Chase, Chance, and Creativity

by James H Austin

Monte Greer, M.D.: head of Endocrinology at Oregon whose sensitive microbalance made it possible to measure small amounts of isolated sulfatides.

  George Jervis, M.D.: pioneering investigator who first showed that an inherited neurological disease (phenylketonuria; PKU) was caused by a deficiency of the enzyme, phenylalanine hydroxylase.

  Lahut Uzman, M.D.: neurological researcher whose article alerted me to the fact that white blood cells in a kindred neurological disease might contain abnormal deposits.

  The McLean children: young brother and sister with a rare form of metachromatic leukodystrophy in which three sulfatases are deficient.

  Margaret De Merritt: sparkling technician, later medical student and colleague, who helped originate new methods and kept things lively in the laboratory.

  John Harris, M.D.: ophthalmologist at Oregon who told me about hyaluronic acid sulfate, a model sulfated molecule.

  Darwin Lehfeldt: medical student whose laboratory work contributed to the experimental studies of sulfatides and cerebrosides.

  Patient D. W.: child with globoid leukodystrophy whose illness drew my attention to the existence of this disease.

  Saul Korey, M.D.: Professor and Chairman of Neurology at Albert Einstein Medical College whose prodding stimulated me to isolate globoid bodies.

  Kunihiko Suzuki, M.D.: neurochemist and associate professor at the University of Pennsylvania who proved that the galactosidase which splits cerebroside was deficient in globoid leukodystrophy.

  Roscoe Brady, M.D.: Chief, Section of Neurochemistry, at the National Institute of Health, Bethesda, who collaborated in the enzymic studies in globoid leukodystrophy.

  George Dana, M.D., and Elizabeth Dana: close friends, who by stimulating an interest in World Federalism created the setting for a sabbatical in India.

  Philip and Rhita Feingold: close friends and fellow World Federalists whose beliefs contributed to the decision to go to India.

  Norman Cousins: President, World Association of World Federalists, whose personal magnetism, international orientation, and editorials in the Saturday Review have been a constant source of inspiration.

  Bimal Bachhawat, Ph.D.: benevolent Indian biochemist whose collaboration made possible the discovery that an enzymic deficiency of sulfatase A was the cause of metachromatic leukodystrophy.

  Peter Rabbit: He led me, repeatedly, on a merry chase.

  Tom Austin: our dog, a Brittany spaniel, who prompted the sequence of events leading to the identification of glucose polymers in Lafora bodies.

  Susumu Yokoi, M.D.: Associate Professor of Neuropsychiatry at Yokohama Medical School; collaborator in the isolation and characterization of Lafora bodies.

  Richard Berry, M.D.: Professor of Neuropathology at Jefferson College of Medicine who contributed rare pathological material containing Lafora bodies.

  Donald Armstrong, M.S.: friend, co-worker, and former graduate student, who went on to investigate cellular oxidative mechanisms in various retinal disorders.

  David Stumpf, M.D.: medical student working toward his Ph.D. in our laboratory at Colorado who helped characterize the abnormalities of sulfatase A in MLD and of sulfatase B in MPS VI (Maroteaux-Lamy disease).

  Edward Neuwelt, M.D.: medical student at the University of Colorado who, with David Stumpf, showed that the enzyme protein was present in MLD but was deficient in sulfatase A activity.

  Norman Radin, Ph.D.: lipid neurochemist and Director of the Mental Health Research Institute at the University of Michigan who originated a system for measuring cerebroside galactosidase and discovered a way to increase its activity.

  Drs. Christian de Duve, H.G. Hers, and F. Van Hoof: investigators at the University of Louvain in Belgium whose work helped establish the existence of lysosomes in cells and the lysosomal theory of disease.

  Bertha Holtkamp Austin: my mother, a former laboratory technician, who stimulated my interest in people and in the biological sciences.

