Tag Archives: Genetics

‘A True Geneticist’s Geneticist’

The papers of Sir Walter Bodmer have been intriguing, not only in terms of what they reveal about the history of science and genetics, but also for providing snapshots into the networks of co-operation, collaboration and relationships formed between prolific scientists. The large correspondence series of Sir Walter’s papers offer insight into how geneticists were continually learning from each other throughout their careers (and often disagreed), and through these exchanges of knowledge and ideas, lasting friendships were formed. The professional and personal correspondence between Walter Bodmer and Guido Pontecorvo (1907-1999) are one example of such a relationship.

As a young graduate student, Walter Bodmer travelled to Glasgow with his wife Julia and two young children, to spend time in the laboratory of Italian geneticist Guido Pontecorvo at Glasgow University. Pontecorvo was head of the new Department of Genetics in Glasgow, which he helped to establish (like Bodmer, who would later be instrumental in initiating the Department of Genetics in Oxford), and Professor of Genetics from 1955 to 1968.

Shortly after Bodmer completed his PhD in 1959, he became increasingly interested in the idea that quantitative genetics could be carried out properly on biochemical characters. Having learned about Pontecorvo’s work on Aspergillus, he hoped to travel to Glasgow and stay for a day or two to learn about this work and broaden his own outlook. In a report, Sir Walter wrote, ‘my reason for learning these techniques is a belief that they provide opportunities for a fundamental approach to the study of continuous quantitative genetics”. However, Pontecorvo firmly believed that basic biochemical and molecular genetics should be undertaken without the quantitative genetics. In addition, Pontecorvo was quite insistent that Bodmer would require several months (not days) to become acquainted with the techniques of biochemical genetics.

Dr. George Owen to Guido Pontecorvo, 28 November 1958

In 1987, Sir Walter looked back to 1959 when he first met Pontecorvo:

My first contact with him was nearly 30 years ago when, under the influence of my Professor, Sir Ronald Fisher, I had developed an interest in quantitative genetics but felt the need for biochemical analysis. It seemed that the Aspergillus system would be a marvellous basis for this, so I asked my formal supervisor, Dr. Owen, to write a letter, which I drafted, to Professor Pontecorvo about this. Perhaps I could visit for a day or so in the first instance and explore the applications of the Aspergillus system. In those days it would have been unusual for a graduate student to write directly to the Professor. I still have his reply. In it he said, “I strongly dislike the subject of quantitative genetics in general, and in particular in micro-organisms, which are so much better suited for the study of variations in fine genetic structure and its correlation with fine differences in proteins”. He was, of course, right.

Sir Walter has noted, “this was my first lesson in the value of persistence and calmness in relationships with others who may be much more senior than you are”.  It was this experience with Pontecorvo that gave Bodmer his first exposure to microbial genetics and modern genetics studies using the Aspergillus system (in addition to ideas on somatic cell genetics, perhaps the most significant influence on Sir Walter career and a major stimulus for the Human Genome Project).  According to Sir Walter, “Ponte’s pioneering insight that the asexual system of genetic analysis which he had developed for a fungus could be applied to human and animal cells in culture and laboratory” provided the fundamental background for later laboratory advances and applications at the molecular level. Indeed, the Bodmer archive contains a range of lab notebooks and papers from experiments using fusions to produce hybrids based on Pontecorvo’s method.

Sir Walter has written, “though my time in Glasgow was short, I count myself as one of Ponte’s students”. In fact, Guido Pontecorvo and Walter Bodmer became very good friends; they would have a lot of contact during Pontecorvo’s later career after he moved from Glasgow to the ICRF in London at the invitation of Michael Stoker (Bodmer’s predecessor as Director of Research at the ICRF). In 1987 Sir Walter initiated and organised a symposium and special edition of Cancer Surveys in honour of Pontecorvo on the occasion of his 80th birthday.

Francis Crick to Walter Bodmer, 18 May 1987 (Pontecorvo was known as ‘Ponte’ to his friends and colleagues).

