Some history of the Human Genome Project

Genomic milestones - The first genome, that of a bacterial virus,  was a mere 5,400 bases and it took years to sequence. Only a decade later, an international collaboration of scientists embarked on an endeavour to sequence the 3 billion bases of our genome.’ BBC, 2003

‘"As clearly the world's most successful [genome] sequencers, John's and Bob's talents soon came to the notice of American venture capitalist Frederick Bourke," says James Watson. "He and Leroy Hood had considered forming a private company, based in Seattle, to sequence the human genome. Through patenting key genes they hoped to effectively dominate the commercial exploitation of the human genome. "When I learned that Bourke was trying to move Waterston and Sulston to Seattle, I worried that the NIH might lose its most successful genome-sequencing effort, and the UK government might abandon large-scale genome research. The Genome Project would then lose the great intellectual resources nurtured by the MRC at the LMB. "I knew that John Sulston would prefer to stay in Cambridge, but he was dependent on procuring committed funding from a UK source."…It was at this point that the Wellcome Trust, which had recently become one of the richest sources of charitable funding in the world, came into the picture. Following an approach to the Trust by Aaron Klug (then Director of the LMB) and Dai Rees (Chief Executive of the MRC), John Sulston and a hand-picked team applied for funding to establish a sequencing operation that would complete the work on the worm (funded by the MRC) and on other model organisms such as yeast, and begin the task of sequencing the human genome. The Trust, then led by Dr (now Dame) Bridget Ogilvie, recognised the importance of this scientific endeavour, and agreed to make an award to establish a major genome sequencing centre at Hinxton, near Cambridge. The Sanger Centre was officially opened in temporary laboratories (soon to be replaced by a state-of-the-art modern campus) in 1993. It quickly established itself as a world-leading institution, playing a key role in the completion of the yeast genome in 1996, the C. elegans genome in 1998, and the first complete human chromosome, chromosome 22, in 1999. ‘ History of the Human Genome Project, Wellcome Trust, 2001

Decisions that will shape the shadows of the future,

picture light; lurking - beasts, demons and angels -

who will align themselves in the ensuing long battle.

Arguments that must be won - for this Project has a soul -

as many quickly saw; how crucial history will view, judge,

these early plans, upholding of what is right, not profitable.

Here the root was formed - already somewhat schizophrenic -

twins at the starting line who look the same - but whose hearts

beat to different rhythm; one sunflower, the other, honeysuckle. 

The worm leads the way - In the late 1980s and early 1990s, national funding bodies in Europe seemed less confident about spending the very substantial sums involved in genome sequencing projects. Many scientists were concerned that giving such a big slice of the biomedical funding cake to a single project would stifle creativity and narrow the range of science that could be supported. Nevertheless, the science that would provide the basis for mapping and sequencing the human genome was already flourishing on a smaller scale. The technology that was needed to move from mapping, locating the positions of known landmarks throughout the chromosomes, to sequencing, spelling out one by one the sequence of bases along each chromosome, already existed. Fred Sanger at the LMB in Cambridge had won his second Nobel prize in 1980 for developing the method of sequencing DNA that is still, with minor modifications, in use today. Sanger and his colleagues had also pioneered whole-genome sequencing - working with phage, tiny viruses that infect bacteria and have genomes only a few thousand bases long…Sydney Brenner's laboratory was trying to come up with a full description of an organism, from genes to behaviour, by working with another simple species - the 1 mm long nematode worm Caenorhabditis elegans. By 1989, his colleague John Sulston, with Alan Coulson and later with Bob Waterston at Washington University in St Louis, had successfully produced a map of the entire C. elegans genome. The map consisted of multiple overlapping fragments of DNA, arranged in the correct order. Each identified fragment had been cloned in bacteria, the raw material necessary for a sequencing project. Watson believed strongly that the Human Genome Project should also encompass the genomes of smaller organisms that would both help to establish the technology and provide valuable sources of comparison once the human project was truly under way. As soon as he saw the worm map, Watson agreed that C. elegans should be the first multicellular organism to have its complete genome sequenced. NIH funded Dr Waterston's lab to begin a pilot project and also, exceptionally, put £500 000 into Dr Sulston's Cambridge lab to supplement funding from the MRC. In 1990 when the worm sequencing project began, the first automatic sequencing machines were just becoming available. The machines, made by Applied Biosystems Inc., operated on the principle established by Sanger but used different coloured fluorescent labels instead of radioactivity and read the data automatically. Working with these machines, the worm pilot project met its target to sequence three million bases in three years, and established that the technology was scaleable - more money, more machines and more people would produce more sequence faster.’ Wellcome Trust, 2001                  

We must be grateful to the worm for showing the way -

We must be grateful to the worm for showing the way -

as it seems we must for an unlikely flowering of species;

I tried to explain to my seven-year-old in the garden

how this poor upturned creature hating air and sun -

slithering, silvery with slime, was somehow ‘mother’;

had also, fittingly, opened the first gate to sequencing

the recipe for Man - he didn’t look convinced.

