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Theory in Biology

Theoreticalembryology: aroute to extinction?

Peter Lawrence

Mathematics is the art of theperfect, physics the art of theoptimal and biology the art of thesatisfactorySydney Brenner

Once upon a time, about thirtyyears ago, there were two speciesof developmental biologists. Thefirst of these were theexperimentalists. These had beenaround for more than a hundredyears and had descended frompredecessors such as Boveri,Morgan and Spemann. Inattempting to understand theawesome complexity and reliabilityof development, they developedexplanations verging on vitalism.They built concepts such asepigenesis (the hypothesis thatdevelopment is essentially aprocess of elaboration from asimpler start), regulation (thenotion that embryos are often ableto correct damage done to themeither by the environment or by theexperimentalists) and fields (theidea that specific domains ofembryos are to some extent selforganising). These concepts wererather abstract and took littleaccount of either cells or genes.Their experiments, whichconsisted mainly of transplantingor excising parts of embryos, werepublished in journals such asJournal of Experimental Zoologyand Developmental Biology, andthey built their careers asscientists always have. As ever,their fields of investigation evolvedthrough a process of naturalselection that was fuelled byfashion.

“Biologists… often have aplodding and somewhat cautiousattitude”

But, around 30 years ago, therewas also a growing number oftheoretical embryologists, a morerecently evolved species, andthese usually came from a physicsor mathematical background.Perversely, they denied themselvesthe pleasure of studying embryosand instead took a mix ofequations and simulation and triedto model developmentalprocesses. They published theirresults in special journals such asthe Journal of Theoretical Biology.They needed the experimentalistslargely to describe phenomena foranalysis. But the experimentalistsdidn’t need the theoreticians andusually ignored them, mostlybecause they could not understandtheir maths, or their language. Thetheoreticians were powered by theconviction that they were clevererthan the biologists (they were) andthat thinking and argument andanalysis alone can solve biologicalproblems (they cannot).

“Physicists are all too apt toconcoct theoretical models thatare too neat, too powerful and tooclean. To produce a really goodbiological theory one must try tosee through the clutter producedby evolution to the basicmechanisms lying beneath ….What seems to physicists to be ahopelessly complex process mayhave been what nature foundsimplest, because nature couldonly build on what was alreadythere.”

“Elegance and a deep simplicity,often expressed in an abstractmathematical form, are usefulguides in physics, but in biologysuch intellectual tools can be verymisleading. For this reason atheorist in biology has to receivemuch more guidance from theexperimental evidence….”

In that period, in 1974, there wasa meeting organised byChristopher Zeeman to bring thetwo species together in the UK. Itwas attended by the great Frenchtopologist, René Thom. Themeeting was set up so that the twospecies could interact, somethingthey usually failed to do; thebiologists gave their talks withpictures, and the theoreticians

theirs with equations. I was thereand I don’t think we understoodeach other much. At the end of themeeting there was a question andanswer session, and one of the fewpeople who could speak bothlanguages (Graeme Mitchison)mischievously asked ProfessorThom how he valued experiments.There was a very long pause, andthen he pronounced “Unexperrimen eez a questionne, eefyou ask a seely questionne you willget a seely answerrr!”

“René Thom was a goodmathematician.. but I suspectedany biological idea he might havewould probably be wrong.”

The meeting then disbandedand it was followed by the gradualdisappearance and near-extinction of those theoreticianswho had attempted to modeldevelopmental processes. Inrelatively few years some of theirjournals died out and their impacton biology faded — they werekilled off partly by the sheer

Interest in quantitative andtheoretical approaches to biologywould seem to be on theincrease, as evidenced forexample by new institutesstarting up that will focus on‘systems biology’, and theincreasing number of theoreticalpapers in high-profile biologyjournals.

In the light of thesedevelopments, we have invitedauthors likely to express a varietyof views on these developmentsto write essays addressing thegeneral issue of what theory canand cannot do for biology. Thispiece by Peter Lawrence is thefirst in what will be an occasionalseries. See also the editorial inour September 16 issue“Biophysics and the place oftheory in biology” (CurrentBiology 13, R719-R720).

Readers with any responses tothese essays that they feel maybe of general interest arewelcome to send in a letter forpossible publication in ourcorrespondence section, in whichcase email the editor at:cbiol@current-biology.com

unpredictability and illogicality ofbiological mechanism. And alsobecause molecular biology as wellas genetics gave theexperimentalists new andpowerful tools to solve problems.For example, one could spendyears making mathematicalmodels of how to form the stripesof a segmentation gene in theembryo of Drosophila, but oneexperimental result on the geneitself could destroy all of them.

“The job of theorists, especiallyin biology, is to suggest newexperiments.”

Amongst the theoreticiansthere was a subspecies whointeracted with experimentalists— these theorists tried to makesure that their ideas weretestable and that someone testedthem. Preeminent amongst thesewas Francis Crick who wrote allthe quotes above shown in reditalics (taken from Crick’sautobiographical book What MadPursuit: A Personal View ofScientific Discovery; BasicBooks, New York, 1990).

It is remarkable that almost anentire species of scientist canarise and die out in such a shortperiod, but it has happenedbefore — fashion influencesyoung people too much whenthey choose their careers so that,at any time and in any one field,there are either too many, or toofew scientists. Of course thereare still theoreticians working indevelopmental biology, but theyare few in number. So few that Ithink we need more, but only ifthey learn the lessonsenumerated by Crick —otherwise they will follow theirpredecessors into oblivion.Indeed just now there seems tobe a new wave of theoristsarriving, and most are recruitsfrom physics, mathematics andcomputing. I hope they won’tmind me warning them that theywould be wise not to try toanswer the problems of animaldevelopment with their headsalone. They must use their handsas well.

MRC Laboratory of Molecular Biology,Hills Road, Cambridge CB2 2QH, UK. E-mail: pal@mrc-lmb.cam.ac.uk

Current Biology Vol 14 No 1R8

Alongside more traditionalseasonal lights, the WellcomeTrust in London has sponsoreda roadside installation in treesopposite its headquartersbuilding. The feature, byDeborah Aschheim, has beeninstigated by the trust’s curatorof contemporary initiatives,Denna Jones. Aschheim isinterested in how ideas frombiology, our understanding ofhealth and disease, havebecome cultural mythology forour rational, secular age.

The installation of lights andbright red cables represents aperipheral human nervous orarterial system, and it is hoped itwill provide a festive anduplifting show. The local councilare also backing the project.“We are delighted to be workingwith the Wellcome Trust to bringthis stunning piece of public art

to one of London's bestconnected roads,” says PeterBishop, director of theenvironmental department atthe London Borough ofCamden. And many thousandsshould see it: both drivers in theheavy traffic along the road andthe many pedestrian commuterswho pass each day from one ofLondon’s busiest rail terminiclose by.

The Wellcome Trust iscommitted to support selectedartworks inspired by, orreflecting on, current scienceand medicine.

Also showing at the Trusts’sgallery at 210 Euston Road, isthe exhibition Pharmakon, aone-woman show by BeverlyFishman, of abstract paintingsinspired by the cultural powerof prescription pills andmedicines.

Net effect: A seasonal installation in trees opposite the headquarters of theWellcome Trust in London (right). Photograph: the Wellcome Trust.

Arbour lights