96
Letters
to
the Editor
CANCER : FAILURE OF LOCALISATION OF THE IMMUNE SYSTEM?
SiR,-There seems little doubt that there is a relationship between the immune system and cancer. Why the immune system fails to control tumour growth remains a major question. In classical animal experiments which produce immunity to a tumour by allowing prior temporary tumour growthit appears that the developing immune response does not attack already established initial nodules but does attack tumour inoculations made after the complete removal of the initial lesion. It may be that local tissue injury resulting from initial implantation fades away as tumour nodules become vascularised, and at this point the developed immune response cannot sense malignant cells behind the screen of autologous capillaries. The usual explanation for this phenomenon is that " " antigen overload " or blocking factors " overcome the immune system upon its first encounter with tumour before it develops the capacity to mount a strong resistance. Yet, in some animal systems, it can be shown that while primary inoculum is being " enhanced ", second inoculum of the same tumour will be destroyed in a second set manner.3 Tumour regression can occur even after the measurable development of blocking factors.4 In any event, the reason that the immune system remains inactive in the early stages of spontaneous malignancy cannot be " explained on the basis of blocking ", since, in the early cases of cancer, usually no blocking activity can be detected. Experimentaland clinical6 evidence suggests the inability of immune lymphocytes to localise at tumour sites. Cellular and humoralimmunity against autologous tumours can be produced in patients by specific and nonspecific vaccination and immunisation techniques, but established nodules in these patients remain largely unaffected.99 Although immunocompetent cells, locally summoned to tumour nodules (in non-anergic patients) through intralesional injections of a variety of agents (e.g., Coley’s toxins,lO Cohn’s fraction of autologous plasma following immunisation," B.C.G.,9 B.c.G. and Vibrio cholera neuroaminidase 12) can destroy local tumour, rarely is there a systemic anti-tumour response. Thus, it seems that the immune system has the capacity to recognise the weak tumour antigens and to cause tumour destruction, but often this does not take place. Although enhancement and tolerance may play a role in allowing tumour growth and metastases, inability of the immune response to localise itself at tumour sites may be the
predominant defect. Abundant information exists demonstrating that the immune response evoked by a particular antigen may differ according to the site of its injection. The skin gives Sophocles, A. M., Jr., Nadler, S. H. Surgery Gynec. Obstet. 1971, 133, 321. 2. Gold, P. Can. med. Ass. J. 1970, 103, 1043. 3. Kaliss, N. Ann. N.Y. Acad. Sci. 1962, 101, 64. 4. Hellstrom, I., Hellstrom, K. E. Int. J. Cancer, 1970, 5, 195. 5. Alexander, P., Deborme, E. J., Hall, J. G. Lancet, 1966, i, 1186. 6. Nadler, S. H., Moore, G. E. Ann. Surg. 1966, 164, 482. 7. Currie, G. A., Lejeune, F., Hamilton Fairley, G. Br. med. J. 1971, ii, 305. 8. Ikonopisov, R. L., Lewis, M. G., Hunter-Craig, I. D., Bodenham, D. C., Phillips, T. M., Cooling, C. I., Proctor, J., Hamilton Fairley, G., Alexander, P. Br. med. J. 1970, ii, 752. 9. Morton, D. L., Holmes, E. C., Eilber, F. R., Wood, W. C. Ann. intern. Med. 1971, 74, 587. 10. Nauts, H. C., Fowler, G. A., Bogatko, F. H. Acta med. scand. suppl. 1953, 276, 5. 11. Finney, J. W., Byers, E. H., Wilson, R. H. Cancer Res. 1960, 20, 351. 12. Simmons, R. L., Rios, A., Kersey, J. H. J. surg. Res. 1972, 12, 57. 1.
