Human Genome Project –

Method (2)

‘Some of the bitterest arguments sparked by the quest to unravel the human genome have been over the merits of the different approaches to decoding the DNA. The publicly funded Human Genome Project (HGP) has taken a slower, more methodical approach. The entire DNA blueprint for humans is contained on 24 chromosomes. So they mapped out the major signposts and then chopped up specific sections for investigation. They are now filling in these details. This is rather like making a road map of the UK by starting with the motorways and then driving around, filling in the A roads and B roads. Craig Venter's company Celera started their effort eight years after the HGP, when computers were much faster and more powerful. Their approach simply chops up the whole genome for sequencing and then uses supercomputers to reassemble all the data. This is like making a roadmap of the UK by taking millions of aerial photographs and hoping that you will be able to recognise enough overlaps to put it all back together. Sceptics said that Celera's method could only work for the relatively small genomes of bacteria and viruses. But the sequencing of 120 million bases of the fruit fly genome, Drosophila melanogaster, proved those sceptics wrong. Humans share 60% of the 13,600 fruit fly genes. So whose data is better? The HGP argue that because they have repeated the sequencing four or five times for their draft, as opposed to Celera's three, their data has fewer inaccuracies. However, Dr Venter counters that the HGP could have an accurate sequence, but that they do not know where exactly on the chromosome each sequence is positioned. "That's important because we can't define the genes until it's assembled in the proper order, as well as being highly accurate." The tit-for-tat continues with the HGP's Dr John Sulston saying: "Celera has got to sell its product and it must convince people that its product is best." The HGP also point out that Celera can use all of its data, freely available on the internet, but they have no access to Celera's work. The actual DNA used by the HGP came from 12 anonymous volunteers - Celera used six volunteers. Such numbers of volunteers may seem too small to be representative of humanity, but the difference in DNA between everyone on Earth is just 0.1%. BBC News, 2000

Spirit of symbolism in sequencing

How the spirit of symbolism will coalesce in the Universe sometimes;

alight its clean, comprehensible lines in shining pictures - name, script,

with such synchronisity, appropriateness; incredible aptness, a snug fit.

That this commercial, money-driven posse of the big Genome quest

should use the sequencing method that sounds so brash and gung-ho -

clumsy, insensitive; like laying dynamite, blasting an ancient artefact

to bits, then trying to reassemble the pieces to see how it works -

which salvaged parts can be turned to cash, and which discarded

to the pure knowledge dustbin; but supporters of the public good

taking such a careful, sensitive approach - donning scientific kid gloves,

showing respect for the sacrosanct nature of the find; and sharing secrets

so that none alone may hold the secret of ourselves, aware that all healing

springing from nature and life’s production of the Genome, her experiment

of four billion years, came from God - or how that concept represents itself

to any man, politician, scientist, however labelled in his own moral compass;

what figuration of good and evil or the grey between, is pictured in his heart;

what higher guide he hears – in the synthesised voice of Earth and Creativity

powering Sun and love; what prompts his decisions, informs his own choices. 

‘In May 1998, Craig Venter, founder of The Institute for Genomic Research in Maryland, announced that he had formed a new company (later named Celera Genomics) with the stated aim of sequencing the entire human genome by 2001. He proposed to use not the map-based approach taken by the Human Genome Project, but 'whole-genome shotgun' methods in which the genome is broken into random lengths, sequenced and reassembled on the basis of sequence overlaps. This method saves time by cutting out the mapping phase, but requires massive computing power to solve the problems of assembly presented by the human genome, which includes many repeated sequences. Coincidentally, the Wellcome Trust was considering an application from the Sanger Centre [UK] to accelerate genome sequencing when the news broke. Within days of the launch of Dr Venter's company, the Trust announced that it was increasing its funding to the Sanger Centre in order to accelerate the production of raw sequence, raising its target from one sixth to one third of the entire genome. ? of the US agencies' 1998 five-year plan was to produce a 'working draft', rather less complete than John Sulston and Bob Waterston had proposed three years earlier, by the end of 2001. In the USA, the Venter announcement galvanized the publicly funded project in this way partly for political reasons. "If the publicly sponsored research was seen to be slow and inefficient," says Dr Waterston, "it would erode Congressional support. We would then be left with the production of genomic information entirely in commercial hands. For something so fundamental, that was simply unacceptable.’ Human Genome Project, Public versus Private, Wellcome Trust, 2001

Hey - show me yours and I’ll not show you mine.

Show me yours and I’ll take yours for mine.

Show me yours and I’ll go faster.

Show me yours and I’ll make it mine.

Show me yours and I’ll try to sell it. 

