Genomic Vision

“The human genome will be the foundation of biology for decades, centuries or millennia to come.” Dr John Sulston, Director, Wellcome Trust Sanger Centre, UK; Head, Human Genome Project, UK

‘Compared with the knowledge to be gleaned from the Genome, the whole of the rest of biology is but a thimbleful.’ Matt Ridley, Genome: The Autobiography of a Species in 23 Chapters, Fourth Estate, 2000

‘The completion of a high-quality, comprehensive sequence of the human genome, in this fiftieth anniversary year of the discovery of the double-helical structure of DNA, is a landmark event. The genomic era is now a reality. Thanks to the vision of the original planners, and the creativity and determination of a legion of talented scientists who decided to make this project their overarching focus, all of the initial objectives of the HGP have now been achieved at least two years ahead of expectation, and a revolution in biological research has begun.The project's new research strategies and experimental technologies have generated a steady stream of ever-larger and more complex genomic data sets that have poured into public databases and have transformed the study of virtually all life processes. The genomic approach of technology development and large-scale generation of community resource data sets has introduced an important new dimension into biological and biomedical research. Interwoven advances in genetics, comparative genomics, high-throughput biochemistry and bioinformatics are providing biologists with a markedly improved repertoire of research tools that will allow the functioning of organisms in health and disease to be analysed and comprehended at an unprecedented level of molecular detail. Genome sequences, the bounded sets of information that guide biological development and function, lie at the heart of this revolution…Furthermore, in genomics research, we have learned to expect the unexpected. From past experience, it would be surprising (and rather disappointing) if biological, medical and social contexts did not change in unpredictable ways. That reality requires that this vision be revisited on a regular basis. In conclusion, the successful completion this month of all of the original goals of the 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, 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, US National Human Genome Research Institute, 2003

“It’s a giant resource that will change mankind.” Dr James Watson, co-discoverer of the structure of DNA

“In four billion years of evolution, we've never had the opportunity to contemplate the recipes of the strands of sequence that represent and encode all the functions that make us who we are… that will set the stage for medical research for the coming century.” Dr Hayden, Professor of Genetics, University of British Colombia

“What a profound responsibility it is to do this work. Historians will consider this a turning point...It will lead scientists to  previously unimagined insights, and from there to the common good.” Dr Francis Collins, Head, Human Genome Project, US

‘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

“Comparative genomics is going to be the single most important tool going  forward in analysing genomes.”  Dr John Sulston, Director, Wellcome Trust Sanger Institute, UK; Head, Human Genome Project, UK

Human Genome Project: Culmination and Revolution

Culmination and revolution - goal and beginning;

the Human Genome shimmers, as Colossus - but

insubstantial as a ghost, trailing her veil of letters;

bride of life, Nature’s fantastic work of art, organic

fabric unwoven – deciphered; Bayeux Tapestry-in-

progress, the live component threads still twitching.

Chemical skeleton calling into that dark matter -

pulling life from blackness, first star molecules;

her mysteries and gifts are enigmatic yet, riches

written at the start of time, augmented but buried.

Sculpted by the simplest tools, our whole body is

a cathedral; each eye is a church of God - a hand,

the divine touch rising, even out of earth -

worms, fish; any vehicle for original light,

fulfilling the urge of Creation. What paths,

processes to come; fine prescriptions, sublime

mechanics to surpass even this - what healing

locked, still sealed within our own living cells,

magical as Jesus touching the sick; genetic

magic firing internal weapons - molecular

guns - re-setting the dance; bringing even

new dancers, motions, spectacular connection

with moons, planetary orbits. One cell shaken

loose is dust enough for a whole new universe,

Eden, Genesis. What lessons will come,

what battles erupt; wrestling the patents

of mankind from private theft, rescuing

the blueprints of Creation, the sketches, original

drawings belonging still to Polar Bear and Tiger

as they go. We will not let them go, surrendering

their DNA back to the dark, to stars before life,

work of a billion years. Neither will we betray

the Genome, barter her sacred spiral filaments,

for she is wild as animals are free, and should

never be enslaved; with freedom as our guide -

principle enshrined in mind and body, as she is.

Direction of this mine upon her living flank –

drilling, digging, nearer yet nearer to the core;

however sacred, mighty, any power residing -

as the oak tree is coded in slumbering nut;

here at the point of any invisibility, source

of germination, this direction is ours to set.

Where ignorance is no excuse - when species

of understanding are possible and application,

struggle, is a duty. To weave our own stories

in the weft - enough threads thus connected

affect pictures of the whole, as the painting

of the world contains us all; in some aspect

focused here, at home, enjoying a living space,

wherein the gallery of ourselves is built, hung;

unsurpassable, with milestones yet numberless.

