Cloning

CLONING STORY

‘The story of cloning is extraordinary, and it will change all our lives. It is hard to overstate its implications. Cliché has it that scientists who do extraordinary things must themselves be extraordinary, and indeed somewhat crazed. Doctors Frankenstien, Moreau and Strangelove are among the ‘weird sisters’ of literature…but scientists for the most part are not like that at all. They think extraordinary thoughts, and sometimes – this is the privilege of the job – they are able to turn those thoughts into reality….As the decades and centuries pass, the science of cloning and the technologies that may flow from it will affect all aspects of human life – the things that people can do, the way we live, and even, if we choose, the kinds of people we are. Those future technologies will offer our sucessors a degree of control over life’s processes that will come effectively to seem absolute. Until the birth of Dolly, scientists were apt to declare that this or that procedure would be ‘biologically impossible’ – but now that expression seems to have lost all meaning. In the 21st century and beyond, human ambition will be bound only by the laws of physis, the rules of logic, and our descendents’ own sense of right and wrong. Truly, Dollly has taken us into the age of biological control.’ Ian Wilmut, Keith Campbell, Colin Tudge, The Second Creation: The Age of Biological Control by the scientists who cloned Dolly, Headline, 2001

‘Regulating cloning and embryo stem cell research - The various approaches taken to regulate cloning and embryonic stem cell research mirror the ethical debates. Despite worldwide rejection of reproductive cloning, less that one-quarter of the world’s nations have formally banned it. However, no country explicitly allows reproductive cloning and regulation would probably be quickly introduced if the prospect arose. In relation to therapeutic cloning, some countries do not allow the creation of embryos for research (allowing only research on IVF embryos) or do not allowany research on embryos at all, and thereby implicitly do not allow the production of a cloned embryo. The most liberal nations, including the UK, allow experimentation on embryos up to a certain number of days, including both those created through IVF and through cloning or other artificial means…A whole range of animal species has now been cloned, including mice, sheep, cattle, pigs, goats, cats, rats and horses, and using nuclei from a variety of adult cells. The success rate is very low: there is less than a 5% chance of a live birth and a range of developmental abnormalities are seen including abnormal placental development, oversize at birth, and disorders of the muscles, skeleton, heart and lungs. However, offspring of cloned mice and cloned cattle conceived naturally appear to have been largely normal, suggesting that developmental problems seen in cloned animals do not arise through gene abnormalities, but because the mechanisms controlling foetal development are not operating properly.’ Genewatch, 2006

Replication

Replication; sexless reproduction.

Such Godly processes re-invoked

from the colossal to the micro -

exactly the same, whatever scale.

What is the new creature; replicant -

organic flame relit, chemical bundle

re-used, re-worked by life, breath -

but never the same; always altered

because death claims the orginal,

from where nothing returns again.

Clones are not the same being - mode

of mortal existence because everything

that lives is spectacularly unique;

from the first amoeba to last tiger,

Einstein to streetsweeper. Nothing

as creative as life can repeat works;

originality is a requisite of art – creation;

guiding principle of Evolution - re-using

her tools, materials, even from the first star;

but never repeating herself, for good reason.

‘Notably, the basic science has turned out to be much more complicated than I had forseen, and the research has far, far greater implications than most commentators seem to have realised. Most, for example, have homed in on the prospect of human cloning, but human cloning is really a side issue – and one that Wilmut and Campbell find distasteful…But the work poses a challenge for everybody; a test case. It is immensely important with ramifications that will affect all our lives in a dozen different ways. If the concept of democracy means anything, then it should imply that people at large understand the forces at work that change society. So everyone in a democracy ought to understand the research at Roslin – not just the cloning itself, but all that flows from it…’ Colin Tudge, The Second Creation, Headline, 2001

‘Thus we can trace the sciences that eventually enabled us to produce Dolly back to the 17th century, when modern science as a whole is generally acknowledged to have begun... mysticism began to fall away as they came to see living systems as explicable mechanisms, controlled in the end by the same laws that regulated the stars and planets… the 1970s produced some excellent advances but also noises off – including works of fiction – that muddied the waters; and then at the start of the 80s the waters were muddied again – not by noises off, but by events within science itself. One minute a scientist with an enviable reputation claimed vitually have solved the problem of mammalian cloning and the next, scientists of equal stature stated that such cloning is ‘impossible’…In 1980, no one could answer these questions. In the 1700s, when science itself was new, most subjects were in this precarious state. In the modern age, such deep uncertainty seemed rather strange …in the early 1980s no one knew for certain that mammals could be be cloned at all by nuclear transfer…All these ideas emerged during the 80s and early 90s, and they came as a series of revelations.’ Ian Wilmut, The Path to Dolly, The Second Creation: The Age of Biological Control, by the scientists who cloned Dolly, Headline 2001

‘Science moves, but slowly slowly, creeping on from point to point.’ Locksley Hall, Alfred, Lord Tennyson, 1809-92

‘The cloning of mammals, by simple nuclear transfer, is biologically impossible.’ David Solter and James McGrath, Developmental Biologists, 1984

Impossible stars

From the dark came impossible stars -

from their dust came impossible Earth;

from blackness, switched unlikely light -

metaphor, branch roots of good and evil.

