Make your own monster Adrian Woolfson MutAnts: On the Form, VArieties And Errors of the HumAn Body by ArmAnd MArie Leroi HarperCollins, 431 pp, £20.00, May 2004, ISBN 0 00 257113 7 JAcob’s LAdder: The History of the HumAn Genome by Henry Gee Fourth Estate, 272 pp, £20.00, March 2004, ISBN 1 84115 734 1 848 an advertisement in the Brooklyn tury, the mood of the public had changed Eagle triumphantly announced a per- and the public display of such ‘human Iformance by ‘the most extraordinary prodigies’ – as they preferred to be called – and interesting man in miniature in the had become unacceptable in many coun- known world’. Charles Sherwood Stratton tries. The profession of ‘museum freak’ was a perfectly formed 25-inch-tall midget, was in terminal decline. who weighed only 15 pounds. It had been Such discontinuous variations on the the idea of the Victorian freak show impre- human form are rare, but we are used to the sario Phineas Taylor Barnum to present continuous everyday variations that com- him in the guise of ‘General Tom Thumb’. prise the full spectrum of the ‘normal’. Before long, the general’s imitations – ‘in They leave the basic body plan intact, and full military costume’ – of Napoleon Bona- are the stuff of evolution by natural selec- parte and Frederick the Great, and a varied tion. The more ‘monstrous’ variations are repertoire including a ‘Scotch song’ and a unlikely to be of direct significance in evo- rendition of the polka, would make him a lutionary processes, but they do offer inval- wealthy man. Following his hugely success- uable insights into the way animal form is ful London debut at the Princess’s Theatre generated. four years earlier (the Illustrated London Unusual characteristics can have envi- News had described him as ‘a little mon- ronmental causes: the skin of the 19th-cen- ster’), he had received three separate invi- tury freak show exhibit the ‘Blue Man’ was tations to visit Queen Victoria at Bucking- ‘the colour of a Maltese cat’ as the result of ham Palace. His unexpected success the prolonged administration of silver ni- spawned a host of copycat acts including trate for dubious medicinal purposes. Most ‘Anita the Living Doll’, ‘Leonine the Lion variation in human form, however, occurs Woman’, ‘Chang the Chinese Giant’, ‘Jo-Jo because the genes responsible for every the Dog-Faced Boy’ and John Merrick, the part of our internal and external make-up ‘Elephant Man’. But by the turn of the cen- come in different versions. Each of these 1 31 August 2016 arises from a process of random gene mod- thing short of human, but modern genetics ification called mutation, which is largely has taught us that all living things share caused by errors of copying, or the damage fundamental generative processes and done by mutagens such as UV light or principles. Indeed, some of the genes that chemicals. Occasionally, mutations pass control human development work equally permanently into the genetic record. The well when transplanted into other species. frequency with which this happens has it- This conservation of generative principles self evolved: if too many errors are intro- between widely different species reflects duced into the genome of an organism, its their shared evolutionary history; evolu- core information will melt away; too few, tion works by tinkering with pre-existing and there would be insufficient variation genetic programs. Gene sequencing initia- for evolution to work with. tives have shown, much to our surprise, In Mutants, Armand Marie Leroi argues that humans have almost exactly the same that in order to understand how people’s number of genes as organisms of broadly bodies are constructed, biologists need similar structural complexity, such as mice now to focus their attention on the bestiary and monkeys. Many of these 25,000 or so of human variation, both normal and ex- genes are, furthermore, similar or treme. As people are not clocks, we cannot near-identical in kind between related spe- simply take them apart and reassemble cies, so that it’s worth asking what exactly them to investigate their inner workings, it is about our own genome that makes us for both practical and ethical reasons. As a distinctively human. result, we must either study nature’s own As the genome project expands, making random ‘experiments’ on human form, as it possible to compare the human genome evidenced in ‘normal’ variation and devel- with those of distantly related organisms, it opmental errors, or focus our attention on becomes easier to assess the extent to animals. The latter strategy has proved which mice, worms, fish and flies provide enormously useful; new technologies ena- models for understanding what goes on in ble genes to be inserted or deleted as re- humans. It turns out that a little circum- quired, so that their effects on form can be spection is needed. A recent study of the studied. The genomes of flies, worms and coral species Acropora millepora, for ex- fish have been randomly mutated using ample, identified large swathes of genes chemicals or radiation so as to generate shared by coral and humans which were bestiaries of bizarre mutants whose de- not found in common model organisms tailed mechanics can then be unravelled. such as the fruit fly Drosophila melano- Such models are the source of the vast ma- gaster or the nematode worm Caenorhab- jority of what we currently know about the ditis elegans, even though flies and worms way animals – including humans – are evolved millions of years later than coral. made. Such findings, which were quite unexpect- It is true that a mouse or a worm is some- ed, suggest that at least some of the genes 2 31 August 2016 thought to be the evolutionary innovations tions are, collectively, ‘a Rosetta stone that of vertebrates have more ancient origins. enables us to translate the hidden meaning Animals may in some instances discard of genes’, there is no new revelation here, genes as they become more complex. It and the importance of human mutations would appear that in order to gain a true has not, as might be inferred, entirely es- understanding of the genetic make-up of caped the attention of contemporary biolo- human beings, we will need to study a far gists. Great efforts have been made to doc- greater range of organisms. ument human genetic diversity, in particu- Leroi, however, believes that if we are to lar that of indigenous populations, in order understand human beings, we should pay to identify the SNPs (single nucleotide pol- more attention to human variation than to ymorphisms) that underlie many of the what other organisms can tell us. He illus- common differences between individuals. trates his thesis with accounts of conjoined Once gene sequencing technology is suffi- twins, developmental disorders of eyes, ciently advanced, it will be possible to as- faces, fingers and limbs, skeletal abnor- semble huge databases of complete ge- malities, giants, midgets, dwarfs, albinos, nomes gleaned from thousands and even- abnormalities of sexuality and excessive tually millions of individuals, so as com- hair growth. Each deviation is supplied prehensively to determine the genetic basis with a specific historic example. Thus we of individual variation and susceptibility to encounter Catherine de Medici, who in the disease. 16th century tried to create a race of minia- But in the end, the key information per- ture humans by arranging a marriage be- taining to the generation of human form tween two dwarfs; and Ritta and Christina will almost certainly come from the further Parodi, the conjoined twins whose dissec- study of animals rather than human mu- tion soon after their death on 23 November tants. Leroi’s project is a recapitulation of 1829 enthralled Paris, at the same time Francis Bacon’s in his Novum organum of provoking moral outrage from the critic Ju- 1620: ‘We must make a collection or par- les Janin that anatomists could ‘bring this ticular natural history of all the monsters monster to the level of ordinary men’. and prodigious products of nature, of every Leroi, in characteristic fashion, follows novelty, rarity or abnormality.’ But unlike this story with a discussion of the molecu- Bacon, who emphasised the utility to which lar genetic mechanisms thought to under- such a collection might be put, arguing that lie such abnormalities. Tellingly, though, ‘once a nature has been observed in its var- as is almost always the case, these were elu- iations, and the reason for it has been made cidated in animals – in this instance newts clear, it will be an easy matter to bring that and mice – rather than in humans. nature by art to the point it reached by Leroi’s book is clever and greatly enter- chance,’ Leroi skirts the issue. In unravel- taining, but not, in the end, entirely satisfy- ling the mechanisms by which nature con- ing. While it is undoubtedly true that muta- structs living things, we are, surely, con- 3 31 August 2016 structing the platform on which we will one ential errors such as Ernst Haeckel’s in his day redesign life from first principles and Generelle Morphologie der Organismen create our own ‘monsters’. Leroi’s decision (1866), where he argued that the develop- not to address this possibility is disap- ment of an organism follows its evolution- pointing; he chooses instead to conclude ary history; or, more succinctly, that ‘on- with an entertaining but trivial discussion togeny recapitulates phylogeny.’ Mutations of beauty. that alter the genetic programs determin- The quest for the secrets of biological ing development are responsible for the form, which we have now located in the ge- major deviations from human form that nome, can itself be traced back to antiqui- occur from time to time.