My father used to say that there is a fine line separating the sublime from the ridiculous, and he was right about this. I have read about people who achieve the sublime. They discover important things that change the world, or perform physical feats, or give speeches, or write books, poems, or songs that serve as an inspiration for millions of people. And then years later I learn these very same people became mired in the ridiculous when they were caught engaging in criminal behavior, or saying or doing embarrassing things, or defending ideas that were wrong, immoral, objectionable, or silly. Even Nobel Prize winning scientists are not immune from this. It seems that for a few scientists, the very thought processes and character traits that led them up the path to the sublime, also thereafter diverted them down the slope to the ridiculous. Today we will take a look at a few of these scientists.
The Sublime – Stark was a German physicist who discovered the splitting of spectral lines of atoms and molecules in an electric field (today known as the Stark effect) which provided an important confirmation of the model of quantum physics of the atom. For this and other discoveries he received the Nobel Prize in physics in 1919.
The Ridiculous – Stark grew very vocal in criticizing mainstream physics and became involved in many disputes and power struggles, growing erratic and disruptive. The German scientific community shunned him, but when Hitler began his rise to power, Stark supported him and attacked the work of Jewish scientists in Germany, especially Albert Einstein. Stark joined the Nazi party, and assumed a leading role in a movement to rid German science of Jewish scientists and their ideas. However, he was eventually sidelined due to his incompetence as an administrator as well as his quarrelsome nature. Stark retired, and after the war he spent one year in jail for his associations with the Nazis.
The Sublime – Shockley was an American physicist who performed vital work for the United States navy during World War II that allowed the US to increase its success in tracking and attacking German submarines as well as evading German bombers, which saved many lives. He led the team at Bell Labs which invented the transistor, and then he improved on the device to produce a version on which most transistors are based today. For this discovery, Shockley and his team were awarded the Nobel Prize in physics in 1956. After leaving Bell Labs, he founded a semiconductor company and attracted the talented people who would later go on to found companies that would usher a technological revolution in electronics in what is now known as Silicon Valley in California.
The Ridiculous – Shockley had a difficult temperament that caused him problems both in his family and professional life. He was rude and arrogant, and his managerial style was that of a dictator. Many people that worked with him for a while ended up leaving or refusing to work with him ever again. After he won the Nobel Prize, he started espousing racist views regarding the excessive reproduction and intellectual inferiority of certain groups of people or races and lashing out against his critics. He died only in the company of his second wife and estranged from his children and former friends and colleagues.
The Sublime – Watson is an American molecular biologist and the co-discoverer with Francis Crick of the structure of the molecule of life, DNA. This single discovery brought about a dramatic transformation in the biological sciences that is still ongoing. Watson along with Crick received the Nobel Prize in Physiology or Medicine in 1962. But what made Watson a household name was his memoir about the discovery of the structure of DNA entitled The Double Helix which he wrote in a brash not-suffer-fools-gladly style which excited the imagination of a generation of scientists.
The Ridiculous – Watson has expressed controversial views including that blacks are less intelligent than whites, that some anti-Semitism is justified, and that women scientists are less effective and not as good at math as men and will not be taken seriously in science if they have children. But he also thinks that having some female scientists around makes things “more fun for the men”. He has also claimed that fat people are less ambitious than thin people, that libido is linked to skin color, and that if it were possible, parents should be allowed to choose the traits of their unborn children such as not choosing to have a homosexual child.
The Sublime – Gajdusek was an American physician who studied a rare and puzzling disease called Kuru prevalent among members of the Fore tribe in New Guinea. He found that it was spread by ritualistic brain cannibalism, and he succeeded in transmitting the disease to chimpanzees by injecting human brain extracts into their brains. Gajdusek observed that Kuru had similarities to another human disease called Creutzfeldt–Jakob disease and to a disease of sheep called scrapie, and he proposed that the pathogen was a previously unknown infectious agent which he termed “unconventional virus”. Gajdusek received the Nobel Prize in medicine and physiology in 1976 for his work on new mechanisms of dissemination of infectious disease. The pathogens in these diseases were later found to be misfolded proteins called prions.
The Ridiculous – Over the years Gajdusek adopted many boys from the Fore tribe, brought them over to the U.S. to live with him, and put them through high school and college. One of these individuals accused Gajdusek of molesting him when he was a child. Gajdusek pled guilty to the charge and spent one year in jail after which he was released, relocated to Europe, and never came back to the U.S.
The Sublime – Mullis was an American biochemist who invented a method to amplify DNA, the polymerase chain reaction (PCR), which brought about a revolution in areas ranging from medicine to forensics. PCR is used in the diagnostic test for COVID-19. Mullis received the Nobel Prize in Chemistry in 1993.
The Ridiculous – Mullis became infamous for his belligerent attitude and outrageous eccentric behavior. For example, he was once invited to give a lecture about PCR, and instead he criticized the science behind the treatment of AIDS, and the only slides he presented were photographs of naked women. His professed belief in astrology, ghosts, and aliens, as well as his denial of the ozone hole, global warming, or that the HIV virus causes AIDs also made him toxic in the eyes of most scientists.
The Sublime – Montagnier is a French virologist who with Françoise Barré-Sinoussi won the 2008 Nobel Prize in physiology or medicine for their discovery of the AIDS virus (HIV). This discovery along with the work of Robert Gallo in the United States made it possible to produce antivirals and save the lives of millions of people.
The Ridiculous – After receiving his Nobel Prize, Montagnier started publishing research claiming that DNA can emit electromagnetic waves and create a memory of itself in the water used to dissolve it. He also claimed that this memory emits such waves allowing the DNA to teleport between solutions. Montagnier’s claims were interpreted as favoring the pseudoscience of homeopathy. He has also given talks at anti-vaccination conferences, claimed that AIDS can be cleared through nutrition and supplements, and that the COVID-19 virus is man-made. Montagnier has become a pariah to the scientific community.
As the above list (which is by no means exhaustive) shows, scientists are human beings, and even Nobel Prize winning scientists can make errors of judgement and display all the character flaws and contradictions that affect average individuals, and this can take some of them all the way from the sublime to the ridiculous.
Photograph of Johannes Stark by A. B. Lagrelius & Westphal is in the public domain. Photograph of William Shockley by Chuck Painter is used here under an Attribution 3.0 Unported (CC BY 3.0) license. The photographs of James Watson and Carleton Gajdusek are works of the NIH and therefore are in the public domain. The photograph of Kary Mullis by Dona Mapston is used here under an Attribution-ShareAlike 3.0 Unported (CC BY-SA 3.0) license. Photograph of Luc Montagnier by Prolineserver is in the public domain.
Suicide is often considered an irrational decision, and while that may be the case in conditions like mental illness or dire emotional states, the situation is not as clear when this action is the product of a well thought out end of life decision. Among all people, scientists have the reputation of being smart individuals, and among all scientists, presumably the smartest are those that win a Nobel Prize. There are few Nobel Prize winners that have taken their own lives. Was this irrational? Today we will take a look at these individuals and their motivations.
