In the March 24, 2006, issue of the Journal of Biological Chemistry, one could count 65 articles with 399 authors listed, an average of 6.1 authors per article. Of those authors, 188 (47 percent) had Asian surnames (Indian, Chinese, Japanese), with 83 (21 percent) working in U.S. labs and 105 in labs abroad (26 percent). Now let’s compare those data with the years of the American apogee.
The March 25, 1986, issue of the Journal of Biological Chemistry contained 76 articles with 260 authors listed, a more modest average of 3.4 per article. Of those authors, 44 (16 percent) had Asian surnames, again evenly split between Asians working in U.S. labs and abroad. That’s less than half the number of 2006!
That doubling of Asian contributions to American science between 1986 and 2006 is directly due to liberal visa and immigration policies. A generation before, these had brought Renato Dulbecco to Bloomington to work with Salvador Luria on oncoviruses and led Rita Levi-Montalcini to discover nerve growth factor with Stanley Cohen in St. Louis rather than in Turin.
(There were Nobel prizes for all—and for Rosalyn Yalow.)
ROSALYN YALOW’S EVOCATION of the Lower East Side of New York as “the Melting Pot for Eastern European immigrants” reminds one that entry of Eastern European Jews into Anglo-Saxon lands was as much of a political issue at the dawn of the twentieth century as is Mexican immigration at the dawn of the twenty-first. In Britain, their exclusion was championed by two leaders of the eugenics movement, Francis Galton and his student Karl Pearson.
In 1925, Karl Pearson, together with Margaret Moul, published an extensive two-part analysis of “The Problem of Alien Immigration into Great Britain, Illustrated by an Examination of Russian and Polish Jewish Children.” The paper was the lead article in the Annals of Eugenics published by the Galton Institute (K. Pearson, ed.). By means of a detailed study, carried out before World War I, of over a thousand Jewish schoolchildren recently arrived in England from Eastern Europe, the authors attacked the problem of whether the intelligence of these immigrants differed from that of the native stock.
The study was a model of biometric detail: Pearson remains a scientist of repute, whose contributions to biostatistics have remained practically untarnished. Not only were the children he studied given the most modern tests of intelligence, but also school records were examined, home visits made, and physical examinations performed. Control groups were found: English-born Jews and native Gentiles. Elaborate scoring systems were employed to evaluate such variables as size and income of family, rent paid, foci of infection, crowding, ventilation, mouth-breathing versus nose-breathing, “cleanliness,” and so on.
The authors directed their inquiry to an applied end, in keeping with the overall aims of the eugenics movement:
We hold therefore that the problem of the admission of an alien Jewish population into Great Britain turns essentially on the answer that may be given to the question: Is their average intelligence so markedly superior to that of the native Gentile, that it compensates for their physique and habits certainly not being above (probably a good deal below) the average of those characters here?
Pearson and Moul found that, for all groups examined, there was no correlation between intelligence and any other variable such as cleanliness, mode of breathing, family size or income, foci of infection, and height-for-age. Consequently, they were led to this rather somber conclusion:
. . . the argument of the present paper is that into a crowded country only the superior stocks should be allowed entrance, not the inferior stocks, in the hope—unjustified by any statistical inquiry—that they will rise to the average native level by living in a new atmosphere. The native level is not a product of the atmosphere, but of centuries of racial history, selection, hybridisation and extermination.
Extermination? Be that as it may, the authors failed to note a curious anomaly among their data. All variables considered, there was a striking difference in “intelligence” between Jewish girls and Jewish boys, the latter being statistically more intelligent:
Namely, that with the Gentile children we have found only a slight difference between the boys and girls. Hence the intelligence of the Jewish girls being much below that of the Jewish boys, even if the latter equaled that of the Gentile boys, the Jewish girls would fall very seriously behind the Gentile girls.
One must point out the genetic fallacy here. If conclusions from such data were possible, we could with some degree of confidence say that in Eastern Jews, by some unusual genetic aberration, intelligence was sex linked, whereas in Gentiles this higher faculty was not.
