THE HUMAN GENOME:
POEMS ON THE BOOK OF LIFE
GILLIAN K FERGUSON
THE HUMAN GENOME:
POEMS ON THE BOOK OF LIFE
GILLIAN K FERGUSON
Gene Therapy
"Gene therapy is a promising field that offers fundamentally new ways of curing human illness." Francis Collins, Director, NHGRI, US
‘Gene therapy, using the genes themselves as medicines, is in many ways the most obvious application of the human genome data. But it is also the most controversial, with a number of deaths linked to experimental treatments. Over 4,000 illnesses are caused by faults in single genes: Cystic fibrosis Huntington's chorea, Sickle cell anaemia, Muscular dystrophy. The ideal focus for gene therapy is on single gene disorders, such as cystic fibrosis. Here one abnormal gene can be cut out and replaced by a healthy version, delivered by a tamed virus. But although over one million people in Britain suffer from inherited illnesses, individually the disorders are rather rare. This means the potential market for a company is small. At best, this would mean the treatment was expensive. At worst, it could mean the treatment was not developed at all.’ BBC Science
‘Pharmaceuticals on the market target fewer than 500 human gene products. Even though not all of the 30,000 or so human protein-coding genes7 will have products targetable for drug development, this suggests that there is an enormous untapped pool of human gene-based targets for therapeutic intervention. In addition, the new understanding of biological pathways provided by genomics should contribute even more fundamentally to therapeutic design.The information needed to determine the therapeutic potential of a gene generally overlaps heavily with the information that reveals its function. The success of imatinib mesylate (Gleevec), an inhibitor of the BCR-ABL tyrosine kinase, in treating chronic myelogenous leukaemia relied on a detailed molecular understanding of the disease's genetic cause. This example offers promise that therapies based on genomic information will be particularly effective. Grand Challenge I-1 describes the 'functionation' of the genome, which will increasingly be the critical first step in the development of new therapeutics. But stimulating basic scientists to approach biomedical problems with a genomic attitude is not enough. A therapeutic mindset, lacking in much of academic biomedical research and training, must be explicitly encouraged, and tools developed and provided for its implementation.’ A Vision for the Future of Genomics Research, US National Human Genome Research Institute, 2003
‘Then came a huge serendipidity – perhaps the greatest in the whole history of biotechnology. In 1973 biologists found that they could introduce new genes into bacteria – in fact the ubiquitous gut bacterium Escherichia coli (or E. coli for short) – simply by sprinkling them with DNA as they grew in culture.’ Ian Wilmut, The Second Creation, Headline, 2001
‘Germline engineering - The most extreme suggested use or the human genome data is editing the DNA inheritance bequeathed from one generation to the next. Such a scenario involves identifying an abnormal gene and then correcting it in the cells which are used to pass genetic information to offspring - eggs and sperm. No subsequent generation would then be afflicted by their ancestors' gene defect. However, such irreversible tampering with the code for life will only be allowed after major ethical reservations and safety concerns over possible unexpected results of the changes, are addressed.’ BBC Science
The modern writer sits in his laboratory -
sweating as he contemplates Shakespeare’s
opened volumes - Keats’ handwritten poetry,
shining at his hand; his own pen inked, hyped
with a new light species - liquid letter-script;
spilling, energetic - even loose drops blotted
growing cells - amoeba, fish, blood, words -
scalpel nib excising, sewing re-written script
practised, rehearsed, a zillion times - trembling
here in reality, glorious unstitched manuscripts,
dusty pages annotated, doodled, amended by time -
preparing to alter, improve, just as original authors
have done, century over century, weaving newer skills
with existing strands, plastic matter, the whole picture;
mobilising invisible schemes, driving codes of dreams,
materiality, existence - interfering cleverly with life’s
old dreaming roots, font of her ongoing adaptive genius;
suddenly he does not feel worthy - is rightfully cautious.
