This Page

has been moved to new address

Cancer Research 101

Sorry for inconvenience...

Redirection provided by Blogger to WordPress Migration Service
Cancer Research 101: 3/4/12 - 3/11/12

Wednesday, March 7, 2012

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

In the last post [World of Genomics Part 2] I tried to give you a flavor of just how far and how fast the science of genomics has progressed in the last decade. We are truly getting to a point where an individual human DNA sequence will be available for $1000 or less.

There is also increasing prospect of what is called “direct to consumer" products where you will be able to order your genome from a company on the Internet without any intervention by your physician. In fact, I suspect this is already happening in limited ways but will pick up steam very soon as the affordability continues to drop.

As much as the technology will afford us an unprecedented technological advance into our understanding of human diseases such as cancer, it is my belief that this era of “cheap” genomes is also ushering in some unprecedented questions of ethics and law that we are not yet facing head on, and need to start debating and discussing as a society ASAP.

Top of the list perhaps are issues of privacy and confidentiality. 

Where is your genome sequence going to be stored? I could imagine an app on your smart phone in the not so distant future! Do we really want to have our genomes floating around in cyberspace? Do we trust some central database (e.g. a government database) to house this information? I will wager that many of you already feel uncomfortable about the fact that the CRA in Canada or the IRS in the United States holds so much informational power over you by having your detailed tax records and related files in their databases. I cannot imagine a piece of information more personal or more confidential than my own detailed DNA sequence; will I really trust that it will be kept secure on the Internet or in someone's file cabinet?

The privacy and confidentiality issues lead us then to questions such as insurability. Suppose an individual is carrying seven particular mutations that might, and I stress might, predispose them to a particular disease. And suppose that information is now made available to an insurance company, and as a result life insurance or mortgage insurance or some other form of insurance is denied because the risk is deemed to be unacceptably high? What happens then?

What, in fact, does “predisposition to disease" really mean anyway? In the vast majority of cases this is not a clarion signal that the disease will develop. It merely says that you MIGHT need to take different levels of precaution than your neighbour in order to prevent or avoid that disease from occurring in the first place.

And if your doctor is able to determine from your mutational status that you have a predisposition to some particular disease, what about your “need to know” vs. your “right to know”? In some jurisdictions, such as France, the obligation of a physician to disclose this information is enshrined in law, as I understand it. In the US and in Canada there are no such regulations yet. Who is going to make the decision about when your health care professional should, or must, advise you of your mutational status, especially if it doesn't actually mean anything finite in the immediate sense of the word? If there is nothing you can do, then how important is it for you to know? Is it your right to know?

And even if it is your right to know, is it possible that we will end up creating so much anxiety and stress in individuals who learn of a particular mutational status that we will in effect “stress” them into the very diseases we are trying to prevent? The notion of creating so many self-fulfilling prophecies is very real in my view .

And then there are issues of economics and policy. The better able we are to define specific sets of mutations and to tailor treatments to those sets of mutations, it could be imagined that we will need more and more targeted drugs. While targeting and specificity are a good thing, most of these drugs are not cheap! One could rightly ask why would we be developing more and more expensive drugs when we can't even afford the ones that we have now.... 

And how will decisions be made about who has access to which drugs? We already see significant differences in Canada from province to province about cancer drugs that are paid for by the public health system in one province but are not available to patients in a neighboring province.

And from a policy maker's point of view, it could be fair to ask "how much is X months of someone's life worth?" If an expensive drug can prolong a cancer patient's life by six months, for example, who makes the decision about "at what cost"? I can easily see that if the patient in question is your mother, or your son, or your sister etc. then you might justifiably argue that ANY cost is worth it - you are prolonging the life of a loved one.

But if you are the Minister of Health and you have to look at this in terms of benefit vs. cost to society at large, you no doubt will need to look at this more objectively and dispassionately.

The answers to these kinds of questions will come from new kinds of cancer research, but it won’t be in the usual laboratory settings. Instead, we need to accelerate our efforts into research in:
  •  health economics of cancer
    • how will money be best spent?
  • health services research
    • how will services be best organized?)
  • health policy research
    • how will information be provided to policy makers for best use?)
  • ethics research
    • how will resources and access to service be maintained in the fairest way for all patients? 
    • how will we protect vital personal and confidential information? 
    • who owns the data? 
    • who defines a patient's “need to know” vs. "right to know”?)  

The point is, that we are at a stage in the development of very powerful technologies that are going to create opportunities but also some very fundamental ethical issues that I do not believe we are ready to deal with at the societal level.

There have been a few other technological “tsunamis” that have broken on society and changed our world irrevocably in the past. One of these was of course the advent of nuclear technology and all of the good and ill that brought with it. 

Another was the development of recombinant DNA technologies that brought with it the modern era of molecular biology, of which these genome science opportunities are the latest wave. I am not old enough to know what sort of public consultations, if any, accompanied our ushering in of the nuclear era, but I do very much remember some of the public debates that happened in the early 70’s around the advent of the new molecular biology.

Without in any way suggesting that the outcomes of those debates and consultations were appropriate or not, at least an attempt was made to engage the public and to inform people of what was coming, and to attempt to assess it from both a benefit and risk perspective. I don't see the same level of engagement happening now with the new genome technologies and I think it is overdue. 

These issues are too important and the ramifications are too far-reaching to not have these debates and discussions right now…

Labels: , , , , , , , , , , ,

Tuesday, March 6, 2012

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...

Labels: , , ,