File on Four – our comments

This week BBC Radio 4’s File on Four series ran a programme claiming that “Millions of pounds of charity donations and taxpayers’ money have been wasted on worthless cancer studies.” The gist of the programme was that scientists across the world had slipped up in how they studied the basic “nuts and bolts” of cancer – and that Cancer Research UK was somehow implicated in this error.

But are these allegations true?

Globally there is evidence that cell line contamination does happen – however this is not an issue that we have seen any evidence of from our researchers. We’d like to reassure our supporters that millions of pounds of Cancer Research UK funds have not been wasted.

According to the BBC, cancer researchers may have been working with cells that are not from the type of cancer they claim to be, or are contaminated by cells from other organisms. By using the wrong cells, the journalists claim, the scientists are “wasting millions of pounds” on essentially worthless research.

Before we look into the story in more detail, let’s backtrack a little and find out where these cells come from, and why scientists use them.

What is a “cell line”?

Most of us have seen pictures of researchers growing cells in plastic pots in the lab. But under most circumstances, cells prefer the pleasant environment of our bodies rather than a Petri dish, and don’t grow well. The exception is cancer cells.

Because the checks and balances that control the growth of cancer cells are faulty, they will proliferate unchecked – even under lab conditions.

These cells, taken from a single tumour, will carry on dividing when grown in the lab. The researchers who develop them then share them with their fellow scientists. The initial sample becomes a ‘cell line’.

All over the world, researchers are studying cells taken from tumours that are now growing happily in the lab. And a vast amount of very basic cancer research is carried out on these cells.

Other cell lines are generated from so-called primary cells – healthy cells from normal human or animal tissue which have been treated (usually with a virus) to make them “immortal” and grow in the lab.

But why do we need to use cell lines at all? It’s because often there isn’t an alternative. It’s impossible to carry out fundamental cancer research on real live humans, and unethical to use animals where replacements – such as cell lines – exist.

These cells provide a useful model system for scientists to study the “nuts and bolts” of cancer.

The expert’s view

But they are just that – a model. Professor Peter Parker is a leading cancer scientist at the Cancer Research UK London Research Institute, and Chair of the charity’s Cell Services User group.

He points out that laboratory-grown cancer cells are just a test system, and there are idiosyncrasies with different cell lines. For example, prostate cancer cells lines have some specific characteristics compared to, say, breast cancer cells.

But there are often crossovers.

“If you’re testing drugs on cell lines you’ll never learn everything about the type of cancer you’re going to treat – testing on a breast cancer cell may eventually lead to a drug that actually turns out to work on a different type of cancer, such as bowel cancer.

“That said, cell lines have been very effective at giving us avenues into the new drugs that are now being tested in the clinic.”

So where has the BBC’s story come from? Speaking to Professor Parker, it seems that this issue rears its head every few years.

This time round, the debate has been sparked by an open letter from representatives of the Catholic University of America to Secretary Michael Leavitt at the US Department of Health and Human Services, written in July 2007.

In their letter, the researchers raise concerns about the possibility that contaminated or misidentified cell lines might still be used in research, potentially wasting time and resources.

On top of this, in September, an international collaboration of scientists published a paper showing that a commonly used oesophageal cancer cell line known as TE-7 – had been mistakenly classed as one sub-type of oesophageal cancer – adenocarcinoma – when in fact it was another – squamous cell oesophageal carcinoma.

But does this evidence suggest that Cancer Research UK is “squandering millions” on research using duff cell lines? Certainly not. For a start, despite the headlines, the documentary does not accuse the charity directly of wasting money.

In fact, in their open letter, the researchers are referring to 30 years of research across the globe, and certainly not fingering any particular organisation. There is nothing to substantiate the claim that “millions of pounds” have been wasted by Cancer Research UK. This figure has been estimated at a global level from a few examples.

The Cancer Research UK Cell Services Team

Of course, our supporters will want to know that we are doing our best to avoid these problems. And for the past 35 years, the Cancer Research UK Cell Services unit has been doing just that.

Set up in order to avoid the very problems with contamination and mislabelling described by the US researchers, the Cell Services team have authenticated cell lines that are available for all Cancer Research UK-funded scientists.

The unit is widely regarded as the “gold standard” in cell provision across the UK. In fact, two of the signatories on the Catholic University’s open letter come from John Masters and R. Ian Freshney, whose expertise played a role in the establishment of the quality control techniques used by Cell Services.

Again, turning to the experts can shed light on the matter. Ruth Peat, Head of Cancer Research UK’s Cell Services, thinks that the programme failed to highlight the vital work that the cell team do to ensure that Cancer Research UK’s cells remain uncontaminated and correctly labelled.

“We’ve existed for 35 years, and have been doing DNA-based authentication of cell lines for the past 15 – since the technology became available. We can also check the species of a cell line by looking at the enzymes that are present.

“We have stringent operating procedures to avoid contamination and errors in handling and labelling cells. For example, we never work with more than one cell line in our tissue culture hood at a time. There are many safety measures that we’re experts in. It’s what we do every day – the provision of cells, quality control and authenticating cell lines.”

In fact, the researcher mentioned in the BBC programme – Dr Chris Tselepsis – worked with Cancer Research UK’s Cell Services team to highlight the problems with the TE-7 cell line.

Ruth continued, “If researchers get cells from other sources, such as collaborating labs, we can “quarantine” them, to make sure they’re not carrying a harmful contaminant called mycoplasma. We’ll also carry out DNA and enzyme analysis to determine whether the cells are really what they claim to be.

“Our services are widely advertised to the charity’s scientists, and many of them use us for all their cell needs. Of course we can’t have full control over every single cell they use, but this service is there for them to avoid these kinds of problems.”

She went on to point out that as far as she was aware, there were only a small number of incidents over the past 15 years where cells had turned out to be contaminated or misidentified. “It’s excellent that Cell Services exists for Cancer Research UK’s scientists, providing them with high quality cell lines. That’s why we’re here, and that’s why the charity has invested in us.”

Professor Parker agrees.

“I have absolutely no concerns that Cancer Research UK scientists are wasting millions of pounds – and in any case, the charity’s Cell Services department exists to prevent these problems.”

But can more be done to prevent the rare cases where rogue cell lines slip through the net? One article in the journal Science suggests that journals themselves should do more, insisting on evidence of cell-line authentication before results are published.

As a research funding organisation, Cancer Research UK is doing its utmost – for example, through the work of Cell Services – to ensure that our researchers have access to genuine cell lines. But we’re not complacent on this issue. We will continue to review the ways we support our researchers to ensure that they continue to produce the best world class science.

Kat