THE HUMAN GENOME:
POEMS ON THE BOOK OF LIFE
GILLIAN K FERGUSON
THE HUMAN GENOME:
POEMS ON THE BOOK OF LIFE
GILLIAN K FERGUSON
Mission
‘The healer-believer - Francis Collins is a committed Christian and heads the publicly-funded National Human Genome Research Institute (NHGRI) in Washington DC, US. He describes himself as a physician-scientist and says his sole aim is to cure disease. Dr Collins has been directly involved in ground-breaking human gene research. With colleagues, he identified the gene for cystic fibrosis in 1989, the gene for neurofibromatosis in 1990 and the gene for Huntingdon's Disease in 1993. Dr Collins draws much of his inspiration and scientific drive from his faith. "It's interesting when you read the life of Christ how much of his time he spent healing the sick. There must have been a reason for that - he was modelling for us what it is we are intended to do by following his path." Dr Collins considers himself, and all humanity, to have a mandate from Jesus to save lives.’ BBC News, 2000
‘...the NHGRI's long-standing mission, to investigate the broadest possible implications of genomics, allows unique flexibility to explore the whole spectrum of human health and disease from the fresh perspective of genome science. By engaging the energetic and interdisciplinary genomics-research community more directly in health-related research and by exploiting the NHGRI's ability to pursue opportunities across all areas of human biology, the institute seeks to participate directly in translating the promises of the HGP into improved human health.To fully achieve this goal, the NHGRI must also continue in its vigorous support of another of its vital missions - the coupling of its scientific research programme with research into the social consequences of increased availability of new genetic technologies and information. Translating the success of the HGP into medical advances intensifies the need for proactive efforts to ensure that benefits are maximized and harms minimized in the many dimensions of human experience.’ A Vision for the Future of Genomics Research, US National Human Genome Research Institute, 2003
‘…O truly Royal! who behold the Law,/ And rule of beings in your Makers mind,/ And thence, like Limbecks, rich Idea’s draw,/ To fit the levell’d use of humane kind.’ John Dryden, Annus Mirabilis, 1631-1700, Apostrophe to the Royal Society
Jesus could look into the Genome
“It's interesting when you read the life of Christ how much of his time he spent healing the sick.” Dr Francis Collins, Head, US National Human Genome Project
Even by unconscious touch of his hem -
Jesus could look into the secret Genome,
through skin, eyes; cure at the genetic level,
without new medicine’s skillful crudities -
drug and knife, an elaborate, difficult education;
stare into a person like a window - as computers
do now, to yellow owl-eyes of disease, malfunction,
broken cells - their rightful chains undone; to assess,
activate - empowering glorious synchronisity -
but that touch like light, healing power to alter
wavering, pre-ordained, ancient script - perhaps
written since the first star limped from darkness,
not yet understood, dissected - what light is left
down here for healing that might be synthesised.
‘I once wanted to be a farmer and am very happy with the idea that scientific research should have practical results… My current interest in medial biotechnology was fired by the suffering of my own father, who was diabetic, was blinded by the disease in the 1960s, and lost part of a leg and much of the use of his hands before his death…we intend to adapt aspects of the technology that produced Dolly to provide a cure for Diabetets.’ Ian Wilmut, The Second Creation, Headline, 2001
From Diabetes to a royal sheep
From Diabetes to a royal sheep -
most high Sheep amongst sheep;
all hail the first cloned mammal -
risen from childhood’s fresh root,
whose brightest green tendrils
spring forever into new years,
perennial, fresh; still smelling
stunningly familiar as Teddy.
Her woolly crown is woven
from the grubby fluffy stuff
of past dreams - glittered products
of old children’s Christmas hands -
most helpless desire never diminished -
standing squirming toys in tiddly hands
as masked pain grew plastic on his face -
and, my light, his eyes went out, leaving
me in impotent dark - until my scaffold
of his legs fell down too; the white stars
that were his two hands under skin, stiff
and cold - wounding as a dead pet found;
unable to wire his heart warmth to me,
neither through blind eyes - just words.
How weird the path to a strange sheep -
born one day after such external labour,
to end such suffering in the future
for some man and his hurt child -
this lamb of healing and her future
lambs; the new art of her making -
some think her unnatural, as damned
when she is intended graceful - holy.
*
I wanted to be a farmer once;
now my flock could number -
well - the abundance of stars!
For the new universe of sheep
is formed from this Big Woolly Bang,
sleeps within one cloven, cloned cell -
her mild Baah is ethereal music -
unlikely sound of hope, research
embodied, living, existing;
an affectionate laboratory -
maybe a future drug factory -
animated research programme.
