A matter of life and death (especially death)

Thus said Matthew Prior, writing 300 years ago, and the aphorism is timeless. What has changed is the public cost of staying the Grim Reaper’s hand that extra day. Stephen Hall’s story concerns the immunotherapy of cancer, and a mesmerising read it is. His dramatis personae range from the wholly admirable to quite a number who one would not wish to meet in an alley on a dark night. The narrative begins with the New York cancer surgeon, William Coley. This single-minded loner observed, around the turn of the century, that patients in the terminal stages of some cancers who were visited by erysipelas infections seemed on occasion to make unaccountable recoveries. Pursuing this lead with fanatical fervour, Coley eventually developed a bacterial toxin preparation, which, if it did not kill, sometimes seemingly cured. As he became more messianic in promoting his treatment, so the hostility of the medical establishment grew and after his death no one was willing to carry the torch. Coley, as we now know, had hit on adjuvant therapy, which almost certainly worked, at least for some sarcomas. The rise of cellular immunology brought with it renewed interests in the prospects for immunotherapy. With the arrival of the interferons, an ominous interest stirred in the boardrooms of the pharmaceutical companies and, as more and more cytokines came to light, a frenzy of activity arose in all branches of the cancer business. And cancer, as Albert Szent-Györgyi famously observed, was already coming close to keeping more people alive than it killed. When Carswell and Old isolated tumour necrosis factor and observed its startling effect on sarcomas in mice they worked for several years more before publishing their results. That was in 1975 and few of those who followed showed such scrupulous restraint. A new breed of clinical researchers had emerged, more concerned to get the latest factor into a hapless patient — usually with appalling side-effects — and claim a first than to establish by painstaking trials whether it actually did some good. An important part of research in this area consisted (and still does) of manipulating the committees that stand in the way of heroic experimentation on the sick. The technique is commonly to denounce these who weigh the arguments while patients are dying. Equally important in committee is to get a thumb in the eye of a rival. One of the players in this game put the matter to Stephen Hall with selfrevealing candour: “The only way to get there first is to make sure nobody else gets there first.” When yet another dramatic claim was heralded in Time, a leading molecular biologist, invited to comment, opined that it was as well the protagonists had given their press conference without waiting for the outcome of the experiment, for otherwise there would have been nothing left to report. Gene therapy, into which cancer immunotherapy has partly merged, has been no more successful and no less ferociously puffed. The eruption onto the scene of the biotechnology industry has compounded the mischief, for neither the companies nor their backers are generally reconciled to a five-year wait to determine whether extravagant claims are matched by survival statistics: months is more the time-scale on which the profit motive operates. A rapacious industry, a voracious press and a raging desire for share options and more especially for that handshake with the King of Sweden make an explosively rich mixture. Concluding his chapter on interferon, Hall reflects that “... from a Dickensian point of view, the story of interferon has evolved into a fascinating tale of biological paupers and princes, of graduate students who became millionaires and visionaries who did not.” Honourable members of this last group were Jean Lindemann, who with Alick Isaacs discovered interferon in the first place, and Kari Cantell, who played such an indispensable part in purifying α-interferon and producing it on an unheard-of scale and made it and his skills available to all comers. Asked why he had received no reward from those who are now selling the stuff to the tune of $500 million annually, he replied “They did not offer, and I did not ask.” There is surely here a conflict of cultures. A drug in more innocent days used to be defined as a substance that, when injected into an animal or a patient, produces a paper. Now it has not earned the name if it does not rather produce $10 billion. One of Stephen Hall’s informants asked a pharmaceutical rep why the recommended dosage for an Magazine R3