HUMOR

Holding Your Own Handling Developments in Developmental Biology by Jonathan Bard
Posted March 31, 2000 · Issue 75

It is only with the perspective of time that one can appreciate the extraordinary progress that has been made in our knowledge of developmental biology over the past few years. The postdoc of today would scarcely believe how naive the subject was, say, even fifteen years ago. A typical meeting of the Society for Developmental Biology then would perhaps have included sessions on cell behavior and migration, on Drosophila homeotic mutations in the context of transdetermination, perhaps something on C. elegans neuronal maps, and a paper or two on the development of the preimplantation mouse embryo. In that 1985 meeting, there would have been no sessions on genes, simply because there were virtually no interesting genes to talk about.

We're drowning in information. That's progress!

p>The molecular revolution has changed things beyond all recognition, and the goods and bads of all this progress are exemplified by the program for this year's meeting. The excitement comes from all those papers comparing the molecular underpinnings of homologous developmental mechanisms across the phyla so as to obtain almost direct insights into how evolution worked its magic. There is also a slight kick to be had from watching the various top groups competing for pecking order on the same territory. The downside is the sheer amount of information pouring out of those groups: we not only have to know the developmental anatomy of a dozen animals, we have to remember every damned gene family. We are drowning in information and losing control.

One can imagine the situation after a typical day at the meeting when, for example, Drosophila developmental genetics has yet again been shown to produce more heat than light, the molecular basis of C. elegans neuronal development has been clearly demonstrated to be irrelevant to the development of anything else, and the absence of an interesting phenotype has been illustrated at tedious length in yet another six transgenic mice. You are in the bar trying to recover your equilibrium with the help of a well-earned beer when a fourth-year graduate student says in a loud voice that some paper in the current issue of Development shows how the results from transfecting the Drosophila antenna spliceform of the mouse Sox9.5 homologue into the early chick limb bud is the key to understanding the basis of apoptosis in the interdigital areas. This statement immediately poses a problem: how should you handle this paragon of virtue, particularly as your own copy of that issue of Development, together with the last six, is actually being used to support your computer monitor.

Read Development? Some of us have work to do.

The obvious thing to do is to is to meet him on his own ground and discuss that heady mix of evolution, genes, organs, and embryos, but to do this, you too have to be up-to-date, and that is not easy. You have to have read all the recent issues of Development (its 24 issues in 1999 had 5,922 pages and was 10 times larger than the mere six issues in 1983) - and some of us have work to do.

It is here that Eingin's new monograph [1], the most recent in a long and distinguished series, is so valuable. He takes as his thesis that it is not what you know that matters so much as how you deploy it to demonstrate your learning and ability in public. While the average academic might feel that he or she has scant training in such rhetorical skills, Eingin points out that all one needs is a little technical knowledge and a touch of confidence.

Rise to the top with the Eingin method.

In essence, the Eingin approach centers around the use of two basic methods that he combines with an oratorical device borrowed from politics. The methods are bringing the subject around to your own area of expertise and, at the same time, making your colleague feel that he or she is out of their depth. The oratorical skill is knowing how to change your ground so fast that, by the time your colleagues have marshaled their arguments to show how thin was the ice on which you were skating, you will have moved onto solid ground.

p>The book, at least in its prepublication form, is short enough to be read during a morning of dull conference papers. Here, however, I can only summarize the ways in which Eingin deploys his extensive and deep knowledge of the conflations of the various contemporary paradigms in developmental biology to provide the reader with a series of case studies that he or she will find both useful and enjoyable.

Learn many ways to put them in their place.

p>The early chapters deal with the essential methodology (changing the subject, taking the initiative, complexifying, trivializing, and simplifying), while the later ones discuss their uses in the key branches of developmental biology. Here, he is particularly good on giving a veneer of sophistication to an otherwise mundane grant application and making reviewers interested in manuscripts that should never have seen the light of day. But his contributions on impressing deans and other bureaucrats, answering questions (denigrating questioners) after seminars, writing tenure documents, and reviewing manuscripts so that the authors are actually grateful that their papers have been rejected are all worth serious attention, while his advice on handling Ph.D. oral exams will be of universal benefit (see below).

p>As an example of his technique, Eingin deals with the limb apoptosis problem by suggesting that you raise the question of the extent to which the paper helps explain the much more interesting (a useful word) question of the apoptosis that occurs between the adjacent condensations that will form the wrist bones, and from this you ought to be able to slide to the morphogenetic events involving the mesenchyme of your own organism and then to home territory - the beauty of this approach is that no one has the first idea as to what is going on in the formation of the wrist bone condensations.

Get mileage out of tissues adjacent to those in fashion.

