 At this point, I wish to acknowledge special visitors and guests. We have a delegation with us today of 20 individuals from the People's Republic of China. And I think I would like to ask them to stand and be recognized. Would the delegation from the People's Republic of China please stand? We also have here today people representing many of the academic institutions in the Midwest. At our last count, we had registered representatives here from 170 high schools and nearly 90 colleges and universities throughout the Midwest. We are pleased that you have joined us and consider with us this important topic at this conference. Also I would like to mention that this year's conference has been approved by the Minnesota Medical Association for eight continuing medical education units and physicians who are present who wish to register for these credits will find a registration table in the back toward the main entrance. A conference like this involves careful planning and hard work by many people. I'm only going to recognize five by name. Professor Robert S. Geirnson, who is the chair of this year's planning committee. Elaine Brostrom, who is our director of public events and responsible for all the myriad of detailed planning that must go into a conference of this sort. To Dennis Paschke of the audio visual department, Linda Miller and her staff in the food service and Mr. Dale Hack and his staff in the area of buildings and grounds. They have all made extraordinary contributions and we are indebted to them. Also a word of apology. We are inconvenienced this year by a major construction project. As you will see as you look around London arena on the outside that we are in the process of completing the health and physical education facility. The building in which we are gathered London arena is the first unit of this project. And we are now engaged in a nine million dollar addition which will include an Olympic sized pool, new classrooms and offices, training facilities, locker rooms and a very large sports forum. We hope that this entire facility will be completed by early in 1985 and should the need be there we are told that the sports forum will hold 11,000 people. And so if the Nobel conference continues to grow we may be looking at that facility in the future. I would also like to take just a moment to mention next year's conference, Nobel 20. The topic of that conference will be the nature of learning explorations in cognitive science and included in the speakers at that conference will be Gerald Edelman, Daniel Danette, Herbert Simon and Roger Shank. And so thanks one and all for joining us to our distinguished speakers who have come to be with us, to those who have joined us from other campuses and around the Midwest, to our own faculty and staff and friends who have worked so hard to make this conference possible. It is my fate which I accept to make announcements that don't get printed and I shall do that before introducing the conference topic. High school delegations who wish to have their pictures taken may sign up for a time slot at the information desk but they can also have photos taken right up on the upper level behind us on the grass immediately after this lecture. The printer failed to perforate so the audience will have to manipulate. If you look at the question forms and back they do not have perforation so you will have to do your best to tear off a piece for your questions. Those questions will be presented immediately at the close of the lecture. Would you please remain seated after the lecture? We will go immediately into the panel and take your questions and the panelists comments right away. Tonight there are three special events that are associated with the conference. You see them in your program, the Carol Horne Fraser talk at eight, the Nobel concert in Christchapel at seven, and then the firing line programs which will be at eight thirty in three different places. We urge you to take advantage of these special events. The campus with the firing line places on them can be obtained at the information desk. What makes a Nobel conference? An interested audience, and obviously that's here probably the largest one we've had attracted by a significant topic presented by competent and interesting persons and prepared for by the hard work of many people. The topic is the key I guess and it is significant because science touches our lives most intimately and personally in the applications of medical care. Significant because the advances in medical technology and care have brought escalating costs which rise very fast so that we are beginning to ask how we can contain these costs. And significant because the knowledge and ability to apply scientific knowledge have brought us to the edges of life and death and the imminent prospect of directly engaging ourselves in altering these boundaries which only a few years ago we thought were fixed and impenetrable walls. We not only have the means of prolonging life at least bodily functions but are on the threshold of our capacity to alter life through genetic engineering. There are many basic questions. No question seems more basic to me than this one. Have we gone too far or not yet far enough? Is the human vocation to settle down into the recurring rhythms of natural life or to venture forth into new seasons and territories? If we should stop, how can we do so without destroying human creativity? And if we should venture forth, how can we do so in ways that will not jeopardize human lives and the life of this planet? Can we really say that our generation is the best generation possible or the last generation? Are we really on the brink of the world's last night to borrow a phrase from C.S. Lewis? He calls attention to our experience of the haunting. Are we haunted by the memory of a paradise lost, some golden age in the past when all was well, or by the vision of a heaven not yet attained? It is to go back or to go forward, which is our vocation? Well, it's not my place to answer these questions, and they may not be the questions on your minds. The Nobel conference is made up of persons who address us, persons who themselves have wrestled with the ideas and the issues that the theme presents. And I believe we have persons this year who are competent and concerned and clear thinking men and women, and I am pleased to present them to you. They will be introduced more fully later. Lewis Thomas of the Sloan Kettering Memorial Cancer Center in New York City was on the platform. Karen Labox of the Pacific School of Religion. Christian Anfanson, John Hopkins University in Baltimore. Willard Galen, the Hastings Center, Hastings-Un Hudson, New York. Clifford Groves-Stein of the University of California in San Diego. And June Goodfield, also the Sloan Kettering Memorial Cancer Center. Let us greet them with our hearty hospitality. Dr. Thomas will be introduced by Dr. Ronald Christensen from the Political Science Department. The English language is a beautiful thing. And Lewis Thomas is one of the masters of its use. Those of you who have read his books, The Life of a Cell, Medusa and the Snail, The Youngest Science, know his imaginative essays. You will be happy to learn that Dr. Thomas has written another book of essays which will be published soon. Late Night Thoughts While Listening to Mahler's Ninth Symphony. In addition to being one of the finest essays of our time, Lewis Thomas is a leading medical scientist, chancellor of the Memorial Sloan Kettering Cancer Center and a member of the National Academy of Science and on its governing board. Among his many honors, one of the most recent is an honorary degree from the University of Wales. Presented to Dr. Thomas in July and Aberwishwith by Prince Charles. An honor especially because of Dr. Thomas's Welsh heritage. Lewis Thomas, we are welcoming you to Gustavus Adolphus College. I know of no person more qualified to begin a Nobel conference on medical advances and human responsibilities than you. We look forward to hearing you speak on the limitations of medicine as a science. Thank