TA-Programme Switzerland

TA 30A/1998

XENOTRANSPLANTATION – GEPRÜFT AUF HERZ UND NIEREN

Kurzfassung der TA-Studie „Xenotransplantation“

XÉNOTRANSPLANTATION – EXAMINÉE SOUS TOUTES LES COUTURES

Résumé de l’étude TA „Xénotransplantation“

XENOTRANSPLANTATION – TESTED ON HEART AND KIDNEYS

Short version of the TA study „Xenotransplantation“

Schweizerischer Wissenschaftsrat • Conseil suisse de la science • Swiss Science Council

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Editorial in german only

Diese Reihe der TA-Publikationen enthält die Die materielle Verantwortung für die Berichte Ergebnisse der Studien, die im Rahmen des liegt bei den Autorinnen und Autoren: TA-Programms des Schweizerischen Wis- Dr. Bärbel Hüsing (Projektleitung) senschaftsrates (SWR) durchgeführt wurden. Dr. Klaus Menrad Dr. Thomas Reiss Mit TA (Technology Assessment / Technolo- Fraunhofer-Institut für Systemtechnik und In- giefolgenabschätzung) werden Studien be- novationsforschung (ISI) zeichnet, welche zum Ziel haben, die gesell- Breslauer Strasse 48 schaftlichen Auswirkungen neuer Technolo- D-76139 Karlsruhe gien möglichst umfassend zu untersuchen. Es geht darum, die allfälligen positiven und Prof. Dr. Eve-Marie Engels negativen Einflüsse der Technologie auf so- Lehrstuhl für Ethik in den Biowissenschaften ziale, politische, wirtschaftliche und ökologi- Eberhard-Karls-Universität Tübingen sche Systeme und Abläufe abzuschätzen. Sigwartstrasse 20 D-72076 Tübingen Nach einer Pilotphase von 4 Jahren haben der Bundesrat und das Parlament den SWR University of Cambridge, Clinical Scool beauftragt, die TA-Aktivitäten für die Periode Department of Surgery 1996-1999 weiterzuführen. Addenbrooke’s Hospital Hills Road Um diese Aufgabe zu erfüllen, hat der SWR GB-Cambridge CB2 2QQ einen TA-Leitungsausschuss aus Fachleuten von Wissenschaft, Industrie, Politik und Betreuung des Projektes: NGO’s (Nichtstaatliche Organisationen) er- Dr. Adrian Rüegsegger, TA-Geschäftsstelle, nannt, welcher die massgeblichen Themen Bern und Fragen definiert, die es im TA-Programm zu behandeln gilt. Redaktion der Kurzfassung Dr. Lucienne Rey, TA-Geschäftsstelle, Bern

Der ausführliche Bericht „Technologiefolgen- Abschätzung Xenotransplantation“ kann be- zogen werden bei:

TA-Programm Schweiz Schweizerischer Wissenschaftsrat Inselgasse 1 CH-3003 Bern Tel. +41 31 /322 99 63 Fax +41 31 / 323 36 59

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A TECHNOLOGY WITH A LONG HISTORY 1

Man has long maintained close relations with animals. They represent food, companions for hunting or play, and embody strange mythological creatures. In the sagas of the Greek gods, figures such as the centaur bear witness to the close links between man and animal. The technology of the late twentieth cen- tury, in the form of so-called „xenotransplantation“, has brought the grafting of animal organs into human bodies within the realm of feasibility.

Transplant surgery was still in its embryonic Here, the pig constituted the most likely sour- phase when the first experiments in xeno- ce: in 1995, it became possible to genetical- transplantation were carried out: cases from ly modify pigs in a way that reduced the high the 18th century record attempts by physici- degree of rejection of their organs by the hu- ans to restore the sight of blind patients by man immune system in comparison with tho- grafting the corneas of cats or dogs. These se of „normal“ pigs (see chapter 3). early transplants were unsuccessful: the new cornea always became cloudy and was of- Seen as a whole, however, all xenografts car- ten accompanied by severe infections. ried out to date have been assessed as clini- cal failures. Previous experience has ne- At the beginning of the 20th century, vascular vertheless also revealed that under certain cir- suturing techniques made it possible to trans- cumstances, the animal organs transplanted plant organs, such as kidneys, hearts or li- survive for a certain time and can fulfil certain vers, whose blood are supplied by large blood- vessels. Here, too, surgeons were initially un- aware of the species barrier. However, they were soon to discover that so-called „allo- grafts“ - i.e. organs that were taken from an individual of the same species as that of the recipient - had far better chances of survival than xenograft transplantations. These dis- coveries contributed greatly towards gaining a better understanding of the human immu- ne system and the body’s own defences.

