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Last Updated: Tuesday, 20 November 2007, 16:30 GMT
How cancer studies wasted cash
By Gerry Northam
File On 4

Lab samples
Cell-line mistakes have made thousands of cancer studies invalid
Expensive and time-consuming work in laboratories around the world has rendered many cancers treatable, bringing added years, even decades, for countless patients and their families.

So it comes as a shock to learn that millions of pounds in charitable donations and from taxpayers are being wasted on "worthless" research for lack of good housekeeping practice in the lab.

BBC File On 4 has discovered that many scientists fail to carry out simple and inexpensive checks to ensure that they are working with the right experimental materials - particular forms of human cancer cells.

As a result, thousands of studies are invalid.

The experience of Dr Chris Tselepis at the Cancer Research UK laboratories in Birmingham University, highlights the problem.

For more than 20 years, researchers in many countries have used a particular experimental culture of cancer cells known as TE7 to study one type of oesophageal cancer.

This 'cell-line' has been sold worldwide and formed the basis of hundreds of published studies.

It is an incredible frustration because brain tumour research is extremely poorly funded and its hard-fought money and when we get money into the laboratory we need to produce good strong results, good strong data and we need to report back to those organisations which are mainly charities who are funding our research.
Prof Geoff Pilkington, University of Portsmouth

But Dr Tselepis and an international group of colleagues discovered that TE7 is the wrong type of cancer, and the implications for two decades of study are grave.

"If there's a study which is claiming that a particular drug has a particular effect on a cell type and potentially you could use this drug for the treatment of patients that clearly is going to be misfounded," he explained.

The result is a waste of time and money.

But how can this happen?

The problem of misidentification of cell-lines arises because to the naked eye they look similar - a cluster of tiny dots on the bottom of a laboratory flask.

Even under a powerful microscope, it can be hard to tell one cancer cell from another.

Professor Geoff Pilkington, of the University of Portsmouth learned this the hard way , "There are two incidences that I'm aware of in the laboratories whereby we've had what we call squeaky contaminants and these are whereby our human cell lines, where those have become contaminated with either rat or mouse cell lines."

It meant the whole research into brain tumours had to be binned and started again.

Breast cancer cells
Some academics have called for tough action to authenticate cell-lines

"It is an incredible frustration because brain tumour research is extremely poorly funded and its hard-fought money and when we get money into the laboratory we need to produce good strong results, good strong data and we need to report back to those organisations which are mainly charities who are funding our research."

The problems created by contaminated or misidentified cell-lines have a wider impact as studies based on the wrong materials regularly find their way into scientific journals and become part of the accepted literature - muddying the foundation for further research.

This danger troubles one of Britain's leading experts, Karol Sikora Professor of Cancer Medicine at Imperial College London.

Although he is quick to point out that no patient is likely to be directly harmed by such invalid lab work.

'Sloppy science'

"One of the problems of course is that investigators are competitive, eager to get the results. They don't want to waste their time doing what they regard as a technical exercise, typing the cell lines. They believe someone else should do it for them. And that's led to this sloppiness, I guess, in science."

And even after a false cell-line has been unmasked, scientists carry on using it as if it were the real thing while other studies are utterly invalidated by the error.

Professor Gertrude Buehring, found a third of studies involving a false cell-line in publications from 1969 to 2004 used it in an invalid way as if it were the cell type of origin and obviously having no idea it was a contaminant.

The expert on leukaemia and breast cancer at the University of California in Berkeley, was one of 19 eminent specialists from Britain and America who wrote this summer to the United States Health Secretary calling for tough action to eliminate such "worthless" research.

The Director of the Federal Research Agency National Institutes of Health responded: "There appears to be abundant evidence that contaminated or misidentified cultures have compromised the validity of many studies and publications."

We would expect labs to authenticate their work or use properly-sourced cells.
Dr Rob Buckle, Medical Research Council

But the response from scientists was lukewarm according to the originator of the Open Letter, Professor Roland Nardone of the Catholic University of America.

"They morphed into ostriches, is the best explanation I have."

He now advocates zero tolerance with respect to advocating "no authentication, no grant; no authentication, no publication in a good scientific journal.

" We wanted to ask the editors of leading UK journals and funding bodies their response to the no authentication, no publication policy.

No-one from the leading British journal 'Nature' was available for interview. Nor was the editor of the British Journal of Cancer.

The journal's parent body, Cancer Research UK, did not put up anyone for interview but in a statement stressed it carried out stringent checks on its own bank of cell-lines, including a DNA authenticating service.

And there was a cautious response from the leading source of public funding, the Medical Research Council, which spends 500m of public money a year - more than 70m of it on cancer research.

Cell authentication

The MRC's Dr Rob Buckle said: "We would expect labs to authenticate their work or use properly-sourced cells."

It may seem unbelievable to those outside the scientific establishment that there should be a problem of using false research samples especially when a relatively cheap authentication process is now available.

But even within the establishment, voices are now calling for science to put its house in order, joined by Prof Sikora.

"I think we as a scientific community have to do something about it. Just no grant or no publication, but no publication is probably more powerful. If one of the leading journals, which all of us want to publish in, said 'okay, you have used cell lines, wonderful, just give us the certificate of authenticity.' Now we can tell all that and it doesn't necessarily cost a lot of money."

You hear the full story on File On 4, Tuesday 20 November 2007, 2000 GMT, repeated Sunday 25 November 2007, 1700 GMT.



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Cancer studies 'wasted millions'
20 Nov 07 |  File on 4

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