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Bluff Your Way in Developmental Biology

Handling the Bioinformatics Explosion

A Review of Bluff Your Way in Developmental Biology

With hindsight, however, those times were dull as the paradigms of research built as they had to be on phenomenology were becoming exhausted. The result was that the field was more than ready for the molecular explosion that was about to hit it and today there is almost too much to be excited about. The equivalent meeting of 1998 has nigh on 1000 people, there are 4 parallel sessions, and so much is happening that one doesn't e riding the zeitgeist. Journal clubs are easy to handle and, in practice, even conferences can be treated as an hors d'oevres table where one can taste the things one likes and ignore the rest.

The sheer difficulty of handling all this information is brought to its sharpest focus in what might seem to be an unexpected context. Picture a meeting of the BSDB at the end of a very hard day where, 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 clearly been demonstrated to be irrelevant to the development of anything else and the absence of an interesting phenotype has been illustrated in tedious depth in yet another six transgenic mice. You are in the bar trying to recover your equilibrium with the help of a well-earned pint and chatting about some inconsequential topic that you actually know something about when a fourth year graduate student says in a loud voice that there is this a paper in the most recent issue of Development that has shown how transfecting the zebrafish homologue of the Drosophila equivalent of Sox9.5 into the early chick limb bud is the key to understanding the basis of apoptosis in the interdigital areas. This statement immediately poses the problem of how to put this paragon of virtue in his place, particularly as your own copy of that issue of Development, together with the last 6, is actually being used to keep your terminal at the right height.

The obvious thing to do is to is to meet him on his own ground and discuss that heady mix of genes, organs and embryos, but to do this, you too have to be up-to-date, and that is not easy. You have to know the whole of Developmental Biology (including the nth edition, the one with too many pages), you have had to have made the devbio.com website your home page so that you can know what has happened since that edition and, worst of all, you have to have unpacked, read, understood and be up-to-date with all the recent issues of Development (it had 5159 pages in 1997 and that was 9 times larger than it was in was in 1983) - and some of us have work to do.

It is here that Einginis new monograph, 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 it might appear that the average academic has little training in such rhetorical skills, Eingin points out that all one needs is a little technical knowledge and a touch of confidence.

In essence, the Eingin approach centres around the use of two basic techniques that he combines with a rhetoric device borrowed from politics. The techniques are bringing the subject around to your area of expertise while, at the same time making your colleague feel that he or she is out of their depths. The rhetorical 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. Anyone with even a modicum of learning shouldn't worry about their narrow knowledge base as no one else knows that much either, and, even if someone does think that they know the field, a little judicious probing and a touch of style should enable you to find a crack of ignorance to exploit. Indeed, if they do know that much, it is probably because they have forgotten what the inside of a lab coat looks like, and all one has to do is to move the conversation from the recent literature to the stability of buffers and the resolution of gels.

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 summarise how 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.

The early chapters deal with the essential methodology (on changing the subject, taking the initiative, complexifying, trivialising and simplifying), while the later ones discuss their use in the key branches of developmental biology. Here, he is particularly good on giving a veneer of sophistication to an otherwise mundane grant application, making reviewers interested in manuscripts that should never have seen the light of day, and getting winter invitations to meetings in the other hemisphere [if all else fails, organise it yourself and know who to invite so that the funders will be impressed]. But his contributions on impressing deans and other bureaucrats, answering questions (denigrating questioners) after delivering 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.

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 question of the apoptosis that occurs between the early condensations that will form the wrist bones, and from this you ought to be able to slide to the morphogenesis in 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.

Eingin suggests that this example actually 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 Kaufmanis Atlas of Mouse Development, Romanoffis The Avian Embryo and Campos-Ortega and Hartensteinis The Embryonic Development of Drosophila melanogaster 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 houris work on the Medline web site to write a good grant application, or at least a review.

Alternatively, a subtle twist can be given to almost anything by invoking the evolutional context and one approach that works well after a few drinks is to raise the extent to which a tissue or gene about which you know nothing is the homologue or analogue of something vaguely similar about which you have recently given a graduate seminar. This allows you to dominate the conversation by discussing the extent to which homologues and analogues are two ends of a continuous spectrum and whether the position along the line can only be determined by molecular sequencing. Actually, this is nonsense, but, by the time that your audience have realised this, you will have levered the discussion towards your own territory - the object of the exercise.

There is also considerable mileage to be obtained from remembering Popperis dictum that proper science is only disprovable 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, it is usually (un)helpful to start with the speakers main conclusion and inquire as to how it could be disproved and whether he 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 if you can invoke Popper and show how your experiments disprove alternative hypotheses.

In addition to disprovability, Eingin mentions that there are a set of words that you should always be able to call on, and trivial is particularly useful. 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 works. Promiscuous and redundant are also nice in the context of receptors but are now in sknow which if any of these sessions one can afford to miss. For the first time, we can not only begin to understand the molecular basis of all those phenomena whose phenotypes were being explored in the dark ages, but compare homologous and analogous mechanisms across the phyla and obtain almost mechanistic insights into how evolution worked.

Although it might seem a mite churlish to mention it, however, there is a slight downside to living in this age of wonderment. Then, we didn't have to know anything outside of our own little area, today we have to know almost too much. We have to remember the details of the ontogeny of a dozen animals, we have to remember the morphogenesis of their cellular organisation and, worst of all because the details change so frequently, we have to remember every damned gene family. We are drowning in information. Most of the time, it should be said, we can stay secure in our own bailiwick and can keep this bioinformatics explosion under control. If editors feel that our papers should show an appreciation of the wider evolutional context, it is the work of seconds to find 17 relevant papers over the web, glance at their abstracts and compose a paragraph that is sufficiently learned to impress any reasonable referee. Lecture courses pose few problems as one's own knowledge is clearly at the key intersection of all the major strands in the subject and the obvious focus for a semester's work, while colleagues can give a few "broader context" seminars to make students feel that they aruch common parlance that their use can be denigrated as old-fashioned. Zeitgeist can similarly be dismissed as referring to last yearis 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 Mortonis fork, other peopleis arguments ineveitably either miss the underlying simplicity or are completely oversimplified.

His appreciation of the 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 Personneis Drosophila lab in the one Cambridge and Niemandis mouse lab in the other, and it will be interesting to follow his future publications in this area. While many will feel that his book fills a much needed gap in the literature, others, particularly those who, in the words of another Gilbert from another time "could also pass for 45, in the dusk, with the light behind them" will feel that Eingin really understands developmental biology properly. As to the monograph series, I hope that the general editor will commission others in areas as important as developmental biology, and I particularly look forward to the one on cognitive science.

Jonathan Bard
Dept. of Anatomy, Edinburgh University.

Eingin, G. Bluff your way in developmental biology. Iceland: Reykjavik University Press. Expected publication date 29.2.01

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