WHY AM I DISCOURAGED? Glad you asked.

Linda and Amenhotep III

This is one of the famous "Colossi of Memnon"  There are two.

One used to sing, but now it doesn't.

I have just been taken to task by an old classmate for publically admitting to being “BORED AND DISCOURAGED”  (Blog for 2/4/14).  Unless I am mistaken, this person (she will be called ‘Margery”) and I went through grades K -  12 together, in tiny classes consisting of people who knew nearly everything about each other.  When I grew out of the age cohort that regarded girls as merely soft tattle-tales that couldn’t play football (for me, probably about age 12), Margery became an object of extreme interest.  From then on, until I left home for college, I wanted to have Margery as my girlfriend.  (Of course, there were another three or four girls who also fell into that category.)  However I was a nerd, and she was a princess.  It never occurred to me to ask her out; I knew what the answer would be.  I stuck with younger girls; they thought I was cool because I needed to shave.       

Anyway, Margery now lives in South Florida and seems to have an idyllic life, despite the fact that she must be daily tormented by heat and high humidity, poisonous snakes, and alligators.  Also, Florida is flat; nearly the worst thing you can say about any state.  But anyway, she asks why I am discouraged.  So, I will attempt to explain. The short answer is: I care a lot about cancer research, and sometimes I despair of its ultimate utility.

For instance, there is an article in today’s NY Times* about The Cancer Genome Atlas (TCGA).  This is an effort, funded by NIH, to investigate which genes are mutated in various kinds of common cancers.  The project was initiated in 2005 and has just reached what appears to be a finish, or at least a convenient spot to stop and take stock.  If my algebra is correct, they seem to have identified about 135 suspicious genes.  The cost to date is $365 million.  The director of TCGA wants to expand their efforts to encompass 50 cancer types.  If I understand the article, this would entail sequencing about 100,000 samples.  So, let’s say completing the Atlas is feasible.  The question then forces itself upon us: SO WHAT?  Cancer is very heterogeneous; what is referred to as ovarian cancer may actually represent the work of many combinations of genes gone wrong.  Some types of ovarian cancer have molecular affinities to breast cancer, while others may more closely resemble the causative factors in – say – colorectal cancer.  Also, few cancers are caused by a single mutation; often two or more are needed.  So, even if we know which genes tend to be screwy in which kinds of cancer, how in heaven’s name do we devise antidotes?  A successful targeted therapy is mentioned in the NY Times article, Tarceva by name, which is effective against non-small-cell lung cancer.  Unfortunately, the gene Tarceva “fixes” is only present in 10% of this particular cancer type, which is but one of several varieties of lung cancer.  How much would it cost to devise a Tarceva-like solution to the hundreds (hell, maybe thousands) of distinct genetic problems that result in what we call cancer?  Can we afford it?  Sure we can, but will we?

So, that is the kind of brooding that renders me “discouraged” My knee is coming along nicely, however, and shortly I will be in Borrego Springs with my friends in the Paleo Society.  We have fun digging up long-dead mammals – as well as throwing pot lucks and giving dinner parties.  I soon will be my old cheerful self again.

*http://www.nytimes.com/2014/02/07/science/a-catalog-of-cancer-genes-thats-done-or-just-a-start.html?ref=research&_r=0