In the event, arguments such as these directed the bulk of immigrants from Eastern Europe to the Lower East Side of New York rather than to Cheapside in London. We therefore have Karl Pearson and his fellow eugenicists to thank for their indirect gift to American science: permitting Rosalyn Yalow with Solomon Berson to develop radioimmunoassay at a Veterans Administration Hospital in the Bronx.
23.
Cortisone and the Burning Cross
RHEUMATOLOGY, THE TREATMENT OF BONES AND JOINTS and widespread miseries, came late to the game of medical science. For many years my medical specialty was a descriptive art; we had no idea, in any meaningful way, of what was going on. The heart doctors had their cardiograms and digitalis, the endocrine people had their thyroid tests and extracts, but joint doctors seemed condemned to stand idly by and watch their patients turn into cripples after one or another stopgap treatment. Oh yes, we had diathermy, gold salts, paraffin injections, and, believe it or not, bee venom. We knew how to treat gout with colchicine and learned to give penicillin to prevent rheumatic fever, but by and large our treatment of joint disease, or serious threats like systemic lupus erythematosus (SLE), was limited to aspirin, aspirin, and more aspirin. All that changed in 1948, the annus mirabilis of our field. That’s the year that cortisone was first given to a patient with arthritis. It’s also a year when bigots were burning the houses of black people in white suburbia and lighting crosses on their lawns.
At a staff meeting at the Mayo Clinic in January 1948, Malcolm M. Hargraves described a strange kind of cell that formed in blood samples of patients with SLE. The disease, which tends to afflict young women, attacks joints, skin, kidney, heart, and brain. Before 1950, we couldn’t really tell who had SLE and who didn’t; we had no clue as to why it was so often fatal. Hargraves had discovered what he called the LE cell, which finally permitted us not only to make a diagnosis of the disease, but also told us what was going wrong with these women. The LE cell, it turned out over the years, is a white blood cell (a neutrophil) that has ingested the dying nucleus of another cell against which lupus patients make antibodies. It also turned out that those antibodies against the nucleus and/or its constituents—the anti-DNA antibodies—were just the tip of an iceberg. SLE patients make a dazzling number of antibodies against bits and pieces of their own cells. Their immune system recognizes such bits of “self” as if they were microbes, tads of “nonself” that want expunging. Hargrave’s discovery of the LE cell sparked the study of autoimmunity and lifted rheumatology over the threshold of science.
In the same month, immunologist Harry Rose and rheumatologist Charles Ragan of Columbia described a factor in the serum of most patients with rheumatoid arthritis (RA) that clumped sheep red blood cells coated with human antibodies, the basis of the “sensitized sheep cell agglutination test.” Tests for this factor not only permitted accurate diagnosis of rheumatoid arthritis, but also taught us how joints are attacked in RA. What came to be called “rheumatoid factor” turned out to be yet another autoantibody, of great size and with a tendency to form sludge in the blood. Normal human antibodies, the “self” in this case, were recognized as “nonself” by rheumatoid factor. The agglutination reaction in a test tube was a pretty good reflection of what happens in life. In patients with RA, blobs of antibodies containing rheumatoid factor form in the blood like îles flottantes; they become trapped in joint spaces, and joint cells try to get rid of the unwanted deb
ris, cry havoc, and let loose the dogs of inflammation. As with Hargraves and the LE cell, the discovery of rheumatoid factor made it possible to make sense of yet one more of our diseases.
On April 20, 1949, William A. Laurence of the New York Times broke news of another discovery announced at a staff meeting at the Mayo Clinic:
Preliminary tests during the last seven months at the Mayo Clinic with a hormone from the skin of the adrenal glands has opened up an entirely new approach to the treatment of rheumatoid arthritis, the most painful form of arthritis, that cripples millions, it was revealed here tonight.
That evening, Philip Hench, Charles Slocumb, and Howard Polley reported their experience with fourteen cases of rheumatoid arthritis treated with a precious material called “Kendall’s compound E” or 17-hydroxy-11-dehydrocorticosterone. Cortisone had entered the clinic.
