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SEYMOUR S. KETY August 25, 1915-May 25, 2000 BY LOUIS SOKOLOFF SEYMOUR SOLOMON KETY, a member of the National Acad- emy of Sciences since 1962, flier! on May 25, 2000. He was an outstanding scientific statesman, but more signifi- cantly an eminent neuroscientist en cl pillar of biological psychiatry. He will Tong be remembered for his legendary scientific achievements, outstanding statesmanship, en cl mag- nanimity of spirit. I was fortunate to have known Seymour for approximately 56 years as a teacher, preceptor, collabo- rator, colleague, en cl friend, en cl in every one of these roles he earnecl an unmatched level of esteem, not just from me but also from almost everyone with whom he interacted. He gracecl every fielcl in which he workocl en cl those with whom he worked, en cl I know of no scientist who was so universally respected, acimirecI, en c! even TovecI. Neuroscience en cl psychiatry have suffered a great loss. Seymour was born in Philaclelphia on August 25, 1915. He was raiser! there in rather humble but intellectually stimu- lating surroundings. In his chilc~hoocl he suffered an auto- mobile-inflictecl injury to one foot that, though not serious, resulted in residual physical limitations that deprived him of participation in the usual athletic activities of chilc~hoocl en cl clirectecl him further toward intellectual pursuits. One 61
62 BIOGRAPHICAL MEMOIRS of his greatest interests was in chemistry, and he spent many hours carrying out chemical experiments in a laboratory he created in his home. Seymour received all his primary en cl secondary school education in Philaclelphia, where he at- tended the prestigious Central High School, the city's pre- mier high school. There he was able not only to pursue his interests in the physical sciences but also to receive a fairly broacl education in the classics, inclucling both Greek en cl Latin, en cl to be inspired by an erudite en cl nourishing faculty. After graduation from high school he attenclecl the col- lege en cl then the meclical school of the University of Penn- sylvania, from which he gracluatec! in 1940. He then mar- riecl Josephine Gross, whom he hacl known from chilc~hoocI, en cl entered into a rotating internship at the Philaclelphia General Hospital. Josephine was also a meclical student en c! eventually a physician who was particularly interested in pediatrics. It may well have been her influence that lecl Seymour to choose an area of research while still in mecli- cal school en cl to pursue further cluring his internship. This research lecl to the first of his many major contributions to meclical science. Pediatricians were at that time concerned about the many children they saw with lead poisoning, probably due to their chewing on the leacI-containing paint on their cribs. Mar- shaling his long-time interest in and knowledge of chemis- try, Seymour conceived of the idea of using citrate to treat lead poisoning, because citrate forms a soluble chelate of leacl that is relatively rapidly excreted in the urine. Better and more effective chelating agents are now in use, but this was the first proof of principle that chelating agents can be usecl in the treatment of heavy metal intoxication. To pursue further his interest in leacl poisoning after completion of his internship, Seymour obtained a National
SEYMOUR S. KETY 63 Research Council postcloctoral fellowship to work with Jo- seph Aub, a well-known researcher on leacl poisoning at the Massachusetts General Hospital in Boston. The fellowship began in 1942, but by then the Uniter! States was at war, en cl when Seymour arrived, he founcl that Aub hacl aban- clonecl his work on leacl poisoning en cl switched to a more pressing problem cluring wartime: traumatic en c! hemor- rhagic shock. Seymour joined the group working on that problem, en cl it was the research on shock that lecl him to clevelop an interest in circulatory physiology. He became particularly intriguccl by the cerebral circulation that ap- pearecl to be relatively preserved in carcliovascular shock by regulatory mechanisms that acljustec! the distribution of the reclucecl cardiac output to favor the brain, heart, en cl lungs at the expense of less vital circulatory becis. To pursue this new interest he electec! to forego the opportunity to re- main at Harvard en cl in 1943 returned to the University of Pennsylvania to work with Carl Schmidt, then a leacling figure in the field! of the cerebral circulation, Schmidt hac! just publishecl his bubble-flow-meter technique for the quan- titative determination of cerebral bloocl flow (CBF) en cl metabolism in anesthetizes! monkeys. Both Seymour en c! Josephine hacl been born, raised, en cl eclucatecl in Philaclel- phia, en cl their desire to return to their roots may also have been a factor in this decision. Seymour was an instructor in Schmicit's Department of Pharmacology when I first met him in 1944 as a student in his first class in pharmacology. He was an excellent teacher who presented lucid, stimulating lectures that emphasized the experimental procedures and results unclerlying the conclusions that were to be drawn. I still remember how he macle even a lecture on analgesics exciting. He was popular with the students en cl reaclily accessible to them. As he was not much oicler than we were, he often joiner! some of the
64 BIOGRAPHICAL MEMOIRS members of our class on the patio of Houston Hall, the university's Student Union, where we usually congregated after lunch. It was in casual conversations on those occa- sions that we first learner! of his interest in the cerebral circulation. He was in the process of formulating icleas about a method for measuring cerebral bloocl flow in human sub- jects that wouic! require the sampling of cerebral venous bloocl from the internal jugular vein. I suspect that he might have been trying to get us to volunteer for the procedure, but if so, it was without success. At the 1944 annual meeting of the Federation of Ameri- can Societies for Experimental Biology there was a sympo- sium on the cerebral circulation that clealt mainly with the methods of its measurement. The dominant theme was the neecl for a method for measuring CBF quantitatively, en cl preferably one applicable to unanesthetizec! man. There were at the time nonquantitative methods for studying CBF in man. One was the thermoelectric flow recorder, a ther- mocouple in the form of a neecIle that conic! be inserter! into the jugular vein to detect changes in flow within the vein by recording changes in the temperature of its bloocl content. This technique conic! indicate only blooc! flow changes within the vein but couIcl not measure perfusion rates within the brain tissue. Another popular method at the time was the measurement of cerebral arteriovenous O2 differences, which shouIcl vary inversely with changes in CBF if cerebral O2 consumption (CMRO2) remained constant, but it clic! not actually measure CBF en c! conic! not clistin- guish between changes in CBF en cl CMRO2. The only method that quantitatively cleterminecl both CBF en cl CMRO2 was the bubble-flow technique of Dumke en c! Schmidt, but this method required not only anesthesia but also such exten- sive surgery that its use was restricted to monkeys. Seymour attenclec! this symposium en c! accepted! the chal-
SEYMOUR S. KETY 65 lenge with a unique en c! conceptually brilliant approach. He was aware of Cournand's application of the direct Fick principle to the determination of cardiac output in man by measuring the rate of O2 uptake into the lungs en c! the difference in O2 concentrations between bloocl going to en cl coming from the lungs. Seymour reasoned that he couIcl apply the Fick principle indirectly by introducing into the bloocl a foreign, chemically inert tracer that cliffusecl freely across the bloocI-brain barrier en cl measuring the cerebral arteriovenous difference (i.e., difference in tracer concen- trations in the arterial bloocl going to the brain en cl in representative cerebral venous bloocl coming from the brain). He initially chose the freely cliffusible gas nitrous oxide (N2O) as the tracer en cl aciministerecl it in low concentra- tions in the inspired air. Arterial blooc! is the same in all arteries, but was usually samplecl in the femoral artery. Venous bloocl varies from vein to vein, but representative cerebral venous bloocl was sampler! from the superior bulb of the internal jugular vein. It was necessary also to know the amount of tracer taken up by the brain. In cleverly designed experiments he showed that after about 10 minutes the concentrations in the brain en cl cerebral venous bloocl were close enough to equilib- rium to allow calculation of brain N2O concentration from the measurer! cerebral venous concentration at that time en cl the relative solubilities (i.e., partition coefficient) of N2O in brain and blood. The same principle applied equally well to other chemically inert tracers, such as 79krypton en c! i33xenon, and these were later used sometimes instead of N2O, because it was more convenient to measure their con- centrations in blood. Another particularly valuable feature of the N2O method was that because it required the sam- pling of both arterial en cl cerebral venous bloocl to cleter- mine CBF, it became relatively simple also to determine the
66 BIOGRAPHICAL MEMOIRS brain's rates of utilization or production of oxygen, glu- cose, carbon clioxicle, en cl lactate by measuring their cere- bral arteriovenous differences en cl multiplying them by the value obtainer! for CBF. This ingenious conceptual approach resulted in the Kety- Schmicit method for the quantitative determination of ce- rebral blooc! flow en c! metabolism in unanesthetizec! man. The experimental work that lecl to its clevelopment was sup- portecl by a grant from the Scottish Rite en cl carried out on conscientious objectors who hac! volunteered! to be user! as subjects in meclical research rather than to be incluctecl into the armecl forces cluring the war. The N2O method en c! five of its applications in various physiological en c! clis- ease states were publishecl in a single issue of the Journal of Clinical Investigation in 1948. Its impact was like a thun- clerciap that revolutionizer! research on the human brain. Numerous applications in neurology, psychiatry, en cl mecli- cine lecl to much of our knowlecige of the normal physiol- ogy, pathophysiology, en c! pharmacology of the circulation en cl metabolism of the human brain in health en cl disease. Carl Schmidt, in whose department Seymour clevelopecl the method, wrote, Now, for the first time, the clinical physiologist is no longer at a disadvan- tage in studying the circulation in the human brain. As a matter of fact he is now able to learn more about this, and its relation to the metabolic functions of the organ supplied, than about any other organ of the body. The change is one of the small profits of the research activities of the war years and is one more example of the benefits to be expected from giving brilliant young men opportunities to develop and test out original ideas. These papers were publishecl while I was serving in the U.S. Army as a neuropsychiatrist en c! uncleciclec! about what to clo when I was clischargecI. The iclea of studying clirectly the circulation en cl energy metabolism of the human brain in normal en c! mentally ill subjects attracted! me, en c! shortly
SEYMOUR S. KETY 67 after leaving the Army in 1949 I joiner! Seymour as a postcloctoral fellow in Julius Comroe's Department of Physi- ology en cl Pharmacology in the Graduate School of Mecli- cine of the University of Pennsylvania, where Seymour hac! been appointed a full professor. It was a fantastic experience. Seymour was an inspiring leacler. Despite his towering intellect, he never allowed! it to overwhelm us. He was always humble en cl unpretentious en cl listenecl to everything we hacl to say. Often he wouIcl raise questions en c! patiently consoler our comments even though, as we wouIcl later learn, he aIreacly knew the an- swers. His attitude stimulatecl us to think critically en cl cleeply. A frequent comment of his was, "Well, think about it." He valuccl conceptualization, originality, en cl uniqueness above all. In my very first project as a research fellow, which was on the effects of hyperthyroiclism on cerebral O2 consump- tion in man, we were scoopecl in the publication of the entirely unexpected fincling that the oxygen consumption of the brain remainec! normal despite very large increases in total belly O2 consumption. He consolecl me with the comment, "Don't feel bacI. It must not have been such a great iclea. Someone else thought of it too" a sentiment typical of his attitude. Seymour's office in the department hacl two Coors. One opener! into the corridor en c! the other into the large room where the research fellows had their desks. The latter door was almost always open, anct we constantly ~nterruptect hIS work, which at that time was mainly on the preparation of his now classical en cl seminal Pharmacological Reviews ar- ticle "The Theory en cl Applications of the Exchange of In- ert Gas at the Lungs en c! Tissues." One clay late in the summer of 1950 the floor was closecl all clay while Seymour was meeting with two U. S. Public Health Service officers in their white uniforms. . . · . . · · ~