  HorstJatzkewitz, M.D.: biochemist at the Max-Planck Institute in Munich who also found increased sulfatides in MLD, and who showed with Ehrenpreisle Mehl, that sulfate is split from these lipids by the enzyme sulfatase A, acting as a cerebroside sulfatase.

  Jock Cobb M.D., and Holly Cobb: close friends whose donation of a book on Zen stimulated my curiosity.

  Nanrei Kobori-roshi: Rinzai master who inspired me to begin Zen training, and to stick to it.

  The international nature of the contributors to research in MLD is shown in figure 13.

  Permissions

  I wish to express my appreciation to the following authors, their copyright owners, and their publishers for permission to reprint excerpts from their copyrighted works as indicated here and specified further in the notes:

  George Allen & Unwin, Ltd., for two selections from Thinking, An Experimental and Social Study, by Frederick Bartlett; and for two adaptations from Creative Malady, by Dr. George Pickering.

  Atheneum Publishers for one quotation and several adaptations from The Dynamics of Creation, by Anthony Storr.

  J. B. Bailliere, for four selections from Introduction a ('Etude de la Medecine Experimentale, by Claude Bernard.

  Bradford Cannon, M.D., for selections from The Way of An Investigator, by Walter Cannon, published by MacMillan Publishing Co., Inc. (Hafner subsidiary).

  J. M. Dent & Sons, Ltd., for a quotation from The Scottish Himalayan Expedition, by W. H. Murray.

  Dover Publications, Inc., for a quotation from Hawthorne on Painting, by Charles Hawthorne.

  Harper & Row, Publishers, Inc., for quotations by Carl Rogers and by H. Anderson in Creativity And Its Cultivation, edited by H. Anderson; for quotations by Benjamin Disraeli and George Bernard Shaw found in The New Book of Unusual Quotations, by R. Flesch; and for a quotation by H. Gutman, from Explorations In Creativity, edited by R. Mooney, and T. Razik.

  W. Heffer & Sons, Ltd., for quotations by Lewis Carroll, Francis Darwin, and Piotr Tchaikovsky, found in An Anatomy of Inspiration, by R. Harding.

  King Features Syndicate for the quotation by Charles Kettering, appearing in the Reader's Digest, October 1961.

  J. B. Lippincott Company for an excerpt from Principles of Research In Biology and Medicine, by Dwight Ingle.

  Little, Brown and Company, for short quotations by Louis Pasteur, Henry Sigerist, and Wilder Penfield, from Familiar Medical Quotations, by M. Strauss; for an adaptation of a story by Henry Forbes, cited in The Difficult Art of Giving: The Epic of Alan Gregg, by Wilder Penfield; for the adaptation of the chapter by James Austin in Modern Neurology, edited by Simeon Locke; and for the quotation from As I Remember Him: The Biography of R.S., by Hans Zinsser.

  Macmillan Publishing Co., for two selections from The Wanderer of Liverpool, by John Masefield, and for a quotation from The Act of Creation, by A. Koestler.

  McGraw-Hill Book Company, for a selection from Aequanimitas, by Sir William Osler, and for a quotation from Present Tense: An American Editor's Odyssey, by Norman Cousins.

  Methuen & Co., Ltd., for two quotations from The Art of The Soluble, by Peter Medawar.

  The New Yorker Magazine for a quotation by Franklin P. Adams, originally appearing in Diary of Our Own Samuel Pepys, by Simon and Schuster.

  New York University Press for two passages by H. Herbert Fox and H. Hughes from Essays on Creativity in the Sciences, edited by Myron A. Coler.

  The News for their article on the rabbit, here entitled "Flashback; The Chase, 1942."

  W. W. Norton & Company, Inc., for a quote by Joseph Conrad from Heart of Darkness, edited by R. Kimbrough, and for a quote from The Courage to Create, by Rollo May.

  Pantheon Books for a quotation from The Way of Zen, by Alan Watts.

