Friday 7 May 2010

Why I Experiment

The sling is off, and my thumb is well on the way to recovery. Soon, the One-Armed Scientist will be no more. But that's not what I want to talk about here.

In the course of my type of research, we make mutants. Not the grotesque humanoids of fiction with special powers, but rather individual cells - bacteria - with changes at a fundamental, microscopic level. Some of them do have special powers, such as antibiotic resistance or increased ability to cause disease. I usually work with mutations for the worst - bacteria which are slower, die more easily, infect less than the pathogenic originals, because an analysis of them says something about how an unmutated strain causes disease. Technology has progressed to the point that we can manipulate the genetic material of an organism to a fine level, precisely cutting out a single gene and inserting it to cause a controlled mutation. Barring random chance, one can practically tailor a single organism to one's desire, especially with a simple, single-celled bacterium.

I think sometimes we forget that they're still living, natural things, with all the variation and unpredictability which that implies.

The standard way to construct a mutant in my lab, is to prepare a stretch of DNA precisely constructed to be identical to the target region in the bacterium under study, with a single point artificially changed. The constructed DNA, through random chance, is then exchanged with the original sequence, causing the bacterium to acquire the mutation. Usually we insert something to make it favourable for the constructed DNA to be taken up, such as adding an antibiotic resistance gene and then growing the bacteria in the presence of that antibiotic. Notwithstanding whatever disadvantage the bacteria may experience from the mutation, the induced survival advantage enables it to survive long enough that the mutation can be studied. The entire process can be controlled carefully, by cutting DNA with enzymes which only cut at certain points, by checking the size of fragments by running them on agarose gels, and, ultimately, by sequencing the constructed DNA so that even a single wrong base can be seen. We can construct a sequence of DNA exactly to specifications using these modern tools.

But then there are the things which happen which don't fit our ideas of how things work.

I once cut a piece of DNA with two enzymes, such that only another piece of DNA cut with the same enzymes could join to it. The second piece contained a gene for a red fluorescence protein - if the two pieces successfully joined and entered a bacterial cell, the bacteria would glow pink. However,  I made a mistake - the second piece of DNA I added had not been cut with any enzyme, much less the correct ones. By all rights, it could never have connected with the first piece.

I got pink bacteria.

If I had straightaway realised my mistake, and thrown out the DNA, I would never had known that could happen.

Science is a systematic way to examine the world, by determining a way in which something can be tested, and then going ahead and testing it. That is the basis of the research I do. But the world is diverse - incredibly so. To systematically examine all phenomena is impossible. There is so much out there to question, one needs a place to start. And there is no better start than the random, anomalous occurance which doesn't fit in with one's preconceptions. Most major discoveries have started from such random occurances.

Which is why I believe one should keep working with things even if logically, they seem to have gone wrong. Accidentally tried to join uncut DNA with a cut sequence? Put it in some bacteria anyway and see what happens, it might be something exciting or unusual. Gel bands don't look right? Maybe you're the one expecting the wrong thing. Look at it again. The mutant bacteria seem to be missing something important which no bacteria should be able to survive without? Maybe that's precisely what you're looking for. If you wait, and keep repeating things until you get the results you were expecting, you might lose the truth.

After all, we are not here to construct precisely-specified pieces of DNA, or mutants with prescribed features. We are here to do research. We are here to examine, and discover. We are here to understand the world better so that we adapt ourselves to live in it better.

We are the children, gathering pebbles on the beach.

It might make more sense to look at each pebble, one by one, starting from one end of the beach and working towards the end.

But then you miss the view of the ocean.

No comments: