Theoretical embryology: a route to extinction?
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Magazine R7 Theory in Biology Theoretical embryology: a route to extinction? Peter Lawrence Mathematics is the art of the perfect, physics the art of the optimal and biology the art of the satisfactory Sydney Brenner Once upon a time, about thirty years ago, there were two species of developmental biologists. The first of these were the experimentalists. These had been around for more than a hundred years and had descended from predecessors such as Boveri, Morgan and Spemann. In attempting to understand the awesome complexity and reliability of development, they developed explanations verging on vitalism. They built concepts such as epigenesis (the hypothesis that development is essentially a process of elaboration from a simpler start), regulation (the notion that embryos are often able to correct damage done to them either by the environment or by the experimentalists) and fields (the idea that specific domains of embryos are to some extent self organising). These concepts were rather abstract and took little account of either cells or genes. Their experiments, which consisted mainly of transplanting or excising parts of embryos, were published in journals such as Journal of Experimental Zoology and Developmental Biology, and they built their careers as scientists always have. As ever, their fields of investigation evolved through a process of natural selection that was fuelled by fashion. “Biologists… often have a plodding and somewhat cautious attitude” But, around 30 years ago, there was also a growing number of theoretical embryologists, a more recently evolved species, and these usually came from a physics or mathematical background. Perversely, they denied themselves the pleasure of studying embryos and instead took a mix of equations and simulation and tried to model developmental processes. They published their results in special journals such as the Journal of Theoretical Biology. They needed the experimentalists largely to describe phenomena for analysis. But the experimentalists didn’t need the theoreticians and usually ignored them, mostly because they could not understand their maths, or their language. The theoreticians were powered by the conviction that they were cleverer than the biologists (they were) and that thinking and argument and analysis alone can solve biological problems (they cannot). “Physicists are all too apt to concoct theoretical models that are too neat, too powerful and too clean. To produce a really good biological theory one must try to see through the clutter produced by evolution to the basic mechanisms lying beneath …. What seems to physicists to be a hopelessly complex process may have been what nature found simplest, because nature could only build on what was already there.” “Elegance and a deep simplicity, often expressed in an abstract mathematical form, are useful guides in physics, but in biology such intellectual tools can be very misleading. For this reason a theorist in biology has to receive much more guidance from the experimental evidence….” In that period, in 1974, there was a meeting organised by Christopher Zeeman to bring the two species together in the UK. It was attended by the great French topologist, René Thom. The meeting was set up so that the two species could interact, something they usually failed to do; the biologists gave their talks with pictures, and the theoreticians theirs with equations. I was there and I don’t think we understood each other much. At the end of the meeting there was a question and answer session, and one of the few people who could speak both languages (Graeme Mitchison) mischievously asked Professor Thom how he valued experiments. There was a very long pause, and then he pronounced “Un experrimen eez a questionne, eef you ask a seely questionne you will get a seely answerrr!” “René Thom was a good mathematician.. but I suspected any biological idea he might have would probably be wrong.” The meeting then disbanded and it was followed by the gradual disappearance and near- extinction of those theoreticians who had attempted to model developmental processes. In relatively few years some of their journals died out and their impact on biology faded — they were killed off partly by the sheer Interest in quantitative and theoretical approaches to biology would seem to be on the increase, as evidenced for example by new institutes starting up that will focus on ‘systems biology’, and the increasing number of theoretical papers in high-profile biology journals. In the light of these developments, we have invited authors likely to express a variety of views on these developments to write essays addressing the general issue of what theory can and cannot do for biology. This piece by Peter Lawrence is the first in what will be an occasional series. See also the editorial in our September 16 issue “Biophysics and the place of theory in biology” (Current Biology 13, R719-R720). Readers with any responses to these essays that they feel may be of general interest are welcome to send in a letter for possible publication in our correspondence section, in which case email the editor at: [email protected]
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Transcript of Theoretical embryology: a route to extinction?
MagazineR7
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:[email protected]
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: [email protected]
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