Guido Pontecorvo has remained an important influence on the career of many geneticists, with Sir Walter referring to him as “a true geneticist’s geneticist”.

Letters from Cambridge

The Archive of Sir Walter Bodmer comprises an impressive sequence of professional, scientific and some personal correspondence. The correspondence spans the extent of Sir Walter’s career, through his early education at Cambridge University to his later career in Oxford.  Importantly, incoming letters have been filed with the geneticist’s copy letters, which should prove invaluable for researchers.

Cataloguing the correspondence has been fascinating, not least because it really does feature a who’s who of the world of genetics and science. I was particularly interested to find a bundle of correspondence from 1963 between Walter Bodmer, Eric Ashby (later Lord Ashby and master of Clare College, Cambridge) and Francis Crick, one of the founding fathers of Genetics, who, at this time, was based in Cambridge’s Laboratory of Molecular Biology (LMB). Cambridge in fact provided the setting for Bodmer’s early genetics career.

Bodmer was first drawn to statistics as a mathematics undergraduate at Cambridge. His interests led to him to the statistically oriented lectures of the Genetics Department by the renowned statistician Sir Ronald Aylmer Fisher. After graduation Walter Bodmer remained in Cambridge researching population genetics under the influence of Fisher (who, in Bodmer’s own words, will always be one of his greatest heroes). After completing his PhD, he stayed in Cambridge on a Junior Research Fellowship and as a Fellow of Clare College and Demonstrator in the Department of Genetics.

Throughout his time in Cambridge, it was through R. A. Fisher that Bodmer was exposed to the world of genetics and geneticists, including Francis Crick. Importantly, not only was Cambridge itself the one of the most stimulating environments for geneticists to be, but the period has been marked as the most exciting time in the history of genetics. This was the early days after the discovery of the double helix structure of DNA by Crick, James D. Watson, Maurice Wilkins and Rosalind Franklin (like Bodmer, Watson was also at Clare College where he later became an honorary fellow).

In an interview with Dr. Max Blythe for the Medical Sciences Video Archive, Bodmer recalls this significant early period in his career at Cambridge:

My first hearing of the structure of DNA was when Fisher, in one of his very mathematical lectures either in ‘55/’56 or the following year, took out his pocket – and I still remember it – a crumpled copy of a paper that Watson and Crick had written for the Cold Spring Harbor symposium on the structure of DNA. He gave a beautiful description of the structure of DNA, very simple, I have still got my notes on it, then proceeded to go on with a very abstruse lecture on the mathematical theory of genetic recombination or something like that. So that was how I first heard about it, but because of that inter-relationship, Francis Crick was quite friendly with people in the Genetics Department and in my early days as a graduate student there, we had contact with him, and that was an important influence.

In fact, Francis Crick was a close friend of R. A. Fisher as they were both at Caius College. Through his connection with Fisher and Crick, Bodmer came to have some contact with the MRC Unit at the Cavendish Laboratory where Watson and Crick had deduced the structure of DNA in 1953 (and it was here, in the late ‘50s, that Bodmer was probably influenced to turn towards molecular biology). It was this contact that essentially marked out his subsequent and highly successful career as a molecular biologist and population geneticist.

ashby to bodmer
Eric Ashby to Walter Bodmer, 17 Jan. 1963

The letters were written when Walter Bodmer was in Stanford undertaking postdoctoral research, and the opportunity to return to Cambridge to further his career in the Laboratory of Molecular Biology was presented to the young scientist. This must have been a thrilling proposition for Bodmer, and it is clear much thought was given to this opportunity, which must have proved a real dilemma.

Eric Ashby to Walter Bodmer
Eric Ashby to Walter Bodmer, 16 Mar. 1963
Bodmer to Crick 1963
Walter Bodmer to Francis Crick, 12 Mar. 1963
crick to bodmer
Francis Crick to Walter Bodmer, 18 Mar. 1963

Bodmer had left Cambridge for Stanford in 1961, initially with the intention of staying for just one year. Yet, the young scientist thrived at Stanford where he worked as Post Doctoral Research Fellow to Nobel Prize winner Joshua Lederberg (whose expertise lay in gene exchange in bacteria). By 1963, Bodmer had been offered the post of Assistant Professor in the Stanford Medical School. However, as the letters illustrate, there was also the possibility of Bodmer returning to a lectureship in the Genetics Department at Cambridge. While an established position with the prospect of tenure, he may not have considered this to be the best option given his switch to an interest in molecular biology (as illustrated in the letters, Eric Ashby and Francis Crick were trying to arrange a more attractive position at the Laboratory of Molecular Biology). In addition, Clare College had separately offered to make Bodmer an official Fellow if he returned, also an established position.

While in America, Bodmer became drawn to studying the more biochemical and molecular aspects of genetics. On his way to Stanford in 1961, he attended a course in molecular biology at Cold Spring Harbor Laboratory in New York, one of the great meccas for molecular biologists. By 1963 (when the letters were written), Walter Bodmer had established a strong career in molecular biology, and was working more or less independently in the Lederberg laboratory in Stanford. He then moved to work on somatic cell genetics, which would become a lasting involvement throughout his career. Another major research area initiated during his time at Stanford was with his wife Julia Bodmer, on work that contributed to the discovery of the major human histocompatibility system, HLA. During his time in Stanford, Walter Bodmer had also made contact with Luca Cavalli-Sforza, whom he first met in Cambridge around 1957.  In Stanford they they began working collaboratively by giving a course in population genetics and working on text book the Genetics of Human Populations (published 1971).

The possibilities offered in Cambridge really must have involved painstaking decision-making, yet as is clear, his time in Stanford really solidified his successful career and he remained here until his return to the UK in 1970 to take up the Chair in Genetics at Oxford University.

post mark

It is evident, both in the letters and other papers in the archive, that Bodmer’s potential as a scientist was recognised at an early stage in his career. Over the next few months I hope to highlight further gems from Sir Walter’s archive that capture his influences from the world of science.

Preserving Science in the Archives (Part 2)

The Bodmer archive is a valuable modern science collection, not only for its importance in documenting the history of human genetics and scientific initiatives, but also for revealing changes in laboratory methodologies and practices.

One of my favourite finds relates to chromosome analysis carried out for work on human gene mapping using mouse somatic hybrids of human-mouse cells and human leukocytes, undertaken by Walter Bodmer and the his then PhD student immunologist Marcus Nabholz. Nabholz worked and collaborated as a graduate student in Walter’s lab at Stanford University, and also later at the Genetics Laboratory in Oxford. The images below illustrate chromosome analysis, which involved taking a print of chromosomes in dividing cells, cutting them all out individually and arranging them crudely by size and shape. This work contributed to a joint publication that  appeared in 1969 edition of the jounal Nature entitled ‘Genetic Analysis with Human-Mouse Somatic Cell Hybrids’.
 1_chromosome-3 3_chromosome-2 2_chromosome-1
This chromosome technique may appear as quite primitive laboratory practice, and such relatively crude miscroscopic images of chromosomes would not end up on paper now. The Bodmer collection perfectly illustrates how technological changes over the last 50 years have fed into scientific research, from the techniques illustrated above, to the latest cutting-edge computer analysis, which is now integral to scientific research.

The archive contains a considerable amount of material that will enable researchers to trace the development and application of information systems and software technologies in science laboratories.

From the earlier period of the Bodmers research when laboratories entered the electronic world, computers became especially important for geneticists. Julia Bodmer in particular -with her abilities in handling and analysing large datasets- embraced the application of computers to population genetics at an early stage at Stanford University, where computing facilities were better than most. Although a novelty in science and medical research at this time, they were mostly used for data crunching in the earlier period, yet computers would play a vital function in the interpretation of serological data. Julia in fact created a computer program that facilitated the identification of the first two genes of the HLA genetic system.

As traditional laboratory notebooks are increasingly eliminated in favour of electronic notebooks, which are often erased or deleted after publication output, the preservation of paper-based research notebooks and scientific data found in the Bodmer collection (a hybrid paper and digital collection) will be an important resource for documenting the history of genetics.



Preserving Science in the Archives (Part 1)

Sir Walter and Lady Julia Bodmer’s archive covers nearly all aspects of their research careers as geneticists. While it is often the case that scientists discard research papers (or delete digital files) such as laboratory notes and datasets once the scientific conclusion results in published output, Sir Walter has been careful to retain every step of the research process leading up to publication. The archive includes sequencing and other experimental data sets, punch cards, lab notes and log books, multiple drafts of scientific papers and grant applications. Importantly, the more informal aspects of the research process have also been kept, adding a real human dimension to the archive. The correspondence, casual memos, jottings and annotations on reprints and lab notes encapsulate the ideas and observations, not to mention the frustrations endured throughout the research process, and ultimately, the thrill of scientific discovery.

Sir Walter Bodmer c.1977

For this post I thought it would be useful to share some examples of the experimental materials enclosed in many of the lab notebooks. The archive comprises an impressive amount of lab work making up around a third of the full archive, which totals over 2000 boxes. This also includes the notebooks of collaborators and junior research staff working in various labs headed by the Bodmer’s in Oxford, Stanford and the Imperial Cancer Research Fund (now Cancer Research UK) in London.

The collection’s research sequences include Sir Walter’s early genetics work on Aspergillus and Neurospora, which he carried out as a postgraduate student at Cambridge University during the 1950s and until he went to Stanford in the 1960s. This covers molecular genetics experiments on DNA transformation in Bacillus subtilis, and work on human lymphocyte antigens. From the Genetics Laboratory at Oxford University research notebooks cover a variety of experiments throughout the 1970s, including those relating to HLA determinants on somatic cell hybrids. There are nearly 200 boxes alone containing lab notes from Julia Bodmer’s ICRF Tissue Antigen Laboratory including work on the production of monoclonal antibodies, in particular, DR antigens. There are also a similar number of boxes relating to colorectal cancer research carried out in Sir Walter’s Director’s Laboratory at the ICRF. Many of these papers offer a window into the development of techniques and methodologies used for work on extracting proteins and DNA.

Lab work relating to polyclonal screening of colorectal cancer cell lines
These images represent a small selection of lab techniques such as Western and Southern blotting, and gel electrophoresis. The technique of Southern blotting was developed by Sir Edwin Southern in 1973, and uses gel electrophoresis for the detection of a specific DNA sequence in a sample of DNA. Western blotting is similar but is used to detect and separate proteins, thereby allowing for the identification of specific antibodies (while Northern blotting detects RNA). Blotting by gel electrophoresis enables the transfer of membranes and involves hybridisation to a probe.
gel 2
gel 3
Western blot gel
Gel electrophoresis
dot blot 1
 There are also a number of dot blots, which is a method of applying proteins directly onto a membrane. Unlike Western blotting, it does not use electrophoresis to separate proteins. Sample proteins are applied directly on a membrane as a dot and hybridized with an antibody that acts as a probe.
From an archivist’s perspective, the laboratory materials are both fascinating and unusual, and have also posed many preservation challenges concerning long-term protection of the archive. The generous support from the Wellcome Trust has enabled us to safeguard these important materials in order to ensure their long-term physical survival and make them accessible to future researchers. As such, we have worked with the Libraries’ preventative conservator and health and safety representatives to find the most suitable enclosures for these materials.Thankfully the majority of lab material is in an excellent and stable condition with no degradation, and we have been taking protective steps to ensure future degradation is minimal and avoids crosslink and damage with other materials. Preservation measures have included the use of acid absorbers and archival quality non-acidic repackaging material.
Western wet transfer
Immunodetection using Amersham ECL Western blotting kit (immunodetection uses antibodies to detect the presence of specific antigens)

Importantly, the majority of the collection has been retained (by the Bodmers and now archivist) within its original order and context. For a non-scientist archivist, the abundance of explanatory documentation that exists with the laboratory papers has proved invaluable for contextualisation, and will also add to the collection’s historical value.

The International Histocompatibility Workshop comes to Oxford

During the early period of Sir Walter Bodmer’s career in Oxford (1970-79) he was able to dedicate his time to research in addition to teaching. The papers of Sir Walter and his wife, Lady Julia, illustrate the development of their valuable laboratory research into human gene mapping, and work on the human leukocyte antigen system (HLA), which they initially collaborated on at StanfordUniversity in the lab of haematologist Rose Payne.In the new Genetics Laboratory at Oxford University, the couple progressed with their HLA research. Walter Bodmer also continued his work on somatic cell genetics and the biochemistry of HLA. Julia had a particular interest in studying the relationship between HLA types and diseases.


Seventh International Histocompatibility Workshop Conference, Oxford, 1977


The gene mapping aspect of genetics and the role of HLA in disease association was flourishing during this period as a major field of research. The first international HLA Workshop Conference had taken place in 1964 at Duke University, North Carolina, and would continue to be a seminal event. The Workshops provided scientists with a forum to collaborate on their investigations into immunogenetics research.  In September 1977 Walter and Julia Bodmer were responsible for bringing the Workshop to Oxford University.


Julia 1977
Julia Bodmer, Oxford, 1977

Approximately 200 laboratories scattered worldwide participated in this Workshop, studying antisera, lymphocytes and typing cells. It was during this Workshop that HLA-D region types were properly defined for the first time, a major step forward in the HLA field. Additionally, as a consequence of the conference, 19 new HLA specificities were given World Health Organisation (WHO) designations.


Bodmer seated 1977
Sir Walter Bodmer (seated), Oxford, 1977

In 1979, the Bodmers left Oxford for the Imperial Cancer Research Fund (ICRF) in London. Sir Walter eventually became Director-General of the ICRF while Lady Julia was head of the Tissue Antigen Laboratory.

Sir Walter Bodmer and the Department of Genetics at Oxford University

As part of the Saving Oxford Medicine blog we will be tracing the distinguished careers of the Bodmers. Currently being catalogued, the archive of Sir Walter includes a significant number of papers relating to his time at Oxford University, both during his earlier career as Professor of Genetics from 1970-79, and later, as Principal of Hertford College from 1996. The archive also comprises the papers of Sir Walter’s wife, the economist and geneticist Lady Julia Gwynaeth Bodmer.

In our previous post we saw a picture taken of Professor Kenneth Franklin and his colleagues outside the old Physiology Laboratory in 1894. Moving forwards to a later generation of Oxford scientists we have a picture taken outside the same building on South Parks Road.

The group picture below shows Oxford’s first Professor of Genetics Sir Walter Bodmer (back row, fourth from right) and his colleagues outside the staff entrance of the Genetics Laboratory, which he headed. Julia Bodmer also worked in the laboratory, also pictured (middle row on steps, far right). The Genetics Laboratory would later become the Walter Bodmer Building, now demolished.


Sir Walter Bodmer (back row, fourth from right) and his colleagues outside the staff entrance of the Genetics Laboratory

In addition to fully representing the development of Sir Walter and Lady Bodmer’s laboratory research into human tissue histocompatibility antigens, the archive also illustrates the development of genetics as an academic discipline at Oxford University. In 1969 the University made the decision to create a chair of genetics after the retirement of geneticist Edmund Brisco Ford, who held a personal chair. Likewise, the distinguished geneticist and Professor of Botany Cyril Darlington was close to retirement. (Follow the links to learn more about the archives of both men, which are available for access at the Bodleian.)