you, Mr. President, colleagues and fellow students. Fifty years ago, it seems a short distance in the records of science and technology, no time at all in the millennia of the long history of medicine. Doctors can trace their roots doctrine by doctrine back through the Roman Empire into ancient Greece, past Esculapius, all the way back to the shamanism of the Indo-Europeans and no doubt further still into the earliest equivalents of which doctors conjuring out the illnesses of the first hunters and gatherers. It is a long professional lineage doctor after doctor. We have the oldest roots for our occupational labels still resonating inside our titles. Doctor from Indo-European deck meaning proper and acceptable with cousin words like orthodox and dogma. Leech from boo meaning nature becoming fruces in Greek and then physics and physics. Leech from leg meaning to collect and speak, turning later into logic and legend. Leech the worm came along later by a process of assimilation from more obscure origins but still meaning collecting like the doctor and used for centuries in medicine signifying measuring out and taking appropriate measures. All our philological instructions are still with us, exhorting the medical profession to behave properly and with decorum and decency to go carefully with nature to provide sound and measured advice. The word medicine has within it as etymological reminders, cognate words like moderate and modern but also modest. This is as it should have been but alas has never been. The history of medicine has never been a popular study for study subject for study in the medical schools partly because it has been for most of its stretch of time so embarrassing. Montaigne in his essay children and fathers lashed out at the profession and its pretensions. The doctors wrote Montaigne are not content with having control over sickness they make health itself sick in order to prevent people from being able at any time to escape their authority. I am not upset he goes on I am not upset at being without a doctor without an apothecary and without help from which I see most people more afflicted than by the disease. Montaigne could serve as the earliest standard bearer for today's proponents of preventive medicine even for those activists pressing for a new holistic medicine and what are called alternative methods of health care. He wrote we disturb and arouse the disease by attacking it head on it is by our mode of life that we should make weaken it by gentle degrees. The drug is an untrustworthy assistant by its nature and enemy to our health. The principal pharmacopoeia at medicines disposal and probably the one that so infuriated Montaigne was the ancient collection of drugs employed for violent purgation. Purging and later bleeding were the two things that doctors did for serious illnesses and they continued to place fervent reliance on these clear up through the 19th century. George Washington is reported to have died hail and hearty at the age of 67 after being bled for treatment of a Quincy sore throat. Two and a half quarts of his blood were removed probably bringing him into shock within an inch of his life and then perhaps beyond. It was not until the late 19th century that medicines ancient motto premium known no care first do no harm was taken seriously and literally. At that time most of medicines science and therapeutic technology were abandoned. Sir William Osler and his school initiated what came to be called therapeutic nihilism. Doctors learned to confine their scholarly efforts to studies of the natural history and pathology of disease. Only a few remedies survived such as digitalis morphine quinine aspirin. The chief functions of the doctor were three fold to make an accurate diagnosis to explain to the patient and family how the illness would most likely turn out and then to stand by making sure that good nursing care nutrition and comfort were at hand. This was essentially the kind of medicine that I was taught at Harvard Medical School in the mid 1930s and none of us students, faculty or patients had any notion that it would ever be any different. By that time we possessed insulin for diabetes, liver extract for pernicious anemia, and vitamin B for pellagra. We regarded these as miraculous anomalies, pure gifts from heaven. But we did not acknowledge them as the fruits of science for we did not really think of therapeutic medicine as any kind of science. And then in the late 1930s, selfanilomide appeared, followed within a few years by penicillin and then the other antibiotics, and medicine was transformed overnight, so to speak, from an ancient art to a modern science. Or so we came to believe. We could henceforth give up, we thought, all the merely supportive functions of standing by. Reassurance would no longer be our principal occupational service. We could abandon all placebos. Montaigne could be exorcised. Plato as well. Plato had hurt our professional feelings long ago by remarking that it is for doctors alone to lie in all freedom since our safety depends on the vanity and falsity of their promises. We were after the conquest of infectious disease that began a half century ago, home and dry. Or so we thought. Almost simultaneously with the emergence of antimicrobial microbial therapy, and in part because of it, surgery began a comparable revolution. In the years since, surgical techniques associated with vastly improved methods for maintaining fluid balance, blood volume, oxygenation, advanced to a level of sophistication and power that was inconceivable before. Organ transplantations, open heart surgery, the repair of minute blood vessels, the replacement of severed limbs and extensive procedures for the removal of previously unapproachable cancers became everyday routine procedures. And these, I think, have been the two great advances in medical treatment. And they are indeed wonderful, but they leave in the public mind the impression that medical care has come along so fast and so far that there are now no diseases beyond the reach of treatment and cure. It is, of course, not so. Still on medicine's agenda of essentially unsolved, untreatable and unpreventable diseases is a long roster of major problems for human health. Coronary heart disease, stroke, at least 50% of cancers, the vascular complications of diabetes, rheumatoid and degenerative arthritis, multiple sclerosis, schizophrenia, the senile dementias, cirrhosis, emphysema, nepritis, a long list in addition of less common but disabling and potentially lethal disorders. Looked at in this way, medicine has a great part of its full distance still to go, while very much better than the medicine of 50 years ago, it owes much of its eminence to paraphrase gibbon to the flatness of the preceding terrain. The real advances celebrated by the biomedical sciences during recent years have been in basic research aimed at what will almost undoubtedly turn out to be the important underlying mechanisms of disease. The new information is exciting, even breathtaking in its implications, but it has to go farther and much deeper before it will open up new approaches to therapy. A recent and exceptional example of what is needed is hypertension, a new and rational pharmacology aimed at intervening at a fundamental level of enzymology is providing tailored drugs for the control of malignant hypertension. The high hope in medicine is that as more is learned about the working parts of all the other diseases on that list, equally effective remedies will be devised. But it hasn't happened yet, and there is an enormous amount to be learned. Meanwhile, we are stuck with a level of technology for managing some of the commonest diseases, which is neither decisive nor conclusive, is enormously expensive, and while it provides some alleviation of symptoms and some prolongation of life, does not deal with any of the real root causes of the diseases in question. Examples of such halfway technologies are cardiac transplantation, kidney and liver transplants, chronic renal dialysis, and costliest and farthest of all from the underlying problem, the