generally stronger and more lasting immune responses.13 Further, pathogenic bacteria produce a strong, often lifelong, immunity, while animal parasites often evoke little or no response.14 Adequate contact is usually required between the foreign configuration and immunocompetent cells before sufficient immune response can develop. This " tissue injury " may well be determined by the degree of caused by the foreign cell or substance. " Tissue injury " and its resultant inflammatory reaction results not only in contact with the " invader " but also with its subsequent localisation by the immune system. The ability of immune cells and antibodies to localise may not be a property of the immune system, but rather a property of the foreign configuration, just as the type of local response (immediate or delayed) and the strength and duration of ensuing systemic response is dependent on the antigen administered. Early tumours, essentially of a parasitic nature, not possessing inflammatory properties, but rather insidiously invading without destroying surrounding tissues, fail to incite locally immunocytes. Thus, both the recognition and effector arms of the immune system are affected. Although this hypothesis of the isolation and inaccessibility of early growing malignant cells to the immune system sufficiently explains the inactivity of the immune response during the initiation of a spontaneous tumour, it remains speculative. Recognition of this difficulty of the immune mechanism to localise at tumour sites has probably been delayed because most attention to the modus operandi of the immune system has been dominated by knowledge of its interaction with bacteria.
implications of the above include: Immunotherapy is probably best suited
Practical 1.
to
prevent
metastases.
Techniques should be developed resulting in immunological destruction of established tumour nodules by the single intralesional administration of an agent, resulting in marked inflammation and an increased local2.
isation of immune response. 3. New means to improve general cancer patients must be developed. Roswell Park Memorial Hospital, 666 Elm Street, Buffalo, New York 14203, U.S.A.
immunoreactivity
of
C. KARAKOUSIS.
THE CONSULTANTS’ CONTRACT
SiR,-Mrs Castle’s proposed new contract for hospital consultants, which involves a 5-day week, together with
being " on call " for 24 hours in case of emergencies, is evidently unacceptable to the majority. It appears that a consultant " on call " would be reimbursed only if he visited his hospital. Since many a consultation can be dealt with over the telephone, this means that all consultants would in effect be forced to be available, unpaid, for long periods. If the junior hospital doctors’ demand for a 40-hour week is implemented the consultant’s lot could indeed become an unhappy one. On the other hand, I believe that the response of the consultants to the proposed contract is mistaken. It is nonsense to pretend that working-to-rule will not harm patients. If this action, sponsored by the B.M.A. and the H.C.S.A., continues, then patients will suffer and perhaps die. Whilst I feel that the contract proposed by Mrs Castle is unacceptable, I suggest that the problems should be S., Wepsic, H. T., Churchill, W. H., Zbar, B., Borsos, T., Rapp, H. J. Science, 1970, 168, 257. 14. Bellanti, J. A. Immunology, 1971, 309, 53. 13. Kronman, B.
97
submitted
to
independent arbitration, presided
over
by
a
judge. Gloucestershire Royal Hospital, Gloucester.
GEORGE FEARNLEY.
it-and I cannot be alone-the militant the consultants is a disaster. The N.H.S., of money-ethos with the withdrawal from India the most generous political concept of British public life, is being castrated by many of those who ought to see in it their supreme chance of serving the community. Are British doctors really anxious to join the backwoodsmen of the American Medical Association ? True, we train longer than any other profession. True, we work longer than most other professions. True, we need all the skill, knowledge, and humane understanding to even start countering the threats to health and a full life inherent in diseases and accidents. But we are privileged beyond all other professions by the unlimited variety of challenges, the opportunities for maximum effort, the satisfaction of becoming worthy of
SIR,-As I
see
calling. Changes we need.
our
We have to support a juster provision of livelihood for nurses, even now vastly underrated in their contribution within the cure-and-care team, for physiotherapists and occupational therapists, radiographers, laboratory teclinicians, and secretaries; and for our younger colleagues whose income at a time they start families is still too low. But for consultants to use extreme left-wing tactics to maintain their differentials is shameful, no less. Theyand I was one of them-have an obligation to get rid of the " bull-frog syndrome ", blowing themselves up with selfimportance. No-one who cares for the quality of a life devoted to a worthwhile cause can see his reward in terms of cash. Let those whose work is dull, physically hard, and dangerous seek compensation in wages. Their jobs are uncertain. Ours are not. Let the curing and caring team lead our renaissance in a spirit of service. Do not let the lack of tact of a Minister push us into responses alien to us. We shall be servants of the community or we shall be in contempt of a higher court. 11 a Acol
Road,
London NW6 3AA.
