Minor unpredictable events critically influenced the way they constructed their factual edifice. These events, however, tended to be edited out when the work was later written up for publication. Soon, a pseudosense of underlying logic was superimposed, and the final publication appeared to be the result of rational processes, not those of long, complex interpersonal interactions or interactions with the setting.
Brief conversations sufficed either constructively to create or to dismantle facts. Who made a given claim was every bit as important as the nature of the claim itself. The critical questions asked about data originating in some outside laboratory were: First, "Has he produced enough hard facts in the past so that I can believe him now?" Second, "If so, can I now use his facts to increase my own production of creditable information?"
To Latour and Woolgar, the laboratory life was one that essentially drew order out of disorder. Order the exception; disorder, the rule. The laboratory team, struggling for originality, recognition and funds, was ultimately preoccupied with sifting grains of fact from mountains of artifact.
Glossary
The nonspecialist will find here a simplified description of some less familiar terms.
altamirage the quality of prompting good luck inadvertently as the result of personally distinctive actions.
centrifuge an instrument, which, as it spins forces more dense particles down to the bottom of a test tube, separating them from the lighter particles that are layered above.
cerebroside a fatty (lipid) molecule made up of three smaller molecules linked together: a fatty acid, a base (sphingosine), and a sugar such as galactose or glucose (figure 6).
cerebroside galactosidase the enzyme that split galactose from cerebroside. This is the salient enzyme deficient in human and canine globoid leukodystrophy (GLD) (figure 6).
chance something fortuitous and unforeseen but open to human influence.
chromatography a technique for identifying chemical compounds. The method is based on the fact that each molecule in a given solution moves at a characteristic rate on a strip of filter paper (paper chromatography) or on a thin layer of silica (thin layer chromatography).
corpora amylacea round structures that accumulate inside certain supportive cells in the human brain. These "amyloid bodies" increase with age and are made up of molecules of glucose linked together in long chains.
creative process currently, the term is chiefly used in the behavioral and descriptive sense to convey imperfectly in words the series of mental events culminating in a novel idea or other new product. The basic internal neurophysiological and neurochemical events going on during creative activity are still unknown.
creativity the long and complex series of interrelationships between an individual and his environment culminating in something new.
creativity in science that creative ability associated with something new, significant, and reproducible in a scientific field.
cytoplasm the portion of a cell that lies outside the nucleus.
deposition disorders diseases in which certain molecules accumulate because of a metabolic error. Deposits of these molecules pile up in the tissues. For example, metachromatic leukodystrophy is a deposition disease in which sulfatides are deposited. Also known as "storage" diseases.
ecology the study of all the interrelationships between an organism and its environment.
formalin a chemical used to preserve tissues. It also hardens tissues so that thin sections can be cut for microscopic examination.
galactosidase an enzyme that splits galactose (a sugar) from another molecule.
globoid bodies rounded phagocytic cells with multiple nuclei that contain an excess of cerebroside; the hallmark of globoid (Krabbe) leukodystrophy (GLD) (figures 6, 7).
globoid leukodystrophy (GLD; Krabbe's Disease) an inherited disease that causes a fatal progressive paralysis, blindness, and loss of mental abilities. The illness usually begins in children around four months of age. Certain dog strains (West Highland and Cairn terriers) also can have the disease. GLD has two major microscopic features. One is a degeneration of the myelin sheaths in the central and peripheral nervous system. The other is large numbers of rounded cells with multiple nuclei, called globoid bodies. GLD is caused by a deficiency of the enzyme that splits galactose from cerebroside (cerebroside galactosidase) (figures 6, 7).
histochemical method a technique in which thin sections of tissue are treated with special chemical reagents before the section is examined under the microscope. Because certain chemical groups have characteristic chemical reactions, it is thus possible to tell if they exist in the cell.
hyaluronic acid sulfate a negatively charged mucopolysaccharide of high molecular weight. It is obtained by attaching sulfate groups onto a molecule called hyaluronic acid, itself a constituent of normal connective tissue.
hypertrophic neuritis an inherited disorder involving multiple peripheral nerves. The nerves become larger and firmer than normal and their individual nerve fibers degenerate (figure 1). Arms and legs become progressively weak.
infrared spectrophotometry a technique for identifying and measuring chemical compounds. It is based on the fact that certain chemical groups absorb invisible rays (beyond the red end of the spectrum) in a distinctive manner. The sulfate group, for example, absorbs at a wave length of 8.02 microns.
