Category Archives: Science

Making science (part VI): Ignorance

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.

Would you rather earn an A or an F in a class on Ignorance?
—S. Firestein, 2012

What is it more important, what we know or what we don’t? It has been argued that ignorance fuels innovation, and this is probably true to some degree, but ignorance is a double-edged sword. One risk is that we turn current knowledge into unknow knowns, a category that even Rumsfeld’s uncanny insight failed to foresee, opening the door to AIDS deniers, creatonists and the like. The bottom line would seem to be that scientists should forget the answers (i.e. controlled neglect, with empahsis on “controlled”) and focus instead on the questions. The problem lies in that, unlike knowledge, ignorance is unbounded. When a sphere becomes bigger, the surface area grows. Thus, as the sphere of scientific knowledge increases, so does the surface area of the unknown.

The more we know, the less we know, and so our ignorance paradoxically expands as our knowledge increases. We’ve got what we don’t have. We’ve got our ignorance, preciously infinite.

Intriguing clinical meta analysis of a unique dataset in traumatic brain injury from the “Asterix” comic books

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) 153:13511355.

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.”

Through painstaking analysis of all 34 Asterix comic books, the researchers identified 700 hundred cases of TBI in the study. “The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%).” Among the most intriguing results, they found that “although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found.”

Epidemiological results indicated that “the largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called “the magic potion (p ≤ 0.05)”.

There is no shortage of curious information in the paper. Among other jewels, the authors found that, among victims of head injuries, 4 out of 700 were extraterrestrials. The generally favorable outcome was surprising, given the severity of the injuries (see figure below). One possible explanation given by the authors lies in the follow-up. In their own words, “in many cases, follow-up was only a few minutes. Here, a secondary deterioration after a “lucid interval” and development of intracranial hemorrhage might have been overlooked. However, most figures returned at later time points without any deficit.”

Clearly, more work needs to be done to follow-up this very interesting research. The authors declared no conflict of interest. The funding source was not acknowledged in the paper, however. 😉

Making science (part V): Bad project

“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.

Making science (part IV): Good science, good writing

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?

As it turned out, the request came from an employee from the grants office of a provincial high school (recently upgraded to the rank of university) located south of Stockholm known as Mälardalenshögskola (MDH). As the story goes, school authorities reasoned that their scientists could learn how to write successful grant applications by looking at successful proposals written by scientists from a high-profile university such as KI. Apart from the fact that MDH has not been known to have a program in biomedicine, let alone any significant biomedical research, the idea that someone could succeed with a grant proposal by simply copying another one is at best controversial and at worst utterly naive.

A successful grant proposal is invariably centered around a good idea. And good ideas come from good scientists, who also happen to write well. So MDH authorities would do better by focusing on the quality of their scientists than on imitating already funded applications. Good science requires analytic capacity, the ability to formulate ideas clearly and logically. In a grant application, as in any scientific text, analytic power and logical reasoning help taking the reader from what is known to what is unknown in a systematic fashion, what to do in order to reveal the unknown and why should one do it. These are attributes inherent to science making, not special faculties restricted to good writers. A good scientist knows how to be analytic, systematic and how to formulate research, its part of the job description. If you are a good scientist, you also know how to write well, it comes in a package. Imitating the writings of others does not help.

Making science (part III): Intuition

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.

Unlike conscious reasoning, intuitive thinking takes place off-line. However, it is possible to direct, facilitate and enhance intuitive thinking, even though the process itself will always remain unavailable to conscious, on-line processing. Intuitive computations are intrinsically soft, but can be made more robust by increasing the amount of data available to intuitive processing. In science, this amounts to acquire as much information and experience as possible by reading extensively, brain-storming with colleagues and sitting at the bench.

There is a neurobiological basis for intuition.Regions of the brain involved in intuitive thinking are likely to show some overlap with areas involved in normal conscious reasoning.Antonio Damasio is one of several scientists currently investigating this and related questions. He has highlighted the importance of emotional states, largely under the influence of peripheral organs (i.e. body viscera and such), in decision-making processes including intuitive thinking. Damasio has identified patients with lesions in specific brain areas that show deficits in risk-taking, decision-making and intuitive reasoning. It is likely that different brains are able to support intuitive processing to different extents. Do non-human primates have intuition? Proof for the evolution of intuition will clearly have to await a better understanding of its hardware. However, its important contribution to decision-making processes suggests that it may have been positively selected in humans.

Intuition is a real mental process that is crucial for creativity. It can not be completely controlled, but it can be trained and enhanced. Sure enough, not all reasoning in science is intuitive, but given the shear volume of scientific data and information currently available (and constantly increasing), intuitive thinking is an indispensable allied in scientific creativity.

Making science (part II): The making of a scientist

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.

Making science (part I): Discovery

Making science is about being where none else has been. Seeing what none else has seen. Walking on an unknown planet for the first time, without leaving the walls of the lab.

