ISSN 1359-9321 The Galton Institute NEWSLETTER

Galtonia candicans Issue Number 67 June 2008 EDITORIAL wife, Julia Bodmer, and Rose Payne, Contents which contributed to the discovery of the Presidency of HLA system. In 1970 he left his Profes- sorship of Genetics at the Stanford The Galton Institute Medical School to become Oxford’s The Galton Institute,

Professor of Genetics. He was elected New President 1 At the end of six active years as FRS in 1974 and in 1979 moved to President of the Galton Institute, London as Director of Research at the Imperial Cancer Research Fund Labora- Conference 2008 2 for which, in acknowledging his constant concern, we can here tories, becoming the first Director- General of the Fund in 1991. Retiring in Medicine may change warmly express sincere gratitude, 1996, he returned to Oxford as Principal our genes 4 Professor Steve Jones of Hertford College. Since the end of his has been succeeded by Professor tenure as Principal he has continued as Sir , on whom head of the Cancer and Immunogenetics The Human Genome 5 Anthony Edwards has provided Laboratory at the Weatherall Institute of the following note. Molecular Medicine, with a special Report of Innovation interest in cancer genetics, particularly and Evolution workshop 9 colorectal cancer. Sir Walter Bodmer, who gave the 2008 Galton Lecture Population genetics Knighted in 1986 for services to Genetic Testing: and the concept of individuality, became science, Sir Walter is a Foreign Associ- Uses and Limitation 10 a Fellow of the Society in 1961 ate of the US National Academy of Sciences and the recipient of more than and served on the Council from 1971 to The Powers of Natural 1974. A Cambridge mathematician, in thirty honorary degrees and fellowships his third year he attended genetics of scientific and medical societies. Selection 12 lectures by Sir , then in his In the 1970s Sir Walter was the Published by: retirement year as Arthur Balfour chairman of a British Association Professor of Genetics. Sir Walter joined committee examining the implications of The Galton Institute his department as a Ph.D. student, and recent advances in genetics which 19 Northfields Prospect happily Fisher carried on in the depart- resulted in a book, Our Future Inheri- Northfields ment pending the election of his succes- tance: Choice or Chance?, co-authored LONDON SW18 1PE sor, greatly influencing a whole genera- by Alun Jones the committee’s secretary. Telephone: 020 8874 7257 tion of students. In the 1920s and 30s His well-known books with L.L.Cavalli- General Secretary: Fisher himself had been influential in the Sforza, The Genetics of Human Popula- Mrs Betty Nixon Eugenics Society, acting as its business tions (1971) and Genetics, Evolution and secretary for a while. Man (1976) are testimony to an out- Newsletter Editor: In 1961 Sir Walter left Cambridge standing breadth of interest in the science Milo Keynes for Stanford University to work with central to the purposes of the Galton

Joshua Lederberg in molecular biology. Institute. Web site: www.galtoninstitute.org.uk While there he initiated work with his A. W. F. Edwards

GALTON INSTITUTE NEWSLETTER 1 JUNE 2008 a single monogenic blood disorder could which is a social construct; and adopt still lead to a very complex phenotype instead the term ‘ancestry group’ which CELEBRATING depending on the influence of other fac- is a more biological and less pejorative 100 YEARS OF MEDICAL tors such as: genetic modifiers; the ef- construct. GENETICS AT THE RSM fects of parental imprinting and other The rest of the lecturers for the first events that modify gene expression dur- day dealt with genetics applied to various ing development (e.g. epigenetic effects disorders including infectious disease A joint meeting of The Galton Institute such as DNA methylation or histone and The Royal Society of Medicine, (Professor Adrian Hill), allergies (Dr. modification); and differing adaptations May, 22-23 2008 John Holloway), male infertility (Dr. to environmental conditions. Ken McElreavey) and the muscular The Galton lecture was delivered by dystrophies (Professor Francesco Mun- Report on the proceedings made Professor Sir Walter Bodmer. He toni). gave a fascinating account of how work by David Galton The second day returned to some on polymorphic systems, starting with more general topics. Professor Peter the ABO blood groups, and then the McGuffin addressed the genetics of be- HLA system, to the knowledge of which Professor Sir Patrick Bateson is a haviour. Some gene abnormalities clearly he made fundamental contributions, has distant cousin of William Bateson (1861- influence behaviour as in Huntington and led to an explosion in the study of how 1926) who invented the word ‘genetics’ Alzheimer’s diseases to give two obvious genetic variation can affect disease sus- in 1905 and who, in his book entitled examples. However other common disor- ceptibility. His own work on the genetics ‘Mendel’s Principles of Heredity’ CUP ders such as schizophrenia or bipolar of colorectal cancer was one of the early 1909, had long adopted the Mendelian disorders have proved more refractory to valuable benefits of this approach; and standpoint whole-heartedly. This led him genetic analysis. Even genome wide his methods are now used routinely to into direct conflict with the biometricians scans have not clarified the issues. But detect subjects who carry such a genetic of the day, notably Karl Pearson, who Professor McGuffin believes that such predisposition in clinics around the believed that heredity involved continu- scans will, ultimately, improve our un- world. His ideas and writings on the ous variation or blending of traits. Due derstanding of the neurobiology of these subject have led to most fruitful develop- to the personalities involved the debate disorders. ments as exemplified by the Wellcome became quite bitter and was still ongoing Trust Case-Control Consortium. The Professor Mandy Fisher then dealt well after 1912. The conflict was finally rapid advances in DNA technology in- with the epigenetics of development, that resolved in 1918 by R A Fisher (1890- cluding the use of polymorphic markers, is how patterns of gene expression are 1962) who showed how both views were DNA hybridisation techniques, and fast established and maintained through cell compatible if one considered that a few DNA sequencing methods have entirely division and changed in an ordered fash- discrete genes acting together could pro- replaced the old serological and electro- ion during development. She described duce the appearance of continuous varia- phoretic techniques and have allowed the three main ways of controlling genes tion in inherited traits as is found, for study of the genetics of 12 common dis- over the long term: 1. Modifying the his- example, in skin colour. eases discussed later in the meeting. tones associated with DNA, 2. Use of Professor Sir David Weatherall small regulatory RNA molecules to si- However Sir Walter’s current interest went on to praise the work of another lence stretches of DNA and 3. Covalent is to use the new technology to study early pioneer of heredity, Sir Archibald modification of DNA by methylation. relationships between various human Garrod (1857-1936). Garrod was fasci- Such changes can alter the packing of populations, their geographical origins, nated by the various colours of the urine nucleosomes to vary the access of tran- their migrations and to relate this to the due to the pigments produced in differ- scription factors and RNA polymerases. available historical and archaeological ent conditions. One in particular, alkap- She illustrated aspects of this in her own information. tonuria causing the urine to become black work of attempting to re-programme on standing, was particularly interesting Professor Marcus Feldman contin- lymphocytes to an induced-pluripotent because in some first cousin marriages it ued on this theme using up to 800,000 state i.e. to be more like stem cells. This occurred in a ratio of 1:3 in the resulting polymorphic DNA markers to track would have important implications for offspring. This was published in the Lan- population movements. It is difficult to regenerative medicine. cet in 1902 and William Bateson recog- do these studies in North America be- nised these numbers as conforming to a cause ethnic status is such a politically Professor Eamonn Maher talked on Mendelian ratio of inheritance as initially sensitive issue – no doubt due in part to cancer genetics taking von Hippel-Lindau described for the garden pea. Alkaptonu- their recent history of slavery. So the disease as his model. This dominantly ria, with the description of several other project was moved to the world stage. inherited cancer syndrome predisposes to metabolic disorders, formed the basis of His work has shown beyond question that retinal and cerebeller haemangioblas- the Croonian Lectures given by Garrod in hominids migrated out of Africa to colo- tomas, renal cell carcinoma, and phaeo- 1908 that firmly placed Mendelian genet- nise the middle and Far East as well as chromocytoma. His laboratory analysis ics into the field of human heredity. Sir Europe. He ended his lecture by suggest- has shown that activation of HIF-2 tran- David ended his lecture by showing how ing that we should drop the term ‘race’ scription factors appears to be a major