Emil Fischer was a German chemist who was one of the towering scientific figures of the early 20th century, and who is considered the father of biochemistry. He discovered and synthesized many molecules such as caffeine, which is the substance in coffee that keeps you awake, and theobromine, which is the substance that makes dogs sick if you feed them too much chocolate. With fellow chemist Josef von Mering, Fischer made the first of the biologically active barbiturates, barbital (sold as Veronal), which has strong sedative properties. He defined the structure of many carbohydrates and was the first to synthesize glucose, the building block of cellulose and starch. For these and other discoveries, Fischer received the Nobel Prize in chemistry in 1902. All the foregoing seems to be something positive to feel good about, but unfortunately in the personal realm, things didn’t go as well.
Fischer’s wife had died 7 years after their marriage leaving him to raise 3 sons alone. During the First World War, Fischer enthusiastically joined the war effort, coordinating the interaction between industry, academia, and the military. However, as the war dragged on, he became disillusioned with it and the heavy toll it was taking on German society. In addition to this, two of his sons died during the war. Fisher himself developed ill-health due to exposure to some of the compounds with which he worked in the lab over the years. Depressed over the effects of the war on his country and the deaths of his two sons, a diagnosis of intestinal cancer seemed to push him over the edge, and he committed suicide in 1919 using cyanide, one of the compounds he had successfully employed in his research.
Hans Fischer was a German chemist who won the Nobel Prize in Chemistry in 1930 for working out the structure of hemin and performing its synthesis (hemin is the core of the hemoglobin molecule that makes possible the transport of oxygen in the blood), and for his work on the structure of chlorophyll, which is the pigment in plants that makes photosynthesis possible. He also figured out the structure of bilirubin (the pigment that gives sufferers of jaundice their yellow color) and synthesized it. He is not related to Emil Fischer, but he worked as his laboratory assistant for two years. Hans married but never had children. Although he was an avid outdoorsman, he was a man mostly devoted to his work. Unfortunately, his laboratory and most of his life’s work was obliterated during a bombing in the last days of World War II. As a result of this, Fischer fell into depression and committed suicide in 1945 at the age of 63.
John Howard Northrop was an American biochemist who won the 1946 Nobel Prize in Chemistry for his work in isolating and crystalizing proteins. One of his critical achievements was demonstrating that enzymes were proteins. Northrop was an enthusiastic fisherman and hunter who remained active into his nineties, but as he got older and weaker, although he remained lucid, he may have viewed his future with concern about becoming a burden for his family and friends. Northrop committed suicide in 1987 at the age of 96.
Percy Williams Bridgman was an American physicist who discovered that the properties of substances change dramatically under high pressures. His work had a profound influence in areas such as the understanding of Earth’s geology at great depths, and won him the Nobel Prize in physics in 1946. Beyond that, Bridgman was an excellent family man, philosopher, teacher, plumber, carpenter, gardener, and piano player! He was admired and loved by many. So why is his name in this list?
Bridgman developed a serious difficulty in using his legs and was afflicted with intense pain and fatigue. He was diagnosed with metastatic bone cancer. When he realized he would be dead in a matter of months he asked the physicians who examined him to provide him something he could take to take his life. When they refused, he committed suicide by shooting himself in 1961 at the age of 80. A note found in his pocket that has been quoted by many proponents of assisted suicide read: "It isn't decent for Society to make a man do this thing himself. Probably this is the last day I will be able to do it myself."
Stanford Moore was an American biochemist who received the Nobel Prize in Chemistry in 1972. His invention of a machine to analyze amino acids (the building blocks of proteins) made it possible to figure out the linear structure of complex proteins and relate their function to their structure. This achievement heralded the “protein era” in biochemistry which had widespread effects on areas ranging from medicine to industry. Moore never married and was not interested in material gain or personal possessions (he never patented any of the methods or instruments he invented). He was extremely organized and led a frugal lifestyle totally devoted to science working long hours and weekends. He was diagnosed with amyotrophic lateral sclerosis (Lou Gehrig's disease), and his mobility and health became progressively impaired. In 1982 at the age of 68 after putting his affairs in order, he committed suicide in his apartment.
Christian de Duve was a Belgian cytologist who won the Nobel Prize in Physiology and Medicine in 1974 for discoveries regarding the structural and functional organization of cells. His approach of “exploring cells with a centrifuge” brought about a revolution in cell biology and biochemistry, and permitted him to discover two important cell organelles, the lysosome and the peroxisome which in turn helped scientists make many advances and understand the etiology behind dozens of genetic diseases. He considered his life to be “extraordinarily rewarding” and full of “joy and pleasure”, but towards the end he developed a host of health problems including cancer, and suffered a fall that incapacitated him. de Duve lived in Belgium where physician-assisted suicide is legal. In 2013 at the age of 95 de Duve surrounded by his family and assisted by two doctors took his life. One of his daughters said, “He bid us adieu, and he smiled at us, and then he left us.”
All the scientists featured here were bright accomplished individuals who changed the world with their work. Whereas dire life circumstances were a component of the decisions made by Emil and Hans Fischer to end their lives, the end-of-life decisions of the rest of the scientists mentioned here had a motivation rooted in infirmity. I do not view the decisions of highly intelligent lucid men like Northrop, Bridgman, and Moore as irrational, but I view the fact that they had to carry them out as secretive affairs alone and away from family and friends as tragic. Contrast their suicides with that of de Duve which was really a formal and celebrated end to an exceptional life.
Science cannot tell us whether suicide is good or bad, or moral or immoral - that is the realm of ethics, philosophy, and religion. But I believe that if we are willing to bestow a Nobel Prize to individuals as recognition for achievements that derived from their intellects, we should be willing to be equally gracious when these intellects decide it’s time for an end-of-life decision. And you should not need to win a Nobel Prize to be worthy of this kind of respect.
Photo of Emil Fischer by Atelier Victoria (Inh. Paul Gericke, gegr. 1894), Berlin is in the public domain. Photos from the Nobel Foundation of Percy Williams Bridgman, Hans Fisher, and John Howard Northrop are in the public domain. The photograph of Stanford Moore is used here under the doctrine of Fair Use. The photograph of Christian de Duve by Julien Doornaert is used here under an Attribution 2.5 Generic (CC BY 2.5) license.
As modern science took off in the late 19th and early 20th century, women struggled to join the ranks of the scientists. There were social mores against the education of women claiming that doing so would make them “unmarriageable”, as well as notions (some enshrined under the guise of “science”) such as that women were more “unreliable” and “unstable” compared to men because the uterus in women made them more prone to weaknesses and illnesses (the word “hysteria” comes from the Greek word for uterus). Some prominent doctors even argued (I’m not kidding) that higher education placed women at risk because diverting blood from the reproductive organs to the brain could result in nervous collapse, physical breakdown, and infertility!
