LUNCHTIME WITH Mr BIG
R Mann
Auckland Jan 2001
The big lecture theatre in the medical school was almost full
by noon on Jan 26 when J Craig Venter, president of Celera Genomics,
was to speak at 12.30. A communist was giving out leaflets in the
main foyer quoting Prof Steve Jones on the failure of gene therapy
and saying the human genome project is mostly a waste of money.
Extra 'security' was on.
I found myself sitting with a yacht broker who was here in NZ
to help Venter buy a luxury yacht. This engaging man was fulsome in
praise of the NZ luxury yacht industry. I felt ashamed that we
aren't doing anything more useful with those skills, but I kept my
peace. Instead I advised him "sign him up quick on the way to the
airport before the bubble bursts".
The yacht dealer arrived with a charming woman, who had
attended one of Venter's big announcements of "completion" and now
gave the general impression of a devotee. She spoke with warm vague
evangelical enthusiasm of the many medical benefits to come from DNA
sequencing of humans and animals. I asked her *what* benefits she
expected; as she recited again the vaguest fantasies, with no attempt
to identify any reality, I felt I was observing a devotee - she
held this faith with a blatant disregard for fact & reason that
reminded me of totalitarian sects.
The reserved seats at the front were occupied at 12.25 by a
phalanx of personages including the chief executive (vice-chancellor)
Dr Hood who is also a director of numerous corporations. The
chairman, Dr Peter Gluckman dean of the med school, then introduced
Venter with fawning adulation - "one of the most distinguished
scientists and entrepreneurs".
J Craig began by simply saying he had followed for 5-6y
'basic science ideas'. Early in his career he had sequenced an
adrenalin-recognition protein, which took a decade by the then best
methods. (He also passed what was to me a welcome quip that
biochemistry had at that time been fixated on a fad attributing
almost everything to cyclic-AMP. Now, if only he could see the
current fad, rather than exacerbating it . . . )
Venter operates, in an area about the size of a football
field, 300 x U$300,000 sequencing machines run by 9 staff. A further
50 staff are employed in making each day 300,000 plasmid clones which
are then sequenced. These 'shotgun' sequences are far bigger than
used in other approaches, necessitating huge computing to assemble
them into the whole from one chromosome or one microbe, etc.
Venter's main impact on sequencing has been by computing. He claimed
he's doing one or two terraflops in 1500 "high-end" CPUs, with more
than 100 terabytes of storage, collaborating with the hitherto kings
of supercomputing, the modellers of nuclear explosions at Sandia.
Thus, he said, the biggest computing effort is devoted entirely to
what he is pleased to call "biology".
Some couple dozen genomes have been caricatured into the
4-letter alphabet by this method at Celera and the similar TIGR. The
first was _Haemophilus influenzae_ which took a year or two but today
would take a day or two. The 5-chromosome plant genome of a
mustard-family plant, _Arabidopsis_, 120M base-pairs, about 4% the
size of the human genome, is to be the basis of crop-GM; a sequence
for it was announced Dec 2000.
The number of genes in the human genome has been whittled
back to 26k and falling (mainly by revising the definition of a CpG
island). I guess this may be intended to help relieve the log-jam at
the Patent Offices - but patents were not mentioned.
The human genome has been classified 1.1% exons, 24% introns,
and great grey lengths of non-coding DNA for which the term 'junk'
was not used but which Venter stated to have "more forensic than
biological function".
J Craig's PR site www.celera.com features many claims of
imminent medical product e.g.
>
>A Fatal Flaw in the Hearts of Children
> Scientists identify a gene involved in the sudden cardiac
>deaths of healthy children.
My favourite gleaning in a quick scan of Celera's website was
> Leverage the same infrastructure and workforce that sequenced and
>annotated the Human Genome!
The popularity of these sequencing fads is, just lately,
overwhelming. Venter says he has spent U$250M without making any
sales. Having got Blair & Clinton to hype his arbitrary 'draft'
human DNA sequence, he now says Feb 15 is to be the real completion.
He still calls this future advanced draft "essentially complete";
nobody asked him what that key adjective 'essentially' means.
So far from claiming imminent benefit from any of this DNA
sequencing, he now mocks genetic determinism. The different genomes
contributed by his "number of" volunteers allow us to "tell the males
from the females", but "there will not be a genetic determination of
African-American". He announced, as if it were a great & recent
discovery, that bowel cancer is caused by not only defective genes
but also toxins from food, so that not only genetics but also
environment contribute to the disease. He mentioned biology with
apparent respect, and used the term 'holistic' at least twice. I
wondered whether U of Ak honchos who had been purging biologists in
favour of gene-tamperers felt any twinge at this stage.
"Your stock rose from about $3 to $300, and now it's about
$30. How do you explain that?" asked Dianne Yates MP (without
identifying herself at all). "Ah yes - there's always one in the
audience - a stockholder!" replied Venter. He ascribed the big
rise to the hope of a new future; blamed Clinton for crashing the
stock market; and added a few glib econobabblings which I couldn't
understand let alone recall.
Dr Jorg Kistler, who recently earned a personal chair at
Auckland in electron microscopy, asked how realistic are hopes of
gene therapy. In a similar vein, but humorously, a local votary of
the gene-tampering fad, director of biological sciences A R Bellamy,
excelled himself by asking "what do you advise Dianne Yates to do
about her insurance?". The responses were a series of ill-connected
sound-bites reminiscent of the style of our babbling minigorilla now
'heading' the WTO. Venter downplayed the utility of DNA sequencing
for predicting medical risks. A dozen 'disease genes' have been
announced in the past couple months, he said with implied
disapproval. Mutations in the CF gene cause not only cystic fibrosis
but also 9 other diseases; and more importantly, many changes in that
gene cause no ailment at all, he said. Indeed, "variation does not
come at a deterministic level." We can crudely find predilections
for some ailments, but at best estimate only a probability (said in
such a way as to imply this is not enough for insurance companies).
