EDITORIAL Human HealthA Concern of Medicine THE CONTINUUM from sickness to health is the business of medicine. The extremes of this continuum are death at one end and well-being at the other, and there is reason to believe that medicine has some expertise to bring to bear even at these extremes. But the traditional emphasis has been on sickness in the form of disease, injury or emotional illness. From time immemorial the aim of physicians and of the medical profession has been to avoid death and to bring patients from sickness to as much health and well-being as possible. Physicians are comfortable when dealing with sickness and restoring health but are somewhat less so when called upon to be experts in health and distinctly less so when it comes to bringing their. expertise to the problems inherent either in death or well-being. Yet the entire continuum of death to sickness to health to well-being is the concern of medicine. Moreover, at present the medical profession is under considerable pressure to view sickness from the standpoint of health rather than the reverse-which has been traditional. And one may add that it does not take a crystal ball to foresee that before long medical expertise will be increasingly involved in many new problems pertaining to the extremes of this continuum. But a new emphasis on health is now clearly being expected and even demanded of the profession of medicine. This has come about subtly and largely because of external pressure. Three forces appear to have played or are playing significant roles. Two of the most important of these forces to date really have little to do with health, while the third-which has only recently come into play -has a direct relation to it. The first important force appears to have been semantic. Quite simply, while accident insurance was an acceptable phrase, sickness insurance was not nor was death insurance for that matter. Health insurance and life insurance were far more salable phrases, even though they insure neither health nor life. But thought is carried on in the
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human mind by means of symbols, and these widely used phrase symbols clearly focus thought on health and life rather than on sickness or death. This has already proven to be of no little social, economic and political consequence. And this conditioning, if you will, of the public mind through semantic symbolism seems now to have gone so far as to have reached the point where health and life are very close to being considered the right of every person, to be somehow insured or assured. This, even though the obvious fact is that assuring these conditions can never really be accomplished by insurance, by government regulation or by anything else. The second force, which also has little to do with health, appears to be the oversell of medical and scientific progress during the past two or three decades. This also has conditioned the public thinking. It has brought about a widespread public belief that health sciences must be capable, and the health care system therefore should be capable, of assuring longer and healthier lives for everyone. A corollary to this is a widely held conviction that more health care will make more people healthy and that more emphasis on prevention and continuing care will not only make more people healthy and lengthen their lives, but will reduce medical care costs as well. These assumptions or beliefs have only partially been borne out in practice. The experience to date, even with massive programs, is that improved health care services have not improved health to any degree near that expected. Nevertheless, health care continues to be an article of public faith, and the public continues to hold the medical profession more or less accountable for any failure to fulfill the public expectations of it. A third force, which pertains much more directly to health, is only just beginning to be recognized for what it is. There is beginning to be a dim awareness that the problems of human health and survival in the closed earth biosphere are in-
EDITORIALS
separable from the problems of air, land and water pollution, from the balance of human population with limited food, energy and other essential resources-and that these in turn are inseparable from the continuum of death, sickness, health and well-being which is the business of medicine. The enormity of this force, which focuses directly on what is actually involved in human health, and how it will shape the future of medicine, can only be imagined at this time. These are some of the reasons why the public emphasis on health and the public expectations from medicine and health care seem here to stay, for the present and foreseeable future. The power of these forces is such that it would be folly to ignore them. It would seem that it is now time for the medical profession to take a new, long and hard look at what is actually involved in health, at what it takes to maintain human health and at how disturbances in human health lead to illness, injury and emotional disorder-as well as the reverse, which has been the traditional approach. If medicine is to continue to serve humanity as it has in the past, it must henceforth make health as much its business as sickness has been. The implications of this for medical education and for the role of medicine in society are considerable but the challenge should be met. -MSMW
