5. W. Krivit, C. Peters, and E. Shapiro, "Bone Marrow Transplantation as Effective Treatment of Central Nervous System Disease in Globoid Cell Leukodystrophy, Metachromatic Leukodystrophy, Adrenoleukodystrophy, Mannosidosis, Fucosidosis, Aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly Syndromes, and Gaucher Disease, Type III," Current Opinion in Neurology 12 (1999): 167-176. My thanks to Professor Hugo Moser for supplying me with a copy of this review article and of the article cited in reference 14 below.
6. Ibid.
7. D. Stumpf, E. Neuwelt, J. Austin and P. Kohler, "Metachromatic Leukodystrophy (MLD). X. Immunological Studies of the Abnormal Sulfatase A., A.M.A. Archives t f Neurology 25 (1971): 427-31.
8. E. Neuwelt, D. Stumpf, J. Austin and P. Kohler, "A Monospecific Antibody to Human Sulfatase A; Preparation, Characterization and Significance," Biochimica et Biophysica Acta 236 (1971): 333-46.
9. N. Radin, "Treating Glucosphingolipid Disorders by Chemotherapy: Use of Approved Drugs and Over-the-Counter Remedies," Journal of Inherited Metabolic Diseases 23 (2000): 767-777
10. N. Raclin, R. Arora, A. Brenkert and J. Austin, "A Possible Therapeutic Approach to Krabbe's Globoid Leukodystrophy and the Status of Cerebroside Synthesis in the Disorder," Research Comnnnnications in Chemical Pathology and Pharrnacology, 3 (1972): 637-44.
11. 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.
12. U. Matzner, F. Schestag, D. Hartmann, et al., "Bone Marrow Stem Cell Gene Therapy of Arylsulfatase A-Deficient Mice, Using an Arylsulfatase Mutant That Is Hypersecreted from Retrovirally Transduced Donor-Type Cells," Human Gene Therapy 12 (2001): 1021-1033.
13. D. Stumpf and J. Austin, "Sulfatase B Deficiency in the Maroteaux-Lamy Syndrome (Mucopolysaccharidosis VI)," Transactions of the American Neurological Association 97 (1972): 29-32.
14. E. Herskhovitz, E. Young, J. Rainer, et at, "Bone Marrow Transplantation for Maroteaux-Lamy Syndrome (MPS VI): Long-Term Follow-Up," journal of Inherited Metabolic Disease 22 (1999): 50-62.
1s. A. Crawley, K. Niedzielski, K. Isaac, et al., "Enzyme Replacement' Therapy from Birth in a Feline Model of Mucopolysaccharidosis Type VI," Journal of Clinical Investigation 99 (1997): 651-62.
16. A. Allison, "Lysosomes and Disease," Scientific American (Nov. 1960): 62-72.
17. J. Monod, Chance and Necessity (London: Collins, 1972), p. 110.
13. Chance and the Creative Adventure
1. M. Austin, "Dream Recall and the Bias of Intellectual Ability," Nature 231 (1971): 59.
2. L. Goodrich, Albert P. Ryder (New York: Braziller, 1959), p. 22.
14. On the Trail of Serendipity
Literary scholars have differed in the past in their interpretations of the origins of the three princes, and will presumably do so in the future. Cammann's view is summarized here because he has presented an authoritative recent review of the subject documented with 113 references and notes (S. Cammamt, "Christopher the Armenian and the Three Princes of Serendip," Comparative Literature Studies 4 (1967): 229-58).
According to Cammann, the emperor Beramo (Behramo in the Peregrinag- gio) of the three princes may well have been Bahram Gur (the Persian King Varkan V) who ruled pre-Islamic Iran from 420-440. A lengthy account of his life, entitled Shananae, was written by the poet, Firdaust, in 1010. Over a century later, between 1171 and 1200, Nizami collected five book-length poems into one volume, entitled Khamse. One of these poems celebrated the life of Bahram Gur, and was called "Haft Paikar" ("Seven Beauties").
The next version of the tales came from Amir Khusrau of Delhi (12531325), the greatest Persian poet India ever produced. Khusrau was the son of a Turkish father and a Muslim Indian mother, and was court poet to the kings and princes of his day. His own version of Khamse and of the "Haft Paikar" contained a poem entitled "Hasht Bihisht ("Eight Paradises"). It introduced some new tales of Indian origin reflecting his own background in Delhi. Khusrau also included in his version the legendary story of the three brothers and the camel driver. It is plausible to think that Christopher the Armenian's later adaptation, the Peregrinaggio, originated in Khusrau's tale. A native of Tabriz (in what is now Iran) before he emigrated to Venice, Christopher would have been able to translate Khusrau easily because Persian would have been his primary language.
2. T. Remer, ed., Serendipity and the Three Princes; Front the "Peregrinaggio" of 1557 (Norman, Okla.: University of Oklahoma Press, 1965).
3. W. Lewis, ed., The Yale Edition of Horace Walpole's Correspondence 26 (1971): 34-35, hereinafter cited as The Yale Edition.
4. Thomas Gray would later be known for his poem, "Elegy Written in a Country Churchyard."
5. The correspondence can be found in The Yale Edition.
6. Mann to Walpole, November 9, 1753, The Yale Edition 20 (1960): 399.
7. Walpole to Mann, January 28,1754, The Yale Edition 20 (1960):407-8. This Horace Mann is not to be confused with the American educator of the next century (1796-1859).
8. Walpole to Mann, January 28, 1754, The Yale Edition 20 (1960): 407-8.
9. Walpole to Hannah Moore, September 10, 1789, The Yale Edition 31 (1961), 335.
15. The Kettering, Pasteur, and Disraeli Principles
1. My thanks to a correspondent who preferred to remain anonymous, and to Philip Archer, Ph.D. for this number.
2. A. Maurois, The Life of Sir Alexander Fleming (New York: Dutton, 1959), p. 109. The sequences by which nasal drippings entered into this experiment are not entirely clear. Has anyone shown that this was, or was not, an accident?
3. R. Taton, Reason and Chance in Scientific Discovery (New York: Philosophical Library, 1957), p. 113.
4. In Biologic de l'Invention (Paris: Alcan, 1932), p. 30, Charles Nicolle says in effect that, "Chance serves only those who know how to win her." ("Le hasard ne serf que ceux qui savent le capter.") To those who would translate carter as "court," Nicolle might seem to be implying a courting action (of an underhanded kind). But if the statement is viewed in the context of the whole paragraph, it seems evident that Nicolle is still talking about receptivity and further refinements of discernment, for in the following sentence, he concludes, "To grasp the significance of a fact, to unravel it, is only within the capacity of well-endowed minds." Chance III does more than favor receptivity and discernment at the initial, tactical level of perception. It also favors this astute grasp of new relationships, and the judgement of their deeper significance, as subtle intuitive properties at the strategic level.
s. M. Csikszentmihalyi. Creativity: Flow and the Psychology of Diseoreryand Inzvention (New York, NY: HarperCollins, 1996).
16. Personal Encounters with Chance I-IV
1. Interestingly, most everyone likes reds and blues. The most preferred colors in first order of preference are: blue, red, green, violet, orange, yellow. See R. Burnam, R. Hanes and C. Bartleson, Color: A Guide to Basic Facts and Concepts (New York: John Wiley and Sons, 1963), p. 209; there is more to color than meets the eye. Farther back, in the brain itself, color tends to evoke an image of form. Red is perceived as being moderately "large," as being spread out horizontally, and as possessing a well-defined boundary line. Blue is the "largest" and it, too, takes on a strong horizontal extension with well-defined edges. Blue, moreover, has the special quality of evoking shapes that are "curvy" rather than straight. See M. Lindauer, "Form Imagery to Colors," Perceptual and Motor Skills 36 (1973): 165-66.
2. J. Austin, Zen and the Brain (Cambridge, MA, MIT Press, 1998). My interests in Zen began during this first Kyoto sabbatical. These led to the decisions to spend the next two sabbatical years first in London and later in Japan.
3. It is interesting to note that the red-purple follows in sequence a field of its complementary opposite color: green-yellow. The correct response to such epiphenomena of meditation (termed makyo in Japanese) is simply to pay no attention to them. They go away with time.
1. The story of the cave is a composite drawn both from a personal visit to Altamira, and from accounts in the following books: H. Wendt, In Search of Adam (Boston: Houghton Mifflin, 1956); G. Bibby, The Testimony of the Spade (New York: Alfred Knopf, 1956); D. and J. Samachson, The First Artists (Garden City, N.Y.: Doubleday, 1970); and P. MacKendrick, The Iberian Stones Speak (New York: Funk and Wagnalls, 1969).
19. The Fleming Effect: Examples of Chance in Biology and Medicine
1. J. Henderson, "The Yellow Brick Road to Penicillin: A Story of Serendipity," Mayo Clinic Proceedings 72 (1997): 683-687.
2. Ibid.
20. Never on Monday; The Unhappy Accidents
1. Dickson, P., The Official Rules (New York: Delacorte, 1978).
2. The Reader's Digest Dictionary of Quotations (The Reader's Digest Association, Inc., 1966), p. 137.
3. Quote from Pogo, by Walt Kelly.
4. In no way did this acronym ever necessarily refer to the National Institutes of Health (the real NIH) in Bethesda, MD, because it was the NIH that was responsible for funding and/or conducting much of the impressive growth in the biomedical sciences during recent decades.
