Tuesday, September 21, 2010

Review: The $1000 Genome

Kevin Davies' "The $1000 Genome" deserves to be widely read. Readers of this space will not be surprised that there are a few changes I might have imposed had I been its editor, but on the whole it presents a careful and I think entertaining view of the past and possible future of personal genomics.

The book is intended for a far wider audience than geeky genomics bloggers, so the emphasis is not on the science. Rather, it is on some of the key movers-and-shakers in the field and some of the companies which have been dominating this space, ranging from the first personal genetic mapping companies (23 and Me, Navigenics, Pathway Genomics and deCodeMe) to the instrument makers (such as Solexa/Illumina, Helicos, Pacific Biosciences, ABI and Oxford Nanopore) to those working on various aspects of human genome sequencing services (such as Knome and Complete Genomics. Various ups and downs of these companies -- and the debates they have engendered -- are covered as well as the possible impacts on society. Along the way, we see a few glimpses of Davies exploring his own genome and some of the biological history which he seeks to enlighten through these expeditions.

It is not a trivial task to try to explain this field to an educated lay public, but I think in general Davies does a good job. The overviews of the technologies are limited but give the gist of things. Anyone writing in this space is faced with the dilemma of trying to explain too much and losing the main thread or failing to explain and preventing the reader from finding it. Mostly I think he has succeeded in threading this needle, perhaps because only rarely did I feel he had missed. One example I did note was in explaining PacBio's technology; hardly anyone in science will know what a zeptoliter is, let alone someone outside of it. On the other hand, what analogy or refactoring of that term could remove it from the edges of science fiction? Not an easy challenge!

For better or worse, once I've decided I generally like a book like this my next thoughts are what could be removed and what could be added. I really could find little to remove. But, there are a few things I wish were either expanded or had made it in altogether.

It would be dreary to enumerate every company which has ever thrown its hat in the DNA sequencing ring. It is valuable that Davies covers a few of the abject failures, such as Manteia (which did yield some key technology to Illumina when sold for assets) and US Genomics. There is scant coverage, other than by mention, of most of the companies which have but nascent attempts to enter the arena. However, the one story I really did miss was anything about the Polonator. It's not that I really think this system will conquer the others (though perhaps I hope it will hold its own), it just represents a very different tack in corporate strategy that would have been interesting to contrast with the other players.

Davies has been in the thick of the field as editor of Bio IT World, so this is no stitching together of secondary sources. I also appreciated that he includes both the ups and the downs for these companies, emphasizing that this has not been easy for any of them. But, that added to my surprise at several incidents which were left out (believe me, many were left in I had never heard before). Davies describes how Helicos delivered an instrument to the CRO Expression Analysis, but not that it was very publicly returned for failing to perform to spec. Nor is Helicos' failed attempt to sell themselves mentioned. An interesting anecdote on Complete Genomics is how a wildfire nearly disrupted one of their first human genome runs; left out is the near-death experience of that company when it was forced to either lay off or defer salaries for nearly all of its staff. The section on Complete's founder Rade Drmanac mentioned Hyseq, but not the company (or was it two) which he ran between Hyseq and Complete to try to commercialize sequencing-by-hybridization. This would have added to this portrait of determination -- and the travails of the corporate arena. I was also surprised that the short profile of Sydney Brenner as a personal genomics skeptic didn't include the fact he invented the technology behind Lynx, which was another early attempt in non-electrophoretic sequencing. Some would see that as irony.

Another area I would like to have seen expanded was the exploration of groups such as Patients Like Me, which are windows on how much people are willing to chance disclosing sensitive medical information. One section explores the fact that several prominent persons interested in this field became so when their children were diagnosed with rare recessive disorders, leading them to ponder whether they would have made the same marriage had they known in advance of this danger. I was surprised that little of the existing experience in this area was explored; I believe the Ashkenazi population has dealt with this in screening for Tay-Sachs and other horrific disorders which are prevalent there.

The book is stunningly up-to-date for something published the beginning of September; some incidents as late as June are reported. Despite this, I found little evidence of haste. I'm still trying to figure out what a "nature capitalist" is, but that's the only case I spotted of a likely mis-wording.

Davies briefly explores possible uses of these sequencing technologies beyond our germline sequences, but only very briefly. Personally, I think that cancer genomics will have a more immediate and perhaps greater overall impact on human medicine, and wish it had gotten a bit more in depth treatment.

Davies in a expatriot Brit, living not very far from me. The sections on the possible impact of widespread genome sequencing on medicine are written almost entirely from a U.S. perspective, with our hybrid public-private healthcare system. I suspect European readers would hunger for more discussion of how personal genomics might be handled within their socialized medical systems and different histories of handling the ethical issues (Germany, I believe, has pretty much banned personal genomics services). On this side of the pond, he does a nice job of showing how different state agencies have charged into the breach left, until recently, by the FDA.

Okay, too many quibbles. Well, maybe one last one -- it would have been nice to see more on some of the academic bioinformaticians who have created such wonderful and amazing open-source tools as Bowtie and BWA.

As I mentioned above, Davies injects a good amount of himself into all this. I've encountered books (indeed, on recently on moon walkers), in which this becomes a tedious over-exposure to the author's ego. This is not such a book. The personal bits either link pieces of the story or make them more approachable. We find out that he has already attained a greater age than his father did (due to testicular cancer, one of the few cancers in which overwhelming progress has been made), leading to questions he hopes his genome can answer. Hence, his trying out of pretty much all of the array-based personal genetic services. But, he does not address one question that the book raised in my mind: will the royalties from this project fund a complete Davies genome?


nexgensequencing said...

Props for mentioning Rade Drmanac in your post. His determination and perseverance is truly inspiring.

Unknown said...

I like the review of Genome, great keep up the good work.

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