From the sea came blood, green leaves;

from wings came angels, arms, fingers -

from the struggles of a worm came man;

impossible is an ancient, eroded concept.

‘We will require much of the rest of this book to describe the long and tortuous journey that has finally produced Dolly – a journey involving several generations of scientists through well over 100 years…The story may seem a bit messy –  but that’s because life is messy; and science is a slice of life.’ Ian Wilmut, The Second Creation, Headline, 2001

‘To use both ICM and TE cells as karyoplasts was a touch of class… Illmensee and Hoppe then selected just sixteen of the ICM devised morulae and blastocysts and tranfered them into the uteri of of five of the white Swiss mice… no fewer than three went to term and were born alive…That any of the reconstructed embryos came through at all was wonderful… But all was not so simple….Eventually yet another embryologist in the great German tradition, Davor Salter, together with his American colleague James McGrath, set out to repeat Illmensee and Hoppe’s 1981 experiemnt... their results were negative: so much so that they effectively ended Illmensee’s research career and severely dented the confidence of many other biologists who were seeking to clone mammals.’ Ian Wilmut and Keith Campbell, The Path to Dolly, The Second Creation, Headline, 2001

Three Cloned Mice

Five Swiss mice, five Swiss mice -

See how they sleep, see how they sleep,

They all had an embryo put inside,

And three had a baby born alive,

Did you ever seen such a thing in your life

As three cloned mice.

Three cloned mice, three cloned mice,

See how they run, see how they run,

They look quite the same as other mice,

And certainly identical to the mother mice,

Did you ever see such a thing in your life

As three Swiss clones.

Three Swiss clones, three Swiss clones,

See how white and bright, see how white and bright,

They ate some seeds and ended careers,

Instead of being miracles, admired by peers,

Did you ever hear such a thing in your life

As three wee miracle mice,

Three wee miracle mice, three wee miracle mice,

See the damage done, see the damage done,

They lived a life of controversy and strife,

Cut off Illmensee’s grants for the rest of his life,

Did you ever see such a thing in your life

As three unsung mice.

“But how had Illmensee and Hoppe apparently succeeded while McGrath and Solter failed with exactly the same procedure? … they could have got lucky. The University of Geneva appointed an international commission to investigate their work, which met in August 1983. The Committee did not conclude that [they] had fabricated results but they did criticise the way they had written them up and declared that their work should be repeated with ‘full scientitic rigour’ – which is, indeed, what McGrath and Solter did. Illmensee resigned from the university in July 1985 when his contract ran out… and now  works in Saltzburg in human IVF. Peter Hoppe was never directly criticised but retired nevertheless in 1985. Modern papers on cloning sometimes cite Illmensee’s work and sometimes do not. Many feel in their bones that his work is important, whatever the details; and so it surely is. The whole episode is a terrible pity in many different ways; and among them we may simply say, ‘What a waste of talent!’ Ian Wilmut and Keith Campbell,  Mammals Cloned, The Second Creation: The Age of Biological Control, by the scientists who cloned Dolly, Headline 2001

‘Finally, McGrath and Solter asked again whether their method of fusion – using Sendai virus – was at fault after all. So they set out to repeat Illmensee and Hoppe’s procedure to the letter… So at last [they]concluded: ‘ICM cell nuclei are unable to support development with enucleated zygotes’. These conclusions, they added, ‘contrast with the resutls of Illmensee and Hoppe’. Then [they] went on to make a statement that resounded through the world of developmental biology – although it has somewhat haunted them since: ‘the cloning of mamals, by simple nuclear transfer, is biologically impossible.’ Authority matters in science, although in principle it should not: and McGrath and Solter were, and are, authorities, and their words had impact. Yet they were clearly wrong…Within a few years of their all-too-gloomy asseveration other mammalian specieshad been cloned: sheep, cattle, goats. As Keith says, ‘Some things really are impossible, but others are merely difficult’.’ Ian Wilmut and Keith Campbell, Mammals Cloned , The Second Creation: The Age of Biological Control, by the scientists who cloned Dolly’, Headline 2001

Nobody better than these poor unsung scientists,

so ahead in their field they’d built a four-wheel

drive while others were still puzzling over wheels -

to understand Burns:‘The best laid schemes o’ mice

an’ men gang aft agley, an’ lea’e us nought but grief

an’ pain for promis’d joy!’ - What better poem could

be written for them; I hope they read its simple but

potent wisdom – some comfort among the cruelties

of science. I hope they kept their miraculous mice

as pets - evidence that one day, maybe even now -

can be genetically tested, the wee miracle mice

stuffed, mounted for the mantelpiece groaning

with retrospective awards - cards expressing regret

and admiration, respect, indebtedness; lots of offers

of prestigious posts, apologies from peers - for this

would be science’s poetic justice; some wrong that

could be righted, reputations resurrected, re-instated,

once more squeaky clean! How sweet the victory, so

long cultured in defeat, a dark Petri dish; cultivation

of such bitter taste, frustration, now tasting of honey.

‘…all the Cox’s orange trees there have ever been, going right back to the first one that grew from a pip in the 19th century, collectively form a clone. Many species of grass reproduce by runners or stolons (as well as by sexual seeds), and then an entire patch of sward may be a clone….thus elm trees clone themselves to form entire copses, and we cloned Dolly from cultured mammary gland cells.’ So what exactly is a clone?, Ian Wilmut, Keith Campbell, Colin Tudge, The Second Creation, Headline, 2001

In imitation of nature - twins presaging science,

natural clones who say their connection is more

than blood, same face; right to the thinking core,

they easily describe as connected spirit and soul.

Yet they are not one - but identical branches

from the same tree, as each apple eaten tastes

and looks the same, but is not the same fruit.

However the seed - each life is unrepeatable.

‘Indeed we should not see cloning as an isolated technology, single-mindedly directed at replication of livestock or of people. It is the third player in a trio of modern biotechnologies that have arisen since the early 1970s. Each of the three, taken alone, is striking; but taken together they take humanity into a new age – one as significant, as time will tell, as our forebears’ transition into the age of steam, or radio, or of nuclear power… genetic engineering… genomics… cloning.’ Ian Wilmut, The Second Creation, Headline, 2001

‘Both male and female adult frogs, fertile and normal in every respect, have been obtained from transplanted intestine nuclei.” John Gurdon, biologist

‘These cloned frogs might say: “Aye, but we’re always dead hungry, which you can’t see”.’ Gillian K Ferguson

‘The rate of development in mammalian cloning – from not knowing whether it was possible at all in the early 1980s, up to Megan and Morag, Dolly and Polly in the mid 1990s – is astonishing. There have been comparable bursts of speed in the history of science and technologies: penicillin was taken from a laboratory curiosity to an invaluable drug within a couple of decades, and NASA put a man on the Moon within 15 years or so of their first, modest, orbiting Earth satellite. In those cases, though, the scientists involved knew where they were going from the start and had a good idea of what they needed to achieve along the way. We who have followed the path of cloning… had very little idea from year to year what could actually be done. We have followed our noses. Along the way, too, there have been diversions and noises off: happnings of the kind that are rare in science, and have become causes celebres… the account is written with the twenty-twenty vision of hindsight. Much of the time in the brief history of modern cloning – from the 1970s to the 1990s – it was impossible for anyone, even those in the field, to know what was actually true, or what to make of all the conflicting information. Megan and Morag and Dolly would be extaordinary even if we had known each other from the outset what we were trying to achieve, and what was actually possible; the way things happened, with all the sidetracks and misconceptions makes them doubly remarkable. But then, perhaps their story is typical – for although science progresses it rarely proceeds in straight lines. Science is, after all, an attempt to explore the unknown. And if you venture into unknown territory, how can you avoid getting lost?’ Ian Wilmut, The Path to Dolly, The Second Creation: The Age of Biological Control, by the scientists who cloned Dolly, Headline 2001

Working on Cloning

We reached into unquantified darkness -

our pink hand-skeletons as two dim stars,

speckles among these brilliants -

original to Creation, spectacularly

accomplished; our begging bowl

extended to the Universe, rattling

small coins, sign about our necks

proclaiming our curiosity, needs -

were the haloes around our heads

still lit by our message of healing

as principle, first root of our searching;

would this motivation stay in control –

no wonder our hands hands trembled,

light blurred, indistinct as we stepped

through cloud, biological swamp,

stumbling; were we still shining?

‘…but the wonder is that it succeeds at all. This is yet another of nature’s serendipity…There seems to be no a priori  reason why nuclear transfer does work. We should not forget, though, that Spemann was right. That this work succeeds at all is ‘fantastical”.’ Ian Wilmut, Keith Campbell, Colin Tudge, The Second Creation, Headline, 2001

In imitation of Nature, a ripple of God

In imitation of Nature, a ripple of God -

blowing on novel seed with technology,

awakening their principles - a homage

to original art; our success part of first

magic - borrowing her processes, dynamic

touch across possibilities, mined darkness;

exhilerated, exulted still, at the thrill of life

felt by each leaf, worm - dancing molecule.