| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Biochemistry and Molecular Pharmacology, Program in Cell Dynamics, University of Massachusetts Medical School, and The Worcester Foundation for Biomedical Research, Worcester, Massachusetts, USA
1Correspondence: The Worcester Foundation for Biomedical Research, 377 Plantation St., Worcester, MA 01605, USA. E-mail: thoru.pederson{at}umassmed.edu
In 1893, a young man named Ragnar Sohlman was hired as the private assistant to a successful industrialist. Sohlman’s name is not recognized today, but he played a key role in events that led to worldwide acclaim and admiration for his employer—Alfred Bernhard Nobel.
Alfred Nobel was born in Stockholm on October 21, 1833. His forebears included a number of scientists and inventors, including Olof Rudbeck, a 17th century engineer of considerable fame within Scandinavia. For some years Alfred’s father was the chief of an explosives plant in Russia and, as a young man, Alfred began to study nitroglycerine. The dangerous instability of this viscous liquid was well known, severely limiting its commercial potential. A factory that Alfred subsequently set up to produce nitroglycerin exploded, killing his brother and four others. Probably as a direct result of this tragic accident, Alfred developed a process by which nitroglycerine could be adsorbed into an inert material ("kieselguhr") and safely packed into sticks that could be activated by a detonator cap that Alfred had also invented. He named his formulation "dynamite." Predictably, it soon made him a very wealthy man.
In 1896, a short three years after hiring Rangar Sohlman, Alfred Nobel died and Sohlman learned that he had been named the executor of Nobel’s estate. The will was contested by the family but in due course its provisions were affirmed. Nobel had directed that a very substantial portion of his realizable estate be invested as an endowment for the purpose of awarding annual monetary prizes in several fields of intellectual achievement. He specified that the Swedish Academy of Sciences was to award a prize in Chemistry and another in Physics, and that the Karolinska Institute in Stockholm was to award a prize in Physiology or Medicine. Prizes in Literature and Peace were also prescribed, and it is interesting to note that Nobel, a patriotic Swede, directed that the Peace Prize be awarded by none other than the Norwegian Parliament.
In 1969, the Bank of Sweden launched a Nobel Prize in Economics. I shall confine my remarks to the Nobel Prizes in Chemistry, Physics, and Physiology or Medicine.
The first prizes were awarded in 1901. It is particularly interesting to note that the selection committees did not wait long to recognize women. Only two years after the Nobel Prizes were instituted, Marie Curie shared the 1903 prize for Physics for her role in the discovery of radioactivity. Moreover, only a mere eight years later, in 1911, she received the Nobel Prize in Chemistry—unshared, for her discovery of radioactive elements. She thus became the first person to win two Nobel Prizes—a distinction she held for the next 61 years until the American John Bardeen won his second Physics prize in 1972. Besides Curie and Bardeen, only one other individual has won two Nobel Prizes in science—the British biochemist Frederick Sanger. After Marie Curie’s second Nobel Prize in 1911, the next science prize to a woman was to none other Curie’s daughter, Irene Joliot-Curie who shared the 1935 Chemistry Prize. The Prize in Physiology or Medicine displayed a long lag time, with no women recipients until 1947, when the biochemist Gerty Cori shared the Prize.
NO PRIZE FOR THE DEAD
Two perenially discussed aspects of the Nobel Prizes are the policy against posthumous awards, and the limitation of a given prize to a maximum of three co-recipients. It is of interest to note that neither rule was stipulated in Alfred Nobel’s will nor in the articles of incorporation and by-laws of the awarding bodies. Rather, these policies were simply adopted as operating rules and there is great resistance to changing them, due to the large number of retroactive injustices that would be instantly created.