But even when women did get an education and became scientists, they faced many obstacles to the advancement of their careers and experienced difficulties in getting paying jobs as scientists and earning the same as men. Some of these obstacles are still in place nowadays. A combination of the early dearth of women in science coupled with the discrimination they had to endure resulted in women being underrepresented in the accolades to scientific achievement, the most important of which is the Nobel Prize. As of 2019, only 20 Nobel Prizes have been awarded to women in a scientific discipline compared to 596 to men. In this post we will learn about the ladies who attained the highest laurel in science.
Marie Curie was a Polish-French physicist who with her husband Pierre Curie won the Nobel Prize in Physics in 1903, which they shared with Henry Becquerel, for work performed in the emerging field of radiation. The French Academy of Science wanted to nominate only her husband and Becquerel for the prize, but Pierre interceded for her and got the Academy to include Marie’s name in the nomination. Marie Curie also won a second Nobel Prize, this time in chemistry, in 1911 for her work in discovering the new elements Radium and Polonium (her husband had died in an accident in 1906). She is the only woman to have won two Nobel Prizes, and one of the two persons who have earned the prize in separate disciplines.
Irene Joliot-Curie was a French chemist and physicist and the daughter of Marie and Pierre Curie. She shared the Nobel Prize in Chemistry with her husband Frédéric Joliot-Curie in 1935 for their discovery or artificial radioactivity. Their discovery made possible the synthesis of radioactive elements for specific applications. Yet Irene Joliot-Curie was often discriminated against by people who argued that she was just an assistant to her husband’s work.
Gerty Theresa Cori was an Austro-Hungarian-American biochemist who with her husband Carl Cori won the Nobel Prize in Physiology or Medicine in 1947, which they shared with Bernardo Houssay, for important work on how the body metabolizes carbohydrates. This work benefited the treatment of diabetes. Gerty Cori became the first woman to win the prize in this discipline, but she encountered discrimination during her life not only for being a woman but also for being Jewish.
Maria Goeppert Mayer was a German-American Physicist who won the Nobel Prize in Physics in 1963, which she shared with J. Hans D. Jensen and Eugene Wigner, for the elucidation of the structure of the nuclear shell of the atom. Goeppert Mayer became the first woman not to share a Nobel Prize with her husband (the exception being the second Nobel Prize of Marie Curie), and the second woman to earn a Nobel Prize in Physics. It had been 60 years since Marie Curie had won hers, and it would be 55 years before another woman won this prize again (see later).
Dorothy Crowfoot Hodgkin was a British chemist who won the Nobel Prize in Chemistry in 1964 for her work in using techniques of X-ray diffraction to determine the structure of many biological molecules, among which were the antibiotic penicillin, vitamin B12, and the hormone insulin, all of which made possible many advances in medicine. Early on in her career at the University of Oxford, she had to struggle with being excluded from male-dominated mainstream scientific activities, and being relegated to work in inferior lab premises with inadequate equipment.
Rosalyn Sussman Yalow was an American physicist who won the Nobel Prize in Physiology or Medicine in 1977, which she shared with Roger Guillemin and Andrew V. Schally. Her work in the development of the radioimmunoassay to measure very low levels of hormones ushered a revolution in the medical sciences. She suffered both sex and religious discrimination, but she had a remarkably strong character and famously declared "I never thought that there was anything the matter with me. I just feel sorry for the discriminators".
Barbara McClintock was an American geneticist who was awarded the Nobel Prize in Physiology or Medicine in 1983 for her discovery of transposable elements, which are popularly known as “jumping genes”. This is the only time that a woman has won an unshared prize in this category. She endured decades of discrimination in many forms and her work with transposons was so ahead of her time that it took more than 10 years for her discovery to be accepted by mainstream science.
Rita Levi-Montalcini was an Italian scientist who with Stanley Cohen won the Nobel Prize in Physiology or Medicine in 1986 for their discovery of Nerve Growth Factor (NGF) which promotes the proliferation, growth, and survival of cells. During her life Rita Levi-Montalcini had to deal with discrimination not only for being a woman but also for being a Jew. During the fascist regime of Benito Mussolini, she was laid off from her job at the University in 1938 and had to go into hiding with her family fearing for their lives. But even in these dire conditions she managed to continue her research by setting up a lab in her bedroom!
Gertrude B. Elion was an American biochemist who with George H. Hitchings won the 1988 Nobel Prize in Physiology or Medicine, which they shared with Sir James Black, for using new methods to design drugs. Unlike earlier methods based on trial and error, the procedures they employed used knowledge of the biochemistry of the diseases they were targeting (rational drug design) and led to the production of numerous pharmaceuticals which are used in areas ranging from cancer and AIDS to organ transplantation. She had trouble starting her career due to both being a woman and the times (the Great Depression). She was turned down by 15 graduate schools to which she applied, and supported herself by working in a number of different jobs while volunteering at labs.
Christiane Nüsslein-Volhard is a German developmental biologist who with Eric F. Wieschaus won the Nobel Prize in Physiology or Medicine in 1995, which they shared with Edward B. Lewis, for their discoveries in the control of embryonic development. These discoveries affected aspects of many disciplines ranging from embryology to evolution. She has remarked that during her career she would often find that many men would have a hard time accepting that a woman could be smarter than them, particularly when she pointed out mistakes that they had made, and this led to many difficulties.
Linda B. Buck is an American biologist who with Richard Axel won the 2004 Nobel Prize in Physiology or Medicine for their work in identifying a family of genes that produce olfactory receptors (the structures in our noses with which we detect smells) and how these receptors are organized to generate the sensation of smell in the brain. She has stated, “As a woman in science, I sincerely hope that my receiving a Nobel Prize will send a message to young women everywhere that the doors are open to them and that they should follow their dreams.”
Françoise Barré-Sinoussi is a French virologist who with Luc Montagnier won the Nobel Prize in Physiology or Medicine in 2008, which they shared with Harald zur Hausen, for their discovery of the AIDS virus, HIV. This discovery, along with the work of Robert Gallo in the United States, made it possible to eventually produce antivirals and save the lives of millions of people. Barré-Sinoussi tells the story of how, as she was nearing the completion of her doctorate degree at the Pasteur Institute, she sought the advice of one of the senior staff members regarding the possibility that she could remain working at the institute. He replied, “A woman in science, they never do anything. They are only good at caring for the home and babies. Forget this dream.” Millions of AIDS patients are lucky that she decided to pursue the dream!
Elizabeth Helen Blackburn, an Australian, and Carol W. Greider, an American, are both molecular biologists who won the Nobel Prize in Physiology or Medicine in 2009, which they shared with Jack W. Szostak, for the discovery of telomeres and the enzyme that maintains them (telomerase). Telomeres protect the integrity of chromosomes, and their discovery has had a large impact in many fields ranging from cancer to aging. Early in her career, Greider had to overcome dyslexia and later, as she described it, she had to “face the challenge of being a woman with children in a man’s world”. Blackburn has written often about the right of every woman to choose a career without fear of discrimination for embracing motherhood.