Lafora bodies round structures inside nerve cell cytoplasm seen in Lafora's myoclonus epilepsy. They contain long chains of glucose molecules (glucose polymers) (figures 10, 11).
Lafora's myodonus epilepsy an inherited fatal disease that usually starts during the second decade of life. Clinically, it causes a progressive seizure disorder, mental deterioration, and poor coordination. Microscopically, it is characterized by the presence of Lafora bodies and by degeneration of nerve cells in the cerebrum and cerebellum (figure 10).
leukodystrophy a disease in which the myelin sheath slowly degenerates. "Leuco" refers to the white color these sheaths normally have. Dystrophy refers to the gradual wasting away of the sheaths. Leukodystrophies are caused by a metabolic error of the cells that normally construct and maintain the myelin sheaths surrounding the nerve fiber (figures 2, 4, 7).
limbic lobe the phylogenetically old cortex that surrounds the upper brain stem, literally forming a border around it.
lipid a fatty molecule.
lipidosis a disease in which lipids (fats) are deposited inside the cells of several organs of the body. Many of these diseases are now known to be caused by an inherited deficiency of the specific enzyme inside lysosomes that normally breaks down the lipid.
lysosomes small digestive bodies inside cell cytoplasm. Collectively, they function as a kind of internal disposal system in the cell. Lysosomes serve this digestive function because they are rich in such digestive enzymes as sulfatase A, sulfatase B, and cerebroside galactosidase.
metachromasia a staining reaction in which certain blue dye molecules change color when they contact other molecules that have an opposite charge. For example, the blue dye, toluidine blue, will stain sulfated lipids a reddish-golden brown color. This new color indicates that negatively charged sulfated lipids are present.
metachromatic leukodystrophy (MLD; metachromatic leukoencephalopathy) an inherited disease that causes a fatal progressive paralysis, blindness, and loss of mental abilities. It begins anywhere from eighteen months of age up into late adult life. It has two major microscopic features. One is a degeneration of the myelin sheaths (which normally "insulate" nerve fibers in the central and peripheral nervous system). The other is an accumulation of metachromatically staining lipids both in nervous tissues and in the kidney. MLD is caused by deficient activity of the enzyme, sulfatase A (cerebroside sulfatase). This, in turn, causes an accumulation of sulfated lipids (called sulfatides or cerebroside sulfates). The abnormally high sulfatide levels are associated with a wasting away of the white myelin sheath (figures 2, 4).
mucopolysaccharide a molecule of high molecular weight t
ypically found in connective and other tissues. It is made up of many sugars with amino groups and other smaller acid molecules. Frequently sulfate groups are attached.
molecule a chemical compound made up of atoms linked together in a specific way. Diagrams of the structure of various molecules are given in figures 3, 6, and 11.
multiple sclerosis a disease of still unknown cause that attacks the myelin sheath in the central nervous system. The disease chiefly affects adults and its multiple patchy lesions of white matter form a sharp contrast with the more diffuse involvement in the leukodystrophies.
multiple sulfatase deficiency a rare form of metachromatic leukodystrophy in which the enzymes sulfatase A, sulfatase B, and sulfatase C all show deficient activity. The condition resembles MLD. Sulfatides are increased. In addition, there is an increase of sulfated mucopolysaccharides (due to decreased sulfatase B) and of various sulfated steroids (due to decreased sulfatase Q.