It was only during the sixties, however, when effective immune suppressive drugs - i.e. me- dication to reduce the body’s defensive sy- stem - came onto the market, that allotrans- plantation techniques progressed rapidly. Heart transplants, and above all kidney trans- plants, became routine operations in many hospitals. This brought with it a new problem: the number of donor organs available was in- sufficient to cover demand (see chapter 2). In the hope of making this lack of organs less critical, attention was once more directed towards xenotransplantation. The centaur - fascinating strength but frightening unpredictabili- ty. Drinking goblet of the Phintias, c. 510 BC.

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functions. Experts are hoping that certain Definitions types of domestic animals and organ recipi- ents can become so compatible that one day, In transplantation medicine today, so-called allogenous trans- animal organs can survive and fulfil their plantations (allografts) are the most widely practised. This functions in human bodies for long periods. term refers to the transplantation of living cells, tissue or or- gans between two individuals of the same species. The term „xenotransplantation“ is used to describe transplants of living cells, tissue or organs beyond the species barrier - for example from pig to man.

2 THE POTENTIAL OF XENOTRANSPLANTATION

Xenotransplantation represents a potential solution to numerous medical pro- blems. However, it is still far from being a routine medical procedure.

Transplantation surgery has been particular- by dialysis. In the long term, kidney trans- ly in the spotlight since December 1967, plants are even considerably less expensive when the first successful heart transplant was than dialysis - not to mention the increased carried out by the South African surgeon Chri- quality of life offered to the patient. But there stian Barnard. Public interest in spectacular are still a few drawbacks in this success sto- operations is understandable - they can pro- ry: the waiting list for new kidneys has been vide a „new life“ for seriously ill patients or at growing for years, and in Switzerland, the least dramatically reduce their suffering. For average waiting time for a transplant is now instance, kidney transplants release patients over two years. from the necessity of regular blood cleansing

The lack of organs and its consequences Decreasing willingness to donate organs

There are also waiting lists for other organs, and not all patients for whom a transplant would be a solution survive long enough: in 1996, a total of 43 patients died before the life-saving operation could take place.

The shortage of available organs implies a whole series of further problems. In cases of emergency, it is often necessary to fall back on organs - for example those from elderly donors - that are not entirely suitable for trans- plantation. The question of the most equita- ble method of allocating organs is also beco-

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ming more controversial, since the supply is by no means sufficient to meet the demand: Awaiting a new life should preference be given to a family man with two small children - or should the severi- ty of the illness be the main criterion? Another 428 danger exists: that of wily businessmen who profit from the urgency of the situation by purchasing organs from the underprivileged in developing countries and importing them into wealthy industrialised countries.

A promising outlook 25 14 18 5 20 10 14 Heart Lungs Liver Kidneys The hope of one day being able to provide animal hearts, livers or kidneys to counter Patients on the waiting list in 1996 the shortage of organs for human patients, Patients on the waiting list who died while at the same time resolving inherent pro- between 1996 and 1997 blems both represent the greatest incentive in the research on xenotransplantation.

Should xenotransplantation become a routi- ne clinical procedure, there would be an unli- with living kidney donors has shown, favou- mited amount of organs available. This would rable basic conditions are of major signifi- de-escalate another contentious debate at the cance for the success of an operation. same time, and one which still divides physi- cians throughout the world today: should a But even under favourable conditions, a trans- brain-dead person who is still warm and still plantation is, and remains - whether it invol- breathing be used as a kind of „spare parts ves the same species or goes beyond the store“ for other patients? Or can a person only species barrier - a major operation. In additi- be considered dead when the other vital or- on, patients remain dependent on medicati- gans cease to function? on for the rest of their lives that weakens the body’s own defences and renders it suscep- Transplant patients, however, could gain some tible to cancers and infections of all kinds. relief from xenotransplantation in the sense Even if all the hurdles with which xenotrans- that they would no longer need to live with plantation is confronted today can be over- the knowledge that they owe their own lives come, it will not be possible to prolong hu- to the death of another human being. man life at will thanks to animal „spare parts“.