Ada E. Yonath is an Israeli crystallographer who won the Nobel Prize in Chemistry in 2009, which she shared with Venkatraman Ramakrishnan and Thomas A. Steitz, for her work in elucidating the structure and modes of action of ribosomes, which are the structures in the cells where proteins are made. Although she has stated that she never felt any gender discrimination throughout her career, she thinks that, “There are fewer women in science because society doesn’t encourage women to become scientists.” Yonath became only the fourth woman to win a Nobel Prize in chemistry, and the first in 45 years since Dorothy Crowfoot Hodgkin won it in 1964.
May-Britt Moser is a Norwegian neuroscientist who along with her husband Edvard I. Moser won the Nobel Prize in Physiology or Medicine in 2014, which they shared with John O'Keefe, for their discovery of neurons in the brain (grid cells) that are responsible for processing the information about the location of an animal with respect to its environment. She has remarked that getting women into science is important to change the culture, because if men are not accustomed to working with women, they will continue to only support other men.
Tu Youyou is a Chinese pharmaceutical chemist who won the Nobel Prize in Physiology or Medicine in 2015, with she shared with William C. Campbell and Satoshi Ōmura, for her role in the discovery of a compound, artemisinin, derived from a traditional Chinese herb (Wormwood). This chemical has been used against malaria saving the lives of millions of people. Since the setting in which Youyou made her discovery was part of a secret military project, her role in the discovery only became known 25 years later when Western scientists from the NIH managed to track her down by reading old government documents. Her contribution had never been recognized in China due to discrimination. Youyou was known as “the professor of the three Nos”: no post-graduate degree, no membership in the Chinese Academy of Sciences, and no research experience outside China.
Donna Theo Strickland is a Canadian physicist who with Gérard Mourou won the Nobel Prize in Physics in 2018, which they shared with Arthur Ashkin, for work that allowed the production of very short and intense laser pulses. This development has now been applied in areas such as eye surgery. Strickland is the third woman to receive a Nobel Prize in physics. She has stated that during her career she has always been treated as an equal by the men around her and she has been paid the same as them. This is quite a change from her predecessor Nobel laureate in Physics, Maria Goeppert Mayer, who was not offered a paying job related to her career until after she did her Nobel Prize winning work!
Frances Hamilton Arnold is an American Chemical Engineer who won the Nobel Prize in Chemistry in 2018, which she shared with George P. Smith and Sir Gregory P. Winter, for her use of directed evolution to engineer enzymes with new activities; a process that has found wide applications in industry and science. She has stated that she has experienced stupid sexist remarks and behavior in her career, but that she is gifted with the ability to ignore the people who made them. She considers the fact that she and Donna Strickland both won a Nobel Prize in 2018 may be the beginning of a steady stream of female Nobel Prize winners, and her message for young women is, “Don’t leave this wonderful, fun work just for the men.”
Photo of Marie Curie from Tekniska museet’s flickr page (author unknown) is used here under an Attribution 2.0 Generic (CC BY 2.0) license. The photograph of Irene Joliot Curie from the Smithsonian Institution has no known copyright restrictions. The photograph of Gerty Theresa Cori from the National Institutes of Health is in the public domain. Portrait of Maria Goeppert Mayer from the United States Department of Energy is in the public domain. The image of Dorothy Hodgkin from nobelprize.org is used here under the doctrine of Fair Use. The photo of Rosalyn Yalow from the United States Information Agency is in the public domain. The photograph of Barbara McClintock from the Smithsonian Institution has no known copyright restriction. Photo of Rita Levi Montalcini by the Presidenza della Repubblica Italiana is free for use with attribution. Photo of Gertrude Elion from the Welcome Collection is used here under an Attribution 4.0 International (CC BY 4.0) license. Photo of Christiane Nüsslein-Volhard by Rama is used here under an Attribution-ShareAlike 2.0 France (CC BY-SA 2.0 FR) license. The Linda Buck photograph from the Royal Society is used here under an Attribution-Share Alike 3.0 Unported license. Photo of Françoise Barré-Sinoussi by Prolineserver is used here under an Attribution NonCommercial ShareAlike 2.0 license. Photo of Carol Greider and Elizabeth Blackburn by Gerbil is used here under an Attribution-Share Alike 3.0 Unported license. Photo of Ada E. Yonath by Hareesh N. Nampoothiri is used here under an Attribution-Share Alike 3.0 Unported license. Photo of May-Britt Moser by Henrik Fjørtoft/NTNU Komm.avd is used here under an Attribution-Share Alike 2.0 Generic license. Photo of Tu You you by Bengt Nyman is used here under an Attribution-Share Alike 4.0 International license. Photos of Donna Strickland and Frances Arnold by Bengt Nyman are used here under an Attribution 2.0 Generic license.
Nobel Prize Winners and the Basics of What it Takes to Do Science at the Highest LevelRead Now
Most scientists have ideas about how science is done, but those that have won a Nobel Prize probably know a thing or two that others don’t. Winning a Nobel Prize in science often means that you had an idea few others had and pursued it to discover something so important that it changed the world. So by virtue of having gone through this process, Nobel Prize winners probably know what it takes to do science at the highest level. Here I have put together a narrative regarding the basics behind doing this type of science, and I have supported it with a few quotes from those who made their pilgrimage to Stockholm to be bestowed the ultimate honor.
The first step in the basics of doing Nobel Prize level science is training. With whom should a would-be Nobel laurate train? The German-British biochemist, Hans Krebs, who won the Nobel Prize in 1953 for the discovery of important pathways in metabolism, had this to say:
What, then, is it in particular that can be learned from teachers of special distinction? Above all, what they teach is high standards. We measure everything, including ourselves, by comparisons; and in the absence of someone with outstanding ability there is a risk that we easily come to believe that we are excellent and much better than the next man. Mediocre people may appear big to themselves (and to others) if they are surrounded by small circumstances. By the same token, big people feel dwarfed in the company of giants, and this is a most useful feeling. So what the giants of science teach us is to see ourselves modestly and not to overrate ourselves.
This concept is not appreciated by many who are contemplating a career in the sciences. In most cases, excellent scientists have been trained by excellent mentors, and excellent scientists are maintained that way by keeping the company of those who are equal to or better than them (more on that later).
The next step is choosing the scientific problem that is to be tackled. Here I am not talking about a problem, I am talking about the problem, the line of research that will define a career and will be pursued probably for decades. The British molecular biologist, Francis Crick, co-recipient with James Watson and Maurice Wilkins of the Nobel Prize in 1962 for the discovery of the structure of the molecule of life, DNA, had this to say about this issue:
The major credit I think Jim (James Watson) and I deserve … is for selecting the right problem and sticking to it. It’s true that by blundering about we stumbled on gold, but the fact remains that we were looking for gold. Both of us had decided, quite independently of each other, that the central problem in molecular biology was the chemical structure of the gene. … We could not see what the answer was, but we considered it so important that we were determined to think about it long and hard, from any relevant point of view.
