University of Minnesota

Michael Oliver on the Atherosclerosis Research in the 1950s in Britain and Europe

In Britain in 1948, we all had to undertake two years of service for the recovering country and I chose to do this by joining a busy general practice in the slums of Leith (the dockland of Edinburgh). Having learned the hard way about how to be a doctor, I returned to the University of Edinburgh and was instructed in 1950 by the senior cardiologist ‘to go into the medical/scientific library for three months and “learn all you can about the causes of coronary disease.”

So I read prodigiously and, since I had a formal training in biochemistry as well as medicine, I joined with George Boyd of the Biochemistry Department to study the relations between cholesterol and coronary heart disease (CHD). In 1951, we developed paper electrophoresis for the quantification of alpha (HDL) and beta (LDL) cholesterol. This led to several published papers on the influence of the menstrual cycle, pregnancy and the effects of sex, thyroid and adrenal hormones on plasma lipoproteins in rats and humans. In 1954, we reported that patients with CHD had a high LDL/HDL ratio[parallel to John Gofman’s finding].

To my great surprise, I received an invitation to Minneapolis-St Paul to present a paper at Ancel Keys’ 1955 Symposium on Arteriosclerosis. A week later I went to Berkeley to meet Jack Gofman whose pioneer work on ultracentrifugal separation of lipoproteins was just beginning to be recognized. This visit also led to meeting an eccentric senior endocrinologist (Jessie Marmorston who was the wife of Sam Goldwyn) in Los Angeles, and through her, Mary Lasker. Mary Lasker was instrumental in “making” Harry Truman start the NHLBI . She subsequently gave huge sums to atherosclerosis research. She also had a magnificent collection of 20th century paintings in her home in New York.

There is the story she once told me about hiring a helicopter which landed on a lawn in front of Harry Truman’s holiday home as he was having breakfast. She refused to leave before the President had signed an undertaking to consider forming a national heart institute. She was surprised not to be arrested but told me that a little, rather overweight middle-aged woman was not regarded as a big threat in those far-off days.

Again to my surprise, I was invited by Zdenek Fejfar to the League of Nations Building in Geneva to advise about the establishment of a Cardiovascular Unit with the World Health Organization. Gunnar Bjork from Stockholm and Clifford Barger from Boston were the other two advisers. Fighting the noise of mating peacocks in the neighboring park, in the spring of 1956, we made a very strong recommendation for such a Unit internationally. This may seem odd now but WHO at that time focused entirely on communicable diseases. This was followed by the initiation within Europe of a Cardiovascular Unit, primarily concerned with coronary heart disease, to study one of the most common conditions. The International Unit was established in Geneva in 1957 under the direction of Fejfar and a European Unit was started under the direction of Zbynek Pisa in Copenhagen a few years later.

In Britain, there were a few pathologists and an occasional epidemiologist interested in atherosclerosis in the middle 1950s but virtually no physicians. McMichael (a powerful figure in London) spoke out frequently against there being any relationship between lipids and atherosclerosis and in 1953 Paul Wood’s Heart Disease carried the briefest speculative account. In those days, the stethoscope dominated all clinical cardiology and laboratory investigations were highly suspect.

But Born (London) developed a method of measuring platelet aggregation and Sinclair (Oxford) studied fatty acids, speculating that a deficiency of arachidonic acid might contribute to the disease. Elspeth Smith(Cambridge and Aberdeen) was defining the lipids in arterial endothelium. Robinson (Oxford) was studying lipoprotein lipase and Popjak and Myant (London) were defining the synthetic pathway of cholesterol production.

Morris (London) proposed that there is an inverse relationship between physical exercise and CHD. Doll (Oxford) incriminated cigarette smoking. With us in Edinburgh, Thorp developed the first fibrate. Pickering and Platt debated the origins of hypertension. Yet there was no specific mention of atherosclerosis in Howard Florey’s (Nobel Prize Winner for Penicillin) 1952 textbook Pathology. However, in the second edition in 1957, John French (Oxford) wrote a chapter on atherosclerosis and included the following visionary account.

“The lipid composition of the tissue fluid is the factor which determines the overall severity of tissue changes. The important factor which leads to clinical symptoms is thrombosis.…The conclusion originally drawn from [animal feeding] experiments was that an abnormally high concentration of cholesterol in the blood was the significant factor causing fatty intimal lesions. There is increasing evidence that the severity of the lesions [are] related more closely to the relative proportions of the different plasma lipids”.

Because of French’s interest, I went in 1958 to Oxford and, together with Sir Howard Florey, we started a small debating club called the Atherosclerosis Discussion Group (ADG). Initially, there were 14 members. The principal aim of this Group was to obtain an exchange of facts and of views concerning the aetiology, pathogenesis and treatment of atherosclerosis between individuals whose interests and experiences differ widely. Now it has become the British Atherosclerosis Society with more than 100 members. This led to the foundation in 1963 of the European Atherosclerosis Society by Gotthard Schettler (Heidelberg) and George Boyd (Edinburgh).

In 1959, the UK Medical Research Council established an Atheroma Research Unit in Glasgow with Brian Bronte-Stewart (from Cape Town) as the director. But Bronte-Stewart died within four years aged 44 and the MRC Unit was not continued.

Elsewhere in Europe, both Ragnar Nicolaysen in Oslo and Gotthard Schettler in Heidelberg identified the striking fall in coronary heart disease in Norway and Germany with the diet low in total and saturated fats that was available during and after WW2. Malmros (Lund) was investigating the effects of different dietary fats on plasma cholesterol. Martti Karvonen and Kalevi Pyorala (Kuopio) and colleagues in East Finland initiated the North Karelia /Kuopio project – the first interventional epidemiological study, directed over the years by Pekka Puska. Garratini and Paoletti (Milan) were exploring pharmacological means of lowering cholesterol. But there was little other focused research, although Carlson (Stockholm) was beginning studies of lipid metabolism in man.

[ed. [Michael] Oliver treated this subject in some detail in this article:
Pioneer Research in Britain into Atherosclerosis and Coronary Heart Disease – a Historical Review. Atherosclerosis, 2000, 150, 1-12. (Henry Blackburn)]