Dolly the Sheep

Virgin and Child, Enthroned, The Master of Moulins, 1499

The Cloning
of Dolly the Sheep

http://www.heaf.freeuk.com/dolly.htm

by David Heaf

Dolly the (white-face) clone
with her (black-face) surrogate mother

Now that 'Dollymania' has simmered down it is possible to take a cool look at what actually happened in the light of the scientific facts, free from the distortion and speculation engendered in the press.

Biotechnologists at the Roslin Institute and the 'farmaceutical' company it spawned, PPL Therapeutics, have been engaged in manipulating genes, germ cells (ova, sperm) and embryos in sheep and other species for several years. Their first major breakthrough was the production of Tracy, a ewe whose milk contains human alpha-1-antitrypsin,¹ a valuable protein which is currently undergoing clinical trial for possible future use in treating emphysema and cystic fibrosis. Roslin's next headline-grabbing announcement came in March 1996 with the 'cloning' of Megan and Morag, two identical lambs produced from embryonic cells grown in culture.² This had already fuelled speculation about human cloning, but in nowhere near as hysterical a fashion as occurred at the beginning of March this year. What was done in 1996 involved only germ and embryonic cells which one might expect would have all the potential needed to develop into adult sheep. So what was so special about Dolly? The answer is that almost all of her genetic material came from a somatic (non-sex) cell of her 'sister'.³

With this, the Roslin experiment overturned a long held view in biology that the somatic cells, which make up the rest of the body apart from the germ cells, are so differentiated or advanced in their development that they have irreversibly lost all potential to develop into a new adult organism. The revolutionary finding that this loss is reversible was achieved by taking mammary cells from the udder of Dolly's sister, a Finn Dorset ewe and culturing them in a nutrient broth or culture medium whose composition was then changed so as to force the cells into a quiescent or non-growing state. This step is believed to be crucial for inducing the genetic make-up of the cell to return to the state of full potentiality characteristic of embryo cells. Apart from that, the rest of the procedure was similar to the Megan and Morag experiment last year (see diagram). There remains a slight element of doubt however, as the Roslin scientists admit,² that would prove the breakthrough to be less dramatic than it at first appears. The mammary cell culture probably contained a few relatively undifferentiated stem cells which are more like those found in an embryo and would therefore have greater potential to develop into an adult.

In a parallel procedure a cell without a nucleus was produced from the ovum of quite a different sheep. This comprises a blob of jelly called the cytoplasm enclosed in the cell outer wall. To bring about the next step in the 'cloning' process this enucleate ovum was placed in contact with the mammary cell containing the donor nucleus. Fusion of the two cells was effected by electrical pulses which at the same time triggered the normal process of cell-division and growth which lead to embryo formation. After 'culturing' the embryo in the tied oviduct of a live sheep until it had formed a little ball of cells, it was placed in the womb of a 'surrogate mother' Scottish Blackface ewe and developed into the Finn Dorset lamb named 'Dolly'.

As an aside, it should be noted that the recourse that had to be made to mother nature's ways by incubating the embryo in an oviduct is mainly because what is known of the conditions necessary for sheep embryo culture lags far behind that of human or mouse. Work is in progress to replace this step with in vitro ('test tube') culture, and one would expect it to be only a matter of time until this is perfected.

The vigilant reader might be wondering why the word 'cloning' is in commas. This is because strictly speaking the process is not cloning. Cloning involves reproducing the cloned organism in such a way that the entire genome, the totality of genes, is faithfully copied each time. To clone potato plants simply place a tuber in the ground at the right time of year and wait for the result. In the case of Dolly, however, about 70,000 genes came via the nucleus of her Finn Dorset sister and some 20 came via the cytoplasm of the Scottish Blackface ovum. This is because in the cytoplasm are sub-cellular particles called mitochondria which help drive the energy-requiring processes of the cell. The genes in the mitochondria are essential to it and it is in a large part due to the presence of these mitochondria that the artificial cell construct resulting from the electro-fusion had any vitality at all and could develop into an adult sheep.

Strictly speaking, therefore, we are talking about a 'partial cloning', and that already dampens some of the fuel for speculation. Although the Roslin team has reported to a parliamentary committee that the technique is in principle applicable to humans, existing differences in its applicability between species cast doubt on whether it would work in practice in its present form. Even so, the announcement in March of the successful cloning in Oregon of two monkeys justifies taking the human cloning issue very seriously.

