that'these elements had more mean­ It was interesting to note that through­ how important ethical thinking will ing than the concepts of 'full disclo­ out the workshop, the particip.ants become, as economic stringencies in­ sure',' competence' and' fully autono­ had used three different 1?tructures for creasingly influence medical practice. mous choice'. examining ethical problems - princi­ It delineated some of the matters pe­ ple-based ethics, virtue ethics find culiar to the discipline of surgery, and · Clinical freedoms and innovation rights and duties. This was perhaps reinforced the College's wisdom in en­ were the subject of some vigorous dis­ not made quite explicit, and some for­ tering the ethical field so publicly. The cussion. In the context of rationing, mal presentation of structures that can workshop concluded with the hope there was some division of feeling be used for ethical thinking might well that the College would continue to about the conflicting needs to collabo­ be incorporated in future workshops expand its ·ethical activities and its li­ rate with management and the duty of this kind. aison with the various centres for eth­ to continue to act as advocates for pa­ ics and bioethics. tients: The conflict between economic In,.summary, this excellent workshop exigency and best practice remains un­ achieved several_ things. It made sur­ Dr Hall and her colleagues deserve resolved, but there was general agree­ geons more aware of the essentially our thanks for both the excellence of ment that this conflict is now a real aporetic nature of moral thinking, and the organis_ation of the meeting and its part of every day practice, and that the of the complex interrelationships it has content. mor~l issues are still not fully defiRed. with the law. It emphasised strongly

The Cloning of Dolly: Heral~:i~g the New F_utur~ ~f Biology? Mark Fisher Senior Scientist, AgResearch, Invermay Agricultural Centre, Mosgiel

he creation _of Dolly, the sheep pected to develop into adult frogs. Forms of embryo cloning T cloned from the mammary cells Similarly, in 1996 researchers in Scot­ of her 'mother', as heralded much in­ land reported that they had cloned The cells of the early embryo are con­ ternational interest. But what is clon­ sheep from an embryo cell line. This sidered to be undifferentiated. This •ing, and why has it generated so much has been repeated for the second time means any cell has the potential to interest? The terminology was first only in New Zealand this year by the grow into a bone cell, or a brain cell, coined at the beginning of this century, Molecular Embryology staff at or a liver cell, etc. However, once dif­ and the technique itself, at least in AgResearch Ruakura. This year the ferentiated, it's generally accepted that horticulture, has been with us for a Scottish group of researchers re­ a bone cell cannot grow into a liver long time. Its botanical use refers to ported that they had cloned Dolly, cell, nor can a brain celrgrow into an the propagation of plants carried out from the DNA contained in the mam­ ear cell. It is this feature which gives by using grafts, cuttings and bulbs, mary cells of Dolly's 'mother'. Hu­ rise to the different forms of cloning. and more recently tissue cultures etc. man embryos were also apparently In embryonic cloning, the undif­ For instance, advances in the technol­ cloned in .1993. They were provided ferentiated embryo can either be bi­ ogy of radiata pine propagation are by an infertility clinic and were de­ sected fo form two identical embryos enabling the development of clonal fective and due to be discarded. The or the cells can be s.eparated and indi­ forestry in New Zealand. But its wider cells of the embryos were separated vidual or small groups of cells, al­ use in biology refers to the asexual re­ and a few individual cells developed lowed to multiply, growing into many production of organisms that nor­ into 32-cell embryos. copies. mally reproduce sexually. Identical twins are in a sense clones, Alternatively, the technique of nuclear· What this means is that the genes or since they share the same genetic ma­ transfer can be used. Here, the nucleus DNA from one organism are copied terial. Identical twins may in fact re­ of each of the cells, containing exact ,and a new organism - a genetic rep­ semble each other more closely than replicas of the DNA or genetic mate- lica - created from it. Like many things clones since, unlike Dolly and her . rial of the original embryo, say a sheep in science that grab the public imagi­ 'mother', identical twins develop from embryo, is then transferred into sur­ nation, cloning is not new. In 1.952 re­ eggs with similar cytoplasmic con­ rogate unfertilised egg cells from searchers took an embryo from a frog stituents, they share the same uterine which the nucleus has been removed and cloned it creating an exact copy environment and they may share simi­ (wfole th~ recipient egg is enucleated, of the original frog.· In the 1980s they lar environments after birth. In con­ the. mitochondria in the cytoplasm still took a red blood cell from a frog, cop­ trast, Dolly and her 'mother' devel­ contains their own DNA). These are ied the DNA and created tadpoles. oped in.separate breeds of sheep and fused and activated by a small pulse However, these tadpoles died at about grew up in a research environment of electricity and then grown and im­ the time they would have been ex- some six years apart. planted into foster sheep, resulting eventuaUy in the birth of a number of s~milar way, valuable farm animals span. However, a clone taken from identical or cloned sheep. such as those demonstrating extraor­ Dolly when she is six years old, in dinary resistance to parasites could be other words a clone of a clone, may Last year the researchers in Scotland rapidly multiplied. Thepretically, the have DNA that is twelve y-ears old at did something unique. They produced technique of cloning is potentially the time of birth. Now the natural life Morag and Megan by nuclear trans­ faster and more accurate than more span of a sheep is something around fer, using early differentiated cells traditional means of increasing num­ twenty years so, that if the DNA ages which had developed from cultured bers, such as superovulatibn, artificial the making of clones from clones may sheep embryo cells. This has been re­ insemination and embryo transfer. It have a limited potential. peated this year at Ruakura with the could lead to large one-off increases birth of Thomas and James - clones The third issue is that of animal integ­ in genetic gain eqtJ.ivalent to many from an embryo cell line which had rity. Is cloning somehow interfering years of traditionaLbreeq.ing. It could been cultured for about two months. with, preserving or-even enhancing also allow animals to be selected for This year however, the Scottish group the integrity of the animal and there­ characteristics which can only be took this procedure one step further. fore SOD).ehow inhei:ently right or_ measured after slaughter - one cl~ne Instead of using _the early differenti- · wrong? Integrity h~s been_ variously is slaughtered and if the desired char­ ated cell of a sheep embryo, they took described as the intrinsic value, acteristic (e.g. some aspect of meat a differentiated somatic cell from a naturality or intactness of the animal quality) is present, the remaining mammary gland culture and pro­ or its genetic material. Obviously clones can be introduced into the duced a cloned embryo which, as be­ more t£ad,itional animal-breeding farming industry fore, was allowed to develop and then teclmiques, and even the cloning of implanted into a surrogate ewe which Secondly, there is the issue of the health plants, may also affect integrity - a eventually gave birth to Dolly. The and well-being of animals produced us­ subject of much philosophic· p.iscus­ Scottish workers have therefore done ing these techniques. It is early in the sion. what was thought impossible -undo­ development of the technology, but The fourth issue is that of genetic uni­ ing the process of differentiation. This there have been reports of problems. formity. Cloning large numbers of a is achieved through starving the cells For.example, in one study of cloning few.valuable individuals will result m~ of nutrients so their active genes in dairy cattle 60 to 70 per cent of an increase in the !'\umber of geneti­ switch off. As before, Dolly has the calves were born completely normal, cally uniform animals within a popu­ same genetic makeup ilS her 'moth­ but a further 20 to 30 per cent were lation, reducing overall genetic diver­ er's' mammary cell; she was named large:r than normal at birth (up to twice sity. If these animals prove _to be ge­ after Dolly Parton. The significance of the normal size) de~pite having a nor­ netically susceptible to a disease, ob- this feat is apparent when you con­ mal gestation. Thes1: required . viously the whole population of sider that it will be possible to clone caesarean births. However; most clqnes will be similarly susceptible animals of known value producing calves survived and developed into and this risk needs to be established. many genetically identical individu­ normal animals within a few months. However, while the technology has als. Possibilities include animals with The final 10 per cent of calves had b~en portrayed with the expectation outstanding genetic characteristics other abnormalities including jo~nt that large numbers of clones will (e.g. lean meat) or the sheep,geneti­ problems. Some of the cloned sheep shortly be farmed, the reality is that cally engineered by the same Scottis)l also appear to have suffered side-ef­ the technology is very inefficient and researchers, to produce the human fects, with lambs dying du~g preg­ is not yet commercially viable - except pharmaceutical alpha-1-antitrypsin in nancy and arouqd birth due to con­ possibly for the multiplication of ge­ their milk in order to treat cystic fibro­ genital abnormalities, ancj. again some netically engineered animals. In any sis and emphysema, or even a highly · born larger than :p.ormal. One objec­ event, this problem is not specific to successful racehorse with a record of tive of the cloning research is to over­ cloning. Perhaps the most famous ex­ winning the Melbourne Cup. In con­ come these problems by developing ample of the proBlem~ resulting frorp_ trast, when an embryo is cloned; al­ the technology to a stage where the genetic uniformity is the Irish potato though it may have a fine pedigree, it offspring are as healthy as non-cloned famine, but modern equivalents exist. has no track record and the clones may animals, if not those animals suscep­ not perform as well as anticipated. tible to such problems can be avoided. The fifth issue is the possibility of so­ In any event, it is suggested that the cial and environmental changes relating What are the issues? principle of conservation of welfare is to the widespread use of this technol­ used - the animals should be no wor13e ogy. For instance, will it increase our First, one of the benefits mentioned off for having been cloned. Another dependency on biotechnology compa­ above is the multiplic_ation of animals measure 6f well-being is life expect- · nies, and will this be an advantage or with desirable traits. Particular animals ancy and there iS" a question regard­ a disadvanfage for farmers, consum­ that are extremely rare can be multi­ ing the age of the cloned animal. Dolly ers· and others? What environmental plied so that we can quickly gain a was cloned from a six-year-old"'sheep. changes might be expected from the reasonable population. As well as ap­ Since genes and DNA tend to age cloning of highly productive dairy· plications in the conservation of en­ along with the animal, does that make cows resulting in,.say,'fewer but larger dangered species, this might also be her six years old at the time of her farms producing our dairy products? applied to animals which have been birth? One scenario m1ght be that Conversely, there may be increased genetically engineered, since the Dolly will die six years earlier -than numbers pI small herds producing present success rate of genetic engi­ normal. This would not appear to be niche products. neering is low and cloning could al­ a problem to farmed animals, since low their rapid multiplication. In a most fail to realise their natural life Continued on page 15 continued from page 14 IA Surrogacy in New Zealand Biotechnology Revisited. Ethical and Legal References continued from page 4 Issues in the Application of Biotechnology Island, or Charisma? In all likelihood to Medical Practice. Bioethics Research The Press, 'Ethical Vacuum Criticised', we will end up doing all three, in some Centre, University of Otago, 1991. 18.3.93. form or another. But on balance I think Ministerial Committee on Assisted The Press, 'Free surrogacy ruled unethical', we are unwise. We would be better to Reproductive Technologies. Assisted 14.2.94. find alternative ways of producing Reproductiqn: Navigating our Future. Daniels, K. 'Attitudes to artificial Wellington, 1994. eggs, to experience the grief that we insemination by donor and in-vitro Moore, A. & Mulgan, T. 'Non-commercial have wiped out yet another species fertilization - A community ptirs­ IVF surrogacy and harm to the child'. (and then allow our grief to motivate pective'. Social Work Review, Vol 1 No 1. Otago Bioethics Repor.t, Vol 5 No 3. (1996). us to look after the world's ecosys­ (1988): pp. 4-10. New Zealand Government. Status of tems), and to accept that it is no great Daniels, K. & Taylor, K. 'Surrogacy: The Children Amendment Act, 1987. Private Troubles and Public Issues'. disaster that equestrian eventing still Amending Status of Children Act, 1969. combines_ a combination of training, Comm.unity Mental Health in New New Zealand Infertility Society. 'Policy on­ Zealand, Vol 6 No 2. (1991): pp. 28-50. skill, and breeding. Surrogacy'. NZIS Newsletter, Vol 4 No Department of Justice, Law Reform 3. (1993). Division. New Birth Technologies: an Royal Society of New Zealand, New issues paper on AID, IVF, and surrogate Zealand Law Society, Medical Council Wellington: Department of motherhood. of New Zealand, Medical Research Justice, 1985. Council of New Zealand, New Zealand . Department of Justice, Law Reform . Medical Association. 'Issues arising Division. New Birth "Technologies: a from in vitro fertilisation, artificial summary of submissions received on the insemination by donor and related Wellington: Department of issues paper. problems in biotechnology'. New Justice, 1,986. Zealand Medical Journal, Vol 98. (1985): Interim National Ethic·s Committee on pp. 396-98. Assisted Reproductive Technologies Wadlington, W. 'When are Mothers and (INECART). Report on Non-Commercial Fathers not Mothers and Fathers?' Surrogacy by Means of In Vitro LawTalk, Vol 140 Non 8. (27 November, Fertilisation. 15 December 1995. 1981). 'Birth technologies - a legal response'. Warnock, M. Report of the Committee of LawTalk, Vol 371. (May 25, 1992): pp. 7- Enql!;iry into Human Fertilization and 8. Embryology. Department of Health and Medical Council of New Zealand. Social Security, HMSO, 1984.

The Cloning of Dolly continued from page 12 animals may help develop human 'Fra~kenstein fear revived'. Thus, at cloning for assisted reproduction and present, we appear to be debating the The final issue concerns th,e implica­ organ transplantation programmes. morality of cloning of animals on hu­ tions for humanity - the cultural ideal However, human cloning raises ethi­ man grounds. Is this sensible for the we want for ourselves. This issue re­ cal issues beyond the scope of this future of both animals and humans? lates to the sort of people we want to paper. It is accepted that animals and hu­ become - people who regard the non­ Undoubtedly, the most well-known mans can be treated differently (for ex­ human world as a meqlls to an end, implication, if notfear, for humans is ample, moribund animals must, by or people who respect the non-human that which we normally associate with law, be euthanased). It would be a pity world for its own sake. It is this as­ Hitler and The Boys from Brazil - the if the benefits of animal cloning were pect which has captured much of the multiplication of undesirable so-called not fully realised, because of the per­ public and media attention. Someone 'elite' individuals. This aspect has ceived harms of human cloning. who sees nature as a resource to be gained most recent attention, leading used might defend cloning, whereas one critic to comment 'The real sheep Further reading someone who considers all life forms are the mtdia who have lilindly followed sacrosanct might not. Many of us take de Boer, I.J.M., Brom, F.W.A. and the cloning story, shrieking ofits horrors.' the middle ground, accepting that Vorstenbosch, J.M.G. (1995) An ethical The newspaper reports of the cloning while nature is a source of raw mate­ evaluation of animal biotechnology: the of Megan and Morag last year, in­ case of using clones in dairy cattle rials, it is also something to be used cluded headlines such as 'scientists breeding. Animal Science, Vol 61, 453- · wisely and with care. Similarly, we welcome move to clone sheep' and that it 463. accept that there needs to be a balance may 'herald a brave new farm world'. Nash, J.M. (1997) 'The age of cloning'. Time, between human and animal needs, However, the newspapers also picked MarchJ0, pp 42-45. and that animals may be used but only ·Rollin, B.E. (1995) The Frankenstein Syn­ up on something which was not pre­ if that use is humane. drome. Ethical and Soaial Issues in the Ge­ sented in the original science article, netic Engineering of Animals. Cambridge It is well to remember that cloning in that some animals suffered serious de­ University Press, Cambridge. animals might well have some posi­ fects. In contrast, this year's report of Wilmut, I., Schnieke, A.E., McWhir, J., tive spin-offs for humans; for instance, the cloning of Dolly resulted not only Kind, A.J. and Campbell, K.H.S. (1~7) cloning animals may produce humans in headlines such as 'science of the 'Viable offspring derived from fetal health products or products which al­ lambs' and 'clone on the range' but more and adult mammalian cells'. Nature, low improved goods to be produced. significantly that such technology Vol 385, 810-813. Also, developing the technology in 'raises alarm over humans', and •