  Random House, Inc., for an extract from Chance and Necessity, by Jacques Monod, translated by Austryn Wainhouse; for the words "future shock," from Future Shock, by Alvin Toff ler; and for an excerpt by Albert Einstein from Einstein: His Life and Times, by Phillipp Frank.

  The Reader's Digest, for the quotation b
y Bruce Barton from The Dictionary of Quotations.

  The Regents Press of Kansas, for a quotation from Neurotic Distortion of The Creative Process, by Lawrence Kubie.

  Simon & Schuster, Inc., for a quotation from Pogo, by Walt Kelly; for two selections from Science and Sensibility, by James Newman, one by James Newman, the other by Lord Rutherford; and for a quotation from Science and Human Values, by Jacob Bronowski.

  Tavistock Publications for a quotation by Lancelot Whyte from The Unconscious Before Freud.

  Teachers College Press for an extract and abridgement of pp. 21-22 from P. Witty, J. B. Conant, and R. Strang, Creativity of Gifted and Talented Children.

  The University of Oklahoma Press for the condensation from Serendipity and The Three Princes, by Theodore Remer.

  Van Nostrand Reinhold, for quotations and abridgements by F. Barron from Creativity and Psychological Health.

  John Wiley & Sons, Inc., for two excerpts from Scientific Creativity: Its Recognition and Development, by Brewster Ghiselin; for a statement by R. Burman, R. Hanes, R. and C. Bartleson, Color: A Guide for Basic Facts and Concepts; for an extract and abridgment from M. Wallach in Manual of Child Psychology, edited by P. Mussen; for extracts and abridgments from M. Stein, C. Taylor and F. Barron, and for quotations from B. Ghiselin in Scientific Creativity: Its Recognition and Development, edited by C. Taylor and F. Barron.

  Wilmarth Lewis for quotations of passages from letters by Horace Walpole in the Yale Edition of Horace Walpole's Correspondence.

  Yale University Press for a quotation from The Furtherance of Medical Research, by Alan Gregg.

  Notes

  Preface to the MIT Press Edition

  1. M. Runco and S. Pritzker, Encyclopedia of Creativity, 2 vols. (San Diego, CA: Academic Press, 1999).

  2. D. Perkins, The Mind's Best Work (Cambridge, MA: Harvard University Press, 1981).

  3. A. Cropley, "Fostering Creativity in the Classroom," in The Crentivih/ Research Handbook, vol. 1, ed. M. Runco (Creskill, NJ: Hampton Press, 1977), pp. 83-114.

  4. A. Tannenbaum, Gifted Children: Psychological and Educational Perspectives (New York, NY: Macmillan, 1983).

  5. A. Bandura, Social Foundations of Thought and Action (Englewood Cliffs, NJ: Prentice-Hall, 1986).

  6. J. Austin, Zen and the Brain: Toward an Understanding of Meditation and Consciousness (Cambridge, MA: MIT Press, 1998).

  Preface

  1. C. Jung, "Psychology and Literature," in The Creative Process, ed. B. Ghiselin (New York: Mentor, New American Library, 1952), p. 219.

  2. J. Nurnberger, "In Memorium. Saul Korey, M.D., 1918-1963," journal of Neuropathology and Experimental Neurology 24 (April 1965): 183-86. 1. London, "Saul Roy Korey, 1918-1963," Transactions of the American Neurohs, ical Association 89 (1964): 278-80; L. Scheinberg, "Saul R. Korey, M.D., 1918-1963," Neurology 14 (January 1964): 158-60.

  By Way of Introduction

  1. A. Roe, "Psychological approaches to creativity in science," in Essays on Creativity in the Sciences, ed. M. Coler (New York: New York University Press, 1963), pp. 161-62.

  1. Of Nerves and Neurologists; Boston, 1950

  1. J. Austin, "Prologue," in Modern Neurology, ed. S. Locke (Boston: Little, Brown, 1969), pp. xix-xxi.

  2. Enlarged Nerves; Oakland, 1951

  1. J. Austin, "Observations on the Syndrome of Hypertrophic Neuritis (The Hypertrophic Interstitial Radiculo-Neuropathies)," Medicine 35 no. 3 (September 1956): 187-236.

