The Child Neurology Knowledge Environment

Three cities have shaped my life: Vienna, Dublin, and Jerusalem. I was bom in Vienna, the offspring of four generations of doctors. My father and grandfather were graduates of the University of Vienna. My great granduncle was said to have been a "Feldscher" in the Austrian army, a title that designates a surgeon of sorts. This probably meant that he repaired gun shot wounds and fractures and perhaps did some bloodletting. I recall quite a number of stories my father and grandfather told me about their teachers, and they involve some of the greatest names in medicine.

I suspect that my grandfather did not have a deep interest in neurology, even though he must have had contact with several renowned physicians in that field. The list includes Richard Freiherr von Krafft-Ebing and Theodor Meynert (fasciculus retroflexus of Meynert, commissure of Meynert). In addition, Meynert proposed the view that the phylogenetically older basal ganglia, the site of involuntary movements, are functionally inhibited by the cerebral cortex, which reaches maturity later than the basal ganglia. Subsequently, he proposed that the antagonism between cortex and subcortical centers is an important key to mental diseases and spent many years trying to put psychiatry on a scientific basis. My grandfather was 17 years old when the Vienna Neurological Institute was established. Some of the members of the Institute included Moriz Benedikt and Franz Chvostek .

Fig 1 John Menkes

Following graduation, my grandfather became a general practitioner and for a long time was the only physician in Waidhofen, a small town in the alpine foothills. When my late wife Joan and I visited Waidhofen some years ago, I met an old man in the local pub, who recalled that when he misbehaved as a child, his mother would threaten to call Dr Menkes.

Like my grandfather, my father, who graduated from medical school in 1922, did not have very much interest in neurology; rather, he dreamt of becoming an ophthalmologist. World War I and the ensuing hyperinflation forced my father to abandon his plans, and caused him to enter dentistry, which, in Austria, was an independent medical specialty.

I recall asking my father whether he ever listened to any of the

lectures ofFreud , who at that time was a Dozent (lecturer) at the medical school. He had not since they were not required. Lectures by Julius von Wagner-Jauregg were required, however, and those were the ones he attended. Wagner-Jauregg’s name is connected with the introduction of fever therapy for cerebral syphilis, work for which he was awarded the 1927 Nobel Prize. One of the assistants in the Department of Otolaryngology who was working on nasal polyps and their removal under hypnosis is one of my spiritual mentors: Arthur Schnitzler, a novelist and playwright of major stature. The movie Eyes Wide Shut is based on his novel, Traumnovelle.

On March 11, 1938, Hitler took over Austria, and overnight our world came to an end. Up to then, we had been assimilated Jews, and our family was proud of being Austrian citizens of the "Mosaic persuasion." Hitler changed all that. As Jews, we were outlawed and faced the prospect of death and emotional dismemberment. Almost all of my family remained and died. Through a nearly miraculous intervention, my parents and I managed to escape to Ireland in 1939, a few days before the start of World War II. A year or so ago, I uncovered a mimeographed letter addressed to my father from the US consulate in Vienna, telling him that it was impossible for America to accept us as refugees. I found the document chilling. So I learned English and perfected it in Dublin, where I attended Wesley College and acquired an Irish accent. At one time, George Bernard Shaw had been a dayboy at Wesley College. Because he had to come to school by train, he escaped the first half an hour, which was devoted to Wesleyan catechism. Nevertheless, to him school was, according to his biographer Frank Harris, a hated prison. By contrast to Shaw, I loved the school and was heartbroken to leave when we finally were able to emigrate to California. It was during my stay in Ireland that I started to study the Torah and began to learn Hebrew, becoming quite proficient in the language. I felt that it was time that I knew why I had lost family, home, and language.

I entered Johns Hopkins University School of Medicine in 1948. Medicine was different in those days. Not only were health maintenance organizations not even dreamt of, but the relative roles of physician and patient were not what they are today. When I was in medical school, I was taught that one of the duties of the physician was that he had to assume the responsibility of deciding what to tell and what not to tell his patient and to decide on the best management of the patient’s illness. The patient, as a rule, deferred to the physician’s decision. Nowadays, the patient, as inadequately informed and as poorly prepared as he or she might be, is put into the position of having the responsibility of deciding the best course of action-this in the name of informed consent and freedom of choice.