This is the essence of being a scientist. Of course, day to day life in a research lab can be difficult. We don’t walk on a new planet everyday. Reagents that don’t work, mice that don’t breed, experiments that don’t make sense… Many things can get on our way to the answers we are looking for. Sometimes we get answers to questions we have not asked. It’s a journey into uncharted territory. And like any journey, it is prone to surprises. Discovery is the driving force. But not every question asked leads to a discovery. How to know what questions to ask? That’s another matter altogether…

Vijay Iyer Trio

FASCH10_0828A remarkable concert featuring Vijay Iyer Trio live at Fasching on April 13 2010 in full power. Here is Vijay in full concentration at the piano (pic taken with my EOS 7d and the 100-400 L, which I took by mistake thinking that it was the 70-200L 2.8!). In addition to Iyer on piano, the trio includes Stephan Crump on bass and Marcus Gilmore on drums. Their most recent album is “Historicity” (2009) on the ACT label. Several of the pieces of that album were featured at the Fasching concert. Vijay Iyer uses thick chords sweeping across the keyboard generating an orchestral backdrop onto which melodic lines navigate. Improvisation remains the central theme. From Vijay Iyer’s website: “his powerful, cutting-edge music is firmly grounded in groove and pulse, but also rhythmically intricate and highly interactive; fluidly improvisational, yet uncannily orchestrated; emotionally compelling, as well as innovative in texture, style, and musical form.”

Vijay Iyer holds a B.S. in Mathematics and Physics from Yale College, and a Masters in Physics and an interdisciplinary Ph.D. in Technology and the Arts from the University of California at Berkeley. He has done research in music cognition, and published an article on “Improvisation, Temporality and Embodied Experience” in the Journal of Consciousness Studies (Vol. 11, No. 3-4, March-April 2004). In the Abstract of that paper, he writes: “… music perception and cognition are embodied, situated activities. This means that they depend crucially on the physical constraints and enabling of our sensorimotor apparatus, and also on the ecological and sociocultural environment in which our music-listening and -producing capacities come into being. I have argued that rhythm perception and production involve a complex, whole-body experience, and that much musical structure incorporates an awareness of the embodied, situated role of the participant. In this paper I focus specifically on improvisational music, and on what it can tell us about consciousness and cognition. Building upon the notion of cognition as embodied action, I would like to propose an understanding of certain improvisational music as quintessentially experiential, in that it leads us to re-experience our own practice of perception.” Listen to Jason Crane’s interview with Vijay Iyer from The Jazz Session, in which he talks about “everything from mirror neurons to math jazz, Fibonacci numbers to the legacy of Roy Haynes”.

FASCH10_0922

Photograph above (taken with the EOS7D and 24L II lens) features Vijay Iyer on stage after the concert alongside PhD student Carolyn Marks. Carolyn has an uncanny ability to persuade musicians to pose by her side. More photographs taken during the concert are available HERE or in the link under Photo galleries.

Journal podcasts: Nature, Science, Cell

After subscribing for over two years to the Nature, Science and Cell podcasts, my preference falls clearly with the former. The Nature podcast is snappy, lively, fun to listen to and has great interviews. The journalists have human voices, sound like real people and manage to confer the excitement of science with a touch of humor.

The Science podcast has several problems, the biggest one is podcaster Robert Frederick. I can not imagine a more unnatural, robotic voice on Earth. Does he speak like that to his friends? Even the text-to-speech voice in my Mac sounds more human that this guy. I also find the usual bit about science policy terribly uninteresting. As in the World Series, this is only concerned with US policy, of course. If listening at night in bed, I am surely asleep by this moment. Both Nature and Science have another feature in common that I think takes unnecessary space, that is the bit on news at the end in which one journalist interviews another. This practice has become very popular in TV talk shows and news programs, and sometimes I can see the point of asking questions to a journalist deeply specialized on a particular topic. But those are not the guys at Nature or Science. I find it totally uninteresting, I much rather have the actual scientists telling the story.

The Cell podcast focuses only on interviews, which is good, but again, I see it lacking on spontaneity. The editors read text, it’s obvious, and this becomes very unnatural and off-putting. I don’t know where they record this, but their voices have a funny echo as if they were speaking from a closet or bathroom. Otherwise the interviews are great and feature terrific scientists. I also like the fact that they draw from different Cell journals. It adds a nice variety. A practice common to the Cell and Science podcasts is to refer everyone by their Dr. title. Dr. this, Dr. that. Thank you Dr. Is this an americanism? It’s very stiff and off-putting. How about calling them by their first names? This is what Nature does. It’s less distracting and so much fresher and friendlier.

In conclusion, the Nature podcast is the favorite one. I’ll keep listening to Science and Cell, but I am very thankful for the fast forward button in my iPod!

UPDATE (23-07-2011)
Robert Frederick is no longer with the Science podcast. Stewart Wills has replaced him and… oh boy, what a difference! Great to have a sentient human being talking to you. Much better!