- Email: [email protected]
John Double
DISSECTING ROOM
LIFELINE John Double John Double’s training was in biology, biochemistry, and pharmacology. He has been involved in anticancer drug development for 37 years. He is director of the Cancer Research Unit at the Tom Connors Cancer Research Centre, University of Bradford, Bradford, UK. Who was your most influential teacher, and why? The late Tom Connors taught me about the basic concepts of therapeutics—true benefit can only be achieved by producing drugs that are selectively toxic to cancer cells at well tolerated doses and also have good pharmacological properties. What would be your advice to a newly qualified doctor? Make sure you understand the “politics” and get involved if you can. It is the only way you can influence the way the profession is run. What alternative therapies have you tried? Did they work? Chiropractic treatment has been very successful in curing various sporting and gardening injuries. Do you believe in capital punishment? Yes. What do you think is the most exciting field of science at the moment? Molecular biology—our increasing knowledge of the fundamental mechanism of life brings real hope of finding cures for many diseases, especially cancer. Do you apply subjective moral judgments in your work? Yes, particularly in the area of animal ethics. We have a real responsibility to use animals in the most humane way possible for the development of new therapeutic strategies for diseases in man. What do you think is the greatest political danger to the medical profession? Widening access to medical school will lower standards, there is nothing wrong with promoting and maintaining excellence. Where were you in your sibling order, and what did you gain or lose as a result? I am the eldest, my brother has severe learning difficulties—he has given me a real understanding of the needs of those less fortunate than myself.
1182
Just say no n the basic books of many religions, the “do nots” are quite abundant and they often cover a whole range of common activities. But do not worry; I am not about to remind you of any of them, or add to any antidrugs or prosexual-abstinence campaigns. I just want to stress the many charms of negative propositions. Let’s start with the basics. Do you recall all the fuss about the problems of introducing a division by zero in your school arithmetic? Infinity was a possible result, but not an easy one to handle. Better follow the advice of a book on mathematics that simply states that “division by zero, as it leads to inconsistencies, is not permitted”. Voilà! no dog, no rabies. And what about physics? Physicists seem naturally to be rather serious people. How do they react to negative propositions? At none other than the Institute for Advanced Studies in Princeton, USA, one physicist is known to have stated after a seminar: “Wonderful! Everything we knew about physics last week is not true”. Negatives can bring happiness. If these things happen in the world of mathematics and physics, the results of a recent study about the survival of the truth of clinical conclusions in published papers ought not to surprise you. In this article, the authors surveyed original articles and metaanalyses published from 1945 to 1999, about cirrhosis or hepatitis in adults, and assessed how many of their findings were still true in 2000. Whatever the half-life of truth was in this series, an important point is that negative conclusions had a significant survival advantage. Only 2% of negative results were rated obsolete, compared with 25% of positive conclusions. Hurrah for the negatives. The charms of negative results have reached the editorial world and a group of editors is said to be working on the launch of a web journal of negative results in biomedicine.
I
Submissions are already being collected at http://www.biomedcentral.com and the venture is expected to be a great success. No wonder. The beauties of negative propositions have not escaped those who make it their business to give advice. To recommend avoidance of what is new seems always safe. Check hospital therapeutics bulletins and you are likely to find such statements as “not enough data are available”, or the more insidious “we are not aware of”. Curiously enough, years ago, a famous, and quite valuable, publication was presumed to make its recommendations on the basis that the only clinical trials that are well designed are those that give negative results. Of course, there is a mirror image in the pharmaceutical industry; new drugs are supposed not to induce any side-effects, and a new drug is always better than the product it replaces. But in the modern pharmaceutical world of mega-mergers and the like, there are times when saying no is a sure path to success in certain management spheres. For instance, if you sit at a drug development board it is best to say no to any proposal, especially if you do not understand what they are talking about. By saying no, everybody will respect your high standards and your prestige will be given a boost. A similar tactic can be used if you work for any public health office; stating that there are not enough data will never harm you, and your saying no will always be perceived as a wish to protect the public. Is there a better goal for a public servant? Finally, if your management world is limited to a simple hospital or care centre, a negative response to any request for money, for whatever purpose, right or wrong, is the best path to promotion. But then again, perhaps you should also say no to promotion? Sergi Erill
THE LANCET • Vol 360 • October 12, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