JUNE 2008 2 GALTON INSTITUTE NEWSLETTER drive for oncogenesis in renal cell carci- nomics was discussed by Dr. Joanna Galton Lecture 2008 noma. Mountain. Selling people the details of Population genetics and the concept of their genome (for about $1000) may pos- Ageing appears a necessary ordeal genetic individuality sibly be of use to them but is also likely that we all have to endure and Professor Professor Sir Walter Bodmer, FRS, to generate a great deal of anxiety in the Tom Kirkwood tried to explain why. Oxford Genes are clearly involved - up to about worried-well population in a field they do not fully understand. After all the scien- 25% of the variance in life span may be The race/ethnicity/ancestry debate: tists who discover these gene markers do genetic - and rare diseases such as a genomics perspective not fully understand their significance. Werner’s syndrome and other progerias Professor Marc Feldman, Stanford illustrate this well. But Professor Kirk- Before these DNA markers are adopted by the medical establishment in most wood’s view is that ageing is due to the Genetic Predisposition to infectious dis- countries as providing cast-iron diagnos- accumulation of a multitude of small eases, past and present tic markers for disease and susceptibil- errors occurring in various bodily sys- Professor Adrian Hill, Oxford tems such as: DNA repair mechanisms, ity, perhaps there should be misgivings about selling the information to the gen- antioxidant defence mechanisms, inabil- Allergies to allergic disease—from 1916 eral public. ity to re-structure proteins properly, mito- to the present day chondrial and somatic cell mutations, and The meeting closed with an impas- Dr John Holloway, Southampton various forms of tissue damage due to sioned argument by Dr. Peter Corry to poor nutrition, trauma etc. The quest for do something about the consequences of Declining male fertility: a threat to all or an elixir of life appears therefore to be a the high incidence of consanguineous just some? very difficult issue. marriages amongst the Pakistani commu- Dr Ken McElreavey, Paris nity of Bradford. First cousin and double Professor Peter Donnelley gave a cousin marriages carry greatly increased Gene therapy for muscle diseases short account of the Wellcome Trust risk of ill health through genetic disease Professor Freancesco Muntoni, Lon- Case-Control Consortium, a collaboration in their future off-spring. But even non- don of more than 200 UK scientists studying cousin biraderi (within clan) marriages the genetics of 12 common human dis- pose risks. These are the occurrence of Day 2: eases. He presented the results of 7 of deafness, metabolic disorders, and micro- Genomic analysis of human behaviour them including coronary heart disease, cephaly, bleeding disorders and neurode- Professor Peter McGuffin, London hypertension and diabetes mellitus generative conditions in their offspring. (Types 1 and 2). The analysis was based Similar conditions apply to other UK Epigenetics and development on 2000 cases and 3000 controls, 1500 of cities with a large Asian immigrant popu- Professor Amanda Fisher, London which came from two different sources. lation. What is to be done? Legislation They were ethnically matched and ge- would probably be ineffective; so advo- Familial cancer genes: from gene to nome wide scans were performed. 19 cacy and persuasion appears to be the clinic loci were associated with Type 2 diabetes best route. Education of the immigrant Professor Eamonn Maher, Birming- and 30 loci with Crohn’s disease. But population about the hazards of cousin ham much further work by fine-mapping, marriages, easy access to medical checks, DNA re-sequencing and functional stud- group discussions amongst families that Ageing: part of the human phenotype or ies are needed to identify the functional already have defective children (this is an inherited disorder? gene variants that underlie these associa- often kept secret) might all help to deter Professor Tom Kirkwood, Newcastle tions. further intermarriages in such families. Professor Rory Collins pointed out The meeting ended with thanks and Stem cells and regenerative medicine that the important problems of gene- congratulations going to Professor Alan Professor Sian Harding, London environment interactions are not being Bittles for organising such an excellent studied properly in either retro- or pro- meeting for the RSM and Galton Insti- Genome-wide association studies spective studies. After giving examples tute. Professor Peter Donnelly, FRS, Oxford he showed how small numbers of cases,

inadequate analysis of all the environ- Programme Gene-environmental interactions in mental circumstances and incomplete Day 1: multi-factorial disorders measures of confounding factors have all Family connections: the 1908 Mendelian Professor Rory Collins, Oxford led to confused and unclear results. He versus Biometrics debates believes the subject needs much larger Professor Sir Patrick Bateson, FRS, blood-based prospective epidemiological Personalized genomics Cambridge studies in a range of environmental set- Dr Joanna Mountain, Stan- ford/23andMe tings with detailed follow-up of cause Garrod: the Croonian Lectures and be-

specific morbidity and mortality to get a yond Medical genetics in a multi-ethnic society clearer picture of such interactions. Professor Sir David Weatherall, FRS, Dr Peter Corry, Bradford The thorny topic of personalised ge- Oxford

GALTON INSTITUTE NEWSLETTER 3 JUNE 2008 time, under the pressure of discernable Maybe we are all more myopic as a result social and historical forces. of medieval lens grinders. Maybe our Medicine May Change The best example so far is the evolu- bones are weaker since we have had Our Genes tion of lactose tolerance in adults. The bone-setting technology for thousands of ability of adults to digest lactose confers years. Maybe the changes in survival of Nicholas A. Christakis evolutionary advantages only when a patients receiving treatment for all sorts stable supply of milk is available, such as of conditions that are wholly or partly after milk-producing animals (sheep, cat- attributable to single or multiple genes tle, goats) were domesticated. The advan- (ranging from sickle cell disease to type 1 A lot of hot air is around at the tages are several, ranging from a source diabetes) are resulting in changes in the moment—and quite a bit of overselling— of valuable energy to a source of neces- human genome. Maybe the introduction about advances in genetics, personalised sary hydration during times of water of penicillin and childhood immunisation genomics, and gene therapy. Only a small shortage or spoilage. has changed our genes. Some have noted part of the variance in human illness is Amazingly, several adaptive mutations that the number of children with Down’s explained by genetics; most is explained have occurred in widely separated popu- syndrome is falling in many industrial- by social factors such as poverty and be- lations in Africa and Europe just over the ised societies as a result of selective abor- haviour. Yet large sums are spent in a past 3000 to 9000 years, all conferring tion. With the onset of personal genetics, quixotic pursuit of the genetic basis for the ability to digest lactose. These muta- it is not hard to imagine this being taken a everything. tions are principally seen in populations step further. Medical technology might The hope—some say fear—is that we of people who are herders and not in change our genes indeed. will be able to use advances in medical nearby populations who have retained a Medicine is not the only thing doing technology to reshape the genome of in- hunter-gatherer lifestyle. This trait is suf- this in ways relevant to health and well- dividual patients, curing ailments by ficiently advantageous that those with the being. There may be genetic variants that changing somatic genes. Some even hope trait have many more descendants than favour survival in cities, consumption of that we will be able to modify our species those without. alcohol, or a preference for complicated for the better by introducing changes into A similar story can be told about rela- social networks. There may be altruistic our germline. tively recent mutations that confer advan- genetic variants that favour living in a Ethicists hotly debate this topic, argu- tages in terms of surviving epidemic dis- democratic society. Maybe even the more ing about the case for or against eases such as typhoid in Europe. As these complex world we live in nowadays “perfection.” Do we have the right to diseases were made more likely when the really is making us smarter. develop technologies that would allow us density of human settlement increased Unfortunately, this also means it may to change the human genome? Some and far flung trade became possible, here be the case that particular ways of living would say this is a duty. After all, if we we have another example of how cultural and particular medical technologies cre- could develop a genetically based treat- change may affect our genes. ate advantages for some but not all mem- ment for patients with sickle cell disease, Of course, our biology and our culture bers of our species. Certain groups may cystic fibrosis, or diabetes, who would have always been in conversation. For acquire (admittedly, over centuries) cer- not support that? example, rising socioeconomic status tain advantages. The idea that the appli- But overlooked in all this debate are with industrial development resulted in cation of medical technology modifies the ways in which—just possibly— people becoming taller (a biological ef- what kind of offspring we have is as trou- medical advances may already be chang- fect of a cultural development), and taller bling as it is amazing. However, it pro- ing our genes at the population level. people required a change in architecture vides a way for us to begin to think about It used to be thought that our genes (a cultural effect of a biological develop- the inevitable genetic revolution in medi- were historically immutable and that it ment). Anyone marvelling at the small cine that is around the corner. was not possible to imagine a conversa- size of beds in medieval houses knows tion between culture and genetics. It was this at first hand. But it seems that it is Reprinted from BMJ, vol.336, p.1101, thought that we as a species evolved over also possible for genetic change to take 2008. Nicholas A. Christakis, MD is a timescale far too long to be influenced place over relatively short time periods. professor of medical sociology, Harvard by human actions. But evidence has been Why does this matter to medicine? Medical School and attending physician, mounting for the past decade that we as a Because many of the things we are al- Mt Auburn Hospital, Cambridge, species are evolving genetically in real ready doing may be modifying our genes. Massachusetts

JUNE 2008 4 GALTON INSTITUTE NEWSLETTER “nurture” mean today and whether they it is to disentangle nature from nurture. In can still be treated as separate entities. London, a trip on the Jubilee Line from Westminster to Newham represents a loss The Human Genome: The human genome project, now more of six months of life expectancy for a past, present and future or less complete, has been much publi-

cized as bringing Galton’s science into baby born close to each of the ten tube by stops. The proportion of the population the modern world. In fact, it has nothing from minorities goes up in parallel to the Professor Steve Jones to do with genetics. Instead it is anatomy – the dissection of a single human (or a decline of a baby’s prospects as we travel from the centre of the city to the East End committee of humans, with bits of DNA – and, needless to say, the skin colour taken from across the world) in ultimate genes are a proxy for poverty and poor When I give my first lecture of the detail. By so doing the genome project housing and have themselves little direct year to genetics undergraduates at Uni- has completed the task begun by Vesalius effect on health. versity College London I ask them to turn in the sixteenth century when he cut up a to the person to their left, and then to cadaver and discovered that the heart had But how much of that, or any other, their right; and I tell them (reasonably four chambers and not, as the Greeks had baby’s chances is due its nurture – in- accurately) that two out of three of those insisted, three. come, education, housing and all the rest involved in the exercise will die for rea- Anatomy, which in its modern guise – and how much to its inborn nature? The question seems simple: most people see sons connected to the genes they carry. includes much of molecular biology, the phenotype as a cake that can be sliced Then I cheer them up by pointing out that looks backwards to those days; it is a into a piece controlled by genes and an- had I been speaking in Shakespeare’s platonic science that turns on the notion other by environment. Every geneticist time, two out of three of them would be of an ideal and perfect form of human knows that is not true, and we all have dead already. being that can stand as the essence of all our favourite ways of explaining the fact. And, of course, the phrase which sets others. Genetics, in contrast, began with Mine is that popular mutant, the Siamese the theme of this conference comes from differences and still depends on them. cat, with its black ears, nose and tail (and, just that author and just that period in Inherited differences are everywhere. if it is a male, testicles) set off against a history. The evil monster Caliban, in The Plato himself seemed to admit as much, white body. Crosses show that the Sia- Tempest, is cruelly cursed with the state- with his men of gold, men of silver and mese is a classic Mendelian recessive. ment that “On thy foul nature, nurture men of iron, each born to his own allotted The gene locus has been tracked down, shall never stick”. fate and each bound to live his life by an and we know the DNA sequence of the agenda set in his very being. Some of our The attempt to separate those two great normal and the mutant allele. Nothing, it physical contrasts are obvious indeed. agents of fate - nature from nurture, gene seems, could be more in the cat’s nature They once seemed to divide the human from environment - goes back to the be- than its elegant fur. ginnings of history. The Old Testament race into distinct groups. , Crucially, though, the mutation is tem- was the first genetics text of all, for much in true Victorian style, produced a dia- perature sensitive; the enzyme that makes of the Book of Genesis is about pedi- gram – one of the first statistical distribu- black pigment has been damaged, but grees. The word “Begat” appears more tions ever published – which (while ad- only slightly. As a result it works per- than a hundred and fifty times in that mitting the superior abilities of the an- fectly well in the cooler extremities of the chapter and elsewhere; and many biblical cient Greeks) put the English at the top of cat’s body but not on the warmer core – themes are concerned with inborn fate. the racial tree, and the Australian Abo- which explains the pattern. To make a riginals at the bottom (with a noticeable Francis Galton, in Hereditary Genius, light Siamese, keep it in a warm room, overlap with “dogs, etc”). Even today, also argued that man’s nature was set at about three quarters of all papers in for a dark one, use a refrigerator. Inside birth. It has become fashionable to decry every Siamese is a black cat struggling to American public health journals show the his views but they are, in these days of get out – and the notion of slicing its at- race of the study population as evidence molecular genetics, still very much alive. of just how important it must be. tributes into a piece called nature and a This conference will explore them and to piece called nurture is meaningless: to get In fact, skin-colour points at how hard ask what, if anything, “nature” and the ingredients back one would have to

GALTON INSTITUTE NEWSLETTER 5 JUNE 2008 unbake the Siamese cake, which is im- acteristics have become murkier than the beta-globin chain that produce more possible. before. Everyone knows that racial dif- or less the same resistance to malaria in ference in the ability to withstand envi- heterozygous form. Many more (the That odd example of the ambiguities of ronmental stress, the inborn ability to thalassaemias as they are called) work inheritance is a pointer to great swathes of modern genetics – much of which will withstand malaria. A fifteenth-century by deleting sections of the alpha or beta chronicle by the first European explorers chain, often with disastrous effects in be discussed during this meeting. Heart of West Africa complained that “For our the homozygote. disease, diabetes, psychiatric illness and sins, or for some inscrutable judgement more: each is a major problem in the Malaria resistance can also emerge of God, in all that we navigate along He modern world and each has, no doubt, from changes in quite unrelated proteins. has placed a striking angel with a flam- some genetic component. Now we are The enzyme glucose 6 phosphate dehy- ing sword of deadly fevers”. Three hun- beginning to see the insights - and the drogenase is active in the red cell. Many dred years later, half the Englishmen ambiguities – that technology offers people have an inactive form – which who went to that part of the world died when trying to understand how much means that their cells are more sensitive within a year. The Africans were by such conditions are in the DNA, how to the waste products of the malaria comparison unscathed. much in a patient’s lifestyle – and how parasite; which leads to death of infected much, like the fur of the Siamese cat, Of course we now know why; sickle cells - and of the enemies within. Other turns on an interaction between the two. cell anaemia – a simple genetic condi- defence mechanisms involve not struc- Genetics has rediscovered its essence, tion that alters the response to infection. tural changes in a protein, but shifts in the search for difference. About one site In fact malaria resistance is not simple at gene expression. The Duffy blood group in every thousand in human DNA varies all. Instead it is a microcosm of how is a cell surface molecule which comes a from person – which means three million complicated the genetics of even what in two forms: Fy in much of the world - potentially variable sites in every popu- seems a simple phenotype can become. and Fy in west Africa. The latter gives

lation. Some of the variants are rare, but almost complete protection against one Many of the defences turn on the red many are common. The hapmap form of malaria. The antigen is the re- blood pigment, haemoglobin. Around (haplotype mapping) project, as it is ceptor by which the parasite binds to the 250 million people carry a single copy - known, sets out to search for relatively red cell membrane. Fy individuals do of a damaged globin gene; which means frequent single-letter changes in the ge- express the substance on many of their that one person in 15, world-wide, is a netic alphabet, and has now found cells, but its production is switched off carrier. One common variant is indeed around nine million of them. Each group in blood cells. The parasite is beaten not sickle-cell, a variant in the beta chain, of variants acts as a milestone in the ge- by structural change in the DNA, but by which in single dose protects against nome. By looking at the patterns of joint gene regulation. infection although those with two copies inheritance of any human attribute, nor- Other protective mechanisms were of the damaged gene may be severely ill. mal or diseased, with those DNA discovered because they have separate, The shift reduces the stability of the changes we should, in principle, be able and apparently unrelated, properties that protein and the cell becomes an un- to track down the genes responsible. may themselves cause problems. The friendly place for parasites to live. The results are fascinating in their inherited illness haemochromatosis is Sickle cell seems simple enough – but ambiguity. After a period when it frequent among people of African ances- complexity soon raises its head. The seemed that technology would track try. It leads to the presence of large hapmap segment around the damaged down the genes for most of the illnesses amounts of iron in the blood which in beta-globin gene shows that the muta- that plague us and – perhaps – reveal our turn can damage the liver. It is common tion has happened independently at least very essence there has emerged an era in because high levels of iron in the red cell four times in different parts of the world which our nature is more complicated, kill malaria parasites, which keeps the – which may explain why homozygotes and our interactions with nurture (the gene in the population. in India suffer less from symptoms of environment as it is otherwise known) sickle-cell disease than do those from In a further, and perhaps general, more equivocal, than anyone expected. west Africa. Now we know over a hun- complication to the malaria story, some Even simple and easily defined char- dred different amino acid alterations in genes interact to produce the phenotype:

JUNE 2008 6 GALTON INSTITUTE NEWSLETTER the children of certain middle-Eastern ics. Even what seems a simple problem - Some groups have suffered more than families with sickle cell disease seem to defining the character of interest – turns others. Native Americans – an Arizonan do rather well – because they have inher- out to be annoyingly complicated. One tribe called the Pima Indians most of all ited another gene that retains a form of measure of excess fat is the body mass – seem to be particularly at risk. Pictures haemoglobin normally found only in the index; a person’s weight in kilograms taken a century ago show them to have fetus in the adult blood stream. Now, divided by the square of their height in been slim, elegant, and healthy. For almost fifty additional genes are known centimetres. That makes for a convenient many Pima today, obesity is a plague to have some effect on the chances of graph onto which people can place them- and they have one of the highest inci- infection by malaria, or on the progress selves - and in Europe now about one dences of adult-onset diabetes in the of the disease. man in six and one woman in four is world. The genes have not changed in

