Fruitful research without human embryo exploitation

In 1988 Dr Jérôme Lejeune was invited to address the UK Parliamentary Medical and Scientific Advisory Committee to the All-Party Parliamentary Pro-Life Group in response to the Government’s consultation paper on legislation on IVF and embryo research. Proposals regarding human embryo experimentation up to the fourteenth day of life were recommended by the Warnock Report (1984), and in his address, Dr Lejeune endeavored to demonstrate that effective research into genetic diseases would not depend on techniques requiring the use of human embryos.

In the introduction to Dr Lejeune’s paper, the Rt Hon Sir Bernard Braine, Chairman of the group said:

“The scope and application of medical and scientific research has grown dramatically during the past forty years. Much of this development has been beneficial for the individual and for society as a whole but there are certain areas in which it has resulted in unacceptable and uncivilised practices. The implementation of the 1967 Abortion Act frequently involves the absolute rejection of any concern and respect for pre-natal human life.

“Our existing law has been used to justify experiments on aborted mid-gestational infants sustained by their own heart action for up to 2 hours after removal from the womb. A Report, The Use of Fetuses and Fetal Material for Research, published by the Department of Health and Social Security in 1972 stated plainly that, ‘In considering whether it is ethically justifiable to undertake such research we noted that society through Parliament, in permitting abortion in certain circumstances has accepted that where an abortion under the Act is carried out the pre-viable fetus is prevented from attaining life’.

“The Report also went on to claim that, ‘The whole pre-viable fetus has offered an important opportunity that cannot be obtained in any other way for making observations of great value …’

“Small wonder then, that once scientists had conquered the technique of generating human embryos outside the womb (in vitro fertilisation) we have been bombarded with propaganda urging the use of the embryonic human being for experimentation. This propaganda is often couched in scientific terms, promising great rewards if such experimentation were permitted. Although the All-Party Pro-Life Group in Parliament rejects human embryo vivisection we felt that expert advice was needed concerning such claims. We, therefore, established our own Scientific and Medical Advisory Committee which included some of the most eminent men and women in the world in their respective disciplines. Their mandate is to advise us on the validity of claims made; on the gaining of information regarding the causes of genetic and chromosomal diseases and their possible cure without the use of human embryos, and on alternative methods of overcoming infertility.

“These papers represent the Committee’s initial work and were submitted to the Department of Health and Social Security in response to its Consultation Paper entitled Legislation On Human Infertility Services and Embryo Research. They provide an authoritative background which should be read and considered not only by all involved in this field but in particular by those of us who will have responsibility for the legislation.”

Despite credible scientific evidence, the UK government chose to listen only to the experts whose opinions aligned with its policy. In 1990, the Human Fertilisation and Embryology Act was passed in the interests of the British research sector and the fertility industry. At the same time, the Abortion Act was amended to allow for “selective reduction” in multiple pregnancies and to remove the upper limit for children with disabilities. The licensing of IVF procedures turned unborn children into a commodity that has been traded, exploited and discarded on an unprecedented scale ever since.

In the 34 years since the following testimony by Dr Lejeune was presented to Parliament, the prospect of medical breakthroughs that would result from destructive embryo research has proven to be an empty promise. Instead, it promoted a false understanding of human nature and has ushered in a new age of eugenics.

by PROF JÉRÔME LEJEUNE

For more than two millennia, medicine has fought against death and disease. It is only in recent years that some have questioned whether our engagement for life and care was truly irreversible.

THE FUNDAMENTALS OF LIFE Life has a very, very long history, but for each of us it has a very definite beginning: the moment of conception. Progeny and parents are united by the threadlike molecule of DNA upon which the

© NIH Image Gallery complete genetic information is written in miniaturised language.

The spermhead carries one metre length of DNA, cut into 23 pieces, the chromosomes, each of which is precisely coiled and visible under the microscope.

As soon as one sperm penetrates the “zona pellucida” in which the ovum is wrapped, it becomes impenetrable to other sperm. In purely operational terms, as soon as the sperm’s 23 paternal chromosomes enter the ovum, with its 23 maternal chromosomes, the total information necessary and sufficient to dictate the genetic make-up of the new human being is established: not a theoretical or a potential human being, but the very human being we will later call Peter, or Paul, or Magdalene.

Soul and body or spirit and matter are intricately interwoven at the beginning of life. Indeed we use the same word, conception, to describe the process by which an idea, a concept, comes to our mind as we do to define the genetic process by which a new being, a conceptus, comes to life.

TECHNICALITIES OF EARLY LIFE Once a month, a ripe ovum is expelled from the ovary and enters the uterine tube where it may

“Soul and body or spirit and matter are intricately interwoven at the beginning of life. Indeed we use the same word, conception, to describe the process by which an idea, a concept, comes to our mind as we do to define the genetic process by which a new being, a conceptus, comes to life.”

encounter the sperm which, among thousands of others, will fertilise it.

