Rockefeller Institute Research Articles

Life With George

“It's a nuisance walking down the hall. If you stop to say ‘Hello!’ to everyone you know, it takes you five minutes to get to the Lab!” Five minutes wasted was something to be avoided, I soon learned, and this suited me fine. I had just arrived in New Orleans, eager to take my place on John Musser's staff in the Department of Medicine at the Tulane School of Medicine. This particular morning, I had met the members in the department and was impressed especially with an earnest looking young man who had just returned from two years of research at the Rockefeller Institute in New York. He was anxious to get to his planned projects in his new lab in New Orleans and I was on my way with him to begin. It was the beginning of a 25-year strong friendship with George Burch.

The "Undiscovered" discovery.

This article chronicles the work of Thomas J. Francis, Jr. on bacterial transformation at the Rockefeller Institute beginning in the late 1920s, and the ways in which Francis influenced Avery's research.

Peyton Rous: in memoriam. 1879-1970.

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 13 · Number 4 · Summer igyo PEYTON ROUS: IN MEMORIAM 1879-1970 CHARLES HUGGINS* An incredible cascade of notable discoveries flowed for sixty years from the laboratory of Peyton Rous at the Rockefeller Institute for Medical Research (Rockefeller University). This astonishing productivity was forged at the laboratory bench by his head and heart and hand. He was a complex man endowed with a felicitous facet of great simplicity enabling him to communicate with Nature. Dr. Rous had an unusual singleness of purpose; nothing could deflect him from his goal. He was highly creative, and his concepts were crystal clear. In the history of science, Dr. Rous will stand in the front rank with the greatest biologists ofthe ages. With Bernard and Pasteur he founded the vast and important field of experimental medicine. The French savants contributed to the new discipline, respectively, physiology and chemistry; Dr. Rous added pathology to these. He was a genius and a genial one. During the six decades 1910-70, the Institute was theheart ofa Periclean creation due to the talented faculty brought together by Simon Flexner. It was the first house established expressly for the work of a scientific elite in America. The creative ferment was stormy. Early among the cohorts were Avery, Landsteiner, Max Bergmann, Jim Murphy, P. A. Levene. Dr. Rous was in the center of the intellectual maelstrom that the young investigators were establishing. He loved the Institute, for it was a good place for gifted experimentalists to work and reflect. His contributions to the Institute and to science were fabulous. Unto him * The Ben May Laboratory for Cancer Research, University ofChicago, Chicago, Illinois 60637. 465 much had been given and ofhim much was required and nobody was disappointed—he returned an overabundance of value. He set standards ofexcellence in life, in work, and he did both supremely well. Doubtless, because of Dr. Rous and his confreres, Family Rockefeller derived satisfaction concerning the worthwhileness of their medical project at the Institute. Dr. Rous found out much which was at variance with all previous experience. He disdained to call his work discovery because this sounded puffed up; his business was "finding out." The pearls ofDr. Rous were always big and lustrous: The first agent to cause cancer; A virus (RSV) which evoked solid tumors of animals, thereby creating the vast field of the cancer viruses; The first blood bank (withJ. W. Turner and O. H. Robertson); Rous-McMaster biliary fistula; Isolation and characterization of R-E cells; Outlying acidosis; Factors which urge on malignancy ofanimal cells. In Dr. Rous's laboratory, J. G. Kidd, one of the disciples, found that normal guinea pig plasma can cure a malignant tumor of a mouse. Many more wonderful things did he come on. Peyton Rous lived in a small world ofhis own comprising his family, a few choice friends, a small band of students. He had an unquenchably happy interest in every aspect of living, which made him such a vital person. The Rous circle was surrounded by a wall which was impenetrable but necessary. Isolation was painful to him, for he was fundamentally gregarious, had great zest for life and people, but he knew that a cloister is prerequisite for high creativity. Admission to the inner circle was attained by aspirants to the badge of excellence. The Rous Virtue rubbed off on the fortunate ones, and there resulted an adornment of character. A junior and well-loved member of the Arbeitskreis puts it: "We had a good time." Peyton Rous possessed the wonderful mystique needed for continuing discoveries. He was born with this rare and awesome talent, and he cultivated it assiduously lifelong. Fortunately he made a great discovery while young; RSV was found out in 1910 when he was age thirty-one. Peyton Rous regarded himself as a naturalist. He was an autodidact because creativity can be demonstrated but not taught. He was a perennial 466 Charles Huggins · Peyton Rous Perspectives in Biology and Medicine · Summer 1970 child ofNature. He grew flowers and learned much about them. He loved his cottage in the country with his garden and a softly flowing river, and the wildlife with the drowsy hum...