Some of the predictions are unjustified, so laws are being
misconceived on no better than novel prejudices. If we can't tell a
black from a white by their DNA, the insurance companies are likely
to be disappointed by attempts to foretell illnesses. Comparing
individuals by 'vertical SNP analyses' i.e. single-base mutations has
yield no clear conclusions. For risk readings, we'll have to move on
to 'proteomics', he averred.
For this *really* up-to-the minute commerce, sequencing
proteins, he showed a large box with few readouts, a prototype
sequencer. A laser source feeds a time-of-flight mass spectrometer
to sequence proteins even in mixtures. (This claim is incompatible
with his desire to ignore post-translation mods such as
glycosylation, which certainly would be identified in such a
sequencer - if it works at all.)
The ultimate response to the misguided hopes for medical
predictions from DNA sequencing would be to sequence everybody's
genome; so many differences would be discovered that nobody would be
able to get life insurance cover. I thought this was a serious
contender for the title 'ultimate cynical nerdism'; although Venter
insists Celera is a non-profit organisation, he made some smug vague
complaint about high personal income taxes, and would not appear to
be the sort of person who much needs life insurance.
In his regular glib flippant way, Venter seemed to affirm
atheism. A dating system for evolution over hundreds of millions of
years is based on sets of at least 3 gene repeats, he seemed to
suggest. These data imply, he expounded, that it has taken 10^8 -
10^9y to create the human, rather than "somebody saying one day,
'let's do it' ". In this flippancy J Celera was impliedly denying
not only the 6-day creation but also the Creator; but he said nothing
definite on these matters, so I hold out some hope that I
misunderstood his vague theological quips.
Gluckman was good enough to let me ask an early question:
"The leader of the Arabidopsis genome project which
you mentioned - a graduate of this university [my first grad
student, but I didn't mention that] - passed thru here a couple
years ago and gave a talk. He said 'odd' bases do not occur in the
copies which are sequenced. But we have known for 4 decades that
'odd' bases exist in DNA. Apart from the role of methylC in CpG
islands silencing transgenes & so forth, he said 'we don't have a
handle on them'. So his sequences are not accurate but are
simplified on the slogan 'The Big Four Rule OK'. What is the role of
odd bases in your work?"
Although so important as to show pictures of
himself speaking at the podium with the crest 'The President of the
United States', with Clinton looking up at him, Venter resorted to a
personal wisecrack, quipping to Gluckman "is this your local version
of a minority?". This childish behaviour may be a sign that he is
not as confident as he seems in his ideas such as the slogan 'The Big
Four Rule OK'.
He proceeded to admit his output is indeed only in the
4-letter alphabet T, A, G & C. This simplification he claimed to be
minor, an attitude he mainly justified by pointing to the similar or
worse backwardness in identifying 'odd' groups tacked on to some
proteins. "It's the same with proteomics - the glycosyl residues
and so on can be pinned down later. It'll take a century to get all
these embellishments."
Carrying on from this reply remarkable in part at least for
its candour, he uttered what I thought was one of his more quotable
conclusions: "There's no single hi-thruput method to solve all
biological problems."
The final questioner, quite possibly a devotee like my
neighbour, cooed in Noo Eege style "how will folks be led to accept
instead of fearing?". Venter replied "it *is* fearsome - given
genetic determinism", and warned that spurious detection of a fault
in the CF gene in a foetal sample might provoke an unwarranted
abortion.
Gluckman asked for confirmation that the way to get ahead
with the "Knowledge Economy" is for universities to transfer
technology to biotech corporations. Venter responded with some
econobabble which I took to be affirmation of this strategy. What is
actually being done is that Bellamy is purging biologists to make
room for gene-tamperers who are expected to bring in money from
venture capitalists; this gives a somewhat different impression from
Gluckman's sketch of the process.
Gluckman appeared to be proximally concerned to use the
occasion to persuade Hood & others that the University of Auckland
should do as Venter said Australian universities had wisely done -
pay to get connected to his database. How easy this might be for
students to use Venter perhaps hinted at in his advocating that
advanced computer skills should be central in the med school.
Gluckman said a formal announcement should be out soon after
negotiations on Feb 26.
What good might come of all this was left completely
unclear, to me at least. But the loud lengthy applause as the
session ended left no doubt that the generally young audience agreed
with Gluckman: J Craig is one of the great scientists and great
entrepreneurs.
Dianne Yates MP departed in the company of the devotee I had
met earlier. I accosted Yates with a brief attempt to disillusion
her - should that be a step still open. She identified her problem
as inability to assess "the discrepancies" - I took her to mean the
differences between Celera's sequences and those of the public team
as he had called it. I replied that almost everyone is similarly
handicapped. She moved on across the carpark, listening to the
devotee.
As J. Craig swept celerically out the med school front door I
cheerfully called out exhorting him to keep after those 'odd' bases.
He smiled - but then he had done that most of the time. I would
be very surprised if he had learned anything from this event, so
great is his cockiness.
And yet the fact remains that he had not even claimed, let
alone proven, any benefit from his sequencing.
Truly, we live in the age of bullshit. The biggest con,
degrading science to junk and technology to disreputable dangerous
furphies, is gene-tampering.
R
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