It is because natural fecundation occurs between a free-floating egg and a free-floating sperm that in vitro fertilisation is possible in a glass tube which replaces the uterine tube. At the cellular level the process is identical.

Because sexually transmitted diseases and other pathological conditions may occlude the uterine tube, it was proposed to bypass the obstructed tube. If the ripe ovum is carefully aspired through a fine plastic tube into a test tube to which sperm is subsequently added, fecundation can occur. Two or three days later the tiny embryo, already feverishly organising itself inside the walls of its private home (the zona pellucida), is transferred to its mother’s womb.

When Drs Edwards and Steptoe took the risk of replacing the tiny Louise Brown into the womb of her mother, it was because everything in the sciences of genetics and embryology assured them that this little berry-looking being was neither a tumour nor a parasite, but a young member of our species, the child of Mr and Mrs Brown.

With many children already born from this technique, it is an established experimental fact that the life of each human being begins at conception. Protected in its life capsule (the zona pellucida and then the amniotic sac) the early human being is just as viable and autonomous as a cosmonaut on the

“The student who cannot identify microscopically the chromosomes of a chimpanzee, gorilla and a man would fail his exam! Human nature is absolutely unmistakable when it comes to reproduction.”

moon: refuelling with vital fluids as required from the mother vessel. At this stage shelter and nurture by the mother organism are absolutely essential.

SUSPENDED ANIMATION In Latin languages we use the same word for that which we measure with a clock and that which we check with a thermometer (le temps). This is appropriate because temperature is a measure of the agitation of molecules, and this random movement defines the passing of time.

Refrigeration reduces the molecular motion so that close to absolute zero “time comes to a standstill” as all movement stops. Because of their extraordinary vitality, human sperm and even early human embryos can withstand deep freezing and can be kept, so to speak, in suspended animation. Hence we have sperm banks, familiar in animal husbandry, and some researchers even want to set up banks of human embryos. Deep-frozen human beings may thus be thawed and transferred into their mother's wombs or into rented wombs of carrier mothers. Such embryo banks of warranted quality may be established with carefully controlled and classified pedigrees. Although the majority of scientists today deny any such intentions this possibility must be considered when society assesses the future of such techniques.

At the present time surrogate mothers are very much “à la mode” – and the biological mother may sell her child to the male buyer, usually with the proviso that it must be normal.

RESPECT FOR HUMAN NATURE The expression “human nature” is not much in vogue these days among some scientists. Nevertheless, human nature does exist: one only has to look at human chromosomes to recognise their number, their size and even their specific banding patterns. The student who cannot identify microscopically the chromosomes of a chimpanzee, gorilla and a man would fail his exam! Human nature is absolutely unmistakable when it comes to reproduction. The most advanced chimpanzee does not relate the act of copulation to the outcome of a baby chimpanzee some nine months later!

Man is the only creature who knows that love and procreation are united by nature. Even the pagans represented the god of love as a child. This discovery comes from the dawn of human memory, the lost paradise.

The Warnock Committee recognised the special nature of the human embryo when in their report they declared: “The status of the embryo is a matter of fundamental principle which should be enshrined in legislation.” (page 63: para 11.17).

They also recognised that the process of human development begins at conception when they stated: “While, as we have seen, the timing of the different stages of development is critical, once the process has begun, there is no particular part of the development process that is more important than another; all are part of a continuous process, and unless each stage takes place normally, at the correct time, and in the correct sequence, further development will cease. Thus biologically there is no one single identifiable stage in the development of the embryo beyond which the in vitro embryo should not be kept alive ... ”

Thus, when referring to this statement, the Australian Senate Select Committee on the Human Embryo Experimentation Bill 1985, concluded: “In this situation prudence dictates that, until the contrary is demonstrated ‘beyond reasonable doubt’ (to use an expression well known in our community), the embryo of the human species should be regarded as if it were a human subject for the purpose of biomedical ethics (Human Embryo Experimentation in Australia.’ page 28; para 3.18).

Thus if we were to take the Warnock reference to early human nature seriously, we must recognise that the embryo is not a perishable commodity to be frozen and defrosted on demand nor a consumable product to be purchased or transferred at will, nor experimental material, nor an item to be stocked for spare parts. From conception, the embryo is an individual human being who should be protected against exploitation.

FUTURE OF MEDICINE Is respect for human nature an impediment to research? No.

To appreciate the truth of that answer let us examine the recent progress made in the investigation and treatment of congenital and genetic disease. Human embryo experimentation up to the fourteenth day of life as recommended by the Warnock Report is not a necessary requirement for effective medical intervention in these conditions.