Eingin suggests that this example exemplifies a deeper truth, that the organs on which we work are actually a very small subset of those within vertebrate and invertebrate organisms and that there is a great deal of mileage to be obtained by looking in traditional embryology books to identify those tissues that are adjacent to the ones in fashion. With luck, indeed, you should be able get enough information from these and an hour's work on the PubMed website to write a good grant application, or at least a review.

There is also considerable mileage to be obtained from remembering Popper's dictum that the only real (another useful word) identifier for proper science is its disprovability and that nothing can ever be proven to be true. The dictum can, as Eingin points out, be used both ways. If you wish to ask a question at a seminar, it is usually (un)helpful to start with the speaker's main conclusion, point to how it could be disproved and then ask whether he or she has done the experiment. When, on the other hand, you are giving the seminar, it adds a touch of sophistication that will flatter your audience (always a shrewd move) if you can invoke Popper and show how your experiments disprove alternative hypotheses.

There's always the modern equivalent of Morton's fork.

In addition to disprovability, interesting, and real, Eingin mentions that there are other words that you should always be able to call on, and trivial has long been used to good effect in mathematics. Thus, for example, should the knockout of a transcription factor lead, for once, to an interesting phenotype in a transgenic mouse, the gene should be viewed as only being important in the trivial sense that its role is to facilitate the activation of a gene pathway. The non-trivial question, of course, is how that pathway produces the change in phenotype. Promiscuous and redundant are also nice in the context of receptors but are now in such common parlance that their use can be denigrated as old-fashioned. Zeitgeist can similarly be dismissed as referring to last year's fashion (and you should have something more up-to-date up your sleeve for emergencies). If all else fails, writes Eingin, there is always the contemporary equivalent of Morton's fork [2]: other people's arguments inevitably either miss the underlying simplicity or are completely oversimplified.

The real test of the book, however, and the chapter that I immediately turned to is the one dealing with Ph.D. examinations. As anyone in the business knows, the examiner is always at a real disadvantage: although you of course understand the principles of the subject far better than the student, he or she starts off with the unfair advantage that they inevitably know far more about the details of their work than you can possibly absorb, particularly as you have had only 3 hours on the train or plane to read their wretched thesis. Although you start from an inferior position, Eingen shows how it isn't too difficult to reverse the situation so that, after a couple of hours of oral exam, the student (1) is grateful to be allowed to pass, (2) despises his or her supervisor for their shallow attempts to educate them and (3) realizes that it is only your understanding and kindness that has been their salvation.

Remember the guiding principle behind the Spanish Inquisition.

p>Eingen starts by reminding you of the guiding principle behind the Spanish Inquisition, "In just one page of any man's prose there is evidence to burn him," before emphasizing the importance of giving the illusion of extensive preparatory work. Here, the assay is to have sticking out from at least 20% of the pages of the thesis a Post-It on which something (anything) has been written so that the student realizes with a sinking heart that you have actually read every word of the text. The student will then be softened up for the first question of the oral, one that is ostensibly designed to put him or her at ease: traditionally, this is something simple about the literature. You thank them for their answer and ask them if they had considered the possibility that the literature here was wrong or superficial, or failed to deal with some point or other where you actually know something.

p>Ten minutes along this line and they are ready for an analysis of their results, and a safe question (for you) is to ask the student to discuss the controls of their key experiments and why they chose that particular statistical method to analyze their results. After 30 minutes of this, you can then go to the third line, another variant on Morton's fork: if the results were clean and conclusive, you can ask them to consider the narrowness of experiments which exclude novel results. If they were messy, you can ask them to spend ten minutes using hindsight to redesign their experiments so that things would have worked better. As to the discussion, a reliable way to handle this is to look for any clever idea in the text and ask the student how it could be disproved. The approach is as ever to keep the initiative and to ask students questions that don't require you to have done more work than is merited by the miserable fee that you are going to receive in six months' time when the administration has finally dealt with the paperwork.

Eingin's book fills a much-needed gap in the literature.

Such an appreciation of both the intellectual and financial nuances of the subject clearly shows Eingin to be a highly sophisticated member of the developmental biology community. While he is currently a professor at Eimissään University in Finland, he has also done a postdoc at Personne's Drosophila lab in the one Cambridge and Nieman's mouse lab in the other. While many will feel that his book fills a much-needed gap in the literature, others will admire Eingin's sensitivity to the realpolitik of developmental biology. As to the future of the series, I hope that the general editor will commission other such monographs in areas of contemporary science as important as developmental biology, and I particularly look forward to the one on cognitive science.

Jonathan Bard is an aging developmental biologist at Edinburgh University.

Andrzej Krauze is an illustrator, poster maker, cartoonist, and painter who illustrates regularly for HMS Beagle, The Guardian, The Sunday Telegraph, Bookseller, and New Statesman.