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Heroes in Medical Research: Dr. Robert Ting, Ph.D. and Retrovirus in AIDS and Cancer

Curator and Reporter: Stephen J. Williams, PhD

This is the second posting in this series in which I highlight the basic research which led to seminal breakthroughs in the medical field, brought on by the result of basic inquiry, thorough and detailed investigation, meticulously following the scientific method, and eventually leading to development of important medical therapies.

In his autobiography, Virus Hunting: AIDS, Cancer & the Human Retrovirus: A Story of Scientific Discovery, Dr. Robert Gallo, M.D. describes a wonderful story of the history behind, scientific biographies, and chronology of the discoveries which led he and his colleagues (including co-discoverer Dr. Luke Montagnier) to recognize retroviruses (in particular HIV) as the leading culprit for the cause of AIDS and in the etiology of Kaposi’s sarcoma.   For anyone who appreciates the history behind scientific discoveries and appreciates learning about the multitude of individual efforts which are the crux of seminal research, this book is a must read.

Recommendations from the back cover include:

Virus Hunting will be read and reread, for years to come.” —New York Newsday

“Provides a human, revealing look into the arcane, usually secret confines of laboratory science.”

Martin Delany, Project Inform

..as well as others.

While a fascinating aspect of this book is the description, like fitting pieces of a puzzle, of the important discoveries throughout history which are the necessary foundations for further investigations and discoveries, more important is a telling, personal narrative of the people involved in those initial and subsequent discoveries.  In fact, the book has over 396 colleagues, mentors, technicians, students, and even critiques who are given credit, in one form or another, for the ultimate discovery of HIV as a causative agent for the development of AIDS. The book is a literal Who’s Who in Science and shows how important personal collaboration and friendships are in the process of scientific discovery.

In 1972, Dr. Seymour Perry had appointed the young Dr. Robert Gallo as head of a new department, the Human Tumor Cell Biology Branch, renamed the Laboratory of Tumor Cell Biology.  The lab was carrying on the work on tRNA that Dr. Gallo had performed in Dr. Sid Perska’s group at NIH.  However, with the help of new lab members Dr. David Gillespie, Dr. Flossie Wong-Staal, and Dr. Marjorie Robert-Guroff the lab focused on the search for disease-causing retroviruses, especially in human leukemias.  This was, in part, due to conversations with Dr. Robert Huebner and Todaro, who insisted that

“within the genetic makeup of this endogenous retroviral material was, they suggested, a special gene, the oncogene, that was the parent of the cancer-causing protein”

which may explain some of the early work by Rous concerning the Rous sarcoma virus.

Enter in Gallo’s good friend Dr. Bob Ting.  Dr. Gallo had known Dr. Ting socially since 1966, shortly after Gallo had arrived at NIH.  Dr. Bob Ting was a well-established NCI investigator, who was doing work on DNA and RNA oncogenic viruses of animals.  Originally from a large and wealthy family in Hong Kong, Dr. Ting had worked with Nobel Prize winners Salvatore Luria (who worked on phages) and Renato Dulbecco, who, along with his well-known cell culture media, had made the seminal discoveries that led to our knowledge how some DNA viruses can transform normal animal cells into neoplastic-like cells in culture.

Bob Ting gave a talk on these oncogenic viruses and Gallo was very interested in his observations that oncogenic viruses like Rous and Maloney, could transform cells in vitro in a matter of days.

A friendship developed between the two over tennis matches and Chinese food.  During this time, Dr. Ting made the important suggestion that they both collaborate and use the viral systems developed by Dulbecco.  Ting also introduced him to RNA viruses, Dr. Robert Huebner, and Dr. Howard Temin.  It was, in part, due to these associations that Gallo started looking, in earnest, at the possibility of RNA retroviruses in leukemias. Thus, just like the internet today, connections and networking provided new insights into current research, and helped lead the advent of new discoveries, therapies, and scientific disciplines.

Therefore, “after some late-night discussion with Bob Ting, I decided to enter the fray. My own laboratory, … would immediately be set up to compare the properties of reverse transcriptase enzymes from many different animal retroviruses”.

Although the rest is more history, this early friendship, collaboration, and mentoring by Bob Ting had “transformed” Gallo’s research efforts to set him up to make some of the important discoveries eventually leading to the discovery of the role of HIV in AIDS.

