"Who's on First?" — Medical Discoveries and Scientific Priority
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《新英格兰医药杂志》
One afternoon, a brilliant medical investigator unveiled before an eager crowd of physicians a stunning series of experiments that would revolutionize how they understood the human body. Realizing that he was making medical history, the investigator repeatedly reminded his audience that he was the first to conceive of these earth-shaking ideas. Not content merely to declare his originality, the scientist went to great lengths to disparage those competitors who offered differing medical theories. Calling his intellectual rivals "lazy" and "ignorant," the scientist exclaimed that his work was "as superfluous to them as a tale told to an ass."
I suspect that many physicians assume that heated assertions of scientific priority are the direct result of such 20th-century trends as the rise of the academic medical center, the mad dash for tenure, promotions, grants, and biotechnology patents, or even the remarkable awards that have been established to canonize those responsible for important discoveries. As a profession, we doctors are not only determined, but also somewhat obsessed with primacy and quite comfortable with intense competition. To the victors belongs more than mere mention in a medical textbook; discovering something first may be a medical investigator's best shot at immortality. Indeed, one wonders whether medical discovery would advance quite so quickly — as, for instance, in the recent race to map the human genome — if we were not all chasing the brass ring that allows us to boast, "I was there first."
But a cursory review of history amply demonstrates that the struggle — and, at times, the outright bad conduct it inspires — over who gets the credit and acclaim for a particular discovery is almost as old as scientific inquiry itself. Indeed, the investigator who derided his competitors as lazy and ignorant asses was none other than Galen, the ancient Roman physician and anatomist (131–201 A.D.), who in his day was almost as famous for cutting remarks about his competitors as for his anatomical dissections.1
And if you are wondering whether Galen was the first to combine keen medical knowledge with a fiercely competitive spirit, you may just be revealing your own competitive bent. In fact, if asked to categorize the types of historical query I most often receive from my colleagues, I would have to reply that, without question, the type beginning with the words "who was first" leads the list.
(Figure)
On the Shoulders of Giants.
Courtesy of the National Library of Medicine, Cold Spring Harbor Laboratory Archives (Franklin, Watson, and Crick), and Roland Magunia/AFP/Getty Images (Gallo and Montagnier).
Yet behind almost every assignment of scientific priority stands a towering list of vexing problems. Should the attribution be based solely on who published a finding first? Does the venue of publication matter? What about those investigators who work at institutions or in arenas that are not in the mainstream of scientific inquiry or part of elite academic medical circles? What happens when a pivotal contributor who is less powerful than a senior coauthor is not given his or her due for a particular discovery?
One of the fiercest disputes over scientific priority occurred between the bacteriologists Robert Koch and Louis Pasteur. At issue was who should receive credit for discovering the cause of anthrax. Koch began his meteoric rise to scientific fame in 1876, when he demonstrated that Bacillus anthracis was, indeed, the cause of anthrax. But in the spring of 1877, Pasteur published the first of several papers on anthrax and claimed that it was he who had first identified the deadly germ's spores and recognized their long dormancy period, as well as demonstrating the disease's causation. Moreover, Pasteur insisted that Koch's 1876 demonstration was not definitive and was methodologically flawed.
Some have hypothesized that the national differences between Germany and France fanned the flames of this incendiary debate; others have taken sides over who was right or who behaved worse. But a simpler explanation of the battle's ferocity seems the most likely. Because B. anthracis was the first microbe to be scientifically linked to what we now call an infectious disease, the issue of who definitively proved "the germ theory" was at stake; both men wanted exclusive credit for establishing the scientific revolution of their day.2
More troubling, from an ethical perspective, was the contest over the scientific discovery that has proved to be the most remarkable of the 20th century — that of the double-helical structure of DNA. The Cambridge scientists James Watson and Francis Crick were awarded the 1962 Nobel Prize in Physiology or Medicine for this achievement, but many remain offended by the lack of credit given to the x-ray crystallographer Rosalind Franklin, whose work was essential to the elucidation of DNA's structure. In his book The Double Helix, Watson admits that he and Crick obtained Franklin's data in a surreptitious manner, but he also derides Franklin personally — although in an updated edition of his memoirs, he apologizes for his behavior and mistaken, if not sexist, impressions of Franklin's character.3
Although Franklin could not possibly have received the Nobel Prize in 1962 (she died of ovarian cancer in 1958, and the award is never given posthumously), her University of London colleague Maurice Wilkins did share the prize. Sadly, the winners barely mentioned Franklin's seminal role in their acceptance speeches in Stockholm. As Franklin's biographer, Brenda Maddox, observed, "From the evidence of her notebooks, it is clear that she would have got there by herself before long."4 But of course, Franklin did not get there soon enough, and despite recent testimonials lauding her brilliant, if tragically short, career, it will always be Watson and Crick who come to mind first when one considers the origins of our understanding of DNA.
More recently, we have witnessed the contentious battle between Robert Gallo and Luc Montagnier as each sought credit for discovering the culprit behind the most serious pandemic of our era, the human immunodeficiency virus. It now seems likely that either Gallo and his associates deliberately used samples of the virus isolated by Montagnier (then called lymphadenopathy-associated virus) without giving due credit to the French team or, somehow, the French sample contaminated the viral specimens in Gallo's laboratory. In December 2003, Gallo and Montagnier issued a peace treaty of sorts as they chose the latter explanation and announced that they would share equally the credit for the discovery. Ironically, the virologists concluded "that effective collaboration among groups of scientists and clinicians is essential — and that it is possible to achieve such a collaboration without excluding a certain dose of the competitive spirit as stimulant."5
But the most serious difficulty with respect to assigning scientific priority is that this exercise runs counter to the fact that scientific knowledge is rarely, if ever, produced in a vacuum — or, as Sir Isaac Newton explained to Robert Hooke, "If I have seen further, it is by standing on the shoulders of giants." For example, in 1543, the Italian anatomist Andreas Vesalius superannuated the teachings of Galen and revolutionized the way we think about medicine by producing the first reliable atlas of human anatomy. His treatise, De Fabrica Humani Corporis, featured, among other revelations, an accurate description of the structure of the human heart. In 1628, the British anatomist William Harvey applied Vesalius's findings to demonstrate how blood from the heart circulates to the rest of the body. It does not take too much imagination to construct a chain of discoveries stretching from Harvey to our present-day modes of understanding, attacking, and preventing cardiovascular diseases. Indeed, a contiguous progression of ideas can be constructed behind almost every "new" discovery — so that, in retrospect (albeit hardly in real time), the question of who was first proves to be more a parlor game than an issue of real historical or scientific concern. History, of course, reveals again and again a characteristic of scientific inquiry that is decidedly unsettling to those of us engaged in this competitive enterprise: primarily because contemporaries all have access to the same giants' shoulders, there are typically many of us hitting on — and trying to prove — the same brilliant idea at the same time.
Source Information
Dr. Markel is director of the Center for the History of Medicine and a professor of pediatrics and communicable diseases at the University of Michigan Medical School, Ann Arbor.
References
Galen. On the natural faculties. Brock AJ, trans. Book III. Section 10. Cambridge, Mass.: Loeb's Classical Library, 1916:279-81.
Markel H. When germs travel: six major epidemics that have invaded America since 1900 and the fears they have unleashed. New York: Pantheon Books, 2004:28-31.
Watson JD. The double helix: a personal account of the discovery of the structure of DNA. New York: Scribner, 1998.
Maddox B. Rosalind Franklin: the dark lady of DNA. New York: HarperCollins, 2002:xviii.
Gallo R, Montagnier L. The discovery of HIV as the cause of AIDS. N Engl J Med 2003;349:2283-2285.(Howard Markel, M.D., Ph.D)
I suspect that many physicians assume that heated assertions of scientific priority are the direct result of such 20th-century trends as the rise of the academic medical center, the mad dash for tenure, promotions, grants, and biotechnology patents, or even the remarkable awards that have been established to canonize those responsible for important discoveries. As a profession, we doctors are not only determined, but also somewhat obsessed with primacy and quite comfortable with intense competition. To the victors belongs more than mere mention in a medical textbook; discovering something first may be a medical investigator's best shot at immortality. Indeed, one wonders whether medical discovery would advance quite so quickly — as, for instance, in the recent race to map the human genome — if we were not all chasing the brass ring that allows us to boast, "I was there first."
But a cursory review of history amply demonstrates that the struggle — and, at times, the outright bad conduct it inspires — over who gets the credit and acclaim for a particular discovery is almost as old as scientific inquiry itself. Indeed, the investigator who derided his competitors as lazy and ignorant asses was none other than Galen, the ancient Roman physician and anatomist (131–201 A.D.), who in his day was almost as famous for cutting remarks about his competitors as for his anatomical dissections.1
And if you are wondering whether Galen was the first to combine keen medical knowledge with a fiercely competitive spirit, you may just be revealing your own competitive bent. In fact, if asked to categorize the types of historical query I most often receive from my colleagues, I would have to reply that, without question, the type beginning with the words "who was first" leads the list.
(Figure)
On the Shoulders of Giants.
Courtesy of the National Library of Medicine, Cold Spring Harbor Laboratory Archives (Franklin, Watson, and Crick), and Roland Magunia/AFP/Getty Images (Gallo and Montagnier).
Yet behind almost every assignment of scientific priority stands a towering list of vexing problems. Should the attribution be based solely on who published a finding first? Does the venue of publication matter? What about those investigators who work at institutions or in arenas that are not in the mainstream of scientific inquiry or part of elite academic medical circles? What happens when a pivotal contributor who is less powerful than a senior coauthor is not given his or her due for a particular discovery?
One of the fiercest disputes over scientific priority occurred between the bacteriologists Robert Koch and Louis Pasteur. At issue was who should receive credit for discovering the cause of anthrax. Koch began his meteoric rise to scientific fame in 1876, when he demonstrated that Bacillus anthracis was, indeed, the cause of anthrax. But in the spring of 1877, Pasteur published the first of several papers on anthrax and claimed that it was he who had first identified the deadly germ's spores and recognized their long dormancy period, as well as demonstrating the disease's causation. Moreover, Pasteur insisted that Koch's 1876 demonstration was not definitive and was methodologically flawed.
Some have hypothesized that the national differences between Germany and France fanned the flames of this incendiary debate; others have taken sides over who was right or who behaved worse. But a simpler explanation of the battle's ferocity seems the most likely. Because B. anthracis was the first microbe to be scientifically linked to what we now call an infectious disease, the issue of who definitively proved "the germ theory" was at stake; both men wanted exclusive credit for establishing the scientific revolution of their day.2
More troubling, from an ethical perspective, was the contest over the scientific discovery that has proved to be the most remarkable of the 20th century — that of the double-helical structure of DNA. The Cambridge scientists James Watson and Francis Crick were awarded the 1962 Nobel Prize in Physiology or Medicine for this achievement, but many remain offended by the lack of credit given to the x-ray crystallographer Rosalind Franklin, whose work was essential to the elucidation of DNA's structure. In his book The Double Helix, Watson admits that he and Crick obtained Franklin's data in a surreptitious manner, but he also derides Franklin personally — although in an updated edition of his memoirs, he apologizes for his behavior and mistaken, if not sexist, impressions of Franklin's character.3
Although Franklin could not possibly have received the Nobel Prize in 1962 (she died of ovarian cancer in 1958, and the award is never given posthumously), her University of London colleague Maurice Wilkins did share the prize. Sadly, the winners barely mentioned Franklin's seminal role in their acceptance speeches in Stockholm. As Franklin's biographer, Brenda Maddox, observed, "From the evidence of her notebooks, it is clear that she would have got there by herself before long."4 But of course, Franklin did not get there soon enough, and despite recent testimonials lauding her brilliant, if tragically short, career, it will always be Watson and Crick who come to mind first when one considers the origins of our understanding of DNA.
More recently, we have witnessed the contentious battle between Robert Gallo and Luc Montagnier as each sought credit for discovering the culprit behind the most serious pandemic of our era, the human immunodeficiency virus. It now seems likely that either Gallo and his associates deliberately used samples of the virus isolated by Montagnier (then called lymphadenopathy-associated virus) without giving due credit to the French team or, somehow, the French sample contaminated the viral specimens in Gallo's laboratory. In December 2003, Gallo and Montagnier issued a peace treaty of sorts as they chose the latter explanation and announced that they would share equally the credit for the discovery. Ironically, the virologists concluded "that effective collaboration among groups of scientists and clinicians is essential — and that it is possible to achieve such a collaboration without excluding a certain dose of the competitive spirit as stimulant."5
But the most serious difficulty with respect to assigning scientific priority is that this exercise runs counter to the fact that scientific knowledge is rarely, if ever, produced in a vacuum — or, as Sir Isaac Newton explained to Robert Hooke, "If I have seen further, it is by standing on the shoulders of giants." For example, in 1543, the Italian anatomist Andreas Vesalius superannuated the teachings of Galen and revolutionized the way we think about medicine by producing the first reliable atlas of human anatomy. His treatise, De Fabrica Humani Corporis, featured, among other revelations, an accurate description of the structure of the human heart. In 1628, the British anatomist William Harvey applied Vesalius's findings to demonstrate how blood from the heart circulates to the rest of the body. It does not take too much imagination to construct a chain of discoveries stretching from Harvey to our present-day modes of understanding, attacking, and preventing cardiovascular diseases. Indeed, a contiguous progression of ideas can be constructed behind almost every "new" discovery — so that, in retrospect (albeit hardly in real time), the question of who was first proves to be more a parlor game than an issue of real historical or scientific concern. History, of course, reveals again and again a characteristic of scientific inquiry that is decidedly unsettling to those of us engaged in this competitive enterprise: primarily because contemporaries all have access to the same giants' shoulders, there are typically many of us hitting on — and trying to prove — the same brilliant idea at the same time.
Source Information
Dr. Markel is director of the Center for the History of Medicine and a professor of pediatrics and communicable diseases at the University of Michigan Medical School, Ann Arbor.
References
Galen. On the natural faculties. Brock AJ, trans. Book III. Section 10. Cambridge, Mass.: Loeb's Classical Library, 1916:279-81.
Markel H. When germs travel: six major epidemics that have invaded America since 1900 and the fears they have unleashed. New York: Pantheon Books, 2004:28-31.
Watson JD. The double helix: a personal account of the discovery of the structure of DNA. New York: Scribner, 1998.
Maddox B. Rosalind Franklin: the dark lady of DNA. New York: HarperCollins, 2002:xviii.
Gallo R, Montagnier L. The discovery of HIV as the cause of AIDS. N Engl J Med 2003;349:2283-2285.(Howard Markel, M.D., Ph.D)