CONGENITAL AND GENETIC DISEASE Two years ago I was invited to address members of both Houses of Parliament at Westminster. I explained that human embryo research as recommended by the Warnock Committee could not produce any positive results in the investigation and treatment of congenital and genetic diseases because at fourteen days the organs and systems affected by these conditions have not yet developed. In addition I suggested that effective research would depend on techniques not requiring the use of human embryos. These comments were attacked from all sides and Nature magazine reported my comments as a “French influence in Britain”.1

Subsequently, Nature made an “appeal to embryologists”2 in which a prize of one year’s free subscription to the magazine would be awarded to the authors of the best submission showing what could be achieved by the use of the embryonic human being. In this way, the magazine suggested, scientists would be able to defeat attempts in Parliament to outlaw the use of the human embryo for experiments.

Today – two years later – Nature has still not published any relevant papers. Such silence demon-

strates the paucity of scientific argument justifying human embryo experimentation.

Furthermore my prediction concerning effective research without the use of human embryos has been amply demonstrated by numerous investigators in several countries. Vitamin supplementation before conception has been shown to protect the embryo from neural tube defects in spina bifida. The new developments in molecular biology applied to cells taken from adult patients with cystic fibrosis3, muscular dystrophy4, Huntington’s disease5 and retinoblastoma6 have also generated a much greater understanding of the genetic factors responsible for these diseases as well as their location within the human genome. In addition there is now the possibility of treating and curing certain genetic blood diseases with bone marrow transplantation.7 None of these achievements has involved the use of human embryos.

In Down syndrome – the disease in which I am particularly concerned – there is an additional chromosome present in every cell of the afflicted individual. This produces an “overdose” of genetic information and is roughly comparable to a four-cylinder engine mounted by mistake with five sparking plugs. The engine cannot run smoothly but the good motor-mechanic will try to disconnect the extra plug rather than discard the engine. Although we scientists do not yet know how to “unplug” an extra chromosome, nature does and does it most efficiently. In the female each cell possesses two X chromosomes whereas in the male each cell possesses only one X chromosome. Shortly after conception one or other of the two X chromosomes in each cell of the female embryo is inactivated or “unplugged” so as to prevent an overdose of the genetic information on the X chromosome. This situation continues throughout life. Through our research we hope to achieve a similar effect with the extra chromosome 21 which is responsible for Down syndrome.

Our work also involves deciphering the genetic content of chromosome 21. Five genes have already been identified on chromosome 21 and it is likely that its full complement of genes will be determined during the next few years. Last year we demonstrated that in Down syndrome the cells are extra sensitive to a drug which blocks the metabolism of monocarbons.8 These monocarbons are the smallest “building blocks” used in the nervous system and perhaps their use can be modified by drugs in children suffering from Down syndrome.

I am not suggesting that the condition of these children will soon be cured. What I do say, however, is that discoveries are being made and that respect for human nature does not impair research but stimulates it. The proponents of the use of the human embryo as a guinea pig were mistaken when they put forward to the public this cruel suggestion: either you accept our philosophy that embryos may be used or else you condemn families affected by genetic diseases and you wash your hands of their sorrows.

Medicine is not forced to choose between playing Herod and Pontius Pilate. There are possible lines of research in full accordance with medical norms and already they are being demonstrated as fruitful.

REFERENCES

1. Walgate R. French influence in Britain. Nature 313, 21 Feb 1985. 2. Editorial. Nature, An appeal to embryologists. Nature 316, 11. 3. Beaudet et al. Linkage of cystic fibrosis to two tightly linked DNA markers: joint report of a collaborative study. J. Hum.Genet 39. pp.681-693, 1986. 4. Monaco, A.P., Neve, R.L., Colletti-Feener, c., Bertelson, CJ., Kurnit, D.N., Kunkel, L.M. Isolation of Candidate cDNAs for portions of the duschenne muscular dystrophy gene. Lancer. 323, pp. 646-650. 1986. 5. Landegent, I.E., Jansen in de Wal, N., Fisser-Gren, Y.M., Bakker, E. Van Der Ploeg, M., Pearson, P.L. Fine Mapping of the Huntington Disease linked D4S10 locus by non-radioactive iii. situ hybridization. Hum. Genes. 73, pp. 354-357. 1986. 6. Friend, S.J., Bernards, R., Rogel. J.S., Weinberg. R.A., Rapaport. J.N., Alheri, D.M., Dryja, T.P., A Human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 323. pp. 643-646 1986. 7. Hobbs, J.R. Displacement bone-marrow transplantation and immunoprophylaxis to treat some genetic diseases. Bone marrow transplantation, 1, pp. 333-335. 1986. 8. Lejeune, J., Rethore, M.O., de Blois, M.C., Maunoury-Burolla, C., Mir, M., Nicolle, L., Borowy, F., Borghi, E., Recan, D. Metabolisme des monocarbories et trisomie 21, sensibilite aux methotrexate. Ann. Genet. 29. pp. 16-19, 1986.