Novel scientific propositions are initially taken with skepticism. Eventually, they become accepted –at least some of them. The transition between heressy and main stream has been debated ad nauseam. British geneticist J.B.S. Haldane (1892-1964) has been famous for many things, one among them was his incisive sarcasm. Haldane was an assiduous contributor to the Journal of Gentics, not only of scientific articles, but often many book reviews. One of those reviews, published in 1963 (Journal of Genetics Vol. 58, page 464), is perhaps the best known among the lot, not because of the book being reviewed, but because of Haldane’s now famous description of the stages in the process of acceptance of scientific theories. In Haldane’s words, theories invariably pass through “the “usual four stages”:
Thank you for sending us your paper “Downregulation of HlpxE-mediated transcription doubles median life-span expectancy in humans”, but I am afraid we cannot offer to publish it in The Current Biologist.
We appreciate the interest in the issue you are addressing, and your results sound potentially significant for the field, but our feeling is that at this stage your paper would be better suited to a somewhat more specialised journal.
I am sorry that we cannot give you a more positive response, but thank you for your interest in The Current Biologist.
Many of us —professional scientists writing research articles— have had to confront this type of letters from journal editors. We have grown accustomed to them. A standard cut-and-paste piece of text used knee-jerkedly by editors without much thought or consideration. We file them promptly, and move on. After all, there are plenty of journals around, both general and specialized. No big deal, right?
In a recent interview for the podcast series of the Proceedings of the National Academy of Sciences of the USA, Ira Mellman of Genentech expressed his views on the utility of science practiced at academic institutions. After an academic career at Rockefeller and Yale University, Mellman joined Genentech in 2007 where he is Vice President of Research Oncology. Mellman is a member of the National Academy of Sciences since 2011. The interview is about current challenges in the field of cancer immunotherapy. But things get a bit more controversial at the end. Scroll the audio featured below to -0:35 and you’ll hear this:
PNAS: “I asked Mellman whether his move from academia to industry has brought him closer to his goal of practicing people-centered science.”
“There are known knowns; there are things we know we know. We also know there are known unknowns; that is to say, we know there are some things we do not know. But there are also unknown unknowns, the ones we don’t know we don’t know.”
— D. Rumsfeld, 2002
The scientific literature increases exponentially with thousands of papers added daily. As the day has only 24 hours, what this means is that every time we sit down to read a paper, we have —consciously or unconsciously— decided to neglect thousands of others which we will most likely never read, ever. Agonizing as this may sound to some, it is equally inevitable. The assurance that we feel when moving a paper to our “to-read” list can be self deceptive, however, and so it is crucial that we choose which papers to read with great care. Or rather, that we carefully decide which papers not to read. In fact, better to do this consciously than as a default consequence of the limited number of hours in the day. The art of selectively ignoring sets of facts has been called “controlled neglect” and it is a crucial tactic to cope with the vast mountain of facts that keeps growing by the day.
Researchers from Heinrich-Heine University in Düsseldorf, Germany, have published an intriguing study on traumatic brain injury using a dataset taken from the Asterix comic series. The report appeared in Acta Neurochir (2011) 153:1351–1355.
We learn that the goal of the study was to “analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern.” One of the major strengths of the study is that clinical data were “correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors.”
“I want good data, a paper in Cell
But I got a project straight from Hell”
“I wanna graduate in less than five years
But there ain’t no getting out of here”
“Oh oh oh… caught in a bad project”
Crazy mice. Smelly brain cells. Empty Western blots. It’s a bad project alright. Or… is it? There are indeed bad projects out there. Research projects begin with a question that is to be answered. If no question has been formulated, however general, and experiments are being done only because they are doable, then a bad project is on the horizon. With a question at hand, hypotheses have to be made as to the posssible answers, ideally covering all logical possibilities. Lack of hypotheses in a project is not a good sign. The question posed may not be answereable. (We’ve all heard about hypothesis-free studies. That’s okey for a group leader with 50 postdocs and lots of other projects. Not recommended to anyone that wants to graduate and get a job in less than five years!) Hypotheses help designing the experiments that are going to distinguish between them. Experiments are typically designed to systematically disprove them one by one. A neat, key experiment to prove one of the hypothesis upfront is more difficult to come by. Some experiments may just add support to a particular hypothesis, but not prove it or disprove it outright. So far so good. But a good project should also allow for serendipitous discoveries. Paradoxically, serendipity is one of the most common ways of advancement in science. Alas, serendipity can not be planned. But it can be encouraged. In addition to concrete goals and defined questions, research projects that allow some amount of open-ended possibilites have greater chances to extend into (positively) unexpected directions. It’s a fine balance, in which informed intuition plays a vital role. (For a discussion of intuitive thinking, see Making Science Part III.) Lady Science in the video above seems to be having more problems than just a bad project. But those are topics of other discussions.
Can a good scientist be a bad writer? The answer, in my opinion, is nope. Here is the story.
The registrator office at the Karolinska Institute has recently received a request to release the full texts of several of their successful grant applications to the European Research Council (ERC) as well as the texts of their respective evaluations and referee comments. ERC grants are both generous and prestigious awards that have come symbolize the success of the European scientific elite. Under Swedish freedom of information legislation, the Karolinska Institute -which is ultimately under state jurisdiction- is obliged to release these documents, as astonishing as this may sound. (A topic that surely deserves a post of its own.) Needless to say, such a request has come down as nothing short of controversial among the scientists involved, since grant applications contain unpublished data and detailed confidential information about their future research programs. Who could have made such a preposterous request?
Intuition is as important in science as it is in the arts and any other creative activity. Intuition can allow the formulation of novel ideas or solutions to complex problems that would otherwise be difficult or improbable to reach via conventional, logical reasoning. Although the popular term “gut feeling” would appear to indicate that intuitive processes take place outside the brain, it is a misplaced metaphor, as intuition is very much a mental activity.
As in conventional reasoning, intuitive thinking computes the odds of competing ideas or solutions. Unlike the former, however, the intuitive process is largely unconscious. We are only aware of the result of the computation but not the process by which it was obtained. It is nevertheless a mental calculation like any other: it utilizes data stored in memory to deduce connections, predict missing bits of information, or generate new hypotheses.
Former postdoc fellow Svend Kjaer has today published his first first-author paper after leaving the lab. It has appeared online at the Nature Structure and Molecular Biology website. He’s got the first glimpse of the three-dimensional structure of the extracellular domain of the RET receptor, giving insights into how it binds ligand and how its mutation causes disease. Something we were striving to see for several years while he was at our lab has now been achieved and it’s one of the great success stories of making science. It took a lot of perseverance, a good measure of ingenuity and the crucial guidance and support of Svend’s current mentor and common friend Neil McDonald from the CRUK institute in London. As if by coincidence, from Svend comes also this link to the one-hour film “Naturally Obsessed: The Making of a Scientist” telling the story of three graduate students in a crystallography lab at Columbia University, NYC and their road to success (or failure) through “years of trial and error and unflinching dedication”. It gives good insights into real science making in a lab, the elusive thrill of its ups and downs, and what it takes to get to the finish line. Link from the picture above.
Limoncello in hand, professor Alun Davies addresses the Molpark crew at the onset of the network meeting in Seiano, Italy, on April 25, 2010. We had a wonderful couple of days with great science and long-missed sunshine in a fantastic location. Video shot with Canon EOS 7D and EF 24mm 1.4 L lens.