‘The main difference between Celera and the HGP lies in how the scientific public can view, review, and analyze their respective findings…From the beginning, the HGP has maintained a commitment to free access to data it produces; all of the HGP sequence data, along with their analysis, is freely available to the broader research community…In contrast, Celera Genomics is a for-profit enterprise that significantly invested stockholder capital in generating, analyzing and annotating their human genome sequence data. In hopes of selling access to its sequence assemblies and annotation, Celera chose to provide a limited-access release for the general and scientific public (no more than one megabase of sequence per week). Their data-release policy was part of an agreement Celera negotiated with the journal Science to secure publication rights.Although this approach adheres to the spirit of making data available, it limits whole genome comparisons and analyses, as it would take about 58 years to download the complete genome sequence (notwithstanding the restrictions on what can be published). This dichotomy in the data-release policies adopted by Celera and the HGP, and the strong feelings that have been developed during the 'genome war,' have resulted in a post-genome 'cold war' of sorts.  The sociology of science is almost always as fascinating as the science itself.’ The Power of Public Access, John Quackenbush, The Institute for Genomic Research, Rockville, USA, Nature, 2001

Beyond the enormity of atoms

Communion with Earth,

dissolving in allegory of death;

beyond the enormity of atoms,

flooding the seamless pockets of space,

held out in invisible hands -

electric cousin-eye which understands

words with no body;

world translated into numbers,

codes for pictures, form, matter

represented - identifiable shapes.

Tombraiders come – the same men

who melted art

from the lost heart of centuries,

just for gold;

rape paintings from public frames;

burn forests, annihilate the ape -

like cutting the throat of a flower

amputated from earth,

and thinking you have its soul -

slipping into your nose and mouth

like perfume as you sniff,

printing yours with her enormous beauty;

when the sweet smell

is the flower’s beautiful death.

Who could watch a bird fly -

then charge for this privilege

of seeing what was once theirs;

free, belonging only to life -

eagles hunting over Morvern’s

broken shore by Ticket Only.

Did they analyse air, oxygen,

nitrogen and carbon dioxide –

write it down - claim the formula

was theirs; they have invented air,

and now you will be charged

just for inhaling, breathing -

there is no grander larceny than thieving

the still beating heart of a communal life.

See then, how they lay the words of life -

birds singing chemicals to flesh, in cages,

private tombs, nailing bars legally shut;

but others liberating, just saying - Look,

see how they fly, is this not fantastic?

What will this bring; is this not holy?

Look, all this is yours - this is everything

you are, owned by no-one; even the man

in the gutter is a bundle of miracles -

his miracles; your children can never

infringe copyright - let no-one tell you different -

offer you silver for the betrayed book of mankind.

‘The power of public access: the human genome project and the scientific process -  Since early 1998, much of the scientific and popular press has been filled with stories about "the race" (or sometimes, even "the war") between the publicly funded HGP and the publicly traded Celera Genomics to finish sequencing the human genome. During that time, much of the focus was on the tension between the groups and their competing approaches rather than on the science that was promised once the sequencing was finally completed. Frankly, the idea that there was a true race never made much sense. Celera always had access to their own sequence data as well as the data produced by the HGP. By any reasonable definition, that had to mean that Celera always had more data and would therefore always be ahead in any contest to finish the genome. As the competition between the HGP and Celera continued, the battle became increasingly acrimonious and threatened to damage both groups. In June 2000, a truce was negotiated, a transatlantic announcement was made that the groups had 'tied' and that the genome was finished (although, in truth, that announcement required a somewhat different definition of 'finished' than the one in my dictionary). These announcements were followed by the simultaneous publication in February 2001 of two papers describing the state of these draft genomes and the results of attempts to identify and annotate the  genes contained therein - in conjunction with another round of press conferences and press releases claiming victory. Leaving these trivialities aside, however, along with the competing egos and scientific politics, the real difference between the competing camps was not how they generated sequence data, but rather, the manner in which they provided the data to the public. The truth is, each group really owes the other a considerable debt of gratitude. Celera relied on data and techniques developed as part of the HGP (their use of the public data admitted as much); the creation of Celera and the announcement of its mission motivated the HGP to get serious about sequencing, resulting in a drastic increase in the speed at which data were collected and released. As such, I believe both Celera and the HGP should be commended for their successes.’ John Quackenbush, The Institute for Genomic Research, Rockville, USA, Nature

Note from the author
exploring the project

    The Human Genome Project
    – Public versus private
        Public Servants,
        Private Masters
        Human Genome Project
        – Method (2)
    Gene Patenting
    Blood Poems
    Holy-Moley-More God!

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