Valery Shumakov
Alexander Tonevitsky ::: Biography

XENOTRANSPLANTATION
AS A SCIENTIFIC AND ETHICAL PROBLEM

Modern methods of transplantation helped physicians to prolong the lives of about 250,000 people who had suffered from serious illnesses. At the same time new, a rather complicated moral and ethical problem has emerged. Nowadays the most pointed problem of allografting (grafting of human organs and tissues) is that of the shortage of donor material. This is the main reason for resorting to kidney, liver or heart transplants only in cases where all resources of ordinary treatment with medical supplies or surgical operation are exhausted, and a patient is doomed to die in the near future.
Statistics prove that in economically developed countries about 150,000 people need donor organs and tissue for transplanting, while the universal need for donor material exceeds these figures many times. Having doubled since 1988, it keeps on increasing, adding 15% to the total rate annually, while the claim is met only in 5-6% of cases even in the group of patients younger than 65. About 30,000 people in the USA and about 6,000 in the UK are put on a waiting list in expectation of donor heart, kidneys, lungs or liver, but only 10% of them stand a better chance by waiting until the transplant happens.
Another problem lies in the high price for donor material and the operation itself. In the USA kidney transplants cost about 90,000 dollars, to say nothing of the expenses afterwards - 7,000 dollars makes up the annual payment for the medication necessary to prevent organ rejection, and which a patient requires for the rest of his life. In Russia the cost of a kidney transplant today is no less than 250,000 roubles, and payment for expensive imported remedies is to be added to the sum. That is why kidney transplants in this country are mainly sponsored by the health authorities, though as a rule they are short of financial resources as well. For this reason the number of such operations has notably reduced here. Famine prices made organ transplants inaccessible to the ordinary person, who works on a limited budget, even if he is doomed to die without the operation.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

From time to time the Russian mass media publish features about the illegal home and international sale of organs and even about murders committed in the process of acquiring certain organs. It should be mentioned that none of these reports has been ever confirmed by the law-enforcement authorities. By and by it became known that in China organs and tissues of prisoners sentenced to death were used for transplantation, facts of organs trade were established in India, Brazil and South Africa, etc. Thus, it is evident that the steady rise in the need for tissue and organs necessary for transplant gave birth to a global problem.

* * *
The operation known as xenotransplantation (when animals' tissues and organs are transplanted to people) seems to be one of the promising ways of solving the problem under consideration. Still, up to recent times the method was explained only in theory - it seemed impossible to prevent such organs from rejection. In fact, even a well-matched pair of a human donor and a patient (except twins) meets with the real threat of a transplant's rejection, and therefore a patient has to take immunity suppressive medication for the rest of his life. The incompatibility of a man and an animal appears to be much higher. Practically speaking, nobody knows how an alien organ is going to function in the human body for a long time even if it settles down.
Indeed, solitary instances of relatively successful attempts to transplant animals' organs to humans have been done. In 1963 Keith Reemstma transplanted a chimpanzee's kidney to a man, and it kept on functioning as long as nine months. [1] Later attempts were made to transplant hearts and livers from primates to humans. [2] Still, the results of such experiments would not seem encouraging. It should be said that the immunity conflict occurs immediately after the operation and continues for several minutes to several hours. The transplanted organ endures complicated morphological and physiological changes, which lead to hypostasis, haemorrhage and thrombosis of minute vessels, and the organ mortifies rapidly.
The process of rejection is set in motion by antibodies constantly existing in the blood and aimed to protect the body from foreign matter. Another activating agent is the so-called complement - a group of nine albumens that normally reside in blood as inactive enzymes. When a foreign agent (antigen) enters into human body in the process of transplanting an animal's organ, antibodies bind with the foreign antigen, and the new antigen-antibody complex causes unregulated activation of the complement. As a result a complicated albumen assemblage is generated on the surface of foreign cells causing irreversible changes and subsequent destruction of them.
The complement's activity in the tissues of xenograft is aimed at the so-called endothelium cells, which line the inner walls of minute blood vessels. In sound tissues endothelium cells work as a barrier to stop penetration of albumen and blood cells into tissue through the vessel wall, and limits intravascular thrombosis. The above-mentioned process, as well as secretion of some other pathological factors into blood, influence endothelium cells. They are altered, and stop functioning as a barrier and stimulate the formation of thrombi, which plug up vessel lumens.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