LIFELINE John Double John Double’s training was in biology, biochemistry, and pharmacology. He has been involved in anticancer drug development for 37 years. He is director of the Cancer Research Unit at the Tom Connors Cancer Research Centre, University of Bradford, Bradford, UK. Who was your most influential teacher, and why? The late Tom Connors taught me about the basic concepts of therapeutics—true benefit can only be achieved by producing drugs that are selectively toxic to cancer cells at well tolerated doses and also have good pharmacological properties. What would be your advice to a newly qualified doctor? Make sure you understand the “politics” and get involved if you can. It is the only way you can influence the way the profession is run. What alternative therapies have you tried? Did they work? Chiropractic treatment has been very successful in curing various sporting and gardening injuries. Do you believe in capital punishment? Yes. What do you think is the most exciting field of science at the moment? Molecular biology—our increasing knowledge of the fundamental mechanism of life brings real hope of finding cures for many diseases, especially cancer. Do you apply subjective moral judgments in your work? Yes, particularly in the area of animal ethics. We have a real responsibility to use animals in the most humane way possible for the development of new therapeutic strategies for diseases in man. What do you think is the greatest political danger to the medical profession? Widening access to medical school will lower standards, there is nothing wrong with promoting and maintaining excellence. Where were you in your sibling order, and what did you gain or lose as a result? I am the eldest, my brother has severe learning difficulties—he has given me a real understanding of the needs of those less fortunate than myself.
1182
Just say no n the basic books of many religions, the “do nots” are quite abundant and they often cover a whole range of common activities. But do not worry; I am not about to remind you of any of them, or add to any antidrugs or prosexual-abstinence campaigns. I just want to stress the many charms of negative propositions. Let’s start with the basics. Do you recall all the fuss about the problems of introducing a division by zero in your school arithmetic? Infinity was a possible result, but not an easy one to handle. Better follow the advice of a book on mathematics that simply states that “division by zero, as it leads to inconsistencies, is not permitted”. Voilà! no dog, no rabies. And what about physics? Physicists seem naturally to be rather serious people. How do they react to negative propositions? At none other than the Institute for Advanced Studies in Princeton, USA, one physicist is known to have stated after a seminar: “Wonderful! Everything we knew about physics last week is not true”. Negatives can bring happiness. If these things happen in the world of mathematics and physics, the results of a recent study about the survival of the truth of clinical conclusions in published papers ought not to surprise you. In this article, the authors surveyed original articles and metaanalyses published from 1945 to 1999, about cirrhosis or hepatitis in adults, and assessed how many of their findings were still true in 2000. Whatever the half-life of truth was in this series, an important point is that negative conclusions had a significant survival advantage. Only 2% of negative results were rated obsolete, compared with 25% of positive conclusions. Hurrah for the negatives. The charms of negative results have reached the editorial world and a group of editors is said to be working on the launch of a web journal of negative results in biomedicine.
I
Submissions are already being collected at http://www.biomedcentral.com and the venture is expected to be a great success. No wonder. The beauties of negative propositions have not escaped those who make it their business to give advice. To recommend avoidance of what is new seems always safe. Check hospital therapeutics bulletins and you are likely to find such statements as “not enough data are available”, or the more insidious “we are not aware of”. Curiously enough, years ago, a famous, and quite valuable, publication was presumed to make its recommendations on the basis that the only clinical trials that are well designed are those that give negative results. Of course, there is a mirror image in the pharmaceutical industry; new drugs are supposed not to induce any side-effects, and a new drug is always better than the product it replaces. But in the modern pharmaceutical world of mega-mergers and the like, there are times when saying no is a sure path to success in certain management spheres. For instance, if you sit at a drug development board it is best to say no to any proposal, especially if you do not understand what they are talking about. By saying no, everybody will respect your high standards and your prestige will be given a boost. A similar tactic can be used if you work for any public health office; stating that there are not enough data will never harm you, and your saying no will always be perceived as a wish to protect the public. Is there a better goal for a public servant? Finally, if your management world is limited to a simple hospital or care centre, a negative response to any request for money, for whatever purpose, right or wrong, is the best path to promotion. But then again, perhaps you should also say no to promotion? Sergi Erill
THE LANCET • Vol 360 • October 12, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.