Yet knows the world still better than an adult -

his palm touch to the muscular pink creature

reading so much that later text will amplify -

wings that shimmer on his thin, downy back

in sunlight as he dances with a branch, birds,

leaves; rubs his face on the cheek of a flower,

meets water still like the sea’s own creature -

embodies Spring in the tenderness of himself -

fresh feel of his skin, original light in new eyes;

where the physical, material and spiritual

meet in ways visible to observing adults -

where it comes as no surprise to learn this way

of conserved embryology - Earth is motherly -

and the humility of mother worm is therefore ours;

her small pink vision - huge endeavours under soil.

‘The success of the pilot worm sequencing project, says Dr Waterston, now Director of the Genome Sequencing Center at Washington University, was the key to getting human sequencing off the ground. "For the first half of the 90s," he says, "there was an underlying scepticism that something as large as the human genome could be done with gel-based approaches. People were waiting for some revolutionary new technology that would do the human genome at the touch of a button, or at least within a year. With the worm, we achieved a high enough throughput at low enough cost to convince people that it could be done with the existing technology." The model organism sequencing projects, says Francis Collins, who succeeded James Watson as Director of the National Human Genome Research Institute in 1993, showed not only that large-scale genome sequencing was practicable, but that the information obtained was of high value…"All the mammalian biologists watched with envy as they saw what could be done with the yeast genome, and the worm was even more valuable," he says. "It was a big shot in the arm for those who wanted to scale up the human sequencing effort." 1993 the US agencies launched a new five-year plan, in which they argued that "priority should be given during the next five years to increasing sequencing capacity by increasing the number of groups oriented toward large-scale production sequencing." Initially progress was slow, with most investment still going into mapping and technology development rather than producing human sequence. In 1995, Bob Waterston and John Sulston began to argue publicly that the biomedical community would be better served by a massive increase in investment in sequencing, coupled with a small relaxation (from 99.99 to 99.9 per cent) in the accuracy of the product, which would be selectively finished later. Based on their experience with the worm, they said that just three centres scaled up to process 84 000 'reads' (DNA fragments a few hundred bases long) per week could cover 99 per cent of the genome to an accuracy of 99.9 per cent by 2000 - five years ahead of the target for completing the project. Dr Sulston said at the time, if it can be done, "why fiddle around?" But the idea had plenty of detractors, not least among those labs that had been involved in mapping chromosomes and feared that the chance to move to sequencing would be snatched from them if the few labs that were further ahead - principally the Genome Sequencing Center and the Sanger Centre - did the whole thing in bulk. "There was also a genuine concern," says Dr Waterston, "that if we went too fast we would never end up with a truly archival product - that biology would lose the chance to put itself on a completely firm footing." These arguments won the day. Systematic human sequencing began on a pilot basis in 1995, and the proposal for a massive acceleration fell into abeyance.’ Wellcome, 2001

‘Funding from the Wellcome Trust for the Sanger contribution to the sequence of the human genome has totalled £150 M.’ Wellcome Trust

Such a map, such a pattern

Such a map - such a pattern -

like learning the blood of stars;

cocktails of gas and light

transfusing the Universe -

deciphering the burning gold heart

of Sun - illusory blue face of Sky.

Logging co-ordinates for life,

brilliant hooks like a swarm

of silver bees, working alone

as one; where life knits itself

from chemical needles – switching -

orchestrating in fantastic movement.

Such a project - such a task -

great endeavour, sacred work;

how will they catch these dreaming codes,

mysterious sequences, with nets of letters -

follow, plot the modest four ingredients,

to instructions for an eye or hand; learn

the making of their peacock coats,

spun from basic hemp and water -

capture the endless buzz and fizz,

organic spark – warping and weft;

force that spurs the chemicals, drives

Creation’s lavish human expansion -

what a plan - what a mountain -

what a goal. What glory awaits.

