House of Commons - Science and Technology

Select Committee on Science and Technology Written Evidence

Annex B

The HFEA and Recent Developments in the Creation of New Human-Animal Embryos and Foetuses

A. INTRODUCTION

Crossing the species barrier is a procedure that has always fascinated humanity. In ancient Greece and Rome, for example, centaurs (human-horse hybrids), fauns (human-goat hybrids) and minotaurs (human-bull hybrids) were accepted as being special and endowed with specific powers. And although they were not considered as being part of the human race, they were neither seen as being entirely animal. Indeed, their distinct and solitary status in mythology resulted in them being sometimes rejected as different and portrayed as lonely monsters. This happened, for example, in the myth relating to the minotaur which was eventually destroyed by Theseus.

But crossing the species barrier is no longer in the domain of mythology and new procedures have recently been developed by scientists which mix human and animals biological elements and thus question the very concept of being entirely human.

In the following paper, the procedures of xenotransplantation and transgenesis are considered in order to put into context the new developments in embryological and foetal animal-human hybrids which will be especially examined in the light of the UK Human Fertilisation and Embryology Act (1990).

XENOTRANSPLANTATION

Xenotransplantation (the transplantation of cells, tissues and organs from one species to another) was first considered almost a hundred years ago. Since then, there have been sporadic instances of clinical applications in the history of medicine but interest was only rekindled in the early 1990s as a result of new progress in the biomedical sciences. Indeed, because of the great success of allotransplantation (human to human) an ever increasing number of operations are being performed and the need for human transplants now exceeds many times the supply. It is because of this shortage and the possibility for scientists to create a virtually unlimited supply of transplants through the use of animal material, that xenotransplantation is currently being studied as a therapeutic solution to several previously incurable diseases relating to heart, liver, lung and kidney disorders. Additionally, there are other unmet medical needs which could potentially be treated by xenotransplantation such as incurable neurological diseases (Parkinson's and Alzheimer's disease), paraplegia due to spinal cord lesions and pancreatic islet or beta cell transplants for treatment of diabetes.

TRANSGENESIS

For many years, scientists have also been creating transgenic animals in which some foreign (human or non-human) genes are deliberately inserted into the genome of animals. Mice with human immune-system cells and organ-donor pigs with human genes have thus been created which can also pass on the human genes to subsequent generations.

However, several technical obstacles have limited the amount of human genes that can be expressed in animals such as mice. Indeed, only a few human genes at a time can be successfully inserted into the mouse genome without interrupting essential mouse gene functions or creating a fatal combination.

Other transgenic animals include sheep and goats which can express foreign proteins in their milk. Transgenic chickens are now also able to synthesize human proteins in the "white" of the eggs which scientists believe may eventually prove to be a valuable source of proteins for human therapy.[175]

EMBRYOLOGICAL AND FOETAL ANIMAL-HUMAN HYBRIDS

The procedures being considered in this report, however, will address new developments in which eggs and sperm in addition to embryological and stem cells are used between animals and humans.

And in this context both hybrid and chimeric embryos and foetuses will be considered. Hybrid embryos or foetuses describing entities created through the general use of eggs and sperm cells of different origins with chimeras generally representing embryos or foetuses whose cells are of specific mixed genetic origin.[176]

ETHICAL DISCUSSION

To many people, the resulting animal-human entities created by crossing the species barrier would give rise to grave and complex concerns.

Xenotransplantation, for example, raises medical, legal, cultural, religious and ethical problems. And at first, public acceptation of such a procedure was minimal. With time, however, and because of the potential to save lives, xenotransplantation has become more ethically acceptable to most sections of the UK population provided the medical problems of rejection and transmission of disease have been addressed.

