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 HLA system. In 1970 he left his Profes- Presidency of 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 Conference 2008 2 for which, in acknowledging his Imperial Cancer Research Fund Labora- 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 Walter Bodmer, 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 Eugenics 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 Ronald Fisher, 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.