At Johns Hopkins Hospital, I had little contact with any of the famous personalities of neuroscience. Walter Dandy had died in 1945, and Earl Walker, who worked under him, was too involved in research and surgery to spend much time with medical students. I did, however, attend the Saturday morning conferences, which were conducted by Frank Ford always dressed in a threadbare dark suit, which was frequently stained with food-Frank B. Walsh, and many important visiting professors, including Sir Charles Symonds . Ford would sit in the front row, with some small cards, and at times would scribble a few words, probably for the next edition of his textbook. I have acquired his habit. Ford gave the neurology course to our group of third-year students. If I remember his final examination correctly, he presented us with paragraph abstracts of 10 neurologic cases and asked us to write down the diagnosis for each. It was a horrendous experience, for I could not come up with a diagnosis for any of them, and neither could anyone else in our group. Afterwards, some of us came up to Dr Ford and asked for the correct answers. "Well, doctor," he replied in his sniffly voice, "I don’t have the faintest idea what’s wrong with these patients." For me, it was a disconcerting introduction to neurology. Many years later, when I returned to Johns Hopkins Hospital, I had him autograph the fourth edition of his textbook, Diseases of the Nervous System in Infancy, Childhood and Adolescence. "Well, doctor," he said, as he signed his name, "there are many things in there I don’t know much about." The textbook is massive and filled with information that cannot be obtained elsewhere, and I still refer to it from time to time.

Some time after I graduated from medical school, and shortly after I had started my psychiatry residency at the Phipps Institute, Frank Ford phoned me, wanting to know more about maple syrup disease for his next edition. I met with him, and he told me that with my chemical background, I should be in neurology rather than in psychiatry. I ultimately followed his advice.

While in medical school, I worked in the Carnegie Institute under George Comer and Arpad Csapo on adenosine triphosphatase and adenosine 5’-diphosphate in the contracting uterus.² Csapo had been a student of Albert Szent- Gyorgy, the 1937 Nobel laureate in medicine. One summer, I spent a few days with Szent-Gyorgy at Woods Hole and even played a game of chess with him. I still see him as a tanned, vital, and joyous old man, who was able to laugh at life.

During my third year of medical school, I took a quarter at New York Hospital. There I had a brief exposure to Harold Wolff, whom I remember as a tense and driven man, a suitable candidate for developing migraine headaches. 

Following graduation from Johns Hopkins University School of Medicine in 1952, I did my pediatric internship and junior residency at Boston Children’s Hospital. Of the neurologists there, I vividly remember Randy Byers, a lovely and kind man, but not one who would inspire a young physician to follow his footsteps and go into pediatric neurology. Work on the neurology ward was not very stimulating; there never were many interesting patients, and a good portion of the duties of the house officer involved performing pneumoencephalograms, an unpleasant chore to say the least.

During the time I was in Boston,William Lennox ran the Epilepsy Clinic at Boston Children’s Hospital, and Bronson Crothers

was in charge of the cerebral palsy clinic, but I rotated through neither clinic. Instead, I elected to follow Alex Nadas and Abraham Rudolph into pediatric cardiology. Both were dynamic and inspiring teachers, and through their influence I came close to becoming a cardiologist. In fact, I even wrote a paper with Alex on a girl who developed ventricular premature contractions following a basilar skull fracture. I considered it a good paper, but somehow it was never published. There was only one drawback to pediatric cardiology: I found it boring. The Saturday morning lectures of Richmond Paine were far more interesting, and his lecture on the facial nerve will always remain with me. There were quite a few outstanding people at the Boston Children’s Hospital. Besides the chief of pediatrics, Charles Janeway, there was David Gitlin, working on immunologic disorders; Jim Gamble, who, a few years prior to my arrival, had demonstrated the importance of potassium in rehydration ; and, of course, Sidney Gellis, long-time editor of the Year Book of Pediatrics. Sid stands out among all those who people my mind as a brilliant man, insightful and possessed with an enviable sense of humor. I have dedicated my textbook to him and to Alex Nadas.

It was during my internship that I described maple syrup urine disease. William Pfeffer, who worked as a pediatric hematologist under Louis K. Diamond, admitted a newborn infant who was believed to be at risk for an atypical form of kernicterus (Figure 2). Two of the three earlier bom siblings had died during the neonatal period with neurologic symptoms that resembled kemicterus, and the plan was to follow the child and perform early exchange transfusions should they become necessary. In obtaining the infant’s history, I was told that the mother had noted that the infants who died had an unusual odor, whereas the girl who was well did not. By about 2 to 3 days of age, our baby did indeed develop an unusual odor to its urine and perspiration and shortly thereafter began to show neurologic symptoms. Peter Hurst, who was junior assistant resident, and I started to collect urine and wondered what the odor was. I am sure I must have asked nearly everyone at the hospital but could get no better reply than that it smelled like maple syrup. After all, we were in New England.