Malaria resistance, which once obese on that measure. Among them, that time; but the environment has. The though, are many fit men and women Pima have had a huge shift in dietary seemed simple, involves many loci, with who are so muscular that their body habits. They have always eaten corn (or many alleles. Different populations, and mass is high, even though they had no maize as we know it) and once called different families within the same one, spare fat. themselves the Corn People to reflect construct the phenotype in different that fact. Corn accumulates isotopes of ways, often with genes that have other, Another measure – a better predictor carbon in a unique way, which means unrelated, effects on quite separate as- of the health effects of corpulence - is that the record of how much has been pects of their being. simpler; a tape-measure. Fat people consumed is laid down in the bones. The intricacy of that phenotype has a come in two flavours, apples – with the Modern Pima eat about the same amount excess around the stomach (a pattern much wider message. Malaria has been found more frequently in men) compared as before – with the crucial difference replaced as a European disease by an that it has been through a cow, a chicken to pears – in which the weight moves to illness which acts as a microcosm of the or a soft-drinks factory first. A Mac- the buttocks (more common in women). nature-nurture problem; the plague of Apple obesity is far more dangerous, donald’s meal is, in effect, corn. The obesity now attacking the developed chicken is fed on it and fried in it, and both because of the pressure on internal world. Two centuries ago, Marie Antoin- thirteen of a Chicken Macnugget’s organs and also because gut fat can be ette told her peasants to eat cake, and more rapidly mobilised to add to blood thirty-eight ingredients come directly they did. Now, for the first time in his- from that crop. cholesterol. A heavy man with a large tory, the poor are fat and the rich are behind may be at less risk than a lighter Why do the Pima pay such a high thin. The English waistline puts our con- one with a generous waistband – which price for the shift in the way they eat tinental cousins to shame, although the is an illustration of a general, albeit their favourite plant? They were once average belt is still drawn somewhat sometimes forgotten, problem in genet- said to be at particular risk of an un- tighter in the Old than in the New World. Pessimists predict that my own genera- ics; defining quite what we are looking healthy diet because of their own DNA; at. they had, it was claimed, a “thrifty geno- tion – those in middle age – may be the type” which was adapted to sudden longest-lived in history, for they gained Nobody denies that fat runs in fami- from the healthy diet of the 1950s while lies but so do frying pans, which makes bursts of feast among long periods of famine. Their special metabolism laid their successors are losing to the pres- it hard to know whether DNA or drip- down fat when food was available, sure to eat more and exercise less. Obe- ping is more to blame for the modern sity kills more Americans than does plague of obesity. Both genes and envi- against the drought to come. smoking and the rest of the planet is ronment are involved, and sometimes Now that idea has been more or less panting close behind. they interact in unexpected ways. Fa- abandoned, for no such gene has ever

Many people believe that they are fat mously, fat cats tend to have fat owners. been found. Even so, genetics certainly Nobody blames that on shared genes, but does have some effect on obesity. In one for genetic reasons; but, rather few deny, instead there is a joint tendency to serve experiment, several pairs of identical the environment is also in part to blame. Is it possible to disentangle the two? up too much food. twins were gorged, or starved, for three months. For the gourmands, the average Diet is, of course, important in weight Obesity, more even than malaria, weight gain over that period was around gain, whatever the effects of genes. shows the problems now faced by genet- seven kilograms. There was a huge range

GALTON INSTITUTE NEWSLETTER 7 JUNE 2008 of increase, with a few gaining only a it is called, contains more than four hun- terone lived a decade longer than their little, and others ballooning towards gro- dred genes supposed to be associated unmutilated fellows, as evidence for just tesqueness. The range was wide; but with excess fat. Most seem to apply in how dangerous the substance must be. there was three and half times more only one study of a single family, or a One clear attribute of the masculine variation between pairs of twins than single population. Cynics – and all good phenotype is murder: men murder, and scientists should include themselves within members of the same pair. Shared are murdered, at several times the rate of among that group - claim that there are genes meant a similar response to caloric women. The effect is quite consistent, overload. absolutely no convincing general fits of with the same pattern in London, Tokyo DNA variation with obesity in human In a few cases, the genes responsible and Detroit. That might seem to prove populations. If genes have any real im- at least for morbid obesity have been the role of nature in that cause of mortal- portance in today’s wave of lard, we tracked down. A mouse mutant – the ity; but the murder rate itself varies by have not found them. obese mutation – turned up a few years twenty times between Detroit and Tokyo ago in laboratory stocks. It eats vora- Obesity is a microcosm of the difficul- (which means that an American woman ciously, because it lacks a hormone ties of sorting nature from nurture. is considerably more dangerous than is a called leptin that normally tells a hungry Genes, the environment, and an interac- Japanese man). The reason lies, of animal when to stop. A very few chil- tion between the two are all important. course, in nurture; in the cultural differ- dren are born with the same problem; We will hear in the Galton Lecture from ence between the two cities, and the they are enormously overweight and Marcus Pembrey about some startling availability of guns. Nature and nurture never become sexually mature. Leptin trans-generational effects that also have interact (although in practical terms it is injections have a dramatic effect. Even an effect: and although I do not want to easier to get rid of guns than to castrate so, every attempt to use leptin to treat the give away the secrets of his talk it may every potential criminal). mark a new departure in the way in great majority of fat humans has failed. Plato admitted that his own notion of which we look at the inheritance of In the same way, a vaccine against an- inborn fate – his men of gold, silver and genes, and of environments. other such hormone as a means of iron – was a “noble lie”, which although weight loss has just been abandoned. His work is another stake through the untrue should be promoted because it led There is quite a lot of variation in the heart of the Shakespearean (and Weiss- to a stable society. The use of genetics as structure of the leptin gene, but there is manian) dogma. It shows that that their a universal alibi for obesity, crime or no fit with corpulence here, either. That shared claim that the germ line is kept anything else is equally dubious. The reflects a widespread finding that genes safe from the thousand natural shocks Nobel Prize winner Sidney Brenner once which lead to a severe pathological state the soma is heir to – is just too dogmatic. told me that the gene for obesity was – obesity, high blood pressure and more found long ago: it is the one that makes The subtleties of that dogma are no- – are often simple, but they have nothing you open your mouth! That was rather a where seen more clearly than in the uni- to do with variation in the “normal” flippant comment on a serious subject. verse of sex. World wide, women suffer range of that phenotype. We shall no doubt learn a lot more about more from obesity than do men, for all the complexities of nature, nurture and The search for genes predisposing to men have an inborn dose of that wonder- the interaction between the two during high body mass has been a disappoint- ful slimming drug called testosterone. this conference. I wish all those who ment. Hapmap has been much appealed Like many drugs, it has unwelcome side attend it - bon appetit! to, with ambiguous results. American effects, for those who use it have a

scientists have found a variant on chro- higher death rate from accidents, para- mosome 3, the French go for chromo- sites, and violence than do their mates. some 10, while some of the Pima may be An experiment carried out in 1930s This lecture was delivered by Professor at risk because of a gene on chromosome America, when many young boys were Jones at The Galton Institute’s 2006 11. The effect of each supposed gene is treated with eugenical castration to stop Conference Nature, Nurture, or Nei- small, and if any have a real effect in one them passing on their genes for mental ther?: Genetics in the post-genome era population it does not seem to apply to defects, and even for shoplifting, proves which was held in association with Pro- the others. its power. Cruel though their punishment gress Educational Trust at The Institute Now the human obesity gene map, as may have been, those deprived of testos- of Child Health in London.

JUNE 2008 8 GALTON INSTITUTE NEWSLETTER sity) who gave an extremely refreshing particular focus on archaeology but draw- powerpoint free presentation looking at ing upon a wide range of examples from Report of Innovation some of the ways in which technological other fields of research. and Evolution workshop innovations might be quantified. Finally The afternoon discussion session, open Prof Chris Sinha (Psychology, Ports- to all, was chaired by two of the work- Hannah Fluck mouth University) explored the themes of shop's co-organisers, Laura Basell (University of Southampton) time, space, semiosis and cognitive arte- (Archaeology, Oxford University/Exeter facts through his work with the Amon- University) and Kathy MacDonald The Galton Institute supported this dawa speaking people of Amazonia. conference with a grant of £1,000 (Archaeology, Leiden University, Nether- After this fascinating start the following lands). Discussions were lively pursuing session, chaired by Dr Marie Soressi, an the key themes of language, communica- The first international workshop on Archaeologist from the Max Planck Insti- tion, learning and transmission that had Innovation and Evolution took place at tute, Leipzig, continued with a little more emerged from the day’s presentations. Southampton University, UK on 27-28 emphasis on archaeology. Dr Mark Rob- April 2007. Thanks to generous funding The second day was opened by the erts (Archaeology, UCL) gave an insight- from the Galton Institute and support workshop's co-organiser, Natalie Uomini ful presentation about his work at the from the University of Southampton the (Archaeology, Southampton University), important Palaeolithic site of Boxgrove in workshop was a huge success. who summarised the topics from the pre- particular exploring the role played by vious day and introduced some potential The workshop was well attended with diet and nutrition in the early hominin directions for the day's discussions. The more than 70 people present over two occupation of northern Europe. Dr Miko- first session chaired by Dr Cintia Rodri- days. Participants came from countries lai Urbanowski (Archaeology, Szczecin guez begun with a paper by Prof Sophie throughout Europe, including Spain, University, Poland) presented some excit- de Beaune (Archaeology, University of France, the Netherlands, Sweden, Ger- ing new data regarding innovative tech- Lyon) about the role that research in neu- many, Poland, Switzerland, and from niques in flint working in the late Middle rological and cognitive sciences can play institutions such as Cambridge Univer- Palaeolithic. Keeping with flint technol- in the understanding of technological sity, Portsmouth University, University ogy Dr Jan Apel (Executive Director of innovations in the Palaeolithic. This was of Durham, the British Museum, Univer- the Societas Archaeologica Upsaliensis, followed by Dr Andreas Kyriacou sity College London, Royal Holloway, Sweden) spoke about the spread of new (Neuropsychology, University of Zurich) and the Max-Planck Institute. A range of flint knapping techniques across Europe. who spoke about innovation and creativ- fields of research were represented with The session was brought to a close with ity from a neuropsychological perspec- scholars from archaeology, psychology, questions and short discussion before tive. The final speaker of the session was primatology, neuropsychology and geog- lunch. Dr Matthew Pope (Archaeology, UCL) raphy and the combination of representa- The final session of papers for the day who looked at hominin behaviour in the tives from such diverse research areas was chaired by Dr Mark White Middle Pleistocene, in particular at mo- promoted some fascinating cross- (Archaeology, Durham University). The bility and landscape interaction. disciplinary dialogue and sparked a num- first speaker of the afternoon was Dr Cin- ber of discussions about potential cross The second morning session was tia Rodriguez (Psychology, Autonoma disciplinary research projects. chaired by Dr Farina Sternke, an archae- University, Madrid) who presented some ologist from University College Cork. The first day began, following a short interesting research into the use of ges- The first speaker, Dr Ignacio de la Torre introductory talk by the workshop's main tures and objects in prelinguistic infants. (Archaeology, UCL) looked at continuity organiser Hannah Fluck, with the first This prompted some interesting discus- and change in Neanderthal behaviour in three papers which set the tone for what sions about the role of language in inno- northern Spain. Next Dr Terry Hopkinson was an extremely diverse and interesting vative behaviour. Dr Rob Hosfield (Archaeology, Leicester) explored the day of papers. The session was chaired (Archaeology, Reading University) spoke role that social networks play in creating, by Dr John McNabb from the Centre for about anthropological research he had transmitting and maintaining innovations. the Archaeology of Human Origins at the undertaken into technological skill trans- Finally Prof Alan Costall (Psychology, University of Southampton. Dr William mission in a range of different extant cul- Portsmouth University) explored in detail Davies (Archaeology, Southampton Uni- tures looking particularly at the social some of the ideas concerning affordances versity) spoke about how innovation can and material context of this. The final and materiality or as he put it ‘doing be approached in the context of mobile paper of the day was given by Dr. Mimi things with things’. populations, with particular reference to Haidle (Archaeology, University of his area of expertise in the later Palaeo- Tübingen, Germany) and explored the The final session of the conference was lithic. This was followed by Dr Gordon issue of detecting innovative behaviour in chaired by Dr Bill McGrew (Primatology, Rugg (Computer Science, Keele Univer- the way in which tools are used, with a Cambridge University) and began with a GALTON INSTITUTE NEWSLETTER 9 JUNE 2008 presentation by Dr Lambros Malafouris pretations by different individuals while ment of innovations as well as some (Archaeology, Cambridge University) scale may not. In particular he consid- questions about the role that innovative exploring some of the debates surround- ered handaxe shape and scale and the behaviours might have played in ing the nature of materiality, human ob- implications of this for human cognitive hominin cognitive evolution. ject interactions and intentionality, with evolution. A closing wine reception was given at a particular emphasis on human evolu- The final discussion was led by Prof the Centre for the Archaeology of Hu- tion. Dr Vasudevi Reddy (Psychology, Paul Mellars (Archaeology, Cambridge man Origins where the discussions con- Portsmouth University) then presented University) and Prof Chris Sinha who tinuing and many new professional links some of her fascinating research into began by summing up their observations were forged. It is intended that the pro- infant communication and objects, look- of the conference. The discussions then ceedings of the conference will be pub- ing at some of the ways in which innova- opened up to the audience with a particu- lished. A conference building on the tive behaviours manifest themselves lar emphasis on including some of the success of this workshop is planned for ontogenetically. The final presentation of participants from primatology who had late 2007/early 2008. The organisers are the conference was given by Prof John not been able to present papers. There extremely grateful to the Galton Institute Gowlett (Archaeology, Liverpool Uni- were some fascinating interdisciplinary without whose generous grant the Inno- versity) and included an audience par- discussions about the significance of vation and Evolution Workshop would ticipation experiment looking at the way language in the emergence and establish- not have been able to take place. in which form may be preserved in inter-

which someone has a particular disease. in a number of different genes. Some In order for genetic testing to be possible genes have been identified and it is possi- Genetic Testing: certain conditions must be fulfilled: ble to test these, but clearly not those that Uses and Limitation are unknown.  The gene or genes must have been Examples of the uses of genetic testing- identified. Case studies Many people believe that since the  The result must be interpretable. Case1 A patient presented with a sequence of the human genome was pub- clinical diagnosis of myotonic dystrophy. lished in 2001 we are now able to test for  The test must be available either in a This is a neuromuscular disorder charac- any genetic disorder. Unfortunately this diagnostic lab or a research lab with the terized by the presence of myotonia and is not yet the case; what we have is a possibility of confirming a positive result progressive muscle weakness. The condi- book in which some of the words can be in a diagnostic lab. tion displays genetic anticipation – that is read easily, but others are still just a se- It is important to remember that muta- the presence of increasing severity and ries of letters. tions in different genes can cause the earlier age of onset in successive genera- The genetic tests requested by a genet- same disease, so that genetic testing may tions – and is caused by a dynamic CTG ics professional, or other clinicians fall involve the analysis of a number of dif- expansion in the DMPK gene. The ex- into two broad categories: chromosomal ferent genes. pansion enlarges when transmitted from analysis, and molecular genetic testing. an affected mother to her child, resulting Tests can be divided up into four cate- The mainstay of chromosomal analysis in increasingly severe disease and pro- gories: remains the standard karyotype, which is vides a genetic explanation for anticipa- (1) Those that give a yes or no answer. an excellent technique for picking up tion. The patient was clearly affected and These tests could be used potentially to major abnormalities of chromosome genetic testing was positive showing a screen the population for a particular ge- number or arrangement, such as Down’s moderate size expansion. When he came netic disorder , for example, fragile X syndrome. However, it is possible that in to receive his results, he attended with his syndrome. the next few years the karyotype will be parents and sister, all of whom initially (2) Those that have a high pick up, with supplanted by more detailed molecular wished to be tested. However, as they all certain common mutations in certain techniques that are capable of picking up had different concerns, testing was de- populations. more subtle chromosome abnormalities. clined and further individual appoint- (3) The gene is known but different mu- Molecular genetic testing is a more ments arranged. When they attended 2 tations account for the disease in different complex area. Genetic testing is indicated months later, none of them wished to be families. Therefore the familial mutation in a variety of situations – as a diagnostic tested, although they were aware that the must be identified in an affected individ- test or confirmatory test for a putative test was definitive. Neither parent wished ual before testing can be offered to other diagnosis, as a predictive test in someone to carry the burden of blame and as they family members. at risk of a particular disease or as a cas- were completely asymptomatic there was (4) The disease is caused by mutations cade test for carrier status in a family in no urgent clinical need to test them. His

JUNE 2008 10 GALTON INSTITUTE NEWSLETTER sister felt that she did not wish to know, family of this child wanted further chil- groups a wide variety of different muta- and that it would not alter her reproduc- dren and requested mutation analysis of tions have been identified, some of which tive decision making. She subsequently the tuberous sclerosis genes in order to are unique to a family. Therefore genetic developed polyhydramnios in her next have prenatal diagnosis. The father had testing is only offered to individuals af- pregnancy, and the baby was born with been diagnosed with a chronic renal dis- fected by breast cancer, unless they are congenital myotonic dystrophy. However, ease in his 20s, which was thought ini- known to come from specific ethnic she would not have wanted early prenatal tially to be unrelated to TSC. Two genes, groups. Mutations in these genes are in- diagnosis, or termination of pregnancy so known as TSC1 and TSC2, cause tuber- herited in an autosomal dominant fashion the outcome for the child would not have ous sclerosis, and mutations are identified with incomplete penetrance; that is, some been altered by genetic testing prior to the in 70% of affected individuals. A muta- individuals in a family may carry the mu- pregnancy. tion was identified in the affected child, tation but never develop the disease. and both parents were tested. Neither was Case 2 A boy of 18 months was A 30 year old woman was referred to referred with developmental delay. Prior found to carry the mutation but in the our service because she had developed to referral the paediatrician had arranged next pregnancy they requested prenatal breast cancer at the age of 29. Her mother genetic testing for Fragile X syndrome. diagnosis. The baby was found to be af- was well in her 50’s, but her maternal Fragile X syndrome is a condition associ- fected, and the couple opted for a termi- grandmother was affected by breast can- ated with learning difficulties and autistic nation of pregnancy. Further investigation cer at 40, and grandmaternal aunts were features affecting boys more frequently of the father revealed that he had multiple also affected. The young age of onset and than girls. It is associated with the pres- small angiomyolipomas, the characteristic histology of her breast cancer was indica- ence of a fragile site on the end of the X renal lesion of tuberous sclerosis. Skin tive of a BRCA1/2 mutation and she was chromosome, now known to be due to a was also sampled but the mutation pre- offered genetic testing. At that time the dynamic CGG expansion in the non- sent in his son and the affected baby was laboratory was able to offer only a 60% coding region of the FMR1 gene. Indi- not found. screen of the genes, and the test was viduals that have fewer than 50 CGG This gentleman must therefore be mo- negative. Despite the negative test she repeats in the gene are healthy, those with saic for the mutation, that is, he carries was advised that the cancer was likely to >200, if male will have Fragile X syn- the mutation in some cells of the body but be genetic and she elected to have both drome and if female have a risk of being not others. The mutation will have arisen breasts removed at the time of her opera- affected, and those with ~60-200 are as a post-zygotic event in one cell. All the tion for the cancer. Two years later a known as permutation carriers and have a descendants of that cell will contain the complete screen of both genes was devel- risk of passing on a larger expansion to mutation, but the other cells are healthy. oped in the laboratory. Further analysis of their children who then may be affected The mutation must be present in renal her sample revealed a mutation in by Fragile X syndrome. The boy was seen tissue and in his germline, but as it BRCA1. Her mother remained clinically in the genetics clinic and the outlook for was not detectable in blood or skin it unaffected, but must be an obligate car- him, and the risk to future pregnancies must be absent or at a low level in those rier and has decided to request bilateral discussed. Soon after the consultation, the tissues. In this situation, mosaicism pro- prophylactic mastectomy and removal of mother found that she was pregnant once vides an explanation for the variability of her ovaries. Genetic testing is now an again. She opted for prenatal diagnosis; expression in the family, but in most option for other family members are risk. the fetus was found to be male, and fur- families there is no such explanation. The ther testing revealed that he would be It is not clear why some women do not couple has gone on to have further af- affected by Fragile X. After much discus- develop breast or ovarian cancer when fected pregnancies, but now have a sion she elected to terminate the preg- they carry a mutation in BRCA1 or 2. healthy girl. nancy. Further testing was arranged in her Non-penetrance may be due to other Case 4 A family history of cancer family and it was revealed that her father modifying genes, or to lifestyle factors now accounts for more than a third of was a premutation carrier. and this is the subject of active research. referrals to the clinical genetics service. It

