 1855. He stayed as farmer at Culmill and married Mary Burns. They had no children. William was a respected farmer, who was also chairman of the local schools committee and chairman of the Parish Council for over 30 years. He died in 1936, aged 81. His sister, Isabella Helen McWilliam, was born 12.10.1859 and died in childhood – at the age of just 11(?) years.

Education and early work

MacWilliam was educated at Kiltarlity parish school until moving on to Aberdeen University at the age of 17 in 1884. It was around this time that he chose to spell his name as MacWilliam rather than McWilliam. At Aberdeen he studied in the Arts faculty for two years before changing course to study medicine.. He graduated M.B, C.M. in 1880, and was awarded the John Murray medal in that year for outstanding achievement. After postgraduate work at the University of Edinburgh and at University College, London, he worked with renowned physiologists Hugo Kronecker at Bern, and Carl Ludwig, director of the famous Physiological Institute in Leipzig. In 1847 Ludwig had invented the Kymograph (to record heartbeat and other muscle contractions or movements). After returning from the continent, MacWilliam received his M.D. degree (with highest honours) from Aberdeen University in 1882 for his thesis: Part 1 – “On the cardiac muscular fibre in various animals”, Part 2 – “On the diaphragmatic fibre in various animals”.

Research work and teaching

In the four years from 1883 till 1886 MacWilliam worked primarily at University College London, as demonstrator under Edward Albert Sharpey-Schafer (previously Schäfer), and working closely with eminent contemporaries in physiology there (W.D. Halliburton and Ernest Starling), and with inspiration and guidance from W.H. Gaskell at Kings College, Cambridge. In 1886 MacWilliam was appointed to the Chair of Physiology at the University of Aberdeen – at just 29 years old – succeeding Professor William Stirling.

During his time at University College he applied himself to the study of the structure of the muscular fibres of the diaphragm and of the heart. The results of this first long period of research were communicated to the Royal Society in a paper “The structure and rhythm of the heart of the eel” – with the results of experiments extending over two years on the origin and conduction of the wave of contraction which sweeps over the eel’s heart, the different ways in which the wave could be blocked, and the manner in which its direction could be changed. From 1885 onwards, there followed three more years of quiet systematic investigation. The mammalian heart became the subject of his experiments. He found that all he had observed in the heart of the (cold-blooded) eel was also to be seen in the mammalian heart. He applied himself in particular to the condition known then as “Herz-delirium” or “ventricular fibrillation” - a condition which became of the highest importance to clinicians in the opening decades of the twentieth century. He sought to explain the manner in which this incoordination in the action of the heart’s muscle was brought about and the manner in which normal contraction could be restored. His conclusions contained observations of the highest importance, at least proving subsequently to be so. He found that there was a “certain area along the septum” where inhibition of the wave of contraction could be easily produced. He observed the condition which became known as “auricular flutter”, and concluded that fibrillation” was a disorder of muscle, not of nerve.

His contributions to cardiac electrophysiology were not limited to ventricular fibrillation. For example, he described the technique of transthoratic pacing for transient bradycardia (abnormally slow heartbeat), and he proposed stimulating the heart during asystole (cardiac arrest) by causing “artificial excitation” with a series of induction shocks (rather than using constant strong electric currents that could trigger fibrillation). He listed several potential triggers of ventricular fibrillation in individuals with underlying cardiac disease that could lead to a “hypersensitive state” of the heart. These included exertion-related changes in blood pressure and heart rate, digitalis, chloroform, and coronary obstruction. MacWilliam made many other contributions to cardiac physiology during his long and productive career. In 1887, when chloroform anaesthesia was a dreaded cause of surgical death, his extensive animal experiments showed that chloroform could affect the heart directly and cause ventricular fibrillation. Between 1912 and 1925 he published articles analyzing the contractile properties of isolated blood vessels, the mechanism of the Korotkoff sounds, the effect of peripheral resistance on blood pressure, and blood pressure measurements in normal and pathological conditions. In 1919 he published “The Mechanism and Control of Fibrillation in the Mammalian Heart”.

In 1923 he reported his sleep studies on humans and dogs, in which he observed that profound effects on blood pressure and heart rate sometimes occurred with “disturbed sleep” which “imposed sudden and dangerous demands on the heart”. He felt that fibrillation could be precipitated during sleep and dreaming, similar to the effects of emotional distress: “Death may come like a thief in the night to a susceptible person living with circulatory conditions that approach the danger line”.

Although his research work continued throughout his career, his focus inevitably moved more towards his teaching role after taking the physiology chair in Aberdeen in 1886. He excelled in his role as teacher and retained enormous respect amongst his students and peers, finally retiring in 1927 at the age of 70.

It is worthy of note that amongst his students at Aberdeen were many who went on to outstanding achievements of their own, including J.J.R. Macleod (joint Nobel prize-winner in 1923 for the discovery of insulin). In 1928 Macleod returned from Canada to take the physiology chair at Aberdeen.

Legacy

It would be more than 60 years before MacWilliam’s pioneering research on arrhythmias and their treatment was translated into clinical approaches that physicians and surgeons could use in patient care. The first successful defibrillation of a human was reported in 1947 by Cleveland surgeon Claude Beck, and the first successful human transthoratic defibrillation by Boston cardiologist Paul Zoll in 1956. Cardiac pacemaker therapy would not become reality in clinical medicine until the 1950s (transthoracic and temporary pacing) and the 1960s (permanent pacing). During the 1960s the care of patients who suffered cardiac arrest or were thought to be at risk of life-threatening arrhythmias was transformed by the introduction of modern cardiopulmonary resuscitation and the introduction of the coronary care unit. John MacWilliam’s important contributions to cardiac electrophysiology had finally moved from the laboratory to the bedside. The value of his work has been increasingly recognised in recent years with acknowledgement in several articles in learned publications around the world.

Honours

MacWilliam was a man of some particular modesty, who did not seek honours for his work. Nevertheless his distinction was recognised in a number of ways during his lifetime, for example by his being elected as a Fellow of the Royal Society (FRS) in 1916, and by the award of the LL.D. degree by Aberdeen University in 1927. He was a member of the University Court (governing body) of Aberdeen University from 1917 until his retirement. At the National Portrait Gallery in London he is remembered in two photographic portraits (approx. 1912 and 1925).

Personal life

In 1889 at the age of 32, MacWilliam married Edith Constance Wise, from a prominent Irish family (and the sister of Berkeley Deane Wise, a leading civil engineer of the time). Sadly Edith died in November 1893 at the age of just 33 – having contracted malaria while in the Canary Islands while her husband travelled on to South Africa. In 1898 he was married for a second time, to Florence Edith Thomas from Wrexham in North Wales, who outlived him by just a few months. For all his married life MacWilliam lived in the village of Cults, now a suburb of Aberdeen.

John MacWilliam suffered for much of his life from an obscure for of dyspepsia, only diagnosed (as duodenal ulceration) and treated in later life.

Death

MacWilliam died of heart failure in January 1937, in a nursing home at 35 Drumsheugh Gardens in Edinburgh. He is buried, along with his wives, at Allenvale cemetery in Aberdeen.