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Garnet Davey — the case for the pharmaceutical industry
N 14
DISCUSSION FORUM Should the industry control pharmaceutical research? Garnet Davey - the case for the pharmaceutical industry
Brian Inglis recommends
change
Brian Inglis is a journalist with a partitular interest in drugs as well as being the author of many books including
‘The History of Medicine’, ‘Drugs, Doctors and Disease’ and most recently ‘The Forbidden Game - a Social HistorJ I of Drugs’.
The custom that the pharmaceutical industry should be committed to the discovery of new drugs started, I suppose, because of the close association between Paul Ehrlich and the Bayer Company in Germany in the early part of this century. Spurred on by the success of salvarsan and neosalvarsan the initial emphasis was the discovery of new drugs utilizing the art of the synthetic organic chemist. Much later, with the advent of penicillin, the search for new drugs amongst natural products gained a new impetus and was added to the synthetic chemical approach. Until the Second World War chemotherapeutic research was dominated by the German and Swiss pharmaceutical companies, a fact which was deplored, in the U.K. at least, by several academic workers who were keenly interested in the subject. Their persuasion led the Medical Research Council in 1936 to decide to embark on a new major programme of research on chemotherapy, but to implement the decision a new building was necessary - hence the erection of the new National Institute for Medical Research at Mill Hill. The new institute was completed shortly before war started and the war, of course, upset many plans. What might have happened had there been no war in anyone’s guess, but the end of the war saw American, British and French pharmaceutical companies also committed to research to find new drugs and considerably lessening the former dominance of the German and Swiss companies. And so it has remained ever since. To pose the question, ‘Should the pharmaceutical industry control pharmaceutical research? suggests things are not well. Is this really so? No one, I am sure, would gainsay the fact that spectacular advances have been made. The isolation hospitals of my childhood, catering for scarlet fever and diphtheria, have disappeared; the tuberculosis sanatoria are put to other uses; pneumonia is no longer the scourge of the middle-aged and elderly that it once was; mental hospitals are far fewer than they might have been; most epileptics lead a relatively normal life; many ‘heart patients’ are no longer obvious invalids, etc. etc. The list is indeed a long one.
Let me begin by agreeing with Garnet Davey; nobody is likely to gainsay the fact that medicine has made spectacular advances since our childhood years. I must question the implication, though, that the credit should go to the pharmaceutical industry. It must be shared not only with individual investigators, but with men like Chadwick, who helped to convince society of the need for improved housing, sanitation and parks. As a result of their efforts, diseases like tuberculosis were in full retreat before ever drugs came on the scene to complete their rout. However, that is not to deny the industry credit for its achievements. In fact there is a sense in which it has been too successful. I have used before the analogy of Prince Rupert, sweeping the Roundhead wing before him in full retreat, but leaving Cromwell’s infantry in possession of the field. The infantry of illness - coughs, colds, flu, backaches, allergies, and the whole range of degenerative disorders - have not been brought under any sort of effective control by drugs. In fact the sickness rate appears to be actually higher than it used to be, even if the mortality rate has fallen. The criticism to which Davey objects, therefore - that diseases of small incidence get neglected, because it would not be prolitable to find and produce the cure - is of small importance compared to the failure of the industry to find and produce the cure for the common cold. This is not, needless to say, for want of trying. I am sure, too, that Davey is right when he points to the massive expense involved in such research. My objection is that I do not believe it represents the right research: the.right approach to finding how to cure - which, basically, means finding how to prevent - colds or any of the more serious disorders. Take the case of heart attacks. Huge sums have been lavished on the search for and the use of drugs to control hypertensioq, on anti-coagulants, and so forth. I happen to believe that it is largely money squandered: that what is needed is far man emphasis on the epidemiological,aspects, research to probe t* links with smoking, diet, lack of exercise and stress - pattiqularq
TIBS - January I9 76
N15
Garnet Davey
Brian Inglk