The policy against making awards posthumously is of course vexing on occasion and by far the most discussed example in recent decades was the 1962 Prize for the structure of DNA. Many believe that had she not died four years earlier, Rosalind Franklin would have received a Nobel Prize (perhaps with Maurice Wilkins in Chemistry), whereas others are certain she would not have. A major point is that she was resistant to advice on the mathematics for solving diffraction by a helix that Francis Crick had offered her (which Crick communicated to me in a letter, and is widely known.) Nonetheless, she had gotten very close by the fall of 1952, recognizing that the bases were in the inside of a two- or three-stranded helix, with the sugar phosphate backbones running along the outside (1
2
3
4)
. But although those were key insights, the dyad symmetry was the necessary breakthrough that Crick instantly recogized. The claim that Crick and Watson got Franklin’s data from an illicitly conveyed document from Max Perutz has been challenged by several historians who have noted that this report was freely available to all labs funded by the British Medical Research Council. Crick’s instant realization of the dyad symmetry (for which he had been prepared by his Ph.D. work on horse hemoglobin) was the enabling discovery because it informed how the anti-parallel alignment of the bases restricted the hydrogen bonding into a subset of possibilities, leaving it for Jim Watson get the base-pairing, arguably the most facile step on the one hand and a most brilliant one on the other.
THE ONES LEFT OUT
Though the rule against posthumous awards has been frustrating on certain occasions, it is the omission of the living that has more often been the basis of controversy. Perhaps the most egregious of all time was the omission of Lisa Meitner, who was passed over by the Committee in selecting Otto Hahn as the sole recipient of the 1945 Physics Prize. Not only was Meitner’s role central to the discovery of nuclear fission, most experts then and now believe that her physical proof of the phenomenon of fission in the transuranium elements ranks with Hahn’s contribution.
In more recent years, a particularly controversial decision was the omission of Keith Porter from the 1974 Prize in Physiology or Medicine. Few doubted that Albert Claude and George Palade were deserving, but some questioned the selection of Christian de Duve over Keith Porter. My own opinion on this is that the Committee viewed Claude as having "fathered" a style of cell research that combined biochemistry and cytology and that, viewed this way, they saw Palade and de Duve as the two direct descendants of this "school." But the winners were not responsible for the key advances that made biological electron microscopy a reality—those contributions were made by Keith Porter. We will have to wait another 18 years to examine this decision, when the 50 year embargo on Nobel nomination deliberations will be lifted for 1974.
Another controversial case was the 1998 Prize in Physiology or Medicine to Robert Furchgott, Louis Ignarro, and Ferid Murad for discoveries concerning the physiological roles of nitric oxide. Two years earlier, the institution of which I am Director, the Worcester Foundation for Biomedical Research, had conferred its prestigious Gregory Pincus Award jointly to Furchgott and Salvador Moncada, regarding them as the two pioneers. When the Nobel Prize was announced, there was an outcry from many scientists including Max Perutz, protesting the Nobel committee’s decision. In the opinion of many, Moncada should have been tapped.
Another aspect of the Nobel Prizes that is a perennial topic of discussion concerns those discoveries, inventions, or advances that go unrecognized altogether. One is the birth control pill. I have just mentioned the Worcester Foundation for Biomedical Research, where pioneering work by Gregory Pincus and M. C. Chang was carried out in the 1950s that led to the first birth control pill. Pincus died in 1967—at the tragic age of only 63, but I doubt that a Nobel Prize would have been awarded in any case. The tributaries flowing into the development of the oral contraceptive were numerous and temporally distributed across two decades, going back to the extraction of a substance from the roots of a jungle plant by Russell Marker that was readily convertible to pregnanediol and then to progesterone in two steps, the subsequent chemical synthesis of progestins by Carl Djerassi, Luis Miramontes, and Alejandro Zaffaroni, and the discovery by Gregory Pincus and M.C. Chang at the Worcester Foundation that a compound sent to be tested by the G. D. Searle Pharmaceutical Company was, contrary to expectations, a potent anti-ovulatory progestin.