One rainy Saturday afternoon Peter and I went to see Louis Fieser, then professor of organic chemistry at Harvard and author of the textbook from which I had studied the subject while working for my master of science degree in organic chemistry. He was not of much more help but allowed us to roam through his stockroom. Urine bottle in hand, we began to sniff our way through the chemicals. I started at the As and Peter Hurst at the Z’s. It was not too long before I found what I then thought was the answer, "acid malic." I was certain that we were dealing with a disorder of the Krebs cycle and an enzyme deficiency that, in analogy to phenylketonuria, the only biochemical disorder known at that time to affect the brain, caused malic acid to accumulate in the urine, and its accumulation was responsible for the neurologic symptoms. It was the first but not the last time that a beautiful theory of mine turned out to be wrong.

A urine sample was sent to David Hsia for amino acid chromatography, but not having established norms for newborns, he was unable to help us. The infant died, and we used up the last bit of urine for silica column chromatography. The odor was eluted in the first few tubes, suggesting a very weak acid, but without more urine, we came no closer to the answer.³ A few months later, I did, however, learn from an industrial firm that artificial maple syrup contained a cyclic ketone, and I kept that fact in mind.

After 2 years in Boston, I returned to Johns Hopkins Hospital, and since in those days I intended to become a child psychiatrist, I started a psychiatric residency at the Phipps Clinic. A few months later, this training was interrupted when I was drafted into the U.S. Air Force and sent to Newfoundland. There I continued to do child psychiatry one afternoon a week, seeing mostly boys with enuresis. By the time I was discharged, I knew that I lacked the patience to become a psychiatrist and, being interested in the brain, decided to go into neurology. I finished my requirements for pediatric boards at Bellevue Hospital under the aegis of Emmett Holt, Jr, an inspiring teacher, who would regularly meet with the senior residents in his office and listen to us present the perplexing cases of the last day or two. I had a brief exposure to Morris Bender while at Bellevue Hospital, but I must admit that I did not have any further neurologic training.

In 1957, I began a pediatric neurology fellowship at the New York Neurological Institute under the direction of Sidney Carter. I think I was the second pediatric neurologist who pursued the full 3-year training program. Elizabeth Decker was the first. Niels Low was also in the program, as was Charles Kennedy. Sid was an exemplary teacher, and his neurologic examinations were thorough and methodical and served as a model to the housestaff. Rounds with H. Houston Merritt, who in those days was chair of neurology, were totally different. He would carefully listen to the patient’s history as presented to him by the housestaff, tap a reflex or two or check a plantar response, and that was it. His diagnostic acumen must have been the result of intuition, for he was almost invariably right.

Fig 2. Clinical summary of the first known case of maple syrup urine disease.

My interest in chemistry continued, and when urine from another case of maple syrup disease became available to me, Sid managed to secure for me a small comer of Abner Wolfs pathology laboratory. Wolf will best be remembered for his classic article on toxoplasmosis in a 1-month-old infant.⁴ Using a budget of some 35 dollars, I set up a chemical laboratory with flasks, beakers, and chromatography equipment (Figure 3). In those days, paper chromatography consisted of a large pickle jar covered with a glass plate sealed with Vaseline. The chromatography paper was sewn up into a roll with needle and white thread and placed in the bottom of the pickle jar, to which the eluting fluid was added. While working as a first and second year pediatric neurology trainee, I used the information on cyclic ketones that had been given to me several years earlier to figure out the defect in branched-chain decarboxylation that was the underlying cause for maple syrup urine disease. I was also able to make a tentative identification of the nature of the maple syrup odor.^5,6 Reading the articles I wrote on this subject, it becomes apparent how difficult it was in those days to identify a urinary substance. The substance had to be isolated and purified, a derivative had to be prepared, and its melting point had to be checked, and then rechecked when mixed with the synthetically prepared derivative (Figure 4). Any depression of the melting point indicated that the two substances were not identical. I had learned all of these techniques in undergraduate school and during my work for a master’s degree in organic chemistry.

