The problem with petri dish science

Over the past week a couple of the blogs I follow (Respectful Insolence for one, check it out) have been bloging about various topics like common lies told by animal "rights" activists and the shit-poor studies conducted by pseudosciences like homeopathy to make their work seem legit. One topic that has come up in these various blogs is the limitations of cultured cells - in particular immortalised cell lines - in scientific research.

This is of particular interest to be, because the current work I do involves extensive use of such cell lines, and prior to this I did my training in a lab where the rule of thumb was "if you cannot show it in an animal, it isn't real".

(above image - an image of a cell line [RAW264.7 macropahge])

To the uninitiated this may all seem a little odd, so to clarify I'll digress into the world of our bodies verses a petri dish. All of the cells in our bodies have a few general characteristics which is vital to our biology - they all maintain a relatively unaltered copy of our genome (mutations do happen in our cells, but are relatively rare), they all experience something called contact growth arrest (i.e. when they find themselves surrounded by other cells, they stop growing/dividing), they do not divide overly much (many do not divide at all) and they all require oxygen for their growth and function. The former three characteristics are central to preventing unwanted cell growth - i.e. cancer.

To make a cell line - basically cells we can grow ad infinitum in petri dishes, we have to overcome the third characteristic; little to no cell division. The ways this is done varries - you can frequently transfer the cells to new dishes, at low density, which stimulates their growth. Do this enough and the cells will eventually loose their ability to turn off their growth. You can also infect them with certain viruses, or derive your cells from a tumor. The only problem with these kinds of methods is they all greatly alter the biology of the cell. For example, getting the cells to divide faster reduces the time they have to check their DNA for errors, leading to accumulation of mutations and chromosomal abnormalities. For reasons not entierly clear, contact growth inhibition is also often lost when you overcome the growth defect.

The end result of this is that the cell lines we use - some of which were first derived in the 1950's - don't represent the tissues they are isolated from very well. Many take on full-on tumor characteristics - warburg respiration (i.e. they grow without oxygen), aneuplody (incorrect numbers of chromosomes), even regression to a more stem-cell like state (something common in tumours). In addition, they often loose protein expression of the very proteins that characterise the tissues they come from.

This has a real impact on science conducted using stem cells. Every day results generated using these kinds of cells are shown to be incorrect when primary cells (i.e. cells freshly isolated from the tissue) or animals/humans are used. That's not to say they are useless - 95% or so of what is discovered in cell lines holds true, but rather the results need to be taken with a grain of salt. And in many cases - particularity drug tests - cell lines cannot replicate the complexities of the mammalian body, including the inevitable metabolic processing of the drug - something which usually occurs in the cells of the liver, rather than the targeted cell/tissue.

This is of real importance when talking about the claims of animal rights activists, or pseudoscientists. For example, a common claim of animal rights groups is that animal studies can be replaced with these cell lines. This is wishful thinking on their part, both because these cells do not replicate the human body, nor do they even represent the tissues they were derived from. The same criticism needs to be kept in mind when talking to promoters of pseudoscience. For example, in this "study" woo-meisters test homeopathic remidies for cancer by comparing their effects on cell lines derived from actual tumours to cell lines derived from breast tissue (Orac demolishes the study here). The problem here (aside from the shit-poor "science" and lack of stats) should be obvious by this point in my post - those "non cancerous" cell lines are going to be close to, if not entierly, cancerous in nature due to what it takes to make a cell line. Regardless of how far along the road to cancer they are, one thing can be guaranteed - they're a long ways away from being real breast tissue.

The take home here is simple - cell lines are a powerful research tool. They've done more to uncover the inner workings of our cells than any other technique I can think of. But results generated in them need to be verified in primary cells or living organisms, and when using them in studies their limitations need to be forefront in our minds.