The importance of the selection of the right problem is something that is not understood even by many very smart scientists. The British biologist, Peter Medawar, who received a Nobel Prize in 1960 for his discovery of acquired immunological tolerance, framed this perfectly when he wrote the following about Crick’s colleague, James Watson:
It just so happens that during the 1950s, the first great age of molecular biology, the English schools of Oxford and particularly of Cambridge produced more than a score of graduates of quite outstanding ability - much more brilliant, inventive, articulate and dialectically skillful than most young scientists; right up in the Jim Watson class. But Watson had one towering advantage over all of them: in addition to being extremely clever he had something important to be clever about.
Those that ended up winning a Nobel Prize often had the vision early on in their careers to choose the right problem to work on.
Once someone gets started in researching the right problem, the next step is asking questions and having ideas as to how these questions will be answered. But all scientists ask questions and have ideas. What is it that allows some scientists to make the great discoveries?
The Hungarian biochemist, Albert Szent-Gyorgyi, who won the Nobel Prize in 1937 for research into how the body uses nutrients and for the discovery of vitamin C, explained what is behind the process of discovery in the following way:
Discovery consists of seeing what everybody has seen and thinking what nobody has thought.
And the German physicist, Albert Einstein, who won a Nobel Prize in 1922 for his work in Theoretical Physics and his discovery of the law of the photoelectric effect, explained it this way:
To raise new questions, new possibilities, to regard old problems from a new angle requires creative imagination and marks real advances in science.
Finally, Hans Krebs (whom I quoted before) was quoted as telling the following to new researchers joining his laboratory:
“I can teach you how to dig, but I can’t teach you where to dig.”
This ability to “think what nobody has thought after looking at what everyone has seen”, to display “creative imagination”, and to “dig in the right place”, is something that unfortunately cannot be taught. It’s a talent like those possessed by high performing athletes, virtuoso musicians, or inspired painters. You either have it, or you don’t. Scientists, like athletes, musicians, or painters, can improve their skills over the years, but being able to perform at a Nobel Prize-worthy level for any significant amount of time is something that can’t be learned or acquired with experience.
Apart from the above, once scientists are on their way to Nobel Prize level discoveries, what else do they need to do? The American physicist, Richard Feynman, who won the Nobel Prize in 1965 for his work in quantum electrodynamics volunteered this wisdom:
The first principle is that you must not fool yourself—and you are the easiest person to fool. So you have to be very careful about that. After you’ve not fooled yourself, it’s easy not to fool other scientists. You just have to be honest in a conventional way after that.
And along the way to becoming experts, scientists will make mistakes and will also see others make mistakes. This experience is important. As the German physicist, Werner Heisenberg, who won the Nobel Prize in 1932 for his work in the creation of quantum mechanics, wrote:
An expert is someone who knows some of the worst mistakes that can be made in his subject, and how to avoid them.
So what can scientists do to avoid fooling themselves and to recognize and learn from their mistakes? A possible answer to this question is: collaboration (the right kind). Francis Crick (whom I quoted before) had this to say about the right kind of collaboration talking about his interaction with his colleague, James Watson:
If, for example, I had some idea, which, as it turned out would, say, be quite wrong, was going off of the tangent, Watson would tell me in no uncertain terms this was nonsense, and vice-versa. If he had some idea I didn’t like and I would say so and this would shake his thinking about it and draw him back again. And in fact, it’s one of the requirements for collaboration of this sort that you must be perfectly candid, one might almost say rude, to the person you are working with. It’s useless, working with somebody who’s either much too junior than yourself, or much too senior, because then politeness creeps in. And this is the end of all real collaboration in science.
I believe the foregoing pretty much sums up the basics for performing science at its highest levels. However, I don’t want to give the impression that Nobel Prize level science is the only worthwhile science. Most scientists make incremental contributions to scientific progress and move their fields along the path of discovery producing useful applications. These scientists will never earn a Nobel Prize, but their research benefits society in many ways.
Photograph of Hans Krebs by the Nobel Foundation is in the public domain and has been modified from the original. Photo of Francis Crick by Marc Lieberman is used here under an Attribution 2.5 Generic (CC BY 2.5) license. Photo of Peter Medawar from the Wellcome Collection is used here under an Attribution 4.0 International (CC BY 4.0) license. Photo of Albert Szent-Gyorgyi by Fortepan from the Semmelweis University Archives is used here under an Attribution 4.0 International (CC BY 4.0) license. The photograph of Albert Einstein by Orren Jack Turner obtained from the Library of Congress is in the public domain. Photo of Richard Feynman from the Yearbook of The California Institute of Technology is in the public domain. Photograph of Werner Heisenberg from the German Federal Archives is used here under an Attribution-ShareAlike 3.0 Germany (CC BY-SA 3.0 DE) license.
Winning the Nobel Prize is a crowning achievement for any scientist. It is recognition that said scientist has had a real world impact and made a major contribution to the advancement of knowledge. Nevertheless, there are some drawbacks to winning the Nobel Prize. Upon reading this, some scientists would reply, “Oh, yeah? Just try me!” I know. I know. Most scientists would rather have a Nobel Prize than not. But one of the problems with a Nobel Prize is the perception that it represents the peak in a scientist’s career, and that from there on it’s mostly a downhill ride.
Now, don’t get me wrong. Most scientists remain active in research and make many important contributions after winning a Nobel Prize. But the majority of scientists remain active in the field in which they won the prize, as opposed to switching to a different field and making a new discovery. Therefore their work after winning the prize is often perceived to be the fill-in work by individuals engaged in an activity characterized by diminishing returns. It is difficult to shake off the notion that, if you’ve won a Nobel Prize, you are a “has been” whose future work will never reach the level achieved by your earlier work.
However, what if you won a second Nobel Prize? Now, that would be something, wouldn’t it? It would very clearly convey the message that you’ve still have “IT”. So has anybody achieved this feat? In the 119 years during which the Nobel Prizes have been awarded, only four individuals have achieved this.
Marie Curie was a Polish-French physicist and chemist who, along with her husband, Pierre Curie, performed important work in the emerging field of radioactivity. For this work they shared the Physics Nobel Prize in 1903 with another pioneer in radiation studies, Henry Becquerel. Interestingly, and reflecting the prejudice of the times, the French Academy of Sciences was considering only nominating her husband and Becquerel for the award, but Pierre Curie complained that her contribution was also important, and they were both nominated and won. Marie Curie won a second Nobel Prize, this time in chemistry, in 1911 for her work in discovering the new elements Radium and Polonium (her husband had died in an accident in 1906). She is so far the only woman to have earned two Nobel prizes, and only one of two persons who has earned the prize in separate disciplines. It should be mentioned here that Marie’s daughter, Irene Joliot-Curie, along with her husband Frederick won the Nobel Prize in 1935 in chemistry for their synthesis of new radioactive elements. This makes the Curies the winningest family when it comes to Nobel Prizes, with a total of five!
Linus Pauling was an American chemist and biochemist who performed important work in the structure of biological molecules and the nature of the chemical bond. For his work he was awarded the Nobel Prize in chemistry in 1954. Pauling remained active in this area, but his concerns regarding the proliferation of atomic weapons led him to spearhead a movement to reduce the number of atomic weapons and ban their testing. For his activism, Pauling was awarded the Nobel Prize in Peace in 1963. Pauling was the second person (after Marie Curie) to win two Nobel Prizes in different disciplines, but in his case he was the sole winner. He did not share his prizes with anyone!