  3. Metachromasia; New York City, 1953

  1. W. Brain and J. Greenfield, "Late infantile metachromatic leukoencephalopa- thy with primary degeneration of the interfascicular oligodendroglia," Brain 73 (1950): 291.

  4. Microscopic Studies; New York City, 1953

  1. J. Austin, "Metachromatic Form of Diffuse Cerebral Sclerosis. I. Diagnosis During Life by Urine Sediment Examination," Neurology 7 (1957): 415.

  2. References to subsequent articles in the series on metachromatic leukodystrophy (leukoencephalopathy) from the author's laboratory are included in a recent review article: J. Austin, "Metachromatic Leukodystrophy (Sulfatide Lipidosis), in Lysosomes and Storage Diseases, ed. H. Hers and F. Van Hoof (New York: Academic Press, 1973), pp. 411-37.

  5. Sulfated Lipids; Portland, Oregon, 1955

  1. M. Lees, "Simple Procedure for the Isolation of Brain Sulfatides," Federation Proceedings 15 (1956): 973.

  6. Molecules and Wanderings, 1957

  1. L. Uzman, "Chemical Nature of the Storage Substances in Gargoylism," A.M.A. Archives of Pathology 60 (1955): 308.

  7. Controls and the Experimental Globoid Response, 1960

  1. J. Austin and D. Lehfeldt, "Significance of Experimentally Produced Globoidlike Elements in Rat White Matter and Spleen," Journal of Neuropathology and Experimental Neurology 24 (1965): 265.

  2. References to various articles by others, and to the author's series of articles on globoid leukodystrophy are included in a review chapter, J. Austin, "Globoid (Krabbe) Leukodystrophy," in Pathology of the Nerruous System, ed. J. Minckler (New York: McGraw-Hill, 1968), 1: 843-58.

  3. K. Suzuki and Y. Suzuki, "Globoid Cell Leukodystrophy (Krabbe's Disease): Deficiency of Galactocerebroside 0-Galactosidase," Proceedings of the National Academy of Science, U.S.A. 66 (1970): 302-9.

  4. J. Austin, K. Suzuki, D. Armstrong, R. Brady, B. Bachhawat, J. Schlenker and D. Stumpf, "Studies in Globoid (Krabbe) Leukodystrophy (GLD). V. Controlled Enzymic Studies in Ten Human Cases," A.M.A. Archives of Neurology 23 (1970): 502-12.

  5. Y. Suzuki, J. Austin, D. Armstrong, K. Suzuki, J. Schlenker and T. Fletcher, "Studies in Globoid Leukodystrophy: Enzymatic and Lipid Findings in the Canine Form," Experimental Neurology 29 (1970): 65-75.

  8. Enzymes and India, 1961, 1962-1963

  1. J. Austin, "Studies in Metachromatic Leukodystrophy. XII. Multiple Sulfatase Deficiency," Archives of Neurology 28 (1973): 258-264. As might be anticipated, any investigator must have mixed feelings about the way this devastating disease has gone on bear his name; see P. Beighton, and G. Beighton, The Man Behind the Syndrome (New York: Springer-Verlag, 1986).

  2. J. Newman, Science and Sensibility (New York: Simon & Schuster, 1961), p. 464.

  10. Tom and Lafora Bodies, 1965

  1. F. White, The Brittany in America, 2d ed. (Chillicothe, Ill.: privately printed, 1965), p. 7.

  2. M. Bischell, J. Austin and M. Kemeny, "Metachromatic Leukodystrophy (MLD). VII. Elevated Sulfated Acid Polysaccharide Levels in Urine and Postmortem Tissues," A.M.A. Archives of Neurology 15 (1966): 13-28.