The most astonishing Nobel non-recognition of a discovery was that of Oswald Avery’s demonstration that genetic material is DNA. The failure to confer a prize on Avery is widely regarded as one of the greatest misjudgments in Nobel Prize history. It would have surprised no one if several years had elapsed after Avery’s monumental 1944 paper before the Nobel Prize was conferred, but for this epochal discovery to have gone unrecognized by a Prize to Avery at the time of his death in 1955, three years after the Hershey and Chase experiment and two years after the double helix, is truly incomprehensible. The reasons behind this error have recently become known, as the running 50-year embargo on Nobel Prize deliberations has now been lifted in regard to the years in which Avery was under consideration. The bottom line is that it apparently took one key member of the Physiology or Medicine Prize committee almost a decade to accept the conclusion that the gene was DNA (5)
.
In some cases of alleged exclusion, the individual omitted was not an established figure but a quite junior scientist. The most famous such case arose in 1974, when the Physics Prize was awarded to the British astronomers Anthony Hewish and Martin Ryle (the first Nobel Prize in astronomy). The discovery for which Hewish was recognized had actually been made single-handedly by a Ph.D. student, Jocelyn Bell. Her totally independent discovery was that the pulsating radio signals that came to be known as pulsars arrived at the Jodrell Bank telescope at intervals of 23 hours and 56 seconds. From this, she recognized immediately that the signal frequency was keeping pace with the rotation of the stars, the sidereal day—the duration of which is four seconds less than the exactly 24 hour terrestrial day. In a letter published in the Times of London, the distinguished astronomer Fred Hoyle said of Bell’s discovery and insight that it "came from a willingness to contemplate as a serious possibility a phenomenon that all past experience suggested was impossible" and "I have to go back in mind to the discovery of radioactivity ... for a comparable example of a scientific bolt from the blue."
The Nobel Prizes in science are worth about one million dollars these days. Although most laureates keep the prize money, which is expected and carries no stigma, once in a while the winnings are put to other purposes. Albert Einstein gave a good share of his Prize money to his ex-wife, Mileva Maric, whom we now know had been a far more significant scientific collaborator than had once been assumed. In recent times, Gunter Blobel of the Rockefeller University donated his entire one million dollars of unshared prize money in 1999 toward the reconstruction of both a cathedral and a synagogue in Dresden, in his native country, unquestionably the most generous and moving philanthropic act of any Nobel Prize winner in many years.
THE POWER AND THE GLORY
One of the most impressive aspects of the Nobel Prizes is the extraordinary dedication and preparation of the Swedish Academy and Nobel Foundation in arranging the award ceremony and related events. The attention to detail by the numerous staff members assigned to each laureate and their accompanying family members is legendary. The colorful week of Stockholm festivities has been recorded by various Nobel Prize winners but no account of which I am aware has exceeded in its richness of detail that of the 1950 Nobel Prize winner Philip Hench, who shared the Prize for his discovery that cortisone is an effective treatment for arthritis. Shortly after his return from Stockholm, Hench delivered a lecture to his colleagues at the Mayo Clinic in Minnesota, in which he detailed virtually every minute in the entire week of events. Here are a few excerpts from the published version of that lecture:
On Friday morning December 8 our train approached Stockholm through a countryside freshly covered by a heavy snowfall. Every scene looked like a Christmas card. We were driven to the Grand Hotel which was being taken over by the new and old Nobel laureates and their families. In our rooms we found many invitations and the official instructions as to what we had to do, where we should be and what we should wear during the next four days(6)
. Later, Hench describes one of the several banquets held during the week:
1,000 guests assembled in the Great Blue Hall. The banquet was served by 132 waiters and waitresses. As each new course was to be served, the waiters appeared on the balcony and accompanied by regal music marched in formation down the marble stairs to their assigned tables. One of the dramatic moments came at dessert time. Suddenly, except for the candles on the tables, all the lights in the Hall were extinguished. 124 waiters appeared on the balcony, each carrying an illuminated tray of sculptured ice cream flanked by a clear ice sculpture. Each ice sculpture had been frozen around a small battery-run light, each one a different color. As a reporter stated in the next morning’s newspaper: It resembled an ice floe which slowly and majestically swept down the stairway on the shoulders of the waiters(6)