A video interviewing Dr. Gallo can be found here:

VIEW VIDEO

https://www.youtube.com/watch?v=ELRlXLGWu4I

A very nice writeup/obituary for Dr. Ting was written by Patricia Sullivan of the Washington Post and is included below.

Robert Ting, 77; Biotech Pioneer

ME/Ting-ob

Dr. Robert Ting’s biotech company in Rockville developed the first FDA-approved diagnostic test kits to test for HIV antibodies. (By Gerald Martineau — The Washington Post)

 

By Patricia Sullivan

Washington Post Staff Writer
Friday, September 22, 2006

Robert C.Y. Ting, 77, a research scientist who started one of the early biotechnology companies in the Washington area, died Sept. 11 of complications after cardiac surgery at the Cleveland Clinic in Cleveland.

Dr. Ting founded Biotech Research Laboratories Inc. in Rockville in 1973, producing cells for government scientists to use in research. Eleven years later, his firm obtained a federal license to develop and produce the first FDA-approved diagnostic test kits for HIV antibody confirmation.

Robert C. Gallo, who co-discovered the HIV virus as the cause of AIDS, called Dr. Ting a pioneer in the field who popularized the term “biotechnology” when he moved from research to entrepreneurship.

“He introduced me to virology, and he did it twice,” said Gallo, director of the Institute of Human Virology in Baltimore. The men had known each other since the 1960s, and while playing tennis one day, Dr. Ting advised the cancer researcher to look at new research in viruses. Later, when Gallo was studying leukemia, Dr. Ting directed him to animal research in leukemia. “First he showed me how viruses change cells. Then he introduced me to retrovirology. . . . I went into retrovirology solely because of those discussions with Bob Ting on tennis courts,” Gallo said.

Dr. Ting, whom Gallo described as a quiet, modest man, was born in Shanghai, the son of a physician to Gen. Chiang Kai-Shek. His family fled the country during the Japanese invasion of China during World War II and moved to Hong Kong. Soon after, he moved to the United States, where he received a bachelor’s degree and in 1956 a master’s degree in genetics from Amherst College.

He received a doctoral degree in microbiology and biochemistry from the University of Illinois in 1960 under Salvador E. Luria, who later won the 1969 Nobel Prize in Medicine and Physiology. Dr. Ting spent the next two years on a postdoctoral fellowship at the California Institute of Technology, working with Renato Dulbecco, who later won the 1975 Nobel Prize in Medicine and Physiology. Their work focused on how viruses cause tumors.

“A lot of molecular biology developed from this,” Dr. Ting told The Washington Post in 1984 from his Rockville office, cluttered with scientific journals, awards and a large blackboard. “There was so much evidence in animal systems [that viruses cause tumors], that the next question was obvious — can you find the equivalent in humans.”

Dr. Ting joined the National Institutes of Health in 1962 as a visiting fellow and then a senior research scientist at the National Cancer Institute. From 1966 to 1968, he was an associate editor for the Journal of the National Cancer Institute.

In 1969, he joined Litton Bionetics Inc. in Rockville as director of experimental oncology, leading a project funded by the institute to search for viruses in human leukemia patients. He became scientific director of the cancer research branch the next year.

With academic, government and private business experience under his belt, Dr. Ting decided to go into business on his own and in 1973 started Biotech Research Laboratories in Rockville. It was a profitable supplier of research services and supplies until 1981, when it went public and produced the HIV diagnostic test kits. It became one of the most successful public biotech companies in the area in the mid-1980s.

The Economic Development Board of Singapore invited him to return to Asia to start a biotech company, which he did in 1985, forming Diagnostic Biotechnology Ltd. He also joined the Institute of Molecular and Cell Biology at the National University of Singapore, which Gallo called “the most prominent Asian academic biotechnology center.”

He returned to the United States in 1998 to join the board of Cell Works Inc. in Baltimore, and became chair and chief executive of a joint venture, Cell Works Asia Limited, in 2000.

Most recently, Dr. Ting was the founding president and chief executive of Profectus Biosciences Inc. of Baltimore, previously known as Maryland BioTherapeutics Inc.