This is why the betting men have come, loaded

with reasons and excuses - conmen, barbarians -

philistines; but the Genome cannot be purchased,

was saved from slavery; each letter is precious,

might save your life, your child you love more

than your life - so must be saved from privacy,

legal safes; bad practice of medicine for profit

not healing. She is revolution – explosive; yet

gentle, invisible - like a wind now blowing on

the face of Earth, temples of men; hurricane,

whirlwind, zephyr or breeze - she is all. Call

her goddess or biology - entity or chemistry,

she does not hear these small voices, tuned

to the Word - listening always for the right

voice, music that will set her dancing - still

tuning stars, grass, everything else alive -

her relatives in life; all one, she cannot be

filleted - her knowledge is interconnected,

sublimely principled. What result might come

from theft, warping of her shining chemistries;

what might be born from larceny of her means

of production - without her skill, her history,

ancient roots; all her agonising experiments,

life and death invented out of light and water.

She is like something we have taken from the wild -

which must be returned in spirit while being studied;

never tamed - made to perform human tricks, bought

and sold as holy commodity traded or betrayed

by the worst aspects of ourselves, for she is us;

disrespect to her, is to all people – everywhere.

We are unworthy kings and queens of Nature,

who are failing, despoiling the garden; being

deaf to the communal music that dances all -

soothes and encourages all - at every next step.

May her arms - shown also to be fin and wing,

her flesh the very earth from whence she came,

still printed, overprinted; her chemical poem, her

genetic art, written by biology, be impetus, grace,

fresh adrenalin to help in the saving of our planet,

floundering as we are in emergency never seen

since the heavens creatively exploded, and end

of this principle of life seemed to be impossible;

perspective for artists, scientists, philosophers all,

of neverending natural order, fecundity, enormity,

immune to the temporary hand of man; beyond his

reach, actions, means of destruction. May her poetry

reach ears which have grown deaf through ignorance

of all complexions - understandable, beautiful, easier,

she is the golden statue freely raised to life, mankind.

And shining still, miraculous in being alive, evolving;

chemical shuddder in ecstatic Universe - love product.

‘Deriving meaningful knowledge from DNA sequence will define biological research through the coming decades and require the expertise and creativity of teams of biologists, chemists, engineers, and computational scientists, among others. A sampling follows of some research challenges in genetics--what we still won't know, even with the full human sequence in hand.

Gene number, exact locations, and functions

Gene regulation

DNA sequence organization

Chromosomal structure and organization

Noncoding DNA types, amount, distribution, information content, and functions

Coordination of gene expression, protein synthesis, and post-translational events

Interaction of proteins in complex molecular machines

Predicted vs experimentally determined gene function

Evolutionary conservation among organisms

Protein conservation (structure and function)

Proteomes (total protein content and function) in organisms

Correlation of SNPs (single-base DNA variations among individuals) with health and disease

Disease-susceptibility prediction based on gene sequence variation

Genes involved in complex traits and multigene diseases

Complex systems biology including microbial consortia useful for environmental restoration

Developmental genetics, genomics.’ Human Genome Project, US?

"Think what would have happened if the human genome had been privatised. People tried very hard to do that in 1998. It was a near thing. The human genome has avoided that, and the crazy notion that the information could belong to one owner. Instead it is internationally, publicly, owned. That is what we are celebrating today – freedom. Freedom of information, freedom of access, and free for all – for the hundreds of thousands of individual scientists, men and women on every continent, who are using the data for their work. The work is often directed at benefiting at their local communities. They don't have to pay for it. It's something that is closing the gap between the poor and the rich in the world, rather than widening it as so many efforts do today. It would be criminal to prevent the use of this data in this free way. People in the developing world would not have been able to have afforded this information. We have made efforts to ensure that the human genome is not for sale and that it remains public property. Unless the Wellcome Trust had stepped in, not only would we have a privatised genome, we would not be here at all." Sir John Sulston, Leader, UK Human Genome Project

The Genome has slipped into knowledge

The Genome has slipped into knowledge,

garlanded with ribbons, fanfare, shouting;

her evolved ears that can hear the tremble

of stars, note wild applause on her arrival.

Her concentration is of a different nature,

illusory the present of the creature; deaf,

blind to many processes - tuned expertly

to the maximum of being alive bearable;

enough of the dancing to listen to spring,

kiss sister plants, animals - bathe in skin

of a silver fish under blue; cool, beading

mercury bubbles - hear sea heart murmur

soothing similar bones, fins, water wings.

