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The Race and the Rivalry to be the First in Science
By Morton A. Meyers
Palgrave Macmillan Copyright © 2012 Morton A. Meyers
All rights reserved.
STOLEN CREDIT: A UNIVERSAL OUTRAGE
There are some things which cannot be learned quickly and time, which is all we have, must be paid heavily for their acquiring. They are the very simplest things; and because it takes a man's life to know them, the little new that each man gets from life is very costly and the only heritage he has to leave.
— Ernest Hemingway, Death in the Afternoon
In the early part of the twentieth century, a bitter conflict erupted over credit for a momentous scientific discovery, that of insulin to treat diabetes. This conflict heralds many of the issues that underlie disputes to this day.
Disordered breakdown of the body's circulating sugar creates the manifold and often lethal complications of what is known as diabetes mellitus. By 1920, the idea was growing that certain groups of cells in the pancreas, known as the islets of Langerhans, might be important to blood sugar metabolism and function independently from the rest of the pancreas cells.
A novice in the field — an inexperienced researcher who was unaware of virtually all of the previous experimental work — attempted to prove this theory with a novel approach. As Michael Bliss notes in his incisive account of this case, Frederick Banting, a twenty-eight-year-old country doctor, set out to isolate undamaged islets of Langerhans in order to extract their internal secretions, that is, a hormone. He did this by tying off the gland's main duct in order to destroy the preponderant pancreatic cells producing the digestive ferments.
Banting approached John Macleod, chairman of the physiology department at the University of Toronto where Banting had obtained his medical training. A more mismatched couple could not be imagined. Macleod, an urbane and distinguished academician, doubted that the cause of diabetes mellitus was hormonal. But he recognized that the experiment that the raw, unsophisticated, and inarticulate — but intensely determined — young doctor proposed was a sound one, even if it were to provide a negative result. So he finally offered Banting laboratory space, some experimental dogs, and the assistance of Charles Best, a young graduate student.
In mid-May 1921, the two started their experimental work on dogs. Conditions were sweltering. They worked in a small, dirty operating room just next to the odoriferous animal quarters, under the gravel-and-tar roof of the University of Toronto's old medical building. In mid-June, Macleod left on summer holiday in Scotland for three months. Initially, many of the dogs died, often from shock and widespread infection. Banting's research program was facing total failure. To compensate for the loss of the university's dogs, he bought others on the streets of Toronto, occasionally leading them back to the lab by his tie. By the end of the summer, Banting had successfully isolated a pancreatic filtrate that substantially improved blood glucose levels in diabetic dogs.
Toward the end of September, Banting demanded more resources from Macleod — a salary, better facilities, an animal caretaker — under the threat of going elsewhere. Macleod was reluctant but acquiesced. This episode engendered ill feelings that heralded Banting's deepening hostility and insecurity.
At the annual meeting of the American Physiological Society at Yale University on December 30, 1921, Banting presented the group's results. He was nervous and spoke haltingly, admitting later that he was "almost paralyzed" and "overawed" before the dignitaries in the audience. Macleod joined the discussion, responding to serious criticism of the research, speaking smoothly and dramatically, and referring to "our work." This only added to Banting's suspicion that Macleod was trying to take credit. Macleod, he was convinced, "had no original ideas. He only knew what he read or was told and then he could rewrite or retell it as though he were a scientist and a discoverer."
Banting and Best wrote up the results of their work, which were published in a paper boldly entitled, "The Internal Secretion of the Pancreas," in the Journal of Laboratory and Clinical Medicine in February 1922. The article concluded, "we feel justified in stating that this extract contains the internal secretion of the pancreas."
The pressing goal now, as it always had been in Banting's mind, was to isolate and purify the extract for clinical use in the treatment of diabetes. To this end, Macleod assigned to the laboratory the service of an expert biochemist, James Collip, who was a year younger than Banting. Within weeks, Collip developed a way to purify what was to be known as "insulin," a name based on the Latin root for the word "islands." "I experienced then and there ... perhaps the greatest thrill which has ever been given to me to realize," Collip exulted.
In January 1922, a fourteen-year-old boy, dying from diabetes at Toronto General Hospital, was given insulin. His rapid improvement was astonishing. This dramatic interruption of a fatal metabolic disorder would go down in the annals of the history of medical science as a medical miracle and would be forever associated with the names of Banting and Best.