Within a week, cinemas nationwide showed newsreels of cripples rising miraculously from their wheelchairs. By May 1949, Hench and coworkers reported the “complete remission of acute signs and symptoms of rheumatoid inflammation” at the Association of American Physicians in Atlantic City. In June they added success with rheumatic fever to the cortisone legend at the Seventh International Congress of Rheumatic Diseases in New York. It was the summer I decided to follow my father into rheumatology and, in retrospect, I’d guess that it was cortisone that convinced me. I will never forget the waves of applause after Hench’s dramatic film clips were shown to a packed crowd at the Waldorf-Astoria. Now we could actually do something about a crippling disease like rheumatoid arthritis.
In October 1950, the Nobel committee announced that Philip Hench and the two biochemists who had painstakingly isolated and described the chemistry of adrenal steroids, Thaddeus Reichstein (University of Basel) and Edward Kendall (Mayo Clinic), would receive the Nobel Prize in Physiology or Medicine for “their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects.” Hench remains the only rheumatologist among Nobel laureates. So universal was the acclaim for cortisone that the Swedish announcement of the 1950 Nobel Prize in Literature, to William Faulkner, was almost a footnote in the world press.
There were other footnotes in the fall of 1950. On Thanksgiving eve, November 22, there was a hate crime in the exclusive Oak Park suburb of Chicago: “Arson Fails at Home of a Negro Scientist” headlined the New York Times. It was one of a string of cross-burnings and arson attempts in the white suburbs of Chicago. The scientist in question was Percy Lavon Julian (1899–1975), the first African-American to buy a home in Oak Park. Julian was described in the story as “director of research in the soya products division of the Glidden Company . . . widely acclaimed for his discovery of life stimulating chemicals [and] drugs for treatment of diseases.” More to the point, in November 1950 Julian was working feverishly on the practical synthesis of cortisone using Reichstein’s compound S, work that resulted in U.S. patent #2,752,339, “Preparation of Cortisone.”
On December 11, 1950, less than a month after Julian’s house was torched in Oak Park, Hench addressed the Nobel audience at the Karolinska Institutet. He rehearsed the long trail of his discovery: how in the twenties he had first noted relief of rheumatoid arthritis in a male physician who had developed jaundice; how in the thirties he had noted that pregnancy relieved the disease in female patients; how in the forties he had discussed with Kendall the possibility that substance X in the blood of jaundiced or pregnant patients might be his compound E; finally, how in September 1948 he had written to Merck for small amounts of the laboriously synthesized material to test in the clinic. His letter noted that jaundice or pregnancy brought almost immediate relief; he promised Merck that “if any adrenal compound is of real significance in rheumatoid arthritis we would expect to see some results within a very few days.” Three days to be exact. Beginning at 100 mg/day, given intramuscularly, the Mayo doctors obtained dramatic results; they soon lowered the dose to a maintenance dose of 25 mg of “cortisone,” Hench and Kendall’s new name for compound E. That’s equivalent to 25 mg tapering to 5 mg of prednisone, and nowadays those results are duplicated daily the world over.
In his Nobel speech, Hench reminded his audience how difficult it was to manufacture practical amounts of cortisone. Merck had got into the steroid business during World War II when the National Research Council subsidized a crash program for synthesis of adrenal steroids. Washington had learned that Luftwaffe doctors were experimenting with injections of adrenal extracts to keep their aviators stress-resistant at 40,000 feet, and several of Kendall’s compounds (E and F especially) seemed likely candidates. Merck’s Lewis Sarret came up with a complex and difficult synthesis of E from bile: by 1944 it had produced 15 mg from the bile of 2,500 cows! Hench averred that “although none of the thirty-six steps required to convert desoxycholic acid into cortisone has been by-passed, some of the steps have been made less costly, less time consuming, and productive of greater yields.” Hench’s fellow laureate, Thaddeus Reichstein, told his Stockholm audience, “For practical purposes [the Sarrett] method is much too laborious. In the last two years, again particularly in the U.S.A., at the cost of a considerable amount of time, much better methods have been discovered [among them by] Julian and his collaborators. . . . For after the clinical results of Hench, Kendall and their colleagues it can hardly be doubted that the future demand for these substances will be very great.”
“Future demand” was met as the cost of production of cortisone fell from $1000/gm in 1948 to $150 in 1950 to less than $7 in 2000. We owe this boon to the synthesis of cortisone from vegetal sources by Percy Lavon Julian, that brilliant “Negro scientist” whose house in Oak Park was torched on Thanksgiving eve of 1950.
Percy Lavon Julian of Montgomery, Alabama, was the grandson of a former slave and son of a postal employee. He worked his way through DePauw University waiting on tables and graduated as class valedictorian with a Phi Beta Kappa key. After DePauw, he served teaching stints at several black colleges and finally received a fellowship to Harvard, where he earned an MA in chemistry. Since Harvard in the 1920s had no place for a black scientist, Julian applied—successfully—for a Rockefeller Foundation fellowship at the University of Vienna to work with the eminent chemist Ernest Späth. He received his PhD in 1931, having dazzled the Viennese with his skills at tennis and piano, fallen in love with opera, and acquired a long-term collaborator, Josef Pikl.
Julian and Pikl returned to DePauw, taught chemistry, and within four years came up with the total synthesis of physostigmine from the calamar bean (Physostigma venenosum). Physostigmine was for many years the only weapon doctors had to fight glaucoma. The bean also contained stigmasterol, an intermediate in sex steroid synthesis, and Julian sought a more abundant source of plant sterols. He wrote to the Glidden Company, a natural-product giant, requesting gallons of soybean oil. This contact led to a job interview at Glidden’s labs in Appleton, Wisconsin. But Appleton had a hoary statute on its books dictating that “No Negro should be bedded or boarded in Appleton overnight.” Chance favored the prepared chemist, and Julian was offered a far better job in Chicago as director of research of the Soya Products Division of Glidden. The rest is chemical history. In more than eighteen years at Glidden, Julian developed lecithin granules, Glidden’s soya oil, and Durkee’s edible emulsifiers, and—not incidentally—worked out the commercial syntheses of testosterone and progesterone from soybean oil. He used soy proteins to coat and size paper, to make cold-water paints practical, and to size textiles. During World War II Julian invented AeroFoam, a soy protein product that quenches gasoline and oil fires; the foam saved lives from Europe to the Pacific. Julian was granted more than 100 chemical patents, and Big Pharma still prepares hydrocortisone from compound S by Julian’s method. In 1953, he founded his own company, Julian Laboratories, Inc., with labs in the United States and Mexico. In 1961, the company was sold to Smith Kline & French for $2.3 million, “a staggering amount for a Black man at that time.”
I
n his lifetime, Julian was honored by membership in the National Academy of Sciences, a U.S. Postal Service stamp, a dozen honorary degrees, directorships galore, and three public schools that bear his name. We also remember that this agile chemist made it possible to make cortisone from beans instead of bile so doctors could give it to patients for a pittance.
Ave Atque Vale
24.
Lewis Thomas and the Two Cultures
Bien écrire, c’est tout à la fois bien penser, bien sentir et bien rendre; c’est avoir en même temps de l’esprit, de l’âme et du goût. Le style suppose la réunion et l’exercice de toutes les facultés intellectuelles.
[To write well is at once to think, feel and express oneself well; simultaneously to possess wit, soul and taste. Style comes from the integration and exercise of all the intellectual faculties.]
—Comte de Buffon
I REMEMBER THE MOMENT THAT LEWIS THOMAS asked me to be his first chief resident in the old redbrick tenement of Bellevue Hospital. He had a reputation of charming young doctors into academic medicine under conditions and for wages that few dockworkers would tolerate. At the time I was still deciding on whether to follow my father into practice or move on to an academic career. Thomas told me that his chief resident wouldn’t have an office, but a lab. He’d be off every third night, and the job would be the first step on the academic ladder. Then Thomas told me what academic salaries were like in the late 1950s, and my rude, younger self quoted: “What is science but the absence of prejudice backed by the presence of money?”
The Fevers of Reason Page 19