John Bardeen was an electrical engineer and physicist who with Walter Brattain invented the transistor while working at Bell Labs in 1947. This invention caused a revolution in the field of electronics and made possible most modern electrical devices that we use today. For their work, Bardeen and Brattain were honored with the Nobel Prize in physics in 1956, which they shared with William Shockley. However, after Bardeen left the emerging transistor field, he developed, along with Leon Cooper and John Schrieffer, a theory to explain the phenomenon of superconductivity (commonly called the BCS theory), for which all three were awarded the Nobel Prize in 1972. In this way, Bardeen became the first individual to receive the Nobel Prize for work carried out in two fields of research within the same discipline!
The British biochemist, Frederick Sanger, was the first person to sequence and determine the structure of the very important protein hormone, insulin. This achievement not only revolutionized the study of proteins but also paved the way for the production of synthetic insulin. For this achievement he received the Nobel Prize in chemistry in 1958. Sanger then, focused his energies on DNA, the molecule that carries the instructions to produce living things. He devised methods to determine the long sequences of this molecule, and this achievement led to the determination of sequences of DNA and related molecules from many organisms including humans, as well as to the identification of the DNA changes underlying genetic diseases. Sanger’s methodological contributions also served to launch the modern disciplines of molecular biology and biotechnology. For these achievements, Sanger received again the Nobel Prize in chemistry in 1980, which he shared with Paul Berg, and Walter Gilbert, thus becoming the second person ever to have received two Nobel Prizes in the same discipline.
No one has won two Nobel Prizes since Sanger in 1980, and no one has won them in the discipline of physiology and medicine. Similarly, no one has won three Nobel Prizes (and some people would argue that the human lifespan and the dynamics of Nobel Prize worthy achievements are such that this is impossible). So far, Marie Curie, Linus Pauling, John Bardeen, and Frederick Sanger represent or are very close to the peak performance attainable by the human mind in the field of science. After winning their first Nobel Prize, these people proved to the world that they still had “IT”!
The 1911 photograph of Marie Curie published in 1912 in Sweden (Generalstabens Litografiska Anstalt Stockholm) is in the public domain. The 1962 photo of Linus Pauling and the 1955 photo of John Bardeen by the Nobel foundation are in the public domain. The NIH photo of Frederick Sanger is in the public domain.
Heroic ScienceRead Now
Most scientists have it easy. By this I don’t mean that science is easy, but rather that scientists experiment on animals or OTHER people. Sure, these experiments are conducted following ethical guidelines to minimize pain to laboratory animals or to ensure the safety of patients, but the point of my argument is that it’s easy to administer a treatment that makes the entity receiving said treatment sick, or that carries other risks, when that entity is not yourself. However, throughout the history of science some scientists have broken through the wall of security that separated them from their test subjects and became their own lab rats, their own patients. These scientists who experimented on themselves conducted what I call “heroic science”. Let’s look at some of these characters.
In a previous post, I mentioned the case of the Australian physician Dr. Barry Marshall who wanted to convince skeptical fellow scientists that ulcers were not caused by excessive stomach acid secretion due to stress, but rather by a bacteria called Helicobacter pylori. Unable to develop an animal model or to obtain funds to perform a human study, he experimented on himself by drinking a broth containing Helicobacter Pylori isolated from a patient who had developed severe gastritis. He developed the same symptoms as the patient and was able to cure himself with antibiotics. As a result of this and other studies, Dr. Marshall was awarded a Nobel Prize in 2005.
Another of these heroic individuals was Werner Forssmann, who as a resident in cardiology in a German hospital wanted to try a procedure to insert a catheter through a vein all the way to the heart. Forssmann was convinced that if this could be done, it would allow doctors to diagnose and treat heart ailments. However, he could not obtain permission from his superiors to perform the experiment on a patient, so he tried it on himself. He made an incision in his arm, inserted a tube, and guiding himself with X-ray photography, he pushed the tube all the way to his heart. At the time there was a lot of opposition to Forssmann and his unorthodox methods, and although he persevered for some time, he became a pariah in the cardiology field and was forced to switch disciplines becoming a urologist. However, eventually other scientists refined the technique of catheterization described in his work, and developed it into valuable medical procedures that have saved many lives. Forssmann had the last laugh when he was awarded the Nobel Prize in 1956.
Most heroic science studies didn’t lead to a Nobel Prize, but some resulted in useful information. For example, John Stapp was an air force officer who experimented on himself to test the limits of human endurance in acceleration and deceleration experiments. He would be strapped to a rocket that would rapidly accelerate to speeds of hundreds of miles per hour and then stop within seconds. As a result of these brutal experiments, Stapp suffered concussions and broke several bones, but he survived, and the knowledge generated by his research eventually resulted in technologies and guidelines that today protect both car drivers and airplane pilots.
Despite its appearance of recklessness, heroic science is seldom performed in a vacuum, but rather it is performed by individuals who believe that, based on other evidence, nothing will happen to them.
Such was the case of Dr. Joseph Goldberger. In the early 1900s, the disease Pellagra afflicted tens of thousands of people in the United States. Dr. Joseph Goldberger performed experiments that indicated that Pellagra was a disease that arose due to a dietary deficiency rather than a germ. Faced with recalcitrant opposition to his ideas, Goldberger and his assistants injected themselves with blood from people afflicted with Pellagra and applied secretions from the patient’s noses and throats to their own. They also held “filth parties” where they swallowed capsules containing scabs obtained from the rashes that patients with Pellagra developed. None of them developed Pellagra. This along with other evidence demonstrated that Pellagra was not a disease carried by germs.
Another case was that of the American surgeon Nicholas Senn, who in 1901 implanted under his skin a piece of cancerous tissue that he had just removed from a patient. As he expected, he never developed cancer. Senn did this to demonstrate that cancer is not produced by a microbe, as it is not transmissible from one human to another, although at the time there were many pieces of evidence that taken together indicated that this was the case.
Of course, the mere fact that you perform heroic science doesn’t mean that you will reach the right conclusions.
Back in 1892 the German chemist Dr. Max von Pettenkofer disputed the theory that germs caused disease, and specifically that a bacterium called Vibrio cholerae caused the disease cholera. He requested a sample of cholera bacteria from one of the most prominent proponents of the theory, Dr. Robert Koch (who won the Nobel Prize in 1905), and when he got the sample he proceeded to ingest it! Pettenkofer fell slightly sick for a while, but did not develop cholera. He claimed that this proved his point, but the vast majority of the evidence generated by others indicated he was wrong, and his claim was never accepted.