What then is wrong, or supposed to be wrong? I have heard three main criticisms of the present system. It is said first that drugs are more expensive than they need be ; second that diseases of small incidence, whilst possibly of tragic importance to the individual suffering from them, are neglected because the finan5al returns to industry would be too small: and third there is too much ‘me-too’ research and too many ‘me-too’ drugs. Let me deal briefly with these three points. It is true that the cost to the user of a new drug is considerably more than the cost of manufacturing the chemical compound which comprises the drug because someone has to pay for the research leading to the new drug, and the cost of this research is high. It is high because well-qualified scientists of various disciplines - biochemists, chemists, pharmacologists, toxicologists - are engaged in the team leading to discovery; because facilities-laboratories and laboratory, etc. equipment, animals, animal houses, animal technicians - ‘are expensive; because the research is intrinsically difficult and success is relatively infrequent, and because development of a new drug takes ieven to ten y$ars. I have said elsewhere that, starting from scratch, a company engaged in research to find a new drug might invest about f 100 million before getting any return. Regarding the supposed neglect of diseases of low incidence, this is an easy criticism to make but I have not heard it justified; that is to say I have not seen the list of diseases which are said to be neglected so that I might make some defence. I suspect that an important point might be forgotten by those who make this criticism and this is the fact that to discover in the laboratory a drug for a disease one must know or strongly suspect how the disease is caused because the drug is aimed to do something in particular. For example, I have been asked why my laboratory was not trying ot discover a drug for disseminated sclerosis, and I had to reply that we did not yet know how to begin to look. Some workers think that the disease might be an auto-immune disease, and others have suggested it is caused by a ‘slow’ virus. Basic knowledge must advance further before an intelligent search for a drug for this disease can begin. The third criticism, that there are too many ‘me-too’ drugs and too many companies pursue ‘me-too’ research can be made too glibly. What appear to be marginal differences in therapeutic effect or toxic action can be very important to large numbers of patients. A drug must be judged on its merits and not dismissed because it is similar to or very like another in chemical constitution. I should also point out that in these present times in which a potential drug progresses through its clinical development slowly, and under the constant surveillance of regulatory authorities, it would be a rash company which tried to develop a drug which it did not believe had some real advantage over existing products. I can see no real disadvantages in the present system but I can see disadvantages in an alternative system which must introduce some element of public (synonymous with political?) control. I believe in competitiveness in research which means individuals responsible to different organizations seeing different ways of possibly solving problems, and I see merit in them having differing opinions on what constitutes worthwhile targets of research. Finally, I remember, the millions of dollars President Nixon poured into cancer research believing that money created ideas and I am aware of kindred spirits in other political spheres. Public money so often means political interference, well-meaning but ill-judged !
stress. Although there is a mass of evidence inculpating it, the amount of money devoted to research in it in Britain is negligible. A recent committee of inquiry on the subject said it could not pronounce one way or the other because of lack of proof: but any researcher trying to get funds to try to provide proof is turned away, on the same grounds. So even if I agreed with Davey about the value of ‘me-too’ products (which I don’t: on balance it appears to me, they have recently been succeeding by good salesmanship, rather than on their merits) I would still feel that any gain from improved drugs is, and will continue to be, marginal. What we deed now is not better drugs, but better therapeutic techniques of prevention, to avoid the need ‘to take drugs. I know no dpctor who does, not agree that far too many patients now take - indeed, demand - sedatives and tranquillizers, antidepressants and stimulants. It is a commonplace that antibiotics are grossly over-prescribed. For all their short-term benefits, I suspect that op balance the steroids have done more harm than good. And there are many other drugs in common use which. we would be better off without. As things are, however, the industry must promote its wares, if it is going to maintain its profits. So we have the ludicrous situation of the British Medical Journal, the Lancet and the rest deprecating the annual increase in the prescription rate for certain drugs, while their advertizing pages contain panagyrics for them. It simply does not make sense. What would make sense? There, I have to admit, I am baffled. I do not care for the idea of government intervention any more than Davey does. It is not so much that the control would be inefficient, though it would be. My fear is that governments, delighted to find a profitable enterprise, would exploit it for revenue - or at least try to. ,I don’t doubt they would soon run the whole industry into the ground. But who, then, should finance and control research? The record of, for example, the Medical Research Council does not inspire confidence. It has tended to follow the example of the Army General Staff, which traditionally is always preparing for the last war but one. Besides - and here again I agree with Dr Davey - there must be competitiveness in research. The trouble is that in the field of prevention, there can be little competition, be&use there are not the funds to sustain it. And where those funds are going to come from, if neither the Government nor the medical profession is to be allowed to control them, remains a mystery.
The debate is now open reader,? &mments whichmay be published.as letteps to the editor are wklcome. ??
