Sir Richard Timothy Hunt, FRS, FMedSci, FRSE (born 19 February 1943) is a British biochemist and molecular physiologist. He was awarded the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Leland H. Hartwell for their discoveries of protein molecules that control the division of cells. In particular, Hunt discovered what he called cyclin: a protein in fertilised sea urchin eggs which cyclically aggregates and is depleted during cell division cycles.

Early life and education

Hunt was born on 19 February 1943[2] in Neston, Cheshire, to Richard William Hunt, a lecturer in palaeography in Liverpool, and Kit Rowland, daughter of a timber merchant.[21] After the death of both his parents, Hunt found his father had worked at Bush House, then the headquarters of BBC World Service radio, most likely in intelligence, although it is not known what he actually did.[21] In 1945, Richard became Keeper of the Western Manuscripts at the Bodleian Library, and the family relocated to Oxford. At the age of eight, Hunt was accepted into the Dragon School,[2] where he first developed an interest in biology thanks to his German teacher, Gerd Sommerhoff.[21] When he was fourteen, he moved to Magdalen College School, Oxford, where the science prizes now bear his name, becoming even more interested in science and studying subjects such as chemistry and zoology.[21][23][24][25]

In 1961, he was accepted into Clare College, Cambridge to study Natural Sciences, graduating in 1964 and immediately beginning work in the university Department of Biochemistry under Asher Korner.[21] There, he worked with scientists such as Louis Reichardt and Tony Hunter.[21] A 1965 talk by Vernon Ingram interested him in haemoglobin synthesis, and at a Greek conference in 1966 on the subject, he persuaded the hematologist and geneticist Irving London to allow him to work in his laboratory at Albert Einstein College of Medicine in New York, staying from July to October 1966.[21] He focused on haemoglobin synthesis in intact rabbit reticulocytes (immature red blood cells), finishing his PhD in 1968.[27][29][31]

Career and research

Following his PhD, Hunt returned to New York to work with London, in collaboration with Nechama Kosower, her husband Edward Kosower, and Ellie Ehrenfeld. While there, they discovered that tiny amounts of glutathione inhibited protein synthesis in reticulocytes and that tiny amounts of RNA killed the synthesis altogether. After returning to Cambridge, he again began work with Tony Hunter and Richard Jackson, who had discovered the RNA strand used to start haemoglobin synthesis. After 3–4 years, the team discovered at least two other chemicals acting as inhibitors.[21]

Hunt regularly spent summers working at the Marine Biological Laboratory at Woods Hole, Massachusetts, which was popular with scientists for its advanced summer courses, and in particular, with those interested in the study of mitosis. The location provided a ready supply of surf clams and sea urchins amongst the reefs and fishing docks, and it was these invertebrates that were particularly useful for the study of the synthesis of proteins in embryogenesis, as the embryos were simply generated with the application of filtered sea water, and the transparency of the embryo cells was well suited to microscopic study.[32]

It was there at Woods Hole in the Summer of 1982 using the sea urchin (Arbacia punctulata) egg as his model organism, he discovered the cyclin molecule.[21] Hunt was a keen cyclist and named the protein based on his observation of the cyclical changes in its levels.[33]

Cyclins are proteins that play a key role in regulating the cell-division cycle.[34] Hunt found that cyclins begin to be synthesised after the eggs are fertilised and increase in levels during interphase, until they drop very quickly in the middle of mitosis in each cell division. He also found that cyclins are present in vertebrate cells, where they also regulate the cell cycle. He and others subsequently showed that cyclins bind and activate a family of protein kinases, now called the cyclin-dependent kinases, one of which had been identified as a crucial cell cycle regulator by Paul Nurse. The cyclin mechanism of cell division is fundamental to all living organisms (excluding bacteria) and thus the study of the process in simple organisms helps shed light on the growth of tumours in humans.[36]

In 1990, he began work at Imperial Cancer Research Fund, later known as the Cancer Research UK London Research Institute, in the United Kingdom, where his work focused on understanding on what makes cell go cancerous, that is: proliferate uncontrollably, with the ordinary inhibitory signals switched off.[37] Hunt had his own laboratory at the Clare Hall Laboratories until the end of 2010, and remains an Emeritus Group Leader at the Francis Crick Institute.[36][38] He is a member of the Advisory Council for the Campaign for Science and Engineering.[39] He also sits on the Selection Committee for Life Science and Medicine, which chooses winners of the Shaw Prize.[40]

