Septo-optic dysplasia

ROSA BEDDINGTON was one of the most skilled mammalian experimental embryologists of her, or perhaps any, generation.

She had an extraordinary ability to perform microsurgical experiments on mouse embryos at a very early stage, so as to ask how the three "germ layers" of the early embryo are established, how cells move to their right positions within the embryo, and how cells know whether they should make head or tail.

Mouse embryos at these stages are less than a millimetre long and Beddington could transplant particular pieces of such embryos, accurately and reproducibly, from one place to another. I watched her at work once; I simply couldn't see how she did it. The combination of micromanipulation and molecular genetics she was able to use in her work proved to be very powerful.

Rosa Beddington was born in 1956. Her father, Roy, was a painter, and she inherited that skill, using it both in her private life and in her research, whether this was sketching colleagues during not-so- interesting lectures or illustrating her work. Developmental biology is a visual subject, but what you see (and also "feel") down the dissecting microscope doesn't necessarily photograph well, and Beddington's drawings of the mouse embryo were very helpful to those of us who didn't have her feeling for this organism.

Her drawings were frequently adopted by colleagues around the world for use in their own lectures and they often appeared in textbooks, including Principles of Development (1998), co-authored by her with Lewis Wolpert, and the "Mouse Manual" (Manipulating the Mouse Embryo: a laboratory manual, 1994) she wrote with Brigid Hogan, Frank Costantini and Elizabeth Lacey. A seminar I went to two days before she died made use of Beddington's drawings.

Rosa Beddington went to Sherborne School for Girls and then to Brasenose College, Oxford (as one of the first generation of women at that college), to read Medicine. But medicine was not for her, and after obtaining a first class BA in 1977 she sought out Richard Gardner to do research for a DPhil in his laboratory, carried out initially under the supervision of Ginny Papaionnou.

Even at this early stage in her career, she had clear ideas about what was important, and she chose to investigate the question of how cells in the early mammalian embryo decide what they will become at later stages. She remained in Oxford, first as a postdoctoral fellow with Richard Gardner, then as a Lister Fellow, and then funded by the Imperial Cancer Research Fund. By this time her reputation as an experimental embryologist was firmly established; one would hear of particularly difficult microsurgical experiments that "you'd need a Rosa Beddington to do that!"

In 1991 Beddington moved to the Centre for Genome Research in Edinburgh, where she carried out some beautiful work on gastrulation, the process in which the three "germ layers" are set up. Then, in 1993, Peter Rigby and John Skehel recruited her to the National Institute for Medical Research (NIMR), where I worked at the time and where she herself said she spent her most productive years.

The environment of the institute was perfect for her, with other skilled mouse embryologists like Robb Krumlauf and Robin Lovell- Badge and also people (such as myself) working on similar problems in different species. This combination of skills was potent, and her work flourished. It was in this environment that she made her greatest contributions to our understanding of mammalian development.

Beddington first made practical use of her manipulative skills to dissect different regions of the early embryo and then prepare from them "libraries" containing copies of the genes expressed by the various tissues. She arranged for the DNA sequences of the genes within the libraries to be obtained and with typical generosity passed the libraries to colleagues for use in their studies. At the time of her death, three of Beddington's PhD students were working on important genes isolated from these region-specific libraries.

Beddington first demonstrated that the "node" of the mouse embryo has a function similar to the "organiser" of the amphibian: on transplantation to another region of the embryo it would cause the formation of an additional spinal cord and backbone, with its associated muscle. This was a remarkable technical achievement. But, to me, most impressive was her insight that these grafts did not induce heads, whereas the analogous grafts in the frog did. When she showed me the results I was less inclined to accept the significance of this observation, because the grafts were so technically difficult: when I did a poor graft in the much larger frog embryo these too lacked heads.

But Beddington knew what she was doing, and of course she was right. Her work went on to show that the head-to-tail axis of the mouse originates in cells that do not contribute at all to the embryo proper and indeed that anterior pattern is established before the formation of the node. She identified two genes involved in the specification of anterior pattern and then, to my chagrin, suggested we do some experiments to ask if frogs might use the same mechanism for anterior patterning. It turned out that they do.

She also demonstrated that mutation of one of her anterior patterning genes causes septo-optic dysplasia in humans, emphasising further the conservation of developmental mechanisms and the way in which work on model organisms such as the mouse can inform medical research.

Elsewhere in her professional life, Beddington served on the committee of the British Society for Developmental Biology, and was awarded that society's Waddington Medal (which she herself designed) in 1999. She also sat on national and international advisory boards and committees and was a member of the Medical Research Council's Molecular and Cellular Medicine Board. She was an International Scholar of the Howard Hughes Medical Institute and was elected a Fellow of the Royal Society in 1999.

More important than any of this, Rosa Beddington was a terrific colleague. She was a loyal friend, she had a fierce intelligence, and she said what she thought. If you wanted to know whether an idea would work, or if a manuscript was any good, it was Rosa you'd ask and you'd be sure of an honest, accurate and critical answer. And she enjoyed the life of the scientist. Meetings, for example, were an opportunity to catch up with friends, to share data and to confront colleagues whose papers and ideas may not have met the high standards she set herself and others. She continued her own work until it became impossible to do so.

Rosa Susan Penelope Beddington, developmental biologist: born Hurstbourne Tarrant, Hampshire 23 March 1956; Research Fellow, Lister Institute for Preventive Medicine, Oxford 1983-88; research scientist, ICRF, Oxford 1988-91; Senior Research Fellow, Centre for Genome Research, Edinburgh 1991-93; Head, Division of Mammalian Development, MRC National Institute for Medical Research 1993-2001; FRS 1999; married 1987 The Rev Robin Denniston; died Great Tew, Oxfordshire 18 May 2001.

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