DISCUSSION FORUM Should the industry control pharmaceutical research? Garnet Davey - the case for the pharmaceutical industry
Brian Inglis recommends
change
Brian Inglis is a journalist with a partitular interest in drugs as well as being the author of many books including
‘The History of Medicine’, ‘Drugs, Doctors and Disease’ and most recently ‘The Forbidden Game - a Social HistorJ I of Drugs’.
The custom that the pharmaceutical industry should be committed to the discovery of new drugs started, I suppose, because of the close association between Paul Ehrlich and the Bayer Company in Germany in the early part of this century. Spurred on by the success of salvarsan and neosalvarsan the initial emphasis was the discovery of new drugs utilizing the art of the synthetic organic chemist. Much later, with the advent of penicillin, the search for new drugs amongst natural products gained a new impetus and was added to the synthetic chemical approach. Until the Second World War chemotherapeutic research was dominated by the German and Swiss pharmaceutical companies, a fact which was deplored, in the U.K. at least, by several academic workers who were keenly interested in the subject. Their persuasion led the Medical Research Council in 1936 to decide to embark on a new major programme of research on chemotherapy, but to implement the decision a new building was necessary - hence the erection of the new National Institute for Medical Research at Mill Hill. The new institute was completed shortly before war started and the war, of course, upset many plans. What might have happened had there been no war in anyone’s guess, but the end of the war saw American, British and French pharmaceutical companies also committed to research to find new drugs and considerably lessening the former dominance of the German and Swiss companies. And so it has remained ever since. To pose the question, ‘Should the pharmaceutical industry control pharmaceutical research? suggests things are not well. Is this really so? No one, I am sure, would gainsay the fact that spectacular advances have been made. The isolation hospitals of my childhood, catering for scarlet fever and diphtheria, have disappeared; the tuberculosis sanatoria are put to other uses; pneumonia is no longer the scourge of the middle-aged and elderly that it once was; mental hospitals are far fewer than they might have been; most epileptics lead a relatively normal life; many ‘heart patients’ are no longer obvious invalids, etc. etc. The list is indeed a long one.
Let me begin by agreeing with Garnet Davey; nobody is likely to gainsay the fact that medicine has made spectacular advances since our childhood years. I must question the implication, though, that the credit should go to the pharmaceutical industry. It must be shared not only with individual investigators, but with men like Chadwick, who helped to convince society of the need for improved housing, sanitation and parks. As a result of their efforts, diseases like tuberculosis were in full retreat before ever drugs came on the scene to complete their rout. However, that is not to deny the industry credit for its achievements. In fact there is a sense in which it has been too successful. I have used before the analogy of Prince Rupert, sweeping the Roundhead wing before him in full retreat, but leaving Cromwell’s infantry in possession of the field. The infantry of illness - coughs, colds, flu, backaches, allergies, and the whole range of degenerative disorders - have not been brought under any sort of effective control by drugs. In fact the sickness rate appears to be actually higher than it used to be, even if the mortality rate has fallen. The criticism to which Davey objects, therefore - that diseases of small incidence get neglected, because it would not be prolitable to find and produce the cure - is of small importance compared to the failure of the industry to find and produce the cure for the common cold. This is not, needless to say, for want of trying. I am sure, too, that Davey is right when he points to the massive expense involved in such research. My objection is that I do not believe it represents the right research: the.right approach to finding how to cure - which, basically, means finding how to prevent - colds or any of the more serious disorders. Take the case of heart attacks. Huge sums have been lavished on the search for and the use of drugs to control hypertensioq, on anti-coagulants, and so forth. I happen to believe that it is largely money squandered: that what is needed is far man emphasis on the epidemiological,aspects, research to probe t* links with smoking, diet, lack of exercise and stress - pattiqularq
TIBS - January I9 76
N15
Garnet Davey
Brian Inglk
