O’Donovan, M. and Stuparich, J (eds), (1994) The Abortion Debate: Pro-Life Essays. ACT Right to Life Association, Canberra, Australia. pp99-111.
Peter McCullagh *
ATTITUDES towards others are as frequently influenced by the roles in which they are cast as by any intrinsic features they possess. Whilst intrinsic features, by their nature, will be subject to little change, the role that the individual fills may be readily altered and, with it, the perception of the individual by the community.
The intention of this paper is to consider several quite disparate roles which the foetus has filled as a direct consequence of trends in medical practice and research and then to examine the impact which those roles have had, and are likely to have, on common attitudes towards the foetus. Of the three roles nominated, that of the foetus as the patient (in the sense that I shall use the term) is the most recent.
Whilst the foetus has been regarded as a "co-patient" throughout the history of obstetrics, I am concerned in this paper not with treatment of the foetal patient by optimal management of the mother's pregnancy but with the burgeoning field of implementing therapy that is directly delivered to the foetus without maternal intermediation. The relative inaccessibility of the mammalian foetus in utero has placed it almost out of reach until recent developments in intra-uterine diagnosis and manipulation became available.
The enormous difference which separates the first role of the foetus, identified in the title, from the remaining two is, of course, that the foetus is a subject in receipt of treatment in the first but an object to be utilised for the treatment of others in the second and third roles. All three roles are of relatively recent development - more or less within the last three decades. What predictions can be made concerning cross-impact? In particular, how will the role of one foetus, selected to receive high technology treatment square with that of another, less fortunate and destined to serve as a commodity? The ultimate outcome of interaction between the differing perceptions is yet to be determined. However, there have been some early indications and they are not especially encouraging.
Both uses of the human foetus, namely as an experimental preparation and as a transplant donor, have developed substantially since the acceptance by many communities of policies allowing abortion on demand. The precise nature of the association between changes in policy on abortion and changes in preparedness to regard the foetus as a medical commodity, and to deal with foetuses accordingly, is not clearcut. However, it would seem reasonably clear that abortion-on-demand policies ensured a considerable expansion in the availability of foetuses collected under optimal conditions (optimal for the experimenter that is, rather than the foetus). It also appears likely that the frequent acceptance of removing a foetus as being of no more moral import than removing a molar smoothed the way for previously unacceptable uses of foetuses that became increasingly available. The acceptance of the procedures entailed in these uses has undoubtedly been facilitated by the success of efforts to distance subsequent uses to which the foetus is put from any unpleasantness involved in its procurement in what passes for the community mind.
Use of the human foetus in experimentation began in the 1960s, flourished in the 1970s and abated thereafter. It is rarely undertaken (at least with government funding) now, with one very notable exception. Human foetal experimentation may conveniently be classified into three groups:
Some comment on each category is appropriate.
Use of the whole foetus ex utero as an experimental preparation was most frequent in the 1960s and 1970s. The stated purpose of these experiments included attempts to design an artificial placenta and various studies of the biochemistry of developing organ systems. It was notable for the frequency with which authorship of reports was shared between the United States and "overseas" experimenters. The tendency was for the former to supply the funds while the latter supplied the foetuses. In one particularly notorious study, the capacity of decapitated human foetal heads, maintained in the laboratory, to break down glucose was examined.(2)
Studies such as this Scandinavian/American collaboration led to allegations of "imperialism" in research: experimentation that was unacceptable within the US was undertaken in other jurisdictions by US researchers.
The realisation of the implications of such offshore research ultimately led theUS National Institutes of Health to introduce a requirement that human experimentation performed outside of the US must comply with the ethical standards applicable within the US if it was to be funded from that source.
Another aspect of regulation of research on the whole foetus ex utero which has seen some restriction during the last two decades concerns the vital status of the experimental subject. The term "vital status" refers to the extent to which a subject manifests signs of life. It should not be confused with "viability" which relates to the capacity for extended existence.
The two expressions have frequently been used interchangeably, and quite inaccurately, by those arguing in support of experimentation on the foetus. A (non-viable) foetus with no prospect of extended survival outside the uterus on account of its immaturity may, nevertheless be alive.