But in crossing the species barrier, the definition of "being human" would no longer be clear cut. And this has given rise to concerns by bodies such as the Pontifical Academy for Life that the ethical evaluation of the practice of crossing the species barrier should be measured against current anthropological considerations, especially if they deal with personal identity. Indeed, it suggests that any ethical appraisal of crossing the species barrier must ultimately address the question of whether the introduction of foreign animal parts into the human body modifies a person's identity and the rich meaning of being human. And if modifying a human body with animal parts is indeed being considered, then questions relating to the acceptable limit of such modifications may then be posed.[177]

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Many indeed believe that the ethical implantation of foreign parts into a human body is related to the degree of change that it may entail in the human identity of the person who receives them.[178] In this respect, it should be noted that not all parts of the human body are generally considered to be equally important in the expression of the identity of the person. Some body parts exclusively perform their specific function such as the heart which is considered as a biological pump. Others, instead, add to their functionality a strong and personal symbolic element which inevitably depends on the subjectivity of the individual. And others still, such as the brain and reproductive cells, are often considered to be intrinsically linked with the personal identity of a person.

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The Pontifical Academy for Life has indicated, for example, that the transfer of animal brain and reproductive cells to human persons should not be possible because of the risks connected with such a procedure with respect to human identity. However, it does suggest that those animal parts which are seen as being purely functional could be transferred into a human person, on a case by case basis, and depending on the specific relation to the symbolic meaning which they take on for each individual person.[179]

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Others, however, disagree with this stance. Indeed, some bioethicists, such as Jason Scott Robert and Francoise Baylis,[180] are unwilling to draw a specific line concerning interspecies hybrids. Indeed they assert that they take "no stance at all" on whether "interspecies hybrids or chimeras from human materials should be forbidden or embraced." This is because they indicate that "the arguments against . . . creating novel part-human beings . . . are largely unsatisfactory."

B. NEW DEVELOPMENTS IN THE CREATION OF NEW HUMAN-ANIMAL EMBRYOS AND FOETUSES

1. The creation of gametal human-animal hybrid embryos

1.1 Gametal Human-Cow Hybrid Embryos

The company Advanced Cell Technologies was reported, in November 1999, to have created the first human embryo clone using a gametal human-animal hybrid. This was achieved when the nucleus of an adult human cell was inserted into a cow's egg stripped of its chromosomes in order to create a cloned embryo. This embryo was left to develop and divide for 12 days before being destroyed.[181],[182].

In addition, Professor Panayiotis Zavos who runs a fertility laboratory in the USA indicated, in September 2003, that he had created around 200 human-cow hybrid embryos that lived for around two weeks and grew to several 100 cells in size and beyond the stage at which cells showed the first signs of developing into tissues and organs. It was also noted that they appeared to have normal human DNA.[183],[184]

http://uk.news.yahoo.com/030916/12/e8k6h.html

http://www.timesonline.co.uk/article/0,,8122-817880,00.html

Theoretically, this procedure could enable a person to produce a human cloned embryo.

Legislation in the UK

Whether or not gametal human-cow hybrid embryos come under the jurisdiction of the HFEA depends on whether or not they are "human". If they are, then the creation of such embryos would be possible provided a licence was obtained from the HFEA following the ruling of R (Quintavalle) v Secretary of State for Health of the 13 March 2003.[185].

1.2 Gametal Human-Rabbit Hybrid Embryos

In August 2003, Hui Zhen Sheng of Shanghai Second Medical University, China, announced that gametal human-rabbit hybrid embryos had been created by fusing adult human cells with rabbit eggs stripped of their chromosomes. Using donor cells from the foreskins of a five-year old boy and two men, and facial tissue from a woman, the researchers created rabbit-human hybrid embryos which developed to the approximately 100 cell stage that forms after about four days of development,[186],[187],[188]

Theoretically, this procedure could enable a person to produce a human cloned embryo.

Legislation in the UK:

Whether or not gametal human-rabbit hybrid embryos come under the jurisdiction of the HFEA depends on whether or not they are `human'. If they are, then the creation of such embryos would be possible provided a licence was obtained from the HFEA following the ruling of R (Quintavalle) v Secretary of State for Health of the 13 March 2003[189].

2. THE CREATION OF NEW GENETIC HUMAN-ANIMAL CHIMERIC EMBRYOS AND FOETUSES

2.1 Genetic Human-Hamster Chimeric Embryos[190]

The hamster test is a well established test in the UK which gives indications relating to the ability of a man's sperm to penetrate a hamster egg stripped of its outer membrane, the zona pellucida. After fertilisation by the human sperm of the hamster egg, this human-hamster chimeric embryo can be left to develop until the two cell stage for observation.