Pathogenesis of Systemic Lu pus Erythematosus THE DISCOVERY of the lupus erythematosus cell phenomenon over twenty-five years ago marked the start of the modern era of research into the pathogenesis of systemic lupus erythematosus (SLE). This initial clinical observation led to the finding of anti-nuclear factor and antibodies to deoxyribonucleic acid (DNA) in the sera of lupus patients. Further studies on renal eluates of lupus patients established the importance of DNA containing immune complexes in the causation of lupus glomerulonephritis, the major cause of death in this disease. As discussed in the paper by Bardana and Pirofsky elsewhere in the JOURNAL, the presence of antibodies to DNA and reduced serum
complement have become routine correlates of active systemic lupus erythematosus, distinguishing this entity from other lupus variants.1 Although the consequences of antibodies to DNA are clear, the cause of this antibody formation is uncertain. Antibodies to single-stranded DNA occur in drug-induced lupus and other related disorders, and lack the specificity for systemic lupus erythematosus associated with antibodies to double-stranded DNA. Moreover, antibodies to single-stranded DNA can be induced by immunization of experimental animals with DNA complexed to protein and emulsified in Freund's adjuvant. Antibodies to double-stranded DNA cannot be provoked by experimental immunization, and occur almost exclusively in systemic lupus erythematosus and in New Zealand Black (NZB) mice, an animal model for SLE.2'3 It is not known whether viral or host DNA iS the immunogen for anti-DNA antibodies. As discussed by Bardana and Pirofsky, several lines of evidence favor a role for virus in the pathogenesis of lupus. The presence of antibodies to viral surface antigens, to double-stranded ribonucleic acid (RNA) and to DNA:RNA hybrids is indirect evidence that immunization to viral antigens may be occurring in this disease. Antibodies to double-stranded RNA have a specificity for SLE intermediate between single and double-stranded DNA. They are seen in almost 50 percent of patients with discoid lupus erythematosus and in 70 percent of patients with the systemic disease. They are not necessarily associated with lupus nephritis, and not generally present in the renal immune complex deposits. An additional antibody activity is also intimately associated with the pathogenesis of systemic lupus erythematosus. Lymphocytotoxic antibodies with specificity for thymic-derived lymphocytes occur in many SLE patients and in New Zealand Black mice. Such antibodies are capable of killing T lymphocytes in the presence of complement and of coating peripheral blood T cells so as to interfere with certain functional activities (such as response in an allogeneic mixed lymphocyte reaction) or with HL-A typing. These antibodies have specificity for T cell surface antigens and can be released from the lymphocyte cell surface in the form of specific antigen-antibody complexes. Such complexes may themselves attach and block other lymphocytes, or may contribute to immune complex deposition leading to vasculitis and nephritis. A better understanding of the pathogenesis of THE WESTERN JOURNAL OF MEDICINE
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FEBRUARY 1975 * 122 * 2
human mind by means of symbols, and these widely used phrase symbols clearly focus thought on health and life rather than on sickness or death. This has already proven to be of no little social, economic and political consequence. And this conditioning, if you will, of the public mind through semantic symbolism seems now to have gone so far as to have reached the point where health and life are very close to being considered the right of every person, to be somehow insured or assured. This, even though the obvious fact is that assuring these conditions can never really be accomplished by insurance, by government regulation or by anything else. The second force, which also has little to do with health, appears to be the oversell of medical and scientific progress during the past two or three decades. This also has conditioned the public thinking. It has brought about a widespread public belief that health sciences must be capable, and the health care system therefore should be capable, of assuring longer and healthier lives for everyone. A corollary to this is a widely held conviction that more health care will make more people healthy and that more emphasis on prevention and continuing care will not only make more people healthy and lengthen their lives, but will reduce medical care costs as well. These assumptions or beliefs have only partially been borne out in practice. The experience to date, even with massive programs, is that improved health care services have not improved health to any degree near that expected. Nevertheless, health care continues to be an article of public faith, and the public continues to hold the medical profession more or less accountable for any failure to fulfill the public expectations of it. A third force, which pertains much more directly to health, is only just beginning to be recognized for what it is. There is beginning to be a dim awareness that the problems of human health and survival in the closed earth biosphere are in-