68 BIOGRAPHICAL MEMOIRS All of us were curious, of course, because we suspected! that whatever this meeting involvecl it wouIcl impact us. There- fore, as soon as the officers left we queried him about the purpose of their visit. It turner! out that they were Robert Felix en cl Joseph Bobbitt, the director en cl the executive officer of the National Institute of Mental Health (NIMH), one of the newly former! institutes in the National Insti- tutes of Health in Bethesda, MarylancI. They hacl come to offer him the position of scientific director of the intramu- ral research programs of both the NIMH en c! the National Institute of Neurological Diseases and Blinciness ( then NINDB, now National Institute of Neurological Disorders en c! Stroke). When we asker! him if he wouic! seriously con- sicler leaving Penn for such an offer, he repliecl that wouIcl incleecI, because he hacl always been interested in mental disease en c! that this offer presenter! a challenging oppor- tunity to study it. We then asked why they would choose him, a physiologist en cl neither a psychiatrist nor a neu- rologist, to direct a program of research on mental en c! neurological diseases. His reply was that he hacl hacl the same question en cl hacl raisecl it with Felix en cl Bobbitt. They explained that it was exactly for that reason that they wan tell him, they thought that the scientific director of a research program on mental and nervous diseases should be a basic scientist and not a psychiatrist or neurologist in order to ensure rigorous en cl scientifically sound research. Seymour clicl not, however, rush to a decision. After several months of agonizing rumination en c! frequent consultations with friends, colleagues, and undoubtedly Josephine, he ac- ceptecl the appointment, en cl in 1951 left Penn to uncler- take the organization of the intramural research programs of the NIMH and NINDB. The Clinical Center of NIH was under construction when he arrived, and Seymour, as scientific director, had what he
SEYMOUR S. KETY 69 consiclerec! almost unlimited! resources in space, budget, en cl positions to organize the intramural research programs of the NIMH and NINDB. He approached this responsibil- ity in characteristic Kety fashion: cautiously, cleliberately, systematically, studiously, and with great humility. He had no preconceived notions about how best to stucly mental en c! neurological diseases but hac! faith that more basic, funciamental knowlecige of the structure en cl functions of the nervous system wouIcl be neeclecI. He therefore empha- sizec! the basic sciences en c! relegates! most of his resources to laboratories organized along more or less traclitional clis- ciplinary lines. Seymour then exhaustively consulted! leaclers in these clisciplines to identify outstanding cancliciates en cl succeeclecl in recruiting a truly impressive array of laboratory chiefs. Some of these were Wacle Marshall, chief of the Laboratory of Neurophysiology, William WincIle, chief of the Labora- tory of Neuroanatomical Sciences, Giulio Cantoni, chief of the Laboratory of Cellular Pharmacology, Kenneth Cole, chief of the Laboratory of Biophysics, David Shakow, chief of Psychology, and John CIausen, chief of the Laboratory of Socio-Environmental Sciences. He retainer! for himself the position of acting chief of the Laboratory of Neurochemis- try while he was trying to recruit an outstanding biochemist with interest in the nervous system, he also reserves! for himself within that laboratory the Section on Cerebral Me- tabolism in which he couIcl carry out his own research. Seymour did not pretend to be expert in all these disci- plines in the program. Once these laboratory chiefs were appointed he gave them full authority and support to di- rect their own laboratories as they chose, but proviclec! them with his advice, counsel, and assistance in recruiting their staffs. The laboratory chiefs were selectecl not because they hac! been working in the latest most fashionable, so-called!
