COUNTLESS research projects around the world into cancer and other major diseases are producing bogus or misleading results because investigators are studying the wrong type of cell.
The mistakes arise when fast-growing 鈥渞ogue cells鈥� contaminate cell cultures and swamp the correct cells. A team鈥檚 work on prostate cancer, for example, might turn out to be worthless because cells researchers thought were prostate cancer cells turn out to be cervical cancer cells.
Although the danger has been known about for decades, most researchers still fail to check the identity of the cells they are working with. And several new types of rogue cell are emerging, 麻豆传媒 has learned.
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Warnings of the potential scale of the problem were issued this week at a conference in Warwick organised by the UK鈥檚 Health Protection Agency. Precise figures are hard to come by because researchers are either unaware that they have worked with the wrong cells, or try to cover it up.
鈥淚f people have spent three years working on the wrong cells, they are not likely to want to tell people about it,鈥� says David Lewis, manager of the European Collection of Cell Cultures, based at Porton Down in Wiltshire. He will emphasise the importance of getting cells from authenticated sources at this week鈥檚 conference.
The best estimates available suggest around a fifth of all experiments in fields such as cancer and microbiology involve the wrong cells. 鈥淰arious figures between 20 and 40 per cent have been aired,鈥� says Rod MacLeod, head of the genetics laboratory at the DSMZ, the German collection of cell cultures in Braunschweig.
In a study in 1999, MacLeod found that of 252 cancer cell lines, 18 per cent were 鈥渋mpostors鈥�. And newly established cell lines were just as likely to be contaminated as older ones. He blames this on the ease with which cell lines can be contaminated.
The most notorious rogue cells are so-called 鈥淗eLa鈥� cells (see 鈥淒ivide and contaminate鈥�). They rapidly overrun more sluggish colonies. 鈥淛ust one HeLa cell could survive and proliferate,鈥� MacLeod says. Attempts to purge cell lines contaminated by HeLa cells have waxed and waned since 1967, when the problem first emerged, but now there are new rogue cells to deal with too.
One posing particular problems in cancer research is the T24 line of bladder cancer cells. MacLeod and Hans Drexler, director of the human and animal cell collection at the DSMZ, discovered them last year 鈥減osing鈥� as healthy epithelial cells that line organs. They are now popping up all over the place, especially in cultures of other cancer cells. Recently they contaminated prostate cancer cell lines, as Adrie van Bokhoven of the University of Colorado Health Sciences Center in Denver discovered. 鈥淭wo years after our research, there are still publications that describe it as prostate,鈥� van Bokhoven says.
In a review to be published this November in The Prostate journal, van Bokhoven will highlight the problems posed by another rogue cell, an unusually lively prostate cancer cell line called PC-3. 鈥淲e reveal that another three 鈥榰nique鈥� prostate lines were actually PC-3,鈥� he says, adding to others he has already discovered.
Before journals publish a paper van Bokhoven wants editors to insist that researchers provide proof that their cell lines are authentic. 鈥淓ditors should demand it,鈥� says van Bokhoven, who points out that the DNA fingerprinting tools now available should allow the problem to be eradicated. 鈥淭here are no more excuses,鈥� he says.
John Masters of University College London, who has struggled for years to highlight the problem, agrees. 鈥淚鈥檝e written to journal editors till I鈥檓 blue in the face on this, and they do nothing,鈥� he says. This unwillingness to confront the issue has been dubbed 鈥渇alse cell-line denial syndrome鈥� by Drexler, who says that the problem will persist as long as it is swept under the carpet.
Senior figures at the American Type Culture Collection have also tried for years to highlight the problem, says Keith Bostian, of the American Society of Microbiology. The ASM is aware of the problem, he says, and its journals 鈥渆ncourage鈥� authors to deposit cell lines in public collections for authentication.
Yet one survey conducted by the ATCC revealed that two-thirds of journals still fail to cite the source of biological materials. Worse, many of the cultures the ATCC receives for deposit are misidentified or contaminated.
Divide and contaminate
Cell cultures are the workhorses of modern biology, used to study everything from cancer and infectious diseases to the genetic workings of our cells. Whole colonies can be grown in Petri dishes from a single 鈥渕other鈥� cell.
But because different cells often look identical, researchers often can鈥檛 tell if they are working with the wrong cells. And such mix-ups can happen easily. Sometimes natural mutations result in 鈥済enetic drift鈥� away from the original cell. But often the culprit is contamination with fast-growing invaders such as 鈥淗eLa鈥� cells, cervical cancer cells that in 1952 became the first human cells to be grown in culture. All it takes is one stray HeLa cell, perhaps in the nutrient medium used to grow cells, and the rogue cells will rapidly overrun a colony.
One cell line called KB, for instance, was supposed come from a mouth tumour. Between 1998 and 2000, it was cited more than 300 times in studies of head and neck cancer. But it turned out to be a HeLa cell line. The same was true of HEp-2, a cell line thought to have originated from a larynx tumour. That was also cited around 300 times.