Chris Potten passed away on 3 August, 2012, as a result of pancreatic cancer. He will be remembered as a pioneer of epithelial and stem cell biology, using radiation as a tool to unravel the mechanisms of tissue renewal and response to injury. Chris started his research career with studies of the radiation responses of different cell populations in mouse skin, obtaining a PhD degree under the supervision of Dr Alma Howard in Manchester and Prof. Jack Fowler in London. He then changed the prevailing view in the 1960s that all cycling cells in epithelia were regenerative cells, by providing clear evidence of a hierarchical cell lineage. In 1974 he described the epidermal proliferative unit (EPU) in mouse epidermis. The EPU consisted of a central stem/clonogenic cell surrounded by three divisions of transit cells all in the basal layer, and above that a stack of differentiating cells with senescing squames at the top. That lineage nicely explained the short latency for UV-induced sunburns (sensitive transit cells) versus the much longer latency for X-ray induced skin reactions (resistant transit cells). Also, he did very detailed studies of radiation effects on melanocytes and hair follicles, and in addition he described the proliferative and structural organization of the filiform papilla of the tongue. The skin studies culminated in his book Radiation and Skin (1985), and later his proposed use of hair follicles/hairs as a biological dosimeter and for assessing the differing radiosensitivities of radiotherapy patients.
Chris moved on to study the gastrointestinal tract where his work led to the identification and characterization of stem cells and their dependent lineages in the small and large intestine, and an understanding of the biological significance of apoptosis in the control of stem cell homeostasis and cancer incidence. He was the first to show that the few stem cells were located at cell position 4 (often called cp4 cells – also his initials!) from the base (above the Paneth cells) in small intestinal (SI) crypts, and at the base in the large intestine (no Paneth cells). Many years after this, some authors were still reporting unrealistically high numbers of regenerative cells per crypt, but now the prevailing view is the Potten view. In recent years he responded to suggestions of a more primitive stem cell at lower cell positions in the SI by reminding readers that in epithelia movement is unidirectional, and based on a vast amount of previous evidence it was hard to envisage two-way trafficking. He was the first to investigate and provide supportive evidence for the immortal-DNA-strand hypothesis of John Cairns, whereby the parental DNA template was retained during stem cell divisions so that their mutational load was kept low. Also he provided a biological explanation, based on differential p53/bcl-2 expression and propensity for apoptosis to delete mutated cells, for the lack of cancers in the small intestine and their presence in the large intestine.
Later he was also actively engaged in an ongoing multidisciplinary study investigating the role of cellular hierarchies, hormones, dietary factors, and extracellular matrix proteins on cell proliferation, apoptosis and carcinogenesis in the breast.
All the above work was done at the Paterson Institute for Cancer Research at the Christie Hospital, Manchester, UK, where for 29 years he led a research team in Epithelial Cell Biology with many collaborators. He was awarded a Life Fellowship from the Cancer Research Campaign (now Cancer Research UK) in recognition of his work, and he received the International Marie Curie and Weiss medals for services to radiation research. He was an advisor to the European Space Agency and a visiting Professor at several universities. During his career Chris supervised 18 PhD students and 10 MD students, and many of these are now Professors themselves. He was a prolific writer and exponent of his field, publishing over 400 scientific papers and 11 books. He was also Chief Editor of the journal Cell and Tissue Kinetics (1988–2003), which included changing its title to Cell Proliferation in 1991.
Chris retired from the Paterson Institute in 2000, and then he decided to put all his energies into the co-founding of the company Epistem Ltd (www.epistem.co.uk) based at the University of Manchester. Various scientists have formed companies, but few have been very successful. Chris was extremely successful in forming Epistem Ltd as it went from strength to strength, and now employs 60 people including members of his Paterson group. He was able to make use of his extensive knowledge of renewing cell systems and their response to cytotoxic agents, in order to provide a testing service to the pharmaceutical industry. He said he wished he had started the company earlier because he enjoyed it so much.
When the company was fully operational, Chris further expanded the arena of the company's activities. In 2006, Epistem Ltd became a major partner in a unique endeavour, a National Institutes of Allergy and Infectious Diseases (NIAID)-funded US Consortium centred at the University of Maryland, USA. The Consortium, Medical Countermeasures Against Radiological Threats (MCART) has been charged with developing medical countermeasures against hematopoietic, gastrointestinal (GI) and lung sequelae. Epistem was the initial and cornerstone entry in MCART. Chris and his team focused on developing countermeasures against the GI acute radiation syndrome. Epistem continues to be the sole research site within the Consortium focused on mitigating lethal radiation effects in the GI system.
Chris reduced his activities in the company when shareholders were formed in 2007. In semi-retirement he remained Chief Scientific Advisor at Epistem and an honorary Professor in Manchester and Nottingham, UK. He also remained as an integral advisor to the MCART Consortium.
Chris's extensive and insightful work over four decades, including his classical papers of fundamental importance, will be referenced for many years to come by current and subsequent researchers. He will be sadly missed by his former colleagues at the Paterson Institute and those at Epistem, his many former students and collaborators worldwide, his wife Carol, and his sons Edward, Stephen and Michael from his first marriage to Sarah, who died earlier.