The discovery of the possibility of using of pigs' organs as donor material for humans stimulated research into immunology, virology, molecular biology and genetic engineering of the animals. The mechanism of a pig's organ transplant rejection was identified, and the way to overcome it was outlined. The next step was to breed special transgenic animals, whose cells contain both, their peculiar genes and also different ones, not characteristic of the species. Such animals produce albumen that prevents the transplanted organ from being damaged by the human immune system. It is put into practice by means of genetic engineering (transgenesis), when corresponding changes in the genetic system of a pig's embryo are realised with the help of special methods. Then the embryo is implanted into a uterus of an ersatz sow, which gives birth to it. The tissue of a newly born piglet appears to be to a great extent compatible with human tissue, and is not subject to acute rejection.
It seems likely that transgenic technologies in xenotransplantation have great prospects for the future. It becomes possible to settle a xenograft down and keep it without constant medical treatment through the rest of the life. Therefore, thanks to the discovery of the mechanism of tissue incompatibility and the achievements in genetic engineering actual prospects of practical xenotransplantation have surfaced. A genetically modified pig really seems to be an instrument of a definitive solution to the problem. British experts foresee that in the near future more than 300 pig farms will work for the programme of organs transplantation.
Though the main hardship is yet to come, there are enough reasons to state that the problem of extra-acute rejection of a xenograft could soon be solved, and pigs, or maybe other mammals, will be used as an unbounded source to provide people with organs, needed for medical use.




Even in view of the most optimistic forecast of scientific prospects in xenotransplantation, practical settling of the method presupposes a prior solution of certain serious ethical and legislative problems.

* * *
Apart from the above-mentioned problem of transplant rejection, others should be pointed out. Recently two scientific groups that work in London have cited the findings of viral varieties in pig tissue. They belong to retroviruses, which can infect human cells after transplantation, and later cause cancer. [4] Usually selection of non-pathogenic animals helps to avoid a source of infection in donor's organs. But in the discussed case retroviruses are present in the germline DNA and may cause an after-transplant illness in the human body.
It is known that the serum of human blood and other immune systems work as protective elements capable of overcoming pathogens, retrovirus included. Still, in case of immune deficiency, when the immune system is treated with certain suppressive remedies to prevent transplant rejection, the protective forces of the body are sharply reduced. As a result the real menace of retrovirus infection and the development of cancer occur. Even when an organ is transplanted from one person to another, and the recipient of the organ has to live on drugs for the rest of his life to prevent rejection, the risk of viral or microbial infections, like AIDS or bronchitis and lungs illnesses, is highly increased, and the probability of developing cancer occurs.
When animal tissues and organs are dealt with, scrupulous examination of a donor animal is especially important to avoid the risk of viral infection. Vaccination of an organ recipient is also necessary to protect him from possible infection.
The clarified information has led to disagreement among specialists. Some of them stick to the opinion that all the endeavours to continue xenotransplantation should be forbidden. Others think that medical progress will help physicians to overcome the risk. The World Health authorities and the American authorities for food and drugs (FDA) have suggested that experiments in xenotransplantation should be given the utmost encouragement, but clinical practice in transplanting animals' organs to a human should come within a moratorium declared for a period of several years. Nevertheless, according to the received information FDA, for the sake of its reputation, is carefully looking for an appropriate reason to repeal the prohibition, and give way to clinical experiment and research in xenotransplantation. [5]
Due to the well known fact that not a single scholarly trend can be stopped by any sort of interdiction, xenotransplantation goes on developing in theory and practice. Such companies like "Diacrin" and "Genzyme Tissue Repair" (USA) have worked out and put into life a method of curing chronic illnesses of the central nervous system, which yield to non-traditional cures, like Parkinson's or Hantington's diseases, [6] by transplanting pigs' nerve cells to a patient. "Neocrin" and "VivoRx" (USA) companies succeed in curing diabetes by grafting cells of pigs' pancreas to apes and humans. Such companies as "Circe Biomedical", "Nextran" (USA) and "Immutran" (UK) announced the start of clinical trials on the liver or liver cell grafting to patients with acute liver deficiency. Though the details mainly remain obscure, successful outcomes of the operation are known from 42 patients of 94, to whom the liver cells were grafted. The State Research Institute for Transplantation and Artificial Organs also succeeded in the development of methods to cure diabetes and acute liver deficiency by grafting animals' cells to people.