What then is wrong, or supposed to be wrong? I have heard three main criticisms of the present system. It is said first that drugs are more expensive than they need be ; second that diseases of small incidence, whilst possibly of tragic importance to the individual suffering from them, are neglected because the finan5al returns to industry would be too small: and third there is too much ‘me-too’ research and too many ‘me-too’ drugs. Let me deal briefly with these three points. It is true that the cost to the user of a new drug is considerably more than the cost of manufacturing the chemical compound which comprises the drug because someone has to pay for the research leading to the new drug, and the cost of this research is high. It is high because well-qualified scientists of various disciplines - biochemists, chemists, pharmacologists, toxicologists - are engaged in the team leading to discovery; because facilities-laboratories and laboratory, etc. equipment, animals, animal houses, animal technicians - ‘are expensive; because the research is intrinsically difficult and success is relatively infrequent, and because development of a new drug takes ieven to ten y$ars. I have said elsewhere that, starting from scratch, a company engaged in research to find a new drug might invest about f 100 million before getting any return. Regarding the supposed neglect of diseases of low incidence, this is an easy criticism to make but I have not heard it justified; that is to say I have not seen the list of diseases which are said to be neglected so that I might make some defence. I suspect that an important point might be forgotten by those who make this criticism and this is the fact that to discover in the laboratory a drug for a disease one must know or strongly suspect how the disease is caused because the drug is aimed to do something in particular. For example, I have been asked why my laboratory was not trying ot discover a drug for disseminated sclerosis, and I had to reply that we did not yet know how to begin to look. Some workers think that the disease might be an auto-immune disease, and others have suggested it is caused by a ‘slow’ virus. Basic knowledge must advance further before an intelligent search for a drug for this disease can begin. The third criticism, that there are too many ‘me-too’ drugs and too many companies pursue ‘me-too’ research can be made too glibly. What appear to be marginal differences in therapeutic effect or toxic action can be very important to large numbers of patients. A drug must be judged on its merits and not dismissed because it is similar to or very like another in chemical constitution. I should also point out that in these present times in which a potential drug progresses through its clinical development slowly, and under the constant surveillance of regulatory authorities, it would be a rash company which tried to develop a drug which it did not believe had some real advantage over existing products. I can see no real disadvantages in the present system but I can see disadvantages in an alternative system which must introduce some element of public (synonymous with political?) control. I believe in competitiveness in research which means individuals responsible to different organizations seeing different ways of possibly solving problems, and I see merit in them having differing opinions on what constitutes worthwhile targets of research. Finally, I remember, the millions of dollars President Nixon poured into cancer research believing that money created ideas and I am aware of kindred spirits in other political spheres. Public money so often means political interference, well-meaning but ill-judged !
stress. Although there is a mass of evidence inculpating it, the amount of money devoted to research in it in Britain is negligible. A recent committee of inquiry on the subject said it could not pronounce one way or the other because of lack of proof: but any researcher trying to get funds to try to provide proof is turned away, on the same grounds. So even if I agreed with Davey about the value of ‘me-too’ products (which I don’t: on balance it appears to me, they have recently been succeeding by good salesmanship, rather than on their merits) I would still feel that any gain from improved drugs is, and will continue to be, marginal. What we deed now is not better drugs, but better therapeutic techniques of prevention, to avoid the need ‘to take drugs. I know no dpctor who does, not agree that far too many patients now take - indeed, demand - sedatives and tranquillizers, antidepressants and stimulants. It is a commonplace that antibiotics are grossly over-prescribed. For all their short-term benefits, I suspect that op balance the steroids have done more harm than good. And there are many other drugs in common use which. we would be better off without. As things are, however, the industry must promote its wares, if it is going to maintain its profits. So we have the ludicrous situation of the British Medical Journal, the Lancet and the rest deprecating the annual increase in the prescription rate for certain drugs, while their advertizing pages contain panagyrics for them. It simply does not make sense. What would make sense? There, I have to admit, I am baffled. I do not care for the idea of government intervention any more than Davey does. It is not so much that the control would be inefficient, though it would be. My fear is that governments, delighted to find a profitable enterprise, would exploit it for revenue - or at least try to. ,I don’t doubt they would soon run the whole industry into the ground. But who, then, should finance and control research? The record of, for example, the Medical Research Council does not inspire confidence. It has tended to follow the example of the Army General Staff, which traditionally is always preparing for the last war but one. Besides - and here again I agree with Dr Davey - there must be competitiveness in research. The trouble is that in the field of prevention, there can be little competition, be&use there are not the funds to sustain it. And where those funds are going to come from, if neither the Government nor the medical profession is to be allowed to control them, remains a mystery.
The debate is now open reader,? &mments whichmay be published.as letteps to the editor are wklcome. ??