Before taking a look at human cloning let us first consider the implications of the technique in animal breeding. The Megan, Morag and Dolly breakthroughs demonstrate that mammalian cells in culture can be used to construct adults. This means that a whole range of in vitro genetic modifications, hitherto only possible for mice, can now be carried out on sheep. For the biotechnologists involved the technique will greatly ease the creation of the transgenic flock founder animals such as Tracy. Commentators also see it as extending the range of possibilities for making new animal models for human diseases, especially genetic diseases, and for producing animals for use in xenotransplantation. Whether the technique will in the long run be transferrable to farm animal breeding in general will depend upon a number of factors not the least of which is the cost of the method. If it is eventually used some safeguards of livestock genetic diversity would need to be introduced. The ordinary process of sexual reproduction has a built-in capacity to maximise variability through the exchange of genetic material, but cloning is a genetic cul-de-sac. However, it is argued that the fact that the cells used for cloning can be stored frozen in liquid nitrogen makes it possible to conserve biodiversity, including rare breeds, in quite a new way. However, because current success rates are very low, as we shall see, it is unlikely that cloning will find its way into farm livestock breeding for a couple of decades. Even then, as a sheep farmer friend put it, 'it will take all the fun out of farming.'

What is it like for the animals? To form proper moral judgements about this new technology it would help if we knew all the details, including those concerning animal welfare. Most of the procedures carried out on the sheep are very similar to those involved in 'test tube baby' manufacture with the difference that the sheep do not give informed consent. Harvesting ova from the Scottish Blackface involved prior injection of the ewe with hormones followed by intrauterine laparoscopy. The Finn Dorset mammary cells were removed in a process which involved dissection and killing the ewe. A third intact sheep was needed for culturing the reconstructed cell at the start of embryo development. This involved two separate surgical interventions, the second of which, because of the Animals (Scientific Procedures) Act 1986, on completion necessitated slaughtering the ewe. The fourth and final 'parent' of Dolly was her surrogate mother, who unlike many of the other sheep in these experiments, did not have to undergo a caesarian section. This operation is often necessitated by the excessively long duration of gestation and the abnormally high weight at term of the lambs generated by this cell fusion method of reproduction.^2,3 Making Dolly required 277 electro-fusions, 247 oviduct-cultured embryos and 29 embryos transferred into 13 ewe's wombs.³ Confronted by these figures, we can marvel at the patience of the biotechnologists who did the work yet at the same time be struck by how much death was needed to purchase a small amount of life.

It is too early to make any general statement about the health and behaviour of sheep made in the way Dolly was, but the dozens of published photographs certainly testify to her sheepishness. Surprisingly, lamb losses from pregnancies in this year's experiment were not dramatically different from those of a normal commercial flock. The transgenic flock to which Tracy belonged has been the subject of a detailed behavioural study and the sheep were said to be perfectly normal.⁴ Furthermore, at the time of writing this article, Megan and Morag are both pregnant.

It is clear therefore that this rather laborious reproductive process is still determined by the sheep archetype in Goethe's & Steiner's sense,⁵ albeit with no small amount of suffering to the sheep. What then is the ethical position? Firstly, have the sheep been respected 'in themselves'? Here we are concerned with the deontological ethical position which gives moral value to the telos or essence of sheepness. It seems pretty clear that in terms of our normal understanding of the nature of sheep, i.e. freely roaming the hillsides and occasionally being rounded up for procedures ranging from shearing to slaughter, the sheep telos is violated. So we must fall back on a utilitarian or consequentialist ethical position.