EDITORIALS
separable from the problems of air, land and water pollution, from the balance of human population with limited food, energy and other essential resources-and that these in turn are inseparable from the continuum of death, sickness, health and well-being which is the business of medicine. The enormity of this force, which focuses directly on what is actually involved in human health, and how it will shape the future of medicine, can only be imagined at this time. These are some of the reasons why the public emphasis on health and the public expectations from medicine and health care seem here to stay, for the present and foreseeable future. The power of these forces is such that it would be folly to ignore them. It would seem that it is now time for the medical profession to take a new, long and hard look at what is actually involved in health, at what it takes to maintain human health and at how disturbances in human health lead to illness, injury and emotional disorder-as well as the reverse, which has been the traditional approach. If medicine is to continue to serve humanity as it has in the past, it must henceforth make health as much its business as sickness has been. The implications of this for medical education and for the role of medicine in society are considerable but the challenge should be met. -MSMW
Pathogenesis of Systemic Lu pus Erythematosus THE DISCOVERY of the lupus erythematosus cell phenomenon over twenty-five years ago marked the start of the modern era of research into the pathogenesis of systemic lupus erythematosus (SLE). This initial clinical observation led to the finding of anti-nuclear factor and antibodies to deoxyribonucleic acid (DNA) in the sera of lupus patients. Further studies on renal eluates of lupus patients established the importance of DNA containing immune complexes in the causation of lupus glomerulonephritis, the major cause of death in this disease. As discussed in the paper by Bardana and Pirofsky elsewhere in the JOURNAL, the presence of antibodies to DNA and reduced serum
complement have become routine correlates of active systemic lupus erythematosus, distinguishing this entity from other lupus variants.1 Although the consequences of antibodies to DNA are clear, the cause of this antibody formation is uncertain. Antibodies to single-stranded DNA occur in drug-induced lupus and other related disorders, and lack the specificity for systemic lupus erythematosus associated with antibodies to double-stranded DNA. Moreover, antibodies to single-stranded DNA can be induced by immunization of experimental animals with DNA complexed to protein and emulsified in Freund's adjuvant. Antibodies to double-stranded DNA cannot be provoked by experimental immunization, and occur almost exclusively in systemic lupus erythematosus and in New Zealand Black (NZB) mice, an animal model for SLE.2'3 It is not known whether viral or host DNA iS the immunogen for anti-DNA antibodies. As discussed by Bardana and Pirofsky, several lines of evidence favor a role for virus in the pathogenesis of lupus. The presence of antibodies to viral surface antigens, to double-stranded ribonucleic acid (RNA) and to DNA:RNA hybrids is indirect evidence that immunization to viral antigens may be occurring in this disease. Antibodies to double-stranded RNA have a specificity for SLE intermediate between single and double-stranded DNA. They are seen in almost 50 percent of patients with discoid lupus erythematosus and in 70 percent of patients with the systemic disease. They are not necessarily associated with lupus nephritis, and not generally present in the renal immune complex deposits. An additional antibody activity is also intimately associated with the pathogenesis of systemic lupus erythematosus. Lymphocytotoxic antibodies with specificity for thymic-derived lymphocytes occur in many SLE patients and in New Zealand Black mice. Such antibodies are capable of killing T lymphocytes in the presence of complement and of coating peripheral blood T cells so as to interfere with certain functional activities (such as response in an allogeneic mixed lymphocyte reaction) or with HL-A typing. These antibodies have specificity for T cell surface antigens and can be released from the lymphocyte cell surface in the form of specific antigen-antibody complexes. Such complexes may themselves attach and block other lymphocytes, or may contribute to immune complex deposition leading to vasculitis and nephritis. A better understanding of the pathogenesis of THE WESTERN JOURNAL OF MEDICINE
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