Revealing the Human Genome

‘In a recent issue of Nature, the landmark paper has appeared that describes and discusses the finished version ('build 35') of the human genome. This International Human Genome Sequencing Consortium's new build of the genome sequence is as finished as current technology allows, which is a major improvement on the initial draft sequence. The finished version of the genome sequence covers 2.85 Gbp or 99% of the euchromatic region, with only 341 gaps, compared to the 150 000 in the working draft. It has a long-range continuity of 39.5 Mb, which is 475 times better than the 81 kb in the working draft, and the sequence has been delivered at an error rate of 1 10-5: almost 10 times better than the quality standard of 10-4 originally aimed for…The authors of this landmark paper emphasize the extremely rigorous quality control applied to achieve and validate this result. And rightly so, this sequence will be the raw material upon which future generations of scientists and healthcare workers will base studies that depend on highly reliable data. To this aim, 40 Mb was independently resequenced, and an overlap study was carried out on 4235 clones from one large insert library. As hoped for, the latter showed a bimodal distribution of base differences, consistent with half of these coming from one haplotype and half from the other. These results confirm that the sequencing error rate is 20−100 times lower than the human polymorphism rate. This confirms the finished human genome sequence as a robust resource for large-scale evolutionary, functional and comparative analyses. The Consortium also resequenced 750 000 clones (8 coverage) from an independent fosmid library to validate over 97% of the junctions of the large insert clones. This analysis also suggests the presence of 50−100 erroneous deletions (average 5 kb).’ European Journal of Human Genetics, 2005

‘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…American institutions have been the major partners in the decoding programme. 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… 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. 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…Identifying genes can now be done in days instead of years.’ Ivan Noble, BBC News Online, 2003

‘Finishing the euchromatic sequence of the human genome - The international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers 99% of the euchromatic genome and is accurate to an error rate of 1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human genome seems to encode only 20,000−25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead… Because the precise scientific plan and the feasible degree of accuracy and completeness were unclear at the outset, the sequencing of the human genome proceeded in phases… Notably, the finishing phase required roughly equal resources of time and expense as the draft phase.’ Human Genome Sequencing Consortium, 2004

Revealing the Human Genome

Such a staggering spillage of secrets -
this walnut-cracking, slow unlocking

of a sacred, long buried biological box,
which we didn’t even know had a lid -

yielding key, cipher - sealed centuries
of blood and death’s fruitful sampling;

Evolutionary time capsule
still roaming modern Earth.

Such rushing into unaccustomed light -
sequencers, processors, spewing pattern,

curious letter fountain in electric air,
for the whole world’s artificial eye -

like finding light has a skeleton,
white bone - aeons before bone,

the honed dream of first light
that commanded itself to be -

and was, illumined even in the cup
of darkness, a shut eye dreaming -

discovering it came from families of light -
pinprick to star to heavenly recipe; sampled

in burning salmon sunset - summer honey
filling sugared flowercups; lickable, sticky

gold of autumn afternoons, the mussel-stomach
colour enchanting the Western Isles at evening.

Like finding dark has skeleton – exoskeleton;
soft blue skull like a squashy baby fontanelle

hardening at late evening under navy skin,
to glossy black turtle - crawling with stars.


The human being is now unspooling
animal skins, our old cast costumes -

our glorious burning tiger robe,
dazzling, missing swan wings -

eye-flower, leaf-palm,
our foot-root, bat-arm -

beyond example flesh,
the enormity of atoms,

marvellous weight of existence;
excising to what remains - left

held in the scientist’s palm
like a magic seed of light -

a description using light
because there is no word,

no suitable explanation,
existing simple symbol,

for the original Word,
which just is; yes - is.


A nest of letters,
written in light -

cocooned in darkness,
dreaming always, life -

translated by computers
trying to learn grace; art.

‘… the successful completion this month of all of the original goals of the Human Genome Project (HGP) emboldens the launch of a new phase for genomics research, to explore the remarkable landscape of opportunity that now opens up before us. Like Shakespeare, we are inclined to say, “what’s past is prologue” (The Tempest, Act II, Scene 1). If we, like bold architects, can design and build this unprecedented and noble structure, resting on the firm bedrock foundation of the HGP (Figure 2), then the true promise of genomics research for benefiting humankind can be realized. “Make no little plans; they have no magic to stir men’s blood and probably will themselves not be realized. Make big plans; aim high in hope and work, remembering that a noble, logical diagram once recorded will not die, but long after we are gone will be a living thing, asserting itself with ever-growing insistency” (attributed to Daniel Burnham, architect).’ A Vision for the Future of Genomics Research, Francis S Collins, Eric D Green, Alan E Guttmacher & Mark S Guyer on behalf of the US National Human Genome Research Institute, Nature, 2003

‘Owing to the emphasis on thoroughness, validation and QC, the flavor of the [Human Genome Sequencing Consortium] paper is rather more technical than the mainly biology-oriented working draft publication, which was therefore, unsurprisingly, more electrifying. …. One revisited issue is the human gene count. This is corrected to an estimate of 22 500 (range 20−25 000): downwards from the already surprisingly low estimate of 31 000 in the working draft.’ European Journal of Human Genetics, 2005

Coaxing our ghost from skin wall,
bone helmet, wild animal, flower;

pattern among drapes of existence -
furred, spotted, fleshed; the running

glory of them to our pinnacle eye -
grown slowly in the rumbling belly

of time, from death’s foetal waters,
stories of continual fertilising birth –

into dazzling light, comes brighter light,
like the skeleton of a star, heart of a star,

star-seed. We have caught ourselves
in the process of life, computer-held,

coagulated a moment - not frozen,
as the Genome is always evolving;

never a Gingerbread man, static pattern,
but man becoming - a work-in-progress,

like water pausing as mercury -
river as silver ribbon from afar

for the benefit of comprehension;
possibility of process, perception.

We have deduced ourselves,
our living poetry, nature -

poetry that speaks our name;
all others - living and dead -

animal, man, fish, plant -
shown to be one structure.


‘For some it's the sense of completion. For others it's the importance of getting it right. Either way, the completion of the human genome project in time for the fiftieth anniversary of the discovery of DNA's helical structure is attended by many sighs of relief… Two groups of scientists revealed draft versions of the human DNA sequence: one from a private company, one from an international and publicly funded consortium. Labs involved in the latter have been slogging to fill the holes ever since. Today they are announcing closure: 98% of the regions that actually contain genes are done…Some bits remain elusive; for unknown reasons, current molecular-biology tools cannot get the better of them. Whether or not the details actually matter is "a matter of bar room fistfights", says Branscomb. But there is pressure to be accurate because this sequence serves as a reference to which people's genomes are compared.’ Helen Pearson, Nature, 2003


The world will hold collective breath a moment;
TV food hang cooling, hooked on frozen fork -

before treacherous sinking sands of everyday,
duty’s ambush; television, bills and pleasure -

our tailored sorrows, fitted panniers on our back,
eclipse interest blinkers, illuminated attention -

snuff wonder, humbling perspective; that stirring -
as we avoid the shattering night beauty of stars.