Yet failures are critical elements of the natural cycle of scientific progress. In fact, failure often predates success. Its absence suggests a paucity of risk taking and a lack of innovative thinking. Failure can be a distressing experience, but its unpleasant sting serves as a formidable motivating force, driving us to redouble our effort. Sometimes, success may be disguised as failure. In The Act of Creation, the writer Arthur Koestler observed that some discoveries represent striking tours de force by individuals who seem to be so far ahead of their time that their contemporaries are unable to understand them.1 For example, the validity of a fresh, creative idea or a novel experimental approach may be attacked because of ignorance or misunderstanding, or worse, because of petty jealousy or personal rivalry. How does one proceed in such a quandary? Here are the stories of some researchers who faced these challenges.
A Patient of Extreme Interest
In the fall of 1972, a middle-aged female patient who was exhibiting progressive loss of memory and difficulty performing some routine tasks was admitted to the neurology service at the University of California San Francisco (UCSF). The junior neurology resident assigned to her case was fascinated to learn that she was dying of a “slow virus” infection known as Creutzfeldt-Jakob disease (CJD), a fatal condition that evoked no response from the body’s defenses.2 It is a blessing that CJD is one of those extremely rare diseases that we often hear about at rounds but seldom get to see firsthand.
The neurology resident began reading about CJD and, in particular, the research led by the noted medical anthropologist, D. Carleton Gadjusek, MD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. He was awarded the Nobel Prize in Physiology or Medicine in 1976 for describing a curiously similar dementing illness, kuru, among the Fore people of New Guinea and its bovine equivalent, scrapie.
Our neurology friend, now a junior faculty member at UCSF, chose the daunting task of trying to isolate and identify a slow virus in culture. Since assays in mice for the scrapie agent were tedious, slow, and very expensive, his progress was stifled. He was stuck, and had no clever idea about how to circumvent this problem. Not surprisingly, his application for support from the National Institutes of Health (NIH) was turned down.
Sound familiar? Our intrepid investigator carried on, working with some noted virologists based at the Rocky Mountain Laboratory in Hamilton, Mont., where he acquired the additional skills that allowed him to collect important data on the scrapie virus. His results, though, were quite puzzling. The scrapie culture preparations contained protein but no nucleic acids. This finding made absolutely no sense. It went against a major tenet of biology.
