30 Mart 2017 Perşembe

Ken Harrap obituary

Ken Harrap, who has died aged 85, was a pioneer in the development of anti-cancer drugs. The research he directed over several decades in the UK resulted in the discovery of three registered cancer drugs, carboplatin, raltitrexed and abiraterone, an outstanding achievement.


When Ken was born there were no effective anti-cancer drugs and, except for patients in the early stage of the disease who could be cured by surgery, a diagnosis of cancer was a death sentence. Today, thanks to treatment in which his drugs play an important role, more than half of cancer patients can expect to be alive 10 years after diagnosis.


Ken’s drug development took place at the University of London Institute of Cancer Research (ICR), which he joined in the mid-1950s. The ICR had developed three early anti-cancer medications – busulfan, chlorambucil and melphalan – but they suffered from serious problems: their effectiveness was limited, they were toxic, and responses were often transient because of the development of resistance. In the mid-70s Ken brought together a team of chemists, biologists and clinicians to address these limitations.


As part of this work, he took over a collaboration with the technology firm Johnson Matthey that had been established by Tom Connors, a colleague at the ICR, and started work in 1976 on developing the drug carboplatin, which was comparable to the very effective but highly toxic chemotherapy medication cisplatin. Carboplatin retained the effectiveness of cisplatin but did not have the same serious side-effects – such as kidney toxicity, nerve damage, nausea and vomiting – that received wisdom maintained would be impossible to avoid.


Approved for medical use in 1986, carboplatin went on to be the top-selling anti-cancer drug worldwide at peak sales, benefiting millions of cancer patients. In 1991 Ken and his colleagues at ICR received the Queen’s award for technological achievement, for the development of carboplatin.


In another major project, conducted in collaboration with ICI Pharmaceuticals (now AstraZeneca), Ken’s team developed the new chemotherapy medication raltitrexed, a next-generation version of the early drug methotrexate. Raltitrexed has been used in the treatment of colorectal cancer since 1998, and a later version, pemetrexed, is now one of the world’s top-selling anti-cancer therapies.


One further drug discovered by Ken’s group, abiraterone, was licensed in 2011 and has become a major new treatment for prostate cancer. While the drug was discovered on his watch, it was only licensed well after his retirement.


In addition to Ken’s anti-cancer drug development, his earlier work on the biology of leukaemia was also groundbreaking, in that it foresaw the possibility of targeted treatments for haematological malignancies that were subsequently realised in breakthrough drugs such as imatinib.


Ken was born in Streatham, south London, to Lilian (nee Critchley), an embroiderer, and George Harrap, a bank messenger. He went to Woking grammar school and then George Green’s school in east London, and for a time during the second world war was evacuated to Wales. After school he trained as a chemist while working at the chemical company Hopkin & Williams in London, and in 1956 he joined the ICR, where his mentor was the Viennese professor Franz Bergel, who had been a student of the Nobel prize-winning chemist Heinrich Wieland. Wieland in turn had studied with the father of organic chemistry, Friedrich Wöhler, and Wöhler had worked under the German chemist Robert Bunsen. Thus Ken used to say that he could trace his scientific heritage in four generations back to the Bunsen burner.


Ken stayed at the ICR for the rest of his career, becoming head of applied biochemistry in 1970, head of biochemical pharmacology in 1977, director of the drug development section in 1982 and head of the Centre for Cancer Therapeutics in 1994, a position he held until his retirement in 1997. He became a professor of biochemical pharmacology in 1984.


His scientific management style involved hard work and leadership by example, but he was non-hierarchical and made science fun. He also clearly communicated a sense of direction, coupled with a light hand on day-to-day activity. This approach sometimes led to conflict between ambitious junior scientists, prompting him to mutter about “too many prima donnas”, but in truth he relished the atmosphere of creative anarchy.


The ethos in Ken’s lab was “work hard, play hard”. Among his non-scientific contributions to the life of the institute was his organisation of the fearsome annual men v women rugby match, and in later years he enjoyed a debased form of rugby known as jumbo, played on hands and knees, usually in a crowded bar-room, with a matchbox for a ball.


Those of his trainees who crossed over to commerce found that replication of his management style, especially his lack of respect for stuffed shirts, did not always go down well in the pharmaceutical industry (though he was a sought-after industry consultant). When, in the 1990s, the creative focus of drug discovery switched to startup biotech companies, for Ken’s people it was like coming home.


His main extracurricular interest was the sea: he was a member of the Island Sailing Club in the Isle of Wight, owned a succession of boats and, after a few years of racing, enjoyed cruising around the seas of the British Isles and France. He continued sailing until well into his 70s, when a knee replacement operation put a stop to it. He was made CBE in 1998.


Ken is survived by his wife, Beverley (nee Weston), whom he married in 1983, by two children, Kerry and Gwynne, from his first marriage, to Kathleen (nee Gotts), which ended in divorce, and by his granddaughters, Hannah and Sophie.


Kenneth Reginald Harrap, cancer researcher, born 20 November 1931; died 9 February 2017



Ken Harrap obituary

Hiç yorum yok:

Yorum Gönder