A. AN OVERVIEW OF THE MODERN GENOME WAR: THE RACE BETWEEN THE HUMAN GENOME PROJECT AND CRAIG VENTER’S CELERA CORPORATION
“In hindsight, it is
hard to imagine there would have been a race to sequence the human
genome without Craig Venter.”225 While it is
impossible and indeed unnecessary to recount in detail the race
between Craig Venter’s private Celera Corporation and the public
Human Genome Project headed by Dr. Francis Collins, some brief
overview of that race is necessary, if nothing else than to
highlight the magnitude of the task, and the technologies and
techniques that eventually accomplished it, for these in turn will
provide a basis to unlock and possibly decode some astonishing
assertions in some very ancient cuneiform tablets.
The genome is often
described as “the book of life,” and indeed, the analogy of a book
is quite apropos to describe the way the DNA helix works.
“Imagine,” says author Matt Ridley, “that the genome is a
book.”
There are twenty-three chapters, called CHROMOSOMES.
Each chapter contains several thousand stories, called GENES.
Each story is made up of paragraphs, called EXONS, which are inter-
rupted by advertisements, called INTRONS.
Each paragraph is made up of words, called CODONS.
Each word is written in letters, called BASES.There are one billion words in the book, which makes it longer than 1,000 volumes the size of this one, or as long as 800 Bibles. If I read the genome out to you at the rate of one word per second for eight hours a day, it would take me a century. If I wrote out the human genome, one letter per millimeter, my text would be as long as the River Danube. This is a gigantic document, an immense book, a recipe of extravagant length, and it all fits inside the mircroscopic nucleus of a tiny cell that fits easily upon the head of a pin.226
To appreciate the
magnitude of mapping the entire human genome, we need to understand
the “bases” that comprise the “words” or codons. These words are
composed of never more, and never less, than three bases or
“letters,” A, C, G and T, which stand for the proteins adenine,
cutosine, guanine, and thymine. The basic “grammar” of these
letters is that A pairs only with T, and G only with C.227
Thus, “to make a
complementary strand therefore brings back the original text. So
the sequence ACGT becomes TGCA in the copy, which transcribes back
to ACGT in the copy of the copy. This enables DNA to replicate
indefinitely, yet still contain the same information.”228 But in the midst
of all this microscopic complexity, there lurks a mystery, and it
may be a significant one for our purposes. As James Shreeve puts
it, “There are a lot of extra letters in the genome, sloppily
referred to as ‘junk DNA,’ which do not spell out protein recipes
but may serve some other purpose, perhaps vital, perhaps
not.”229 In other words, a
significant portion of the human genome contains genes for which
biologists and geneticists cannot divine any function whatsoever.
Indeed, what was so unusual about the human genome as distinguished
from any other species was the sheer amount of this “junk DNA,” for the human genome,
consisting of over a billion such “letters,” was mostly comprised
of this “so-called junk, possibly without any biological purpose at
all.”230
But as James Shreeve
observes,
“Junk” is a misnomer: although protein-coding genes account for less than 3 percent of the DNA in the human genome, inferring that the rest is worthless is like saying there is no value in the deserts of the Middle East because they are composed mostly of sand and only a little bit of oil. The fact is, we don’t know what purposes lie hidden in that alleged junk. We do know, however, that some of it performs the vital function of regulating when a gene is turned on or off. Without those switches, there would be no difference between a liver cell, a brain cell, or a cell in your big toe, and we would all be a dysfunctional chaos of overexpressed [sic] protein.231
In other words, the
so-called “junk DNA” functioned as a kind of “computer algorithm”
telling the rest of the code when to execute certain functions in
the program, and when not to. But that still left the all-important
questions, where did it come from? Why
is there so much of it in the human
genome by comparison to other species?
But “junk DNA” played
an important role in the “genome war,” for it was precisely because
of these “regulatory regions” that James Watson, codiscoverer of
the double helix with Francis Crick, decided to go after the entire
sequence of the human genome.232 The enormity of
the task, however, meant that the project would take — or so the
thinking ran at that time — a great deal of time and effort, years,
if not even almost a decade.
Enter Dr. Craig
Venter, and his private Celera Corporation, founded for the express
purpose of mapping the entire human genome. In May of 1998, Venter
announced that with the financial backing of the Perkins-Elmer
Corporation, he was founding Celera (from the Latin word for
“speed”), a “private company to unravel the human genetic code.”
Venter announced that he planned to complete the entire project in
the unheard-of time of a mere three years!233 It was a
bold, perhaps even brazen announcement, for “nothing like the
particular scheme he was proposing had been attempted before. If it
were broken down into its various technical components, most of
them had never even been attempted before, either.”234 In essence, if one
wishes to compare the initial strategies of the public Human Genome
Project and Venter’s private Celera venture, the aim of the former
was quality, whereas Venter’s aim was speed. Thus, the Human Genome
Project’s early strategy was to map each individual gene first, and
then assemble the pieces — like a gigantic jigsaw puzzle — into
their proper sequence later.235 Venter’s goal was
much more ambitious, for not only did he wish to map every single
human trait,236 but, by using
massive amounts of DNA-sequencing machines in a Manhattan
Project-sized assembly line that would blast the DNA into millions
of tiny segments, reassemble and sequence the entire “book” of
human DNA using supercomputers and very complex computer algorithms
to reassemble the pieces of the jigsaw in their proper order. It
was this “shotgun” approach of Venter that called forth rounds of
denunciation from scientists within the public project,237 and yet that
galvanized its leader, Dr. Francis Collins, to recentralize what up
until then had been a variety of public laboratories and university
efforts into a more coordinated effort,238 and that also
caused him to re-evaluate the basic strategy the public project was
pursuing. After Venter’s announcement, the public Human Genome
Project adopted a mediate strategy between its initial
“qualitative” approach and Venter’s shotgun approach, determining
that it would go after a “rough draft” of the human genome
sequence.239
However, for the
public project, there was a fly in the ointment, and that fly was
the “Bermuda Accords,” to which all participants in the public
project had subscribed. By mutual consent, all participants in the
public Human Genome Project had agreed that, once individual pieces
of data — the bits of the “jigsaw map” — had been completed by the
project, these data would be made publicly accessible to everyone.
This meant, of course, that Venter’s “Celera could grab their data
off the web like everyone else.” The faster the public project
went, “the faster their enemy could go.”240 This placed the
Human Genome Project in a Catch-22.241
By adopting a kind of
“Manhattan Project” approach using massive numbers of DNA
sequencers and supercomputers with complex algorithms to assemble
the pieces, Venter had in fact, reversed the initial roles that the
public and private projects had assumed. After a few months into
the race, Venter’s Celera was in fact pursuing a detailed quality
map of the entire genome, while the public project was aiming for a
“rough draft.”242
In the end, the race
was so close that the Clinton Administration stepped in, and
brokered what can only be described as a “truce” between Collins’
public Human Genome Project and Venter’s private Celera corporation
in a declared “tie.”243