Where do we go from here in biomedical science (or why is context so damn important)
I’ve been to a conference recently. Not a particularly great one, for that matter, but the food was OK, so I didn’t complain too much. What it made me realize, though, is what kind of science I DON’T like. I don’t like basic pharmacology and I don’t like people making assumptions and generalizations based on very scant evidence from a very limited experimental paradigm. So what that cell line A shows inhibition of blabetyblab upon exposure by blibetyblib and that blabetyblab was shown to be upregulated in a bunch of tumors. It doesn’t mean that blibetyblib is going to be the new silver bullet against cancer!!! Geez. People always seem to forget the most important thing: the CONTEXT. Cell line A is sitting on a polystyrene dish, for pete’s sake, it is bathing in a friggin’ ambrosia of growth factors and God forbid it ever becomes overcrowded. A tumor is a heterogenous, ever-changing, living thing with the host organism trying to eliminate it, millions of cells of different kinds surrounding it and either helping it grow or inhibiting it, growth factors coming from blood, lymph, cerebrospinal fluid and whatnot, itself undergoing mutations, evolving, adapting to the environment. If we just chuck at it whatever we found was effectively blocking blabetyblab, it is just going to evolve to not need blabetyblab any more.
So how do we ever factor the CONTEXT in, you might say. We cannot possibly find out what the context of a particular diseased cell is at the moment. Or can we? Let’s see… Context is: 1. genetics (which is variable in the case of tumors at least) 2. epigenetics 3. environment. These three (interdependent) factors constitute what you might the current, ever changing context of the cell and pretty much determine how the cell will behave upon stimulation with blibetyblib or anything else for that matter. How do we find out, though, what the current context of the cell is and how it relates to the context of cell A? Well, we cannot exactly take everything into account, but we can do the next best thing – look at the general output of the context. How? We now have an answer – gene expression microarrays.
Here’s what I postulate: Every experiment done on cell lines, primary cells or any other in vitro system should be accompanied by a gene expression microarray for the control group. This would provide a wealth of data for data interpretation and for comparisons of results between studies and labs, and finally, if the results had medical significance, would allow us to select therapies based on the similarity of CONTEXTS between experimental systems and diseased cells. Such information would also enable another, in my opinion very important, venture: providing context-dependent gene expression signatures of the activation of specific signaling pathways. I am actually surprised that so little is known about what genes are likely to be up- and down-regulated in response to the activation of specific signaling pathways. Again, this is probably mostly due to the fact that the gene expression signatures of these pathways are so damn context-dependent. However, if we had a huge database of well-annotated microarray data, we could employ computers to mine through that data and find, to a best approximation, experiments that were done in similar context to ours and therefore would likely provide important background information for our studies and/or clinical case. I am not sure how much computing power and resources that would require, but it is just an idea…