It is only in recent years that Janet Elizabeth Lane-Claypon (1877-1967) has been recognised as a pioneer in epidemiology. Her findings on breast cancer and infant nutrition have stood the test of time. Furthermore, she introduced new concepts into how epidemiology should be done, notably what are now known as case-control studies and the recognition and treatment of confounding factors. She introduced newly established statistical techniques into her analyses of the data. Recognition has been late coming but there is now a Janet Lane-Claypon Building at the University of Lincoln in her county of birth.
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| Janet Lane-Claypon in 1907 Extracted from a group photograph taken at the Lister Institute |
Of her important epidemiological findings I will only deal with one: breast cancer. Lane-Claypon compared data on the lifestyle of 500 individuals recently treated or being treated for breast cancer (the ‘cases’) with 500 patients with no past history of breast cancer (the ‘controls’). These data were obtained from six hospitals in London and three in Glasgow. She used age at marriage as a proxy for age at first pregnancy. In the 1920s that was a reliable proxy; today it would not. That information produced one of her key findings: the higher the age at first pregnancy, the higher the risk of breast cancer later in life. These findings were confirmed by independent studies in the U.S.A. Her data were reanalysed in 2010. The conclusion was clear:
Findings from the quantitative reanalysis were consistent with contemporary epidemiologic evidence for age at menopause, parity, age at first birth, and duration of lactation.
Those of us not in the cancer field—or even those who were but who were not familiar with epidemiological studies—but who were working on the normal mammary gland in the latter quarter of the 20th century were not aware that research earlier than that led by Brian MacMahon (1923-2007) at Harvard had been done, let alone been re-confirmed. Although MacMahon did refer to Lane-Claypon in his papers, the impression gained from a talk he gave at a Gordon Conference I attended was that the finding of an association between age at first pregnancy and the incidence of breast cancer was not just an important finding but a novel one.
The impression that MacMahon had demonstrated something new clearly persists. For example, Wikipedia’s entry on MacMahon:
His best-known research relates to breast cancer. An international study, published in 1970, on which MacMahon was the lead author showed for the first time that the age at which a woman first gives birth significantly affects her risk of later developing breast cancer; giving birth at a young age was found to be protective. Subsequent work by MacMahon's group showed that every year a woman delays giving birth after the age of eighteen increases her risk of developing breast cancer by 3.5%. The 1970 study stimulated later research into hormonal causes of breast cancer.
In addition to the ‘for the first time’ I have underlined those who studied the hormonal control of breast cancer in the 1940s, 50s and 60s will either be rotating at high speed in their graves, rattling their ashes in their urn or guffawing from their wheelchairs if reading that last sentence. Sir George Beatson (1848-1933) may also have had something to say for he discovered the link between the development of breast cancers and the ovaries before hormones and oestrogens from the ovary had even been thought about.
What MacMahon’s results did stimulate was an interest in trying to find the mechanism by which early first pregnancy is protective. They came at a time of a major increase in funding for cancer research in the U.S.A.—President Nixon’s ‘war on cancer’ was launched by the National Cancer Act of 1971. Fifty years later that search continues but as in many aspects of breast cancer research there has been activity but, I would argue, relatively little progress given the resources made available by governments and charities.
Lane-Claypon also detected from her data that breast cancer sometimes runs in families. In 1994 and 1995, nearly seventy years after her report was published, two of the genes responsible for the inherited propensity, BRCA1 (for BReast CAncer gene) and BRCA2, were discovered.
But Janet Lane-Claypon had not started out as an epidemiologist. Her first research was in physiology at University College London. And her foray into breast cancer in the 1920s was not her first research on the mammary gland. She worked on the hormonal control of the mammary gland with Ernest Starling, co-discoverer of the first hormone, and one of the great, even, arguably, the greatest, physiologist of his day. The paper they wrote in 1906* from work done in 1904-05 has rarely been cited probably because it was, with hindsight, overambitious and ended in uncertainty. However, a key finding was not explained until over 50 years later. Like in her work in epidemiology, Lane-Clayton developed a new technique to examine and stain the mammary glands of rodents and lagomorphs for histological examination. It has been used ever since, although its originator has rarely been cited†.
Lane-Claypon and Starling were looking for a hormone that controlled lactation. They did not know—and could not have known at the time—that a number of different hormones are now known to be involved in controlling mammary growth and milk secretion. However, their basic hypothesis, that a hormone is first responsible for the growth and development of the mammary gland and then, as it disappears at birth of the offspring, triggers the onset of milk secretion is basically correct if hormones in the plural are substituted for hormone. It is the dramatic fall in the concentration of one, progesterone, which is, along with other hormones involved in mammary development, and is at high concentrations in the blood during pregnancy, that triggers the onset of copious milk secretion around the time of birth of the young.
In their search for the source of hormones that could cause mammary development they injected various tissue extracts into rabbits. The results of individual experiments were reported but the results were difficult to interpret, as they wrote, because the amount of material they had was inadequate. The length of treatment, site of injection, method of preparation and amount of extract varied, while the group sizes were very small. Having found no effect with aqueous extracts of ovary, uterus or placenta, they did a series of experiments involving longer treatments using fetal, placental and uterine endometrium. Some of these extracts, notably those of fetus and placenta clearly caused mammary development.
