The Polyposis Registry represents one of the longest running research projects in the world
1924 to 1948
The Polyposis Registry was founded in 1924 when the pathologist at St Mark’s, Dr Cuthbert Dukes, began to collect data with his young assistant, the then 17 year old Dick Bussey (later Dr Bussey). By the 1940s enough information had been recorded to establish that the condition, polyposis, was inherited in a dominant fashion and what had started as a register of patients with multiple polyps and a family history of bowel cancer became the first Polyposis Registry in the world. Throughout this period St Mark’s hospital was funded by charitable donations for people who could not afford to pay to see a doctor. Patients would queue up outside the gate to be seen in the out-patient clinic on a first come first served basis; the gate was opened for a limited period. Most people with polyposis would already have bowel cancer by the time they felt ill enough to pay a visit to the hospital. Major surgery during this period was a risky business; surgeons had to operate quickly and would only remove a bowel cancer if it were in the early stages of development. The remainder of the colon would be left along with the polyps and over time another bowel cancer would usually develop. From the records collected at this time it is known that the average age of a person, with what is now called familial adenomatous polyposis (FAP), developing bowel cancer is just 39 years.
1948 to 1958
By 1948 enough had been learned about post-operative shock and blood transfusions to allow major surgery to be carried out safely. Also around this time the NHS was established making it easier for people to seek medical help. Mr Oswald Lloyd Davies, a surgeon at St Mark’s, decided to try to prevent bowel cancer developing in young people with adenomatous polyposis by removing the colon and joining the small bowel to the rectum (colectomy with ileorectal anastomosis, known as an IRA). He thought that, even with the basic form of sigmoidoscope in use at that time, he would be able to monitor the polyps that continued to develop in the rectum and cauterise them before they progressed to cancer. Many of his colleagues disagreed with him and said that his patients would develop cancer in the rectum. This disagreement led to Dr Dukes and Dick Bussey extending the data they recorded to include the details of the surgery, the results of subsequent examinations and treatments and all other major illnesses. During the 1950s, surgeons other than Mr Lloyd Davies had become convinced that the IRA was the right treatment for patients with adenomatous polyposis and a “call up” programme was started. Letters would be written to patients asking them about their relatives and advising them to attend hospital for an examination. Sometimes Dr Dukes and Mr Henry Thompson, another St Mark’s surgeon, would go to the patients’ homes to try to convince them and their relatives to be examined.
In 1958 Dr Dukes made this statement:
“It would be difficult to find a more promising field for the exercise of cancer control than a polyposis family, because both diagnosis and treatment are possible in the precancerous stage and because the results of surgical treatment are excellent.”
Dr Basil Morson became the Consultant Pathologist at St Mark’s when Dr Dukes retired and, like Dr Dukes, he was fascinated by polyps. The Polyposis Registry flourished and grew.
1958 to 1978
During this period the work of the Registry became known both nationally and internationally through regular publications in various medical journals. This resulted in more patients with polyposis being referred to St Mark’s from all over the UK. Doctors from around the world, many of whom had visited St Mark’s, set up a Polyposis Registry themselves with the Swedish and Danish registries being two of the first to follow St Mark’s example.
By this time it had become clear that there was more than one type of polyposis. Microscopes and the methods of preparing pathological slides for examination of the polyps had improved and in addition to adenomatous polyposis, Juvenile Polyposis and Peutz Jeghers Syndrome were described. In the Registry the phenotypic features of the different types of polyposis were recorded. In 1970 the laboratory assistant known as “Bussey” became Dr HJR Bussey when he was awarded a PhD for his work on adenomatous polyposis. With the increased workload Dr Bussey needed help and was joined by Dr Sheila Ritchie who worked with him on a voluntary basis.
Sir Alan Parks, a surgeon at St Mark’s at this time, had little interest in polyposis as such but his work was to have a major impact on patients with FAP. He developed an operation most commonly known as “the pouch operation”, mainly for patients with ulcerative colitis. When this condition was very severe and it became necessary to remove the colon and rectum, by forming an internal pouch from the small intestine it was possible to treat these patients but avoid the need for a stoma. He soon realised that it was the perfect solution for patients with FAP when the polyps in the rectum became too large or numerous to control. In order to avoid the development of cancer it was advisable that the rectum should be removed. The first patient on the Registry database to have the pouch operation for FAP was in 1977.