‘One possible way of manipulating an embryo’s genetics will be to use artificial chromosomes as an inert platform for modules of genes and their control elements. Adding artificial chromosomes to an embryo may sound like wild science fiction, but these structures already exist and may be safe and reliable within a few decades. Indeed, researchers have already passed rudimentary artificial chromosomes from generation to generation in mice, and maintained them in human tissue culture cells for a hundred divisions. Debate about the ethical implications of germline technology usually occurs without any reference to the specifics of the technology itself, but this is a mistake. The two realms are intimately linked. A common criticism of human germline manipulation, for instance, is that the procedure would be too dangerous because it would alter all subsequent generations. Researchers have already created mouse artificial chromosomes programmed not to pass to the next generation. With such a trick, modifications to an embryo would never unintentionally pass to distant future humans. Another technical device used by geneticists keeps inserted inserted mouse genes switched off until activated by an external chemical signal the researchers supply. Such technology could allow future children to decide whether to turn on genetic modules they received as embryos - a sort of retroactive consent for them. As the sophistication of germline technology grows, the nature of the ethical debate is bound to shift, but we need to give up the idea of reaching consensus in this area. It won’t happen. The issues touch us too deeply. Some will see these possibilities as the invasion of the inhuman and fight them with all their strength; others will see them as the flowering of human possibility and embrace them with open arms. It will take all our wisdom and tolerance to navigate these coming developments, but the question is almost certainly not whether human reproduction is going to shift dramatically in the next few generations, but rather how it will, what choices will confront us, and who will be making the decisions.’ Gregory Stock, Direct, Program on Medicine, Technology, and Society, UCLA’s School of Medicine, US
‘But flinging (so to speak) life’s gates too wide,/ Making a clear house of it too suddenly,/ The first conceit that entered might inscribe,/ Whatever it was minded on the wall/ So plainly at that vantage, as it were,/ (First come, first served) that nothing subsequent/ Attaineth to erase those fancy-scrawls…’ An Epistle Containing the Strange Medical Experience of Karshish, the Arab Physician, Robert Browning, 1812-89
To lay a hand on an existing poem
To lay a hand on an existing poem is a special trespass;
on the poem of a person - written by Nature, principles
of life; to interfere in the sacred, inviolable seal of body,
but for healing, sex - physical and mysterious emotional
exchanges of love; transmutation of beating red heart
into symbol you can touch, feel with your right hand.
Taking your trowel to the cathedral to effect repair,
separating bricks under crumbling edifice - moving,
mending, renovating; apprentice at the masterwork,
chiselling with a fantastic tool, modelled that year
among stones built of stardust, labours of millennia;
adaptation of given molecules over reaches of time -
incomprehensible to the huge mind thus manufactured -
become capable of such shining feats, inventive dangers;
planting in the brickwork, soft mortars, such bombs
that make flowers come; written seeds in the garden,
never intended to be weeds from where they came,
undisciplined, riotous, taking over all the sunshine.
‘Gene therapy is any medical procedure in which a disease is treated or cured by introducing DNA into the cells of the patient. Transfer of DNA is usually achieved either by mixing the DNA with a substance that enhances its uptake or by packaging it inside a disabled virus (a virus that can carry DNA into a cell but cannot cause a disease). Gene therapy may be carried out by first removing cells from the patient and then re-introducing those that have been appropriately modified. Alternatively, the direct introduction of DNA into the patient’s body may be the only effective strategy. There are several types of gene therapy:
Gene augmentation therapy - this is appropriate for the treatment of inherited disorders caused by the loss of a functional gene product. The aim is to add a functional copy of the lost gene back into the genome and express it at sufficient levels to replace the missing protein. It is only suitable if the pathogenic effects of the disease are reversible.
Gene inhibition therapy - this is suitable for the treatment of infectious diseases, cancer and inherited disorders caused by inappropriate gene activity. The aim is to introduce a gene whose product inhibits the expression of the pathogenic gene or interferes with the activity of its product.
Killing of specific cells -This is suitable for diseases such as cancer that can be cured by eliminating certain populations of cells. The aim is to express within such cells a suicide gene, whose product is toxic. One approach is the expression of an enzyme that converts a harmless prodrug into a highly toxic molecule. Another is the expression of a protein that makes the cells vulnerable to attack by the immune system. It is very important to ensure that suicide genes are appropriately targeted, otherwise the therapy would result in widespread cell death.
Somatic and germ line gene therapy - there is an important distinction between somatic gene therapy (DNA transfer to our normal body tissue) and germ line gene therapy (DNA transfer to cells that produce eggs or sperm). The distinction is that the results of any somatic gene therapy are restricted to the actual patient and are not passed on to his or her children. There are some arguments in favour of germ line gene therapy (for example, it would allow the correction of disease-causing mutations that are certain to be passed on) but many more arguments against. The principle objections are: the technology is imperfect. The effects of gene transfer are unpredictable and, even if the target disease was cured, further defects could be introduced into the embryo. Denial of human rights. Individuals resulting from germ line gene therapy would have no say in whether their genetic material should have been modified. Potential abuse - Germ line gene therapy could by used not only to eliminate disease, but also to enhance favourable characteristics and suppress unfavourable ones. On a small scale, this would result in a generation of ‘designer children’ with traits chosen by their parents. On a large scale, gene therapy could result in eugenics - manipulation of the genetic properties of a population.’ all Wellcome Trust
Gene Therapy
Introducing a nouveau dancer into the dance,
steps choreographed over four billion years -
but old revellers tripping over bunioned feet,
stumbling to life’s perpetual music; patterns
disturbed like the drunken Eightsome Reel
at Hogmanay when too many Englishmen
and any other rarer - more distant, exotic visitors,
create tumbling, laughing fray; Strip-the-Willow
turns shambolic, all bumping into one another,
faltering, linking arms with the wrong people;
or a handless man trying to string broken pearls
exploded on the floor - rolling in all directions –
she will slip elegantly in - linking her flexible
green arms; so pliant, well schooled in the art
of dance and conversation - for she was created so -
goes whirling as if practised over long centuries too.
Cells smell her, like dogs, uneasy, but she seems right -
yet something strange, like an animated warm replicant
who bleeds, beats, but has lost something vital in the eye -
though she mends the marked dance, heals squiffy patterns,
formations askew; spreading her influence, ballet skirts –
who is she, this beauty, skilled girl, young thing appearing
from nowhere like Cinderella - a mystery - beguiling, slick;
as long as she keeps on dancing, doesn’t sit down, suddenly
stick out her feet at awkward hockey-stick angles; at midnight
inexplicably flee - leaving a shattered slipper - broken ankles -
arms; shedding her magic gown, her natural-looking raiment,
showing her artificial bones, chemical Meccano construction;
the formation breaking down into a rickle of unglued molecules;
old smitten dancers falling down catastrophically, like dominoes.
‘More common diseases, such as cancers, diabetes and schizophrenia, involve complex interactions between faults in several genes and so are not so amenable to gene therapy. Furthermore, knocking out a faulty gene is not without risk - for example, the gene for sickle cell anaemia also gives some resistance to malaria. Nonetheless, recent successes for gene therapy in treating haemophilia and "bubble" children with Severe Combined Immunodeficiency means gene therapy research will continue.’ BBC Science
Interior, invisible genetic mending
Interior, invisible mending -
informing exterior garment;
coding new stitches, alterations
to life’s woven frame, her base.
What chaos to her embroidery,
contamination of her old art -
if one foreign needle pierces;
counter-stitches, re-patterns,
integrates threads
that go on linking,
spreading with viral nature,
webbed pictures – ladders -
gleaming spirals of DNA;
alien infiltrating Nature’s
tools and stories - unpredictable -
silently becoming something new.
‘Germline engineering - The most extreme suggested use for the human genome data is editing the DNA inheritance bequeathed from one generation to the next. Such a scenario involves identifying an abnormal gene and then correcting it in the cells which are used to pass genetic information to offspring - eggs and sperm. No subsequent generation would then be afflicted by their ancestors' gene defect. However, such irreversible tampering with the code for life will only be allowed after major ethical reservations and safety concerns over possible unexpected results of the changes, are addressed.’ BBC Science
‘Laboratory experiments suggest it may be possible one day to genetically alter human sperm cells to permanently eradicate genetic diseases. Japanese and US researchers managed to insert foreign DNA into zebrafish sperm cells - then successfully mature them into working sperm. Previous attempts have led to offspring with a mixed genetic identity. However, attempts to tinker with the human "germline" are considered fraught with danger by most scientists. This is because of the danger of inadvertantly introducing genetic problems which then persist from generation to generation. The UK's fertility watchdog says no-one has tried to do it here - there is likely to be strong opposition to any attempt. So far, gene therapy is restricted to treatments which try to insert new genes into adult human cells, rather than ones which attempt to correct the problem permanently by inserting them into germ cells. Fish breakthrough - The research team, from Fukui Prefectural University and the National Human Genome Institute in Bethesda, US, wrote up their experiment in the journal Proceedings of the National Academy of Sciences. They infected immature zebrafish germ cells with viruses designed to insert a particular gene. Afterwards, using combinations of laboratory solutions, they managed to induce these germ cells to mature into sperm themselves. More than 1,000 zebrafish eggs were then exposed to these modified sperm and 104 eggs were fertilised. Of these, only five of the 89 offspring carried the gene, but experts still believe that this is a significant advance. Dr Shawn Burgess, from the National Human Genome Institute, said: "To our knowledge this is the first time that sperm cells have been cultured entirely in vitro and used to produce a transgenic animal." No go area - Anyone in the UK who wants to use this kind of technology to prevent the birth of human babies with gene defects would have to seek approval from the Human Fertilisation and Embryology Authority. A spokesman for the authority said: "There's a huge path to cross before that happens. No-one has ever made such an application." At present, there would be stiff resistance from the scientific community if anyone wanted to do it. It is more likely that the research could assist the development of transgenic animals - perhaps which have been designed to mimic human diseases so that cures can be tested.’ BBC, 2004
Germline Engineering
Desecration; as gold Pharoahs’ tombs
are violated for information, treasure,
making kings paupers in the Egyptian afterlife -
surely interfering with the holiness of our script.
Editing the word of ourselves, long deified
in egg and sperm - re-making the principle
at root - casting our amateur spell
among old world magic; Nature’s
chemical mechanisms rehearsed
with the generous aid of deaths -
luxury of aeons; but aped in a decade.
The hand yet shovel, the eye a marble
lit from behind with harsh laboratory light -
predicting outcomes in blank, blind futures;
our flower made of glued white tissue paper,
compared to the breathing lily of the field -
yet what messages to be written into this future;
what bold carriages to send good fortune, luck -
vehicles and cargoes of letters to end suffering.
What Hosannas at the foot of such invention -
utilising of good tools; this manipulation
of the miraculous - what tales might be
re-written, what new children born and live,
spread; altered spores, changing everything.
‘Genetic engineers’ transfer genes from one organism to another – and, which is truly miraculous, the transferred genes may function perfectly in the new organism…the modern genetic engineer [however] can in principle take genes from any organism and put them into any other: fungal genes into plants, mouse genes into bacteria, human genes into sheep. Again we see that traditional breeders were bound by the restraints of biology, whereas modern genetic engineers are in theory bound only by the laws of physics, by their imagination, and by the laws and ethics of their societ… they can add just one gene at a time – or they take out individual genes, or take them out and alter them and put them back, or indeed (in principle) create quite new genes that have never existed before in nature. In evil hands such power could be ghoulish. Ethically directed, the potential for doing good is immense.’ Ian Wilmut, The Second Creation, Headline, 2001
‘Researchers at the National Human Genome Research Institute (NHGRI) may have taken a major step towards safer gene therapy for patients. In a report in this week's issue of Science, a research team from NHGRI's Division of Intramural Research demonstrates for the first time that the genetically engineered mouse virus used in gene therapy trials tends to insert itself at the beginning of genes in the target cell, potentially disrupting the genes' normal function…The discovery may lead to safer gene therapy techniques. Provided this new insight, researchers can now aim to improve the design of gene therapy techniques that can insert genes in less risky areas of the genome… In January 2003, the U.S. Food and Drug Administration (FDA) placed a "clinical hold" on 27 gene therapy studies after two children being treated by French researchers for a form of severe combined immunodeficiency disease developed a leukemia-like condition. Most current gene therapy experiments attempt to cure genetic illnesses by inserting normal, functional copies of a gene into target cells of the body. Researchers have learned to genetically engineer different types of viruses so they can infect target cells and integrate their genes into the chromosomes of those cells. Among the most widely used in gene therapy studies is the Moloney murine Leukemia Virus (MoMuLV), a mouse retrovirus that also can infect human cells. Physicians now believe that the children in the French study developed leukemia because the MoMuLV inserted therapeutic genes next to a gene known to promote blood cancer…Previously, researchers believed that MoMuLV randomly integrated into the genome of target cells. But scientists lacked the means to study these integration events in a large-scale fashion. "Now that a high-quality, finished copy of the human genome is available in public databases, it only takes the sequence of 30 base pairs to know exactly where you are in the genome," Dr. Burgess said. The scientists literally went to the computerized databases of the human genome sequence and looked it up in each case. "Without the success of the Human Genome Project, knowing precisely where the retroviruses inserted would have been nearly impossible," Dr. Collins said. "These are the kinds of laboratory applications for which the finished genome sequence was intended, applications that will end up improving the practice of medicine." Genome.gov, 2003
Go tiny ship
Go tiny ship, good messenger -
carry your living cargo into red,
rocking sea; among ancient scripts,
the dancing silver spirals - open up
your pages - let sick cells read
your revelation, healing words.
*
Manipulation, alteration - beneath
my hands the tools of life, pliable,
plasticine; no wonder I shake, tremble
the starry skeletons of my skin fingers.
I feel like an amateur god, learning
how to influence the future, safely
alter the world; starting, I well know,
with just one person - but one person,
remember, always alters the world.
Are they my responsibility, always,
the way saving a life in Accident and Emergency
affects the sequence of the whole planet forever -
or is progress impersonal,
nobody’s responsibility -
but a collective act, allowed
or disallowed; used, abused?
The authors of progress
are never morally free -
how can the inventor escape
his own creations, any more
than God can run away
from these wicked men;
the destroyers of Earth -
men of violence and war.
Not fault, but humble responsibility;
science is never free of moral force,
cannot operate among the stars -
black vacuums inspired by space;
motive matters in the planet court,
even if everything does go wrong.
There can be no glory without goodness -
desire to benefit, help, alleviate, aid, cure;
discovery is cold without a human heart
to feel, direct - inform practice of itself.
‘Unsurprisingly, and very properly, genetic engineering in its early days gave rise to debates at least as cogent and emotionally fraught as those that have surrounded Dolly. President Clinton called for a moratorium: the Nobel laureate Paul Berg, himself a pioneer of genetic engineering, called for one in the early 1970s.’ Ian Wilmut, The Second Creation, Headline, 2001
“Science advances by carefully weighing all of the evidence at her command. When a decision is not warranted by the facts, experience teaches that it is wise to suspend judgment, until the evidence can be put to further test." Thomas Hunt Morgan, Geneticist and Embryologist, 1866-1945
‘If sex selection of embryos is allowed, there will be no barrier to choosing embryos or terminating pregnancies according to whatever genetic tests are available, GeneWatch warned today in response to the Science and Technology Select Committee’s report on Human Reproductive Technologies and the Law. "Currently, making decisions about whether genetic tests on embryos are allowed is based on the implications for the future health of the baby. If people can chose the sex of their baby on purely social grounds, there can be no reason to deny people making other choices about the eye or hair colour of their babies if the tests become available", said Dr Sue Mayer, GeneWatch UK’s Director. "The Science and Technology Committee do not seem to have considered the inevitable consequences of their recommendations". Research conducted by the HFEA has shown widespread public disapproval of sex selection for other than serious medical reasons. GeneWatch has also provided evidence to the HFEA on the commercial influences behind sex selection and companies’ desire to introduce new technologies and increase the market." The Science and Technology Committee wants to treat babies as another variety of baked beans or washing powder. The public have already expressed their horror over sex selection and are unlikely to support MPs having more influence over such decisions if ‘babies as fashion accessories’ is their starting point", said Dr Mayer.’ Genewatch, 2005
What Kind of Frivolous Human Manipulation of the Genome
Imagine the mysterious, ornate, artful door of the gene;
like those Italian cathedral doors by artists everyone’s
heard of - being kicked in with great tackety boots, size 20,
by a flying squad who come not to heal, nor bomb disposal
to stop explosion of a gene - time travellers to prevent the future
suffering of a child - but hunting genes for a cow’s lick, slightly
thin lips, lumpy hips, donkey laugh, stubby fingers; or bearing gifts,
welding the ear for music, poetry - blow-torching the business brain,
hammering in intellect like an artificial limb, more brain-power zapped
through the molecule, alive, like a Frankenstein charge - imagine brain
cells fusing, the spirit rejecting fresh-grown transplant love - inflicted
beauty of the body, becoming fashionable flesh android, human plant,
as Michelangelo would not sculpt silicon boobs; absurd balloons
lurking under spherical skin - worse than the sock, banana down
the trousers - silicon growths where a woman’s gorgeous texture,
give, should be - erotic as a nylon wig to hair. Imagine six-packs
genetically implanted so every bloke can be dickless Action Man.
Imagine the Genome confused, the possible wonky consequences;
explaining to the brilliant child who’s also nuts - who looks model-
thin but cannot love pesto, chocolate, cakes and oil; makes millions
but cannot love Mozart, sunlight, who is champion of the world,
but cannot love. Imagine the children whose recipes go wrong -
the crash and burn of genetic meltdown; conflict of pleasure,
intellect, appearance, peace. Imagine the Genome confused,
when it’s taken four billion animated years of life, trial, death,
to get this much right, create this gorgeous body - sure, I don’t
like my knees, my nose 100%, but who the fuck cares - help,
everyone, we’ve gone mad, obsessed; appearance as dictator.
Nobody from the crappy-healthed past would believe we could
have defeated so much disease, starvation, premature death, but
squander our health and peace on such self-loathing, hatred
of our miraculous body; no sense of wonder, joy, gratitude -
a new survey says 98% of UK women hate their own bodies -
if that’s not a fucking sad statistic, then what is; symptomatic
of this quiet mutation of sexism to the tyranny of the thin body,
unnatural, unachieveable without starving, or fucked up eating.
Held up as example, goal - some bird who’s never eaten properly
for months, is seriously underweight, uneducated and boring, yet
praised for this feat. Let’s instead praise genomes that brought
us all out of the swamp, out of stardust, so shining in the world;
which built, sculpted us from every lifeform that ever was -