A rather remarkable example of misguided heroic science is the work of Doctor Stubbins Ffirth. This individual studied the incidence of Yellow Fever cases in the United States back in the 1700s and noticed that Yellow Fever was much more prevalent during the summer months. Thus he developed the notion that Yellow fever was due to the heat stress of the summer months, and that therefore it was not contagious. To prove this he embarked on a series of gross experiments where he exposed himself to the bodily fluids of Yellow Fever patients. He drank their vomit, he poured it in his eyes, he rubbed it into cuts he made in his arms, he breathed the fumes from the vomit, and he also smeared his body with urine, saliva, and blood of Yellow Fever patients. Since he never contracted the malady, he concluded that Yellow Fever was not contagious. However, not only did Ffirth employ bodily fluids from late-stage Yellow Fever patients whose disease we now know not to be contagious, but he also missed the fact that Yellow Fever is transmitted by mosquitoes (see below), which is the reason why it’s more prevalent during the summer!
And finally, some of the scientists who engaged in heroic science suffered or died as a result of their experiments, but their sacrifice saved lives or resulted in advancements in the understanding of terrible diseases as the following two cases show.
In 1900 the army surgeon Walter Reed and his team in Cuba put to test the theory that Yellow fever was spread by mosquitoes, which at the time was not taken seriously by many scientists. They had mosquitoes feed on patients with Yellow Fever and then allowed the mosquitoes to bite several volunteers, among whom were two members of Reed’s team, the American physicians James Carroll and Jesse Lazear. Several of the people bitten by these mosquitoes developed Yellow Fever including Carroll and Lazear. Lazear died, but Carroll recovered, although he experienced ill health for the rest of his life. After this demonstration that Yellow Fever was transmitted by mosquitoes, a program of mosquito eradication was implemented that succeeded in dramatically reducing the cases of this disease.
In the Andes in South America there is a disease called Oroya Fever that periodically decimated the population in some localities. In the 1800s many physicians suspected that this disease was connected to another condition that led to the production of skin warts (Peruvian Warts), but no one had ever demonstrated they were connected. Daniel Alcides Carrión, a student of medicine in the capital of Peru, Lima, set out to prove that these two diseases were the same. He removed a wart sample from a patient with the skin condition and inoculated himself with incisions that he made in his arms. Carrión developed the symptoms of Oroya Fever thus demonstrating that these two diseases were different stages of the same disease, which is now called Bartonellosis. Unfortunately, he died from the disease, but he is hailed as a hero in Peru.
The above are but a fraction of the cases of individuals who risked life and limb performing heroic science. Many people criticize the usefulness of most cases of heroic science, especially when it just involves a sample size of “one”, and these critics have a point. In the end, heroic science should be held up to the same standards of rigor as regular science. However, whether those that experimented on themselves did it out of need to overcome bureaucratic obstacles, the belief in the correctness of their ideas, scientific curiosity, or because they were crazy, you always have a certain degree of admiration for the individuals who put their lives and health on the line for a scientific idea. They are willing to cross a line of security that most researchers wouldn’t dare to cross.
The Photograph of Barry Marshall by Barjammar is in the public domain. The photograph of Dr. Goldberger made for the Centers for Disease Control and Prevention is in the public domain. The photograph of Max von Pettenkofer is in the public domain in the US. The photograph of Jesse Lazear from the United States National Library of Medicine is in the public domain.
Oh, Those Gene NamesRead Now
I published a post regarding the names taxonomists give to new organisms they discover and how these names can be flattering, witty, rude, insulting, or downright funny. As it turns out there is another crowd in the biological sciences that has been having a jolly good time naming things, and these are the scientists who study genes. And among these scientists, those who study fruit flies seems to have had the most fun.
Now why on earth would someone want to study flies? To begin with, flies share about 60% of their DNA sequence with us, so many fly genes have equivalent human genes. Furthermore, flies have very short life cycles (which allows the study of several generations in a short time), they are easy and cheap to work with, and not only can fly mutants be studied to find out which genes are responsible for any alterations, but also the technology has been developed to modify, delete, or insert genes, and observe how these modifications change the anatomy, physiology, or behavior of the flies. All this has made fruit flies tremendously important in the study of human genetics. More than 100,000 research articles have been written by scientists employing these organisms as a model system, and a total of 6 Nobel prizes have been awarded to scientists who have used these insects to make key advances in several fields of science.
So, not surprisingly, the fly researchers have discovered and named quite a few genes. But what do you name a gene when you discover it? More often than not, fruit fly scientists have selected gene names based on whatever the particular condition that the fly experienced upon mutation of the gene reminded them of. Let’s take a look at a few.
There is a gene that when mutated in fruit flies leads to problems in the development of external genitalia in the male and female. What possible name would you have given this gene? Fruit fly scientists christened it the Ken and Barbie gene after the anatomically imprecise plastic dolls.
There is a series of genes involved in the synthesis of steroid hormones in fruit flies. Mutations in these genes cause the fly embryos to develop scary-looking malformations in their exoskeleton. The names of the genes are: disembodied, phantom, shade, shadow, shroud, spook, and spookier. They are collective known as the Halloween genes.
There are several genes that affect alcohol tolerance in fruit flies. One lab discovered a gene that when mutated made flies more resistant to alcohol (named Happyhour), a gene that when mutated made flies more sensitive to alcohol (named Cheapdate) and a gene which helps flies become tolerant to alcohol over time (named Hangover).
Fruit flies have 8 photoreceptors in their compound eyes. Scientists discovered a gene that when mutated results in flies that lack the seventh photoreceptor in their eyes. Thus the gene was named Sevenless. Other genes that interacted with Sevenless were named in serial horror movie fashion: Bride of Sevenless (also known as BOSS), Daughter of Sevenless, and Son of Sevenless.
My favorite fruit fly gene is one that when mutated doubles the fly’s lifespan. The gene was christened INDY, which is an acronym for “I’m Not Dead Yet”. This is in reference to the Bring Out Your Dead scene from the Monty Python and The Holy Grail movie.
And the examples go on and on. What would you call a fly gene that when mutated results in flies with no hearts? Scientists named it, Tinman, after the character in The Wizard of Oz who did not have a heart. What would you call a fly gene that when mutated causes neurological degeneration with the production of holes in the brain? Swiss Cheese! What would you call genes that control the death of cells in flies? Grim and Reaper!
But the name doesn’t have to be related to what a mutation does to the gene. For example, several fly genes code for proteins that are located in an area of the fly’s tissue cells called “the matrix”. Accordingly these genes were named Trynity, Nyobe, Morpheyus, Neyo (Neo), and Cypher after characters in the movie The Matrix.
Despite the role of fruit flies in gene research, new genes have also been identified and named in other living things. For example, in the plant Arabidopsis thaliana there are two genes called Clark Kent and Superman that when mutated result in a plant with a large number of male parts (stamens) on their flowers. Interestingly, there is another gene called Kryptonite that when mutated causes the plants to lose their male parts and become sterile. A gene in the zebrafish that when mutated makes the fish extremely sensitive to light (so much so that light kills them) was christened “Dracula”. A gene in sheep that when mutated causes the animals to develop very prominent rear ends was named “Callipyge” which translates from Greek as “beautiful buttocks”. One final example is a gene in mice that codes for an enzyme that transfers a molecule of the sugar fucose to a protein. It was found that when this gene is mutated it causes the females to reject the sexual advances of the males. The name of the gene is the fucose mutarose gene, but it is better known by its acronym FucM !