‘After 1998, production of sequence by the main centres in the Human Genome Project accelerated to an unprecedented degree, going from 6 per cent to 90 per cent of the genome in under two years. Most of the work was carried out by just three centres - the Genome Sequencing Center at St Louis, the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, and the Sanger Centre (which is responsible for a third of the total) - but many other labs around the world made important contributions. Having a major sequencing centre in the UK has prevented the project from being an almost entirely American affair. "It's been of the highest possible importance," says Francis Collins. "There were some members of Congress who did not see why, if the information was to be given away, the USA should foot a disproportionate share of the bill. The very strong presence of the Sanger Centre added to the legitimacy of what the US centres were doing.’ Wellcome Trust, 2001

Science puts on her tiara

Science puts on her tiara,

sparkle and high heels -

this is truly The Big One -

a glamorous extravaganza;

biggest, most fabulous event

in the whole historic calendar.

Roll up, come see, read, understand,

come wonder beneath bright lights -

come view, see this sparkling chemical chain,

that made you - drew you from inspiring mud.

We have laid you under your feet.

We have surpassed our dreams...

Imagine the recipe for a hand

Imagine the recipe for a hand,

writing it out for your friend -

to the last half-moon nail,

crescent root - sheathing

cuticle; this brittle claw

civilised into pink shell.

Describing calcification

of wristed star skeleton,

flexible skin production -

gloved over bone scaffold;

the muscle-powered hinges -

rigid but smoothly moveable;

tubular blood stems, journeys,

branches, to every lacy rivulet

blushing in time with the heart -

the Celtic print of each fingertip.

And the words you must find

for the hand’s fine capacities -

music, healing, strength, comfort;

communication of love by touch -

its embroidery and art -

own sculpture in prayer;

how soon you would find

you were writing a poem.

I see a Da Vinci and Gingerbread Man shape

I see a Da Vinci and Gingerbread Man shape,

arms outstretched, as if wings would appear -

now we know they are sleeping somewhere

under the skin like a crumbled, folded swan.

Outline inked to keep the pattern there;

stop shifting - shaped dance and music,

but words scrolling, stripped beyond

sense and expression - streaming out

like embroidered banners, the name

of their house; bright golden threads

making and remaking like flowers

blossoming from the same stems -

the scientist as chronicler,

spread across the world -

churning through what underlies the art,

chemical composition of illusory paint -

everything the artist ever does,

to a last molecule of pigment -

presenting us with a book

like, ‘This is Your Life’ -

to read ourselves - know

what touch and love add;

what powers our hearts beyond

this fiery recipe, kindling DNA.

‘Dr John Sulston claims that he became Director of the Sanger Center, spearheading the UK’s contribution to large-scale human genome sequencing, only because he couldn’t see how else he would get the funding to finish his real life’s work, the genome sequence of the nematode worm.  Dr Sulston originally trained as an organic chemist. In 1969 he joined Sydney Brenner at the MRC’s Laboratory of Molecular Biology (LMB). Dr Brenner was attempting to link genes, and behaviour through the study of a very simple organism, the tiny nematode worm Caenorhabditis elegans. Dr Sulston’s first major contribution was to document the lineage of every cell in the adult worm, right back to the fertilized egg. This global approach led him inexorably to think about describing a whole organism at the level of the genome. With Alan Coulson at the LMB and Bob Waterston at Washington University in St Louis, he went on to make a complete physical map of the worm’s six chromosomes. 1989 the map was complete, and with James Watson’s backing the team obtained funding from the National Institutes of Health and the MRC to begin to sequence the worm clones. Three years later they had been so successful that sequencing the human genome suddenly seemed a real possibility. The Wellcome Trust saw the opportunity to establish a world-class genome sequencing centre in the UK, using the high-throughput approach that the worm project had pioneered. In 1992 they founded the Sanger Centre jointly with the MRC, and invited John Sulston to be its first Director. It meant, among other things, that he could get the worm finished, and in December 1998 he and his colleagues published the complete sequence, the first of a multicellular organism. “I was not personally going for the human genome,’ he says. “It was more a question of wanting to get genomics going, and then more specifically to study the genome of the worm. But I also believed very strongly that the UK should become involved in large-scale genomics, and so when the opportunity came to head the Sanger Centre and help to make a serious attempt on the human, I was ready for it.’ Between 1992-2000, Sir John Sulston was Director of the Sanger Centre and led the UK’s involvement in the Human Genome Project.’ Wellcome Trust, 2001

Inspiration might come from anything –

a letter burning dramatically in the grate;

love-words, kiss-prints, turning to smoke,

to molecular ashes blown back to heaven -

blue sky burning above an autumn leaf cremation,

where a Golden Eagle on fire spirals up to heaven;

or snow healing the broken world, just at Christmas,

turquoise sea floating starfish hands to touch shore -

but also the battered shoe discarded in a gutter,

dead silver fish flashing on a pink shell beach;

cheap nylon flags in mud after great events,

your own hand in the act of touching down.