Legislation in the UK

The Human Fertilisation and Embryology Act (1990) indicates in Article 4. (1)(c) that:

"No person shall mix gametes with the live gametes of any animal, except in pursuance of a licence."

But, as indicated under Schedule 2, Article 1. (1)(f) of this Act, a licence may authorise, in the course of providing treatment services, "mixing sperm with the egg of a hamster, or other animal specified in directions, for the purpose of testing the fertility or normality of the sperm, but only where anything which forms is destroyed when the test is complete and, in any event, not later than the two cell stage".

2.2 Genetic Human-Mouse Chimeric Embryos

In 2003, Scientists at the South Korean firm Maria Biotech, were reported to have injected human embryonic stem cells labelled with a fluorescent protein into 11 mouse embryos which developed to about the 100 cell stage. The embryos were then carried by foster mice, whereby five offspring were born with fluorescence in tissues including the heart, bones, kidney, and liver. However, the scientists terminated the project after having to address "severe protests" from the public.[191]

Legislation in the UK

This procedure is not covered by the Human Fertilisation and Embryology Act (1990).

2.3 Genetic Human-Sheep Chimeric Fetuses

In 2001, researchers at the University of Nevada, USA, injected human stem cells coming from bone marrow or umbilical cords into sheep foetuses. The sheep then grew up with a small proportion of human cells throughout their bodies.[192] More recently (December 2003) it was announced that human stem cells which were injected into sheep fetuses were able to produce a surprisingly high proportion of human cells in some organs.In some cases between 7-15% of all the cells in the sheep's liver were human.

The human cells were injected around halfway through gestation—before the fetus' immune system has learned to differentiate between its own and foreign cells, so that the animal does not reject them, but after the body has formed. This procedure ensures that the resulting animals look like normal sheep rather then human-sheep hybrids. The researchers recognised, however, that there was no way for them to determine whether the sheep fetuses had human brain cells.[193]

Legislation in the UK

This procedure is not covered by the Human Fertilisation and Embryology Act (1990).

2.4 Genetic Human-Monkey Chimeric Fetuses

Researchers have also injected human neural stem cells into the skulls of three unborn monkeys. They then showed that these cells were incorporated into the developing brains of the animals.[194]

Legislation in the UK

This procedure is not covered by the Human Fertilisation and Embryology Act (1990).

2.5 Genetic Human-Pig Chimeric Fetuses

Pigs grown from fetuses into which human stem cells were injected were shown to be made up of three kinds of cells. Indeed, in January 2004, researchers indicated that such pigs were made up of (1) pig cells, (2) human cells and (3) hybrids cells, the latter being fully fused pig-human cells in which the DNA from both species were mixed at the most intimate level.[195]

Legislation in the UK

This procedure is not covered by the Human Fertilisation and Embryology Act (1990).

C. CONCLUSION

In March 2004, the President's Council on Bioethics of the USA indicated in a report entitled "Reproduction and Responsibility: The Regulation of New Biotechnologies"[196] that the crossing of the human-animal boundary was, in some respects, quite complex and subtle but that the mixing of human and animal tissues and materials was not by itself objectionable. In other words, in the context of therapy and preventive medicine, the President's Council accepted that the transplantation of animal parts to replace defective human ones could be considered as ethical. In addition, it had no overriding objection to the insertion of animal-derived genes or cells into a human body—or even into human foetuses—where the aim would be to address a serious disease in the patient or the developing child.Likewise in the context of biomedical research, the US Council did not see anything objectionable in the practice of inserting human stem cells into animals.But in the context of procreation—of actually mixing human and non-human gametes or blastomeres at the very earliest stages of biological development—the Council indicated that the ethical concerns raised by violating that boundary were especially acute. Thus, the drawing of clear lines limiting permissible research in this area should be specifically considered.

In this respect, the President's Council recommended that one bright line should be drawn at the creation of animal-human hybrid embryos, produced by the fertilisation of human eggs by animal (for example, chimpanzee) sperm (or the reverse). This is because the Council accepted that society should not be put into a position to judge the humanity or moral worth of such ambiguous hybrid entities (for example, a "humanzee," the analogue of the mule). Moreover, the Council stated that it did not want to see the possibly of a human being having other than human progenitors.A second bright line proposed by the Council would be drawn at the insertion of ex vivo human embryos into the bodies of animals. Thus, an ex vivo human embryo entering a uterus belongs only in a human uterus.

Therefore, the Council recommended that the US Congress draft legislation to address these biological possibilities by making it illegal to cross both these lines before having received a clear public assent.

But in the UK, there is also a need to consider these issues. Indeed, apart from the mixing of gametes with the live gametes of animals to form two cell embryos hybrids which, as indicated by Section 4. (1) (c) of the UK Human Fertilisation and Embryology Act (1990), is prohibited except in pursuance of a licence, in most of the experiments presented in this report, the resulting human-animal entities would exist in a legal vacuum. Moreover, there seem to be some confusion in the UK Act. Since it does mention the above, it may be assumed to have been drafted with the possibility of addressing the crossing of the species barrier. But the Human Fertilisation and Embryology Act (1990) does not, unfortunately, provide adequate clarifications concerning the specific status and nature of human-animal entities. Because of this situation, it is also uncertain whether the Human Fertilisation and Embryological Authority is even entitled to regulate the creation of most of the human-animal entities presented in this paper. In other words, whether or not these entities come under the jurisdiction of the HFEA depends on whether or not they are `human'. And it is probable that controls relating to the creation of such human-animal entities would only exist if the HFEA chooses to consider a broad definition of a human embryo.[197].

To conclude, the HFEA should initiate an extensive consultation of the general public and stakeholders relating to the complex ethical questions arising from the creation of animal-human hybrid embryos and foetuses. If this is not undertaken, experiments and research projects could be authorised by the HFEA, which is an 18 member non-representative and non-elected committee, without society having given an informed decision relating to the very nature of the future of humanity. This can only be considered as a very unethical and tragic situation.

175 http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/TransgenicAnimals.html Back

176 A chimera was a Greek mythological fire-breathing female monster with a lion's head, a goat's body, and a serpent's tail. In: The Oxford English Reference Dictionary, Oxford University Press, second edition, 1996. Back

177 Prospects for Xenotransplantation-Scientific Aspects and Ethical Considerations (September 26, 2001), Pontifical Academy for Life, http://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20010926 Back

178 Prospects for Xenotransplantation-Scientific Aspects and Ethical Considerations (September 26, 2001), Pontifical Academy for Life, http://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20010926 Back

179 Prospects for Xenotransplantation-Scientific Aspects and Ethical Considerations (September 26, 2001), Pontifical Academy for Life, http://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20010926 Back

180 Jason Scott Robert; Franc"oise Baylis, Crossing Species Boundaries, American Journal of Bioethics, Volume: 3 Number: 3 Page: 1-13, http://oberon.ingentaselect.com/vl=2197681/cl=54/nw=1/rpsv/cgi-bin/linker?ini=ajob&reqidx=/catchword/mitpress/15265161/v3n3/s2/p1 Back

181 BBC News-18 June 1999, Details of hybrid clone revealed, http://news.bbc.co.uk/1/hi/sci/tech/371378.stm Back

182 BBC News-13 November 1998, Company "cloned human cells", http://news.bbc.co.uk/1/hi/sci/tech/213663.stm Back

183 Coghlan, A, NewScientist.com-15 September 2003, First human clone embryo ready for implantation, Back

184 Leake, J, TimesOnline-14 September 2003, Cloning expert claims to have created "human-cow" embryo, Back

185 Lord Bingham of Cornhill indicated in his decision that Parliament could not have intended to distinguish between embryos produced by, or without, fertilisation since it was unaware of the latter possibility. The reference to fertilisation was not therefore integral to the definition but was directed to the time at which an embryo should be treated as such. In R (Quintavalle) v Secretary of State for the Health, http://www.lawreports.co.uk/hlpcmarc0.1.htm Back

186 Abbot and Cyranoski, D, Nature 413, 339 (27 September 2001), China plans "hybrid" embryonic stem cells Back