myelin sheath the coating around the nerve fiber (axon) that serves as a kind of insulation. The sheath is made up of lipids, including cerebrosides and sulfatides. If the fatty sheath breaks down due to disease the nerve fiber stops conducting impulses.
negatively charged molecule a molecule with a net negative charge conferred by its content of ionized sulfate groups, phosphate groups, or carboxylic acid groups.
neurologist a physician specializing in diseases of the nervous system and muscles.
neuropathologist one who studies the mechanisms of diseases of the nervous system, chiefly by the techniques of light and electron microscopy.
neuropathology the study of the mechanisms of diseases of the nervous system.
phagocytic cells cells that engulf or digest outside material.
polyglucosan a glucose polymer (figure 11). Examples include: the materials deposited in Lafora bodies and corpora amylacea; starch; and glycogen.
polyneuropathy a disease in which the peripheral nerves stop conducting nerve impulses. This causes weakness of the legs and arms and frequently numbness of the hands and feet, as well.
preconscious a term used by Kubie to describe the subliminal mental processes of scanning and sorting that serve creative ends. Preconscious activities lie nearer consciousness than do unconscious activities. The term subconscious includes both.
recessive disease an inherited disorder clinically expressed in a child both of whose parents contribute the abnormal gene. Although the mother and father appear clinically normal, one out of four of their children will develop the disease on an average.
resident physician one who has completed internship and who receives specialized training on the junior staff of a teaching hospital. A residency training period in neurology is currently three years long.
sagacity keen perception linked with the astute grasp of new relationships and the sage judgment of their significance
serendipity finding valuable things without actively seeking them as a result of accidents, general exploratory behavior, or sagacity.
sheath cells cells responsible for the formation and maintenance of the myelin sheath. In the peripheral nerves these cells are termed Schwann cells (figure 1). In the central nervous system (brain and spinal cord) they are called oligodendroglia.
substrate a reagent molecule acted on by an enzyme. For example, cerebroside sulfate is the substrate for the enzyme sulfatase A.
sulfatase an enzyme that splits a sulfate group from a sulfated compound. Sulfatase A splits the sulfate group from cerebroside sulfate (sulfatide) as shown in figure 3.
sulfatide a sulfated lipid (fat), specifically a sulfated cerebroside molecule (figure 3). Sulfatides are normally concentrated in the myelin sheath that surrounds the nerve fiber and reach abnormally high levels in metachromatic leukodystrophy (figure 2).
toluidine blue a special blue dye that is charged positively. It is used to test for the presence of negatively charged molecules. When the two come together they form a complex. The complex has a new color which is not blue but rather shades of red to golden-brown. The phenomenon is termed metachromasia.
urine sediment the heavier portion of urine that settles out after standing or centrifugation. It contains cells, casts, debris, and the granular bodies of MLD.
white matter the inner portion of the nervous system that contains many myelin sheaths packed together. It appears white because the lipids in myelin are white.
Cast of Characters
Experimental thinking ... is fundamentally co-operative, social, and cannot proceed far without the stimulus of outside contacts.
Frederick Bartlett
Each cherishes in his memory the remembrance of those who have fanned his flame.
Charles Nicolle
This was not my story alone. As in a good-sized Russian novel, there were many other people involved. There could have been many more. Everyone mentioned in the narrative is cited for a specific reason: each made some pivotal contribution that shaped the course of events at one or more points. Without the vital input of all these men and women the story might not have happened at all. It was no effort for me to summon up a flood of images about the facial expression and form of the person involved, of the exact spot in the hall or laboratory where an incident occurred, and of the texture of the moment itself. In fact, years ago I began to find these encounters so fascinating that I seem to have laid down the original mental traces of every episode in rich detail. Since then, my memory has been reinforced by automatically playing itself back every now and then. Warm memories linger in the mind not only because they were noteworthy earlier, but also because they are fanned repeatedly and replayed.