Dr. Ting was past chairman of the F.F. Fraternity, one of the oldest Chinese fraternities in the United States. He was also a member of the Organization of Chinese Americans in the D.C. area since its inception in the early 1970s. He enjoyed tennis, golf, ballroom dancing and international travel. He also was a wine connoisseur.

Survivors include his wife of 44 years, Sylvia Han Ting of Potomac; three children, Anthony Ting of Shaker Heights, Ohio, Andrew Ting of Beverly, Mass., and Jennifer Chow of Potomac; seven sisters; and seven grandchildren.

An obituary written from his son Anthony can be found here:

https://www.amherst.edu/aboutamherst/magazine/in_memory/1953/robertting

Sources:

http://www.amazon.com/Virus-Hunting-Retrovirus-Scientific-Discovery/dp/0465098150

http://www.washingtonpost.com/wp-dyn/content/article/2006/09/21/AR2006092101936.html

Other articles/postings related to this topic and HIV on this site includes:

Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin

History of medicine, science, and society: 200 Years of the New England Journal of Medicine

Why did Pauling Lose the “Race” to James Watson and Francis Crick? How Crick Describes his Discovery in a Letter to his Son

John Randall’s MRC Research Unit and Rosalind Franklin’s role at Kings College

Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin

Otto Warburg, A Giant of Modern Cellular Biology

Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

Nanotechnology and HIV/AIDS treatment

HIV vaccine: Caltech puts us One step further

Getting Better: Documentary Videos on Medical Progress — in Surgery, Leukemia, and HIV/AIDS.

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New England Journal of Medicine an Interview with Allan M. Brandt, Ph.D.

N Engl J Med 2012; 366:1-7 January 5, 2012

http://www.nejm.org/doi/full/10.1056/NEJMp1112812

Reporter: Aviva Lev-Ari PhD, RN

With this issue, the New England Journal of Medicine marks its 200th anniversary. In January 1812, as the first issue came off the handset letterpress, few of its founders could have predicted such continuity and success. (See Figure 1FIGURE 1Illustration from “Cases of Organic Diseases of the Heart and Lungs,” by John C. Warren, April 1, 1812, Issue of the Journal., from an 1812 issue.) John Collins Warren, the renowned Boston surgeon, his colleague James Jackson, a founder of Massachusetts General Hospital, and the small group of distinguished colleagues who joined them in starting the New England Journal of Medicine and Surgery, and the Collateral Branches of Science expressed modest and largely local aspirations for the enterprise. Boston, a growing urban center, and the wider New England environs had no medical journal of their own, although much medical knowledge and practice was considered region-specific. Although the name and format of the Journal would vary until 1928, 7 years after its ownership passed to the Massachusetts Medical Society, it remains the longest continuously published medical periodical in the world. The prospectus for the Journal, a call for papers issued in late 1811, explained the goals of Warren and his collaborators: “The editors have been encouraged to attempt this publication by the opinion, that a taste for medical literature has greatly increased in New England within a few years past. New methods of practice, good old ones which are not sufficiently known, and occasional investigations of the modes in common use, when thus distributed among our medical brethren in the country, will promote a disposition for inquiry and reflection, which cannot fail to produce the most happy results.”1

At a time of intense debate and controversy regarding the causes of disease, the nature of therapeutics, and the basis of professional authority, the young Journal worked to steer a middle course. This was certainly advisable from a commercial point of view, since it could easily alienate diverse medical readers by endorsing a particular therapeutic system or theory. But this approach also established the ecumenical temper of theJournal, which based its early publications on a commitment to empirical observation and an outlook skeptical of conventional medical wisdoms. As the editors explained in 1837, “It has been a point of ambition with us . . . to make these pages the vehicle of useful intelligence, rather than the field of warfare. . . . The Journal is to all intents and purposes, designed to be a record of medical and surgical facts. It is the medium through which the profession may interchange sentiments and publish the results of their experience” (see Historical Journal Articles Cited).