Oswald Theodore Avery and DNA.

OSWALD THEODORE AVERY AND DNA ALVIN F. COBURN, M.D* To one who had no scientific association with Avery's work it seems appropriate to place the following information on the record. I am motivated to make this report because repeatedly I note that many persons in high echelons ofscience are unaware that Oswald T. Avery envisaged the implications ofthediscovery ofhis "transforming factor." As early as 1943 Avery did indeed understand the significance ofDNA in microbial genetics , the discovery ofwhich culminated his extraordinarily creative life as a member of the Rockefeller Institute. Avery practiced meticulously the sermon that he often preached to his assistants and to the many younger colleagues who came to him for guidance : "Apply your brakes when tempted to blow your own horn." His rigorous self-discipline, along with constant modesty and a deep humility —in the noblest sense ofthe word—made it impossible for Avery to go far beyond the "facts" in his published work. His high regard for the printed word deterred him from theorizing in print—only the "facts" were admissible—and his own wisdom certainly prevented him from pointing out the great significance ofhis discoveries, perhaps even to the many young men who had the great good fortune to work with "the Fess" (short for professor), as he was called. Prior to 1940 O. T. Avery was only a name—a name which belonged with Theobald Smith, F. Gowland Hopkins, and Marie Curie, persons who had created new disciplines for mankind to explore. Avery had opened the doors to the world of immunochemistry, an achievement vividly brought home by Michael Heidelberger, who occupied the laboratory contiguous to mine. Whenever Fess Avery was mentioned, Heidelberger manifested reverence to such a degree that there was a distinctpause * Visiting professor of pathology and research professor of orthopedic surgery, University of Virginia, Charlottesville, Virginia 22903. 623 in the conversation. ForHeidelbergerand themany younger scientistswho had sought outAvery for advice on their research, the Fess was considered the mentor par excellence. It was well known that Avery examined every facet ofa problem so thoroughly that the "consultation" rarely lasted less than two hours, and the researchproblem was frequently explored indepth for three to five hours. However, the Fess maintained a silence on his own work. This creative and sympathetic interest in the research ofothers touched me personally in April 1942. Because I was ignorant ofAvery's studies in progress, our first meeting was exceedingly painful to me. I had just been called on active duty by the U.S. Navy and was invited to attend an April meeting of the National Research Council in Washington, D.C. The subject to be discussed was streptococcal problems in the armed services, for already the navy was confronted with a high incidence of rheumatic fever in the recruit training camps at the Great Lakes Training Center. More than a dozen distinguished civilianbiologists were assembled in the conference room. There were tedious harangues about the streptococcal menace. Each speaker seemed to concentrate on the periphery but declined to take an aggressive stance. Finally, I was questioned. Nervously, I stated that without adequate preventive medicine or control measures, three things could reasonably be expected to happen: (1) There would be a high incidence and rapid spread of hemolytic streptococcal respiratory infections. (2) Certain strains would develop "mutants" or "sports" that would be highly infective (as contagious as postinfluenzal streptococcal pneumonia in World War I at army camps in Texas). (3) Perhaps one or more ofthe streptococcal mutants would be genetically resistant to sulfonamides. There was dead silence when I had finished. Nobody spoke a word of agreement or approval; there seemed to be no interest in what was obviously a figment ofmy imagination. Presumably I had used words that were not acceptable in scientific circles—;genetic changes, bacterial variation, mutants, sports. Soon it was time to recess, and we paraded to the lower level for a standup snack lunch. Chagrined, depressed, and fearful ofreprimand for my shocking verbal goof, I picked up a sandwich and a bottle of Coca Cola and slunk into a far corner to recover from my embarassment. Then, although I had thought that not one person at our conference table...

Solid-phase peptide synthesis.

It is a privilege to be able to contribute to this volume in which Professor Zervas’ friends, students, and colleagues have joined together to honor him and his remarkable contributions to peptide chemistry. Although I did not know him until after his days in the Bergmann Laboratory at the Rockefeller Institute, I can claim the distinction of now working in those very same rooms that they occupied back in the mid-1930s. Like all peptide chemists, I am greatly indebted to Professor Zervas, having depended so heavily on the carbobenzoxy group and on the various modified urethan protecting groups which have been direct extensions of the revolutionary advance that Bergmann and Zervas made.

Determining the Location of Intrauterine Devices with the Beolocator

From the Division of Reproductive Biology, Department of Obstetrics and Gynecology, Harbor General Hospital, Torrance, Calif., and the University of California at Los Angeles School of Medicine, Los Angeles, Calif. Supported by a grant from the Ford Foundation. The Beolocator was a gift of The Population Council of the Rockefeller Institute, New York, N. Y. Submitted for publication June 23, 1967. * Ford Foundation Fellow in Reproductive Biology. †Present address: Department of Obstetrics and Gynecology, Faculty of Medicine and Siriraj Hospital, University of Medical Sciences, Bangkok, Thailand.

Tom Rivers: Reflections on a Life in Medicine and Science

This is an unusual and fascinating book about an unusual and fascinating man. When you read it you may hear the sounds of heavy breathing, from some important people of American medicine who will be reading this book with an attention as rapt as yours, although perhaps even a little more so. They will be anxious to see how they fared in the opinion and judgment of Tom Rivers, MD, of the Rockefeller Institute for Medical Research, a power in American medical science until his death in 1962, a man noted for his frank opinion, frankly and sometimes brutally expressed, and a man who was warm to his friends, hot to his enemies, a firebrand, a curmudgeon—a great guy. He was chairman of the Virus Research Committee of the National Foundation from 1938 until 1955. And he was Director of the Hospital of the Rockefeller Institute for Medical Research. During

Society's stake in responsible parenthood.

ON Nov 25, 1966, 85 religious and scientific leaders released a statement on the problem of population control.1Twenty-one of them were Nobel laureates. The document was drawn up by Dr. Edward L. Tatum of the Rockefeller Institute and Dr. John C. Bennett, President of Union Theological Seminary, New York. Among other things, they said Future generations will hold today's leaders morally responsible if we fail to recognize and deal with the world population crisis while it is still manageable on the basis of free Although the appeal was primarily to the Pope, it applies equally well to physicians, for it is they who are in a position to provide women with the knowledge to make pregnancy a matter of free choice. The people are ahead of their leaders, as is so often the case. A recent survey conducted by the Population Council uncovered the fact that 84%

A History of the Rockefeller Institute, 1901-1953: Origins and Growth by George W. Corner (review)

BOOK REVIEWS A History of the Rockefeller Institute, 1901-1953: Origins and Growth. By George W. Corner. New York: Rockefeller Institute Press, 1965. Pp. 635. $12.50. The Rockefeller Institute for Medical Research was incorporated on June 14, 1901. This history covers the period from its incorporation to the retirement ofHerbert Gasser as director in 1953 and his replacement by Detlev W. Bronk, with the title ofpresident. There is only briefreference to the subsequent events, which include the transformation ofthe institute to a university faculty of science, with a change in the corporate name, in 1958, to the Rockefeller Institute, and again, in 1964, to the Rockefeller University. The charter ofthe institute was amended in 1954 to make it a part ofthe University of the State of New York, with authority to grant the advanced degrees of Doctor of Philosophy and Doctor of Medical Science and the degrees, honoris causa, of Doctor of Science and Doctor ofLaws. In a foreword by the president, it is stated that "The Rockefeller Institute for Medical Research had so successfully fostered research in the academic world that a career ofteaching and research in a university had become more desirable than life in an intellectually limited research institute that lacked the vital stimulus of eager graduate students." The above paragraph constitutes a thumbnail sketch ofthe history ofthe Rockefeller Institute for Medical Research, the Rockefeller Institute, and the Rockefeller University, which George W. Corner has expanded to a volume of 635 pages. Included as an Appendix is a memorandum by Frederick T. Gates to Starr J. Murphy, not previously published in full, which relates "the prenatal history of the Institute," as the idea originated with Mr. Gates and eventually came to fruition. To appreciate the history ofthe Rockefeller Institute, and especially its impact upon medicine in the United States, one needs some familiarity with the state of medical education, medical research, and of medicine itself at the turn of the century. Medical research was almost non-existent; medical education was in a backward state, largely under the control ofthe numerous proprietary schools until after publication ofa report by Abraham Flexner in 1910; and the quality ofthe practice ofmedicine reflected that of medical research and medical education. The history of the Rockefeller Institute, covering the period to 1953, is thus to a large degree the history ofthe progress ofmodern medicine in the United States in the first half ofthe twentieth century. Even the concept of medical research required revision to permit the Rockefeller Institute to make the contributions related in this volume possible. In 1910 the board 309 ofdirectors ofthe institute appointedJacques Loeb, one ofthe most distinguished biologists of his generation, as a member of the institute. Before this action was completed, however, Loeb had to meet the objections ofthose who did not regard biology, especially with its concern with the lower forms of life, as a medical science. Loeb wrote: "The question is whether or not the R.I. desires to add a new department, namely that of experimental biology—the latter on a physico-chemical instead ofon a purely zoological basis. In my opinion experimental biology—the experimental biology of the cell—will have to form the basis not only ofphysiology, but also ofgeneral pathology and therapeutics . I do not think that the medical schools in this country are ready for the new departure. . . . The only place in America where such a new departure could be made for the cause ofmedicine would be the Rockefeller Institute or an institution with similar tendencies. The medical public at large does not yet fully see the bearing of the new science of experimental biology (in the sense in which I understand it) on medicine." As the author of this history states, "When the Board of Directors installed Jacques Loeb as a Member of the Rockefeller Institute, they committed themselves, once and for all, to the principle he so clearly stated. The institute's definition of the key words in its title, 'Medical Research,' was henceforth to include any kind ofinvestigation that might contribute to the understanding of health and disease, no matter how widely it ranged, from the body of a suffering man to subatomic particles." What the...

PRE-SCHOOL MALNUTRITION: PRIMARY DETERRENT TO HUMAN PROGRESS

PRE-SCHOOL MALNUTRITION: PRIMARY DETERRENT TO HUMAN PROGRESS Virginia A. Beal CopyRight https://doi.org/10.2105/AJPH.56.12.2166-b Published Online: August 29, 2011

Transplantation antigen-like activity of streptococcal cells

Departments of Surgery and Medicine, and the Institute of Reconstructive Platic Surgery, New York University Medical Center, and the Rockefeller Institute, New York.

Book Reviews

Journal Article Book Reviews Get access RENÉ J. DUBOS. The Unseen World. New York, The Rockefeller Institute Press & Oxford University Press, 1962. 112 pp. $4.75. CLAUDE E. DOLMAN CLAUDE E. DOLMAN Professor of Bacteriology and Immunology University of British ColumbiaVancouver, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of the History of Medicine and Allied Sciences, Volume XXI, Issue 1, January 1966, Page 89, https://doi.org/10.1093/jhmas/XXI.1.89 Published: 01 January 1966

History of Sulfonamides

THE DEVELOPMENT of sulfonamides, the most profound therapeutic revolution in the history of medicine, is recounted in the Current Medical Digest ( 32: 855 [Oct] 1965). Sulfanilamide was synthesized by a German chemist as early as 1908, and in 1917 at the Rockefeller Institute this chemical was added to quinine derivatives in an effort to increase bactericidal properties. Unfortunately for mankind in neither instance was the substance tried in experimental animals or in man. In 1927 the Bayer subsidiary of the I. G. Farbenindustrie began to screen various dyes for antibacterial effect in animals, under the direction of Dr. Gerhard Domagh. On a hunch that combining a sulfamyl group into the dye molecule might enhance the dye's antibacterial activity such a compound was tested on mice in 1931 and found to be effective against streptococcal infections. In December 1932 a sulfonamide-containing dye called Prontosil was found to be even more specific

Relationship Between the Competence Antigen and the Competence-Activator Substance in Pneumococci

Tomasz, Alexander (The Rockefeller Institute, New York, N.Y.), and Samuel M. Beiser. Relationship between the competence antigen and the competence-activator substance in pneumococci. J. Bacteriol. 90:1226-1232. 1965.-Antisera prepared against pneumococci in their competent phase inhibit deoxyribonuoleic acid (DNA)-mediated genetic transformation as well as binding of radioactive DNA by the cells. The same sera do not inhibit transformation of competent Haemophilus influenzae and Bacillus subtilis cells, but transformation of a Streptococcus strain genetically related to pneumococci is inhibited. The kinetics of immune inhibition of transformation resembles the inactivation of bacteriophage by phage-neutralizing antisera. The appearance of the competence antigen on the surface of pneumococci can be induced by the competence-activator substance. Antisera prepared against competent pneumococci can also inhibit the conversion of incompetent cells to competence by the competence-activator substance. The possibility is considered that part of the new antigenic determinant appearing on the cell surface during competence may be the activator itself.

Relationship of the major constituents of the Neurospora crassa cell wall to wild-type and colonial morphology.

Mahadevan, P. R. (The Rockefeller Institute, New York, N.Y.), and E. L. Tatum. Relationship of the major constituents of the Neurospora crassa cell wall to wild-type and colonial morphology. J. Bacteriol. 90:1073-1081. 1965.-The relationship of cell wall to morphology in Neurospora crassa was studied by correlating the levels of structural polymers of the cell wall with wild-type and colonial morphology. The cell wall of N. crassa contains at least four major complexes: a peptide-polysaccharide complex; two glucose polymers, one of which was found to be a laminarinlike beta-1,3-glucan; and, lastly, chitin. The levels of one or more of these structural polymers are consistently altered in single-gene mutants with colonial growth, and in sorbose-induced colonial growth. The proportions of these polymers, particularly of the peptide-polysaccharide complex and the beta-1,3-glucan, appear to be important to morphology.

Pathogenicity of murine hepatitis virus recovered from infant Swiss mice.

SummaryA murine hepatitis virus designated MHV (SR4) was recovered from infant Swiss mice of an outside source during a natural outbreak of disease. Intraperitoneal injection of 1- and 2-day-old nurslings from the Swiss colony of the Rockefeller Institute resulted in focal or semi-diffuse necrosis of the liver and mortality rates of 45 and 39%. The virus was less active in 5-day-old nurslings and essentially inactive alone in weanlings. It was established in the latter, however, on combination with ascites tumor cells.MHV (SR4) was also transmitted to 1- and 2-day-old nurslings by feeding and was demonstrable in their intestinal washings. It was not communicable from either injected or fed nurslings to untreated litter mates exposed to them. One-, 2-, and 5-day-old nurslings injected intracerebrally with the virus showed incoordination and mortality rates of 73-75% but weanlings were unaffected. Necrotic lesions were demonstrable in the brains and livers of the nurslings.

SEXUAL SELECTION, GEOTAXIS, AND CHROMOSOMAL POLYMORPHISM IN EXPERIMENTAL POPULATIONS OFDROSOPHILA PSEUDOOBSCURA

Journal Article SEXUAL SELECTION, GEOTAXIS, AND CHROMOSOMAL POLYMORPHISM IN EXPERIMENTAL POPULATIONS OF DROSOPHILA PSEUDOOBSCURA Get access Lee Ehrman, Lee Ehrman The Rockefeller Institute New York City Search for other works by this author on: Oxford Academic Google Scholar B. Spassky, B. Spassky The Rockefeller Institute New York City Search for other works by this author on: Oxford Academic Google Scholar O. Pavlovsky, O. Pavlovsky The Rockefeller Institute New York City Search for other works by this author on: Oxford Academic Google Scholar Th. Dobzhansky Th. Dobzhansky The Rockefeller Institute New York City Search for other works by this author on: Oxford Academic Google Scholar Evolution, Volume 19, Issue 3, 1 September 1965, Pages 337–346, https://doi.org/10.1111/j.1558-5646.1965.tb01724.x Published: 01 September 1965 Article history Accepted: 10 April 1965 Published: 01 September 1965

Automated peptide synthesis: R. B. Merrifield ( The Rockefeller Institute, New York, N.Y., U.S.A.)

Automated peptide synthesis: R. B. Merrifield ( The Rockefeller Institute, New York, N.Y., U.S.A.)

The search for peptides with specific antibradykinin activity: John Morrow Stewart and D. W. Woolley ( The Rockefeller Institute, New York, N.Y., U.S.A.)

The search for peptides with specific antibradykinin activity: John Morrow Stewart and D. W. Woolley ( The Rockefeller Institute, New York, N.Y., U.S.A.)

Centennial Celebration of the National Academy of Sciences

The Scientific Endeavor Contributed by Melvin Calvin and 23 other authors. (Centennial Celebration of the National Academy of Sciences.) Pp. vii + 331. (New York: The Rockefeller Institute Press, 1965.) 2.50 dollars.