Some recognition that vital status has moral status, even in a non-viable foetus, is reflected in the changes effected in the United Kingdom guidelines on foetal experimentation. Whereas the "Peel Report" (1972)(3) approved the experimental use of foetuses of less than 20 weeks gestation irrespective of the presence of vital signs, the "Polkinghorne Report" (1989)(4) concluded that signs of life must be absent, before experimental use, regardless of the extent of foetal immaturity.
Experimentation on the foetus in anticipation of abortion has been undertaken in particular to define the capacity of novel therapeutic agents under trial (such as antibodies and vaccines) to cross the placenta from mother to foetus. The agent under test is administered to the mother, who has elected to abort her foetus, at an appropriate interval before that event. Following abortion, the body of the foetus is examined both for the presence of the agent and for any early manifestations of damage attributable to it. The general rationale of this type of experiment is that if an agent is able to enter the foetus it may produce damage. The use of the foetus as an experimental preparation in anticipation of abortion is now precluded by the codes of most bodies which award research funds. This does not prevent the performance of such experiments if private funding is available. For example, whilst the Australian National Health and Medical Research Council would not support such research, there were anecdotal reports in the 1980s of a pharmaceutical company undertaking it in Australia.
The conduct of experimentation on human embryos produced by in-vitro fertilisation (IVF) has been undertaken, and vigorously advocated, in a number of countries during the past decade. The purposes of such research have ranged from seeking to improve foetal health, (improvement in IVF technology, study of normal developmental processes, detection of genetic abnormalities) to the other end of the spectrum, namely improvement in contraceptive and abortion technology. I am unable to discern any significant moral distinctions between experimentation on the IVF embryo and the foetus produced by traditional means. Nevertheless, IVF embryo experimentation has often been presented as fundamentally different from foetal experimentation on the basis of the morphological features of the subject - an item without resemblance to a human being on visual inspection is readily excluded from that category.
Use of the human foetus as a source of transplantable material has concentrated on three procedures, although almost everything has been attempted on occasion. The three procedures that have been trialled most frequently entail the transplantation of tissues capable of forming white blood cells (foetal liver and thymus), of foetal pancreas and of foetal brain. The transplantation of foetal thymus and/or liver has been undertaken into infants and young children with congenital deficiencies of the immune system. I believe that it would be fair comment to say that it has never achieved any widespread acceptance because better alternative forms of therapy are available and foetal tissue has failed to produce reliable results. The technique is now the preserve of enthusiasts in a relatively small group of clinics.
Transplantation of the insulin-producing cells of the foetal pancreas into diabetic patients was undertaken in many clinics during the 1970s and 1980s. The aim was to prevent the occurrence of long-term diabetic complications in patients' blood vessels. Whilst alternative forms of transplantation of insulin-producing tissue (for example, the transfer of segments of pancreas from "brain-dead" adult patients) have yet to become so effective as to be adopted as standard forms of treatment, the use of foetal pancreatic tissue transplantation as a therapy for juvenile diabetic patients has been discontinued in all except a very small number of clinics. Once again, I believe it would be fair comment to observe that abandonment of this procedure was not the result of any political pressure. Expressed simply, it consistently failed to deliver the outcomes predicted by its advocates.
The third form of foetal tissue transplantation, and certainly the one which has become fashionable in the 1990s, entails the transfer of nerve cells from the foetal brain to the brain of patients with Parkinson's disease. At the time of writing (late 1993), this procedure has been adopted enthusiastically in an increasing number of neurosurgical clinics. It can be categorically stated that its likelihood of long-term success remains to be demonstrated, let alone convincingly confirmed.
Accompanying the outbreak of the foetal tissue transplantation procedures outlined above have been a number of "ancillary" developments. One of these has been the establishment of a niche industry to facilitate the supply of foetal tissue to transplant surgeons whilst distancing the procurement process from the end user. These include, for example, non-profit organisations such as the International Institute for Advancement of Medicine which undertakes the collection of tissues from aborted foetuses in clinics and hospitals, together with more commercial operations such as the publicly listed Hana Biologics which has set itself the goal of developing transplantable products from foetal tissues.