She smiles always in air and ocean, happy

to have been there -  remembering kindly

her efforts to drag through mud and crawl

onto shores; among dragonflies, partake

in such a fabulous unfolding, legendary

change; her own shifting and shuffling,

sky revelation - invisible air supporting

hollow bones and fluttery scales, until

iridescent; some million years buffing

dull colours, spun into salvaged stuff

of heaven, water - then loss of wings

to be king of dexterity, progress. But

weeping in a numbed cerebral space -

genes slowed, spelled, then suspended,

crumbling to disrepair, decay, slumber,

at such sacrifice of wings, flight; dreaming

still of angels, travel, of flying to the moon,

but cerebral explosions into compensations

of art and language; society, communication.

And now describing herself to herself;

subject researching herself as object -

our shuttered mind so long oblivious

to physical stories - odd, inexplicable

echoes - ripples in its sparkling folds;

arcane passages, hidden starry bursts,

small galaxies that once understood -

navigation by stars, as grace of Earth.

Astounded by tales, adventures, myths,

legends, all engraved within the code –

written revelations of the very personal

and communal history of every person;

his shocking kinship and connectedness,

interelatedness to all - surely impossible,

via the unlikely; the mouse as his cousin,

she can call the leaf his old green brother,

clashing into less artistic science, less

romantic science, which has scalpelled

poetry, aethetics. Biologically canny -

our beautiful survivor who cannot yet

be seen as she truly is, perceived complete,

no harnessing of unknown senses possible;

for now she is naked in letters, transcribed,

presented, pattern under the ornate creature,

marvellous example of her work,

artistic product of her chemistry;

life’s active forward propulsion,

recognising advantage – benefit.

Evolution as beneficial aid, as help

for sustenance of the whole garden;

as light - incubator for life, growth.

Always remembering, with honour,

how poor the code looks; letter string,

artless list - when it should be a poem

as summation of her beauty, wisdom -

experience. How clinical – unmusical;

inappropriate. But elegant and austere;

like using the Moon to explain the Sun,

when we cannot look upon such light -

understand this, without interpretation.

‘Being able to read the Genome will tell us more about our origins, evolution, nature and our minds that all the efforts of science to date, and will revolutionise anthropology, psychology, medicine, palaentology and virtually ever other science - it is the greatest intellectual monument in history…’ Matt Ridley, Genome: The Autobiography of a Species in 23 Chapters, Fourth Estate, 2000

“Researchers will go on mining the data from the human genome for ever.” Dr John Sulston, Head, Human Genome Project, UK

Enquiring Biological Poem

As she figures the past - biological poem,

chimeric entity - shifting syllables, verse;

organic expression of sophisticated beauty

reflecting Earth, bound to the soil, history -

proud individual with old, communal heart;

her sampling of life - chemical symphonies,

sound to the stars - she is life, called here,

now, to a compatible dimension - present

tense - with comprehension, doubt, faith,

all wired to the root; questions on her lips.

‘We stand on the brink of great new answers, but, even more, of great new questions.’ Matt Ridley, Genome: The Autobiography of a Species in 23 Chapters, Fourth Estate, 2000

Her archive is open – after four billion years,

her secrets, mechanisms, processes available;

her library is lit, showing her as dreaming,

imagining prefigured form, as somewhere

secreting her means, knowledge of a voice

calling her from the place we call darkness.

Her sublime manipulation of chemicals

is art; nexus of physical and immaterial

connection - her understanding of time

is absolute, barriers astute, preservation

of the essential; experience squirreled,

lighting her way, brighter and brighter,

until this strange daylight; everyday,

the eyes of men she codes watching,

deciphering. She makes the beating heart -

yet cannot tell why these ones slip a noose,

others cry out for her protection -

ownership is a mystery, anathema;

her wings are notion enough to tell us

money-cages, moral traps, are wrong -

being us, she must be protected well;

as we protect ourselves, so diligently.  

‘The Human Genome Organisation (HUGO) has recently released a new mission statement, based on the principles laid down in HUGO's aims and objectives: to investigate the nature, structure, function and interaction of the genes, genomic elements and genomes of humans and relevant pathogenic and model organisms; to characterise the nature, distribution and evolution of genetic variation in humans and other relevant organisms; to study the relationship between genetic variation and the environment in the origins and characteristics of human populations and the causes, diagnoses, treatments and prevention of disease; to foster the interaction, coordination, and dissemination of information and technology between investigators and the global society in genomics, proteomics, bioinformatics, systems biology, and the clinical sciences by promoting quality education, comprehensive communication, and accurate, comprehensive, and accessible knowledge resources for genes, genomes and disease; and, to sponsor factually-grounded dialogues on the social, legal, and ethical issues related to genetic and genomic information and championing the regionally-appropriate, ethical utilization of this information for the good of the individual and the society.’ HUGO, 2007

‘Fulfilling the true promise of the Human Genome Project will be the work of tens of thousands of scientists around the world, in both academia and industry. It is for this reason that our highest priority has been to ensure that genome data are available rapidly, freely and without restriction….Finally, it is has not escaped our notice that the more we learn about the human genome, the more there is to explore.’  "International Human Genome Sequencing Consortium" International Human Genome Sequencing Consortium