* * *
Even in view of the most optimistic forecast of scientific prospects in xenotransplantation, practical settling of the method presupposes a prior solution of certain serious ethical and legislative problems. When acceptable bounds of any method as applied to medical treatment and human health are defined, it is necessary to follow the principle of balance between the goal and the lowest possible risk, which may be formulated as a general rule stating that "even occasional failure of medical treatment should never threaten a patient more than the illness itself." The legal grounds of an organ recipient's juridical rights, in accordance with the Law of the Russian Federation, is written in issue 1, articles 5 - "The medical conclusion about the necessity of transplantation of a man's organs and (or) tissues" and 6 - "The organ recipient's consent to the transplantation of man's organs and (or) tissues." It is stated therein that in particular "Transplantation of man's organs and (or) tissues can be undertaken upon the written consent of an organ recipient. At the same time an organ recipient should be notified in advance about possible complication from diseases dangerous for his health as a result of surgical operation." [7] These judicial points are given here to let everyone know that, as has been mentioned, that there is risk involved, which is not directly connected with transplantation.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

The adherents of Islam would certainly oppose the transplant of pigs' organs to humans, especially since the law of some Arab countries forbids even an ordinary operation of human organs transplant. [10] In one of his recent messages on the problem of cloning, the Egyptian mufti sheikh Nasr Farid has said: "The Lord God has created us entirely complete, and it is impossible for man to make changes trying to repeat the higher work." [11]
The Orthodox Church has not yet announced its official position on the problem of xenotransplantation. It is only known that its general position in respect to transplantation is tolerant because organs transplant doesn't conflict with canon law.
Despite the wide usage of animals organs and tissue in today's medicine, we entirely agree with the conclusion of the World Health authorities: experiments and research in xenotransplantation should be undoubtedly encouraged, but at the same time serious operations carried out to transplant animals organs to people should come within a moratorium declared for a period of several years until absolute safety of the procedure is proved once and for all.
Currently the Committee for biological ethics of the European Council has been working out additional addendums to the Convention of Human Rights and biomedicine concerning the problem of xenotransplantation.

Translated from Russian by Nadezda Zizina.