artificial heart. As long as the mechanisms of the diseases remain unknown, measures such as these, heroic in a sense for both the doctor and the patient, are all there is to offer. The existence of a workable artificial heart and the fact that it has already undergone one human trial ought to be regarded as the most urgent of spurs for more basic research on myocardial disease. If we are compelled to develop this device for anything like the widespread use for which it will be demanded, the cost of health care will go through the roof. The costs are going to go through the roof anyway, between now and the end of the century, unless we can discover more effective and economic ways of coping with the problem of aging. Already in 1983, 10 percent of the American population is over the age of 65, and by the year 2000, that figure is expected to rise higher than 20 percent. If you are looking around for something to worry about for medical science and technology, you should place this problem high on the list of anxieties. The array of specific questions to be asked is long and impressive. Each question is a hard one needing close and attentive scrutiny by the brightest and best of clinical and basic science investigators. As the answers come in, and sooner or later they will come in, there is no doubt that medicine should be able to devise new technologies for coping with the things that go wrong in the process of aging. This is an optimistic appraisal, but not overly so, provided we go carefully with that phrase, things that go wrong. There is indeed an extensive pathology of aging, one thing after another gone wrong, failure after failure. The cumulative impact of these is what most people have in mind as the image of aging, and most people fear. But behind these, often obscured by the individual items of pathology is a quite different phenomenon, normal aging, which is something else again, not at all a disease, a stage of living that can only be averted or bypassed in one totally unsatisfactory way, but is nevertheless regarded in our kind of society as a sort of slow death. Everything in the world gone wrong. The two aspects of the problem are quite different. One can be approached directly by the usual methods of science, but I am not sure about the other. The list of pathologic events is a long but finite one. Away at the top are the disorders of the brain leading to dementia, the single threat dreaded most by all aging people and by their families as well. Bone weakness and fractures and arthritis and incontinence and muscular wasting and cancer and Parkinsonism and ischemic heart disease and pneumonia and an increased vulnerability to infection in general, all these and more. These represent the discreet, sharply identifiable disease states that are superimposed on the natural process of aging, each capable of turning a normal stage of life into chronic illness and incapacity or premature death. Medicine and biomedical science can get at them one by one, dealing with each by the established method of science, which is to say by relying upon the most detailed and highly reductionist techniques for research. If we succeed in learning enough about the still deeply obscure facts about Alzheimer's disease, we may have a chance to turn it around and in the best of worlds to prevent it. But lacking these facts, we are going to be stuck with no way at all to alleviate and no way to help. So reductionist science is the way to go for as far ahead as we can see. If the science is successful, we can hope for a time when the whole burden of individual disease states is lifted away from the backs of old people and they are left to face nothing but aging itself. And what then will such an achievement by biomedical research remove aging from our agenda of social controls? If old people don't become ill without right diseases, acute or chronic, right up to the hours of dying, are there health and social problems at an end, should we then give up the practice of geriatrics and confine our scientific interest to gerontology? Of course not. It is possible that there will be more things to worry about for old people than is the case today and more of them coming to the doctor's office for advice. Aging will still be aging. A strange process still posing problems for every human being faced with the prospect and science will still have much to do and much to learn. But there will have to be a different kind of science capable of comprehending more than the intricate mechanisms of individual diseases large enough in its vision to perceive the existence of a whole person. The classical reductionist approach will not do for this. The word holistic was invented in the 1920s by General Jan Smuts to provide a shorthand for the almost self-evident truth that any living organism and perhaps any collection of organisms is something more than the sum of all its parts. And I wish holism could remain a respectable term for scientific usage, but alas, it has fallen in bad company. Science itself is really a holistic enterprise and no other word would serve as well to describe it. Years ago, the mathematician Poincaré wrote that science is built up with facts as a house is with stones. But a collection of facts is no more a science than a heap of stones as a house. But anyway, the word is becoming trendy, a buzzword, now almost lost to science. What is called holistic thought these days in medicine is more like the transition from a mind like a steel trap to a mind like steel wool. Holistic medicine, if it is anything, is an effort to give science a heave hoe clear out of medicine to forget all about the working parts of the body and get along with any old wild guess about disease. And we do need another word to tell a system from the components of a system, but I haven't been able to think of one. I went through my dictionary and got sidetracked, as usually happens. Leaping through, I ran across geriatrics and gerontology and I went looking for other cognates from the Indo-European root, gear. Zarathustra, I found, and Zoroastrianism. Aha, I thought. Here's a new line between the wisdom of the ages and the wisdom of the ages. But then when I looked more closely, I learned that Zoroaster and Zarathustra really meant nothing more than the owner of old camels. But it is a line of thought to think about. The mind of an old person ought to be more than just the assemblage of sequential experiences lined up one by one, seriatim, in the lifetime of that mind. And indeed, it sometimes is. And when we observe this phenomenon, as we do in a few people in their 80s and 90s, we call it wisdom. The Indo-Europeans had that word better set on its course, by the way. Wisdom came from this ancient root, wade, meaning simply to see. And from that same root we have as cousins, wise and wit in both its meanings vision and advice, the things we should be expecting from old people. And also rig Veda, by the way, a hymn to wisdom. The trouble with looking at aging from the point of view of a scientist is that we are only accustomed to the reductionist way of looking. We can construct hypotheses about the possible mechanisms of senile dementia and then set about looking for selective enzyme deficiencies or scrappy like slow viruses in the brain. And that is surely the way to go. We can make up stories about the failure of cell to cell signals in the cellular immune system of aging animals and examine at close quarters the vigor of lymphocytes and all their various stripes. Probably at the end, not only finding what goes wrong in an aging immune system, but also how to replace what's missing. And that is surely also the way to go. We have somewhere within grasp the information needed for explaining bone demineralization and fixing it. Given some luck and a better knowledge of immunology and microbiology and the inflammatory process, we ought to be able to solve the problems of rheumatoid arthritis and osteoarthritis once and for all. And we are learning some things about nutrition and longevity that we used to be ignorant about. If we keep at