  3. S. Yokoi, J. Austin, F. Witmer and M. Sakai, "Studies in Myoclonus Epilepsy (Lafora Body Form). I. Isolation and Preliminary Characterization of Lafora Bodies in Two Cases," A.M.A. Archizars of Neurology 19 (1968): 15-33; M. Sakai, J. Austin, F. Witmer and L. Trueb, "Studies in Myoclonus Epilepsy (Lafora Body Form). II. Polyglucosans in the Systemic Deposits of Myoclonus Epilepsy and in Corpora Amylacea," Neurology 20 (1970): 160-76; T. Nikaido, J. Austin and H. Stukenbrok, "Studies of Myoclonus Epilepsy. III. The Effects of Amylolytic Enzymes on the Ultrastructure of Lafora Bodies," Journal of Histochemistry and Cytochcnustry 19 (1971): 382-85.

  4. M. Sakai, J. Austin, F. Witmer and L. Trueb, "Studies of Corpora Amylacea. 1. Isolation and Preliminary Characterization by Chemical and Histochemical Techniques, A.M.A. Archives of Neurology 21 (1969): 526-44; J. Austin, T. Nikaido and H. Stukenbrok, "Studies of Corpora Amylacea. 11. Histochemical and Electron Microscopic Observations," Proceedings of the 6th International Congress of Neuropathology (1970): 1029-30.

  5. T. Nikaido, J. Austin, R. Rinehart, L. Trueb, J. Hutchinson, H. Stukenbrok and B. Miles, "Studies in Ageing of the Brain. I. Isolation and Preliminary Characterization of Alzheimer Plaques and Cores, A.M.A. Archives of Neurology 25 (1971): 198-211; T. Nikaido, J. Austin, L. Trueb and R. Rinehart, "Studies in Ageing of the Brain. II. Microchemical Analyses of the Nervous System in Alzheimer Patients," A.M.A. Archives of Neurology 27 (1972): 549.

  6. M. Sakai, J. Austin, T. Nikaido an
d R. Rinehart, "Lewy Bodies." This important project continued to be underfunded and was unfortunately never completed.

  7. D. Armstrong et al., eds., Ceroid Lipofuscinosis (Batten's Disease) (Amsterdam: Elsevier, 1982).

  11. Fingerprints on the Window; Filling in the Hole

  1. Profiles of US Medical School Faculty, 1971, US Department of Health, Education, and Welfare, report #20, Resources for Biomedical Research (Dec. 1974), p. 36.

  2. Doctoral Scientists and Engineers in the United States. 1975 Profile, National Academy of Sciences, Washington, D.C.

  3. R. Scheffler, The Economic Rate of Return to post-M.D. Training in the Biosciences, NIH Publication Contract Number NO 1-OD-4-2512 (Feb. 28, 1975), p. 41. The numbers are now substantially higher.

  4. W. Penfield, The Difficult Art of Giving: The Epic of Alan Gregg (Boston: Little, Brown, 1967), p. 83.

  12. Overview: What Next? So What?

  1. J. Austin, "Recurrent Polyneuropathies and Their Corticosteroid Treatment," Brain 81, no. 2 (1958): 157-192.

  2. V. McKusick. Mendelian Inheritance in Man, 3 vols. (Baltimore, MD: Johns Hopkins University Press, 1998). Interested readers should consult this set for further information on the various genetic diseases cited.

  3. H. Nadler and A. Gerhie, "Role of Amniocentesis in the Intrauterine Detection of Genetic Disorders," New England Journal of Medicine 282 (1970): 596-99.

  4. N. Bass, E. Witmer and F. Dreifuss, "A Pedigree Study of Metachromatic Leukodystrophy: Biochemical Identification of the Carrier State," Neurology 20 (1970): 52-62; D. Stumpf and J. Austin, "Metachromatic Leukodystrophy (MLD). IX. Qualitative and Quantative Differences in Urinary Arylsulfatase A in Different Forms of MLD," A.M.A. Archives of Neurology 24 (1971): 117-24.