As small and great a thing as a sunflower

dying in a vase - bowing its great head -

just looking at you once last black time;

and seeing it has tears among the seeds –

so fantastically wired - willing, this brain,

to make art of anything, get itself thinking.


Dark Wardrobe of Ourselves

Such a shimmering man-shape hauled now

from the mysterious wardrobe of ourselves;

plotted from the dark, our human outfit – but

such secrets and creatures – thrills, concealed

and revealed in archiving cells; unravelling

spirals of chemical threads, read as a scroll,

typed plan, letter-run - then re-stitching

the familiar guise, embroidered illusion,

back to recognisable elements; a whole.

Brain like a grey vegetable, ugly flower,

hands with radiating fingers - two bone

stars, gloved with skin, animated nerves;

two incorporeal light-stars shining also

in every black hole of a celestial eye –

heart, too, a red star, transmuted rose,

in dark chest space - scarlet and blue

arterial radials; pumping cosmic muscle

to plain pulse music that keeps the beat

for the whole dance, until the last note.

But trailing dimmer figurative shapes –

a chimeric litter, like the furthest stars

still sparkling – fantastically different

creatures; flocks of waltzing amoebae,

with the taste of sea still in their frills -

transparent ghost of mother earthworm

like a Victorian supernatural trickster –

undulating, insubstantially substantial;

whiskery snuffling presence, nocturnal

shrew turning over leaves 80 million years

ago, sewing his alertness, night memories,

to the Genome which forgets nothing –

even comatose, ruined genes dreaming

still in the landscape of the cell; communal,

chemical geography of life on planet Earth.

Skin and time are a blinding illusion -

an ease of perception perfected by life;

looking distinct, we are blurred like a print

made over and over - but slightly different

on the same page; the change so incremental

over four billion years, nobody became thus

overnight, could be called anything but brother,

until one day seeming utterly unrelated - alien.


Human genome finally complete - The biological code crackers sequencing the human genome have said they have finished the job - two years ahead of schedule. Their announcement came less than three years after a "rough draft" was published to worldwide acclaim…The decoding is now close to 100% complete. The remaining tiny gaps are considered too costly to fill and those in charge of turning genomic data into medical and scientific progress have plenty to be getting on with. The Wellcome Trust Sanger Institute, the only British institution taking part in the international effort, completed almost a third of the sequence - the biggest contribution by a single institution. Its director, Professor Allan Bradley, said that completing the human genome was a vital step on a long road, but that the eventual health benefits could be phenomenal... When the Human Genome Project was formally launched, there were some who thought it could take 20 years or more to complete. But robotics and supercomputers speeded up the process hugely. And it is arguable that competition from a privately funded company, Celera Genomics, which produced a rival sequence, hastened the end stages of the project as well. The purpose of the last three years has been to fill in gaps in the DNA sequence and "proof read" the data to produce a "gold standard" that will inform genetic research for years to come. Dr Jane Rogers, head of sequencing at the Sanger Institute, said: "We have reached the limits we set on this project, achieving tremendously high standards of quality much more quickly than we hoped.” The working draft allowed researchers to kick-start a multitude of biomedical projects. Now they have a highly polished end product which will assist them even more. "It's a bit like moving on from a first-attempt demo music tape to a classic CD," she said. Knowing virtually the entire sequence of the roughly three billion letters of genetic code in our DNA gives scientists the chance to explore everything that is genetically determined about our lives. Sir John Sulston, who ran the British end of the project for much of its history, said earlier in April that researchers would "go on mining the data from the human genome for ever".’ BBC News, 2003

‘The Human Genome Project is the largest international collaboration ever undertaken in biology. Between 1990 and 2003, thousands of scientists worldwide undertook the immense task of sequencing the 3 billion bases of genetic information that resides in every human cell. ‘ Wellcome Trust, 2006

The Skins of the World are Falling

The skins of the world are falling -

earth and eye; starfish, bird, hand,

washed from the beautiful blurred pictures

of existence; of particular matter clustered

in its rightful pattern - even light

characterising life is left behind,

here in the sacred dark - scripted

skeletons mapped with old stars;

as the snowflake’s crystal is stern

and gorgeous both under her fuzzy

rabbit-tale blobs – the stunning Polar Bear

is savage in genetically perfected white fur.