it, sticking to the facts that our reductionist best, we ought to be able to move geriatrics and medicine itself onto a new plane in science. But we will still have people who must grow old before dying and medicine will have to learn more than medicine knows today about what growing old is like. The behavioral scientists and the psychiatrists and psychologists and the sociologists and anthropologists, even the economists and the historians will all have a part in the work that needs doing. Looking for data, piecing facts together, trying to make sense of the whole after the out of their separate parts of the problem. But their efforts, although probably indispensable, will not be enough. I suggest that we need a reading list for all young physicians and investigators to consult at the outset of planning for a career in science and particularly in the scientific study of aging. Young people can't start to construct hypotheses without having the ghost of an idea what it means to be old. To get a glimpse of this matter, you have to leave science behind for a while and consult literature, not the literature, as we call our compendium of research, just plain old pure literature. One solid source book was written by the novelist Wallace Stegner, as good a writer as anybody around, better than most, who wrote a book called The Spectator Bird in 1976 about a literary man and his wife getting on into their late 60s and early 70s. To qualify for my list, you have to be old enough to know what you're writing about, and Stegner was the right age for his book. The novel is, or it ought to be, required reading for any young doctor. Indeed, The Spectator Bird is good enough to educate doctors for any specialty career, even cardiac surgery, and come to think of it maybe especially cardiac surgery. Stegner was a friend of Bruce Bliven, the former editor of The New Republic, and Bliven is brought into the novel for a short episode and a wonderful quotation. Someone asked him when he had reached the age of 82 what it was like to be an old man. Bliven said, I don't feel like an old man. I feel like a young man with something to matter with him. Another on my book list is Malcolm Cowley, and his book of personal essays called The View from 80. This is better than anything to be found in any textbook on medicine, infinitely more informative than most monographs and journals on geriatrics. Cowley writes with all the authority of a man who has reached 80 on the run, and is just getting his second wind. He, like Wallace Stegner, was also attached to Bruce Bliven. He quotes something that Bliven wrote to some friends three years later when he had reached 85. Bliven wrote, we live by the rules of the elderly. If the toothbrush is wet, you have cleaned your teeth. If the bedside radio is warm in the morning, you left it on all night. If you are wearing one brown and one black shoe, quite possibly there was a similar pair in the closet. I stagger when I walk and small boys follow me making bets on which way I'll go next. And this upsets me, children shouldn't gamble. Malcolm Cowley writes in great good humor, and to most of the people he admires who made it into their 80s and 90s seemed to share this gift, but it is not always the light humor that it seems. An octogenarian friend of his, a distinguished lawyer said in a dinner speech, they tell you that you lose your mind when you grow older. What they don't tell you is that you won't miss it very much. A few old people have written seriously about their condition with insight and wisdom. Florida, Scott Maxwell, once a successful actress, a scholar, and always a writer, wrote, age puzzles me. I thought it was a quiet time. My 70s were interesting and fairly serene, but my 80s are passionate. I grow more intense with age. To my own surprise, I burst out with hot conviction. I must calm down. I am too frail to indulge in moral fervor. Living alone in a London flat after the departure of her grandchildren for Australia, nearing her 90s, she wrote, we who are old know that age is more than a disability. It is an intense and varied experience, almost beyond our capacity at times, but something to be carried high. If it is a long defeat, it is also a victory, meaningful for the initiates of time, if not for those who have come less far. When a new disability arrives, she writes, I look about me to see if death has come and I call quietly death is that you, are you there? And so far the disability has answered, don't be silly, it's me. It's possible to say all sorts of good things about aging if you're talking about aging free of meddling diseases. It is, I suppose, an absolutely unique stage of human life, the only stage in which one has both the freedom and the world's blessing to look back and contemplate what has happened to her life instead of pressing forward for new high deeds in Hungary. It is also obviously a period for others, younger and filled with questions to draw upon. It is one of the three manifestations of human life responsible for passing along the culture from one generation to the next. The other two are, of course, the children who make the language and pass it along and the mothers who see to it that whatever love there is in a society moves into the next generation. The agent hand along the experience and the wisdom if they are listened to and this in the past has always been a central fixture in the body of a culture. We do not use this resource well in today's society. We tend always to think of aging as a disability in itself as sort of long illness without any taxonomic name, a disfigurement of both human form of spirit. Aging is natural, we say, just as death is natural, but we pay our respects to the one no more cheerfully than to the other. The science could only figure out a way to avoid aging altogether. The zipping us straight from the tennis court to the death bed at the age of, say, 100, we would probably vote for that. And even if it could be accomplished by science, which is well beyond my imagining for any future time, society as a whole would take a loss. In my view, human civilization could not exist without an aging generation for its tranquility and every individual would be deprived of an experience not to be missed in a well run world. We need reminders that some exceedingly useful pieces of work have been done in the past and are still being done by some very old people in good health or in bad. Johann Sebastian Bach was a relatively old party for the 18th century when he died at age 65, but he had just discovered a strange new kind of music and was working to finish the art of fugue, an astonishing piece based on the old rules but turning the form into the purest of absolutely pure music. Montaigne was even younger at his death, 59, but that was an old man in the 1500s. And he was still revising his essays and adding notes for a new edition for which he chose the appropriate epigraph. He picks up strength as he goes. In our own time, Santayana and John Dewey and Bertrand Russell and Shaw, Robert Frost and E.M. Forster, you could make a list lengthened by the score. We're busy thinking and writing their way into their 70s, 80s and beyond. The great French poet Paul Claudel wrote on his birthday, 80 years old, no eyes left, no ears, no teeth, no legs, no wind, and when all is said and done, how astonishingly well one does without them. Of all the things that can go wrong in aging, the loss of the mind is far and away the worst and the most feared. Florida Scott Maxwell wrote down what most old people fear the most and have in the back of their minds. Please God, I die before I lose my independence. But in the face of today's ignorance about so many different diseases, including those of aging, there is the most surprising optimism amounting to something like exhilaration within the community of basic biomedical researchers. There has never been a time like the present. Most of them, the young ones especially, have only remotely on their minds the connection of their work to human disease problems. They have an awareness that something practical and useful may come from their research with luck sooner or later, but this is not what drives the work along. What they are up to and now becoming supremely confident about is finding out how things work. This is true for the immunologists threading their way through the unimaginably complex network of cells and intercellular messages comprising the human immune system. It is true for the experimental pathologists and their biochemist colleagues at work on the components of the inflammatory reaction with new reactants turning up every month. The cancer biologists are totally confident that they are getting close to the molecular intimacies of cellular transformation and the virologists among them are also riding high. Out in the front lines are the molecular biologists and geneticists in possession of research techniques that permit them to ask and then answer almost any question that pops into their minds. And perhaps these people will turn up items of information needed for the prevention of arterial disease and intravascular coagulation or for the control and reversal of the immunologic reactants in charge of autoimmune disease. I have no doubt in my mind that the lines of research now open for cancer cell research will soon have laid out the names and numbers of all the players and we will have choices to make among totally new kinds of pharmacology and perhaps immunology. I see no reason to think that neurobiology is in any sense the impenetrable science that it seemed to everyone 10 or 15 years back. And the possibility of reaching a deep biochemical comprehension of the events gone wrong in schizophrenia and the manic depressive psychosis is becoming a quite realistic prospect. The senile dementias, Alzheimer's and the rest are beginning to look like proper biological problems. Ultimately to be solved if the work is done by good people at a deep level. This is one way to put the case. If you're feeling as I do optimistic and hopeful but most of all fascinated by today's science you can predict major advances in medical care somewhere ahead in real time. But there is of course another way of viewing the scene. All the excitement, each confrontation of total surprise in the research signifies they really didn't know very much to begin with and perhaps we are just beginning to penetrate surfaces with miles and miles to go and with decades of research still to be accomplished before any goal can be reached. It may turn out a much harder and longer task than any of us can guess and the extent of our ignorance much more profound. Either way you look at it we are not about to change the world nor are we in any position to begin talking or worrying about changing a human being much less the species. Yet this is precisely what some people are worrying about and for the life of me I cannot understand why. If we are extremely lucky in the research and can learn much more than we know today about the insertion of normal genes and the switching off of flawed genes in mammalian cells we might discover how to correct a few heritable diseases in which single gene defects are the cause of disease and this could mean a technology for installing cells able to manufacture normal hemoglobin instead of sickle cell hemoglobin as well as methods for correcting a fair number of congenital enzyme deficiencies now responsible for death in infancy and early childhood. Inserting isolated genes into the somatic cells of a human being is a genuine possibility for the future although it is by no means near at hand. Changing the genes in germ plasm cells is quite another matter. I doubt that any accredited cell biologist has a good idea about how to go this about this formidable step in experimental animals or in man. So far and for a long time to come the human genome seems to me quite safe from meddling nor is this likely to become a matter of either scientific interest or concern if medicine can achieve success in changing the code within the single genes of somatic cells. That step, if it works would serve the whole therapeutic purpose in sickle cell disease and others of a similar nature and I can see no harm or imaginable risk in trying. But I think this is not really what is on the minds of people who are apprehensive about the manipulation of human genes or what has become fashionable to call and I wish the term had never been invented genetic engineering. I think they are worried about the prospect of altering human behavior or breeding up races of humans with different sorts of intellect. I doubt that anyone would have misgivings about the substitution of normal genes for the defective ones in congenital disease of children. If it were not for the apprehension that one thing will lead to another and before we are aware of it the door will open to experimental modification of the mind of the human race. To evaluate this risk it is necessary to appraise the present state of our understanding of behavioral genetics. I cannot think of a field in biomedical science about which less is understood by the public at large and by the scientists who study behavior than the genetics of behavior. Not just human behavior but animal behavior in general. In the case of humans the problem is so complex and so obscure as to be almost beyond stating. It may well be that such behavioral traits as general intelligence or artistic talent or aggressive behavior are heritable characteristics but it may equally well be that they are not and they are the matter rests. As far as genetic manipulation goes it makes no difference for there is nothing to manipulate. It is true that one can use the technique of recombinant DNA to introduce an isolated gene from the cell of one animal into the genome of the cell of another and the recipient cell will then begin producing the protein or peptide coded for by the transplanted gene and so will all the progeny cells of the recipient. But mind you this is all done in cell cultures not in animals. One can accomplish the same end result by infecting an individual cell with a virus that happens to be carrying along bits of genetic information from a previously infected cell. The great usefulness of this refined technology is that it permits the most detailed chemical scrutiny of individual genes as well as their gene products. The ability to clone genes in this way has led to an entirely new method for analyzing the central genetic abnormalities that work in cancer cells for instance and is presently illuminating the puzzling capacity of lymphocytes to recognize with high specificity a near infinity of foreign antigens. Sooner or later we will maybe begin to understand the strange business of embryologic development and differentiation employing techniques derived from the kinds of research being done on recombinant DNA today. But none of this has anything to do with behavior so far as is known. The genetic controls which govern the construction of an embryonic brain and those which will later determine how an adult brain functions are absolute mysteries. Whether they are in any way related to the molecular genetics of protein synthesis is unknown. If it turns out ultimately that there are indeed genes that act as determinants for various aspects of human behavior or intelligence, which I am temperamentally inclined to doubt in the absence of evidence one way or the other, it is inconceivable that single genes could act as such determinants. If it is so, myriads of different genes lodged in different chromosomes would have to be involved even for an act as simple as a smile. We are, I think, centuries away from this kind of science. I acknowledge that statements like this have been made before by elderly prophets of science, sometimes followed soon thereafter by cascades of astonishing new information to transform the field, but in this case I do feel secure. The human mind I feel safe in asserting is still a way over our heads. And even if I believed otherwise and felt that recombinant DNA technology might someday be put to work to change human beings and also felt, as I surely would, that such a