During my residency, I also found the defect in tyrosine metabolism that was responsible for one form of tyrosinosis.⁷ During my second year of pediatric neurology training, in conjunction with Milton Alter, Yoo Soong, and two dermatologists, Gert Steigleder and David Weakley, I described a condition that I initially wanted to call G disease (H disease or Hartnup disease had just been described). This was the entity that later was named kinky hair disease or Menkes disease.⁸ For me, delineating the clinical and pathologic aspects of this X-linked condition lacked the excitement of locating the site of the metabolic defect in maple syrup disease. I did run a ceruloplasmin level on the affected sibling of the propositus but unfortunately drew blood at too early an age to detect its absence. As a consequence, it remained for Danks and his group working in Melbourne to find the underlying defect in copper metabolism a few years later.⁹ My first wife, an Australian, suggested that I write to the Australian Wool Institute, for they might know something about strange-looking hair. I did, enclosing a sample of hair and asking for suggestions, but as this was before the copperdeficient lambs had been described, the people at the Wool Institute were as perplexed as I was as to the cause of the boys’ Brillo pad-like hair.

Figure 4. Paper chromatography of the urinary keto acids from a patient with maple syrup urine disease. The keto acids were converted into their 2,4-dinitrophenylhydrazine derivatives and chromatographed, using a mixture of butyl alcohol, ethanol, and ammonium hydroxide (Bu Et NH3) as a developing fluid. The left-hand column contains the standards: pyruvate and a-ketoisocaproate (KICA). Both form two isomers that are separated by chromatography (Pyr I, Pyr II, and KICA I, and KICA II). KIVA = a-ketoisovaleric acid. The righthand column contains a sample of the urine from a patient

There were quite a few prominent persons on the staff of the New York Neurological Institute during my stay there. Most were clinical neurologists of considerable skill: they included Mel Yahr, Jim Hammill, Ernst Herz, who was interested in movement disorders, notably hereditary dystonia,¹⁰ Daniel Sciarra, and Lester Mount, who a few years earlier had described one form of paroxysmal choreoathetosis. ¹¹ I must not overlook Carmine Vicale, an elegant and dynamic teacher, with exemplary bedside manners. Lewis B. Rowland and Robert Fishman were fellows in neurology at that time, and their astuteness was impressive even then. Dom Purpura gave the neurology housestaff and the pediatric neurology trainees a series of lectures on neurophysiology. The lectures were dramatic, to say the least, but I could never comprehend them, and to this day neurophysiology has remained a total mystery to me. I did my electroencephalography rotation under Paul Hoefer and his young assistant, Eli Goldensohn. For my neuroimaging rotation, I worked under Juan Taveras. In those days, pneumoencephalography and carotid arteriography were the mainstays of imaging, and residents had to learn how to insert a catheter into the carotid artery. It was not an easy procedure, and I never became proficient at it. For a time, I also worked in the neurochemistry laboratory under David Nachmansohn on acetylcholine esterase inhibitors. Sid Carter gave me 3 months leave from the training program to work on the project, but I never got very far because at the same time I was chasing down the branched-chain keto acids in maple syrup urine disease.

Other pediatric neurology trainees who were at the New York Neurological Institute at the same time as I, or followed me closely, included Mel Greer, Arnold Gold, Ray Chun, Isabel Rapin, and Gerry Nellhaus. 

In 1960, I completed my pediatric neurology training and returned to Johns Hopkins Hospital as assistant professor of pediatrics and neurological medicine, much to the chagrin of Houston Merritt, who predicted that, some day, I would be back at the New York Neurological Institute. That was one of the few wrong prognoses he ever made.