How we have held our breath in funded labs;

who among us - atheists et al - did not think

we looked into the mind of God, Creation,

life; beyond the known bones of existence,

to a place where possibility and reality

in our breathing world meet - and who

dared look beyond to speculate

on origination of such a script.

It is enough for now - to read this holy writing;

wonder, stagger at the consequences. Will we

not shout out; can we not explain, coming forth

from our screens? Here is The Code - read, rejoice -

right here is how you make a man; if you want God,

here He is too - He has written the world, this flower

in my hand, and my hand; earth and water that

gave the flower, light that it drinks, synthesises.

To see the hand and rose pouring out as script -

heavenly recipe, letters, is almost more than we

can take, communicate; to hold the word of man

is our work, our great privilege in a new century. 

Our labour began as a slug, trailing even then its silver,

shining; but so tedious, laborious, exploring in the dark,

ugly already compared to what we saw - nearly blinded.

Our eyes grew round as owls’; our work now speeding

into jumping squirrel, oh, the elegance of our big leaps,

gorgeousness of what followed behind - that starriness,

elongated halo. Our project became a comet, hurting

the eyes, travelling the heavens, wished upon - glory

began streaming like a burning light - eclipsing stars

like atoms - Relativity, The Origin of Species, Evolution -

set around us like bright handmaidens; on and on we sped

until light was shed in the almost ultimate darkness of life;

exact spot, energy, where life and potential shimmer.

Who would have thought writing there - which must

be silver; embroidery upon the face of nothing, coal

black space, colossal and simple as the night sky,

riddled with stars; and on we flew, evolving wings,

reconciling our computer prints with the colourful

storms of existence; that which is described, annotated -

written in essence with no decoration of diverse species.

Great truths came buzzing around us, insistent as wasps;

resist as some did, it was hopeless to pretend

we were not one with our world - our Earth -

our trees and flowers, the animal in our home;

seahorses and leaves, soil alchemising beneath

our feet. And at our peak, we were humbled -

not feeling like God but like we had stumbled

skillfully into His presence, were reading His work

for the first time, even to our own soul co-ordinates

for hooking life - culturing flesh, the means of love;

building a beating heart capable of breaking -

tear factories; organism who would lay down

his life for a friend - martyrdom, selflessness,

and all the evils and shortcomings simmering

in the holy bowl; the dark recipes for betrayal,

murder, sickness - a culturing of new darkness.

At our moment of greatest achievement,

we were smitten - stumbled for words -

we knew grace when we saw it but now

lacked sufficient vocabularies to explain

such magnificent simplicity; such power,

sublime ingenuity - how life itself, is art.

The Human Genome Project - End of phase one – 2003. Come April 2003 or thereabouts, when an international public consortium plans to wrap up its large-scale gathering of human genome sequence data, the Human Genome Project will be over. "We'll have the sequence," as the University of Washington's Maynard Olson dryly observed at a recent gathering of project researchers in Airlie, Virginia. "That's something we all agree on - even though it's not true”.’ Nature Editorial

Expected to take 15 years until 2005, the Human Genome Project was finished two years ahead of schedule in 2003, and published in 2004. It involved hundreds of scientists in the UK, China, Germany, Japan and the US. The UK was the largest contributor to the project: one third of the Human Genome was sequenced at the Wellcome Trust’s Sanger Institute.

‘The International Human Genome Sequencing Consortium has published its scientific description of the finished human genome sequence, the product of the 13-year effort to read the information encoded in the human chromosomes that reached its culmination in 2003. The paper, which appears in the 21 October issue of the journal Nature, examines the current genome sequence, which contains 2.85 billion nucleotides, encompasses around 99 per cent of the euchromatic (or gene-containing) portion of the human genome and is 99.999 per cent accurate - 10 times more accurate than the original goal.’ Wellcome Trust Sanger Institute, UK, 2004

‘A more complete picture of living cells and organisms will necessitate a fuller description of protein function.’ Medical Research Council, UK 

‘The technology now available cannot readily close these recalcitrant gaps in the human genome sequence. Closing those gaps will require more research and new technologies, rather than industrial-scale efforts like those employed by the Human Genome Project.’ Wellcome Trust Sanger Institute, 2004

Note from the author
exploring the project

    Gene Story
        Mendel’s Peas
        The Human Genome Project
        Some history of the
        Human Genome Project
    Romantic Science
    Some Special Genes
    X & Y

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