thing should be prevented by any means possible, I would not know what line of research to stop. If such a thing were to come about, it could only happen as the result of the purest kind of basic science. And when it happened, it would have to come as a total overwhelming surprise. Nobody could possibly have foreseen in the early 1970s the emergence of recombinant DNA as a laboratory technique. It happened as the result of a series of unexpected, unanticipated surprises in different research laboratories studying the structure and function of DNA. Step by step, each one taken in the dark, there came into view a procedure so simple and at the same time so beautiful that everyone realized that biology would never again be the same. It has turned out to be the most important set of scientific observations to be made in biomedical research since Darwin, in my view. And it will turn out further on almost incidentally to be the surest way into the problem of cancer. But my point is that if you still view the recombinant DNA technology as a hazard to life and wish we had never developed it and were to think your way back to the steps that a committee might have taken in the late 1960s in order to foreclose the possibility, there is in retrospect nothing that could have been done except to put a stop to cell biology and genetics research across the board in short to stop biological science. And if that hypothetical committee had acted in that way, we would have no knowledge of oncogenes or their gene products today and no attractive way into the depths of the cancer problem. You either have science or you don't. Technology is another matter. If ever it happens that the kind of information is at hand to make it possible to transfer human intelligence genes into the human genome, the undertaking itself could never be launched without the expenditure of a substantial proportion of any nation's gross national product. For all of my instinctive misgivings about politicians, I would trust the prudence and the good sense if not the economic reservations of any government. I can think of a great many things to worry about for mankind's future with nuclear warfare at the top of the list, but I simply do not have the time or inclination to worry about cloning brains or behavior. Even less do I intend to worry about cloning a whole human being. Theoretically, of course, it is a possibility. All somatic cells contained within the DNA of their nuclei, all the genetic instructions needed for reconstructing the entire precise same organism. In a skin cell or a brain cell, the genes for being anything, but that specialized cell type have been shut off, but the silenced genes are still there. It is known that the nucleus of a tadpole cell can be transplanted into the enucleated egg of an adult frog and the combination will then proceed to reinvent exactly the same tadpole. And there is some evidence, still highly controversial, that something like this can be done in mice. But to extrapolate from this to the assertion that the same thing can be done with a human cell combined with a neutral human egg is a piece of science fiction already written out by Rorvik, but still a very long shot in real life. The question about the procedure is not so much whether it can be done as to why anyone would ever want to try. I can imagine doing it just as I once was persuaded to imagine the landing on the moon, and I do suppose that if you took the entire resources of the National Institutes of Health, including the clinical center, and spent 10 times the NIH budget plus a large piece of the DOD budget for the next 10 or 20 years, you might get it done at least once. Suppose then you had cloned the genome of an eminent scholar and diplomat of exceedingly high intelligence. What would the expensive product be? It would be a newborn baby, much like any other with a remarkable resemblance to the baby pictures of the scholar diplomat. But then what? Unless you had immediately at hand the diplomat's original parents, themselves at the same age they were at his birth, plus all the siblings and aunts and cousins, the clone would be raised and nurtured in a different environment, speaking a different accent, thinking about the world in different ways from the moment of opening his eyes. Very well you could get around this problem by first cloning the parents and the relatives, and waiting for these clones to grow up before starting on the Xerox diplomat. But that would only be the beginning of the matter. Schoolmates, teachers, friends, the odd person across the aisle and the subway, the novelists, journalists, and movie makers of the diplomat's childhood years, all of these would have to be duplicated along with all their relatives and friends unless all our ideas about the influence of environment on early childhood development are wrong. Before you had finished laying out the protocol, you would find yourself planning to clone the whole world, bringing the environment back to its present highly unsatisfactory state. As for the plight of the original subject, the parent scholar diplomat, try to imagine his fate, doomed to see the upbringing and disciplining of himself all over again, through adolescence, juvenile delinquency, acne, high school mathematics, insecurity, vanity, and all the rest. I cannot imagine it, nor do I believe Congress would ever vote for it. I am of course professionally biased, and I tend to overreact. I confess to a certain crankiness in my reaction to the warnings of imminent danger to society from basic biomedical science. Perhaps there are some risks ahead even if my bias blinds me to them, but I will stay unrepentant, cranky, unwilling to listen for as long as these small, improbable risks continue to engage the obsessive attention of a society that ought to be spending all of its worrying time and all of its insomnia on the immediate, close at hand danger of thermonuclear warfare. I will gladly join in the anxiety about changing the human species by science once I become convinced that another kind of science is not about to wipe us out, thank you. Good grief, the jackpot already. I invite now the members of the panel to come forward to the table, and will you, who are ushers, collect questions from the audience and bring them forward to Dr. Christensen as soon as possible. One of the most interesting features of Nobel conferences are the exchanges between our guest speakers. And I want to begin this first session with an invitation to you to respond to the lecture that we have just received, either with questions or with comments. You may not in the back be able to see the names on the table. Dr. Grobstein, Dr. Goodfield. I'm reading from my left. Dr. Galen, Dr. Thomas, Dr. Anfanson, and Dr. LaBax, can I, yes, Dr. Goodfield. Well, this is not going to be the first time in my life that I find myself in a situation where I agree almost absolutely with what my dear friend, Lou Thomas, has said. And I think that because I agree so much, one thing I wanted to do was to say something which would establish where I think I'm going to come every time, the angle from which I'm going to come every time at all the questions we are raising here. And I want to tell you this, I want to begin just saying this before I just particularly take up one aspect of what Lou said by telling you a story. There are four people in a railway carriage. I think you call it a railroad train. Two have just got married. There's an old man and there's also a young student. The train goes into the tunnel and the sound is heard of a smacking kiss followed equally by a very heavy slap. And as the train comes out into the light once more, the reactions of the four people inside are as follows. The husband says, how virtuous my wife is. The old man kisses her and he slaps her. She slaps him, sorry. The wife says, how chivalrous is my husband? The old man kissed me and he slapped him. The old man said, it's awful to be old. The student kisses the girl and I get the slap. And the student says, how clever I am. I kissed the young lady and hit the old man. Now, I tell this story because one aspect of Lou Thomas' presentation, which he spoke about and which I think we have to develop, is concerned with what we in society, what attitudes have to change within society to deal with the particular problems that we are facing. I come here as somebody who can offer only, I think, rumble gumption, which is a Scottish word for a degree of common sense. And I don't want what we discuss about to degenerate into professional knocking or science knocking. What I do want to do is to thrust this back squarely upon the people who are in the audience and us in society. Because if we are going to deal with the problems that Lou has articulated and I believe that those are the real problems, the ones we should be more seriously concerned about, especially with that that concerns aging, we as a group are going to have to take a completely different attitude towards aging, towards the old people in our society and get into a situation where if I told you that story again, you wouldn't laugh because you wouldn't think it funny. Thank you. Dr. Galen? If I'd like to address this one question to Dr. Thomas, it's unfair because he answered so many and because he raised so many questions, but there's one that I would hope he might attend to. If I understand correctly and I do agree with him, at one time, access to a physician was as likely to encourage your death as to discourage it. In those days, it didn't necessarily represent a privilege to be able to buy the services of a physician, but all of that has changed in the last 50 years and we really have become the life-saving profession that only the uninformed laity at one time thought we were. That being the case, even as an entrepreneurial society and as capitalistic society as ours, to my knowledge, we have never sold lifeboats to my knowledge. We have never sold lifeboats in a sinking ship or places in a lifeboat. I wonder if Dr. Thomas, you would like to address the whole question of access to medical care. Now that medical care is not a matter of comfort, which we've always traditionally sold, but which is indeed a life-saving mechanism, and this is in response to the kind of despair at seeing a father advertise for kidney transplants or liver transplant. How are we to fairly use these fruits of our scientific progress of the last 50 years? How can we handle this within the entrepreneurial aspects of medicine as we now run it? Yes. Dr. Thomas has touched on so many things, as is already clear from the two questions that have been asked, that he's opened himself up, of course, to very many queries, more than probably he can answer. But I would like to emphasize what he has said about the problems of reductionist versus holistic approaches to medical problems, and of course, the same polarization occurs in almost all areas of human knowledge. Whether Dr. Thomas has any advice to those young people who are today making up their minds about how best to prepare themselves for careers in the health profession, and since it is the case that the disciplines tend to emphasize either holistic or reductionist approaches and very few have found a way to integrate these, what kind of advice should be given to young people these days in terms of their preparation for function as health professionals? Dr. Thomas, respond to the two questions, please. Well, the first, Dr. Galen's question is one that the entire profession of medicine and also I'm happy to say our colleagues and sometimes friends in the nursing profession are worrying over and debating among themselves and there are as yet no clear answers. It used to be easy to answer the question of how to provide access for everyone to high quality healthcare in life or death situations. The answer was simply to train up more physicians and have more medical schools. It is now clear that that doesn't work and it's probably not going to work if we keep on doing it. One of the problems is that people from the social sciences who look at the medical profession have come to the conclusion that we must be wasting an awful lot of our time. Something like 80% of the visits made to a doctor's office or to the outpatient clinic of a hospital are for illnesses that are probably going to go away within the next 24 to 48 hours no matter what is done or illnesses that in real life don't exist at all. Anxieties worry about being ill. The other, somewhere in the other 20%, perhaps half of the other 20% are illnesses about on which life or death or incapacitation may very well hang and where the technology of medicine is absolutely essential. And how you sort things out by some new system where the first 80% don't crowd out the 10 or 15% who really need quality care is an open problem. We have large segments of the population in this country who never see a doctor from in a year's turning. These are the residents of what we call these days the ghetto areas in cities like New York and Chicago and I have no doubt Minneapolis and St. Paul. There isn't any equity in the distribution of care. I have thought that now that the cost of obtaining a medical education has assumed its present astronomical levels with costs ranging anywhere from $15,000 a year on up for tuition and room and board. A level of cost beyond the reach of most middle economic class families and all families with less means. There may be a little more give to the situation. Perhaps somebody will decide that either state or federal governmental agencies ought really to be underwriting a substantial part of the cost of medical education in return for a quid pro quo and the quid pro quo would be some kind of national service for some substantial period of time like four or five years in places where doctors are really needed. And while we're worrying about this problem I would worry still more about the health problems in the part of the world we like to call the third world where disease problems really are of crucial importance where the only solution to the population and overpopulation problem in the poorer nations of this country is to do something in aid of the health of newborn babies and children under the age of five who are now being wiped out in some societies 70% of them and within the first five years by diseases that we should find it very easy to treat if they were to turn up in this country. These people need medical service. I will end on a note of high controversy. I think what the country needs is more nurses, more highly trained nurses of either sex to be trained to be able to cope with most of the things that doctors are confronted by and then for the things that can't be coped with by them technologically be able to refer them on quickly to more specialized care. And if we had an international health service where Americans and I would say European youngsters as well would be coming out of medical school and serving time in the impoverished countries of the earth, I would like to see the nursing profession involved at a very high level in that. Cliff Grobstein asked me what kind of advice to give young people these days who are either entering or contemplating medical education. What is the future going to be like? And I'm old enough to go very carefully with both that question and the answer. All I know from my own experience is that when I was at that age, I thought medicine was going to be exactly like what it was. I was absolutely convinced that what I observed in my own household, in my father's practice of general medicine and surgery, that this is what it would be like all through the rest of time. And it's changed to such an extent that I could no longer recognize and I no longer understand what on earth was going on in the medicine 50 years ago. So about all I can think of that's safe to say to youngsters, thinking of going into medicine is that whatever it seems like now, it's going to be a totally different profession within the next 10 years. And maybe everything is moving so fast these days within the next five years. Dr. LeBax. I have one comment and two quick questions. My comment is one of appreciation for your pointing us in the direction of literature, particularly that literature that expresses the experience of people as a forum from which we might learn in medicine. That then also sparks my first question. You have not mentioned non-western forms of medicine as another forum from which we might have much to learn and I would be curious to see whether you are also incorporating concern for non-western forms of medicine and a not altogether unrelated question. Why are you so pessimistic about the wheels of bureaucracy related to war and yet so optimistic about the wheels of bureaucracy related to medical research and action? I don't, thank you, those are two good and hard questions which will require at least one of them some evasive footwork on my part. The way I shall get out of the question about having left out non-western, which is I suppose to say eastern, medicine. But not only eastern, I think medicine, you also would include medicine from the cultures of Africa and Aboriginal South America, especially Chinese though, I knew you had that in mind. And my answer is I don't know enough about it and I don't understand most of what I'm told but I'm open-minded and I become goggle-eyed when acupuncture is described to me. The trouble is I've never had it done to me and until I have it done to me, I'm not gonna believe it. But there is a lot that we're gonna learn. I mentioned when I was talking The Great Discovery by George Minot and Murphy and Whipple of the specific effectiveness of liver extract, liver and then liver extract in the treatment of pernicious anemia. Pernicious anemia for those of you who don't know it was and still is one of the major and most lethal of all inborn errors of metabolism and it tends to strike people in their youth or adolescence or even later on in their early middle years and it used to be regarded as a totally fatal disease until Murphy and Minot and Whipple by a series of accidental discoveries found that liver worked. And it has been called to my attention since then that an ancient Arab scholar left records, this was Avicenna, left records from, I think, I've forgotten his century, but it was a long time ago, that the feeding of liver was useful in patients who had lost or were unable to make blood. At least six centuries went by before that was rediscovered and I'm quite prepared to be just. Let me deal with a second question about why I seem as pessimistic as I am about statecraft and the kinds of levels and the cast of mind of the bureaucracies that deal with the problem of thermonuclear warfare and what we call defense and why I am optimistic about the scientific enterprise. The question is about the optimism, not about the pessimism. Why are we not pessimistic about both? I'll tell you about the pessimism any day, you'd like to hear it at some length, but about the optimism, I think that there is in the world today a network of scientists, working scientists who do to be sure receive funds from their own governments in order to do the science but who behave in a totally non-nationalistic way. The biological scientists today are in close touch with each other across all national boundaries except that of the Soviet Union. Young molecular biologists at my own institution seem to know from day to day exactly what is going on in Melbourne and in Edinburgh and in London and Paris and their opposite numbers in foreign countries work with them as though they were colleagues down the corridor. There is no, as far as I can see, there's no such thing as French science from the point of view of a French biological scientist. Indeed, they're proud of being French and they wish we would all speak French but when they do their science, they do it because it is an international effort. I rather trust to the persistence of this because I see no other way of having science done. Science is, of all things, an entirely communal effort. It's the most communal enterprise that I've ever thought of despite it being at the same time highly individual. And I just hope that governments in general don't ever catch sight of the fact that they have on their hands an international network that is genuinely subversive where there are, there are lots of antipathies and lots of rivalries but one's national origin has nothing to do with whether or not this kind of collaboration works. I think Chris may have a feeling about this as well because he's had a closer look than I have at how well the international system works. I just wish that we had some way of drawing in the Soviet biological sciences. There's nothing wrong that I can think of, not much you can do in the way of weaponry with the kind of biology that is most interesting today. I don't know how far along the Soviet sciences have come in the fields that are most attractive today but I have an idea that no matter where they are, they would profit a great deal by having closer contact, easy contact of this amiable non-national sort with their opposite numbers in this country and in Europe and the UK and Australia and Japan and Israel. I would like to see this happen as a matter of fact. I think I'm perfectly willing for the time being to confine my objections to grumbling about the inability of the physicists to move back and forth and the computer scientist, God knows, can't move back and forth. But those innocent ones of us who are interested in biology and especially in developmental biology and neurobiology and immunology and molecular genetics ought to be flocking back and forth and having the times of our lives. We don't do it now because, I suspect because we haven't thought much about it. I want to bring the session to a close, Sue, but before I do, Dr. Anfanson, you wish to comment? I can, short one, I hadn't thought of commenting, but I might just mention that I disagreed at some extent with Lou as my lecture this afternoon will enlarge on. I too have been terribly pessimistic about the possibilities of thermonuclear warfare. I think it's number one, A1, to worry about. But as contrasted to what he said, I feel that the current genetic evolution, a revolution, sorry, will soon have to be put in the same class. I think, A, you have scientists, young and old, who simply are gonna do what they wanna do, generally. It's very hard to tell a scientist not to do something because he has to, he'll go into a cellar and do it. But you do it because of the interest in science and excitement about science. That's the one aspect of this. The other is that there seems to be no way to control this. I mean, I think governmental panels and any kind of panels are unlikely to be successful, although it is something we will have to devise in the next 10 or 20 years, because this field moves very rapidly and we're gonna have to work out some sort of a system that'll be worldwide. I mentioned the Davy Crockett hats the other night. So everybody should wear a Davy Crockett hat to indicate that they're in favor of something. Belong to an international club, which will be the control and supervision of biomedical research and genetics, et cetera, preventing people from making people with three heads and by genetic engineering. I'm just more pessimistic than Louie. Thank you. We have some excellent questions from the audience, which we'll hold till this afternoon since the lunch hour is drawing near, but there is one that I think could be answered quickly, Dr. Thomas. Someone needs to have the term reductionist science clarify it a bit more. The kind of science that is done after, one has guessed what nature might really be like and has made up a hypothesis, then some experiments are done and the experiments are designed to inquire into the details and then the details of the details and to go as deeply as one can. And running, as we all know, the risk of losing sight of the whole affair because of the engaging interest that is presented by the details is the way science is done and there it is. Thank you. At 20 after one, there'll be a brief concert of music as you see in your program and we'll see you at 1.30 also for the next session.