L. S. MICHAELIS.
to my consultant colleagues situation coolly and carefully before
appeal
to
consider the whole a step.
taking such
Walton Hospital,
P. M. ROBB.
Liverpool.
SIR,-Mr Houghton’s letter (Dec. 28, p. 1566) has a wider significance than a casual glance would suggest. General surgery is still an individualistic branch of medicine and this makes it difficult for many surgeons to grasp how complex modem medical practice has now become. It is rubbish to imply that the only doctors who can make valid contributions towards solving the problems of the N.H.S. are those who have patients directly under their care. Analysis of the causes of the present consultant contract chaos reveals that the reverse might almost be true. We have organised ourselves into trade-unions (B.M.A. and H.C.S.A.) and almost immediately they have developed a complication common to such organisations. This it that policy is dictated by a minority group with extreme views. All the recent negotiations have been dominated by surgeons (see composition of negotiating team 1) who often appear to care more about private medicine than about the N.H.S. Probably many of them are part-timers. Like many other trade-unions who find themselves in this situation, we must try to rouse the politically apathetic members of the profession and obtain truly representative negotiators. Many independent observers2 find that the Government’s proposals form a reasonable basis for negotiation; certainly they would satisfy the trade-union requirement that payment would be related to work done. Mr Houghton, battling against the " unpredictable aggression " of disease at the weekend, would be paid extra for his efforts, if this is what he wants. In this particular instance, one of Mr Houghton’s basic assumptions is probably invalid. It may take some time to percolate up the ivory surgical towers, but many hasmaiologists are now caring directly for patients and this may already have happened at his own hospital. Department of Haematology, St. Bartholomew’s Hospital, M. E. J. BEARD. London EC1. SiR,-The Houghton report on teachers’ salaries, which cost the country E432 millions, includes the following
will
" We wish to stress that we believe the salary levels we recommend justify expectation of professional standards of performance in return ", and that the levels were in part " recognition of the fact that the job cannot be compressed within a rigid structure of prescribed duties, hours or days ". It might also be noted that the teachers’ scales include levels well above that of the maximum of the full-time consultant, and periods of leave which doctors comment:
SIR,-My study of the proposed new consultant contract, and of the various documents issued by the B.M.A. and the H.C.S.A., leads me to the conclusion that the main issue which has caused these bodies to recommend their members to apply sanctions is the Government’s proposal to maintain a salary differential between those who make a whole-time commitment to the N.H.S. and those who retain the right to private practice. I see no issue of principle here. Moreover, I believe it is desirable that a whole-time commitment to the N.H.S. should be made more attractive than it is at present in order to stimulate recruitment into those branches of the profession where private practice is not available. I know from personal experience on appointment committees that it is, at present, often difficult to find suitable applicants for consultant vacancies in, for instance, some branches of laboratory medicine. True, there are parts of the proposed new contract that are not acceptable-for instance, the lack of payment for on-call and standby duty, and the failure to make expense allowances for cars and telephones. But these are not issues of principle and are surely negotiable. We are now asked to apply sanctions. Soon we may be asked to resign from the N.H.S. and hire ourselves out to our health authorities through employment agencies. These actions jeopardise the future of the N.H.S. I would
can
only imagine.
we less of a profession that we should scramble for a piece-rate contract simply as a means of obtaining more money ? It is even more inappropriate that full-time
Are
new
consultants should now be asked to support sanctions whose avowed aim is to make complete commitment less attractive-after all, we are given the choice. Bridgend General Hospital, Quarella Road, Bridgend, Glamorgan.
D. E. B. POWELL.
TIGHT GLOVES
SiR,-Dr Morgan (Dec. 21, p. 1510) makes an interesting observation on the association of arthritis and the wearing of tight gloves. She is, however, mistaken in supposing 1. Br. med. J. Nov. 2. Times, Dec. 27,
16, 1974, p. 419. 1974, p. 9.
Letters
to
the Editor
CANCER : FAILURE OF LOCALISATION OF THE IMMUNE SYSTEM?
SiR,-There seems little doubt that there is a relationship between the immune system and cancer. Why the immune system fails to control tumour growth remains a major question. In classical animal experiments which produce immunity to a tumour by allowing prior temporary tumour growthit appears that the developing immune response does not attack already established initial nodules but does attack tumour inoculations made after the complete removal of the initial lesion. It may be that local tissue injury resulting from initial implantation fades away as tumour nodules become vascularised, and at this point the developed immune response cannot sense malignant cells behind the screen of autologous capillaries. The usual explanation for this phenomenon is that " " antigen overload " or blocking factors " overcome the immune system upon its first encounter with tumour before it develops the capacity to mount a strong resistance. Yet, in some animal systems, it can be shown that while primary inoculum is being " enhanced ", second inoculum of the same tumour will be destroyed in a second set manner.3 Tumour regression can occur even after the measurable development of blocking factors.4 In any event, the reason that the immune system remains inactive in the early stages of spontaneous malignancy cannot be " explained on the basis of blocking ", since, in the early cases of cancer, usually no blocking activity can be detected. Experimentaland clinical6 evidence suggests the inability of immune lymphocytes to localise at tumour sites. Cellular and humoralimmunity against autologous tumours can be produced in patients by specific and nonspecific vaccination and immunisation techniques, but established nodules in these patients remain largely unaffected.99 Although immunocompetent cells, locally summoned to tumour nodules (in non-anergic patients) through intralesional injections of a variety of agents (e.g., Coley’s toxins,lO Cohn’s fraction of autologous plasma following immunisation," B.C.G.,9 B.c.G. and Vibrio cholera neuroaminidase 12) can destroy local tumour, rarely is there a systemic anti-tumour response. Thus, it seems that the immune system has the capacity to recognise the weak tumour antigens and to cause tumour destruction, but often this does not take place. Although enhancement and tolerance may play a role in allowing tumour growth and metastases, inability of the immune response to localise itself at tumour sites may be the
predominant defect. Abundant information exists demonstrating that the immune response evoked by a particular antigen may differ according to the site of its injection. The skin gives Sophocles, A. M., Jr., Nadler, S. H. Surgery Gynec. Obstet. 1971, 133, 321. 2. Gold, P. Can. med. Ass. J. 1970, 103, 1043. 3. Kaliss, N. Ann. N.Y. Acad. Sci. 1962, 101, 64. 4. Hellstrom, I., Hellstrom, K. E. Int. J. Cancer, 1970, 5, 195. 5. Alexander, P., Deborme, E. J., Hall, J. G. Lancet, 1966, i, 1186. 6. Nadler, S. H., Moore, G. E. Ann. Surg. 1966, 164, 482. 7. Currie, G. A., Lejeune, F., Hamilton Fairley, G. Br. med. J. 1971, ii, 305. 8. Ikonopisov, R. L., Lewis, M. G., Hunter-Craig, I. D., Bodenham, D. C., Phillips, T. M., Cooling, C. I., Proctor, J., Hamilton Fairley, G., Alexander, P. Br. med. J. 1970, ii, 752. 9. Morton, D. L., Holmes, E. C., Eilber, F. R., Wood, W. C. Ann. intern. Med. 1971, 74, 587. 10. Nauts, H. C., Fowler, G. A., Bogatko, F. H. Acta med. scand. suppl. 1953, 276, 5. 11. Finney, J. W., Byers, E. H., Wilson, R. H. Cancer Res. 1960, 20, 351. 12. Simmons, R. L., Rios, A., Kersey, J. H. J. surg. Res. 1972, 12, 57. 1.
generally stronger and more lasting immune responses.13 Further, pathogenic bacteria produce a strong, often lifelong, immunity, while animal parasites often evoke little or no response.14 Adequate contact is usually required between the foreign configuration and immunocompetent cells before sufficient immune response can develop. This " tissue injury " may well be determined by the degree of caused by the foreign cell or substance. " Tissue injury " and its resultant inflammatory reaction results not only in contact with the " invader " but also with its subsequent localisation by the immune system. The ability of immune cells and antibodies to localise may not be a property of the immune system, but rather a property of the foreign configuration, just as the type of local response (immediate or delayed) and the strength and duration of ensuing systemic response is dependent on the antigen administered. Early tumours, essentially of a parasitic nature, not possessing inflammatory properties, but rather insidiously invading without destroying surrounding tissues, fail to incite locally immunocytes. Thus, both the recognition and effector arms of the immune system are affected. Although this hypothesis of the isolation and inaccessibility of early growing malignant cells to the immune system sufficiently explains the inactivity of the immune response during the initiation of a spontaneous tumour, it remains speculative. Recognition of this difficulty of the immune mechanism to localise at tumour sites has probably been delayed because most attention to the modus operandi of the immune system has been dominated by knowledge of its interaction with bacteria.
implications of the above include: Immunotherapy is probably best suited
Practical 1.
to
prevent
metastases.
Techniques should be developed resulting in immunological destruction of established tumour nodules by the single intralesional administration of an agent, resulting in marked inflammation and an increased local2.
isation of immune response. 3. New means to improve general cancer patients must be developed. Roswell Park Memorial Hospital, 666 Elm Street, Buffalo, New York 14203, U.S.A.
immunoreactivity
of
C. KARAKOUSIS.
THE CONSULTANTS’ CONTRACT
SiR,-Mrs Castle’s proposed new contract for hospital consultants, which involves a 5-day week, together with
being " on call " for 24 hours in case of emergencies, is evidently unacceptable to the majority. It appears that a consultant " on call " would be reimbursed only if he visited his hospital. Since many a consultation can be dealt with over the telephone, this means that all consultants would in effect be forced to be available, unpaid, for long periods. If the junior hospital doctors’ demand for a 40-hour week is implemented the consultant’s lot could indeed become an unhappy one. On the other hand, I believe that the response of the consultants to the proposed contract is mistaken. It is nonsense to pretend that working-to-rule will not harm patients. If this action, sponsored by the B.M.A. and the H.C.S.A., continues, then patients will suffer and perhaps die. Whilst I feel that the contract proposed by Mrs Castle is unacceptable, I suggest that the problems should be S., Wepsic, H. T., Churchill, W. H., Zbar, B., Borsos, T., Rapp, H. J. Science, 1970, 168, 257. 14. Bellanti, J. A. Immunology, 1971, 309, 53. 13. Kronman, B.
97
submitted
to
independent arbitration, presided
over
by
a
judge. Gloucestershire Royal Hospital, Gloucester.
GEORGE FEARNLEY.
it-and I cannot be alone-the militant the consultants is a disaster. The N.H.S., of money-ethos with the withdrawal from India the most generous political concept of British public life, is being castrated by many of those who ought to see in it their supreme chance of serving the community. Are British doctors really anxious to join the backwoodsmen of the American Medical Association ? True, we train longer than any other profession. True, we work longer than most other professions. True, we need all the skill, knowledge, and humane understanding to even start countering the threats to health and a full life inherent in diseases and accidents. But we are privileged beyond all other professions by the unlimited variety of challenges, the opportunities for maximum effort, the satisfaction of becoming worthy of
SIR,-As I
see
calling. Changes we need.
our
We have to support a juster provision of livelihood for nurses, even now vastly underrated in their contribution within the cure-and-care team, for physiotherapists and occupational therapists, radiographers, laboratory teclinicians, and secretaries; and for our younger colleagues whose income at a time they start families is still too low. But for consultants to use extreme left-wing tactics to maintain their differentials is shameful, no less. Theyand I was one of them-have an obligation to get rid of the " bull-frog syndrome ", blowing themselves up with selfimportance. No-one who cares for the quality of a life devoted to a worthwhile cause can see his reward in terms of cash. Let those whose work is dull, physically hard, and dangerous seek compensation in wages. Their jobs are uncertain. Ours are not. Let the curing and caring team lead our renaissance in a spirit of service. Do not let the lack of tact of a Minister push us into responses alien to us. We shall be servants of the community or we shall be in contempt of a higher court. 11 a Acol
Road,
London NW6 3AA.