The vividness of these recollections made it relatively easy to write the first part of the book quite accurately. Some of the characters may have long ago forgotten their own role in this story, but I could not. Only rarely was it necessary to consult laboratory workbooks for dates, sequences, or other details.
This book was concerned not only with people but also with process. If I were to have attempted a full character delineation of each of the fifty-eight people, one rabbit, and one dog-all deserving characters in this story-there would have been no room left to consider the ecological processes that brought them together. This needed to be a smaller volume, and so I have given a thumbnail description of the essential contribution made by each person. The list of characters' given below should emphasize how complex is the web of human interactions involved in any creative endeavor.
James H. Austin: a curious, various persistent child, and neurologist to be.
James Austin, Jr.: liberal judge, active puzzle-solver, my paternal grandfather.
Henry Holtkamp: teacher, organ builder, grandfather on my mother's side.
Gus Weber: outdoor enthusiast and dog owner, my paternal great uncle. I never saw him, but I know Uncle Gus in my bones.
Sophia Holtkamp: model gardener and grandmother who stimulated my interest in Indian artifacts.
Frank ("Gibby") Gibson, M.D.: gracious uncle; inspiring model physician.
Raymond Adams, M.D.: outstanding teacher at Harvard Medical School; neurologist and Chief of Neuropathology at Boston City Hospital.
Paul Weber Austin: my father and model of the creative artist, pianist, and composer.
Derek Denny-Brown, M.D.: stimulating professor; my Chief of the Neurology service at the Boston City Hospital.
Joseph Foley, M.D.: genial Boston Irishman and attending neurologist, Boston City Hospital.
Naval Seaman Knox: a patient whose illness prompted the studies on hypertrophic neuritis.
H. Houston Merritt, M.D.: eminent Chief of the Neurology Department at The New York Neurological Institute.
Abner Wolf, M.D.: Chief of Neuropathology at Columbia-Presbyterian Medical Center.
Lord Russell Brain, M.D.: eminent English neurologist who wrote a key article on metachromatic leukodystrophy.
J. Godwin Greenfield, M.D.: noted neuropathologist and co-author of the above article.
Th
e Clausen children: two young children afflicted with metachromatic leukodystrophy whose admission to the hospital in New York prompted my research on this disease.
Charles Poser, M.D.: a fellow neurological resident who directed my attention to the Clausen children.
Robert Katzman, M.D.: a fellow neurological resident who called my attention to an important series of articles about lipids.
Jordi Folch-pi, M.D.: pioneering lipid neurochemist at Harvard.
Judith Austin: supportive wife, mother of our three, and indescribably more.
Roy Swank, M.D., Ph.D.: generous head of Neurology at the University of Oregon Medical School and stimulating investigator.
Jack Fellman, Ph.D.: lively organic chemist and neurochemist at the University of Oregon Medical School.
Warren Thompson: an older child afflicted with metachromatic leukodystrophy in Oregon.
Gerald Phillips, M.D.: medical school classmate and lipid biochemist who directed my attention to an important article about sulfated lipids.
Marjorie Lees, Ph.D.: lipid neurochemist who worked out an original method for isolating sulfated lipids (sulfatides) from the brain.
Lowell Lapham, M.D.: medical school classmate; neuropathologist, who gave me the first kidney tissue to study from metachromatic leukodystrophy.
Frank Witmer, Sc.D.: helpful chemist (and raconteur) whose interpretations of infrared spectroscopic data made possible the measurement of sulfated lipids in metachromatic leukodystrophy.
Sig fried Thannhauser, M.D.: pioneer in lipid storage diseases who provided the authentic reference standard of sulfated lipids.
Mrs. Erma Thompson: mother of the sick Thompson child whose consent to the autopsy of her son made it possible to define the chemical basis of metachromatic leukodystrophy.
Chase, Chance, and Creativity Page 26
