sion, intelligence, and wit. He once Past and Present described his technique this way:

I make the wildest theories, con- necting up the test tube reactions with the broadest philosophical Albert Szent-Gyorgyi: ideas, but I spend most of my time in the laboratory, playing with living matter, keeping my eyes open, observing and pursuing the The Art in Being Wrong smallest detail — Usually some- thing crops up. some small dis- crepancy which, if followed "n, When Dr. Albert Szent G^rgyi goes ogy. He is hopeful that his study of may lead to basic discoveries. The fishing in the waters around Woods the failure of malignant cells to re- theories serve to satisfy the mind, Hole, Massachusetts, he fixes a gar- constitute healthy submolecular prepare it for 'an accident' and gantuan hook to his line, explaining structures will one day throw new keep one going. I must admit that that "it is far more exciting not to light on the nature of the disease. most of the new observations I catch a big fish than not to catch a That is the work he projects for his made were based on wrong theo- small one." tenth decade. ries. My theories collapsed, but In a career that has spanned He operates on insight and on something was left afterward. most of the twentieth century, this the hunches that come to him as biochemist, now in his eighty-ninth he fingers the instruments in his It has been 45 years since Albert year, still pursues with the passion of laboratory. For him, science has al- Szent-Gyorgyi received a Nobel Captain Ahab the grandest and often ways been an art involving the in- prize for studies of cellular respira- the most elusive of objectives. Those terplay of sensory perceptions, pas- tion and for isolating the substance he has already attained are far more than enough to satisfy most people: those that have escaped him have usually proved to be such beguiling chimeras as to inspire whole generations of re- searchers. A brash young man at Cambridge University who once tried to dis- parage "the Prof," as Szent-Gyorgyi is affectionately known, was gently but firmly put down by the re- nowned parasitologist David Keilin, who told him, "I much prefer the stimulating ideas of Szent-Gyorgyi, even when he is wrong, to the dull correct ones advanced by most others." Now somewhat grizzled and crag- gy as a weather-beaten cliff, Szent- Gyorgyi still drives daily the mile or so from his home to the Marine Bi- ological Laboratories—that work- shop, proving ground, and nursery of science on the shore where Cape Cod begins. He gave up his motor- cycle when he was 85 and water- skis only occasionally now. It is a The figures of this paper are not reproduced. sport he took up on his eightieth There are about 10000 pictures given with a GOOGLE picture search birthday. for “albert szent gyorgyi” Currently, Szent-Gyorgyi is busily seeking an explanation of cancer in the Albert Szent-Gyorgyi is perhaps best known for his work on the muscle protein com- unexplored world of quantum plex, actomyosin. His 1937 Nobel prize was for the discovery of titamin C and for mechanics and submolecular biol- his pioneering explorations of mechanisms of cellular respiration.

H Hospital Practice May 1982 179 that became known as ascorbic art, and all things intellectual, to of Uncle Michael's advice, devoted acid, . the proud neglect of commercial his first scientific paper to the His subsequent work, always values. Religion was rarely dis- epithelium of the anus. characterized by his talent at play- cussed. Mrs. Szent-Gyorgyi was "an In time, his uncle encouraged Al- ing creatively with living matter, enlightened agnostic," her son re- bert to rise into the lofty precincts led him to discover the proteins of calls, "who would go to church only of histology, but by his third year of muscle contraction and, for the when her boys were in trouble, so medical school, Albert became dis- first time, to demonstrate the in- that she could bribe St. Peter with enchanted with that discipline. teraction of and myosin in a florin to lobby for her." Uncle Michael or no. "Morphology vitro. The Lenhosseks wove science and told me little about life," he re- It is the same appetite to under- music into a family tradition. His called. He was considering a change stand the cell in a^l its workings mother sang, and his maternal to , when the Austrian that has carried him past the fa- grandfather and great grandfather, Archduke was shot, throwing Eu- miliar landscape of molecular biol- who had been professors of anato- rope into war and Albert into uni- ogy into the submolecular, the elec- my and physiology in Vienna, also form. tronic. Colleagues, even when they played at least one instrument. Al- He served in the medical corps, are critical, do not scoff at the pos- bert admits that he must have and 65 years later still recalls with sibility that he may be right in been a dreadful disappointment. keen satisfaction that "there was maintaining that cancer is not He loved music but showed no ap- never any need for me to kill." He many diseases but one and that it titude in performance. "I do not was sent to the Italian front and can be understood electronically. have the gift," he says sadly. His then north to the Austrian slice of He has been as consistent and as older brother, Paul, outshown him Poland. He was awarded the Silver indefatigable in politics as in sci- scientifically and musically in the Medal for Valor but waves away all ence. He has used his prestige and early grades. "The fact is," this questions of how he won it. "Noth- his pen to oppose tyranny and war. Nobel laureate confesses, "I must ing special," he says. As the war His battles, whether scientific or have been a very dull child. Nothing dragged on, the slaughter seemed political, have always been fought happened to me." doubly futile with the seeming cer- with gusto and sometimes with a With a little help from tutors, he tainty of defeat. He yearned for a disarming directness that his crit- squeaked by in his examinations, wound that would send him home ics have mistaken for naivete. but his record depressed Uncle Mi- to his studies. When the enemy This life of challenge, adventure, chael Lenhossek, who had been failed to oblige, he shot himself in and misadventure began in the something of a child prodigy and the arm and returned to Budapest. peaceful setting of a pedigreed Hun- was then a celebrated histologist. It There he finished his medical garian family whose title of petty was to him and not to her husband courses and was awarded his doc- nobility dated to the seventeenth that Albert's mother turned for ad- toral degree. century. It was a family of comfor- vice on the education of boys. Mi- With the war still on. he resumed table respectability, generally well chael viewed Albert's prospects in national service in the army's bac- represented on the bench and in science as exceedingly dim. teriological laboratories. Almost the ministries of the Austro-Hun- In early adolescence, however, immediately, he tangled with his garian Monarchy. Here and there, a young Albert's habits took an superiors over risky experiments of maverick spiced the lineage, such abrupt turn. Suddenly he showed dubious value that were being per- as an earlier Szent-Gyorgyi who an omnivorous appetite for books formed on Italian prisoners of war. joined the doomed revolution of of all sorts and seemed to be devel- His protests won him an assign- 1848. oping a late-blooming passion for ment to a zone of malarial swamps Into this solid family there was science. Uncle Michael, not entirely in northern Italy, from which he born on September 16. 1893. a convinced by this sudden change, was saved, in a matter of weeks, by boy who was given the ponderous came to consider a possible career the collapse of the Central Powers. name of Albert Szent-Gyorgyi von in something elementary, like the He returned to Budapest and mar- Nagyrapolt—the last bit a piece of concoction of cosmetics. As Albert's ried Cordelia Demeny, the charm- aristocratic baggage that he record improved. Uncle Michael ing daughter of the Postmaster dropped very early in life. thought he might aspire to dentis- General, an official whom Albert He tends to dismiss his father. try, and as the boy's high school remembers fondly as a man of Nicolaus. as a man totally preoccu- grades positively soared, he sug- "good social feelings" rare in a bu- pied with his role as a semifeudal gested a modest career in medi- reaucrat. landholder. The family style was set cine—perhaps proctology. Defeat brought to Hungary six by the lady of the house, Josefine In due course, Albert received the months of a fierce Communist cru- Lenhossek. Albert Szent-Gyorgyi avuncular blessing allowing him to sade under Bela Kun. For part of unhesitatingly credits his mother apply for entry into the University that time, the newly licensed Dr. and her side of the family with in- of Budapest Medical School. In his Szent-Gyorgyi was working at a culcating him with a love of science. freshman year, Albert, ever mindful pharmacological laboratory in what

180 Hospital Practice May 1982 was then the Hungarian city of returning to Hungary after serving Pozsony. The map makers of Ver- as an associate professor under W. sailles, however, gave Pozsony to Storm van Leeuwen at the Institute the Czechs, who promptly renamed of Pharmacology of the University it Bratislava and assigned border of Leiden. He suggested that Szent- guards to shoot on sight any Hun- Gyorgyi take his place in Leiden. garian crossing the Danube in ei- The proposal was accepted, and ther direction. the Szent-Gyorgyis, in high spirits It was then that Albert Szent- once again, moved. "I felt I had a Gyorgyi cultivated a flair for un- future there that did not exist in derground maneuvers that was to Hamburg," Albert recalls. Unfortu- serve him well in another war. The nately, Albert's boss in the labora- laboratory had been equipped by tory, who had enjoyed a career as a young Hungarian scientists, who cavalry officer before he took up now plotted to ferry across the Dan- medicine, began to pay overly cava- ube whatever instruments were lier attentions to Mme. Szent-Gyor- portable or could be dismantled. gyi. He could not be easily discour- On one occasion, when Albert took aged, and the resulting tension advantage of a surreptitious cross- sent the Szent-Gyorgyis packing. ing to visit his mother, he had to Once again, the prospect of a stand all night in deep snow to tropical backwater rose like doom avoid the Czech patrols. He came before the wandering Szent-Gyor- out of it with a case of pneumonia. gyis. They stopped at Groningen, The Bela Kun regime lasted just where Albert was to prepare for the long enough to ruin the fortunes of Dutch licensing examination that the Szent-Gyorgyi family, so that by would qualify him for a job in the the time Albert could make it back East Indies. He easily passed the Otto Warburg's work on cellular respira- to Budapest with his wife and their first part of the test, becoming a tion was the springboard for Szent-Gyor- newborn daughter, he faced an un- "semi-Arzr (half a doctor), as the gyi's own. Both later studied the yellow certain future. He was a man with Dutch put it. He was running out luminescent protein that came to be a family, no money, and few rela- of money, when a job opened at the known as vitamin B2, or riboflaiin. tives in a position to help him. laboratory of Dr. H. J. Hamburger Searching for a niche in medical at the Physiological Institute in research where he could do some- Groningen. The elderly Dr. Ham- living cell by which the energy nec- thing useful and even marginally burger was pursuing an idea that essary not only for growth but for profitable, he traveled to Prague for seemed highly improbable to the the maintenance of cellular struc- a stint at electrophysiology with young Szent-Gyorgyi, but it prom- ture was derived from foodstuff. Armin Tschermak, to Berlin for an ised a salary, however minuscule. Warburg had stressed the activa- introduction into physical chemis- Dr. Hamburger wanted to implant tion of oxygen, and Wieland that of try, and to Hamburg's Institute for fistulas in dogs, enabling him to hydrogen. Szent-Gyorgyi had a Tropical Hygiene. inspect their digestive processes in hunch that both were right. He set The last move was an act of des- vivo. about proving as much by adding peration. Very nearly broke, he saw The difficulty was that few dogs cyanide to minced tissue, thereby a dubious salvation—but the only survived the surgery long enough eliminating the possibility of oxy- one left to him—in some outpost of to afford Hamburger more than a gen activation. Then he added empire where there might be an glimpse. Szent-Gyorgyi, however, methylene blue and delightedly ob- opening in a jungle laboratory. Now achieved a record number of long- served the action of hydrogen re- sitting in his pleasant old house on term survivors, to Hamburger's de- storing the respiratory process. the Massachusetts shore, with a light. In the time he could spare He took to working on plant distinguished career behind him from the operating theater, Szent- tissue, convinced, as he now puts and perhaps ahead of him as well, Gyorgyi was free to carry out his it, that "there is no basic difference Szent-Gyorgyi reflects, "In the trop own ideas. It was in those years, between man and the grass he ics I would have been lost forever" from 1922 to 1926. in Groningen mows." He had noted that when he He had already outfitted himself that he hit upon a field of explora- added peroxide to a peroxidase and for the jungle when a reprieve ar- tion that was to change not only benzidine, the mixture instantly rived. The Dutch Physiological So- his life but the course of twentieth became intensely blue, caused by ciety was meeting in Hamburg that century physiology. the oxidation of the benzidine. How- year. Albert Szent-Gyorgyi attended Otto Warburg and Heinrich Wie- ever, if he worked with the juice of the sessions and there met a com- land had begun to explore the patriot, Fritz Verzar, who was then mechanism of respiration in the