Case 3 Another boy of 18 is estimated that approximately 5-10% of months was referred to the genetics clinic There remain many conditions for all breast and colorectal cancers occur as which the gene or genes are unknown. after a diagnosis of tuberous sclerosis was result of a dominantly inherited genetic made by the paediatrician. Tuberous scle- Diagnosis in these conditions still relies susceptibility to cancer. Two genes, on clinical acumen, and indeed the identi- rosis (TSC) is a multisystem disorder BRCA1 and BRCA2, when mutated are with variable expression characterized by fication of the genes requires careful known to predispose to breast and ovarian the presence of seizures in approximately clinical delineation of the condition cancer. In certain ethnic groups, for ex- 70%, learning difficulties in ~60%, renal ample the Ashkenazim, there is a high Frances Elmslie complications, characteristic skin changes prevalence of specific mutations. How- Consultant Clinical Geneticist and perinatal cardiac involvement. The ever, amongst most other population St George’s Hospital, London

GALTON INSTITUTE NEWSLETTER 11 JUNE 2008 pelagic fishes laying hundreds of thou- cannot be expected to have reasonably

sands of eggs with no care of them, in happy lives, by comparison with those The Powers of contrast with the three-spined stickle- without such afflictions, or, in the worst Natural Selection back, Gasterosteus aculeatus, which lays cases, even reasonably pain-free lives; a few score of eggs and has nests built and they are bound to place a serious 15. Natural Selection and and the eggs and young guarded by the burden on parents, siblings and society. Eugenics male. Once such individuals are born, of course, they deserve all possible help and ‘The ultimate achievement of progress care. But if we can prevent such births in organic evolution has been cultural W.M.S. Russell by genetic counselling, aided by amnio- evolution, together with human individ- centesis (Berry, 1990), this is wholly to ual creativity… lower animals are in gen- In the 1930s there was a widespread eral enormously fertile… no such system the good. worry about more intelligent people hav- could progress to cultural evolution… In doing so, we need not fear conflict ing fewer children than the less intelli- The first step was a huge reduction in with natural selection, such as occurs gent; it was believed that the heritable fertility and the evolution of parental care when artificial selection favours extreme component of intelligence would deterio- and parental behaviour’. (Russell and characters (as in the Mather-Harrison rate as a result. This belief was totally Russell, 1990a) Many mammal species experiment). On the contrary, in helping irrational, and due to ignorance about have already had their litter size reduced to reduce unfitness, we are co-operating evolution. Quite apart from the fact that to 1 or 2, but many lower mammal spe- with natural selection. We have seen that intelligence is an obvious component of cies have larger litters, some much larger. some serious diseases of homozygotes persist because of selection in favour of fitness, we can be absolutely sure that The Virginian opossum, for instance, the the heterozygote, for instance Tay-Sachs natural selection will cause people with common American shrew, the Indian disease. I have described in an earlier fewer children (and correspondingly bet- mole rat and the mink can have litters of issue the ingenious eugenic policy in- ter parental care) to have more descen- up to 10. The Western skunk and the vented by Rabbi Joseph Ekstein for re- dants. Again and again in evolution antelope rat can have up to 12, the gray ducing the incidence of this disease. natural selection has lowered fecundity, wolf up to 13, and Bachman’s squirrel up (Russell, 1999) Such counselling proce- which is just another way of saying that to 16. But the two highest orders, the dures are again not in any way in conflict individuals with fewer off-spring have Primates and the Cetacea (whales and with natural selection. In preventing the had more descendants. dolphins) regularly have one or two birth of badly diseased homozygotes by Already in the classical 1858 paper young per litter, and in man, with the counselling, we are not opposing natural that (along with Darwin’s) introduced highest degree of parental care, ‘twinning selection’s favouring of the heterozygote: natural selection to the world, Wallace usually occurs once in about 83 births; we are merely avoiding the price other- noted the fact of selection for low clutch triplets are said to occur once in 832 and wise paid for this. size in birds (1958-1858); and many ex- higher numbers in increasing powers’. amples of this are given by Lack (1954) (Asdell, 1946) and Wynne-Edwards (1962) ‘In a few In view of all this, if the more intelli- This is the last in the series by Bill Rus- highly specialised cases the remarkable gent have fewer children, we can confi- sell. There is a comprehensive list of references for the whole series which can condition has evolved, that only one egg dently expect the heritable component of be obtained from the General Secretary, is ever laid in one year, and even if it is intelligence to increase and spread. So The Galton Institute, 19 Northfields Pros- removed or destroyed when newly-laid, there is no conflict between the two con- pect, London SW18 1PE or there is no attempt to re-nest or replace cerns of the Galton Institute – birth con- [email protected] it’. (Wynne-Edwards) There are also trol and eugenics. plenty of examples in fishes. ‘It is a Indeed nothing in my account of natu- The Galton Institute has also published a commonplace observation that an evolu- ral selection in any way weakens the case book by Claire and W M S Russell: tionary advance in the degree of parental for rational eugenics. Individuals with Population Crises and Population Cy- care given to the eggs and young is corre- very severe genetic defect or disease, cles. This volume can be obtained from lated with a lowering of fecundity’. anatomical, physiological or biochemical, the General Secretary and costs £5. (Wynne-Edwards, 1962) He instances

JUNE 2008 12 GALTON INSTITUTE NEWSLETTER