5. For one example of Chance III in Pasteur's remarkable career, please refer to Appendix B.
21. Some Dimensions of Creativity
1. A. Tannenbaum, Gifted Children: Psychological and Educational Perspectives (New York: Macmillan, 1983).
2. H. Hughes, "Individual and Group Creativity in Science," in Essays on Creativity in the Sciences, ed. M. Coler, (New York: New York University Press, 1963), pp. 93-101.
3. H. Fox, "A Critique on Creativity in Science," in Essays on Creativity in the Sciences, ed. M. Coler (New York: New York University Press, 1963), pp. 123-52.
4. The experiment cited is not novel. The idea that some new surge of "electrical activity" occurs during a moment of inspired thought is an old one. The early cartoonists (perhaps reminded of Thomas Edison's invention) drew a lightbulb glowing above the head of a character whenever he was seized by a new idea.
22. The Creative Personality: Pro
1. P. Witty, J. Conant and R. Strang, Creativity of Gifted and Talented Children (New York: Bureau of Publications, Teachers College, Columbia University, 1959), pp. 21-22.
2. M. Wallach, "Creativity," in Manual of Child Psychology, ed. P. Mussen (New York: John Wiley and Sons, 1969), 1: 1211-72.
3. Ibid.
4. The Creative Process in Science and Medicine, H. Krebs and J. Shelley, eds. (New York: American Elsevier, 1975), p. 19.
5. M. Wallach and N. Kogan, "A New Look at the Creativity-Intelligence Distinction," Journal of Personality 33 (1965): 348-69.
6. B. Eiduson, Scientists: Their Psychological World (New York: Basic Books, 1962).
7. 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. 153-82.
8. H. Zuckerman, Scientific Elite (New York: Free Press, 1977), p. 165.
9. C. Tuska, Inventors and Inventions (New York: McGraw-Hill, 1957).
to. Scientific Creativity: Its Recognition and Developrnent, ed. C. Taylor and F. Barron (New York: John Wiley and Sons, 1964), pp. 385-86.
ii. A. Roe, The Making of a Scientist (New York: Dodd, Mead, 1953); Eiduson, Scientists.
12. S. Hetrick, R. Lilly and P. Merrifield, "Figural Creativity, Intelligence, and Personality in Children," Multivariate Behavioral Research 3 (1968): 173-87.
13. R. Harding, An Anatomy of Inspiration (Cambridge, England: Heffer and Sons, 1942), p. 89.
14. W. Cannon, The Way of An Investigator (New York: Hafner, 1965), p. 28.
15. Roe, The Making of a Scientist.
16. A. Koestler, The Act of Creation (New York: Macmillan, 1967).
17. Creativity and intelligence are not synonymous, even though existing psychological tests do not always separate them. As one example, in the following reference creativity tests correlated as high with intelligence tests as they did with each other. R. Cave, "A Combined Factor Analysis of Creativity and Intelligence," Multivariate Behavioral Research 5 (1970):177-91. Wallach ("Creativity") gives a good critical discussion of this point.
18. See Cave and Wallach.
19. F. Barron, Creativity and Psychological Health (Princeton: Van Nostrand, 1963), p. 242.
20. H. Gough, "Identifying the Creative Man," Journal of Value Engineering 2 (1964): 4, 5-12. For a differing viewpoint, see K. Dewing and G. Battye, "Attention Deployment and Nonverbal Fluency," Journal of Personality and Social Psychology 17, No. 2 (1971): 214-18.
23. The Creative Personality: Pro and Con
1. J. Getzels and P. Jackson, "The Highly Intelligent and the Highly Creative Adolescent," in Scientific Creativity: Its Recognition and Development, ed. C. Taylor and F. Barron, (New York: John Wiley and Sons, 1964), p. 161.
2. F. Barron, Creativity and Psychological Health (Princeton: Van Nostrand, 1963), p. 212.
3. H. Selye, From Dream to Discovery: On Being a Scientist (New York: McGraw-Hill, 1964), pp. 21-28.
4. F. Barron, in Scientific Creativity: Its Recognition and Development, p. 223.
5. Ibid., p. 224.
6. T. Kuhn, "The Essential Tension: Tradition and Innovation in Scientific Research," in Scientific Creativity: Its Recognition and Developrnent, p. 342.
7. A. Gregg, The Furtherance of Medical Research (New Haven: Yale University Press, 1941), p. 93. Pasteur might not always have qualified. So powerful was his intuition that he could almost write the conclusion without first having done the experiment. It was his faithful colleague, Roux, who exerted a critical brake on this situation (C. Nicolle, in Biologie de I'Inz'ention [Paris: Alcan, 19321), p. 62.