At Johns Hopkins Hospital, I came under the tutelage- I nearly wrote spell-of David Clark. Dave was a master clinician, with a fantastic knowledge of the medical literature, and a superb teacher in the best Queen Square tradition. I set out to model myself after him, but I must admit that as much as I tried, he remained in the words of Dante and T.S. Eliot "il miglior fabbro" (the better craftsman). Dave and I described a new clinical entity, an X-linked agenesis of the corpus callosum, which manifested itself by seizures and profound mental retardation.¹² A few years after my arrival, politics at Johns Hopkins Hospital became too much for Dave, who wanted Neurology to become a separate department independent of the Department of Internal Medicine. His efforts were unsuccessful, and when a position at the University of Kentucky opened up, Dave reluctantly left Baltimore and went into exile, leaving me to take over Pediatric Neurology. I trained Ted Chronister, who currently practices in Wilmington, Delaware, and Marvin Weil, who is partly retired and works at Oxford University. Marv has been a prominent contributor to all editions of my Textbook of Chid Neurology. During my time at Johns Hopkins Hospital, I continued work on the various inborn metabolic errors. I tried to sort out the phenylalaninemias ¹³ and assayed an understanding of the mechanism of brain damage in phenylketonuria and maple syrup urine disease. ^14-16 Toward the end of my stay at Johns Hopkins Hospital, I was approached by the editors of Lea and Febiger. They wanted me to prepare a textbook on pediatric neurology oriented toward the rapidly expanding neurosciences. I accepted and started work on the first edition, which was published some 8 years later. It was and continues to be the aim of the textbook "to incorporate some of the knowledge derived from the basic neurologic sciences into the clinical evaluation and management of the child with neurologic disease." The sixth edition of the text appeared in 2000.¹⁷

In 1966, Robert Ulstrom, who had just moved to Los Angeles from Minnesota, offered me a position as head of pediatric neurology at the University of California-Los Angeles. I accepted and returned to Los Angeles. I set up a superb division-the best on the West Coast-with Marvin Weil at Harbor General Hospital, Richard Schain, Rebecca Hanson, and Charlotte Loring as our developmental neuropsychologist. Ronald Gabriel was our first trainee, and Hobart Wiltse, Lydia Eviatar, Ernesto Aeberhard, Jorge Grippo, and Ephraim Yavin all worked in our division. We were extremely productive and published numerous articles, mostly on metabolic and genetic disorders that affect the brain. One of our neurosurgeons, Ulrich Batzdorf, and I set up neuronal cultures derived from a brain biopsy of a patient with GM2 gangliosidosis and demonstrated that they continued to store the ganglioside while in cultures. ¹⁸ My most notable work of that time dealt with cerebrotendinous xanthomatosis. I was able to demonstrate that the characteristic defect in this entity was the cerebral and cerebellar deposition of cholestanol.¹⁹

The discovery of the defect was, once again, the result of luck and serendipity. I had extracted cerebral white-matter sterols and ran a thin-layer chromatograph of the sterol fraction without finding any abnormality. By chance-I forget for what reason-I had a silver nitrate-coated plate lying around the laboratory. I spotted the lipids on it, and, lo and behold, after developing the plate-I forget in what solvent-the cholesterol spot became two spots: cholesterol and what turned out to be cholestanol (Figure 5) This important finding allowed Cali and his group to uncover the underlying defect in mitochondrial sterol 27-hydroxylase some 23 years later.²⁰

After a few years, I became frustrated with the heavy hand of politics on academic medicine and on the growth of the Division of Pediatric Neurology and transferred my research laboratory to the Brentwood Veterans Hospital. I hoped that, by working there, I would be able to spend less time on administrative chores and more time on research. David Barkley and I studied the behavior of fibroblast cultures obtained from patients with Huntington’s disease. We observed a cellular growth pattern, which still puzzles me: namely, that Huntington’s disease fibroblasts reach a higher confluence than do cells obtained from normal subjects.^21,22 Budget restrictions and the fact that I was in charge of a neurology laboratory in what was essentially a psychiatric Veterans Affairs hospital took its toll, and our laboratory was requisitioned for psychiatric research. I elected to go into part-time private practice. Except for a 3-year period when I studied molecular biology in the laboratory of Allan Tobin, I have since primarily been involved in clinical work and teaching. I have always enjoyed teaching and consider it a challenge and an occasion when new questions and ideas can appear. In this way, I am able to infuse clinical pediatric neurology with my knowledge of the basic neurosciences. In short, I consider myself to be one of the last of an endangered species, the physician scientist.

Figure 5 Thin Layer Chromatography

What are the factors that have led to the gradual decline and will ultimately cause the disappearance of the physician scientist? The way I view it, the physician scientist is an individual whose research work is the consequence of creative inspiration triggered by interacting with a patient as much as a sonnet is the outcome of creative inspiration. Over the last few decades, two factors have placed serious constrictions on scientific creativity. The first limitation is inherent in all true scientific investigation, whereas the second is the consequence of external and potentially avoidable factors.