But can inflicting the additional suffering of biotechnological procedures on sheep be justified in terms of the consequences, for instance, its giving rise to a new drug for treating a life-threatening human illness? The usefulness of the Megan, Morag and Dolly clonings is still somewhat academic. The main emphasis is that the ease of manipulating the starter cultures will allow all kinds of in vitro genetic manipulations to be carried out relatively easily and inexpensively. In the concrete case of Tracy, our society has answered this in the affirmative. So too did an Ifgene public ethical analysis event held at Edinburgh International Science Festival in March,⁶ and a report on this issue by the Church of Scotland Society, Religion and Technology Project in which some of the key Roslin biotechnologists cooperate.⁷ But this project and other views on biotechnology by representatives of the Church base their moral judgements on the Old Testament principle of dominion,⁸ perhaps tempered with an element of stewardship.⁹ Other approaches are possible, for instance partnership with nature, in which nature is regarded as having intrinsic worth and may only be exploited if, in Kockelkoren's words, 'it does not involve unnatural forcing of the life forms involved".¹⁰ The difficulty of this proviso lies in the old argument that man is part of nature, so nothing man does is unnatural.¹¹ At the other pole from dominion comes 'participation' where humanity strives to respect the needs of other life forms, a stance vis a vis nature into which Kockelkoren places the biodynamic agriculture initiated by Rudolf Steiner.¹⁰ How one answers the question posed at the beginning of this paragraph very much depends, therefore, on where in the spectrum of world views one places oneself. Once a biotechnologist or scientist admits to having a world view, then it follows that he must relinquish any claim that his findings are based solely on value-free facts. Indeed, what goes on in the laboratory is shaped by that world view. Dolly is thus not so much a revelation of scientific truth as a construct of the society which produced her. In it, the dominant paradigm is one of materialistic determinism, matter - the genes - reigns supreme. We return to what motivates the biotechnologists later.

A full and open public engagement with such issues in a way that would have consequences for legislation has never taken place in Britain. Over the 20 years since modern biotechnology began, the ethical concerns it has raised have been dealt with on the basis of ad hoc committees or through existing, more general legislation. The result has been an increasing call for ethics before the fact rather than after it. Otherwise, the 'slippery slope' approach might bring us to the brink of the almost unthinkable: cloning humans, for instance. Did our society ask those at Roslin to clone a sheep? It seems so, because Dolly's genesis was funded by a grant from our government, a fact that came to public attention in the somewhat ironic circumstances of the announcement of its withdrawal shortly after the cloning story broke. Whilst Tracy seems to serve the laudable purpose of relieving human suffering, Dolly seems pure Machbarkeitswahn, 'can do, must do' mania. Even with Tracy, as the MD of the company that owns her was forced to admit at the Ifgene meeting, it would be far better if the pharmaceutical she produces were to be made in microorganisms, as is indeed technically possible.

I turn now to anthroposophical perspectives on this technology and take a lead from a conversation between Rudolf Steiner and Ehrenfried Pfeiffer, one of the founder members of the Natural Science Section of The School of Spiritual Science in Dornach and a prime mover in the spread of the biodynamic movement in the USA. Whether tinkering with life is on the continuum which leads to a technology based on the 'etheric formative forces'¹² which Steiner spoke about with Pfeiffer¹³ is a debatable point especially as the Roslin work is based on a combination of physical micro-manipulation, chemical nourishment and electrical pulses. However, it is worth noting that Pfeiffer was warned by Steiner¹³ of the grave consequences for humanity if the forces he was pointing to were developed before the people controlling them had adequately developed their moral capacities and before a large part of the world had established the threefold social order.¹⁴ Indeed Steiner attributes the gradual decline and eventual destruction of the Atlantean civilisation to misuse of natural forces:

"The men of that time still had the faculty to place at their own disposal the forces of growth and reproduction in animal and human nature... Now the forces of growth and reproduction, when torn from their mother soil, stand in a mysterious relationship to certain forces that work in air and water. Mighty and ominous powers of nature were thus let loose by the deeds of men, leading eventually to the destruction of the whole territory of Atlantis by catastrophes of air and water."¹⁵

A more concrete link to the necessity for moral development for the safe use of these forces can be found in Steiner's more detailed account of the soul and social conditions which prevailed in the Atlantean civilisation in Cosmic Memory:

"The development of memory had led to a super-abundant force of personality; man came to crave esteem for the mere sake of his inordinate power. Indeed the greater the abundance of power at his command, the more inclined he was to use it for his own gratification, and the pride which now developed soon revealed itself in the quality of pronounced ambition. Abuse of power had set in. If we consider all that the Atlanteans were capable of accomplishing by reason of their power over the life-force,¹⁶ it will be easy to see how disastrous the results of such abuses were bound to be."¹⁷

In case all this seems a little fantastic, we should bear in mind that in 1923 Steiner explicitly forecast that mad cow disease would arise if animals were fed to animals.¹⁸

So far as abuse of power is concerned, it is interesting that biotechnology is raising at least as much hoo-ha in the social sphere of rights as it seems to be doing in the cultural-spiritual-moral sphere. Some of the most vehement campaigning by opponents of the technology is focused on the intellectual property rights conferred by patents. 'No patents on life!' is a cry from what must surely be described as an intuitive sense that there is something wrong about this. Extremely powerful forces are at work, involving an unhealthy influence from the economic sphere, in the form of multinational companies, on the sphere of rights represented by the regulators. No conspiracy theory this, since one only has to look, for instance, at the make up of our regulatory committees. With the way smoothed by patents on life, the effect could be to put control of a new technology, which many say will eventually have far greater impact on civilisation than does nuclear technology, in the hands of a relatively small number of people. The patents issue, however, is a complex one and the reader who wishes to go more deeply into it may find a helpful starting point in a recent issue of the Bulletin of Medical Ethics which contains several articles from widely divergent points of view including that of the anthroposophist and patent attorney, Reinhold Salgo.¹⁹ Perhaps one can take heart from the fact that the populations of some countries are not entirely asleep to the implications of patenting life forms. As this article was being written the people of Austria voted against it in one of their biggest referenda polls of all time.

Now we come to a more speculative aspect of the technology heralded by Dolly, namely cloning human beings. Let us be perfectly clear that nature already clones human beings in the truest sense of the word 'clone', at least so far as their physical make-up is concerned. Human identical (mono-zygotic) twinning, tripleting etc which occurs at the very early stages of embryo formation after fertilisation of the ovum is nature's cloning. The resulting siblings are truer physical copies of each other than Dolly was of her 'sister'. During March it was announced from a fertility clinic in Belgium that doctors had 'accidentally' triggered a natural twinning reaction by rubbing the surface of a fertilised human ovum with a glass rod. This apparently thinned the cell wall allowing the subsequent formation of two embryos and the eventual birth of two boys.²⁰ Now, human in vitro fertilisation, implantation and pregnancy has a very low success rate which can be very distressing for the couples involved. What could possibly be wrong with using this in vitro twinning technique, if indeed it is reproducible, to improve the take-home baby rate for infertile couples? I suspect that the answer to this question which has a strong consequentialist (instrumental) ethical slant can only be found through examining the whole in vitro fertilisation (IVF) issue itself, a task which would lead us too far away from our topic.

What is human cloning in reality? Is it in principle the same as in sheep or something quite different? I would come down in favour of the latter option and to see why, we need to look at the make up of the human being versus the sheep. Long before Rudolf Steiner began to write about anthroposophy, i.e. shortly after the turn of the century, he wrote a philosophical work called Theory of knowledge implicit in Goethe's world conception.⁵ The importance he attached to this early work can be seen from the fact that it, together with his Philosophy of Freedom¹⁹ could form the basis for a path of esoteric training,²² a path which he admitted many would find too hard. In the 'Theory' he clearly distinguishes what is necessary for the cognition of organic nature from that of human nature. We have grasped the essence of 'sheepness' when we have grasped the archetype. But for humanity we must concern ourselves with the 'human individual in general...The spiritual being of man is not one formation of its Idea', but the formation thereof.'²³ In man we have to deal with the individuality, (self, I or ego) which is in a certain sense equivalent to a whole species so far as sheep are concerned.²⁴ Cloning a human being brings in a new factor, and therewith indeed a new level of moral consideration which many people must already sense intuitively if the widely voiced repugnance at the idea of cloning humans is anything to go by.

At the physical level, aside from the Belgian twins example, artificial in vitro human cloning has already taken place. The most famous example is the HeLa cell line, which came from a virulent cervical cancer specimen taken in 1951 from Henrietta Lack and which has been cultured over the decades in thousands of laboratories throughout the world.²⁵ Where no spontaneous mutations have set in these, cells preserve living copies of the genome of the patient. Many human cell lines are cultivated in this way, thus creating a kind of immortality for the human being concerned. This practice continues almost unchallenged. Not so the short lived cloning of human embryos which took place in the USA in 1993. Jerry Hall and Robert Stillman of George Washington University Medical Center caused public outrage when they created identical twins and triplets from embryos which were later destroyed.²⁰ But in the UK, although using human cells for the type of procedure which made Dolly is not expressly forbidden by law, the Human Fertilisation and Embryology Authority (HFEA) would be unlikely to approve it at present. However, Ruth Deech, the HFEA director argues that there should not be an absolute ban on human cloning.²⁶ Indeed, many people argue that it might one day be used to mankind's benefit, both medical and social. If it were possible to grow organs from cloned cell lines these could be used in transplantation without the risk of immune rejection. People have even suggested it might justifiably be used to help childless couples or even to recreate a child who has died. Neither of these suggestions nor any of the more bizarre ideas is designed to benefit the individual who is cloned. They become a victim of other people's selfishness.

The shortage of eggs for routine human IVF work would rule out, for the foreseeable future, using the Dolly technique, which was, as we have seen, highly wasteful of eggs. The fact that women are paid to donate ova shows that they are in short supply. Even if it were applied to humans, there would be no need for recourse to explanations based on the incarnating individuality or the fact that Dolly was only a partial cloning to see that a whole host of nurture factors come into play from the moment of cell fusion, if not before. One has to consider the entire development and education of the individual through to adulthood. When one ponders the potential for variability due simply to external influences, especially as the size of safe pregnancy is limited to twinning or at most triplets, the whole absurdity of speculation about creating replica human beings becomes apparent.

Even so, if human cloning were to continue to creep in by degrees, as seems to be the case at present, some consideration should be given to the consequences for the incarnating individual. This is a whole research project in itself and only brief indications can be given here. Wirz distinguishes two contrasting arguments: either the spirit is supreme and can make use without restriction of the physical basis of its existence, namely the cloned or partially cloned body, or, the individuality cannot incarnate or cannot do so properly because in the production of that body essential preconditions are not fulfilled.²⁷ Certainly there are people who experience being out of place in the bodily or family circumstances in which they find themselves. However, we all to some extent experience resistance to incarnating. No longer does the human being simply gather round itself the substance necessary for earthly life, but, according to Steiner, it has to work with a model provided by the stream of heredity.²⁸ We have to transform the model and shape it to our needs, thus genetic determinism is met by quite another force, one originating from the individuality. This individuality adapts its model to a greater or lesser degree according to need. The process of physical development and renewal means that after several years, little if anything is left of the original substance. One only has to think of the dramatic change which includes the change of teeth and the childhood illnesses which are witness to the struggle which takes place. People stamp their individuality on their physiognomy to a greater or lesser degree in spite of their genes.

Returning now to what motivates the cloners, we can gain some insight into the wider connections of this, as well as some helpful indications about the replication of form which will not be discussed here, from Rudolf Steiner's lecture in Dornach on 4th October 1918. There he describes two definite aspects of the adversarial forces: firstly the Lucifer-inspired dreams of making the world happy through universal adoption of particular ideas and secondly the Ahriman-inspired dreams of world domination by a particular realm of human endeavour. Of course, we are not suggesting that the Roslin biotechnologists dream these dreams, at least not consciously, but it is not difficult to discern in the foregoing that they are at work in society. And this brings me to my closing question: if anthroposophists want to engage with the issues facing society outlined in this article, what are they to do? As well as replying, in the sense of the Philosophy of Freedom,²¹ that it is up to the moral intuition and imagination of every individual to decide for themselves, we can add that there are possibilities worth considering for joint action.

One is the ongoing project called Ifgene, the International Forum for Genetic Engineering which is a initiative of the Science Section of the School of Spiritual Science in Dornach.²⁹ This seeks to deepen and broaden the public debate on biotechnology in a non-partisan way, that is by creating the conditions of a genuine forum for the meeting of different points of view leading to a firmer basis for judgement-forming.

The other is a project already mentioned above which the wider anthroposophical movement has at most started but which Steiner emphasised was essential for the future of humanity: "Humanity will have no say in matters if it cannot arrange its social organism in a threefold way. This is what will have to be regarded as the only healing, the true salvation of humanity."³⁰

Rudolf Steiner saw the need for the involvement of 'not hundreds, not thousands, but tens of thousands of individuals'³¹ if the threefolding project were to be realistically put into action even if only in the central Europe of his day. But turning to Pfeiffer's autobiography we come upon a note of regret: "...we live today in a world which is further away than ever from the solution of the social problem, where selfishness and personal advantage, profit and, because of these, national conflicts have the upper hand... the Anthroposophical Society has never put the solution of the social question at the forefront of its aims and has not acheived what was asked of it Rudolf Steiner."¹³ ('Translated' by DJH, please see note 13 for original English version)

If there is indeed a deep connection between the safe unfolding of biotechnology and the working out of a threefold social order, then in view of the potential power of biotechnology, might not the threefolding project be the project for the Anthroposophical Society to put the full weight of its resources behind as we approach the millennium?

1. Carver, A. S. et al. (1993) Transgenic livestock as bioreactors. Bio/technology 11, 1263-1270.

2. Campbell, K. H. S. et al. (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64-66.

3. Wilmut, I. (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810-13.

4. Hughes, B. O. et al. (1996) Behavioural comparison of transgenic and control sheep. Animal Science 63, 91-101.

5. Steiner, R. (1886) Theory of knowledge implicit in Goethe's world conception. (GA 2) Trans. O. D. Wannamaker. Anthroposophic Press, 1968.

6. Mepham, B. (1997) Ethical analysis in genetic engineering: A report on two public workshops at EISF, 27th March 1997. Available from Ifgene UK.

7. Bruce, D. M. (1997) Cloning - a step too far. Church of Scotland: Society, Religion & Technology Project. Orders: 45 High St, Edinburgh, EH1 1SR.

10. Kockelkoren, P. in 'Agriculture and Spirituality', International Books, ISBN 90 6224 980 9.

12. Steiner, R. (1922) Theosophy. (GA 9) Rudolf Steiner Press, Trans. Cotterell & Shepherd, 1965, p.25ff & Addenda

13. Pfeiffer, E. Autobiography, (unpublished) "...we live today in a world which is farer away than ever from the solution of the social problem, when selfishness and personal advantage, profit and national conflicts because of them have the upper hand, since especially the anthroposophical society has never put the solution of the social problem in front of all its aim and not contributed that w[h]ich was demanded by R. St. to be done[.]" (With permission, Perseus Verlag, Basel)

14. Steiner, R. (1919) Towards Social Renewal. (GA 23) Trans. F. T. Smith, Rudolf Steiner Press, 1977.

15. Steiner, R. (1925) Occult science - an outline. (GA 13) Trans. G & M. Adams, Rudolf Steiner Press, 1963, p.198.

16. The complete distinction of the 'life-force' from anything which belongs to the rightly discredited theories of vitalism can be found in reference 12.

17. Steiner, R. (1904-1908) Cosmic memory. (GA 11). Harper & Row, Trans. K.E.Zimmer, Ch.2, 1981

18. Steiner, R. (1923) Health and Illness 2, lecture on January 13th. (GA 348). Trans. M. St Goar, Anthroposophic Press.

20. Rogers, L. (1997) Revealed: doctors accidentally clone twins. The Sunday Times, 9th March.

21. Steiner, R. (1894) Philosophy of Freedom. (GA 4) Trans. R. Stebbing, Rudolf Steiner Press, 1988

22. Steiner, R. (1920) The boundaries of natural science. (GA 322) Lecture VII, October 2, Dornach. Trans. Amrine, F. & Oberhuber, K., Anthroposophic Press, 1983.

27. Wirz, J. (1997) Unheimliche Allianz - Dolly das klonierte Schaf. Das Goetheanum - Wochenschrift für Anthroposophie, 16th March.

28. Steiner, R. (1924) Karmic relationships I (GA 235), Lecture 1st March, Dornach.

29. Ifgene UK coordinator: Dr D. J.Heaf, Hafan, Cae Llwyd, Llanystumdwy, Cricieth, Gwynedd, LL52 0SG. Tel/Fax 01766 523181. Email: 101622.2773 (at) Compuserve.Com

30. Steiner, R. (1919) Education as a Social Question, (GA 296) Spring Valley, Anthroposophic Press 1969, lecture of 9 August, Dornach.

Acknowledgements I wish to thank Jane Fennell, Christoph Podak, Margaret Jonas and Thomas Meyer for their help with the research for this article and Pat Cheney for her careful scrutiny of the manuscript. This article was first published in New View (3^rd Quarter 1997, Issue 4, pp26-29).


Arrows show a titanium cage, in which patient’s new jaw was grown, implanted under his shoulder blade.	CT scan shows jaw in place. The jaw has shown continued bone growth after the transplant. Patient ate bread and sausages in hospital.

BACKGROUND: A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient.

METHODS: Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 ml of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect.

FINDINGS: In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure.

INTERPRETATION: Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

CNN article. LONDON, England (AP) -- A German who had his lower jaw cut out because of cancer has enjoyed his first meal in nine years -- a bratwurst sandwich -- after surgeons grew a new jaw bone in his back muscle and transplanted it to his mouth in what experts call an “ambitious’’ experiment. [

Growth and transplantation of a custom vascularised bone graft in a man P H Warnke, I N G Springer, J Wiltfang, Y Acil, H Eufinger, M Wehmöller, P A J Russo, H Bolte, E Sherry, E Behrens, H Terheyden Lancet, Volume 364 Issue 9436 Page 766

According to this week’s issue of The Lancet medical journal, the German doctors used a mesh cage, a growth chemical and the patient’s own bone marrow, containing stem cells, to create a new jaw bone that fit exactly into the gap left by the cancer surgery.

Tests have not been done yet to verify whether the bone was created by the blank-slate stem cells and it is too early to tell whether the jaw will function normally in the long term.

But the operation is the first published report of a whole bone being engineered and incubated inside a patient’s body and transplanted.

Stem cells are the master cells of the body that go on to become every tissue in the body. They are a hot area of research with scientists trying to find ways to prompt them to make desired tissues, and perhaps organs.

But while researchers debate whether the technique resulted in a scientific advance involving stem cells, the operation has achieved its purpose and changed a life, said Stan Gronthos, a stem cell expert at the Institute of Medical and Veterinary Science in Adelaide, Australia.

“A patient who had previously lost his mandible (lower jaw) through the result of a destructive tumor can now sit down and chew his first solid meals in nine years ... resulting in an improved quality of life,’’ said Gronthos, who was not connected with the experiment.

The operation was done by Dr. Patrick Warnke, a reconstructive facial surgeon at the University of Kiel in Germany. The patient, a 56-year-old man, had his lower jaw and half his tongue cut out almost a decade ago after getting mouth cancer. Since then, he had only been able to slurp soft food or soup from a spoon.

In similar cases, doctors can sometimes replace a lost jawbone by cutting out a piece of bone from the lower leg or from the hip and chiseling it to fit into the mouth.

This patient could not have that procedure because he was taking a potent blood thinner for another condition and doctors considered it too dangerous to harvest bone from elsewhere in his body since extraction leaves a hole where the bone is taken, creating an extra risk of bleeding.

Artificial jaws made from plastic or other materials are not used because they pose too much of a risk of infection.

“He demanded reconstruction,’’ Warnke said. “This patient was really sick of living.’’

Warnke and his group began by creating a virtual jaw on a computer, after making a three-dimensional scan of the patient’s mouth.

The information was used to create a thin titanium micro-mesh cage. Several cow-derived pure bone mineral blocks the size of sugar lumps where then put inside the structure, along with a human growth factor that builds bone and a large squirt of blood extracted from the man’s bone marrow, which contains stem cells.

The surgeons then implanted the mesh cage and its contents into the muscle below the patient’s right shoulder blade. He was given no drugs, other than routine antibiotics to prevent infection from the surgery.

The implant was left in for seven weeks, when scans showed new bone formation. It was removed about eight weeks ago, along with some surrounding muscle and blood vessels, put in the man’s mouth and connected to the blood vessels in his neck.

Four weeks after the operation, the man ate a German sausage sandwich, his first real meal in nine years. He eats steak now, but complains to his doctor that because he has no teeth he has to cut it into such small pieces that by the time he gets to the end of the steak, it’s cold.

He has reported no pain or any other difficulties associated with the transplant, Warnke said, adding that he hopes to be able to remove the mesh and implant teeth in the new jaw about a year from now.

Paul Brown, head of the Center for Tissue Regeneration Science at University College in London, said it’s not clear any major scientific ground has been broken, and tests may not be able to show whether the new bone came from stem cells, rather than from the growth factor alone.

The operation put established techniques together, resembling a well-known experiment in which University of Massachusetts scientists grew a human ear using a mold on the back of a mouse in 1995, he said.

“If you put loads of blocks of bone mineral into a hole and you induce cellular activity by putting in growth factors, it’s a standard approach that people have used to induce the body’s own response,’’ said Brown, who was not connected with the study. “Clearly some of them are going to work and it sounds like for this patient, this has worked.’’

Biopsies of the jaw bone could later provide some answers on the quality of the bone, experts said.

“Just making the gross tissue shape right isn’t really the problem,’’ Brown said. “It’s what the shape of the tissue is at the microscopic and ultramicroscopic level. That’s the architecture which is so tricky and which is what gives function.’’

BACKGROUND: A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient. METHODS: Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 mL of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect. FINDINGS: In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure. INTERPRETATION: Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

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