They then suggested that their active substance produced possibly by the fetus and transferred to the mother’s circulation through the placenta could not in fact be the only hormone involved since previous workers had show that the presence of the ovary was also necessary. They also plumped for the fetus as the site of production of their active substance since in their experiments extracts of placenta alone had no effect in three rabbits. In that they differed from a previous report on the effects of placental extracts. That conclusion was later proved to be wrong; the placenta is the source. However, the results which showed the presence of something interesting was largely ignored as the rôles of the hormones of the pituitary emerged and received most of the attention. Only after the discovery of placental lactogens in the 1960s could Lane-Claypon and Starling’s admittedly incomplete results be explained. Their paper, as hormones were discovered and the sequence of events leading to mammary development and the onset of milk secretion worked out, fell by the wayside. But as an early illustration of the presence of placental lactogens it appears along with other early work in Lothar Hennighausen’s and Gertraud Robinson’s review of mammary development which relates research done in the early 1900s to advances made since in the 1960s.
The paper with Lane-Claypon was Starling’s only foray into the physiology of the mammary gland.
Janet Elizabeth Lane-Claypon was born on 3 February 1877 in Boston, Lincolnshire. She was not born with that surname because later that month her father, a banker, first-class cricketer for Cambridge University and Surrey, and local magistrate, changed his name from William Ward Claypon Lane to William Ward Lane-Claypon. She was educated at home, University College, London (first-class honours in physiology in 1902 and DSc in 1905 (these were the days before the PhD) and at the London School of Medicine for Women (now the Royal Free); she became medically qualified (MB, BS) in 1907. She was awarded the MD degree in 1910, thus becoming one of those very rare beasts to have research degrees in both science and medicine.
She had various jobs and roles in London over a period of 30 years, including medical practice at hospitals in London and Essex. She travelled around Europe in 1908 on a Jenner Research Scholarship of the Lister Institute. There she studied services for mothers and infants. She was lecturer in physiology and hygiene at Battersea Polytechnic in 1910-12 and then, from 1912 to 1916, Assistant Medical Inspector at the London Government Board. It was there that she compared the nutritive value to infants of breast milk and boiled cow's milk. She obtained data in Berlin and introduced new methods and statistical procedures to epidemiology. The report was published in 1912. Her work was being noticed and one of the first decisions taken by the newly established Medical Research Committee (which later became the Medical Research Council) was to commission a report by Lane-Claypon on the hygiene of milk; that was published in 1916.
Until asked to report on breast cancer, Lane-Claypon worked on and wrote about health and welfare policies for women and children including advocacy of the German system of poor-law for Britain. She also proposed major changes in the training and status of midwives as well the greater provision of antenatal services to reduce infant and maternal mortality.
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| From an article in The Sphere of 9 December 1922 on the Household and Social Science Department |
In 1916 she was appointed Dean of the Household and Social Science Department at King's College for Women. This department was the sole occupier of a new site in Kensington. A few years after Lane-Claypon’s departure it became an independent college and was renamed as Queen Elizabeth College in 1953. Her time there was not a happy one. Throughout, she had poor relations with the committee responsible for the place. The chairman was described as a ‘despot’ and ‘master of biting sarcasm' much of it 'directed quite openly at the Dean. By 1923, Lane-Claypon had had enough. She resigned during a period of financial difficulties and threats of a reorganisation that would have reduced the College’s autonomy. She wrote: 'I should have been able to continue, had it not been for the difficulties which have been created by the attitudes of certain members of the Executive Committee’. She returned to the Ministry of Health, and that is when her seminal contributions to breast cancer began.
Janet Lane-Claypon was active in the Medical Women's Federation and, in 1920, was one of the first female magistrates to be appointed; she was on the bench for the London borough of Kensington in 1922. She was a member of the Women's Subcommittee of the Advisory Council to the Ministry of [Postwar] Reconstruction in 1918, and vice-president and president of the Women Sanitary Inspectors And Health Visitors Association between 1918 and 1920.
In August 1929 came what the newspapers described as a surprise to their colleagues. At the age of 52, Janet Lane-Claypon married the Deputy-Secretary at the Department of Health, Edward Rodolph Forber. The same newspapers reported that after the ceremony on a Friday the couple were both back working at their desks in the Ministry of Health after the weekend. Forber was 53; his first wife had died in June 1928. The newspapers may have deemed it a surprise but colleagues knew that the liaison had developed during Forber’s wife’s long and terminal illness.
The new Dr Forber was obliged to resign from the civil service on her marriage and thereafter seems to have disappeared from the medical and scientific scene. We do not know if she was pleased to retire in her early fifties or if she was not.
After their marriage Forber was promoted in the civil service and became chairman of the Board of Customs and Excise and then of the Inland Revenue. He was knighted (KCB) in 1932 and Dr Janet Forber became Lady Forber. The Forbers lived in London and for a time (certainly 1939-1942) at a house, Ragged Lands, in Glynde, East Sussex. They later moved 9 miles to Bishopstone Manor, near Seaford. By 1959 they were living in a flat at Seaford. Edward Rodolph Forber died in 1960. Janet died at Seaford on 17 July 1967.
I end with a question: have we done enough to recognise Janet Elizabeth Lane-Claypon’s seminal work in the early decades of the 20th century?
*Lane-Claypon JE, Starling EH. 1906. An experimental enquiry into the factors which determine the growth and activity of the mammary glands. Proceedings of the Royal Society B 77, 505-522.
†Catherine Hebb and Jim Linzell did refer to and use Lane-Claypon’s method in their paper, Innervation of the mammary gland. A histochemical study in the rabbit, published in Histochemical Journal in 1970.
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