‘Global genome - is a 'genome browser' - it acts as a zoom lens to take a researcher from an overall view to the finest detail currently available. Moreover, it includes analysis of the reference human genome, predicts genes that are new to biology, includes all publicly available DNA variation information, analyses the genomes of mouse and other organisms and links all this information to known disease states. Weekly traffic at Ensembl has grown from 30,000-40,000 page impressions in June 2000 (the announcement of the to about 100,000 in February 2001 (the publication in Nature of the draft sequence), to almost 600,000 today. UK and US institutions are the heaviest users, but the top 50 also includes nations such as India, Brazil, Mexico and Slovenia as well as all major developed countries.’ Wellcome Trust

‘We shall not cease from exploration. And the end of all our exploring will be to arrive where we started, and know the place for the first time.’ T. S. Eliot

We have discovered we are like angels

We have discovered we are like angels;

our sleeping wings, the stuff of dreams.

Angels of Earth, sculpted from water and clay,

understanding of light, as holy as every animal,

all original molecules in the perpetual dance;

music of stars, seas - synapses and terrapins -

nothing is silent in the Universe of Music,

nothing insignificant in Evolution’s story;

not one blue butterfly hunted by extinction,

sunset of the tiger, Orang Utan, Polar Bear,

as a poem is altered with every word repeated,

erased; added syllable or fabulous vocabulary.

In the histories and mind of Nature - each leaf

and seed, ancient child freshly written, matters.

‘One almost wonders what, other than genes that make humans embark on sequencing genomes, does set us apart from flies and worms.’ European Journal of Human Genetics, 2005

‘A corollary of the highest importance may be deducted from the foregoing remarks, namely, that the structure of every organic being is related to the most essential yet often hidden manner, to that of all other organic beings.’ Charles Darwin, The Origin of Species, 1859

The Human Genome is a chemical dream

The Human Genome is a chemical dream -

realising hand, leaf or worm with equal art;

her proof is life - reality in natural light;

fastening of darkness, singular identity -

she has dreamt us all from the start of time;

each life a strange honour awarded by God.

       *

Written in the unformed syllables of Big Bang -

libretto to the music of star molecules and light;

chemical binding into water, birth of liquid,

what arose from the breath across the water;

coagulation of life in RNA, DNA - already

miracle enough to impress the heavens, see

that it was good, its possibilities as endless,

beautiful as dreamt - swimming in freedom.

This book was already written before the liquid

of black night sky was turned to ink - language;

pure Word with no meaning possible but love -

energy, imagining of life; dream of the organic,

thickening of light to green, flesh, reciprocity;

symbiosis of such processes and beauty, in art

coming from the water; from the sea, this flower,

her tears are sugar from salt, the blood of berries,

our blood, stained from the sea around Eden -

this red is a startling line of poetry alone; life,

the black-bound volume, gilt-edged - conceptual

writing as spirit; not static, but shifting, building,

powerful enough to charm the skeleton and flesh

from nothing palpable - but ecstatic irresistibility

of the Word. Art can be anything, a grasshopper

singing, beetle-shine, or fabulous efforts of man

in his fantasial kingdom, marvellous cathedral

of his existence, as drawn from time and earth;

distinguished by the same brain, still evolving,

deciphering its own texts - revising, enjoying.

Not one atom of us disconnected; look up

and the stars are your mother, Father Sun

is branding red messages in your skin, altering

DNA, burning with some hot, primitive truth -

look down, the leaf is your hand; a bat wing,

starfish - the eagle still soars on your wings,

for yours are become dreams, stories, pictures

still flocking imagination; infesting memories

as pigeons inhabit a dusty abandoned building -

will not budge, cooing in soporific summer sun.

Not one molecule of you is immune; everything

in commune - skin, illusion; atoms, a smattering

of matter, belonging more to energy, mystery.

Only a thought separates you from the tiger -

stops a flower and your hand becoming one,

as they are in nature - drawing solid pictures

in perpetual dance that recombines materials

to aesthetic end; art as a universal principle -

organic guide. The Genome can be approached

as art, maybe nothing else - she will not submit

to cruder scrutiny, less ecstatic science -

this science being also art, not restricted,

limited by human vision, artificial boundaries;

herself a work of art - biological, chemical art,

unimaginable complexity, interplay, connection,

for she was imagined at the blind start of time -

possible, emergent, developmental, evolutionary -

nexus of different elements, dimensions, intention.

How must she look if we could see - trailing

her chimeric gowns of the creatures she was,

their secrets preserved, adapted, lost, decaying;

imagine her DNA a moment, unbound by time.