Controversy over lunchtime toast at WCSJ 2015

The toast

On 8 June 2015, during the 2015 World Conference of Science Journalists in Seoul, at a lunch for female journalists and scientists, Hunt was asked on short notice to give a toast. Hunt's impromptu speech was later recounted by an unnamed EU official:[42][43][44]

It's strange that such a chauvinist monster like me has been asked to speak to women scientists. Let me tell you about my trouble with girls. Three things happen when they are in the lab: you fall in love with them, they fall in love with you, and when you criticise them they cry. Perhaps we should make separate labs for boys and girls? Now, seriously, I'm impressed by the economic development of Korea. And women scientists played, without doubt an important role in it. Science needs women, and you should do science, despite all the obstacles, and despite monsters like me.

A short recording was made at the event by Natalia Demina. In it, Hunt said:[42]

So, congratulations, everybody, and I hope – I hope – I hope – I really do hope there is nothing holding you back, especially not monsters like me.

In the recording, one can hear Hunt's concluding remarks being followed by a very brief piece of laughter and applause before the recording ends.[41]

Public reaction

A member of the audience, Connie St Louis, tweeted her recollection of parts of this speech on 8 June. These comments without context were widely re-tweeted, but not until a day later, on 9 June; they were then condemned in a reaction that The Observer described as a "particularly vicious social media campaign",[45] Hunt being subject to "intense, vitriolic online abuse".[46] A number of women scientists responded by posting photographs of themselves at work under the hashtag "#distractinglysexy".[47]

That same day the Royal Society formally distanced itself from Hunt's comments as reported and emphasised its commitment to equality in the sciences.[48][50]

Two days later, 10 June, Hunt gave an interview to BBC Radio 4's Today programme, in which he apologised and described his comments as "light hearted ironic remarks". Hunt also stated that he "did mean the part about having trouble with girls," characterising falling in love in the laboratory as "very disruptive to the science," and clarified that his comments on women in labs crying when criticised had the background that it was important in science to be able to criticise idea without criticising people – while if somebody "burst into tears, it means that you tend to hold back from getting at the absolute truth."[51] Hunt went on to say "I'm very sorry if people took offence. I certainly did not mean to demean women, but rather be honest about my own shortcomings."[45][52]

Numerous media outlets reported on the incident and the BBC interview, citing portions of Hunt's original remarks and criticising them as sexist.[53][54] Science journalist Connie St Louis gave 37 words of the remark (from "Let me tell you about my trouble with girls" to "when you criticise them they cry") but said "he just ploughed on for about five to seven minutes."[7]

Hunt felt he had made it clear he was joking because he had included the phrase ‘now seriously’ in his statement.[56] The reconstruction of his words by an unnamed EU official corroborated the inclusion of these words.[7] On 27 June, The Times reported that St Louis had, contrary to some of the previous statements, accepted that Hunt's comments were made "in jest".[7] It was only on 18 July, thirty-nine days after Hunt's comments, that the recording of part of them (and the laughter and applause) became public.[41]

Resignations and reappointments

On 10 June Hunt resigned from his position as an honorary professor with the University College London's Faculty of Life Sciences[60] and from the Royal Society's Biological Sciences Awards Committee.[7] Hunt's wife, immunologist Mary Collins, had been told by a senior [at UCL] that Hunt "had to resign immediately or be sacked."[45] An EC politician called Sir Tim, and demanded he resign his ERC post. Internal ERC documents show deep unhappiness within the scientific council at this interference. Hunt was invited to the ERC's farewell dinner for all its retiring members in November, where Prof. Dame Athene Donald stated he received a 'warm welcome'. Several female scientists and commentators defended Hunt. Dame Athene Donald, ERC, a physicist who is President of the British Science Association, Master of Churchill College, Cambridge and a fellow of the Royal Society, said Hunt "was always immensely supportive of the ERC’s work around gender equality".[45]

The decision to ask Hunt to resign from his honorary position at UCL was taken without consultation with the council, the university's governing body.[7] The UCL president, Michael Arthur, released a statement, reported on the BBC on 26 June, stating that there would be no reinstatement of Hunt as it would send "entirely the wrong signal".[63] The university's council later confirmed this decision.[7] However, in July, Hunt was reappointed by the Royal Society to represent them on a working group on European funding. The report was released in December, and a Royal Society spokesman said that Hunt was 'a leading expert' and 'a natural choice'.