A second consequence of the promotion of foetal tissue transplantation has been advocacy for and, in some cases implementation of, modified abortion techniques likely to deliver foetal tissue in optimal condition for transplantation. This has been particularly noticeable in the case of foetal brain cell transplantation for Parkinson's disease. Animal experimentation has suggested that the gestational age of foetal
brain tissue to be transplanted is crucial as also is the condition of that tissue when collected. To meet these requirements, both the timing and technique of abortion will have to be modified (and this has occurred in some clinics).
Neither of the two foetal roles considered so far, namely as experimental preparations and as sources or "donors" of tissue for transplantation connote a good outlook for the foetus. In contrast, the notion of foetus as patient implies that the foetus will become the beneficiary. The emergence of this third role alongside two others in which the foetus serves as a commodity would seem likely to produce some contradictions in attitudes towards foetal subjects. Before considering these, it is appropriate to review the events that have underpinned the concept of the foetus as patient.
As indicated at the outset, the category of foetal patient in this article is intended to refer to the foetus subject to direct therapeutic intervention, as distinct from the indirect benefit accruing to the foetus in consequence of optimal management of the mother throughout pregnancy. The initiation of direct foetal therapy is usually identified with the introduction of in utero blood transfusion by Liley in 1963.(5) More recently, a number of techniques designed to alleviate foetal pathology by direct surgical intervention on the foetus in utero have been developed. These may be best summarised by considering the abnormalities that the protocols are intended to rectify.
Hydrocephalus, an abnormal enlargement of the brain that can occur as a result of blockage of the normal movement of cerebrospinal fluid, can now be diagnosed in the foetus in utero. Intervention at the earliest possible time to place a catheter in position to bypass the blockage offers the opportunity of minimising the extent of permanent brain damage. The operation has now been undertaken before birth in a number of cases.
A second type of abnormality that has been diagnosed and surgically treated in the foetus in utero is obstruction of the urinary tract. Once again, relief of the obstruction at the earliest possible time is likely to reduce the damage sustained by the kidney. These operations have been the most successful examples of foetal surgery.
Congenital diaphragmatic hernia is a condition in which the muscular tissue which normally separates the chest from the abdomen is poorly formed with the result that the abdominal contents occupy the chest. This prevents the normal expansion
of the lungs. As breathing is not an essential activity until after birth, it might be assumed that congenital diaphragmatic hernia could be left until then to be treated. However, when this is done, the capacity of the lungs to expand and to function normally appears already to have been permanently compromised. For this reason, a number of clinics have undertaken surgical repair in utero.
Sacrococcygeal teratomas are tumors which develop in the sacral region of the foetus. Whilst these tumors are generally benign they can attain considerable size in the foetus and lead to a potentially catastrophic side effect, namely the "short circuiting" of large volumes of blood from the arteries of the tumor to its veins. The resulting circulatory overload predisposes to heart failure. Hence, it is imperative to excise the teratoma at the first opportunity if irreversible damage to the heart is to be avoided.
Finally, another type of foetal therapy, which is technically an adaptation of Liley's original intra-uterine transfusion procedure has been developed for the in utero treatment of congenital deficits of the immune system. In these deficits, particular types of stem or precursor cells capable of giving rise to the equivalent types of mature, immune system cells are lacking. A therapeutic response to the conditions has entailed the transfusion of the missing type of stem cell from another individual into the deficient foetus.
The success rate of all the forms of foetal therapy (apart from exchange blood transfusion) has been low. Nevertheless, the success rate of treatment of the same conditions, if this is deferred until after birth is generally even poorer. A general ethical difficulty arising with any form of foetal surgery relates to the necessity to trial procedures that are likely to have a very high mortality rate (even though a trial may show that mortality is even higher in the absence of intervention in utero). My specific interest in this subject now is not, however, the ethical difficulties of introducing these new forms of foetal therapy but the impact that they are likely to have on attitudes to the foetus given their co-existence with other practices such as use of the foetus in experimentation or as a transplant donor. How compatible, within society, are attitudes which seek to provide the highest order of technological assistance to the foetus with other attitudes which regard the foetus as a commodity to be utilised for the assistance of others? Is foetal therapy likely to impact upon attitudes towards foetal tissue use, even perhaps on attitudes towards abortion itself?