Too late for that man and little boy -
but for all these future children, I do.
Sifting for gold molecules
We are panned, sifted
for our gold molecules;
the dreaming genes,
written with our fate
like a soothsayer’s script,
physical psychic -
and all the money in the world
will not unlink some letters’ little arms,
nor ink the document anew -
not yet, not yet!
the feverish scientist cries,
seeing the face of Alzheimer’s disease,
dark villain unmasked, stripped bare;
from symptomatic veils of suffering
to the revealed means of tears.
His purple heart speeds
when he sees his mother in the sequence -
remembers how the poem of her was ruined
by these dancing molecules -
tripping and broken, crushed.
The light in his laboratory shines,
late, unpaid - in service of others.
‘Over 30 microbial genomes have been completely sequenced, more than for any other group of organisms. This is partly because microbial genomes, like the organisms themselves, are small. But it is also because microbes are extremely important. Pathogenic bacteria, fungi and viruses are major causes of death and illness for most of the world’s human population and are responsible for massive losses of crops and livestock world-wide. Most microorganisms, however, do not cause disease. Organisms on our skin or on the leaves of plants, for instance, help exclude pathogens, and virtually all antibiotics originate in microbes. We rely on microbes to produce much of our food and drink, and to recycle waste. Furthermore, certain microbes that live in unusual conditions represent life at the extremes.’ Medical Research Council, UK
When You Were Ill
When you burned - your skin shone
wrongly, oddly like petrol’s ill slick;
my hand lay limp, a sick bird
on your mushroom forehead -
drenched briar of wet-wheat hair,
white wing-fingers just fluttering.
The young sun that missed playing
with you out in the garden, wanted
to be nurse - crept smilingly, coy,
around blinds into the dark room;
blowing small universes of dust,
Bonsai skies, for your diversion -
I begged his unblinking light
smiles frown in our dim pool
among dark weeds of silence -
where your breath was as trees
fundamentally feeding earth -
heart’s cantering pulse, bump,
was the purpose of everything;
and he stayed obligingly quiet
but loyal, sitting still - silent
with his back to the window
all day, politely waiting -
until blushed with thanks,
slipped a few sparkly gold dancing bars
through the curtains, crept slowly away.
The night doctor had long gone,
like some visiting Dickens spirit;
viral fire in your boiling blood
was a figurative Red Dragon -
flaming from mouth and nose -
on my cool moon face bending.
I lay down beside you like sea,
moulding - ballasting the flank
of a tiny threatened island -
having read the soul of stone;
dosing my new chilled skin
with snow white thoughts -
rebuking my burning heart-drum;
stilling the passionate red waters
with the constant dour voice
of a stone’s enclosed heart –
it is all one cold grey idea;
just a still, simple thought.
I tasted myself like aspirin,
where my tongue had been;
my old blood become a drug,
blue, gluey - the salve of me,
melting into ointment -
gummy, resinous elixir;
all of me for a jar of most costly oil,
that I would sell everything to buy -
asking that you took, drew me, used me;
human poultice, living medicine cabinet.
I was petrified - inhaling germs
swarming disgustingly like flies
from the holes of your eyes and mouth -
skin-sieve flaring, tiny pore haloes bright;
you were prickling with light,
mapped with speckled stars -
I said to take everything you needed -
even to the very last spark of anything
required for me, my own health, life;
and when you did not mumble reply
from your dumb furnace of brassy sleep -
I asked it of the nurse; Nurse of Everything
in every sick room - Spirit of Nurse
in her pure white, her shining white;
the way her hand fluoresces on skin,
burns light on your shivery forehead,
understands pulse, wiring power of hands
comforting - she looks quite like an angel.
Lips whispering madly like a manic nun -
I promised myself, my own ghostly future;
offered, bargained all, in any pact.
I had opened myself like a letter -
read only your name still written,
with everything else, rubbed out.
I swore all this to the overbearing Moon,
who understands the ways of madness -
makes deathly white and blue
all living things – luminous -
as if lying on their own tombs -
spooky mobile effigies; and she,
imperious, interested -
but professionally cool,
looked in the naked window,
impersonal as a blinded eye -
but drew so spectacularly from her well
of supernatural light, enchanting nature;
began pouring her ancient, witchy spells,
liquid silver bandages; phosphorescence -
mummying your twitchy sleeping shape,
bonfire of blankets swaddling the bed -
mesmerising the Red Dragon; charming,
exorcising, until called - extinguished -
and bird-breath came regular,
sea-natured like small waves;
showing her talent for water,
old relationship with blood.
You lay like a plaster cast
of your usual sleeping self;
the bird of my hand -
a curled white ember.
Soon the Moon was smiling;
old crone, toothless spinster -
a hardened medicine woman
in her marked harvest smock,
scrubbed bloodstains from the birth
of Earth, labour of so many planets -
even though it was her own idea,
as if an old, old, original mother,
her children the stars -
scattered now, hopeful;
you would be well, recover,
but only my love survive -
I would be only light -
the colours of me gone
from the organic world -
kindgom of the Genome;
but still in your blood -
always shining, for you.
I clasped the dove of my hands
together, in a physical prayer –
the feathers were warm and settled;
strangely, I still seemed to be alive.
‘As well as providing the antibiotics erthythromycin, streptomycin,and tetracycline, Streptomyces has been the source of antiparasite andantifungal agents, an immunosuppressant,and an anti-cancer drug. Streptomycesgenes for antibiotic synthesis can be ‘mixed and matched.’ Once the full complement of genes is known, there will be opportunities to design novel antibiotics and therapeutics. Understanding the genes that regulate natural biosynthesis will enhance industrial manufacture of natural and semi-synthetic antibiotics. Genomics will help guide the design of new drugs against specific microbial pathogens, and suggest strategies for minimising the evolution of drug resistance. The complete genomes are, or soon will be, available for many important microorganisms, including those that cause syphilis, tuberculosis, Weil’s disease, and some types of food poisoning. Similar data are being generated for other human and animal diseases including anthrax, whooping cough, thrush, gonorrhoea, bubonic plague and malaria.’ Medical Research Council, UK
‘Newly-sequenced parasite genomes could yield triple-whammy drugs against three major diseases. By comparing newly published genomes of parasites which cause sleeping sickness, Chagas disease and Leishmaniasis, researchers have discovered thousands of genes common to all three. “It’s a major milestone for all of us, and the first big step towards finding solutions to these diseases,” says Najib El-Sayed of the Institute for Genomic Research in Rockville, Maryland, US. He is a leading researcher among hundreds worldwide whose sequencing work is published this week in seven papers in Science. By finding drugs that disable shared genes vital to all three parasites, it might be possible to treat all three with the same medicine. But many of the 6200 shared genes may also be present in the human genome – performing very basic functions such as sugar or amino acid metabolism, for example – and so might be just as vital for patients.“So the next task is to find a subset of genes that perform core processes for the parasites, but which are not shared with the human host,” says El-Sayed. Parasite lifestylesAs well as providing a platform for developing drugs to fight all three trypanosome parasites – collectively called the “Tritryps” – the sequences have also revealed differences between them. Although they look the same under the microscope, they cause vastly different diseases in different hosts and are transmitted by different vectors. “The genomes give us an insight into the specific lifestyles of each of the parasites,” says El-Sayed.’ New Scientist, 2005
Streptococcus pyogenes/Group A streptococci
‘Flesh-eating bug decoded – Scientists have decoded the genetic make-up of a bug that causes "flesh-eating disease". The strep A bacterium is responsible for more human diseases than any other, including sore throat, scarlet fever and rheumatic fever. In rare cases, the bug is able to invade the whole body, triggering so-called flesh-eating disease, necrotising fasciitis, which rots the flesh away. The genetic breakthrough is expected to lead to new treatments for strep A infections, and possibly even a vaccine. Researchers at the University of Oklahoma Health Sciences Center, US, revealed on Monday that they had completed a five-year project to sequence the genome of Streptococcus pyogenes, or group A streptococci. Joseph Ferretti, the molecular biologist who led the project, said it was only the second bacteria of its kind to be sequenced. "What makes this different is that the group A streptococci cause such a wide variety of diseases - more so than any other micro-organism," Mr Ferretti told BBC News Online. "Knowledge of the complete genetic make-up of the organisms will allow novel drug design and new possibilities for vaccines that specifically inhibit the organism." The strain of bacteria examined was isolated from the infected wound of a patient. It contained about 1,752 genes, 40 of which seem to be linked to the bug's ability to cause human disease. "We need to know more about how group A strep interact with humans to cause so many different illnesses," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, US, which funded the project. "The genetic sequence should shed light on these questions and pave the way for better treatment and prevention”.’ BBC News, 2001
Streptococcus pyogenes/group A streptococci:
“The tree of life as it appears in virtually every textbook may be upside down… it now looks as if bacteria came later, highly specialised and simplified descendants of the Lucas… it is we that have retained the primitive molecular features of the Lucas in our cells; bacteria are much more highly evolved than we are.” Matt Ridley
“How frilly, wasteful you are -
spinning yourselves so complex;
not even stopping at bodies -
making these noises, marks.
And so easy to invade!
Such messy red acres -
warm, wet nursery insides;
so many dark dormitories -
cosy pink incubators;
dripping, hot caves.
“You are our home; we love you,
you know - though, easily bored,
like to move on, colonising;
some might say, Imperialist.
“How you have wasted your time
on all this texture, colour, softness;
stiff white scaffold, calcification,
that pointless shine in your eyes -
starry hands, gloved in tissue,
extravagance of skin and hair.
We love best the long hot tunnel
of you, the dark red/black throat
where we kiss you, tenderly;
and our children kiss, kiss -
kiss you; inflammation, throat infection,
rheumatic fever, and even sometimes -
our extravagant surprise attack -
spectacular necrotising fasciitis;
our rare feast of flesh,
our greatest festival -
as you digest cows, sheep
and lambs for your needs.
“Did we not try to hone you -
toughen, simplify, select you?
To make you more like us,
bloom of our Scarlet Fever
like a hot blunted scythe,
leaving fields of poppies.
Are we not the victors,
to us are the just spoils,
for we took your children
to create more of our own.
“We are streamlined, perfected -
so many ways of sickness, death
have we found for you;
our home creatures -
our most cherished - and you for us;
our ruthless creativity equals yours.
You are ingenious, dogged, cunning,
we’ll give you that, (and much else) -
but you will never win,
until you shed so much;
to become only as much more
than essence needed to survive,
above all, survive - breed -
why, become quite like us.
We are perfect economy, adaptation -
being nothing more than we need to be;
perfect for spreading,
smaller than pollen -
and still we are havoc in the world -
big players, destroyers; just like you.”
‘First, total sequencing and characterisation of the genes of pathogenic organisms will reveal new ways to attack them, and explain how the organisms resist existing treatments. An example is current research on Campylobacter jejuni, one of the world’s most successful food poisoning bacteria, probably responsible for more than twice as many reported cases of enteritis as Salmonella. Its genome sequence contains about 1700 genes. Over a third of the ampylobacter genes appear to have no known counterparts anywhere in nature. On the other hand, the organism seems to have several copies of a gene thought to code for an enzyme that makes changes to the bacterium’s surface – a possible clue to Campylobacter’s ability to evade its host’s immune system. Second, microbial genomics will reveal new antibiotics and other natural therapeutics.’ Medical Research Council, UK
‘The most nomadic of the three – Trypanosoma brucei – causes sleeping sickness as it roams the bloodstream of its victims, and is transmitted by the tsetse fly. To avoid detection by the immune system, it has developed an elaborate wardrobe of surface proteins. “It hides behind the smokescreen of 10 million molecules on its surface,” says Matthew Berriman, project leader at the Welcome Trust Sanger Institute in Hinxton, Cambridge, and another major partner in the sequencing effort. The genome trawl showed that T.brucei has 800 genes for reshuffling the protein coats of its progeny – a huge number compared with the 51 which do the job in the malaria parasite, for example. The bad news is that this makes a vaccine almost impossible to produce, because the parasite is such a chameleon, said Berriman…The other two parasites – Trypanosoma cruzi which causes Chagas disease and Leishmania major which causes leishmaniasis – pose different challenges for drug makers. They both hide in human cells, living undetected as stowaways and scavenging the plentiful nutrients within. The sequencers discovered that both have an overabundance of genes for scavenging food from their hosts. Extra genes in T. cruzi, for example, enable it to metabolise histidine, an amino acid abundant in the guts of the insects which transmit the parasite. By focusing on these genes, the researchers hope to find targets for drugs and vaccines. The quest will not be easy or cheap, but researchers are hoping that money might materialise thanks to the increased focus on diseases of the poor at the G8 meeting last week in Gleneagles, Scotland. New drugs are desperately needed, as the existing ones are very toxic, expensive and increasingly useless. Melarsoprol, the major drug for combating sleeping sickness, is a case in point. Five per cent of recipients die because the drug has to be given with arsenic, and with an antidote to the poison. Also, in some areas, a third of patients carry parasites resistant to the drug. “The main concern is to convince the international community to use these new possibilities, but the road from genes to a new drug is very long,” warns Jean Jannin of the World Health Organization’s sleeping sickness control programme.’ NewScientist online, 2005
Trypanosoma brucei
Such brilliant horror, monster of adaptation -
tinier than a hair of a flea, master of disguise;
10 million molecules shifting in appearance,
fooling the immune system - its crack squad.
