If you have ever worked in a molecular or medical biology research laboratory, chances are one of the first things you learnt was cell and tissue culture (TC) or the microbiology equivalents. Even if you know nothing about biology, you've probably heard mentions of cell culture on the news, or at the very least heard about the results of studies in cell culture. If you hear about "cell lines", you've got culture. If you hear about a "laboratory study" showing that your favourite chemical is carcinogenic, you've probably got culture. If you hear about new trials on a miracle cancer cure that has been shown to be effective in "preliminary laboratory tests", you've probably got culture. Everything from zombie epidemics to £10,000 animal-free beef is cell culture. Knowing a little bit about what cell culture is, and what its uses and limitations are, is therefore important when answering such questions as "is my baby's bottle poisonous?", "is stem-cell research ethical?" and "is vitamin C an effective cure for colds/cancer/HIV?"

So. What is TC? It's when you take specific cells from a multi-cellular animal and grow them in a dish full of nutrients (a mimic of your blood serum). The point of doing this is to create a system on which to experiment which does not require growing and killing lots of individuals -- something that is time consuming, messy, and, for some reason, considered unethical. Especially when it's humans you propose using. Typically, human or other mammalian tissues are used -- especially "model organisms" such as mice, whose biology we already understand in some detail. You can use healthy or diseased cell lines from all sorts of different organs. Once you've grown up a nice batch of cells in your dish, you can see how they respond to your cancer drug, environmental contaminant, or new junk food ingredient. You can see exactly how the behaviour of your cells changes over the minutes, hours and days of exposure; how they recover after the chemical has been flushed away; how your cancer drug works in dozens of different tumours; how your junk food ingredient works in the old and young, male and female, fit and fat; and how your environmental contaminant interacts with other environmental contaminants. It's great. If you work hard enough, you can know everything you want to know about your chemical within a week. Wipe out cancer and save the world by next Monday. At least, that's what the animal-rights movement would have you believe. And the tabloid press fall for it daily.

Trouble is, it's very easy to get superficially interesting answers using TC. Which makes it very easy to convince a journalist that you have important results, but very difficult to convince a scientist. That's not to say that TC is not important. But everything that we measure in TC is a crude estimate of what happens in real life situations. It is a simplified model of life that puts aside as many details and complications as possible in order to study surrogate measures of a cell's activity, from which we can develop our hypotheses about what happens in reality. And it's OK that it's simplified and sometimes crude: all fields employ simplified models. Engineers in the early stages of designing a car will take each of the individual components out of the context of the car and the road to test alternative materials for each piece. But the isolated and individually tested pieces don't form a car when chucked together. Studying isolated parts in simplified laboratory environments is only the first step in finding out how those parts perform on the road.

Cells in a dish are not merely parts isolated from the whole. They are parts prised and wrenched from the whole. Cells did not evolve for growth in a dish. They evolved in the context of cooperation with a vast number of other specialist cells in a body. They are not fine tuned for survival in the absence of skin, an immune system, a digestive system, liver and kidneys. They are not supposed to live like barnacles on plastic. But if you've worked with research quality cell lines, you'll know that it's surprisingly easy to make them grow in a dish. Feed them every couple of days, and they'll happily live for many months. Well go and say that to the post-docs and technicians who made them that way. They were up until midnight processing disgusting lumps of freshly excised tumour. They spent months trying out different combinations of nutrients and fungicides in an attempt to make the cells survive longer than a week. They may be easy to grow now, but don't think there wasn't any effort involved; don't think there weren't dozens of cell lines that didn't make it. Under these circumstances, you can hardly expect the cells not have evolved a little. You are introducing them to a vast number of novel mutagens by taking them away from the protection of skin. And putting anything into a new environment is going to mean new selection pressures. When you finally manage to immortalise your cell line, is it because you've perfectly adjusted the conditions to the cells, or because the cells have adapted to the conditions?

So. There are all sorts of reasons why TC can not be anything more than an approximation of what is happening in real life. A useful approximation, but unreliable in the absence confirmatory evidence from in vivo and population studies. But these are only the intrinsic limitations of TC. When judging the merits of TC based research, you must also take into the account the fact that TC is easily misused and misrepresented, and that charlatans are doing it all the time. TC is a favourite of cargo-cult healers and nutritionists -- those who like to keep up a superficial appearance of having a scientific basis for their quackery. Take, for example, the shamen who pedal vitamin C as an HIV/AIDS drug (Patrick Holford, for example) or as a cancer therapy. They will tell you that in TC, vitamin C has been shown to kill tumour cells, or those cells that are infected with HIV. Therefore, the reasoning goes, we should abandon proven therapies, in favour of taking some vitamin supplements. Trouble is, you can chuck a big lump of any chemical in a dish of cells and the cells will die. I could pour a bag of vitamin C into a dish of healthy cells. They will die. Conclusion: those vitamin supplements are deadly poisonous. Except that your cells will never be exposed to a bag of vitamin C, because you have skin, a digestive system, a liver, and kidneys. I could spit in a dish of cells and tell you that spit is a killer. It's not.

But it's not just charlatans that abuse TC. Many legitimate scientists bend the rules a little. They may not even be aware that they are doing it. Take the case of Bisphenol A (BPA), something I did a little work on a few of years ago. BPA is a component of some plastics, particularly bottles. It is known to very slowly leach out of the bottles and into your drink. There is a little bit of evidence (mostly from rats) to show that consuming BPA may be harmful. And there are a lot of TC experiments on the chemical. BPA is a xenoestrogen, meaning that it mimics the activity of estrogens. Estrogen, of course, regulates prolactin release and cell division (particularly in the breast). We know that BPA mimics estrogens because when we put some in our dish of tumour cells, we see that within seconds the estrogen receptors have been activated, and all the effects of estrogen follow. There are loads of results to confirm this because there are a lot of experiments into the effect of estrogen (there's plenty of money in breast cancer research). If you're doing an experiment on estrogen anyway, it's hardly any more effort to look at BPA while you're at it. And you can then pretend that your research has multiple medical applications. But since it's not the primary aim of your research, the journal's reviewers won't notice that you're using the chemical at a thousand times the concentration that you would ever find it in the body. Maybe enough BPA does leach out of your bottle to be a concern, and certainly BPA is theoretically capable of doing interesting things in the body. But a large proportion of the TC studies into BPA will be irrelevant in understanding how it does those things and whether it is really anything to worry about.

So, next time you are flicking through the health pages of the Daily Mail -- which I know all of you like to do -- engage healthy skepticism when they update the list of miracle cures and carcinogens. Like statistics, tissue culture is incredibly useful -- whether you're searching for the truth, or a convincing lie.

This is an updated re-post of an article I wrote at cotch dot net two years ago.