THE ENDURING PROBLEM OF DISEASE

The observation and investigation of disease is perhaps the most salient consistent feature of theJournal. From the meticulous description of angina pectoris in the first issue to the early descriptions of AIDS in the early 1980s, there has been an ongoing recognition that therapeutic approaches must await the sharp articulation of symptoms. The first decades of the Journal‘s history reflected the intensive concern with the epidemics affecting New England and the new nation, and it was not unusual during the early years for authors to direct attention to the environment as a critical variable in the production of disease. John Gorham, an editor writing in 1828, offered a “Medical Report of the Weather and Prevalent diseases for the last Three months.” Such articles may appear both quaint and humorous from our contemporary scientific perch, but they reveal a serious commitment to understanding more fully the vagaries of epidemic disease that could devastate town and country in short order. Furthermore, they offer a complex notion of causality that characterized much 19th-century medicine, in which disease was seen as the result of interactions of the patient’s individual “constitution” with an ever-changing and often dangerous environment.2 By the late 20th century, many observers would renew concerns voiced more than a century earlier about the environment’s relationship to disease.

DOCUMENTING THERAPEUTIC INNOVATION

The Journal provides a powerful record of the course taken by medical science and its applications over a 200-year period. It quickly became a conduit for reporting new investigations and findings and for summarizing and disseminating evolving medical knowledge across the widest range of practice. After issuing favorable reports on bloodletting, herbal treatments, and other “heroic” practices of the early 19th century, the Journal began to reflect a growing skepticism toward such approaches. Authors increasingly pointed to the benefits of the healing powers of nature — vis medicatrix naturae — as physicians came to recognize some of the iatrogenic effects of their interventions that had previously been difficult to differentiate from the course of serious disease.3Therapeutics based on ancient notions of humoral excess and depletion gave way to a renewed emphasis on empirical observation and experiment. The first demonstration of surgical anesthesia, conducted at Massachusetts General Hospital in 1846 in an amphitheater soon to be renamed the “Ether Dome,” was first reported in the Journal (Figure 2FIGURE 2“First Operation under Ether,” 1846, with Related Journal Report.). Others quickly began using ether in their practices. One surgeon wrote in the Journal, “I performed the amputation of an arm, the second under the use of ether, while the patient was dreaming of her harvest labors in Ireland, and felt grating but not painful sensations, `as if a reaping-hook was in her arm’” (1850).

EDUCATION AND THE DISSEMINATION OF MEDICAL KNOWLEDGE

From the beginning, the Journal has critically covered essential debates about the character and quality of medical education. The editors considered one of their primary goals to be educating the profession, so assessment of medical school programs was in harmony with their mission; after all, these schools produced their readers. In the late 19th century, the Journal frequently noted the great inconsistencies in educational standards and quality. A decade before the publication of the Flexner reforms, prominent Boston physician Henry Bowditch anticipated many key aspects of the report when he called for linking medical education to universities, lengthening the course of study, and demanding deeper preparation in the sciences and wider domains of knowledge (1900). He argued for active learning to replace didactics, a theme that would echo through the debates about medical education. As late as 1900, when Bowditch proposed his reforms in the Journal, less than half the students at Harvard Medical School had completed a college education. After the publication of the Flexner Report in 1910 and the massive changes that followed, the Journalapplauded the consolidation of medical education on a new scientific foundation.

TOO MUCH TO KNOW

With the radical expansion and shifting of the scientific basis of medicine at the turn of the 20th century, the Journal recorded growing interest in and concern about specialization. From a largely undifferentiated notion of medical training and expertise, many new and specific divisions of the medical profession developed.6 Whereas the Journal came to view specialization as the inevitable result of exploding medical knowledge, the creation of medical “specializm” was viewed with considerable skepticism and lamentation, if not outright hostility. Much ink was spilled in attempts to determine the relationship of general knowledge and practice to increasingly specific (and limited) areas of expertise. How would the “whole patient” be treated when specialties had divided the body into organ systems and medicine into categories of disease and authority over various technologies and techniques?

THE PERMEABLE BOUNDARIES OF SCIENCE AND MEDICINE

Despite the Journal‘s deep commitment to empirical reasoning and scientific rationality, cultural and political beliefs and values are ever apparent in its pages. In some instances, professional prerogatives and social assumptions are exposed. For example, when the introduction of women students at Harvard Medical School was debated in 1878, the Journal expressed concern: “It would . . . be impossible to avoid an indiscriminate mingling of the sexes in the dissecting or autopsy rooms, and in the amphitheatres, to witness exercises which justly have hitherto been thought of a character to be witnessed by one sex alone.” Harvard would ultimately admit women in 1945, when the war caused a shortage of male candidates. In the 1950s, the Journal expressed regret that some women physicians with children “have found it impossible to carry on their practices” (1954).