Trypanosoma brucei – a chameleon parasite,
Nomad; spreading undetected in the blood -
malevolent in intention; reshuffling proteins
while plotting collapse of this warm planet.
On his spaceship he comes, flying, hitching
airborne - from any galaxy he can pretend
he hails, no medicine able to catch him out -
he is alien, immune to the most sophisticated
detection tool; spy germ, tricksy infiltrator, loyal
only to the principles of sickness - reproduction -
kitting out cunning progeny in magical garments,
invisibility cloaks to stalk new territory - empires.
What dreams come to the human archipelago,
doomed to unnatural sleep - comatose under
Trypanosoma’s wicked spell - unseen enemy
making for the heart through ouwitted blood.
‘Such a programme would routinely screen human blood and rapidly identify new pathogens, such as Sars, that might become a threat to human health. Scientists want to sequence the genetic structure of the collected viruses to form a database of the genetic code of all those associated with humans. They are calling it the Human Virome Project. It is the brainchild of Norman Anderson, of the privately funded Viral Defense Foundation in Maryland, US. His proposal is contained in the journal Emerging Infectious Diseases, published by the Center for Disease Control and Prevention in the US. Increasing threat The threat from new viruses as well as from those that break out from their normal areas of infection is an ever present one. Some scientists say that clearing tropical forests is bound to allow unknown and dangerous viruses to escape. In the past few months, Sars, monkeypox and West Nile virus have all hit the headlines. When such outbreaks occur, it is important to identify and marshal as much information about the new virus as possible so that potential treatments can be investigated. Consequently, a database of known virus genomes would prove invaluable. For example, genetic information about coronaviruses helped scientists to rapidly identify the Sars agent, determine what family of virus it belonged to, and quantify how it causes damage. Its genome was sequenced and released to researchers worldwide at astonishing speed. The new plan is to collect blood samples from laboratories and hospitals every week. The blood would be filtered to extract viruses. At centres spread around the world, robotic genetic sequencers would start to unravel the genetic structure of the viruses. Things are not quite as straightforward as sequencing the human genome, however. Not all viruses have DNA. Instead, their genetic code is carried in its sister molecule, RNA. This means that viral RNA would have to be transcribed into DNA, which is a tricky process. On the other hand, virus genomes are small and therefore should be sequenced relatively swiftly. The Human Virome Project is similar to one being carried out by scientists at San Diego State University in California. There, marine biologists are attempting to sequence the genome of microbes and viruses that live in seawater. The project is still in its early stages but the researchers say it could be up and running in about a year if it attracts sufficient funding.’ BBC, 2003
‘In a study published in the April 7 issue of the journal Nature, a multi-institution team, led by Washington University School of Medicine in St Louis, described its analysis of the high-quality reference sequence of chromosomes 2 and 4. Chromosome 4 has long been of interest to the medical community because it holds the gene for Huntington's disease, polycystic kidney disease, a form of muscular dystrophy and a variety of other inherited disorders. Chromosome 2 is noteworthy for being the second largest human chromosome, trailing only chromosome 1 in size. It is also home to the gene with the longest known, protein-coding sequence: a 280 000 base pair gene that codes for a muscle protein called titin, which is 33 000 amino acids long. The new analysis confirmed the existence of 1346 protein-coding genes on chromosome 2 and 796 protein-coding genes on chromosome 4. As part of their examination of chromosome 4, the researchers found what are believed to be the largest 'gene deserts' yet discovered in the human genome sequence. These regions of the genome are devoid of protein-coding genes, but researchers suspect that they are important to human biology because they have been conserved throughout the evolution of mammals and birds. Work is now underway to figure out the exact function of these regions.‘ Wellcome Trust, 2005
There are no stories in picture books about germs
There are no stories in picture books about germs -
viruses, disease; it’s all dragons, monsters, witches,
imaginary killers instead of true villains of the piece.
For what illustration could we grasp, like those beads
on sticks are supposed to help us comprehend molecules’
spatial beauty - the Genome riddled with analogy, simile,
metaphor, but slipping away still; sparkling golden ghost
creeping back to dark - wand trail, Tinkerbell dust behind.
How to capture that invisible stealth, swiping cat’s paw
the size of a million billion cathedrals; to translate viral
genomes into evil armies - contagion into black swarms -
snarling bats; evil knights in green shining beetle-armour.
Still easier for the human mind - centuries of dreaming art,
to picture snorting dragons; a wicked witch, green monster,
than the germs of the common cold - flu virus annihilating