Hospital Practice May 1982 181 a peroxidase-rich plant—such as Actually, a small journal did ac- sounded at the door of his study, the orange or the cabbage—there cept the potato paper for publica- Sir Frederick would slip quietly out was a delay before the mixture tion, but this was minor consola- the back way. Whenever it became turned blue. That pause, of no tion to Szent-Gyorgyi, who once urgent to confer with him, Szent- more than a second or two, held a again was sliding into despair. Gyorgyi would knock at the door possibly pregnant mystery of the There seemed no way to do re- and then race wildly down the cor- sort that has always attracted search work and maintain his fam- ridor to catch Sir Frederick as he Szent-Gyorgyi. ily in a European city. Sadly, his emerged from his escape hatch. There must be an agent in the wife left for her mother's home in Nevertheless, in ways that to this plant, he reasoned, that inhibits Hungary, taking their daughter day Szent-Gyorgyi calls mysterious, oxidation of the benzidine. The with her. Sir Frederick exerted a powerful in- agent may be present in such mi- Albert prepared for a final fling fluence over all those who worked nute quantities that its supply is before the shattering of his young under him, endowing the daily rou- quickly exhausted, he reasoned, af- career in science. The International tines of research with the glow of ter which the oxidation proceeds. Physiological Congress was sched- "an intuitive artistic vocation." Further work suggested that the uled to meet in Stockholm in 1926. In his Cambridge laboratory, adrenal cortex might be a more It would serve, he thought in a Szent-Gyorgyi concentrated on abundant source. (That theory was mood of romantic gloom, as the oranges, lemons, cabbages, and ad- among those that Szent-Gyorgyi setting for his farewell to science. renal glands, seeking to isolate the abandoned without a struggle when "Actually," he confesses, "I only ingredient he had noted in Gro- it was shown that the material was wanted a good time." ningen for its ability to momentari- not made but only stored in the ad- He listened with only casual in- ly inhibit oxidation. When he finally renal cortex.) terest to the presidential address of crystallized the substance, he iden- Engrossed in an original project Sir Frederick Gowland Hopkins, un- tified it by the formula CHH8OB, but he for the first time in his career, til, to his astonishment, he heard could not describe it further. In an Szent-Gyorgyi worked at it relent- this reigning celebrity of physiology article prepared for the Bio- lessly, pausing only when Dr. Ham- refer no fewer than three times to a chemical Journal, he candidly ad- burger had another dog waiting for most interesting paper on the pota- mitted, even proclaimed, his igno- a fistula. He was convinced that he to by Dr. Szent-Gyorgyi. No one else rance by referring to the substance was on the verge of an important received anything like such atten- as "Ignose." When the editor found insight into the respiratory pro- tion from Sir Frederick. Elated and this a trifle flippant, Szent-Gyorgyi cess. It was not a matter of simple bewildered, like a man snatched suggested an alternative: "God- metabolism, it seemed to him, but from the gallows and knighted on nose." The editor insisted on a dig- rather of a catalytic action. He had the spot, Szent-Gyorgyi introduced nified scientific name for the sub- only the barest suspicion then that himself to the speaker, who took an stance, and reluctantly Szent-Gyor- this might one day be regarded as immediate fancy to him. It was gyi agreed to call it "hexuronic a momentous discovery and that suggested that he come to Cam- acid." It was an absurd misnomer, the elusive substance he had de- bridge, where Sir Frederick headed he points out. since it is not a tected in orange and cabbage juice the department of physiology. uronic acid at all. Although Cam might affect the nutritional habits When Szent-Gyorgyi explained bridge University gave him a Ph.D. of the world and make possible his state of bankruptcy. Sir Freder- for the discovery, Szent-Gyorgyi therapies then unimagined. ick reassured him, "Never mind, I then only dimly saw its potential The work came to an abrupt halt will see to it that you get a Rocke- importance. when Dr. Hamburger died. His suc- feller fellowship." So he did, and He was stymied in his work be- cessor was a young man who was Szent-Gyorgyi summoned his fami- cause of the enormous difficulty in interested only in animal psychol- ly to follow him to Cambridge. To gathering enough hexuronic acid ogy, a field that required no fistulas him, Cambridge was then, and re- to analyze, much less to "play with," and no assistant with sufficient mains now, a temple of pure sci- in the laboratory. He could put to surgical talent to install them. ence. With due respect to other in- gether from the plants available at When Szent-Gyorgyi sought per- stitutions that have claimed him, Cambridge no more than a few mil- mission to publish a paper he had he declares, "Cambridge is my sci- ligrams of the stuff at any one time. prepared on the respiration mech- entific homeland." Adrenal glands yielded more, but it anism in the potato, his new boss Once ensconced at Cambridge, would take massive numbers of suggested that he might toss it Szent-Gyorgyi saw very little of his them to obtain even a working into the wastebasket at once, or try sponsor. Sir Frederick rarely spoke modicum of the substance. Danish to have it published if he cared to in public, and Szent-Gyorgyi can- colleagues tried shipping adrenals make the effort, but that in any not remember ever having a private to supplement the British supply, case it was totally irrelevant to the discussion with him on a scientific but the glands did not travel well laboratory's major concern: canine matter. Actually, it was difficult to even by air and proved unusable on psychology. talk with him at all. If a knock arrival.