8. M. Dellas and E. Gaier, "Identification of Creativity; the Individual," Psychological Bulletin 73 (1970): 55-73.
9. M. Stein, "A Transactional Approach to Creativity," in Scientific Creativity: Its Recognition and Development, p. 224.
10. R. Brimblecombe and R. Pinder, Hallucinoc,'enic Agents (Dorchester: Bristol, Wright-Scientifechnica, Dorset Press, 1975); B. Wells, Psychedelic Drugs (New York: Aronson Press, 1974); D. Sankar, LS: A Total Study (Westbury, N.Y.: PJD Publications, 1975).
11. W. Harman, R. McKim, R. Mogar, J. Fadiman, and M. Stolaroff, "Psychedelic Agents in Creative Problem-solving: a Pilot Study," Psychological Reports 19 (1966): 211-27.
12. L. Zegans, J. Pollard and D. Brown, "The Effects of LSD-25 on Creativity and Tolerance to Regression," Archives of General Psychiatry 16 (1967): 740-49.
13. S. Krippner, "Research in Creativity and Psychedelic Drugs," international Journal of Clinical and Experimental Hypnosis 25 (1977): 274-308.
14. R. Fischer and J. Scheib, "Creative Performance and the Hallucinogenic DrugInduced Creative Experience, or One Man's Brain-Damage Is Another's Creativity," Confinia Psychiatrica 14 (1971): 174-202.
15. See note 10 supra and J. Austin, Zen and the Brain (Cambridge, MA: MIT Press, 1998), pp. 418-443, for further discussion of these issues.
24. Motivations Underlying Creativity
1. A. Storr, The Dynamics of Creation (New York: Atheneum, 1972), p. 178.
2. Ibid.
3. Ibid.
4. Ibid.
s. B. Eiduson, Scientists: Their Psychological World (New York: Basic Books, 1962), p. 126.
6. J. Conrad, in Heart of Darkness, quoted in Essays in Criticism, ed. R. Kimbrough (New York: Norton, 1963), p. 29.
7. J. Austin, Zen and the Brain (Cambridge, MA: MIT Press, 1998), pp. 37-51.
8. Storr, Dynamics of Creation, p. 178.
9. G. Pickering, Creative Malady (London: George Allen and Unwin, 1974), p. 309.
to. Ibid., p. 282.
11. R. May, The Courage to Create (New York: Norton, 1975), p. 31.
12. May, The Courage to Create.
13. J. Masefield, The Wanderer of Liverpool (New York: Macmillan, 1930), p. 94.
14. G. McCa
in and E. Segal, in The Caine of Science (Belmont, Cal.: Brooks/Cole, 1969), p. 106.
15. G. Hardy, A Mathematician's Apology (London: Cambridge University Press, 1967).
26. The Search for Novel Stimuli
1. H. Harlow, M. Harlow and D. Meyer, "Learning Motivated by a Manipulation Drive," in Explorations in Exploration, Stimulation Seeking, ed. D. Lester (New York: Van Nostrand Reinhold, 1969), pp. 83-95.
2. E. Berlyne, "The Influence of Albeds and Complexity of Stimuli on Visual Fixation in the Human Infant," in Explorations in Exploration, pp. 115-20.
3. A. Gottfried, S. Rose, and W. Bridger, "Cross-Modal Transfer in Human Infants," Child Development, 48 (1977): 118-123.
4. R. Spitz and K. Wolf, "Anaclitic Depression; an Inquiry into the Genesis of Psychiatric Conditions in Early Childhood, II," in The Psychoanalytic Study of the Child, A. Freud, et at., eds., (New York: Int. Univer. Press, 1946), 2: 312-42.
5. W. Bexton, W. Heron and T. Scott, "Effects of Decreased Variation in the Sensory Environment," Canadian Journal of Psychology 8 (1954): 70-76.
6. D. Schultz, "Evidence Suggesting a Sensory Variation Drive in Humans," in Explorations in Exploration, pp. 181-97.
7. W. Greenough and F. Volkmar, "Pattern of Dendritic Branching in Occipital Cortex of Rats Reared in Complex Environments," Experimental Neurology 40 (1973): 491-504.
8. M. Rosenzweig, E. Bennet and M. Diamond, "Cerebral Effects of Differential Experience in Hypophysectomized Rats," Journal ofComparativeand Physiological Psychology 79 (1972): 55-66.
9. P. Eriksson, K. Perfilieva, T. Bjork-Eriksson, et al., "Neurogenesis in the Adult Human Hippocampus," Nature Medicine 4 (1998): 1313-1317.
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