When Paul Nurse was a student in the 1960s, scientists knew that cells divided and make copies of themselves. Yet key questions remained a mystery: What controls these divisions? How is the copying of DNA initiated? What drives cells to divide? Gripped by these puzzles, Nurse, Chair of EMBL\u2019s Scientific Advisory Committee and Secretary-General of EMBO, would go on to win a Nobel Prize for identifying crucial mechanisms underlying the cell division process. Yet things could have turned out very differently.<\/p>\n\n\n\n
\u201cI had very good grades in school and was offered a place at every university I applied for,\u201d says Nurse, who now heads the Francis Crick Institute in London. \u201cHowever, the offers were conditional on me passing a very elementary French exam, and I failed it six times \u2013 it\u2019s not like I wasn\u2019t trying, but I am completely incompetent at languages.\u201d<\/p>\n\n\n\n
Struggling with his French re-sits, Nurse left school and spent time working as a technician in a laboratory run by a local Guinness brewery. Each week he quickly completed his work, leaving plenty of time for research projects, which he loved. But he just could not pass French and it took a chance encounter with Birmingham University Professor of Genetics John Jinks to ignite his scientific career. Jinks recognised Nurse\u2019s potential and arranged for him to enrol as an undergraduate biology student. \u201cThere was a sting in the tail because the University Senate insisted I study French in my first year!\u201d Nurse recalls.<\/p>\n\n\n\n
The cell is the simplest thing that demonstrates life<\/p><\/blockquote>\n\n\n\n
But there were more hurdles to come. \u201cI was initially interested in ecology, but a field trip collecting specimens in freezing waters taught me I was better suited to the warmer environment of the lab,\u201d Nurse says. It was here, under the guidance of an eccentric zoology lecturer Jack Cohen, that he undertook a project measuring the respiration rate of dividing fish eggs.<\/p>\n\n\n\n
\u201cCell division is the basis of all growth and development \u2013 I was immediately fascinated by it,\u201d he recalls. Over the course of the following months, Nurse carefully collected eggs from the University aquarium, placing samples in a sealed chamber. He then measured ambient oxygen levels, painstakingly observing the effects of different inhibitors. \u201cI soon saw that the respiration rate oscillated every fifteen minutes or so, which is also roughly the time needed for the fish eggs to divide,\u201d he says. \u201cStrangely this pattern persisted no matter what I did to the system \u2013 it seemed incredibly robust.\u201d<\/p>\n\n\n\n
Do controls early on in your study, as soon as it becomes interesting!<\/p><\/blockquote>\n\n\n\n
Yet a week before Nurse was due to hand in the work, a seemingly routine control test left him stunned. \u201cI ran the experiment with no eggs in the chamber and I measured the same, perfect, oscillation,\u201d he says. \u201cI repeated the experiment again and again, convinced there must be a mistake. But I eventually realised that rather than measuring the respiration rate of the eggs, all the time I had been monitoring the effects of a thermostat in my apparatus. It was a complete failure from beginning to end.\u201d<\/p>\n\n\n\n
With his grades at stake and just one week to go before presenting the study, Nurse faced a big problem. \u201cThe only thing that I could think of to salvage my degree was a piece of theatre,\u201d he recalls. \u201cIn my presentation I re-lived the whole study, from its exciting beginnings to its disastrous ending \u2013 and somehow the audience was impressed. One key message was: do controls early on in your study, as soon as it becomes interesting!\u201d<\/p>\n\n\n\n
Keep going<\/h2>\n\n\n\n
\u201cAt my low points, I contemplated alternative careers,\u201d he says. \u201cBut I am very much an experimentalist at heart and I have been lucky over the course of my career to have had very supportive colleagues.\u201d Ultimately undeterred, Nurse successfully completed his degree and PhD. As a postdoc, he saw the cell cycle as a way to learn more about what fascinated him most: the nature of life. \u201cThe cell is the simplest thing that demonstrates life,\u201d he says. \u201cKey to understanding that is knowing how information is managed in the cell to generate order in space and time.\u201d<\/p>\n\n\n\n
Inspired by studies showing how genetics could be used to study the budding yeast cycle, Nurse returned to a research subject that he first encountered working in the Guinness laboratory: brewer\u2019s yeast. \u201cI wanted a model organism that would be simple and effective,\u201d he recalls. He led work that treated yeast in a way that induced mutations randomly in genes throughout the yeast genome.<\/p>\n\n\n\n
Sometimes nature provides the best leads<\/p><\/blockquote>\n\n\n\n
Nurse figured that the key to identifying genes controlling cell division in the yeast would come from studying cells that divide particularly slowly (creating bigger cells) or particularly quickly (creating smaller cells). The second category he discovered by chance. He observed some unusually small cells that divided more rapidly before they could grow and identified a mutation in a gene called cdc2 that appeared to play a role in initiating key stages of the cell division cycle. \u201cSometimes nature provides the best leads,\u201d he says.<\/p>\n\n\n\n
After discovering that a cdc2<\/em>-like gene was also in another type of yeast, Nurse wondered if the gene might exist in all organisms \u2013 a question he began to tackle at the Imperial Cancer Research Fund labs in 1984. \u201cThere were a few eyebrows raised as to what exactly a yeast researcher was doing at a cancer research centre,\u201d he says. His team took a human gene library and added it to yeast lacking the cdc2 gene. Incredibly, after one of the human genes was added to the yeast, it resulted in the cells dividing as normal. It enabled Nurse to go on to draw the astounding conclusion that a fundamental engine driving the cell cycle was the same in all species, a mechanism that had traversed 1 to 1.5 billion years of evolution.<\/p>\n\n\n\n
It is important to know the real stories behind science to inspire the next generation of scientists<\/p><\/blockquote>\n\n\n\n
The work led to the discovery (together with friend Tim Hunt) of cellular messenger molecules called cyclin dependent protein kinases \u2013 cellular messengers that pass signals and other insights into the nature of the cell cycle, all crucial for understanding health and disease.<\/p>\n\n\n\n
\u201cIt is important to know the real stories behind science and the failures and successes that are part and parcel of our work to inspire the next generation of scientists,\u201d Nurse adds. \u201cThere is still a lot we don\u2019t know about how cells organise in space and time, but I think we will make real progress in the coming half century because of the methodologies that we have developed in the past five decades. And of course, as I learned from my fruitless experiments on fish egg respiration, from the countless failures we have made along the way.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
Paul Nurse\u2019s failed experiment inspired a career that would uncover key mechanisms of cell division<\/p>\n","protected":false},"author":10,"featured_media":8824,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[64,66,41],"embl_taxonomy":[],"class_list":["post-8782","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cell-biology","tag-cell-division","tag-genetics"],"acf":{"article_intro":"
Paul Nurse\u2019s failed experiment inspired a career that would uncover key mechanisms of cell division<\/p>\n","related_links":[{"link_description":"Paul Nurse's laboratory at the Francis Crick Institute","link_url":"https:\/\/www.crick.ac.uk\/research\/a-z-researchers\/researchers-k-o\/paul-nurse\/"}],"article_sources":false,"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"\n
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