BSCB Newsletter, Summer 2001

Features

A distinguished career in cell biology: Chris Potten

Goblet cells in intestinal crypts. EpiStem, Chris Potten’s new company, is using growth factors and cytokines to modify stem cell behaviour in gut and oral mucosa.

Chris Potten retired from his position at the Paterson Institute for Cancer Research at the Christie Hospital in Manchester in November 2000, mainly to spend more time for other pursuits and his family. However, his involvement in science persists: he remains an Honorary Professor of Stem Cell Biology at Manchester University and is Chairman of EpiStem Limited, a biotechnology services start-up company. Joan Marsh visited him in his new office in Manchester’s Incubator Building to talk about aspects of his distinguished career and some of his hopes for the future.

Chris graduated from the University of London with a degree in Botany and Zoology in 1962. He then went to Guy’s Hospital to study for a Master’s degree in Radiation Biology and Radiation Physics. At that time there was a worldwide preoccupation with radiation, particularly the Manhattan project with which several of his advisors were involved. It was also shortly after the Windscale accident in the UK, which had demonstrated to the British Government that there was a need for radiation biologists. The government instigated a training programme and Chris was one of the first students. It was also the heyday for radiotherapy and there were many new developments in that area.

From Guy’s, Chris moved north to the Paterson Institute in Manchester to investigate the effects of radiation on the skin and hair follicles under the guidance of Alma Howard. "Alma was the first person to divide the cell cycle into phases: G1, S G2 and M, which was before the discovery of DNA structure by Watson and Crick. The Director of the Paterson was Laszlo Lajtha, a haematologist who was a pioneer in the study of stem cells in the bone marrow and the concept of G0. Laszlo’s enthusiasm for these ideas influenced Chris to develop similar concepts in epithelial tissues.

In 1968, Dr Potten went to the US, initially to continue his research on skin under Herman Chase at Brown University in Providence, RI. He then moved to Pittsburgh Hospital, where his interest started to broaden to include the intestine, in collaboration with the Director, Sam Lesher. The Director of the Paterson Institute kept a post open for Chris for three years and in 1971 he returned to found an epithelial biology group. This was built up from three people to twenty-six at its height. "We developed the concept of stem cells in the skin and the epidermal proliferative unit. We also devised models for the organisation and proliferation of cells in the intestine and identified and characterised the stem cells there. This was when the philosophical concept of a stem cell first became widely established."

After that, he says, "I gradually switched from the study of radiobiology to using radiation as a tool. It is very useful because it is a controllable and precise form of insult. Using radiation as a tool enabled one to study how stem cells responded and regenerated the tissue". For his work on radiation biology, Chris was awarded the Marie Curie Medal in 1998.

From cell birth to cell death

Epidermis, hair follicles and sebaceous glands

Chris was also one of the earliest people to work on apoptosis. The concept arose with Professor John Kerr, a pathologist from Brisbane, and Sir Alastair Currie in Aberdeen. Kerr spend a year with Currie in Aberdeen (later Edinburgh), when Andrew Wylie was a PhD student. They published their pioneering paper in 1972, but there was little worldwide interest at the time.

Two years later Dr Jeffrey Searle from the Pathology Department in Brisbane spent some time in Chris’ lab as a visiting scientist and worked on apoptosis in the intestine and skin, introducing Chris’s lab to the concept. "During the early 1970s, there were only three groups in the world interested in apoptosis — in Brisbane, Edinburgh and Manchester". Chris’s Nature paper in 1977 helped keep the field alive. The transatlantic scientists did not really accept the concept until the 1980s; then it took off.

One of Chris’s keynote papers in the apoptosis field was published in Carcinogenesis in 1992. "The hypothesis was that apoptosis among the stem cells in the small intestine constituted a protective mechanism that partially accounted for the absence of cancer in that large, rapidly proliferating tissue mass. In the large bowel, which has a similar structure but has a high incidence of cancer, the protective mechanism is compromised by the presence of the survival gene bcl-2."

Chris has also been continually involved in developing the concept and definition of stem cells and understanding the properties of adult tissue stem cells — a field in which he has an international reputation. A much quoted seminal paper on the topic of intestinal stem cells was published in Development in 1990, with a long time collaborator Professor Markus Loeffler. The issue of stem cells and their potential in curing disease is a current rapidly expanding field.

Chris spent at least three sabbaticals abroad, working with Renato Baserga at Temple University, with Howard Maibach, a dermatologist in sans Francisco, and in the Pathology Department in Brisbane with John Kerr. "My work spanned several scientific disciplines and I feel that the strength of my research group was its breadth of interest. However, I had a few run-ins with funding agencies which wanted a more focused approach."

Looking ahead
EpiStem opened its offices in the Incubator Building in January 2001, under the management of Chris and his colleague, Catherine Booth. "During my last few years at the Paterson, I was approached by several pharmaceutical or biotech companies that wanted to establish collaborative projects. The idea was to investigate the possibility of manipulating the sensitivity of epithelial and intestinal cells to protect them during radio- and chemotherapy." The major side effect of such treatments used to be bone marrow damage, but that has now been at least partially alleviated. The current limitations are due to oral and gastrointestinal mucositis.

EpiStem has been doing proof of principle studies, using growth factors and cytokines to modify the stem cell behaviour in gut and oral mucosa. Initially, it will act as a service company for the pharmaceutical and biotech sector, but they also plan to develop a research and development arm. The benefits that Chris Potten has brought to many aspects of biological study look set to continue for some time to come.

Joan Marsh