Finally, xenotransplantation would also im- ply a number of practical advantages. For nor- Hope on the research front mal transplantations today, organs are usually harvested from brain-dead accident or suici- Although the xenotransplantation of organs de victims. The operation takes place at very has never yet been successfully practised, little notice and under emergency conditions, (see also chapters 1 and 3), trials on grafting in order to avoid any damage to the organ animal cells onto humans have progressed whose blood supply has been cut off. Xeno- somewhat further. The reason for this is that transplantation, however, could be planned cells from other species can be encapsula- ahead. The patient could be prepared for the ted in semi-permeable sheathing. These cap- operation - and its far-reaching consequences sules permit the exchange of certain sub- - and the required infrastructure could be pre- stances, but separate the foreign tissue from pared under ideal conditions. As experience

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the immune system of the recipient, thus pre- Pioneering research is also carried out in venting major rejection reactions. Switzerland The most advanced research is that on the xenotransplantation of islet cells from the pan- Trials involving the treatment of diseases by using cells from creas as a therapy to treat diabetes (diabe- other species are also being carried out in Switzerland. Amyo- tes mellitus). By successfully receiving islet trophic lateral sclerosis is a rare disease of the nervous sy- cell transplants, the patient would no longer stem leading to severe paralysis and eventually to death. A be dependent on regular insulin injections and Swiss team led by Professor Aebischer at Lausanne Univer- would be spared to the greatest possible ex- sity has developed a new approach, consisting of treating tent the sequelae of diabetes (such as kid- patients with encapsulated cells from baby hamsters’ kid- ney failure and blindness). In various experi- neys, genetically modified to secrete a nerve-stimulatory ments on animals, some xenogenous islet substance. Results to date indicate that this is feasible. cells functioned for over one year. In Swe- However, comprehensive research is still necessary before den, three diabetic patients have received it will be clear wether the progresion of the disease can be transplants of islet cells from pigs, but suf- slowed down by this procedure. ficient functioning could not be ascertained.

Experiments related to pain relief for cancer patients are also Research using the new xenotransplantation being carried out in Switzerland. This consists of implanting methods applied to brain diseases is also pro- encapsulated calf cells with natural painkilling properties. gressing. In patients suffering from Current clinical trials will define whether pain can genuinely Parkinson’s disease, for example, nerve cells be relieved in this way. die off in the midbrain. Research will reveal, in time, whether it will be possible to treat these patients by replacing these dead neu- rones by foetal nerve cells. Work using hu- man foetal tissue, however, raises practical and ethical problems, even if it could be ob- tained in sufficient quantities. Pig cells may represent a solution here: clinical trials are currently being conducted in the USA that involve transplanting nerve cells from pig foetu- ses into 12 Parkinson patients. The results to date reveal that at least some of the cells transplanted have survived, and connections between pig and human neurones are forming.

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THREE MAJOR HURDLES 3

According to the current level of knowledge, there are three major obstacles that stand in the way of successful xenotransplantation: the hyperacute rejec- tion of transplanted organs by the body of the recipient, various areas of incom- patibility between human and animal physiology, and finally the risk of infection. At present, these hurdles represent virtually insurmountable obstacles to the xenotransplantation of organs. For cell grafts, however, these are often consi- derably less problematic.

The rejection of transplants constitutes a ma- suffering, scientists are keeping their distance jor problem for both allografts and xenografts. from using large numbers of man’s older brot- The immune system of the recipient consi- hers for xenotransplantation purposes. ders the graft to be ‚something foreign‘ and rejects it. For allografts, this problem can be overcome by matching the donor and recipi- Bodies fit for fighting ent in order to achieve a maximum compati- bility of specific tissue characteristics, and The pig seems to be the most suitable sour- by administering immune suppressive medi- ce animal - but not as far as rejection is con- cation throughout the recipient’s lifetime. cerned. Because of the considerable genetic Despite this, a considerable proportion of differences between pig and human, blood transplants are still condemned to chronic clots would immediately form after transplan- rejection. If organs from apes were to be trans- ting a pig’s organ into a human body, thus planted into human beings, a similar strate- cutting off the blood supply to the organ, which gy - even if different medication were required would die within hours or even minutes. Sci- - might well be successful since men and entists call this extremely severe rejection apes are closely related. As apes are threa- process „hyperacute rejection“. It is only tened with extinction, however, and have a thanks to a specific type of genetic modifica- refined sense of perception and capacity for tion to pigs that it has now become possible,

Apes are threatened with extinction, and both their social behaviour and their perceptions are highly de- veloped. They are thus hardly sui- table as "organ donors". This photograph shows a two-day old baby gorilla born in Zurich Zoo on 12th July 1998.