Of course, as long as gene naming remained confined to insects or animals, all was fun and games. Unfortunately gene naming hit a snag. This was due on the one hand to how successful scientists were in finding counterparts of the genes of fruit flies and other animals in humans, and on the other hand to the fact that some of these genes were found to be associated with diseases.
Consider for example the gene Hedgehog. When this gene is mutated in flies, it causes the fly embryos to be covered with tiny spikes. The counterpart of this gene in mammals including humans was christened Sonic Hedgehog after Sega’s video game character Sonic The Hedgehog. It turned out that a mutation in the human Sonic Hedgehog genes produces a disease called Holoprosencephaly which causes brain, skull, and facial defects. So visualize the following situation:
“I’m sorry, Mr. John and Jane Doe, your child was born with cranial and facial malformations, due to a mutation in Sonic Hedgehog. He may die from the disease, or if he survives, he may experience a certain degree of mental retardation or behavior problems and seizures. What is Sonic Hedgehog? Oh, it’s a gene named after a video game character. Ha, ha, ha, funny isn’t it?”
As Sonic Hedgehog and other genes became linked to deadly or life-altering human diseases, clinicians became uncomfortable with explaining the inside jokes behind these playful but sometimes rude or insensitive names to patients and their families. Because of this the Human Genome Organization Gene Nomenclature Committee consulted with many scientists and renamed several of the worst offenders. So now, for example, the committee recommends that Sonic Hedgehog be known by the acronym SHH.
From all the foregoing you may derive the impression that the scientists who name these genes are foolish, but nothing could be further from the truth. These funny names represent some much needed levity in what is very hard and at times very frustrating work, and these scientists have produced key advances that have increased our knowledge of how our body works and that have also saved lives. The first drug that fights cancer by targeting the Sonic Hedgehog signaling pathway in cells, Vismodegib, was approved by the FDA in 2012.
So next time you hear about the Moonwalker fly (a fly that walks backward when certain neurons are activated by genetic manipulations in a manner reminiscent of Michael Jackson’s famous dance move), or the Stargazer mouse (a mouse that rears its head upwards due to a mutation in a signaling gene), think about the many nights and weekends that the scientists that worked with these critters spent in the labs and give them a smile.
Image of a fruit fly by Sanjay Acharya, used here under an Attribution-ShareAlike 4.0 International (CC BY-SA 4.0). license. Image of Sonic the Hedgehog by Chris Dorward used here under an Attribution 2.0 Generic (CC BY 2.0) license.
I an earlier post I wrote that anyone can be a scientist. The only requisites are to follow the scientific method and ask scientific questions. Scientific questions are those that can generate testable answers (hypotheses). Scientists ask these questions. That seems like a very straightforward concept, right? As it turns out, there is a lot of subtlety involved in asking scientific questions. In fact, I would argue that asking scientific questions is not a science, it’s an art, and I believe that there are three levels of complexity in the process of formulating effective scientific questions
First level: Asking questions within the right framework
While both amateur and professional scientists may be “scientists”, asking minor scientific questions just for fun or curiosity is very different from asking important goal-oriented scientific questions within the context of a funded research project. The relative difference is much the same as the difference between playing in your neighborhood baseball team and playing in the major leagues. At the professional level, more than a decade of training and study is required for participants to both mature and master the intricacies of science and the methods within a particular field of study. This is because the complexities of the questions that are addressed by professional scientists are very unlikely to be answered unless they are articulated within this context. Effective questions are those queried within a framework that leads to their eventual solution.
Second level: Asking questions while having in mind a way to answer them
Some scientists may formulate a question and then seek the answer. This perfectly logical procedure, paradoxically, is not an optimal way of asking scientific questions. This is because it is not enough to ask a question. You need to have an idea or a hunch as to how you are going to answer the question, and this idea or hunch inevitably affects the formulation of the question. The question refines the answer which refines the question which refines the answer and so on. The process is not unlike the one depicted in the lithograph by the Dutch artist M.C. Escher where the first hand draws the second one which in turn draws the first. This process allows for the solution of scientific problems with razor sharp accuracy, and it requires an in-depth knowledge of the fields of science involved, as well as the capacity to integrate, simplify, and pick and choose relevant data from large amounts of potentially conflictive information. The ability to master this process is often the difference between clear thinking and fuzzy thinking among scientists.
Third level: Asking “THE question” type of questions
The Nobel Prize winning biochemist, Hans Krebs, used to tell new arrivals to his lab that he could teach them how to dig, but he could not teach them where to dig. By this he meant that he could teach them all the necessary techniques, ways of thinking, and approaches to answer questions, but what he could not teach them was what questions to ask. To non-scientists (and even to a good number of scientists) this may seem odd. After all, what can be so possibly complicated about asking a question? The answer is, of course, nothing. There is nothing complicated about asking “A question”, but this was not what Krebs was talking about. He was talking about asking “THE question”.
This distinction is a very important one. A researcher capable of asking “THE question” type of questions is to a researcher only capable of asking “A question” type of questions what an architect is to a bricklayer. The truth is that most scientists are incapable of asking “THE question” type of questions and many are not even aware that this is a limitation. Indeed, a good number of researchers would even dispute that this is an issue. These researchers have trained with other scientist who only asked “A question” type of questions, and that is all they know. From their vantage point this is how science works. You ask a series of little specific questions and subject them to test and make incremental advances that build upon each other.
Now, I don’t want to imply that asking “A question” type of questions is not useful. Large numbers of researchers asking these type of questions produce valuable information that moves scientific fields forward, and when these researchers team up with applied scientists this results in practical applications. These scientists create the stepping stones on which science advances most of the time.
However, it is the scientists who have the ability to ask “THE question” type of questions the ones who are responsible for the milestones. These scientists have the depth, vision, and inspiration to, going back to Krebs’s analogy, know “where to dig”. And as Krebs pointed out, this ability is something that can’t be taught. The scientists who ask these questions that get to the fundamental nature of things are very much like the artists who have the ability to create a masterpiece that will endure through the ages and captivate the imagination.
I consider that, in terms of asking questions, level 1 separates the professional scientists from the amateurs, level 2 separates the good scientists from the average ones, and level 3 separates the truly exceptional scientists from the merely good ones. Of course, there is more to successful science than asking questions. There is luck, there is being at the right place at the right time, there is the capacity to promote yourself and your research, to network, to establish collaborations, to request funds, and many other activities that are not mastered by locking yourself up in a lab or an office and thinking up questions. However, those scientists who can function at level 3 are in the highest echelon of sophistication in the art of articulating scientific questions, and this is pretty darn close to the stuff Nobel Prizes are made of!
Escher-inspired figure by Robbert van der Steeg used here under an Attribution-ShareAlike 2.0 Generic (CC BY-SA 2.0) license.