At this point, however, a schism in the team effort created a personal confrontation — also remarkable in the history of science. Collip declared his intention to patent in his own name the method for purifying the extract. Banting, who regarded Collip as one of Macleod's allies, was so enraged, in one account, that he "suddenly and unexpectedly knocked [Collip] cold." This episode not only became scuttlebutt among contemporaries, but it has also entered medical legend. On a positive note, however, it promptly led to an agreement whereby the U.S. patent was assigned to the University of Toronto, which could license firms for the manufacture and sale of insulin and collect royalties. A similar arrangement was made with the British Medical Research Council.
On May 3, 1923 — only fifty weeks after Banting and Best started their work — Macleod presented a summary paper before the Association of American Physicians in Washington, D.C. This served to widely announce the discovery of insulin. The breakthrough was hailed as "epoch-making" and "one of the greatest achievements of modern medicine."
In an effort to record what each had contributed, and as a further indication of bitter divisiveness, the Banting/Best team and Collip published separate reports describing the methods for making the insulin-containing extracts. Everyone, including Macleod, had developed grudges, suspicions, and misunderstandings regarding appropriate credit for the discovery of insulin, leading to an irreconcilable rupture.
By mid-September 1923, the clinical program was a huge success with strikingly dramatic results. Up to 25,000 diabetics were receiving insulin, and terms like "resurrection" and "salvation" were being applied to the seemingly miraculous recovery of debilitated and comatose patients.
On October 25, 1923, the Nobel Assembly — in an unusually rapid decision — awarded the Nobel Prize in physiology or medicine to Banting and Macleod. When Banting heard that Macleod was a co-recipient and Best had not been included, he was furious. He had always considered Best not as an assistant but as a partner in his work. He immediately decided to share his award with Best. Macleod, learning of this, announced his intention to share his prize money with Collip.
The acrimony Banting felt toward Macleod flowed from Banting's deep sense of injustice. He had undertaken his experiments with a fresh, albeit untutored, mind and with imagination, unshakeable faith, and determination. Macleod, on the other hand, felt that he had offered encouragement, advice, and resources. Furthermore, having been trained in Europe, Macleod probably had incorporated the hierarchical attitude that work successfully accomplished in his department should bear his co-authorship.
A fundamental issue throughout this episode is the issue of intellectual property. Who has priority? The discoverer, or the individual who helps to illuminate the concept to others?
THE ECSTASY OF DISCOVERY, THE AGONY OF STOLEN CREDIT
Many of us have had a fresh idea or proud accomplishment appropriated by somebody else — perhaps a boss, a manager, a teacher, or a colleague.
An original idea, a novel approach, a creative effort — whether in the arts, the sciences, technology, or business — stirs not only pride but also an intense proprietary attachment within an individual. The passions aroused by claims over credit are acute. Credit is, after all, the basis for getting recognition, jobs, promotions, and awards. Its appropriation by another, particularly without attribution, is an act of plagiarism, a violation of intellectual property. The hurt this engenders in the originator results in a deep and long-lasting scar.
Although the practice of supervisors claiming credit for the work of subordinates is widespread, most complaints are voiced privately. Grumbling is generally restricted to the locker room or the water cooler.
Going public with such complaints is far less common. The accuser may not voice his or her distress for a long time and may express righteous indignation or seek passionate retribution.
Consider these examples:
The Polio Vaccine
On April 12, 1955, following nationwide clinical trials on 1.8 million American school children, the Salk vaccine against polio — at the time the leading crippler of children — was announced as "safe, effective, and potent." Euphoria swept the country. As Richard Carter notes in his biography of Jonas Salk, "people observed moments of silence, rang bells, honked horns, blew factory whistles, fired salutes, kept their traffic lights red in brief periods of tribute, took the rest of the day off, closed their schools or convoked fervid assemblies, therein drank toasts, hugged children, attended church, smiled at strangers, forgave enemies."
In his role as director of the laboratory, Salk had been coldly distant from his staff, communicating through notes and memos, but was adept at self-promotion in his dealings with reporters. But an incident in 1954 showed that he was capable of duplicity. Julius Youngner, Salk's top research assistant, developed a critical test to measure the amount of polio virus in living tissue culture and handed a draft of the report to Salk for his comments. The original report listed only Youngner and an assistant as authors. Youngner asserts that Salk had done nothing to initiate, advise, or carry out the work. After a few days, Salk returned a "revised" draft to Youngner, but with Salk's name as first author. He claimed that he had lost the original draft, explaining that he nevertheless found Youngner's tables of data, from which he had to reconstruct the entire paper. On this basis, he made it clear that he considered it only fair that his name go first.
At the formal announcement of the vaccine's success the following year, attended by more than 150 reporters, Salk's coworkers sat proudly together, expecting to be honored. They were, however, painfully snubbed and felt betrayed.
More than thirty-eight years later, Julius Youngner, then a distinguished service professor in the University of Pittsburgh's School of Medicine, had an opportunity to release the hurt he had long been harboring to Jonas Salk. He said to his former boss: "Do you still have the speech you gave ... in 1955? Have you ever reread it? We were in the audience, your closest colleagues and devoted associates, who worked hard and faithfully for the same goal that you desired ... Do you realize how devastated we were at that moment and ever afterward when you persisted in making your co-workers invisible?" He then asked Salk if he understood what he was saying, and Salk answered that he did. It's not clear if the response gave Youngner any solace.
A Breakthrough Antidepressant
"Scientists, like everyone else," an editorial in the New York Times commented, "are motivated by more than the search for truth. They lust after reward and recognition and frequently dispute the credits that are distributed." The editorial was reflecting on the outcome of a long and bitter conflict surrounding iproniazid, a breakthrough antidepressant of the 1950s.
In the early 1950s, Nathan Kline, a bold and energetic psychiatric researcher and director of the massive Rockland State Hospital in Orangeburg, New York, had introduced the use of tranquilizers to the practice of psychiatry, which steered the specialty onto a whole new path that focused on the chemistry of neurotransmitters in the brain. For this he received the prestigious Albert Lasker Medical Research Award in 1957. He went on to oversee clinical trials with the antidepressant iproniazid on over 800 patients at Rockland, and a paper attesting to its positive effects was read by Harry Loomer, the physician in charge of the Rockland clinical unit, at the regional meeting of the American Psychiatric Association in Syracuse, New York, in 1957. However, the New York Times incorrectly credited the presentation to Kline. This probably happened because at a press conference in New York a few days earlier, details of the success of the trial had been provided solely by Kline.
When a scientist presents the common work of a group in which he is a co-worker, but mentions only his own name and none of the co-workers, it crosses the line from a simple violation of etiquette to the perception of scientific dishonesty. Loomer was infuriated, and the New York Times printed a retraction. Another member of the team, John Saunders, a physician and clinical pharmacologist who supervised the project and had correctly attributed the mode of action of iproniazid to monoamine oxidase (MAO) activity, also felt exploited. The following year, under his single authorship, Kline published a paper on the clinical experience with iproniazid. Within one year of Kline's report, more than 400,000 patients had received the drug for treatment of depression. The spark of discontent burst into flame in 1964 when Kline became the single recipient of a second Lasker Award for work with iproniazid. (The accompanying citation said: "Literally hundreds of thousands of people are leading productive, normal lives who — but for Dr. Kline's work — would be leading lives of fruitless despair and frustration.")
Loomer and Saunders objected, saying they had made the discovery, and brought suit, asking for $1 million in damages from Kline for "false and fraudulent" claims for complete credit and from the Lasker Foundation for failure to make a "proper investigation into the facts." Seventeen years of litigation followed. Their decision to undertake the suit is all the more startling in the face of Kline's accomplishments and reputation. At some point, Loomer dropped out. Iproniazid had been introduced in clinical use originally as an anti-tuberculosis drug, and Saunders maintained that it was he who observed its euphoric effects and realized its potential. A jury ruled for Saunders, and the State Court of Appeals upheld that ruling and finally laid the case to rest in 1981. Saunders received one-third of the $10,000 Lasker award from 1964, and Kline was required to pay certain court fees totaling about $20,000.
This research culminated in today's multi-billion-dollar mood-altering drug industry. These MAO inhibitors have been replaced by the now-dominant class of antidepressant compounds, the tricyclics.
A New Radionuclide
A precedent-setting case that shook the halls of academic medicine in the late 1980s through the early 1990s established the right that faculty members have to their intellectual property. The case flared with issues of plagiarism, sex discrimination, due process, and institutional ruthlessness.
Something of a wunderkind, Heidi Weissmann started college when she was fifteen, began medical school when she was nineteen, and by age thirty-three, her supervisor was calling her one of the nation's premier authorities on biliary imaging in nuclear medicine. As an assistant and subsequently associate professor at the Albert Einstein College of Medicine of Yeshiva University, and an attending physician at its teaching hospital, the Montefiore Medical Center in Bronx, New York, she pioneered the clinical usefulness of a new radionuclide, iminodiacetic acid (IDA), for imaging the gallbladder and biliary system. This quickly proved to be a major advance in the diagnosis of cholecystitis (inflamed gallbladder), gallstones, and tumors of the bile ducts.
Excerpted from Prize Fight by Morton A. Meyers. Copyright © 2012 Morton A. Meyers. Excerpted by permission of Palgrave Macmillan.
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