Welcome to the World of Genomics... [Part One]

Although chronic myelogenous leukemia (CML) which is the main target of Gleevec, would not be considered one of the "major" cancers, I consider Gleevec to be the "poster child" for rational cancer drug design. I think that its importance goes far beyond CML but really creates a "proof of principle" that this kind of approach really will pay huge dividends in the future.

But as I stressed in the last post, approaches like this can only work when we understand more and more at the gene and molecular levels exactly what are the nature of the mutations that underlie particular cancer diagnoses. Which brings us to the brave new world of genomics…

With the success of drugs like Gleevec, combined with huge advances in technology, the field of cancer genomics is exploding and researchers around the globe are trying to catalogue as many cancer-causing mutations as we possibly can. So, what exactly is the study of genomics, and why should we care?

To understand cancer genomics we need to step back and understand what exactly is meant by the "human genome". Simply put, the human genome is the full collection of genetic material in each one of us.

You will recall that normal human beings have 23 pairs of chromosomes, and these chromosomes are comprised of long strands of DNA. If you remember your high school biology you will remember that DNA is comprised of four different chemical building blocks which we abbreviate as "A", "T","C", and "G". In each of our genomes there are about 3 billion(yes, that's billion with a 'B') of these building blocks arranged along each of the 23 chromosomes, but in a very particular order for each unique individual. It is this unique sequence of your DNA that defines the genes that make you an individual, different from me as an individual, different from your friend, different from your siblings etc. So, genomics is simply the study of the genome, and our attempts to understand how differences in the sequences of DNA contribute to human life and to individual variation.

So why is this important for cancer? Simply put, cancer is a disease of genes and mutations, i.e., mistakes in this “DNA alphabet”. The more and more we understand the genome alphabet and the more we learn about the different mutations that are associated with cancer, the better able we will be to understand, prevent, diagnose, treat and even cure cancers.

Now we have known about some fundamentals of DNA for a long time. The famous paper in the journal Nature by Jim Watson and Francis Crick was, after all, published on April 25, 1953! But knowing about some of the fundamentals of DNA is not nearly enough until we developed some tools to really study this in detail. Fast-forward from the famous publication by Watson and Crick about 25 years and you find me, as a postdoctoral fellow at the University of Calgary, doing some sequencing of DNA genes. In those days, in the late 70’s, I would have been able to routinely analyze a few dozen base pairs of DNA at a time, and that would have typically taken me several days to perhaps a week in order to accomplish. When you're dealing with 3 billion base pairs, this is very slow progress indeed.

Let's put the genome challenge in perspective in a different way. The human genome is comprised of about 3 billion base pairs. If your job was to read aloud your own genome starting from one end of chromosome number 1 and going all the way to the tip of chromosome 23, how long would it take you to read your own DNA sequence? Let's assume that you can read at the rate of about five bases per second, and that you work eight hours a day straight, five days per week (I'll give you your weekends off!), and you do this 50 weeks per year. How long would it take you to read your own DNA sequence?

The answer is something in the order of 84 years!! More than a lifetime for many of us…

So when I tell you that on February 15, 2001, the same prestigious scientific journal Nature (the one that published the original Watson and Crick paper in 1953, published a paper from an international consortium of scientists that reported, for the first time in history, the entire DNA sequence of a human genome, I think it's more than fair to say that this was a truly monumental accomplishment.

In fairness, this was not the full DNA sequence of a particular individual - that would come later - but rather what could be termed to be a “typical" sequence or a "reference" sequence. It was created via a precedent-setting, historic worldwide scientific effort, combining the efforts of many, many researchers and laboratories around the world, and stitching together bits and pieces of human DNA sequence to form this prototypical reference sequence.

While I personally don’t consider this accomplishment to be the absolute holy Grail of molecular biology,  I cannot over stress how pivotal, historic and important this accomplishment was. It lays the very groundwork for an unprecedented understanding of human life, genetic variation, and even human disease. And it will have a profound impact on how we view cancers, and how we deal with cancers.

In a future post, I will show you just how far we've come even since 2001 when this first reference human genome was published, and by doing so, give you a glimpse into a future filled with optimism and excitement, yet one that we may not be quite ready for…