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

In an earlier post [World of Genomics, Part 1], I began a discussion of the powerful new world of genomics, and how this kind of technology has the potential to turn cancer research on its head. The publication in February, 2001 of a complete sequence of a full human genome was indeed a watershed event. But as I indicated, this was what might be termed a "reference sequence" in that it was not the full sequence of an individual person, but rather a compilation of sequences from around the world that were pieced together to indicate what a "typical" human genome would look like.

In 2007 another major leap forward occurred with the publication of the full genome sequence of an actual living individual human being. The individual who contributed his DNA for this purpose was a familiar name to those who were following the world of genomics: Dr. Craig Venter.  

Craig Venter's Chromosomes

Dr. Venter has been one of the pioneers in this field, and was one of the principal architects behind the sequencing of the first human genome. Since I don't know Dr. Venter personally, I cannot comment on whether the contribution of his DNA to science was an act of supreme selflessness, or one tinged with egotism, or both, but it did help to pave the way for another major chapter in the unfolding world of human genomics.

 

By sequencing Dr. Venter's genome we learned many, many important things. First of all, we learned that he has 23,224 genes to be precise!

Far more importantly for our basic understanding of human genomes was the fact that almost half of his genes had variations or mutations of some sort. The genetic diversity that was shown was several-fold higher than anyone would have imagined prior to seeing the actual sequences.

Indeed, the day after Dr. Venter's sequence was published, Carolyn Abraham wrote in the Globe and Mail newspaper (September 3, 2007) that 

"the full human DNA sequence of one healthy middle-aged man is a boggling array of genetic quirks, burps and hiccups".

She then quipped, perhaps whimsically, that "there are 7 billion more humans to go".

I can't say whether or not her tongue was planted firmly in her cheek when she wrote that last comment, but I can tell you that it may have been more prophetic than she knew at the time. Consider that the original human genome program that culminated in the 2001 publication of the reference sequence was a truly international effort that probably took over 10 years to accomplish at an estimated cost of perhaps as much as 1-3 $Billion.

Contrast that with the fact that the determination of the Venter genome took far less time and far less money, perhaps in the order of $10 million. Of course, that is still a huge amount of money but compared to the original project, a significant improvement.

Where can we expect the future costs to be?

Genome scientists have been 100% correct in their assertion that the costs will continue to go down dramatically. Will they ever get to a point where we can see genome sequencing on a much more widespread basis? One look at the graph below suggests that this indeed will be the case, and probably very soon! 

The graph is courtesy of the National Human Genome Research Institute in the United States, and it shows how the cost per genome has been steadily going down over the last number of years. You will see a line on the graph called "Moore's Law". You may be familiar with Moore's Law from the world of computers, where the principal is that the number of transistors per square inch on integrated circuits had doubled every year since the integrated circuit was invented. In other words, computing power approximately doubles every two years.

On this graph, you see an inverse variation of that general concept, because in this case the cost of determining a genome is going down by approximately half every two years. Notice however, that right around the time of the determination of Craig Venter's genome there is a huge downward shift in the curve and the cost per genome has been plummeting ever since (note the log scale - this is an exponential decline!). This is due in the main to new technologies for automated sequencing that have truly revolutionized the field.

To emphasize the point, a company called Life Technologies based in Carlsbad California announced in January of this year that they will be debuting, later this year, an automated sequencing machine called the Ion Proton that will be capable of determining the entire sequence of a complete human genome in less than one day for a cost of less than $1000!

While $1000 is not exactly pocket change for most of us, it does put this into the realm of many other medical tests that might be done today. In other words, is not out of the question that your own doctor may one day be ordering a test for you that will see the complete determination of your genome as part of your doctor's diagnostic regimen.

So, what is the significance of all of this, aside from it being an astounding technological achievement? What it promises is an unprecedented understanding of human genetic variation, human disease (including cancer) that will also teach us much about predisposition to disease, including cancer.

This is where the idea of personalized cancer diagnosis and treatment comes truly to the fore. Instead of a "one-size-fits-all" approach with a cocktail or treatment "off-the-shelf", imagine instead the opportunity to treat your cancer taking into account your genetics and your specific underlying mutations. This idea of much better tailoring your treatment to your specific cancer mutations is the basis of "personalized" medicine that you have no doubt been hearing more and more about in the popular press lately.

Does this truly mean that every single person will be treated differently than every other person? Although one might actually think so based on some of the hyperbole that has accompanied this technological breakthrough, this is in fact not a reasonable extrapolation, in my opinion. Instead, what will be done is to better group individuals to ensure that the treatment that they are getting will actually benefit them.

We already know that many cancers that might appear to be the same to a classical pathologist under a microscope are not actually the same to a molecular pathologist once the genetics and specific gene mutations are better understood. And we also know that based on those specific sets of mutations, that some patients will benefit from certain therapies while others will not benefit at all. Rather than treat everyone the same we will increasingly be placing patients into subgroups to make sure that the treatments they are getting are actually going to produce positive outcomes. Perhaps this is why there is a growing trend away from the term "personalized" medicine and a growing adoption of the word "precision “medicine instead.

I think that there is also a huge significance in terms of the way it is going to impact society, and that is not necessarily all positive. More on that in the next post...