Genome Project: C'est magnifique, mais ce n'est pas ...

The publicly funded International Human Genome Project (HGP) consortium using the "hierarchical shotgun approach," and Dr. Craig Venter's Celera Corporation using the "whole-genome shotgun approach" (WGS) achieved the nearly complete joining of all the sequence fragments of the human genome into one. The tentative identification of some 40,000 genes was announced in the New York Times of 11th February 2001:

"In principle," the consortium's biologists concluded in their report, "the string of genetic bits holds long-sought secrets of human development, physiology and medicine. In practice, our ability to transform such knowledge into understanding remains woefully inadequate."

    Dr. Venter said simply that the effort to sequence and interpret the human genome had been "mentally exhausting, in part because we are not mentally equipped to absorb all this." ... "We feel like midgets describing the universe and we can't comprehend it all," he added.

It is for the reader to ponder Venter's mental exhaustion. His organizational and marketing skill are hardly to be doubted. But if those seeking to understand the genome through bioinformatic and evolutionary analysis had had just one fraction of a percent of the funds available to the Consortium and Celera, they might have already achieved the transformation of mere data (let us not dignify it as "knowledge") into understanding? Sydney Brenner pointed out:

"Sequencing large genomes has nothing to do with intellectual endeavour. The creative work was done earlier by Fred Sanger and by others who improved the technology. The rest is about two things: money and management. As the various projects developed, their demand for money increased. The nematode sequencing project quickly consumed most of the funds available for genome work at a time when money was short."

(2002; Nature 416, 794-5)

Along similar lines Margaret Somerville commented:

"Conditions that are attached to government funding can affect the purposes and values upheld, especially when those conditions require academic-industrial partnerships for research to be eligible for funding, as in the case of the Canadian government's C $300 ... million investment in a series of genomics research centres (Genome Canada). Structuring funding in this way leaves out the funding of research that will not result in marketable products, and excludes those researchers who undertake it."

(2002; Nature Reviews 1, 316-320)

 

    And let us not pretend that we actually needed the sequence of the entire human genome in order to complete our understanding. Just as one does not need access to an entire dictionary if one wants to understand how a dictionary works, so one does not need access to an entire genome to find out how genomes work. And for most of us an entire dictionary is redundant. Our needs are highly selective. Few of us want to look up the word "and."  Many might want to look up the word "esoteric." 

      Similarly, techniques developed in the early 1980s (e.g. Forsdyke 1985) allow us to selectively access genes likely to be of importance (Click Here). We now have an excess of human genomic sequences, not because they might reveal "long-sought secrets of human development, physiology and medicine," but because the project is highly marketable, and because of patent possibilities. Those who really want to understand the human genome know that it is far more important to sequence comparable segments of non-human genomes. For more on this please go to my bioinformatic web-page (Click Here), and see below.

                                                               Donald Forsdyke

 

Did Celera invent the internet?

The Lancet 357, 1203 (#9263; 14th April 2001)

Sir--The overtaking of publicly funded research teams by Celera Genomics in its completion of the sequencing of the human genome, to which you refer in your Jan 13 editorial,1 smacks  somewhat of the Sputnik episode.

     The United States of Soviet Russia scaled up the payload of their rocket and put a man into space before the USA, but did not make parallel progress in the other technologies required to capitalise on this advance. Craig Venter, the chief executive officer of Celera, has stated that understanding the genome may help resolve previously unanswerable questions.2 But Celera has merely made available the full text of the genome a little sooner than we might otherwise have had it. Those of us working to understand the genome3 no more need the full text of the genome than you would need the full text of a dictionary if you were trying to understand how a dictionary works.

     You state that, courtesy of Celera, the entire sequence will be available free of charge;1 a Celera spokesman has declared that academic users will have to pay US$7000 per year.4 That the beneficence, and perhaps the integrity, of Celera might not be relied on, was suggested by a full-page colour advertisement in Canada's leading newspaper. This advertisement, in large capital letters, declared "The skeptics were right when they said Craig Venter would never crack the human genetic code on schedule. He was two years early".

    We smiled when Al Gore told us he had invented the Internet, and he quickly apologised and expressed remorse. Yet, here is the chief executive officer of Celera claiming to have cracked the genetic code--a feat achieved in the 1960s, and for which Nobel prizes were awarded in 1968. My protest in a letter to the newspaper on Jan 15,5 which was forwarded to Venter's corporate sponsors, was answered by repeats of the advertisement on Jan 16, 22, and 25.

Donald R Forsdyke

1 Editorial. Human genome draws in journals. Lancet 2001; 357: 81.

2 Broder S, Venter JC. Whole genomes: the foundation of new biology and medicine.  Curr Opin Biotech 2000; 11: 581-85. [PubMed]

3 Forsdyke DR, Mortimer JR. Chargaff's legacy.  Gene 2000; 261: 127-37. [PubMed]

4 Marshall E. NIH considers paying to use private database.Marshall Nirenberg (born 1927) in about 1968.  Science 2001; 291: 223-24. [PubMed]

5 Forsdyke DR. Code already cracked. Toronto: Globe & Mail, 2001; Jan 15.

For more on Marshall Nirenberg, who was one of those who received the Nobel Prize in 1968 for cracking the genetic code (Click Here)
Let the Cobbler Stick to his Last   

The human sequence was deposited in various electronic databases. However, the sequencers, having delivered up the human genome, had to report the fact in the scientific literature. Their task was to describe any novel aspects of the methodology, compare the two sequence approaches, and outline the general features of the genome. That was all. To his credit Venter expressed some diffidence (see above). However, the temptation to go beyond their brief was too great. The speculations of the genome amateurs were soundly quashed by the great "genomographer" of our times, Giorgio Bernardi, in a two part article in Gene (2001; 276, 3-13) euphemistically entitled "misunderstandings." (not reproduced here)

 

Did Celera independently sequence the human genome?
To this question the answer seems to be negative. In March 2002 (Proc. Natl. Acad. Sci. USA 99, 3712-16) some members of the publicly funded consortium who had used the hierarchical shotgun approach pointed out that:

"In principle, the availability of two papers on the human genome has much potential scientific benefit. In addition to the comparison of two independently derived genome sequences, it should allow methodological analysis of the sequencing strategies used for insights concerning the design of future genome-sequencing efforts."

The authors concluded that the Celera approach:

"Primarily depended on the HGP's sequence-tagged site maps, BAC maps, and clone-based sequences. Our analysis indicates that the Celera paper provides neither a meaningful test of the WGS approach nor an independent sequence of the human genome."

The Celera group considered that "this conclusion is based on incorrect assumptions and flawed reasoning." (2002; PNAS 99, 4145-46.

 

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This page was last edited on 19 September 2010 by Donald Forsdyke