The lights dim, the projector flickers into life, and an imposing figure takes to the lectern. The audience watches in silent awe as we are taken elegantly from the first intriguing observations of a decade ago to today's cutting-edge results. These big shots, who seem to have it all sussed, have clearly scaled the ivory tower with gravity-defying surety.

But have things always run so smoothly for them? Have they never endured terrible failures or wanted to jack it all in and sign on for trolley-pushing at the local supermarket?

Intrigued with what may lie just slightly beneath the big shots' veneer, I embarked on a restless quest for the "disasters of the famous." And if many claimed to have had completely trauma-free careers at first, when pushed, they would often admit to running gels the wrong way, breaking equipment, throwing irreplaceable samples down the drain by accident, or contaminating things--so rest assured that these things do happen to everybody! (Although I doubt if any of them have broken my personal record: exploding two centrifuges in as many months!) Here's what they had to say:

Hugh Pelham, Head of Cell Biology at the MRC Laboratory of Molecular Biology, Cambridge, UK

It is true that most of us have had scientific disasters of one kind or another. One of my low moments was around 1983, in my second year as an independent scientist. I had successfully mapped the Drosophila hsp70 heat shock promoter, which turns on genes in response to heat stress. I had also shown that when I fused it to the herpesvirus thymidine kinase ( TK) gene, I could get heat-inducible TK transcripts in mammalian cells. With reckless ambition, I decided to add this fusion back into cells and then screen for mutants that could not either switch on or switch off the response to heat shock. My colleague Mike Lewis and I spent almost a year selecting cells (mostly getting them contaminated in the process), to eventually find out that they all behaved pretty much the same way. I did realise that the project was a bit of a long shot, but what I hadn't appreciated was how long it would take to fail. Eventually, we put it "on hold" and froze the cells we had while we thought what to do next. As far as I know, they are still in our liquid nitrogen tank.

We turned instead to trying to understand what the hsp70 protein actually did, and things went a bit better. I learned that sometimes, although it can be hard when a lot of effort has been put in, giving up is the best thing to do. I well remember the feeling of liberation, and the determination (desperation?) to make the next project work. A bit of failure is probably a good thing.

Sir John Gurdon, previous Director of the Wellcome Trust/Cancer Research UK Institute and Professor of Zoology, Cambridge, UK

The low point in my morale was when a referee (anonymous, as usual) accused me of falsifying my data by showing the same figure twice at different magnifications. Regrettably, I was unable to find the original histological slide of either of the figures in the manuscript. I eventually escaped the aggressive accusation by inviting the referee to come to my lab so that we could repeat the work under his or her supervision. I received no response to this offer! The paper was then accepted--without any further problems--but the experience taught me that it is probably impossible to provide 100% proof of anything. Therefore, if results are questioned or attacked, it is best to offer to repeat the work, if necessary in the presence of the challenger.

Baroness Susan Greenfield, Professor of Pharmacology, Oxford University

My major disaster happened in about 1992. Up until then, I had enjoyed excellent funding from a big drug company for my research. The £2 million grant allowed me to have about 15 people in the lab working on lots of exciting cross-disciplinary projects--something that would have been impossible on public grant money. Unfortunately the company then merged and the funding dried up with only 1 year's notice. Obviously this was a massive crisis! I had not applied for public grants for a while and found that every application was being rejected, despite the fact that we were regularly publishing good papers. I suspect this is because I had become used to visualising "big picture," high-risk projects, which are not well-loved by the public grant-awarding bodies. In my opinion, it's better to fund one novel, exciting paper than 10 pedestrian "dotting i's and crossing t's" papers, but such high-risk research seems to go against the prevailing attitude of grant review panels. Perhaps also there was an aspect to it that I was finally receiving my comeuppance for having enjoyed such good commercial funding for so long.

Science magazine features Susan Greenfield in a 2005 profile. Subscription required

In the end, money started to come in, bit by bit. Odd grants from industry added up, and many of my researchers found their own fellowships or came from abroad with their own money. Cash was certainly tight, though--we were living hand to mouth--and unfortunately I had to let some people go, which was very hard. But eventually, as I have always believed, what counts is the quality of your work and not the size of your group or grants. We continued to publish and in the mid-'90s with my colleague David Vaux I set up my own company, Synaptica, which attracted money from business angels and venture capitalists. With this funding came the resources to conduct basic research "on the side" in the lab. Ironically, the company has since spun out and is no longer under my control, so I am back to applying for grants again to fund my research interests! The whole experience has taught me that you must believe in your research, because the originality of your work is what's important, and that somehow things will work out in the end.

Jim Smith, Director of the Wellcome Trust/Cancer Research UK Institute, Cambridge

This particular event happened on 5 November--I think it must have been 1984. I was responsible for doing the annual fireworks display at the then-Imperial Cancer Research Fund and decided to retreat to the local pub for some lunchtime refreshment with my fellow gunpowder conspirators so that we could plan the event. I may have had a pint or so of beer at this point. When I came back to work, I remembered that I had to get something from the darkroom in the basement, so I went downstairs, pulled back the curtain over the door, entered, and switched on the light. To my horror I saw someone's autoradiograph slides drying on the bench, and realised I had exposed them to the light. I ran out, switching off the light and wondered what to do. In the end, I realised they probably belonged to Phil Ingham (now director of the Centre for Developmental Genetics in Sheffield) and went to confess. Phil was furious--he had been working on some of the early key in situ hybridisation experiments showing the expression of the segmentation gene Hairy in Drosophila, and I had ruined the lot. He had even gone to the trouble of pinning a rather small notice on the darkroom door saying "Do Not Enter" which I had failed to spot.

All in all it was not an auspicious day ... and it got even worse. Later that evening at the fireworks display, one of us managed to hold a burning taper over the box of fireworks and exploded the lot at once!

Dr. Tim Hunt, Nobel Laureate, Cancer Research UK

Probably the biggest disaster we ever suffered was when the lab burned down (or should that read "up"?) in June 1974. Everything was lost except for the samples we stored in liquid nitrogen, but we recovered in about 6 weeks thanks to a timely relocation that brought us within range of the MRC Laboratory of Molecular Biology. It was a blessing in disguise.

Kat Arney is currently sweeping up the latest batch of broken glass and hoping that nobody noticed.

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