The answers to the preceding questions are yet to come but the portents are anything but encouraging. Perhaps the question should have been to what extent is abortion and subsequent foetal utilisation likely to impact upon, and to pollute, attitudes towards foetal therapy?
An early indication of the likely direction of interaction between attitudes engendered by foetal utilisation and foetal treatment is provided in some of the medical reports of the latter. Reading a review of the use of surgery in utero to repair congenital diaphragmatic hernia, one comes upon the incidental comment that, in an indicated number of cases, "foetectomy was performed at the same time as hysterotomy".(6) Succinctly expressed, as the patient could not be successfully treated, he or she was successfully put down. What started as an attempt at surgical cure became an abortion.
An article reviewing the use of surgery to treat hydrocephalus in utero is similarly disconcerting. Of (foetal) patients who had a catheter inserted to bypass a blockage to cerebrospinal fluid circulation and were then replaced in the uterus, approximately one fifth were subsequently electively aborted because blood samples obtained from them at the time of placement of the catheter had revealed chromosomal abnormalities.(7) What of the transfusion of stem cells into the foetus to correct immune deficiencies? The majority of instances of this procedure appear to have utilised cells taken from another foetus which had been aborted and which was normal (clearly, it would be unethical to transfer abnormal cells to a patient). We may conclude that innovations in "foetal therapy" are not necessarily examples of regarding the foetus as the patient.
The ultimate outcome of interplay in societal attitudes between the three roles for the foetus identified in the title remains to be determined. However, at the risk of appearing unduly pessimistic, it may be that recognition of the role of the foetus as patient may not have the favourable impact on attitudes towards the foetus that one might have predicted. Even more significantly, rather than the role of patient advancing the status of the foetus in general, it could even be that the status of other (non-foetal) patients may be adversely affected by foetal assumption of this role. The preparedness to reassess a foetus, already submitted to surgery to correct hydrocephalus and returned to the uterus, and to undertake an abortion on the basis of cytogenetic abnormalities discovered during that surgery indicates that the foetal patient is regarded as a foetus rather than a patient. The recourse to abortion in the course of surgery when the available resources prove insufficient to correct a diaphragmatic hernia implies that the line separating foetal experimentation and foetal therapy can be thin and ill defined. It also raises some interesting implications for surgery on non-foetal patients: "we were unable to rectify so-and-so's ailment, so we put him/her down".
Finally, the situation in which a normal, but unwanted, foetus is used to provide stem cells to attempt repair of an abnormal, but wanted, foetus appears to me to raise some alarming questions about the directions in which community attitudes towards individuals are evolving. External, highly subjective assessments of the value of persons seem to be replacing any absolute standards. Are biologically identical and morally equivalent individuals to be arbitrarily assigned widely divergent roles and then dealt with accordingly?
* Peter McCullagh MD (Melb) DPhil (Oxon) MRCP is a Senior Fellow in Developmental Physiology at the John Curtin School of Medical Research, Australian National University.
1. Based on a presentation to the New Zealand Society for the Protection of the Unborn Child, May 22, 1993.
2. Adam, P. et al (1973), Cerebral oxidation of glucose and D-BOH-butyrote by the isolated perfused human head. Pediatric Research, 7, 309.
3. The Use of Fetuses and Fetal Material for Research: Report of the Advisory Group to the Department of Health and Social Security, Scottish Home and Health Department and the Welsh Office. H.M. Stationery Office. London, 1972.
4. Review of the Guidance on the Research Use of Fetuses and Fetal Material. H.M. Stationery Office. London, 1989.
5. Sir William Liley, after completing a PhD degree at the John Curtin School of Medical Research, ANU, returned to New Zealand and pioneered clinical foetology. He was the first president of New Zealand's Society for the Protection of the Unborn Child.
6. Longatier, MT et al (1991), Maternal outcome after open fetal surgery. A review of the first 17 human cases. Journal of the American Medical Association, 265, 737-741.
7. Manning, FA et al (1986) Catheter shunts for fetal hydronephions and hydrocephalus. Report of the International Fetal Surgery Registry. New England Journal of Medicine, 315, 336-340.
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