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The Genome War
2007JUN25 14:19:01 by VIOLETTA PRIESTLEY

There are two posters of the human genome on the wall of the Biology Office at the University of Southern Maine. One is titled “The Human Genome”. The other is called “Annotation of the Celera Human Genome Assembly”. In the past I have avoided looking at these posters. They intimidated me. I could not make sense of them, and I assumed this was due to my modest understanding of genomic science. However, after reading The Genome War by James Shreeve, I know the reason for the two posters. They are not made necessary by science. They are made necessary by man and especially by competition between men. This is easy to understand so I now look at both posters willingly.

Sequencing the human genome began as a publicly funded project. Its goal was to create an open access data base of ordered nucleotides by chromosome.

The Human Genome Project officially began on October 1, 1990, with Watson as its director. Congress proffered an increasing flow of money that would eventually bring the program an estimated $200 million annually for the next fifteen years. ...by 1998 even the scientists who had originally opposed the Human Genome Project as ill conceived and not cost-effective were utterly convinced that its fruit would be well worth the $3 billion investment of taxpayer money.

Not surprisingly it is possible to build a business model around data access ...especially if the data are scientifically strategic, unique, of quality or timely, and this is what the emerging biotechnology industry did. By the late nineties the academicians of The Human Genome Project had a serious competitor in the private start-up company Celera Genomics, and a goal of Celera Genomics was to make money by sequencing the human genome more accurately and faster than the Human Genome Project.

The major pharmaceutical companies were betting that it would lead to new drugs worth a whole lot more (than $3 billion - ed).

The Human Genome Project was slated to deliver by 2005. Celera Genomics claimed it could be done by 2001. A race ensued. During the race, Francis Collins led the Human Genome Project and J. Craig Venter led Celera Genomics. The goals of the race became not only to sequence the human genome but also to undermine the integrity of one’s opponent. It was a nasty competition.

Francis Collins, Wikipedia
Francis Collins had never seen Craig Venter in a modest mood. But what Venter said next left him at a loss for words. “So while we do the human genome,” Venter continued, in an offhand, casual sort of way, “you can do mouse.”
Over three years the animosity between these two strong, determined, gifted men grew.
J. Craig Venter, Wikipedia
Venter and Collins could barely look at each other. Directing his words to the other NIH representatives, Venter launched into a history of the perceived sins committed against Celera by the government program, starting with the Mad Magazine comment two years before (In USA Today Collins said Celera’s version of the human genome would be the Mad Magazine version -ed.), moving to the shutdown of the Celera-DOE deal, the leaked letter (misstating Celera’s position on intellectual property -ed.) and the devastation wrought by the Clinton-Blair statement. Collins sat rigid and dour.

Personal histrionics aside, the execution of the two projects, public and private, had much in common and differed in only one fundamental way. Both projects used the same machinery provided by the same company to accomplish the first major process - ripping the DNA apart to identify each nucleotide. The projects diverged at the second major process - fitting the nucleotide fragments back together in correct order. This required a system of software. Celera Genomics used a software design called the “whole-genome shotgun technique”, and it made all the difference. In 2001 when the two sides called a tie, 95% of the Celera Genomics genome fit together making it more complete and useable than the draft data from the Human Genome Project.

This explains the two posters on the wall in the Biology Office. They symbolize a race. Since that time the two data sets have merged and you can access the amazing results here.

References

Shreeve, J., (2004). The Genome War. New York, NY: Alfred A. Knopf.

The End

Nobel Prize Winning
2007MAY22 09:32:00 by VIOLETTA PRIESTLEY

The semester ended, I have taken to meandering my way through each day. Schedules banished, I relax from one thing to another, productive but not pressed. Delight creeps in.

So it was with my recent reading of the short (232 small pages) fiction work by James D. Watson titled The Double Helix. This work was published in 1968 so its science is well-worn. But this is not a tale about the science. It is a tale about the winning. It features three strong competitors and a race to the finish, and amidst the mounting tension we glimpse the seeds of success and especially failure.

James Dewey Watson, Wikipedia

The first competitors we meet are the team of James Watson and Francis Crick. Because he is the author and not self-reflective, we are told few personal details about James Watson. However, we learn that Francis Crick has a theoretical bent and a facility for insight, especially when applied to pattern recognition. He also is impatient, even manic, and where discovery is involved, a risk taker:

...Francis felt...that you did not move cautiously when you were holding dynamite like DNA.

Together Watson and Crick make a good team. They enjoy each others company and share their lives inside and outside the laboratory. Throughout they approve, support and depend upon one another.

Affable relations are not possible between the second set of competitors, the "team" of Maurice Wilkins and Rosalind Franklin. Maurice is an expert in DNA but not in a pivotal method needed to advance his work, X-ray diffraction. To fill this gap he brings Rosalind Franklin, a trained crystallographer, into the lab. It is not a happy coupling. Together they indulge a power struggle:
Rosalind Elsie Franklin, Wikipedia
Clearly Rosy had to go or be put in her place. The former was obviously preferable because, given her belligerent moods, it would be very difficult for Maurice to maintain a dominant position that would allow him to think unhindered about DNA.
Lastly, we meet Linus Pauling, 1954 Nobel Prize winner for his work in chemical bonding. Pauling has recently discovered the uniquely beautiful α-helix, so he is well positioned to discover the double helix. He has experience, drive and focus. However, he also has an almost burdensome record of success:
Linus Carl Pauling, Wikipedia
There was no one like Linus in all the world. The combination of his prodigious mind and his infectious grin was unbeatable. Several fellow professors, however, watched this performance with mixed feelings. Seeing Linus jumping up and down on the demonstration table and moving his arms like a magician about to pull a rabbit out of his shoe made them feel inadequate. If only he had shown a little humility, it would have been so much easier to take!
In the end, Watson and Crick discover the double helix. Interestingly, their competitors concede willingly, pointing to the fairness of the race, the grace of the participants and the worthiness of the winners...also marking the importance of good relations and good will in matters of winning.

References

Watson, J.D., (1968). The Double Helix. New York, NY: Antheneum.

The End

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