. Here is a final excerpt from Hench’s account, describing the famous Lucia Festival of Light held near the end of the week:
The young woman portraying Lucia, Miss Elisabeth Myerhoffer, was an authentic Swedish beauty, with blond hair and perfect features. As she and her eight attendants slowly entered the Great Hall, they were followed by a choir of boys, singing. As she drew near, I noticed a man in a dark suit walking unobtrusively just a few feet behind her. He was carrying a wet towel just in case Lucia’s hair caught fire from her crown of lighted candles(6)
. UP THE DOWN STAIRCASE
Then there is the perennial question of whether there is some common attribute or attributes that Nobel Prize winners share. It seems a rather silly question really. My own opinion is that the most relevant parameter is the quality of one’s training, often but not always with a Nobel laureate or a Nobel laureate to be. Beyond that, I doubt that there is any common characteristic. But it is likely that sheer determination is often at play in these careers. Let me share one vignette. In 1982, I was the Program Chair for the annual meeting of the American Society for Cell Biology, held that year in Baltimore. One evening we held a social event at the lovely Aquarium situated at the inner harbor there. Around 8 PM, the event was winding down, as scheduled. To convey the approach of the closing, the Aquarium staff turned off the "up" escalators (which had been taking people up to the party on the mezzanine.) At this time, two Nobel laureates arrived, Chris de Duve and George Palade, 65 and 70 years of age respectively. After assessing the escalator situation, they bolted up the still-running "down" escalator instead of using the now-stationary "up" escalator as a regular staircase. As I watched this performance, the thought came to me that although the quality exemplified by their bold, competitive assault upon the "down" escalator was surely not the only reason they had won the Nobel Prize, there could be little question that it was indeed part of the reason.
Finally, let’s return to Alfred Nobel himself. Historians have long debated whether the charitable focus of his will was based on a sense of guilt over the military uses of his invention or perhaps the factory explosion that killed his brother. But whatever were his true motivations, his name deservedly lives on—attached to the greatest Prizes in science, literature, and peace. Let us note that a little inversion of the last two letters in Alfred’s last name transforms it from "Nobel" to "noble." Alfred Nobel has indeed earned true nobility, now known down through the years in all the halls of science and medicine, and in the public eye as well. We thank him for launching his enduring prizes, which serve as spotlights on our profession but also shine as beacons that illuminate the uncharted waters of the future. His prizes have transformed the snows of Stockholm into the stardust of science, for the betterment of mankind. That Alfred also chose to commission a Prize for Peace is a further testament to his ethical core. And, it reminds us that the scientific and technological advances that are recognized by the Nobel Prizes in science can have their full impact on improving the human condition only in a world that is at peace.
We also must thank Alfred for standing up for basic science. He would not be happy to see how ill-conceived downward research funding trends for individual investigators, here in the U.S. and elsewhere, are discouraging the best young people, when all the available evidence indicates that small labs outpace large ones on a dollar spent vs. discovery made ratio (7
8
9)
.
|
FOOTNOTES
Note: This article is adapted from the banquet lecture presented at the Symposium "Optical Analysis of Biomolecular Machines," held at the Max Delbrück Center for Molecular Medicine, Berlin, July 13-16, 2006. Delbrück would have been 100 on September 4, 2006. This essay is dedicated to the longevity of his influence.
The opinions expressed in editorials, essays, letters to the editor, and other articles comprising the Up Front section are those of the authors and do not necessarily reflect the opinions of FASEB or its constituent societies. The FASEB Journal welcomes all points of view and many voices. We look forward to hearing these in the form of op-ed pieces and/or letters from its readers addressed to journals{at}faseb.org
REFERENCES
Related Articles
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