On 30 June, The Guardian reported that broadcaster Jonathan Dimbleby had resigned from an honorary fellowship at UCL in protest at its treatment of Hunt.[65] Also, author and journalist Jeremy Hornsby wrote University College London out of his will in protest, leaving it "about £100,000 worse off".[66]

Wider reaction

At least eight Nobel prizewinning scientists and 21 honorary fellows had criticised the treatment of Hunt following his resignation.[67][68] Boris Johnson,[69] the mayor of London, and Richard Dawkins[43] also expressed their indignation at the treatment of Hunt.

Imran Khan, Chief Executive of the British Science Association, speaking to the BBC, described Hunt's comments as "careless," adding that it is "hard to find Sir Tim's comments funny if you've been held back by systemic bias for years - whether those remarks were intended as a joke or not[.]"[51] British neuropsychologist Dorothy Bishop, while noting Hunt's being described as a "decent human being" by most of the women who knew him, noted that he had still "set back the cause of women in science" and should not sit on any Royal Society committee involved in making decisions about fellowships, prizes or policy.[70]

Physicist and broadcaster Brian Cox, speaking on BBC Radio 4's The World at One, described Hunt's comments as "very ill-advised", but criticised what he saw as the hounding out of Hunt as a disproportionate response to concerns over his comments, and part of a "wider problem of trial by social media".[71]

In a letter to The Times a group of 29 staff scientists, students and postdoctoral fellows, both male and female, who had worked with Hunt, wrote in support of his character. They described how his help had been "instrumental in the advancement of many other women and men in science beyond those in his own lab" and how he had "actively encouraged an interest in science in schoolchildren and young scientists, arranging for work experience and summer students of both genders to get their first taste of research in his lab." They urged the ERC and UCL to "reconsider their rush to judgment".[72][73]

Trish Greenhalgh said that only ‘those who went on hearsay’ would call him sexist.[74]

Paul Nurse, head of the Royal Society, who shared the 2001 Nobel prize in medicine with Hunt, while stressing his esteem for Hunt as a person, originally stated that Hunt had said "some stupid things which cannot be supported and they had to be condemned," and that the affair had been bad for science and for the Royal Society in particular, adding that the discussion had "become totally polarised with extreme views on both sides".[68] In a later statement, Nurse described the response to Hunt's comments as "a twitter and media storm, completely out of proportion", adding that "he should never have been sacked by University College London".[75]

In October 2015, Sir Colin Blakemore resigned as honorary president of the Association of British Science Writers (ABSW) in protest over its decision to support the claims made by Connie St Louis. He maintains that her account was "unbalanced, exaggerated, and selective" and criticises the ABSW's decision not to investigate the issue. Blakemore's position was backed by Athene Donald, who had written to the ABSW asking them to investigate the way the story was reported writing that "Tim Hunt's reputation has been destroyed because careful journalistic due diligence was not followed by many who wrote about the event, and the ABSW decision not to take any further action appears to endorse such behaviour." ABSW president Martin Ince replied that the association's statement had simply supported St Louis's "right to report a story without fear of personal attack," stating that Hunt had "acknowledged the accuracy of St Louis’s reporting" [46] However, it later emerged that Hunt had said her reporting of his toast was "quite inaccurate, and very selective"[76]

One unnamed female scientist who had been critical of Hunt said that she had been subjected to "a torrent of abuse" on social media and that it was "not worth the aggro of waking up to calls for me to be sacked". For his part, Hunt has distanced himself from the controversy, commenting that he had been "turned into a straw man that one lot loves to love and the other lot loves to hate and then they just take up sides and hurled utterly vile abuse at everyone."[77]

Awards and honours

Hunt was elected a member of the European Molecular Biology Organization (EMBO) in 1978, serving as a member of the organisation's Fellowship Committee 1990–1993, its Meeting Committee 2008–2009, and its governing body, the Council, 2004–2009.[16] He was elected a Fellow of the Royal Society (FRS) in 1991,[19] his certificate of election reads:[79]

Distinguished for his studies of the control of protein synthesis in animal cells and for the discovery of cyclin, a protein which regulates the eukaryotic cell cycle. Together with Jackson and their students, he defined steps in formation of the initiation complex in protein synthesis, showing that the 40S ribosomal subunit binds initiator tRNA before it binds mRNA, and that this step was the target of inhibitors such as double-stranded RNA or haem deficiency. They showed that inhibition of protein synthesis is mediated by reversible phosphorylation of initiation factor eIF-2 by two distinct protein kinases and they elucidated the unexpected roles of thioredoxin and thioredoxin reductase in protein synthesis. With Ruderman and Rosenthal, he demonstrated selective translational control of mRNA in early clam embryos. This led to Hunt's discovery of cyclin as a protein which is selectively destroyed in mitosis. He subsequently cloned and sequenced cyclin cDNA from sea urchins and frogs and showed by elegant mRNA ablation experiments that cyclin translation is necessary for mitosis in frog embryos. He has also shown that cyclin is a subunit of the mitosis-promoting factor which regulates entry into mitosis. His discovery and characterization of cyclin are major contributions to our knowledge of cell cycle regulation in eukaryotic cells.

Hunt was elected a fellow of the UK's Academy of Medical Sciences (FMedSci) in 1998,[80] and a foreign associate of the US National Academy of Sciences in 1999.[81]

In 2001, he was awarded the Nobel Prize in Physiology or Medicine with Leland Hartwell and Paul Nurse for their discoveries regarding cell cycle regulation by cyclin and cyclin-dependent kinases. The three laureates are cited "for their discoveries of key regulators of the cell cycle," while Hunt in particular

is awarded for his discovery of cyclins, proteins that regulate the CDK function. He showed that cyclins are degraded periodically at each cell division, a mechanism proved to be of general importance for cell cycle control.[82]

In 2003, Hunt was made an honorary Fellow of the Royal Society of Edinburgh (HonFRSE).[20] In 2006, he was awarded the Royal Society's Royal Medal, two of which are presented annually for "the most important contributions to the advancement of natural knowledge", in his case for "discovering a key aspect of cell cycle control, the protein cyclin which is a component of cyclin dependent kinases, demonstrating his ability to grasp the significance of the result outside his immediate sphere of interest".[83]

Hunt was knighted in the 2006 Birthday Honours, but has said that he rarely uses the title 'Sir' and that it should not affect his scientific standing.[84]

Personal life

Hunt is married to Mary Collins, who was also educated at the University of Cambridge. The couple have two daughters.[2]

As of 2015, Collins is a professor of immunology at University College London. Collins, one of the UK's most distinguished women scientists, was appointed director of research at the newly founded Okinawa Institute of Science and Technology in Okinawa, Japan. In summer 2016, the couple will move to Japan for an extended stay expected to last five years.[77][85]