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in animal experiments, to overcome the see- It has long been known, and not only in the mingly insuperable problem of hyperacute medical field, that new human infectious rejection. Organs from transgenic pigs that diseases - such as AIDS or a new variant of were transplanted into apes did manage to Creutzfeld-Jakobs disease - could derive from survive for up to 60 days. However, the doses pathogens successfully transmitted from ani- of immune suppressive medication given were mals to humans. In doing so, their capacity so high that the animals died. for creating disease has changed in an unex- pected way: the pathogens often create vir- Introducing the organs of transgenic pigs into tually no symptoms in the animal, but once humans therefore does not yet represent a transmitted to humans they become highly feasible alternative. Moreover, even greater „aggressive“. These types of disease are de- precaution is necessary since current rese- scribed as „xenozoonoses“. arch results indicate that even if hyperacute rejection could be overcome, further rejection Scientists are issuing warnings that this same mechanisms would take effect, and on which phenomenon could also occur during xeno- virtually no research has been carried out to transplantations. The objection that man has date. Here, there is an urgent need for scien- been living in close contact with pigs for thou- tific research to be carried out. sands of years is not a valid one, since in xenotransplantations all natural, human me- chanisms for defence against infection would Man is a special type of animal be consciously suppressed.

A further obstacle is that of overcoming any Once aware of this, scientists began an acti- incompatibility in the metabolism between ve search for pathogens in pigs that could organ donors and recipients. Very little data possibly break through the species barrier and concerning this problem is available to date. be transmitted to humans. And they found Hypothetically, however, the differences in the what they were looking for: a certain type of species-specific nutritional needs of the or- virus (members of the so-called retroviruses), gans (for example trace elements and vit- that was previously only known to exist in amins) could damage the xenograft. For in- pigs and was believed to be not transmissi- stance, the pig’s natural cholesterol levels are ble to other species, could be transmitted to lower than those of humans. Man’s high cho- human cell cultures in laboratory experiments lesterol levels could therefore lead to arte- and multiplied there. This does not, however, riosclerosis in the case of a transplanted pig’s mean that this type of transmission could also heart. Moreover, organs such as livers, kid- take place „in real life“, outside the laborato- neys, lungs and pancreases are controlled ry, and nor does it mean that these viruses by hormones. It is not yet known whether could really cause diseases in humans. The animal organs could be controlled by human experiment nevertheless reveals that the sci- hormones. One case has been documented entists’ fears are not just a case of pessi- whereby a patient having received a baboon mism but that this risk must be examined in kidney transplant began to urinate in a com- depth. pletely uncontrolled way, and finally died as a result of extreme dehydration. Should xenotransplantation lead to the ap- parition of new diseases, it is by no means certain that these would be restricted to the Pandora’s box? recipient of the foreign tissue. It is much more a case of these new types of illness sprea- Recently, indications for further risks inherent ding to the rest of the population. Here, the to xenotransplantation are increasing: they specialists’ greatest fear is not deadly patho- could act as a vehicle for transferring pa- gens such as the Ebola virus that produces thogens to humans that were previously only immediate and dramatic symptoms. They are present in animals. much more concerned about pathogens such

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as the AIDS virus, which can spread comple- bers of the British Kennedy Commission, who tely unnoticed over a number of years, is dif- are seen as a reference in this connection - ficult to detect because of a lack of sym- strongly recommend that no foreign organs ptoms, and thus represents the danger of an be transplanted into humans until the advan- epidemic, even on a worldwide scale. tages outweigh the risks. Certain clinical tri- als involving the xenotransplantation of cells, however, appear acceptable. Foresight rather than hindsight Even with the most extensive research and Safety measures that prevent any transmis- the most stringent safety measures, howe- sion of pathogens from animals to humans ver, the risk of infection remains, and not only are therefore urgently needed. patients but the entire population are expo- sed to this. Here, bio-medical ethics are ba- Various groups of researchers are developing sed on the principle of „informed consent“: screening methods to detect possible retro- this means that those affected must be infor- viruses in the genotypes of source animals. med of the possible consequences of a spe- In recent years, the National Retrovirus Cen- cific procedure. Being fully aware of all pos- tre in Zurich developed two highly efficient me- sible inherent dangers is the only way for thods of detecting and identifying unknown people to decide whether or not to accept retroviruses. Carrying out xenotransplantati- such a procedure. ons using the healthiest possible, „germ-free“ animals is the best guarantee of avoiding the transmission of xenozoonoses. Naturally, it is also essential for the source animals to be kept under particularly hygienic conditions (see also chapter 5).

Specialists also recommend further preventi- ve measures to patients receiving animal tis- sue and cell transplants, i.e. medical surveil- lance over several years and repeated exa- mina-tions. The first of these concomitant in- vestigations are already in progress: Novar- tis is moni-toring the health of several pati- ents who have received pig tissue for the tre- atment of severe burns.

Finally, a whole series of legal prescriptions and international agreements is currently being drawn up, which are intended to mini- mise the risk of infection inherent to xeno- transplanta-tion (see chapter 6).

Detailed assessment is essential

Hyperacute rejection, physiological incompa- tibility and the risk of infection mainly occur in the xenotransplantation of organs. The graf- ting of foreign cells is often much less affec- ted by this. Given the current level of know- ledge, specialists - and for example mem-

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4 SIGNS OF THE FUTURE

Xenotransplantation is today still far from being a routine medical procedure. Specialists are not unanimous regarding if and when this will become a reality.

Seen as a whole, xenotransplantation plays fice would bring with it another series of ethi- something of a marginal role within current cal problems, and could lead to the develop- medical research. Although an area de- ment of a „two-level“ medical system. veloping at a pace faster than the average, it is still a small domain of transplantation me- Immediate effects on the allocation of rese- dicine, worked on by individual scientists at arch funding could be expected: it can be the forefront of basic research into the sub- assumed that more money would be invested ject. The gaps in knowledge that still exist in further research into xenotransplantation - are considerable (see chapter 3). and probably at the expense of research into the reasons for organ failure. The greatest Statements on the future prospects of xeno- threat, however, is that research into disea- transplantation are equally ambiguous: se prevention would be relegated to a positi- • Numerous researchers agree that wi- on of secondary importance if a successful thin the next five years, the status of high-tech procedure for treating these disea- research into human immun reactions ses were available. will be advanced to a point where it will be possible to assess whether xe- The consequences for transplantation medi- notransplantation will be feasible at all. cine could well follow this movement. The • Specialists predict that it will take at transplantation of organs and tissue would least between one and seven years most certainly increase. The caveat remains, until an organ from a genetically modi- however, that the population’s willingness to fied pig can be successfully transplan- donate organs would decrease still further if ted into a human body. animal organs could also be used for trans- • It will be at least 10 years before it is plantation purposes. possible for the first xenotransplant re- cipient to survive for one year. And it It is questionable whether xenotransplanta- could be another 15 to 20 years befo- tion could represent a solution to the lack of re this treatment becomes widespread. organs: specialists do not exclude the pos- sibility of animal organs being used, at best, as a bridging solution until a transplant from An uncertain future a human body is available. This would ne- vertheless mean that xenotransplantation Xenotransplantation does remain a possibili- would foster an increased scarcity of organs. ty for the long-term future, but in comparison to alternative therapies (chapter 7), it has no advantages in terms of time. The consequences for the economy and for society A further concern is that xenotransplantation would be a less viable alternative to allotrans- Should xenotransplantation become a wi- plantation in the long term, since the difficul- despread alternative, the effects on society ties to be overcome are so great. The decisi- and the economy can hardly be conceived. on regarding which patients would benefit from receiving „better“ organs, i.e. allografts, and The cost impact of xenotransplantation on those for whom an animal organ would suf- medical care is difficult to estimate. Calcula- ti

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on models reveal, for example, that the pro- If xenotransplantation were to become an „ev- portion of elderly people - and thus candida- eryday issue“, this would also affect our atti- tes for a heart xenotransplantation - is gro- tude towards illness and dying. Death would wing constantly in industrialised nations. no longer appear as an existential counter- Here, too, the ethical question of a possible point to living, and a danger would lie in so- „two-level“ medical system is relevant: if me- ciety gaining the illusion of a technically fea- dical insurance companies were to refuse the sible extension to life, available at will costs of xenotransplantations, only wealthy patients would be able to afford this expensi- ve treatment.

5 FROM A CREATURE WITH A SOUL TO AN ANIMAL SPARE PARTS DEPOT?

Xenotransplantation is not only a challenge from a medico-technical point of view. It is far more an issue that raises numerous ethical and moral questions.

Since it has been possible in recent years to be reconciled with the conception of the „digni- produce genetically modified pigs whose or- ty of animals“ as laid down in the Swiss Fe- gans are rejected less violently by human im- deral Constitution. mune systems, these intelligent omnivores have become the greatest source of hope for Sceptics believe xenotransplantation to be a xenotransplantation. dubious alternative not only on animal pro- tection grounds, but also as far as the psychi- The argument that it makes little difference cal consequences for humans are concerned: to a pig if its life ends as a source of meat or the possible psychological effects on patients as an organ donor is only partially valid. Sour- of having a pig’s heart beating in their body ce animals are raised under conditions that are not clear. A person’s self-image is, in fact, have little in common with those of normal to a large extent determined by the symbolic animal husbandry. In order to minimise the meaning of the various organs - for example risk of transmitting pathogens, the breeding the heart. It cannot, therefore, be totally ex- and husbandry of a herd of transgenic pigs cluded that a person receiving foreign tissue would have to take place under conditions of might develop identity problems. increased hygiene and in specially built in- stallations sealed off from contact with the environment. Pig-lets would be born by Cae- sarean section, and would be strictly isola- ted from the sow and her milk. During the first weeks of their life, they would be raised in isolation units, given sterilised feeds and supplemental fortifiers, and later raised in small groups, under constant supervision. It is at the very least questionable whether such extensive „instrumentalisation“ of animals can

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6 DEVELOPMENTS CONCERNING LEGAL REGULATIONS

In view of the need for regulations governing xenotransplantation, the legal au- thorities are by no means inactive. On a national level and in international colla- boration, a great deal is being done to provide an acceptable legal basis for transplantation medicine.

In the opinion of experts, the aspect of pro- infection seriously and to proceed with cauti- tection against infection is the most urgent on. Nevertheless, much remains to be done: issue to be handled. Switzerland has there- first, Swiss regulations must be harmonized fore given priority to this area. with international regulations and secondly, procedural prescriptions must be drawn up and compliance monitored. Protection against diseases

The security aspects of xenotransplantation Transplantation law and the are currently governed by the Federal Di- protection of the environment and rectives on the control of blood, blood of animals products and transplants, drawn up by the Federal Public Health Department. According Measures are thus in progress to ensure that to this directive, the removal of animal organs more comprehensive legislation governing xe- for use in humans must be notified to the notransplantation will exist in Switzerland Federal Public Health Department. Those than those of the Federal Directives on blood, responsible for carrying out the transplantati- blood products and transplants. Two further on must confirm that the source animal has laws that should pave the way are presently been screened for pathogens. In order to re- undergoing the ratification process. The first duce the risk of transmitting „animal“ disea- of these is to expand Article 24 of the Fe- ses to humans in a more effective way, the deral Constitution in order to give the Fe- Federal Council believes that these regulati- deral Government the authority to enforce le- ons should be made more stringent. The Fe- gislation on transplantation medicine throug- deral Public Health Department has therefo- hout the confederation. By the beginning of re drafted a corresponding amendment that next century, a uniform, Federal law could is currently in the process of ratification on then succeed the Cantonal regulations cur- various levels. The draft proposes a moratori- rently valid. This Federal law on transplanta- um on xenotransplantation in humans with tion could also include comprehensive regu- effect as of 1st September 1998 until the year lations on xenotransplantation. Fierce deba- 2002. Despite this, xenotransplantations are tes can be expected, however, before the not fully excluded within this period: certain details of this federal law become definitive. applications that have proved safe will be pos- sible, if requests are officially authorised by The second issue now under discussion is the Federal Public Health Department follo- the so-called Gen-Lex Motion. By modifying wing in-depth investigation. the law on the protection of the environment, this would also govern extra-human genetic By prohibiting xenotransplantation, the autho- engineering - and thus the production and use rities have opted for a comparatively rigorous of genetically modified pigs for xenotransplan- solution in comparison with other nations. tation. The Gen-Lex motion is highly signifi- This confirms their wish to take the risk of cant, since the more radical initiative con-

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cerning genetic modification - aimed at pro- hibiting the production, acquisition and trans- mission of transgenic animals - was rejected by popular referendum in June 1998.