L. S. MICHAELIS.
to my consultant colleagues situation coolly and carefully before
appeal
to
consider the whole a step.
taking such
Walton Hospital,
P. M. ROBB.
Liverpool.
SIR,-Mr Houghton’s letter (Dec. 28, p. 1566) has a wider significance than a casual glance would suggest. General surgery is still an individualistic branch of medicine and this makes it difficult for many surgeons to grasp how complex modem medical practice has now become. It is rubbish to imply that the only doctors who can make valid contributions towards solving the problems of the N.H.S. are those who have patients directly under their care. Analysis of the causes of the present consultant contract chaos reveals that the reverse might almost be true. We have organised ourselves into trade-unions (B.M.A. and H.C.S.A.) and almost immediately they have developed a complication common to such organisations. This it that policy is dictated by a minority group with extreme views. All the recent negotiations have been dominated by surgeons (see composition of negotiating team 1) who often appear to care more about private medicine than about the N.H.S. Probably many of them are part-timers. Like many other trade-unions who find themselves in this situation, we must try to rouse the politically apathetic members of the profession and obtain truly representative negotiators. Many independent observers2 find that the Government’s proposals form a reasonable basis for negotiation; certainly they would satisfy the trade-union requirement that payment would be related to work done. Mr Houghton, battling against the " unpredictable aggression " of disease at the weekend, would be paid extra for his efforts, if this is what he wants. In this particular instance, one of Mr Houghton’s basic assumptions is probably invalid. It may take some time to percolate up the ivory surgical towers, but many hasmaiologists are now caring directly for patients and this may already have happened at his own hospital. Department of Haematology, St. Bartholomew’s Hospital, M. E. J. BEARD. London EC1. SiR,-The Houghton report on teachers’ salaries, which cost the country E432 millions, includes the following
will
" We wish to stress that we believe the salary levels we recommend justify expectation of professional standards of performance in return ", and that the levels were in part " recognition of the fact that the job cannot be compressed within a rigid structure of prescribed duties, hours or days ". It might also be noted that the teachers’ scales include levels well above that of the maximum of the full-time consultant, and periods of leave which doctors comment:
SIR,-My study of the proposed new consultant contract, and of the various documents issued by the B.M.A. and the H.C.S.A., leads me to the conclusion that the main issue which has caused these bodies to recommend their members to apply sanctions is the Government’s proposal to maintain a salary differential between those who make a whole-time commitment to the N.H.S. and those who retain the right to private practice. I see no issue of principle here. Moreover, I believe it is desirable that a whole-time commitment to the N.H.S. should be made more attractive than it is at present in order to stimulate recruitment into those branches of the profession where private practice is not available. I know from personal experience on appointment committees that it is, at present, often difficult to find suitable applicants for consultant vacancies in, for instance, some branches of laboratory medicine. True, there are parts of the proposed new contract that are not acceptable-for instance, the lack of payment for on-call and standby duty, and the failure to make expense allowances for cars and telephones. But these are not issues of principle and are surely negotiable. We are now asked to apply sanctions. Soon we may be asked to resign from the N.H.S. and hire ourselves out to our health authorities through employment agencies. These actions jeopardise the future of the N.H.S. I would
can
only imagine.
we less of a profession that we should scramble for a piece-rate contract simply as a means of obtaining more money ? It is even more inappropriate that full-time
Are
new
consultants should now be asked to support sanctions whose avowed aim is to make complete commitment less attractive-after all, we are given the choice. Bridgend General Hospital, Quarella Road, Bridgend, Glamorgan.
D. E. B. POWELL.
TIGHT GLOVES
SiR,-Dr Morgan (Dec. 21, p. 1510) makes an interesting observation on the association of arthritis and the wearing of tight gloves. She is, however, mistaken in supposing 1. Br. med. J. Nov. 2. Times, Dec. 27,
16, 1974, p. 419. 1974, p. 9.