Publications

Selected articles

  • Mochida, Satoru; Maslen, Sarah L; Skehel, Mark; Hunt, Tim (2010). "Greatwall phosphorylates an inhibitor of protein phosphatase 2Α that is essential for mitosis". Science. 330 (6011): 1670–1673. doi:. PMID . 
  • Mochida, Satoru; Hunt, Tim (2007). "Calcineurin is required to release Xenopus egg extracts from meiotic M phase". Nature. 449: 336–340. doi:. PMID . 
  • Rouse, John; Cohen, Philip; Trigon, Sylviane; Morange, Michel; Alonso-Llamazares, Ana; Zamanillo, Daniel; Hunt, Tim; Nebreda, Angel R. (1994). "A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins". Cell. 78 (6): 1027–1037. doi:. ISSN . PMID . 
  • Evans, Tom; Rosenthal, Eric T.; Youngblom, Jim; Distel, Dan; Hunt, Tim (1983). "Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division". Cell. 33 (2): 389–396. doi:. ISSN . PMID . 
  • Farrell, Paul J.; Balkow, Ken; Hunt, Tim; Jackson, Richard J.; Trachsel, Hans (1977). "Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis". Cell. 11 (1): 187–200. doi:. ISSN . PMID . 
  • Poon, R. Y.; Yamashita, K.; Adamczewski, J. P.; Hunt, T.; Shuttleworth, J. (1993). . EMBO Journal. 12: 3123–3132. PMC Freely accessible. PMID . 
  • Nebreda, A.R.; Hunt, T. (1993). . EMBO J. 12: 1979–1986. PMC Freely accessible. PMID . 
  • Craig, D.; Howell, M.T.; Gibbs, C.L.; Hunt, T.; Jackson, R.J. (1992). . Nucl. Acid. Res. 19: 4987–4995. doi:. PMC Freely accessible. PMID . 
  • Standart, N.; Dale, M.; Stewart, E.; Hunt, T. (1990). "Maternal mRNA from clam oocytes can be specifically unmasked in vitro by antisense RNA complementary to the 3' untranslated region". Genes Dev. 4: 2157–2168. doi:. PMID . 
  • Gautier, J.; Minshull, J.; Lohka, M.; Glotzer, M.; Hunt, T.; Maller, J.L. (1990). "Cyclin is a component of MPF from Xenopus". Cell. 60: 487–494. doi:. PMID . 
  • Standart, N.; Minshull, J.; Pines, J.; Hunt, T. (1987). "Cyclin synthesis, modification and destruction during meiotic maturation of the starfish oocyte". Dev. Biol. 124: 248–258. doi:. PMID . 
  • Minshull, J.; Hunt, T. (1986). . Nucleic Acids Res. 14: 6433–6451. doi:. PMC Freely accessible. PMID . 
  • Hunt, T.; Herbert, P.; Campbell, E.A.; Delidakis, C.; Jackson, R.J. (1983). "The use of affinity chromatography on 2'-5'ADP- Sepharose reveals a requirement for NADPH, thioredoxin and thioredoxin reductase for the maintenance of high protein synthesis activity in rabbit reticulocyte lysates". Eur. J. Biochem. 131: 303–311. doi:. PMID . 
  • Rosenthal, E.T.; Hunt, T.; Ruderman, J.V. (1980). "Selective translation of mRNA controls the pattern of protein synthesis during early development of the surf clam, Spisula solidissima". Cell. 20: 487–494. doi:. PMID . 
  • Hunter, A.R.; Hunt, T.; Knowland, J.S.; Zimmern, D. (1976). "Messenger RNA for the coat protein of tobacco mosaic virus". Nature. 260: 759–764. doi:. PMID . 
  • Darnbrough, C.H.; Legon, S.; Hunt, T.; Jackson, R.J. (1973). "Initiation of protein synthesis: evidence for messenger RNA- independent binding of methionyl transfer RNA to the 40S ribosomal subunit". J. Mol. Biol. 76: 379–403. PMID . 
  • Kosower, N.S.; Vanderhoff, G.A.; Benerofe, B.; Hunt, T.; Kosower, E.M. (1971). "Inhibition of protein synthesis by glutathione disulfide in the presence of glutathione". Biochem. Biophys. Res. Comm. 45: 816–821. doi:. PMID . 
  • Ehrenfeld, E.; Hunt, T. (1971). . Proc. Natl. Acad. Sci. USA. 68: 1075–1078. doi:. PMC Freely accessible. PMID . 
  • Hunt, T.; Hunter, A.R.; Munro, A.J. (1968). "Control of haemoglobin synthesis: distribution of ribosomes on the messenger RNA for a and b chains". J. Mol. Biol. 36: 31–45. doi:. PMID . 

Books

  • Murray, Andrew; Hunt, Tim (1993). The Cell Cycle: An Introduction. Oxford: Oxford University Press. ISBN 978-0195095296. 
  • Wilson, John; Hunt, Tim (2014). Molecular Biology of the Cell: The Problems Book (6th ed.). Taylor & Francis Ltd. ISBN 978-0815344537.