REFLECTIONS ON THE JOURNAL AT 200

While the Journal embraced new science and the critical apparatus of peer review, it rejected a narrow notion of specialism, continuing to cover the widest range of contributions to medical knowledge. In an increasingly atomized medical world, the commitment to publish on cross-cutting educational, professional, ethical, and policy issues pulled together diverse readers, including physicians and other health care providers, public health experts, and policymakers, around issues that were often beyond their immediate expertise. The radical growth of teaching hospitals, federal funding for basic science and clinical research, and academic medical centers (all developments reflected in the Journal) have been crucially linked to the Journal‘s growth, stability, and success.

During the Journal’s first 200 years of publication, medicine and health care moved from the social periphery to become dominant aspects of our science, culture, and economy. The Journalunquestionably owes its success and stability to this monumental shift in the status, authority, and impact of biomedicine. But the Journal has also played a critical role in these developments. By combining a commitment to publishing papers of scrupulous scientific merit across wide-ranging domains, with a recognition of the central questions and values uniting the profession, the Journalhas remained true to its founders’ vision. It has recognized that advances in medical science can finally be assessed only in the context of delivery, care, and outcome. The Journal reflects today, as at its inception, a view that medical science and its applications are fundamentally tied to patient care and public health. It therefore continues to draw a range of readers wider than Warren could have imagined. Today, the ability to disseminate publications so widely through digital technologies promises to bring innovations in medical knowledge to a new set of global constituents. The first hundred issues of Warren’s journal were, of course, distributed on horseback.

HISTORICAL JOURNAL ARTICLES CITED.

New England Journal of Medicine and Surgery, and the Collateral Branches of Science

1812. Warren J. Remarks on Angina Pectoris. 1:1-11.

The Boston Medical and Surgical Journal

1828. Gorham J. Medical report of the weather and prevalent diseases for the last three months. 1:10-12.

1832. Editorials and Medical Intelligence. 6:401-2.

1837. Editorials and Medical Intelligence. 16:16-17.

1846. Bigelow HJ. Insensibility during surgical operations produced by inhalation. 35:309-17.

1850. Peirson AL. Anæsthetic agents. 42:229-32.

1871. Seaverns J. Recent advances in medicine and their influence on therapeutics. 85:113-20.

1878. Reports of Meetings. Female medical students at Harvard. 98:786-7.

1891. Ernst HC. Records for cases of tuberculosis treated with Koch’s parataloid. 124:75.

1900. Bowditch HP. The medical school of the future. 142:445-53.

1919. Editorial. Science and medical teaching. 180:108-9.

1923. Phippen WG. The relation of the specialist to the general practitioner. 189:204-6.

1924. Specialism versus Competence. 190:475-6.

1926. Editorial. The teaching of medicine. 195:1124-5.

1928. Appel KE. Medical education: the retrospect of a recent graduate. 197:1265-7.

The New England Journal of Medicine

1928. Lombard HL, Doering CR. Cancer studies in Massachusetts: habits, characteristics and environment of individuals with and without cancer. 198:481-7.

1928. Editorial. Sterilization of defectives. 199:1225-6.

1934. Editorial. Sterilization and its possible accomplishments. 211:379-80.

1935. Henderson LJ. Physician and patient as a social system. 212:819-23.

1939. Mallory TB. Richard Clarke Cabot and the clinicopathologic conference. 220:880.

1948. The Case Records of the Massachusetts General Hospital. 239:690.

1949. Alexander L. Medical science under dictatorship. 241:39-47.

1954. Editorial. Practice of medicine by married women. 250:486.

1966. Beecher HK. Ethics and clinical research. 274:1354-60.

1970. Swan HJC, Ganz W, Forrester J, et al. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. 283:447-51.

1981. Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. 305:1425-31.

1981. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia. 305:1431-8.

1981. Siegal FP, Lopez C, Hammer GS, et al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. 305:1439-44.

Special Anniversary Articles

We are publishing a series of engaging Review and Perspective articles from established authors who are preeminent in their fields. Each article explores a story of progress in medicine over the past 200 years. These articles will appear every other week during 2012 and be collected here. Check the News & Eventssection of this site for announcements about upcoming articles.
http://nejm200.nejm.org/explore/special-anniversary-articles/

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