Mutations – beyond the X-Men

This week, I have been reviewing research grant applications for the National Cancer Institute, including a number of grants proposing detailed evaluation of the gene mutations that can cause cancer. After spending hours looking at figures and data, I needed a break from mutations and decided to watch a movie.  One that has been on my “I should see that someday” list for some time is “X-men.”   So much for taking a break from mutations.  For those of you who are not familiar with “X-men,” it features a group of mutant humans with unique powers.   There are good mutants and bad mutants, epic battles, heroes and villains, etc., etc.   I won’t go into the details of the plot, but simply say it is worth seeing if you like special effects and over-the-top science fiction action, but not so much if you are a stickler for scientific plausibility.

Nevertheless, the movie certainly solidified “mutations” as my theme for the day, and got me thinking about the nugget of scientific truth that is the basis of the movie’s plot – namely the good and bad of mutations.  So … I will put Wolverine, Sabertooth, and Magneto on hold for a moment, and talk about actual mutations.

The simple truth is that mutations happen in our DNA all the time (for those “scientific sticklers,” see a nice, brief review at http://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409 ).  The process of DNA duplication is incredibly accurate but not perfect.  When a cell divides, every one of the 3 billion base pairs in DNA is duplicated, and a huge number of cells divide in our bodies every day.  Even a very low error rate will lead to DNA mutations in some of our cells.   Most of these mutations have no effect.  In fact, every cell has molecular machinery that can detect and repair mutations.  Other times, a mutation that gets through will result in abnormal behavior of the cell.  Cells are programmed to commit suicide when something goes haywire as a result of DNA mutations.  The loss of a single broken cell here and there is not an issue and happens all the time.

The problem results when a mutation hits in just the wrong place, and results in uncontrolled growth and survival of the cell.  When those cells divide, the  mutations are passed on each time, so eventually you have billions of rogue cells that all have the same mutation and are no longer playing by the rules – this is cancer.  In fact , some mutations can be even trickier.  They can occur in the genes that repair DNA or in those that induce death of misbehaving cells.  Such mutations are truly evil in the eye of the oncologist, as the bad cells accumulate even more mutations and become harder to eliminate.

How can mutations ever be good?  If DNA duplication was perfect, we would all still be single cell organisms swimming around in the primordial soup.  Evolution is dependent on mutations.  However, mutations that provide an evolutionary advantage are incredibly rare.  Not only do they need to result in a change that improves the change of survival, they also need to occur in the “germ line” cells that are passed from one generation to another.  Thus, a lot of mutations need to occur for the occasional beneficial mutation to emerge.  The study of genetics has demonstrated DNA duplication is accurate enough to allow cells to divide and duplicate effectively, yet with just enough of an error rate to allow organisms to evolve over millennia.

As a cancer biologist and oncologist, it helps me to think of cancer as an unavoidable byproduct of imperfect DNA duplication, which itself was vital for organisms to evolve.    Simply put, without mutations, we would not be here.

So, I still have a bit of “X-men” on my mind but it is time to get back to reality.  Time to call on my inner Wolverine and get back to our battle to defeat the evil mutants known as cancer.