References:
[1]. See: Calne, R.Y. "Organ transplantation between widely disparate species." In: Transpl. Proc. 1970. N 2, p.550-556.
[2]. Starzl, T.E., Fung J., Tzakis A. et al. "Baboon-to-human liver transplantation." In: Lancet 1993. N 341. p.65-71.
[3]. Cooper D.K.C., Ye Y., Rolf L.L.,et al// Xenotransplantation. Heidelberg, 1991. Р. 481.
[4]. Patience, C., Takeuchi, Y., and Weis R.A. "Infection of human cells by an endogenous pig retrovirus." In: Nature Med. 1997. N 3, p.282-286.
[5]. Fox, J.L. "FDA seeks 'comfort factors' before removing hold on porcine xenotransplantation trials." In: Nature Biotechnol. V. 16., p.224.
[6]. Zawada, W.M., Cibelli, J.B. et al. "Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats." In: Nature Med. 1998. V.4. N.5, p.569-574.
[7]. See: Transplantologija (russ.) [Transplantation], (Shumakov, V. (Ed.), Moscow: 1995), p.17-20.
[8]. См.: Circulation. 1998. V.97., р.1431-1432.
[9]. For a brief overview, see this edition: Iojrish, A. "Legal aspects of genetic engineering."
[10]. See: Dolbin, A.G. "Moralno-eticheskie i juridicheskie polozenija transplantologii v Rossii", in: Transplantologija (russ.) [Transplantation], (Shumakov, V. (Ed.), Moscow: 1995), p.9-20.
[11]. See: Krasovsky, O.A. Pravovie osnovi gennoj ingenerii (russ.) [Legal basis of genetic engineering], (Moscow, 1998), p.36-50.





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COLOPHON

CONTENTS:

I. LABORATORY: science and technology

Svetlana Borinskaya. Genomics and Biotechnology: Science at the Beginning of the Third Millennium.

Mikhail Gelfand. Computational Genomics: from the Wet Lab to Computer and Back.

Irina Grigorjan, Vsevolod Makeev. Biochips and Industrial Biology.

Valery Shumakov, Alexander Tonevitsky. Xenotransplantation as a Scientific and Ethic Problem.

Abraham Iojrish. Legal Aspects of Gene Engineering.

Pavel Tishchenko. Genomics: New Science in the New Cultural Situation.
II. FORUM: society and genomic culture

Eugene Thacker. Darwin's Waiting Room.

Critical Art Ensemble. The Promissory Rhetoric of Biotechnology in the Public Sphere.

SubRosa. Sex and Gender in the Biotech Century.

Ricardo Dominguez. Nano-Fest Destiny 3.0: Fragments from the Post-Biotech Era.

Birgit Richard. Clones and Doppelgangers. Multiplications and Reproductions of the Self in Film.

Sven Druehl. Chimaera Phylogeny: From Antiquity to the Present.
III. TOPOLOGY: from biopolitics to bioaesthetics

Boris Groys. Art in the Age of Biopolitics.

Stephen Wilson. Art and Science as Cultural Acts.

Melentie Pandilovski. On the Phenomenology of Consciousness, Technology, and Genetic Culture.

Roy Ascott. Interactive Art: Doorway to the Post-Biological Culture.
IV. INTERACTION CODE: artificial life

Mark Bedau. Artificial Life Illuminates Human Hyper-creativity.

Louis Bec. Artificial Life under Tension.

Alan Dorin. Virtual Animals in Virtual Environments.

Christa Sommerer, Laurent Mignonneau. The Application of Artificial Life to Interactive Computer Installations.
V. MODERN THEATRE: ars genetica

George Gessert. A History of Art Involving DNA.

Kathleen Rogers. The Imagination of Matter.

Brandon Ballengee. The Origins of Artificial Selection.

Marta de Menezes. The Laboratory as an Art Studio.

Adam Zaretsky. Workhorse Zoo Art and Bioethics Quiz.
VI. IMAGE TECHNOLOGY: ars chimaera

Joe Davis. Monsters, Maps, Signals and Codes.

David Kremers. The Delbruck Paradox. Version 3.0.

Eduardo Kac. GFP Bunny.

Dmitry Bulatov. Ars Chimaera.

Valery Podoroga. Rene Descartes and Ars Chimaera.
VII. METABOLA: tissue culture and art

Ionat Zurr. Complicating Notions of Life - Semi-Living Entities.

Oron Catts. Fragments of Designed Life - the Wet Palette of Tissue Engineering.
VIII. P.S.

Dmitry Prigov. Speaking of Unutterable.

Wet art gallery

Biographies

Bibliography

Webliography

Glossary


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