182 Hospital Practice May 1982 At that point, another chance dapest was within range of the dis- was a trifle disappointed because encounter pointed Szent-Gyorgyi comforting noises emanating from vitamins seemed to him to be "the- westward: Edward Calvin Kendall, German beer halls. Hungary was oretically uninteresting" and taint- an American a few years older than then a kingdom without a king. ed by the sensationalism of Sunday Szent-Gyorgyi, who would one day Admiral Nicholas Horthy, as regent, supplements. Nevertheless, he ac- be honored in Stockholm for the ruled in the deepening shadow of cepted the verdict. He and Svirbely isolation of cortisone and was al- Hitler. Although hitherto removed tested the antiscorbutic effective- ready preoccupied with the prod- from political battles, Szent-Gyor- ness of hexuronic acid and found ucts of the adrenal glands. Szent- gyi was so outspokenly antifascist that one milligram of the substance Gyorgyi's search for an adrenal that the conservative University of administered daily was enough to source of hexuronic acid brought Budapest held him at arm's length. protect a guinea pig against scurvy him into a territory they had in The , however, for 56 days. common. The American invited his offered him the chair of medical Szent-Gyorgyi communicated the Hungarian colleague to take a leave chemistry. Although a few noisy news to Haworth in Birmingham, of absence from Cambridge and fascists threatened to disrupt his and the two of them rechristened spend a year at the Mayo Clinic, lectures, Szent-Gyorgyi assembled the substance "ascorbic acid." where Kendall was then director of an enthusiastic corps of students Szent-Gyorgyi did not leap into the division of . whom he could take along on his print with the results but pains- Szent-Gyorgyi had been to the explorations into the mysteries of takingly set about reworking the United States once before, briefly oxidation. experiments. By the time he was but memorably, when he attended He was struck by a pigment he ready to write his report, the supply an international congress in Bos- encountered in his meticulous ton. He now recalls nothing of that study of cellular life. He named it meeting except the lobster that he "cytoflave" for its "splendid yellow tasted on a picnic at Woods Hole. luminescence." Without a spectro- He insists that the haunting flavor scope, Szent-Gyorgyi could not de- of that lobster remained with him scribe it in detail, but it was to through all the years of war and prove important in the scheme of poverty and that it eventually served cell restoration taking shape in his to bring him back to the Massa- mind. Later that brilliant yellow chusetts shore. protein, studied also by Warburg, He found Minnesota "not espe- came to be called vitamin B2. cially interesting but the people very The lack of a spectroscope was nice." His scientific needs were sat- only one of the frustrations of work isfied, not at the Mayo Clinic, but at in Szeged. Szent-Gyorgyi still re- the stockyards at nearby St. Paul, calls the maddening frustrations where adrenal glands were to be he experienced when, seeking to had by the carload. At the end of the analyze a particular hydrolysate, he year, Szent-Gyorgyi returned to found that the bottle of platinic Cambridge with 25 grams of his chloride needed to precipitate the mysterious hexuronic acid pains- substance was empty. Not a drop takingly gathered from tons of ad- was to be had in all Hungary, and renal cortical tissue. He gave most the hydrolysate withered away. of it to Sir Norman Haworth, the re- Szent-Gyorgyi was delightfully nowned investigator of carbohy- surprised one day when an amiable drates at Birmingham University. Hungarian-American chemist There was little that could entice turned up in the laboratory eager Szent-Gyorgyi to leave Cambridge to work. It happened that the new- for good, but it was impossible to comer, named Svirbely, had had withstand a patriotic appeal from considerable experience with vita- the Hungarian Minister of Educa- min C. It was his opinion that tion to help restore the scientific there was very little connection be- community of his native land. tween vitamin C and hexuronic Szent-Gyorgyi's prestige had soared acid. Szent-Gyorgyi, who had long with the discovery of hexuronic held a hunch that the two were acid, making him too significant to identical, turned over his last bit of Sir Frederick Gowland Hopkins recog- the acid to Svirbely for testing. nized the potential of Szent-Gyorgyi's be left in exile. first paper, in an obscure journal, and The year was 1930. Viewed from It became clear in less than a obtained a fellowship for him at Cam- cloistered Cambridge, the rise of month that hexuronic acid very bridge, where he did his early work on Hitler was a distant event, but Bu- likely was vitamin C. Szent-Gyorgyi vitamin C.

Hospital Practice May 1982 183 out to investigators around the consumed by combustion, were not world who might analyze it down ordinary nutrient substances, but to its essentials and reconstitute it were, on the contrary, themselves in pure form for clinical use. active groups of catalysts that The little laboratory at Szeged served to maintain the combustion was now working with the intensi- without themselves suffering any ty and passion of Szent-Gyorgyi's diminution thereby." imagination. Reasoning from the The prize money of $8,000—then demonstrated effectiveness of as- a very large sum—was a "hot pota- corbic acid against scurvy, asso- to" to the impecunious Szent-Gyor- ciated with subcutaneous bleeding gyi. With war apparently inevitable, from fragile capillaries, he decided the new laureate told a broker in to use it on a colleague who was London to find an investment that suffering from Henoch's purpura. would go up in peace and down in The ascorbic acid derived from war. In that way, he told the mysti- raw paprika greatly relieved the fied broker, his opposition to war stricken man. Later, however, when could be unalloyed without any Szent-Gyorgyi tried the purified subversive subconscious hope of crystalline ascorbic acid, he found it profit from the coming slaughter. useless. There was, then, still an- The broker complied, and accord- other therapeutic ingredient in that ingly, within a few years the Nobel sweet Hungarian red pepper. prize money was wiped out. Reflect- The active ingredient against pur- ing on that transaction, Szent-Gyor- pura turned out to be a flavone. gyi now says, "I lost my money, but Szent-Gyorgyi called it vitamin P, I saved my soul." For this anti- Edward Calvin Kendall invited Szent- not for the purpura it helped to Faustian, it was a fair bargain. Gyorgyi to spend a year at the Mayo cure nor for the paprika that was The war did not at once shut Clinic. Nearby stockyards proinded tons its source, but for a more whimsi- down the laboratory at Szeged. The of adrenal cortical tissue, which yielded cal reason. The next unclaimed let- aura of the Nobel prize may have 25 grants of hexuronic add. ter in the alphabetic progression of shielded it from the mounting vitamins was G, but Szent-Gyorgyi power of the local Nazis. Szent- of the substance, which had been was unsure about the qualifica- Gyorgyi was immersed in the chem- replenished, was again exhausted. tions of his substance as a vitamin. istry of muscle contraction, which, The amounts needed for analysis- If it had to be ousted from that he considered, might "lead him much less for clinical use—seemed order, he reasoned, it would leave closer to an understanding of life." hopelessly beyond reach. an unfortunate alphabetic gap. By With him in the laboratory, in ad- One evening, as he recalls, his naming it P, he thought to buy dition to Bruno Staub, was Ilona wife served a side dish of that mild, time, allowing the credentials of Banga, a colleague who, he em- slightly sweet red pepper of Hun- the substance to be validated or re- phasizes, never received adequate gary called paprika. In no mood for jected before a vitamin O appeared. credit for the discoveries that flowed paprika that evening, Szent-Gyor- However quiet may have been from her work. gyi sought a diplomatic way to Szent-Gyorgyi's satisfaction at his Szent-Gyorgyi was puzzled—a avoid the vegetable without offend- discovery of ascorbic acid, excite- state of mind he finds conducive to ing his wife. "I must save this for ment in the rest of the world was creation—by the failure of myosin the laboratory," he told her. "I have less restrained. He was called away to provoke muscle contraction in tried every other plant I know. Why repeatedly to lecture at medical vitro, even though it was known to not paprika?" Once in the labora- meetings throughout the world. be vitally involved in the process in tory, he felt he had to go through And in 1937, a telegram from vivo. He and Ilona Banga noted with the tests. By midnight, he Stockholm summoned him to re- that attached to the rod-shaped found that paprika was "a treasure ceive the Nobel Prize in Physiology particles of myosin was another chest" of ascorbic acid. A gram of and Medicine. protein hitherto undescribed. They paprika yielded at least two milli- In presenting the award. Profes- combined threads of this newly iso grams of the vitamin. sor E. Hammarsten of the Karo- lated protein with the myosin in a By the time the paprika season linska Institute cited not only his soup of muscle tissue. Then, in ended that year, Szent-Gyorgyi had work in isolating ascorbic acid and that soup containing the essential amassed half a kilogram of crystal- doing so much to make it available adenosine triphosphate (ATP), the line ascorbic acid, and in the fol- clinically but his pioneering explo- experimenters saw the signs of mo- lowing year, he produced three kilo- rations of cellular respiration. He tion. It was a clear contraction of grams. As quickly as the substance had proved. Professor Hammarsten the muscle, down to a tenth of its could be prepared, he shipped it said, "that the plant acids were not length, produced for the first time