Finally, the animal protection issue is gover- ned by the law on the protection of animals. This is not, however, specifically applicable to xenotransplantation. Further study must still be carried out in order to ascertain whe- ther xenotransplantation requires this law to be modified. The question of whether patients on whom new therapies such as xenotrans- plantation will be tested have sufficient legal protection in Switzerland has been under dis- cussion for some time.

Switzerland has therefore taken the first steps Interest in xenotransplantation in the right direction. However, much ground remains to be covered before comprehensive In Switzerland, various groups representing highly diffe- legislation on xenotransplantation is availa- rent standpoints are involved in xenotransplantation. ble. First, patients suffering from organ failure are particular- ly interested in the issue. Scientists also see it as an International agreements area of considerable significance, and are at present mainly engaged in basic research. The Swiss National In order to steer the development of xeno- Science Foundation for the promotion of scientific re- transplantation along the correct path, it is search is also involved in xenotransplantation. This insti- not sufficient for the basic criteria to be defi- tution is responsible for decisions regarding the allocati- ned in such a small country as Switzerland on of research funds. The Swiss Academy of Medical alone. It is much more a question of interna- Sciences has formed a working group on xenotransplan- tional or even global regulation. tation, which will draw up recommendations for Swiss physicians in due course. The joint Ethical Commission The countries where the debate on this legis- for Animal Experiments of both the Swiss Academy of lation is most advanced are the USA and Medical and of Natural Sciences is handling animal Great Britain. England plays a pioneering role protection issues linked to xenotransplantation. For he- in formulating the most stringent conditions alth insurance companies, the ques-tion of whether to be fulfilled in order for clinical trials on xe- xenotransplantation costs will be included in their cover- notransplantation to take place. The regulati- age will be decisive in the medium term. Some biotech- ons are so strict, that in fact they represent a nology companies and several global pharmaceuti- moratorium on the xenotransplantation of or- cal companies that develop immune suppressive drugs gans. The various regulations within the USA have a major economic interest in xenotransplantation. are highly significant, since other countries The Parliament is handling legislation on xenotransplan- usually align their own with them. Their gui- tation. delines are particularly oriented towards pre- venting infection and keeping in line with the recommendations of the World Health Orga- nisation (WHO).

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7 THERE ARE MANY OPEN DOORS

Xenotransplantation is not the only alternative to circumvent the lack of donor organs. The public should be involved in deciding on the relative value of xeno- transplantation compared with alternative methods of treatment.

Medicine already possesses a number of dead patients unless relatives formally oppo- measures to prevent organ failure. One pos- se this, is practised in many European coun- sible means of prophylaxis against the po- tries (such as Spain, Belgium and Austria). tentially liver-damaging hepatitis B would con- The highest proportion of organ transplantati- sist of vaccinating the entire population. Tar- ons take place per million inhabitants in the- geted awareness campaigns against the ab- se countries. use of alcohol and medication could contri- bute towards the prevention of liver and kid- At present, transplantation medicine in ney damage. Switzerland is governed by Cantonal laws, and the „presumed consent solution“ is only One promising alternative to xenotransplan- included in the legislation of a few of them, tation would be increasing research into even if it is not applied in practice. Willing- diseases that ultimately lead to organ failu- ness to donate organs could also be impro- re, and to develop therapies that would strike ved by providing better training for medical at the very root of the problem. staff and physicians, who require special pre- paration for the difficult task of approaching Today, research continues in the field of arti- relatives of a potential donor. In addition, it ficial organs. First prototypes do exist, but would be wise to increase public awareness the choice of materials is difficult and the of problems arising from the lack of organs, energy supply has not yet been guaranteed and to stimulate greater confidence in the to a sufficient extent. Experts believe that institutions involved in the field of organ trans- artificial organs might be capable of assuming plantation. a role within medical practice in approxima- tely 15 years, and from a timing point of view All these possibilities remain open. At pre- would thus keep pace with xenotransplanta- sent, it is difficult to assess with any cer- tion. tainty whether they are more promising than xenotransplantation. One thing is sure, howe- New legislation could contribute towards in- ver: paving the way for medicine in the future creasing the number of organs donated. should not be the exclusive domain of a few The socalled „presumed consent solution”, persons or groups. Decisions affecting such witch permits the use of organs from brain- a large spectrum of the population require extensive public discussion. This is the only way of defining the relative value of xe- notransplantation in comparison with its al- ternatives.

Page 14 TA Xenotransplantation: short version