Foetal Tissue Transplantation

Foetal Tissue Transplantation

by Susan McLernon

Pope John Paul II, in his Encyclical , declared that the proclamation of the Gospel of life has become especially urgent,

". . . because of the extraordinary increase and gravity of threats to the life of individuals and peoples, especially where life is weak and defenseless... new threats are emerging on an alarmingly vast scale" (, n 3).

It is difficult to imagine anything more weak and helpless than the unborn child, and procured abortion has been condemned by the Church since the first century. She has affirmed the moral evil of abortion, and has sought to defend the inalienable right to life of every human individual. (, n 2271) But with recent advances in the biomedical sciences, a new crime against the dignity of the embryo as a human being is emerging: the use of foetal tissue as 'biological material' for transplantation. In contrast with many other developments in the biomedical sciences, there has been relatively little discussion of the advances made in the field of neural transplantation outside the scientific and medical journals. As a result, very few people are aware of how far these experiments have progressed, and what is involved. This is compounded by the 'careful' terminology used in the journal articles, which serves to disguise the ugly truth that foetuses are being used as donors in experimental brain tissue transplants. The present article aims to expose what is happening already in laboratories and hospitals around the world, and to highlight the directions in which such experiments might proceed if allowed to continue unchallenged.

In human pregnancies, the term "zygote" is used to refer to the fertilized ovum from conception to implantation in the womb (about two weeks later). "Embryo" is then used to describe the next stage of prenatal development which ends at seven or eight weeks post- conception, and finally, the term "foetus" applies from the end of the embryonic phase until birth. The length of a normal human pregnancy is approximately 38 weeks from conception, and is traditionally split into three stages or trimesters. The trimesters are not equal in length: the first is counted from conception to 12 weeks old; the second trimester is taken as 12-28 weeks; and the final trimester is the period from 28 weeks to delivery.

Because much of the literature in the field of neural transplantation is written by non-clinical scientists, the distinction between "embryo" and "foetus" is not always observed; therefore, in this review paper, the terms are used interchangeably. In addition, in direct quotes from articles published in American journals, the American spellings have been preserved.

There is some scope for regeneration of damaged nerve tissue in the peripheral nervous system; a severed finger, for example, can be surgically repaired, and, in time, some restoration of function will occur. This potential is lacking in the neurons of the brain and spinal cord which together comprise the central nervous system (CNS). (Granholm , 1989) The failure of the adult CNS to repair following injury has significant clinical consequences. Damage caused by physical trauma, vascular defects (such as a stroke) or chronic inflammation (for example, meningitis) can result in lasting impairments for which, at present, there are no effective remedies.

Consequently, a primary goal of neuroscience research IS to devise strategies for effective repair following CNS damage, and transplantation is one of the - most important of these strategies. The aim of this approach is to transplant cells into the damaged brain either to replace nerve cells directly or to stimulate the CNS to repair itself. (Ffrench-Constant & Mathews, 1994) Although there are scattered re ports of attempts to transplant neural tissues in mammals going back before the turn of the century, it is only two decades since several laboratories in the USA and Sweden first characterized the necessary conditions to yield reliable graft survival. During the 1970's the technique was considered somewhat obscure, and was used by only a few groups studying development and regeneration in the CNS, predominantly at the anatomical level. (Dunnett & Bjorklund, 1992)

The first reports of successful functional neuron grafts in rats appeared in the late 1970's. (Perlow , 1979) This proved to be a turning point, with the subsequent two decades showing a rapid expansion of interest in the technique, and a proliferation of laboratories using neural transplantation for a wide variety of purposes in basic experimental biology as well as applied research. As a result, an increasing effort was directed towards its use in novel therapies for surgical reconstruction following damage or disease in the CNS. (Brundin , 1987; Dunnett & Bjorklund, 1992) Despite the recent surge of interest in transplantation of neuronal elements to ameliorate such diverse conditions as Huntington's disease, spinal cord injury and Alzheimer's disease, it is only with Parkinson's disease that such speculations have approached reality as yet. (Granholm , 1989)

Parkinson's disease is a progressive disorder of unknown aetiology and insidious onset which is due to degenerative changes in the ganglia at the base of the cerebrum and a loss of nerve cells in the substantia nigra. This results in a lack of dopamine, a neurotransmitter essential for brain function. The disease usually begins between 40 and 60 years of age. The prevalence of the disease has been estimated to be between 85 to 187 per 100,000 population. (Lindvall, 1994)

The characteristic symptoms of Parkinson's disease include tremor, muscle rigidity, a slow shuffling gait, and difficulty chewing, swallowing and speaking. Intelligence remains unimpaired. Despite being improved during the early part of its course by chemical increase of dopamine activity through drug therapies such as L- dopa, the disease is often fatal: this is seen as justifying more radical therapeutic experiments. (Brundin , 1988; Redmondetal., 1993)

Following the experimental phase (1979 onwards), which was considered insufficient by some authors, the first nerve tissue grafts in humans were performed in 1982. By 1994, an estimated 140 patients with Parkinson's disease had received implants of human embryonic mesencephalic tissue into the striatum. (Lindvall, 1994)

As already explained, adult nerve tissue from the CNS does not survive to any appreciable extent after transplantation; this means that the vast majority of transplants use tissue derived from foetuses.

Because of the potential for defects, spontaneous (naturally occurring) abortions are not suitable sources of tissue for transplantation: the foetus may have been aborted due to viral or bacterial infection, for example. At the moment, therefore, the only source for human foetal brain tissue is from the brains of babies which have been deliberately aborted. (Hoffer & Olson, 1991)

Scientific and medical articles are naturally written in a formal manner, using highly technical language. However, the articles describing the experiments on human foetuses appear to be couched in terms which are even more technical than usual. Thus, in an article by Kamo , published in 1986, the term "a human abortus" was used, while a paper from 1992 was entitled "Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women" (Freedman , 1992). The latter is a particularly good example of technical language removing the reader from the stark reality of the experiments: it doesn't sound quite as unacceptable as "First studies of transplants of brain tissue obtained from the unborn babies of schizophrenic women."

The mothers who have had the abortions are almost never referred to as such: if they are mentioned at all, (generally stressing that they had given consent for the experimental procedures to take place), it is as "the women" (Stromberg , 1986; Humpel , 1994; Freed , 1992;Widneretal., 1992),as "patients" (Freeman , 1991; Freedman , 1992), or, totally inconsistently, as the "donors". (Freedman , 1992) One article even went so far as to refer to the "gravida" (a technical term meaning "pregnant woman").

Scientific terminology is also being utilised to obscure inconsistencies in the reports themselves. Thus, for example, one article by Freedman . (1992) is at great pains to stress that, under United States Public Health Service regulations and Swedish law, tissue from first-trimester abortions is considered to be cadaveric material (that is, of the same standing as the body of a dead accident victim, for example) which can be used for experimental study with permission of the donor (in this case, the mother of the aborted foetus). In the same section of the article, the authors mention that one of the foetuses used was actually 13- 14 weeks old. However, the first trimester of pregnancy only lasts until 12 weeks after conception: the careful legal justification given for the experiments is not, therefore, strictly valid.

In the main, though, the papers reporting these experiments tend to avoid direct references to the use of a human "foetus": instead, the emphasis is on the cells obtained. Hence there are studies using "human fetal cortical fragments" (Humpel , 1994), "fetal cadavers" (Kontur , 1993; Spencer , 1992), and "embryonic dopamine cells present early in gestation 45-55 days [approximately 6-8 weeks] post conception". (Freed , 1992)

In all the reports of experiments involving the use of human foetal tissue, the authors have gone to great pains to justify their work. There are references made as to the legal status of the experiments (Freedman , 1992); in addition, the fact that the experiments conform to national, regional or institutional guidelines is used to stress that such experiments can be considered acceptable, that they are Thus:

"[The study was] ...carried out observing federal guidelines and under a protocol approved by the Human Investigation Committee". (Kontur , 1993)

"All studies were performed with Institutional Review Board approval" (Freeman , 1991).

' . . . with the approval of the Research Ethical Committee" (Brundin , 1988).

Further emphasis is placed on the fact that each woman having an abortion is only asked to give her consent to the use of the foetus in experimental procedures she has made the decision to terminate the pregnancy, and that she had no prior knowledge of the experiment.

The Human Fetal Tissue Transplantation Research Panel submitted a report to the Director of the National Institutes for Health in the USA towards the end of 1988. They concluded that funding of research involving human tissue obtained at induced abortions was acceptable as long as certain safeguards were in place. One of these was the observation that the timing and method of the abortion should not be influenced by the potential uses of foetal tissue for transplantation. (Hoffer & Olson, 1991) From a perusal of the literature already published, one can see that this particular safeguard is unlikely to be accorded anything more than the most cursory adherence. It has been noted that the single most important factor in achieving viable CNS grafts is the selection of the appropriate developmental age of the foetal tissue: too young and the relevant populations of nerve cells have not yet developed sufficiently, and if the foetus is too old, the neurons will have established extensive connections which will be irreparably severed by dissection for transplant (Dunnett & Bjorklund, 1992). Foetuses used in transplantation experiments have varied in age from 6 weeks (ea. Widner , 1992; Geny , 1994; Peschanski , 1994)to 19 or 20 weeks post- conception. (Brundin , 1986; Gumpel , 1988) The most successful age range for the embryos used in treatment for Parkinson's disease has been identified as between 6-8 weeks post- conception. (Brundin , 1988) Once the techniques become more widely utilised (for disorders such as Alzheimer's disease etc.) it is unrealistic to assume that this optimum age range will never be taken into account.

Tissue has been collected from embryos obtained in a variety of ways: by caesarian section (Gumpel , 1987), by careful removal using forceps prior to a suction curretage (Brundin , 1986), by removal during a hysterectomy (Freedman , 1992), by suction abortion (ea. Widner , 1992) and obtained after expulsion provoked by prostaglandin injections (Gumpel , 1987). In the same study, the authors went on to note that, in embryos obtained by routine suction abortion,

"Fragments of CNS could be easily recognized. It was not possible, however, to specify their anatomical origin inside the brain". (Gumpel , 1987)

Another article stated that,

"When using routine suction abortion procedures, over 90% of the embryos, and especially their brains, are severely damaged and grossly distorted... in some cases... it may be difficult even to locate actual embryonic tissue in the material evacuated from the uterus". (Brundin , 1987)

As the general area of origin within the brain of the tissue for transplantation is very important in identifying which major cell types are being implanted, and thus ensuring maximum success for the procedure, the failure to identify the original location of the embryonic tissue is a major handicap. As a result, the routine procedures are modified to enable the brain to be taken out almost intact. (Stromberg , 1986; Peschanski , 1994) This modification, while not affecting the mother in any appreciable way, demonstrates quite clearly that the guidelines and recommendations for such experiments are already being regarded as optional.

One viewpoint which is used to help justify the use of foetal tissue in transplants is that the foetus is dead, so that the same legal and moral regulations would be applied to foetal tissue as to postmortem organ donations from adults and children. There are some people who would argue that, just as a murder victim's relatives might give permission for the organs to be donated but still deploring the murder, an aborted foetus could also be used for research or medical treatment. (Hoffer & Olson, 1991) The problem with such a viewpoint is that the foetus is definitively dead - a point made very clear in a study which used foetuses expelled after prostaglandin administration:

". . . it must be noted that we never obtained survival of these embryos - the embryo was probably dead several hours before expulsion". (Gumpel , 1987)

There is, after all, no point transplanting dead tissue; the nerve cells must be alive and capable of continued development and integration within the brain of the recipient.

The use of human foetal tissue for the purposes of alleviating human suffering is at least understandable, whatever one's views. But, there is a more horrifying aspect to these experiments. Because the exact course of development of the transplants is not yet fully understood, some scientists are studying the effects of taking human foetal tissue and implanting it into the brains of rats and mice and allowing it to develop, sometimes for several months. (Stromberg , 1986; Brundin , 1988; Humpel , 1994; Gumpel , 1987; Granholm , 1989) As the moratorium on all foetal tissue transplantation research declared in 1988 by the U.S. Department of Health and Human Services applies only to transplants into human patients (Freedman , 1992), the transplanting of human foetal tissue into animals is likely to continue at a steady pace.

As neural transplantation techniques as a treatment for disorders such as Parkinson's disease are developed, further issues will emerge. There is the possibility that women will be 'encouraged' in their decision to have abortions. The thought that the baby could be donated to 'help someone else' might be used to justify the abortion (however implicitly). The potential for financial inducements also gives cause for alarm: a wealthy patient, faced with the prospect of a debilitating and ultimately fatal disorder, might seek to induce a woman to have an abortion so that the brain tissue could be used. This is not an unrealistic concern; as similar instances have occurred with kidney donations, and with surrogate motherhood. Another point for consideration is the possibility that a woman might even go so far as to become pregnant deliberately, in order to provide a source of tissue for themselves or for family members, as under current organ donation guidelines the donor is permitted to specify the recipients of the tissue. (Hoffer & Olson, 1991) Finally, there is the possibility that, in the not too distant future, IVF techniques could be employed to 'create' embryos as potential tissue banks, further eroding the concept of the sanctity of human life from the very moment of conception.

For Catholics, there is, quite simply, no moral dilemma. The Holy Father, Pope John Paul II, explicitly condemned all such experiments:

"... procedures that exploit living human embryos and fetuses - sometimes specifically 'produced' for this purpose by fertilization - either to be used as 'biological material' or as providers of organs or tissue for transplants in the treatment of certain diseases. The killing of innocent human creatures, even if carried out to help others, constitutes an absolutely unacceptable act". ( n 63)

References

Bakay, R.A.E., Barrow, D.L., Fiandaca, M.S., Iuvone, P.M., Schiff, A. & Collins D.C. (1987) Biochemical and behavioral correction of MPTP Parkinson-like syndrome by fetal cell transplantation. 495: 623-640.

Bartus, R.T. (1987) Neural tissue transplantation: comments on its role in general neuroscience and its potential as a therapeutic approach. 495: 355- 361.

Brundin, P., Nilsson, O.G., Strecker, R.E., Lindvall, O., Astedt, B. & Bjorklund, A. (1986) Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease. 65: 235-240.

Brundin, P., Strecker, R.E., Lindvall, O., Isacson, O., Nilsson, O.G., Barbin, G., Prochiantz, A., Fomi, C., Nieoullon, A., Widner, H., Gage, F.H. & Bjorklund, A. (1987) Intracerebral grafting of dopamine neurons: experimental basis for clinical trials in patients with Parkinson's disease. 495: 473-496.

Brundin, P., Strecker, R.E., Widner, H., Clarke, D.J., Nilsson, O.G., Astedt, B., Lindvall, O. & Bjorklund, A. (1988) Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. 70: 192-208.

Brundin, P. (1992) Dissection, preparation and implantation of human embryonic brain tissue. In: Dunnett, S.B. & Bjorklund, A. eds. Oxford: Oxford University Press.

(1994) London: Geoffrey Chapman.

Dunnett, S.B. & Bjorklund, A. eds. (1992) Oxford: Oxford University Press.

Ffrench-Constant, C. & Mathews, G.A. (1994) Brain repair: lessons from developmental biology. 242(Suppl 1): S29-S32.

Freed, C.R., Breeze, R.E., Rosenberg, N.L., Schneck, S.A., Kriek, E., Qi, J., Lone, T., Zhang, Y., Snyder, J.A., Wells, T.H., Olson Ramig, L., Thompson, L., Mazziona, J.C., Huang, S.C., Grafton, S.T., Brooks, D., Sawle, G., Schroter, G. & Ansari, A.A. (1992) Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease. 327: 1549-1555.

Freedman, R., Stromberg, I., Seiger, A., Olson, L., Nordstrom, A.L., Wiesel, F.A., Bygdeman, M., Wetmore, C., Palmer, M.R. & Hoffer, B.J. (1992) Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women. 32: 1148-1163.

Freeman, T.B., Spence, M.S., Boss, B.D., Spector, D.H., Strecker, R.E., Olanow, C.W. & Kordower, J.H. (1991) Development of dopaminergic neurons in the human substantia nigra. 113: 344-353.

Geny, C., Naimi-Sadeoui, S., Jeny, R., el Majid Belkadi, A., Juliano, S.L. & Peschanski, M. (1994) Long-term delayed vascularization of human neural transplants to the rat brain. 14: 7553-7562. Granholm, A.C., Stromberg, I., Gerhardt, G.A., Seiger, A, Olson, L. & Hoffer, B.J. (1989) Transplantation in Parkinson's disease: experimental and clinical trials. In: Seil, F.J., ea., New York: Alan Liss, Inc. 227-237.

Gumpel, M., Lachapelle, F., Gansmuller, A., Baulac, M., Baron van Evercooren, A. & Baumann, N. (1987) Transplantation of human embryonic oligodendrocytes into Shiverer brain. 495: 71-85.

Hoffer, B.J. & Olson, L. (1991) Ethical issues in brain-cell transplantation. 14: 384-388.

Humpel, C., Bygdeman, M., Olson, L. & Stromberg, I. (1994) Human fetal neocortical tissue grafted to rat brain cavities survives, leads to reciprocal nerve fiber growth, and accumulates host IgG. 340: 337-348.

John Paul II (1995) Encyclical Letter

Kamo, H., Kim, S.U., McGeer, P.L. & Shin, D.H. (1986) Functional recovery in a rat model of Parkinson's disease following transplantation of cultured human sympathetic neurons. 397: 372-376.

Kontur, P.J., Leranth, C., Redmond, D.E., Roth, R.H. & Robbins, R.J. (1993) Tyrosine hydroxylase immunoreactivity and monoamine and metabolite levels in cryopreserved human fetal ventral mesencephalon. 121: 172-180.

Lindsay, R.M., Emmett, C., Raisman, G. & Seeley, P.J. (1987) Application of tissue culture and cell-marking techniques to the study of neural transplants. 495: 35-52.

Lindvall, O. (1994) Neural transplantation in Parkinson's disease. In: Dunnett, S.B. & Bjorklund, A., eds., New York: Raven Press Ltd. 103-137.

Perlow, M.J., Freed, W.J., Hoffer, B.J., Seiger, A., Olson, L., & Wyatt, R.J. (1979) Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. 204: 643-647.

Peschanski, M., Defer, C., N'Guyen, J.P., Ricolfi, F., Monfort, J.C., Remy, P., Geny, C., Samson, Y., Hantraye, P., Jeny, R., Gaston, A., Keravel, Y., Degos, J.D. & Cesaro, P. (1994) Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon. 117: 487-499.

Redmond, D.E., Roth, R.H., Spencer, D.D., Naftolin, F., Leranth, C., Robbins, R.J., Marek K.L., Elsworth, J.D., Taylor, J.R. & Sass, K.J. (1993) Neural transplantation for neurodegenerative diseases: past, present, and future. 695: 258-266.

Sladek, J.R., Collier, T.J., Haber, S.N., Deutch, A.Y., Elsworth, J.D., Roth, R.H. & Redmond, D.E. (1987) Reversal of Parkinsonism by fetal nerve transplants in primate brain. 495: 641-657.

Spencer, D.D., Robbins, R.J., Naflolin, F., Marek, K.L., Vollmer, T., Leranth, C., Roth, R.H., Price, L.H., Gjedde, A., Bunney, B.S., Sass, K.J., Elsworth, J.D., Kier, E.L., Makuch, R., Hoffer, P.B. & Redmond, D.E. (1992) Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson's disease. 327: 1541-1548.

Stromberg, I., Bygdeman, M., Goldstein, M. Seiger, A. & Olson, L. (1986) Human fetal substantia nigra grafted to the dopamine- denervated striatum of immunosuppressed rats: evidence for functional reinnervation. 71: 271-276.

Widner, H., Tertrud, J., Rehncrona, S., Snow, B., Brundin, P., Gustavii, B., Bjorklund, A., Lindvall, O. & Langston, J.W. (1992) Bilateral fetal mesencephalic grafting in two patients with Parkinsonism induced by l-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP). 327: 1556-1563.

This article was taken from the July 1996 issue of "Faith Magazine", published by The Faith-Keyway Trust, 16a off Coniston Way REIGATE Surrey RH2 OLN, Phone 01737-770016, email pwbutcher@cix.compulink.co.uk.

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