184 Hospital Practice May 1982 outside the body. For Szent-Gyor- Istanbul, whereby Szent-Gyorgyi would assign to the job. The Brit- gyi, that astonishing moment re- would test the waters in that city of ish would then be able to explore mains one of the most thrilling of spies and counterspies for a Hun- matters with Teleki while secretly his life. He called his new protein garian switch of alliances. obtaining verification and advice "actin"; however, the conclusive Szent-Gyorgyi went armed with from Szent-Gyorgyi and others in work on the combination of merged the name of a friendly antifascist the underground. Unfortunately, by proteins, "actomyosin," would have journalist who was to pass him on the time he made his way back to to wait for a quieter time and place. to British diplomats. These, in turn, Budapest, his secret had been The strains of war were begin- sent him to British agents. The leaked. First, he was placed under ning to show at the laboratory and rest is melodrama, which Szent- house arrest, but when the Ger- at home. They may have been in- Gyorgyi relates with boyish relish. mans occupied Hungary, Szent- strumental in the breakup of the He was directed to arrive at a cer- Gyorgyi was tipped off, so that he Szent-Gyorgyi marriage. By 1941, tain corner in Istanbul precisely at could go into hiding. As he recalls r howeve , Albert had recovered from six in the evening. A black car those days, his face takes on a look that trauma sufficiently to woo and would be waiting. Unhesitatingly, of pride mingled with a sense of marry a young scientist, Marta Bor- without a word, he was to climb mischief. He glows when he cites biro, who had worked with him in into the backseat. reports that Hitler, in a frenzy over the laboratory. They were shortly to He followed his instructions to the effort at Istanbul, shrieked at work together in the war. the letter and was driven far out of his Hungarian Gauleiter to "deliver A delegation from the under- town to a country house, where two Szent-Gyorgyi." ground came to fetch Szent-Gyor- cheery British agents exclaimed, For years after that, he led the gyi, for he was known not only as a "How wonderful you've come!" life of one on the run, slipping from scientist but as a man with influ- Count Teleki had been in touch one hiding spot to another. His ential family connections. Hungary with them, and they were trying to face was too well known to risk had been digesting bits of Slovakia, resolve their doubts concerning appearing in the shelter during air Transylvania, and the Carpathian him. That very day London had raids. He stayed in his room, pre- Ukraine as crumbs from Hitler's sent a message suggesting that tending to be a dying old man. His table, but the alliance was nonethe- they contact Szent-Gyorgyi. Before wife, acting the part of nurse, as- less uneasy. Even high Hungarian they could act, he had arrived. sured nosy neighbors and air raid officials privately and discreetly The British worked out a scheme, wardens that he could not be chafed at the increasingly odious according to which Szent-Gyorgyi moved. connection. Count Teleki, the Pre- was to set up a wireless station When German agents seemed to mier, had been uncomfortable from with the help of an engineer they (continued on page 188) the start. On the very day he signed his country over to the Axis, he sent telegrams to Berlin and Rome stip- ulating, as if on second thought, that "on moral grounds" Hungary could not join any military action against Poland. Hitler was so in- furiated that the Hungarian ambas- sador begged him to forget that the Premier's message had ever been sent. Utilizing his family background, Szent-Gyorgyi cautiously ap- proached the Count to see whether he might be interested in negotiat- ing a way out of the Axis. He was enormously relieved when the Pre- mier did not throw him into jail but, on the contrary, expressed a willingness to talk. Count Teleki had publicly thundered against Jews, but if he behaved any less maniacally, he now pleaded, the Nazis would come in and swiftly wipe out the entire Hungarian-Jew- ish community. In the end, he gave his blessing to a secret mission to As Szent-Gyorgyi approaches his eighty-ninth birthday, he works in the laboratory five days a week, searching for submolecnlar clues to cancer.

Hospital Practice May 1982 185 SZENT-GYORGYI (from page 185) be closing in at last, the Szent- Gyorgyis fled to the Swedish Em- bassy. A royal proclamation in Stockholm granted Swedish citizen- ship to the two of them, but no one expected that such legal niceties would deter the Gestapo. Before plunging from Szeged into the resistance, Szent-Gyorgyi had taken one precaution, but now that act of foresight was proving disas- trous. He had sent a record of his work on muscle contraction to his Swedish friend and colleague Hugo Theorell for publication in a Scan- dinavian journal. Still attentive to courtesies that had been obviated by war. Theorell felt he had to acknowledge receipt of the article. Having no other ad- dress, he sent a letter to Szent- Gyorgyi in care of the Swedish Embassy in Budapest. The Gestapo arrived not far behind the letter and began to seal off the embassy from the adjoining houses. Word came from friendly contacts in high places that the Germans were about to break in. It was then that the acting head of the embassy. Per Anger, smuggled the Szent-Gyor- gyis out in the trunk of his car. Marta went to her parents' house, and Albert went on the run, edging as close as possible to the advanc- ing Russian lines. When Soviet troops reached Szent-Gyorgyi's street, he came out and followed them until they liber- ated the area in which his wife and her family lived. Their reunion was interrupted by a Russian officer with a direct order from Molotov to take Szent-Gyorgyi to safety. Marta insisted that she could not leave without her parents, and her par- ents could not leave without at least 13 other relatives. Most of the family were settled in southern Hungary, already out of hostilities, but the Szent-Gyorgyis were escorted, first, to Soviet headquarters in Budapest and, then, to a posh suite in a Mos- cow hotel. They had caviar at lunch and dinner, he recalled, as well as lavish tours through sunny Armenia. Szent-Gyorgyi had shared the

188 mingled hopes and fears that the nomic shortages and political pres- Soviet Union inspired among intel- sures. Szent-Gyorgyi thought the lectuals in the 1930s, although he United States—rich, democratic, had indignantly sent the Finns his and scarcely touched by the war Nobel gold medal as a gesture of that left Europe ravaged—might support when their country was offer him a bench in a laboratory. invaded. Despite growing disen- He went to Paris to apply for a visa, chantment concerning the Soviet but the United States was then in Union, he thought that some of the the grip of acute Russophobia. The evils, at least, could be ascribed to evidence of Soviet favors granted to the "excesses of subordinates." He Szent-Gyorgyi was enough to damn thought, therefore, that it might be him despite his war record. His useful to inform Stalin directly of visa was therefore denied. In 1947, the sometimes outrageous behav- however, following intervention by ior of his troops in Hungary. U.S. scientists, the authorities He was asked to meet first with a granted him the right to enter. man named Decanozov, who, Szent- In New York, immigration offi- Gyorgyi notes—with the barest cials asked only the routine ques- trace of a grin—was subsequently tions. "Do you read and write?" one sentenced to be shot. When he de- asked. "I don't read much," said scribed the cruel treatment meted Szent-Gyorgyi, "but I write a lot." out to Hungarians, even to those who had thrown down their arms Once in the United States, he rather than fight for Hitler, Decan- was at a loss for a place to settle. ozov exploded. He was not shocked Out of his memory there rose the by the revelations and did not deny flavor of a lobster, boiled over a the reports, but he shouted that beach fire, which he had enjoyed Hungarians had committed atroci- some 20 years earlier. In that fra- ties as bad or worse on the eastern grant recollection it seemed there front. It was plain that Szent- had also been a laboratory nearby Gyorgyi could convey no news to where a scientist could rent a table the Kremlin. and equipment. And so they came Without seeing Stalin, he went to Woods Hole. back to Hungary to help in the re-, The years at Woods Hole have not construction of the shattered sci- always been gentle. True, he could entific community. Organizing an take off from the beach at his door- "Academy of Science" meant not step and swim far out to sea where only assembling scientists and men half his age would hesitate to equipment but finding a way to feed go. He could fish and water-ski and them. It was not a matter of money play tennis and chess. He also has but of potatoes. While Albert pre- found disciples and colleagues who sided over a laboratory, Marta or- admire him unreservedly. ganized a kitchen to feed the staff. Szent-Gyorgyi, however, has never Despite the off-putting conversa- been able to work away from the tion with Decanozov, the Russians searing political heat of his times, cooperated handsomely with Szent- and he has never been discreet Gyorgyi. Marshal Voroshilov re- about his convictions. He has cam- sponded to every appeal for trans- paigned against war wherever it port, then at a premium in Bu- has been waged. In a book entitled dapest. The academy put the The Crazy Ape written for young Soviet-supplied trucks to double people in the 1960s, he thundered: duty, taking war-weary Budapest neighbors out for a holiday in the Armies are a curse of man- countryside, charging them for the kind, a threat to peace, a threat to ride,* and using the money to bring our very existence, a blot on the back fresh food to the laboratory. face of human culture and intelli- Still, although the Szent-Gyorgyis gence. The greater the army, the enjoyed a somewhat privileged po- greater threat to peace it is__ sition, all hope of major scientific Who will defend us against the work seemed frustrated by eco- defense departments?

189 In a letter to the Bulletin of the had any talent in writing grant ap- that myosin was an enzyme with Atomic Scientists, he offered an plications. "They want to know just ATPase activity. And previously, he ironic disarmament proposal. Mind- what I am going to do," he points had markedly facilitated the study ful of the economic dislocations out. "If I knew that, there would be of ATP and its effect by utilizing ex- inherent in disarmament, he sug- no point in my doing it." Grants tracts of the contractile proteins gested that military budgets be vot- are not readily given to people who made by glycerol extraction. His ed as usual, that firms be given con- anticipate only the unexpected. "glycerinated fiber bundle" has be- tracts and subcontracts, and that Szent-Gyorgyi also fails to impress come a versatile laboratory concept. thousands of workers be hired—all most givers of grants because he The death of Marta, who had provided that they produce abso- asks for so little. Once, when things been a colleague as well as a com- lutely nothing. At no greater ex- were going well, he accumulated a panion, left him bereft and lonely, pense than usual, the nation would staff of 12 people. "It was the least but that is a condition that has go through the motions of arms creative period of my entire life," he never endured for very long in production, but no weapons would recalls. "I spent all my time looking Szent-Gyorgyi's life. There followed roll off the assernuiy lines. Industry after my staff and correcting their a whirlwind courtship of another then could slowly adapt to produc- mistakes." He does not want to di- woman, a third marriage, and a di- tive peacetime activity, and the war rect experiments; he wants to ex- vorce after a few months. "It was an budget, which would have harmed periment—with his hands and eyes experiment that failed," he says, no one because its stockpiles would as well as his brain. "—a catastrophe." have been fictitious, would wither The 1960s brought him the joy of By the mid-1970s, he was "at the away in the reality of peace. refining his work on the nature of end of his tether," as he recalls. His Such antiestablishment fantasies muscle contraction to an elegant grant applications had fallen may have stood in the way of ob- point. He not only demonstrated through. When he was hospitalized taining grants, but Szent-Gyorgyi the presence of actin but was one briefly, his wry humor showed admits that, in any case, he never of those who early showed clearly through sad reflections. "Every-

Nohel prize winners in 1937 were Walter N. Haworth of Eng- Chemistry, Clinton J. Davisson, American physicist; Szent- land and Paul Karrer of Switzerland, who shared the Pnze in Gyorgyi; and French author Roger Martin du Card.

Hospital Practice May 1982 191 ture so touched Szent-Gyorgyi that he responded warmly. The exchange of correspondence led the Salis- burys to visit the Szent-Gyorgyis at Woods Hole. The comparatively small sums that he needed and the frigid reception given him by the major organizations funding cancer research moved the Salisburys to embark on a new venture. They formed the National Foundation for Cancer Research, raised the funds he needed, and have gone on to support other scientists as well. Albert Szent-Gyorgyi goes to his laboratory five days a week. Only when the parking is difficult does Marcia drive. During the winter, he has a devoted and highly compe- tent staff of two. They are all he 1 A career that has spanned nearly the entire twentieth century continues. needs. In the summer, scientists For Szent-Gyorg\i, science has always been an art, often based on insight and from many parts of the world come hunches. to Woods Hole to see how best they can collaborate with him. The foun- thing has an end," he told his cousin. Dr. Andrew Szent-Gyorgyi, dation meets all his modest re- head of the department of biochemistry at Brandeis University. quirements. Even in the heyday of Then he added: "Except a sausage, which has two... but I am grant-giving, he never asked for not a sausage." more than $150,000 a year, and In 1975, Albert Szent-Gyorgyi, at the age of 82, took off on a now he gets along on far less. new course of life and work. One of his colleagues and His work shows enough progress enthusiastic admirers. Dr. Benjamin Kaminer, head of the to absorb him for years to come. department of physiology at Boston University, gathered a group His home—in the house he has oc- of distinguished scientists, each with a profound debt to pay to cupied since he came to Woods Albert Szent-Gyorgyi. Among them were Fritz Lipmann, Linus Hole—is as supremely comfortable Pauling, Hans Krebs, Annemarie Weber, Hugh Huxley, and, of as a well-worn slipper There is course, Cousin Andrew Szent-Gyorgyi. nothing luxurious in it except the It was at that glittering symposium at Boston University that sight and sound of the sea. It has Szent-Gyorgyi announced his departure into the submolecular not only a sense of Albert but of aspects of biology. In the uncoupling of electrons and in the Marcia, who delicately and unob- formation of magnetic fields, he said, he hoped to find the trusively creates a life for herself strange anomaly that gives rise to the cancer cell. and the extraordinary man whom .It was also at that meeting that he introduced his colleagues she married. "This is," says Albert to a young artist, Marcia Houston, who, he declared, had Szent-Gyorgyi, "an ideal life for a consented to marry him. His world was indeed beginning again. scientist." His finances, however, were almost as straitened at the Marcia and his home are clearly beginning of his fourth marriage as they had been at his first. major components of that quiet ec- That, too, was about to change. The first sign of the reversal stasy, but for Albert Szent-Gyorgyi, seemed no more momentous than a smile from a stranger. the essential requirement for life is Franklin and Tamara Salisbury of New York had heard of the freedom to follow a trail of Szent-Gyorgyi's plight and had sent off a token of their good clues, hunches, and insights to wishes: a check for $35. The ges- some hitherto unglimpsed vista of reality. He has clearly stated the goal that he still pursues with charac- teristic panache: "To see what ev- eryone has seen and think what no one has thought."

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HOSPITAL PRACTICE®. (USPS 783 280). May 1982. Volume 17. Number 5. I Hospital Practice May 1982

PAST AND PRESENT

179 Albert Szent-Gyorgyi: The Art in Being Wrong

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