One of the tenets of scientific creativity is that whatever scientific theory is being put forward-often the consequence of creative intuition or speculation-being an empirical theory, it must withstand detailed and severe tests. Should ensuing facts falsify the theory, it has to be abandoned, regardless of its beauty and emotional attractiveness to its creator. It is, however, true that "facts that fit into a preconceived hypothesis attract attention, are singled out, and remembered. Facts that are contrary to it are disregarded, treated as exceptions and forgotten. ²³ Feynman stressed the importance of the imagination and the judgment of what to record and what to omit, adding, "You can’t look at everything. When you look at everything you can’t see the pattern."²⁴ Yet, too much imagination is discouraged since it will inevitably lead to falsification of data and outright fraud. A second fact inherent in scientific creativity is that, as Popper states, the game of science is, in principle, without end. There are always further questions, and there is a need for further theories. ²⁵ These inherent restrictions are acceptable to anyone who embarks on a career of scientific research, just as the inherent restrictions of a sonnet are acceptable to anyone who proposes to write one.

Rather than being a deterrent, they represent a challenge, which the scientist must confront and overcome. It is the external factors that have become burdensome and, in the last decade or two, progressively less tolerable. The first of these is the increasingly prevalent tenet that control of research, that is, what work can or cannot be performed, should be in the hands of the funding agency, be it government, industry, or patient advocate group. It is the contention of these bodies that scientific research must be conducted either for the public good or to improve the bottom line, and that its direction must therefore be at their behest rather than that of the investigator. These bodies support work that appears to follow these tenets and disapprove of work that appears to run counter to them. To a lesser extent, publication or rejection of scientific articles has a like effect. The powers who have initiated this type of control and the scientists who have acquiesced to this directional pruning must have defective memories. Otherwise, they would recall similar instances of subordinating research to state or public directives under the guidance of the Nazi and Communist parties. The fact is, however, that no government directive can subordinate art, and scientific research, at its best, is an art. It is, in the words of Michael Polanyi, the art of making certain discoveries. ²⁶ The second external obstacle to scientific creativity is the overgrowth of administration. The number of different laws and regulations that affect the cost or conduct of research and that ensure that the hospital or university medical school obtains some degree of remuneration for the patient care conducted under its roof has increased by leaps and bounds. To comply with these regulations, there has been an enormous expansion of the number of university administrative personnel. At a time when young researchers are struggling to find funds to support themselves and their investigations, the administrative personnel of universities and medical schools has increased many-fold and continues to increase like rampant rabbits. This diversion of university and medical school funds into administration has resulted in a climate in which even the top medical investigators are spending an increasingly greater percentage of their time and energy on paper work. In short, bookkeeping and bean counting have taken precedence over creativity.

The third obstacle to creative research is the need for an academic physician to provide his or her medical schools and universities with a significant proportion of their income. At a time when allowances for patient services are being constricted, the physician, even though he has received solid training in a neuroscience, must spend more and more time on the ward and in the clinics to earn the funds required to ensure the survival of his department. As a consequence, he has no time to work in the laboratory, let alone any leisure time for the meandering of the mind such as prompted Fleming to look at the plates of staphylococci and find that an antibacterial substance had attacked the colonies secreted by the fungi. "What-a contaminated plate?" the researcher of the 21st century might tell his technician, as he glances at his watch, for he still has to write up and countersign a set of patient records and see several new admissions to the ward. "Throw it out, for God’s sake, and make sure you don’t get any more contamination." After all, there is no way he could ever obtain a research grant to study the contamination of bacterial plates.

The powers that control the future of medical schools and universities have ignored or forgotten an observation stressed by Polanyi, namely, that the wider the freedom of the scientist, the more fully he will be able to throw the force of his personal conviction into an attack on what he considers to be his own problem. ²¹

For the greater part of my life, I have required creativity of one form or another to express myself. For that reason, I have, over the last few years, turned to writing stage plays and novels, and the recent publication of my first novel has been one of the high points of my life.²⁷ I currently have secured a literary agent, who has three other novels of mine in her hands. Nevertheless, I can clearly remember the day when, while working on my master’s degree in organic chemistry, I finally synthesized 2-nitrofluoranthene, a new carcinogen, a substance that had never before been prepared. I looked at the small vial containing a few milligrams of orange crystals, and the excitement at the thought that I was the first to see this piece of nature overwhelmed me.