1978 to 1998
This twenty-year period was eventful for St Mark’s, the Polyposis Registry and patients with FAP. Although the number of patients with Juvenile Polyposis Syndrome and Peutz Jeghers Syndrome attending St Mark’s was gradually increasing the number of patients with FAP was much larger by far. In 1984 Kay Neale, a registered nurse, joined the Registry staff funded by the Imperial Cancer Research Fund (ICRF, later Cancer Research UK). She had already worked at St Mark’s as a research nurse for ten years so knew Dr Bussey, who was now 77 years old, quite well. One day she told him that when Dr Morson approached her to suggest that she might consider working in the Registry he had said that someone needed to find out how the department was organised and what was in Dr Bussey’s head. “Dr Bussey is getting old and one day he will go under a bus” he said. Dr Bussey laughed when he heard this and said that something similar had been said to him about Dr Dukes many years before but it had been suggested that Dr Dukes would “go under a taxi” indicating that Dr Dukes was of a different class.
In 1985 St Mark’s celebrated its sesquicentennial and doctors from all over the world who specialised in colorectal disease came to London for a week long meeting at the Barbican Centre. This presented a perfect opportunity for Sir Ian Todd to invite a small group of about 30 doctors who specialised in polyposis to an extra one and a half day meeting over the weekend at the end of the main event. The meeting was held at Leeds Castle in Kent and the purpose was to discover if anyone knew how to treat desmoid tumours, a rare growth, occasionally life threatening, which affects about ten percent of people with FAP. At that meeting, the St Mark’s doctors learned that no one knew more about polyposis or desmoid tumours than they did. It was agreed that it would be good to find out how many patients with the different types of polyposis and the rare associated conditions there were around the world. The St Mark’s Registry staff agreed to send out questionnaires and the group agreed to meet again in 1987. This group became known as the Leeds Castle Polyposis Group and continued to meet every two years until 2005 when it merged with a group interested in a form of hereditary bowel cancer without the polyps. This new group was called the International Society for Gastrointestinal Hereditary Tumours, known as InSiGHT, and in 2010 became a registered company and charity.
Around this time Dr Morson, who was Director of Research at St Mark’s and, therefore, the informal Director of the Registry was contemplating his retirement. It occurred to him that in order to safeguard the future of the Polyposis Registry it needed to become a formal hospital department. Mr James Thomson, a surgeon with many patients from polyposis families and an interest in the condition agreed to become the first Director. Headed paper was printed with the red St Mark’s Lion at the top and the names and degrees of the staff at the bottom. To this point it was made clear to the staff in the Registry that the patients were the responsibility of the doctors and even though they were writing to patients and GPs giving advice regarding the advisability of screening, they had not been allowed to sign their own letters; a signature from one of the doctors had to be obtained. Now, with headed paper and names at the bottom, Dr Ritchie decided that enough was enough and the person who wrote the letter would sign it. Another great step that arose as a result of Dr Morson’s decision to give the Registry autonomy was that it was allowed to have it’s own account under the umbrella of the Research Foundation. Patients often gave donations which were put into the general fund but which the Registry had little access to.
In 1989 Sheila Ritchie retired. She had given at least twenty years of voluntary service to St Mark’s, having been responsible for the St Mark’s library before moving to the Registry. Her knowledge of polyposis was equal to that of Dr Bussey and she was vital to the process of computerisation. She was fiercely protective of the patients, always making sure that research projects were worthwhile before agreeing to help enrol them. In the early 1980s, St Mark’s collaborated with Professor Jerome DeCosse from Memorial Hospital in the USA to carry out the ascorbic acid (vitamin C) trial. The patients who agreed to take part in the trial had to be examined every six months to find out if the number of polyps in the rectum had changed as a result of taking the tablets. Professor DeCosse would come to London every three months to examine half of the group taking the pills, some of which were Vitamin C and some placebo. It was Sheila who recognised the benefit of arranging for families to attend hospital together and the reassurance they found in meeting other families with the same, rare, condition. As a result she arranged for the consultants to hold “polyposis weeks” after the trial had finished. Each consultant’s clinic in the last week of January, April, July and October would book patients from polyposis families only. The patients were extremely fond of her and many continued to send her a Christmas card, years after her retirement.
Dr Morson persuaded the St Mark’s Hospital Foundation to allocate funding to appoint Judith Landgrebe to help to continue the work of the Registry. Judith did not have a medical background and immediately set about gaining a masters degree in counselling psychology. She obtained distinction in the Open University genetics course and having passed the genetic counselling course was invited back to lecture on polyposis.
In 1991 the exaction location of the APC (adenomatous polyposis coli) gene was indentified by Sir Walter Bodmer’s team at ICRF. The Registry had been collaborating with them for many years by sending blood samples from well established families but there was more work for the scientists to do before this discovery became of use.
To be continued…..thanks to Kay Neale for writing this history. Watch Kay talk about The Registry and working with families.