Sheldrake became a Fellow at Clare College where he was Director of Studies in Biochemistry and Cell biology, and a Research Fellow of the Royal Society. From 1974 to 1985 he worked in Hyderabad in India as Principal Plant Physiologist at the International Crops Research Institute for the Semi-Arid Tropics. For a year and a half he lived in the ashram of Bede Griffiths, where he wrote his first book, A New Science of Life.
As a biochemist, Sheldrake researched the role of auxin, a plant hormone, in the cellular differentiation of a plant's vascular system. He ended this line of study when he concluded, "The system is circular, it does not explain how established to start with. After nine years of intensive study, it became clear to me that biochemistry would not solve the problem of why things have the basic shape they do." More recently, drawing on the work of French philosopher Henri Bergson, Sheldrake has proposed that memory is inherent to all organically formed structures and systems. Where Bergson denied that personal memories and habits are stored in brain tissue, Sheldrake goes a step further by arguing that bodily forms and instincts, while expressed through genes, do not have their primary origin in them. Instead, his hypothesis states, the organism develops under the influence of previous similar organisms, by a mechanism he has dubbed morphic resonance.
From September 2005 until 2010, Sheldrake received the Perrott-Warrick Scholarship for psychical research and parapsychology, which is administered by Trinity College, Cambridge. Sheldrake then took his current position as Academic Director for the Learning and Thinking Program at The Graduate Institute in Bethany, Connecticut.
In April 2008, Sheldrake was stabbed in the leg during a lecture at the La Fonda Hotel in Santa Fe, New Mexico. He was presenting as part of the tenth annual International Conference on Science and Consciousness. Sheldrake has since recovered. The assailant, Japanese-born laborer Kazuki Hirano, allegedly stabbed Sheldrake because he believed that Sheldrake was using mind-control techniques on him. He had followed Sheldrake to New Mexico from England to purportedly ask him how to block mental telepathy when he stabbed him. Sheldrake fears that if he is released and extradited to Japan, he will continue to stalk him.
Sheldrake has a Methodist background but after a spell as an atheist found himself being drawn back to Christianity when in India, and is now an Anglican.
Sheldrake has made appearances in popular media, both on radio and on television. He was one of the subjects of a six-part documentary series called Heretic, broadcast on BBC 2 in 1994. On May 18, 2009, he appeared on The Museum of Curiosity on BBC Radio 4.
Sheldrake has entered into a scientific wager with fellow biologist Lewis Wolpert on the importance of DNA in the developing organism. Wolpert bet Sheldrake "a case of fine port, Quinta do Vesuvio 2005" that by the First of May 2029, "given the genome of a fertilised egg of an animal or plant, we will be able to predict in at least one case all the details of the organism that develops from it, including any abnormalities." Sheldrake denies that DNA contains a blueprint of morphological development. If the outcome is not obvious, the British Royal Society will be asked to determine the winner.
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