70 BIOGRAPHICAL MEMOIRS "hot" research areas but because they hac! clemonstratec! originality and conceptual ability in their choice, design, en cl execution of their previous research. He was unim- pressec! by mere descriptive research or research driven more by ambitious, wish-fulf;~ling (though unrealistic) goals than by insight. His acumen in his selection of laboratory chiefs, as well as some members of their staffs that he hac! helpec! to recruit for them, was eventually confirmed, one won a Nobel Prize, at least three received Lasker awards, en cl at least a clozen, if not more, were eventually electec! to the National Academy of Sciences. While engaged in the organization of the intramural research programs of the NIMH en c! NINDB, Seymour col- laboratecl with several biochemists in Europe en cl the Unitecl States (e.g., Heinrich Waelsch, Paul Manclel, Derek Rich- ter, Henry McIlwain) in efforts to bring greater recognition en cl respect to en cl interest in the fielcl of neurochemistry. Their efforts resultecl in the initiation in 1954 of biennial neurochemical symposia, later transformer! into the Inter- national Society for Neurochemistry, the foundling of the journal of Neurochemistry in 1956, en cl the establishment of the International Brain Research Organization (IBRO) in 1960. Seymour allocatecl to his own Section on Cerebral Me- tabolism a moclest amount of laboratory space in which to conduct his own research. Because his nitrous oxide method measured only average bloocl flow en cl metabolic rates in the brain as whole, it conic! not localize changes in these functions in discrete regions of the brain. He therefore undertook the clevelopment of a method to measure local cerebral blooc! flow baser! on his theory of inert gas ex- change between bloocl en cl tissues that he hacl previously developed and published in 1951. With the help of several research fellows (i.e., William Landau, Walter Freygang, Lewis
SEYMOUR S. KETY 71 RowlancI, en c! myself) he ingeniously translates! his theories into an operational method for measuring local CBF. The method couIcl be usecl with any chemically inert tracer that conic! diffuse freely across the bloocI-brain barrier, but they selectecl i3iI-labelecl trifluoroloclomethane ~ ki3iI] CF3I), a gas with the requisite properties. Localization within the brain was achieved by a unique quantitative autoradiographic tech- nique that limitecl its use to animals. The method en cl its use to determine local CBF in incliviclual structural en cl functional units of the brain in conscious en c! anesthetizes! cats was first reported in 1955. When usecl to examine the effects of visual stimulation, the autoracliograms clearly vi- suaTizec! the increases in CBF in the various structures of the visual pathways en cl lecl to the very first publishecl clem- onstration of functional brain imaging, a fielcl now enjoy- ing enormous popularity. Because the trifluoroloclomethane method was clesignecl for use with autoracliography, it couIcl be usecl only cluring uptake of tracer by the tissues. The unclerlying principles on which it was basecl were, however, equally applicable to clearance of the tracer from tissues after they hacl been pre-Ioaclec! with the tracer. Seymour hac! in fact user! the clearance approach to determine bloocl flow in muscle of human subjects. He hacl injected i4NaCl clirectlyinto the muscle en c! measurer! its clearance from its site of injection with a Geiger counter. The publication in 1949 that de- scribed these experiments included a detailed description of the theory and procedure for calculating local blood flow from the rate of clearance of the tracer. The 24NaCl clearance method couIcl not, however, be usecl in brain because 24NaCT is not freely cliffusible in either direction across the bloocI-brain barrier, but Niels Lassen, David Ingvar, en cl colleagues later aciaptecl it by using radioactive gases, first radioactive krypton (85Kr) and subsequently i33xenon.
72 BIOGRAPHICAL MEMOIRS The i33Xe methoc! has been extensively en c! very effectively usecl as a clinical en cl research tool for several clecacles. More recently the trifluoroloclomethane method has been resurrected! for human use, but with i50-labelec! water as the tracer en cl PET scanning in place of autoracliography, en cl is now wiclely usecl in the functional brain imaging of cognitive processes in humans. All these fantastic new cle- velopments in neurobiology were clerivecl from Seymour's · ~ pioneering won a. In ~ 956 Seymour stepper! clown from the position of scientific director to become the chief of the Laboratory of Clinical Science. Having completecl organization of the ba- sic research components of the intramural research pro- grams of NIMH en cl NINDB en cl being too humble to feel that he shouIcl or couIcl direct or interfere with the re- search of the outstanding en c! diverse cacire of laboratory chiefs that he hacl assemblecI, he no longer founcl the posi- tion of scientific director sufficiently challenging. As he put it, he no longer enjoyed! the role of "clecicling where to put the broom closets." There were also other reasons, he was anxious to become more immersed in his own research in new areas in which he hac! become interested. He hac! been impressed by clevelopments in psychopharmacology, par- ticularly those involving the monamine neurotransmitters and the actions of psychotomimetic drugs, such as LSD, mescaline, inclole derivatives, en cl the like. There were sug- gestions at the time that abnormal metabolites of amino acicis or of epinephrine might be involves! in schizophre- nia. There were also a few publishecl studies, which though flawed and inconclusive suggested genetic influences in schizophrenia. All this reinforcer! Seymour's suspicion that schizophrenia might be a biochemical clisorcler that was at least partly inherited. He therefore establishecl in the Labo- ratory of Clinical Science a program of research on the
SEYMOUR S. KETY 73 biology of schizophrenia. One of his projects was to exam- ine the hypothesis that abnormal disposition of epineph- rine might be involvecl in schizophrenia, en cl to facilitate this stucly he contracted! for the first commercial synthesis of radioactive epinephrine and norepinephrine. The labelecl compounds later proved to be of immense value to Julius AxeirocI, a member of the laboratory, in his Nobel Prize- winning research. Although no definitive evidence of a biochemical defect linkocl to schizophrenia was clerivecl from these studies, they clic! serve to organize Seymour's think- ing about the subject en cl lecl to his publication of several critical en cl heuristic papers in Science that almost certainly lair! the foundation for moclern biological psychiatry. He was quite amused by my quip that he had transmuted psy- chiatry from psychoanalysis to urinalysis. His research at NIMH was interrupter! in 1961, when he accepted the position of chairman of the Department of Psychiatry at Johns Hopkins University. He had, however, never received formal training in clinical psychiatry, and he felt very uncomfortable being in the position of psychiatrist in chief at Johns Hopkins University Hospital. Therefore, after one year he resigner! en c! returnee! to his position as chief of the Laboratory of Clinical Science at NIMH en cl resumed his research on schizophrenia, this time focused on the question of genetic contributions to the disease. Previous studies of siblings en cl monozygotic en cl clizy- gotic twins hacl suggested a genetic influence, but they hacl failer! to clisentangle convincingly the roles of "nature en c! nurture." He conceived the brilliant idea of studying the adoptive en cl biological family lines of schizophrenics who hac! been acloptec! at birth. The necessary ciata were avail- able in the Danish Case Registry, en cl he in collaboration with colleagues, mainly David Rosenthal en cl Paul Wencler at NIMH en c! Fini Schuisinger in Denmark, initiates! such
74 BIOGRAPHICAL MEMOIRS studies. In 1967 he left NIMH for Harvarc! University, where he first became director of psychiatric research at the Mas- sachusetts General Hospital, then director of the Laborato- ries for Psychiatric Research, Mailman Research Center, McLean Hospital, en cl finally professor of neuroscience in the Department of Psychiatry. In ~ 983 he retired from Harvarc! en c! returnee! to NIMH from which he retiree! once again in 1996. Throughout all these clecacles en cl all his moves he con- tinucc! his studies on acloptec! schizophrenics. The results clemonstratecl far greater incidence of the disease in the biological than in the adoptive family lines and thus pro- viclec! unequivocal evidence of a major genetic component in the etiology of schizophrenia. The conclusions were not reaclily accepted by many committed to a social ancI/or en- vironmental basis for the disease. Seymour acknowlecigec! that schizophrenia was not a purely genetic disease, like phenylketonuria or Huntington's disease, only that there was an inherited! susceptibility in a group of patients that fell within what he callecl a "schizophrenia spectrum." He responclecl to sometimes severe criticism with his character- istic wit en c! wisdom. For example, in response to the state- ment "Schizophrenia is a myth," he wrote, "If schizophre- nia is a myth, it is a myth with a strong genetic component." The adoption studies contributes! not only to our uncler- standing of schizophrenia but also their underlying strategy en cl design proviclecl a research moclel that has been en cl continues to be follower! in studies of a number of other psychiatric disorders. Seymour Kety's legacy encompasses at least three differ- ent areas of endeavor. As a physiologist he made extraordi- nary contributions mainly to the fielcl of cerebral circula- tion en cl metabolism but also to general circulatory en cl respiratory physiology. As a wise and adroit statesman he
SEYMOUR S. KETY 75 clevelopec! at NIMH en c! NINDB outstanding research pro- grams in neuroscience, contributed substantially to the rec- ognition of neurochemistry as a respectable en cl important field! of neuroscience, was a powerful force for the clevelop- ment of biological psychiatry, en cl was a sage counselor on countless advisory boards en cl committees. As a psychiatric geneticist he conceptualizes! en c! clevelopec! a methoclologi- cal approach for separating the contributions of nature en cl nurture in the etiology of mental disease en cl usecl it to prove the existence of a strong genetically cleterminec! vul- nerability to schizophrenia. There is, in aciclition, Seymour Kety the man. His pro- fessional achievements gainer! him enormous international recognition en cl acclaim. He received many awards, honor- ary degrees, en cl honorary titles en cl was electecl into some of the most honorific societies, such as the National AcacI- emy of Sciences, the American Academy of Arts en cl Sci- ences, en cl the American Philosophical Society. In 1999 he receiver! his last award, the Lasker Awarc! for Special Achieve- ment in Meclical Science, which touched him cleeply. None of these honors changecl him. He remained the same humble, moclest, self-effacing, unselfish, considerate, kincI, generous, en cl warm human being that he was when I first met him 56 years earlier. He always remained reaclily accessible to all and never used his razor-sharp intellect to overwhelm or intimidate. He was intensely loyal en cl supportive of his col- leagues en cl truly relishecl their successes whenever they occurred. Perhaps his wife, Josephine, a master of one-liner repartee, kept him humble. For example, Seymour once expressed to her his surprise that a newly arrival research fellow from India clic! not appear to be very impresser! when Seymour had proudly escorted him through NIH's newly opened Clinical Center, the worIcl's largest all-brick builcI- ing furnisher! with the most moclern hospital facilities. Her
76 BIOGRAPHICAL MEMOIRS response was, "Dic! you ever hear of the Taj Mahal?" When Seymour was scientific director of NIMH, psychoanalysis was a powerful influence in psychiatry, en cl the NIH aciministra- tion felt that the director of its research program shouic! undergo a personal psychoanalysis. Seymour resisted, but finally, when they offered to pay for it, he was inclinecl to accept. Josephine's comment was, "Suppose they offerer! you a free appendectomy. Would you take it?" The Ketys were generous en cl genial hosts en cl wouIcl often entertain at their home. These were always clelightfuT experiences full of scintillating conversation en cl humor from guests with a wicle variety of backgrounds. Seymour hacl an a enormous reservoir of jokes en c! amusing anecdotes that he enjoyed telling and occasionally using to make a point. The Ketys were also great art lovers, en cl Seymour was enam- orec! of goof! foot! en c! wine. Seymour Kaufman en c! I, both of us in the intramural program of NIMH, were present at what was probably the zenith of his experience with the French cuisine. In the summer of ~ 958 the three of us attenclecl in sequence an International Neurochemical Sym- posium in Strasbourg, France, an International Biochemi- cal Congress in Vienna, Austria, en c! finally the inaugural meeting of the Collegium Internationale Neuro- Psychopharmacologicum (CINP) in Rome, Italy. During the meeting in Strasbourg Kety inquirer! from Kaufman en c! me whether, if he bought a car, we wouIcl be willing to rifle with him to these meetings en cl then onto Paris, France. We, of course, gratefully accepted, but it was not until we reached France on the leg from Rome to Paris that we Earned his intentions. He hacl longecl to but hacl never previously eaten at any of the three-star restaurants in the almost biblical Guide Michelin. He hacI, therefore, plannecl a route that lecl us to four of only twelve such restaurants in all of France so honoree! at that time by the guicle. Because
SEYMOUR S. KETY 77 of time constraints we ate in four consecutive clays at Baumaniere in Les Baux, Provence, De La Pyramicle in Vienne, Burgundy, Hostellerie cle la Poste in Avallon, Bur- guncly, en c! La Tour cl'Argent in Paris. Kaufman en c! I were thoroughly saturated with fowl but not iron-man Kety, who attributed our weakness to lack of stamina clue to our youth. Those restaurants probably represented! the epitome of the traclitional French haute cuisine with its rich, flavorful sauces that he hacl come to admire so much. He later lamentecl the subversion of the classical French sauces by the advent of the nouvelle cuisine en cl cuisine minccur. Seymour is survivecl by his wife, Josephine, daughter, Roberta Kety, son, Lawrence Kety, en c! two grancichiTciren. He will be greatly missecl not only by them but also by his many colleagues en cl friends whose lives he so greatly influ- encec! en c! enriched.
78 BIOGRAPHICAL MEMOIRS SELECTED BIBLIOGRAPHY 1942 The lead citrate complex ion and its role in the physiology and therapy of lead poisoning. 7. Biol. Chem. 142:181-92. 1948 With C. F Schmidt. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: Theory, procedure, and normal values. 7. Clin. Invest. 27:476-83. With R. B. Woodford, M. H. Harmel, F. A. Freyhan, K.E. Appel, and C. F. Schmidt. Cerebral blood flow and metabolism in schizo- phrenia. The effects of barbiturate semi-narcosis, insulin coma and electroshock. Am. f. Psychiat. 104:765-70. 1949 The measurement of regional circulation by local clearance of ra- dioactive sodium. Am. Heart f. 8:321-28. 1950 Circulation and metabolism of the human brain in health and dis- ease. Am. f. Med. 8:205-17. 1951 The theory and applications of the exchange of inert gas at the lungs and tissues. Pharmacol. Rev. 3:1 -41. 1955 With W. M. Landau, W. H. Freygang, L. P. Rowland, and L. Sokoloff. The local circulation of the living brain; values in the unanesthe- tized and anesthetized cat. Trans. Am. Neurol. Assoc. 80:125-29. 1959 Biochemical theories of schizophrenia. A two-part critical review of current theories and of the evidence used to support them. Sci- ence 129:1528-32, 1590-96.
SEYMOUR S. KETY 1960 79 A biologist examines the mind and behavior. Many disciplines con- tribute to understanding human behavior, each with peculiar virtues and limitations. Science 132:1861-70. 1968 With D. Rosenthal (eds.~. The Transmission of Schizophrenia. Oxford: Pergamon Press. 1971 With D. Rosenthal, P. H. Wender, and F. Schulsinger. Mental ill- ness in the biological and adoptive families of adopted schizophrenics. Am. f. Psychiat. 128:302-306. 1976 With D. Rosenthal, P. H. Wender, F. Schulsinger, and B. Jacobsen. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic. Behav. Gen. 6: 219- 25. 1978 With P. H. Wender and D. Rosenthal. Genetic relationships within the schizophrenia spectrum: Evidence from adoption studies. In Critical Issues in Psychiatric Diagnosis, eds. R. L. Spitzerand and D. F. Klein, pp. 213-23. New York: Raven Press. 1983 Mental illness in the biological and adoptive relatives of schizo- phrenic adopters: Findings relevant to genetic and environmen- tal factors. Am. f. Psychiat. 140:720-27. 1 999 Mental illness and the sciences of brain and behavior. Nat. Med. 5:1113-16. 2000 With L. J. Ingraham. Adoption studies of schizophrenia. Am. f. Med. Genet. (Semin. Med. Genet.J 97:18-22.