Then felt I like some watcher of the skies
When a new planet swims into his ken
Or like stout Cortez when with eagle eyes
He star’d at the Pacific-and all his men
Look’d at each other with a wild surmise
Silent, upon a peak in Darien

These are moments that have made my life worth living and have made valuable the reprieve I gained in 1939 through a stroke of sheer fortune.

References

1. King W, Menkes JH, Kloetzel MC: Fluoranthene derivatives: 2-nitro and 2-aminofluoranthene. J Am Chem Soc 1956;78:1165-1168.

2. Menkes JH, Csapo A: Changes in ATP and creatine phosphate content of rabbit uterus. Endocrinology 1952;50:37-50.

3. Menkes JH, Hurst PL, Craig JM: A new syndrome: Progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics 1954;14:462-467.

4. Wolf A, Cowen D: Granulomatous encephalomyelitis due to Encephalitozoon (encephalitozoic encephalomyelitis); new protozoan disease of man. Bull Neurol Inst N Y 1937;6:306-371.

5. Menkes JH: Maple syrup disease: Isolation and identification of organic acids in the urine. Pediatrics 1959;23:348-353.

6. Menkes JH: Maple syrup disease: Investigations into the metabolic defect. Neurology 1959;9:826-835.

7. Menkes JH, Jervis GA: Developmental retardation associated with an abnormality in tyrosine metabolism. Pediatrics 1961;28:399-409.

8. Menkes JH, Alter M, Weakley D, et al: A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics 1962;29:764-779.

9. Danks DM, Campbell PE, Steven BJ, et al: Menkes’kinky hair syndrome : An inherited defect in copper absorption with widespread effects. Pediatrics 1972;52:653-657.

10. Herz E: Dystonia. I. Historical review: Analysis of dystonic symptoms and physiologic mechanisms involved. Arch Neurol Psychiatry 1944;51:305-318.

11. Mount LA, Reback S: Familial paroxysmal choreoathetosis. Arch Neurol Psychiatry 1940;44:841-847.

12. Menkes JH, Phillipart M, Clark DB: Hereditary partial agenesis of the corpus callosum: Biochemical and pathological studies. Arch Neurol 1964;11:198-208.

13. Menkes JH, Holtzman NS: Neonatal hyperphenylalaninemia: A differential diagnosis. Neuropaediatrie 1970;1:434-446.

14. Menkes JH: The pathogenesis of mental retardation in phenylketonuria and other inborn errors of amino acid metabolism. Pediatrics 1967;39:297-308.

15. Menkes JH, Solcher H: Maple syrup disease: Effects of dietary therapy on cerebral lipids. Arch 1N96e7;6u:4r86-o49l1.

16. Menkes JH: Cerebral proteolipids in phenylketonuria. Neurology 1968;18:1003-1008.

17. Menkes JH, Sarnat HS: Textbook of Child Neurology, 6th ed., Philadelphia, Baltimore, Lippincott Williams & Wilkins, 2000.

18. Batzdorf U, Sarlieve L, Gold V, Menkes JH: Tay-Sachs’ disease: Demonstration of the stored ganglioside in cultured cells from brain biopsy. Arch Neurol 1969;20:650-652.

19. Menkes JH, Schimschock JR, Swanson PD: Cerebrotendinous xanthomatosis: The storage of cholestanol within the nervous system. Arch Neurol 1968;19:47-53.

20. Cali JJ, Hsieh CL, Francke U, Russell DW: Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem 1991;266:7779-7783.

21. Barkley DS, Hardiwidjaja S, Menkes JH: Abnormalities in growth of skin fibroblasts of patients with Huntington’s disease. Ann Neurol 1977;1:426-430.

22. Menkes JH, Hanoch A: Huntington’s disease: Growth of fibroblast cultures in lipid-deficient medium. Ann N eurol 1977;1:423-425.

23. Levi-Montalcini R: In Praise of Imperfection. New York, Basic Books, 1988.

24. Feynman RP: "Surely You’re Joking Mr. Feynman!"Adventures of a Curious Character. New York, WW Norton, 1985.

25. Popper KR: The Logic of Scientific Discovery. New York, Science Editions, 1961.

26. Polanyi M: The autonomy of science. Psychol Issues 1974;8:15.

27. Menkes J: The Angry Puppet Syndrome. New York, Demos Publications, 1999.

This autobiography originally appeared in J Child Neurol 2001; 16; 191. The online version with further features can be accessed at http://jcn.sagepub.com

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