Howard Skipper

Pioneer of cancer chemotherapy

Howard Earl Skipper, biochemist: born Abon Park, Florida 21 November 1915; research scientist, Southern Research Institute 1946-81, Vice-President 1964-74, President 1974-81; married 1940 Margaret Edwards (died 1984; one son, one daughter); died Birmingham, Alabama 2 January 2006.

Fifty years ago, cancer chemotherapy was rudimentary and doctors felt that the idea held little promise. Howard Skipper's painstaking and brilliant animal work changed their minds. It was then thought that, if most cancer cells were removed or destroyed, the immune system would kill off the rest, as it did with bacteria, but Skipper also showed that it was necessary to kill every cancer cell in the body. He inspired people to think about cancer in new ways.

Skipper had an extraordinary capacity to take the larger view of things and to steer research in the right direction. He built up a superb research team who worked well together at the Southern Research Institute in Birmingham, Alabama, where he led the search for new drugs and the best ways of evaluating them.

His contributions and insights laid the foundation for modern chemotherapy. It is thanks to Skipper's work that childhood leukaemia is now usually cured. In 1974, when he received a Lasker Foundation award for basic science (a sort of mini-Nobel), the citation described how he

demonstrated the curability of cancer in several animal tumor model systems, and first introduced the concepts of total cell kill. His experimental work elucidated the logic of chemotherapy as an adjunct to surgery and has delineated the idea of prompt eradication of all evidence of disease.

Skipper increased our understanding of the biological, biochemical and pharmacological relationships between tumour cells, normal cells and anti-cancer drugs. He researched the best doses, intervals between doses, and treatment duration, and he showed that delivering drug combinations overcame the problem of resistance.

He would test compounds in mice with leukaemia, lymphomas and solid tumours as models of investigating human cancers. (He called himself a "mouse doctor.") When he found compounds that worked, he tested them in combination. This meant that their therapeutic effects were potentiated, but their side-effects were diffused.

Skipper discovered the mode of action of many drugs, and handed those that proved effective to the physicians. He constantly searched for the best methods of evaluating compounds, using mice with leukaemia. He found ways of measuring the sensitivity of resting and dividing cells, as cancer cells are more susceptible to chemical destruction when dividing.

Howard Skipper was born at Abon Park, Florida, in 1915. From Sebring High School he went to the University of Florida, graduating in biochemistry and nutrition and taking a PhD. In 1941 he joined the US Army for five years, conducting toxicology research, including an assignment to the British government in Australia. He left in 1946 with a commendation citation medal for research and the rank of lieutenant-colonel.

That year, Skipper joined the Southern Research Institute to establish its cancer research programme. This became the foundation for one of the world's greatest drug discovery programmes, funded by the US government and charitable foundations. When he was made president of the institute in 1974, he insisted that he did the job in name only, and continued his research. Although he retired officially when he was 65, he continued to work until 1989. He loved his work and his colleagues, and they loved him.

Howard Skipper was a modest and unassuming man, with a gentle but pointed sense of humour, who always shared the credit for discoveries with his colleagues. His hobbies were growing roses, playing the organ and cutting gemstones.

He disliked the format constraints of scientific papers, although he published 150. He wrote brilliant chemotherapy booklets for distribution to clinicians, and a chapter on chemotherapy in the book Cancer Medicine (1974).

Caroline Richmond

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