Prior to this period there had been relatively little in the way of genetics available to Oxford students and it was felt that the discipline should be established on a more permanent teaching basis. Upon arrival in Oxford it was left to Bodmer to decide what department genetics would be allied with; zoology, botany or biochemistry. As a molecular biologist increasingly moving towards biochemical work, he chose to bring this newly created sub-department of genetics within the Department of Biochemistry. In his capacity as Professor of Genetics, Bodmer and his colleagues held the responsibility of all genetics teaching at undergraduate level, from medical students to biochemists and biologists. By Sir Walter’s own description, himself and his colleagues “built up a small lively department, with interests in biochemical genetics…and human genetics”.

Sir Walter Bodmer’s Archive

Sir Walter Bodmer

Sir Walter Bodmer

In 1992, in an answer for a Daily Telegraph questionnaire, the eminent geneticist, and then Director-General of the Imperial Cancer Research Fund, Sir Walter Bodmer identified his chosen last words as, ‘To my wife: please do not shred all my papers!’.

His concern to retain his papers is commendable and the resultant archive, which has just been boxlisted by archivists Tim Powell and Adrian Nardone, is huge: over 2,000 archive boxes.

As the size of the archive indicates, Sir Walter kept good records of his activities and the collection documents nearly all aspects of his career, from schooldays at Manchester in the early 1950s to his recent research at the Weatherall Institute of Molecular Medicine.  It includes voluminous documentation of areas of research and activities with which Sir Walter is particularly associated: research and publications into HLA and immunogenetics, cancer research, his Professorship of Genetics at Oxford 1970-1979, and terms as Director of Research and Director-General of the Imperial Cancer Research Fund 1979-1996. Other major responsibilites included his presidency of HUGO – the international human genome organization, chairmanship of the Board of Trustees of the Natural History Museum and chairmanship of the National Radiological Protection Board.

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The archive of Professor Sir David Weatherall

In the late 1950s, David Weatherall, a Medical Officer on National Service with the RAMC, met Jaspir Thapa, daughter of a Gurkha soldier, in the children’s ward of the British Military Hospital, Singapore. Jaspir was profoundly anaemic and being kept alive by blood transfusions.  Weatherall studied the child and diagnosed her illness as thalassaemia. Thus began a distinguished research career.

The first portion of the archive of Professor Sir David Weatherall, molecular geneticist and Oxford Regius Professor of Medicine from 1992 to 2000, has been acquired by the Bodleian Library through an initiative of the Saving Oxford Medicine project. Sir David’s groundbreaking work on thalassaemia, a set of inherited blood disorders that affect the body’s ability to create red blood cells, has resulted in improved clinical treatment of the disease and the introduction of programmes for its management, particularly in developing countries. Largely due to him, Oxford University is recognised as a world leader in global health. Under his leadership, an Institute of Molecular Medicine was established at the University in 1989, renamed the Weatherall Institute of Molecular Medicine on his retirement in 2000. Its scientists work on areas of molecular and cell biology that can improve the understanding and treatment of diseases such as cancer and HIV/AIDS.

Sir David with patients at a clinic in Sri Lanka

The sections of the archive now acquired include Sir David’s reminiscences of his time in Singapore and Malaya in 1959-61, correspondence regarding the setting up of the Oxford Tropical Medicine Research Programme at Mahidol University, Bangkok, in the late 1970s; papers relating to the development of the Institute of Molecular Medicine, beginning with Sir David’s initial proposal in 1983; papers relating to his evidence to the House of Lords Select Committee on Science and Technology in the 1980s and 1990s, and to his roles as WHO consultant and lead writer of its Advisory Committee on Health Research report ‘Genomics and World Health’, 2002, and chair of the 2006 working group on the use of non-human primates in research. There is also material relating to his publications and contributions to conferences, meetings and medical debates, and his many appointments, honours and awards. Additions to these in due course will be Sir David’s scientific correspondence and laboratory records.

The archive will be catalogued before being made available to researchers in the Special Collections Reading Room.Listen to some of Sir David’s stories at: