House of Commons - Science and Technology

Select Committee on Science and Technology Written Evidence

Annex A

THE HFEA AND RECENT DEVELOPMENTS IN THE CREATION OF NEW HUMAN GAMETES AND NEW HUMAN EMBRYOS

A. INTRODUCTION

In the recent ruling of the House of Lords relating to R (Quintavalle) v Secretary of State for Health on the 13 March 2003,[106] entities created through cloning (cell nuclear replacement) were judged to come within the definition of an "embryo" in the Human Fertilisation and Embryology Act (1990) and were, accordingly, subject to regulation by the Human Fertilisation and Embryology Authority (HFEA) which is a quasi-autonomous non-governmental organisation (quango).

However, this decision also means that embryos resulting from other non-fertilisation procedures may, potentially, be subject to regulation by the HFEA. This has arisen because, as indicated by Lord Bingham of Cornhill, the UK 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.[107]

Thus, as a direct result of the House of Lords ruling, the HFEA is now potentially responsible for regulating a whole new range of procedures, such as the prospect of persons being able to "self-fertilise" their own artificial eggs (the creation of which no HFEA licence would even be required). And this regulation would not need any prior public debate even though these new possibilities would, in all probability, be even less ethically acceptable to society than human cloning. Indeed, the procedure of parthenogenesis, in which human eggs are stimulated on their own and without any sperm to give human embryos, has already been given a licence by the HFEA without any appropriate societal consultation taking place.[108]

In the light of this situation, the following report was prepared in order to review some of the new reproductive procedures currently being considered.[109] And even though much uncertainty remains as to their biological feasibility, this report may be useful in notifying and forewarning the wider society of the possible consequences resulting from some of these new procedures.

B. NATURAL CREATION OF HUMAN SPERM, EGGS AND EMBRYOS

Spermatogenesis (the development of male sperm cells)

Starting from an immature sperm cell precursor containing two sets of chromosomes (each set coming from a parent of the man), spermatogenesis is the production (through a chromosome copying and division process) of four sperm cells each containing only one set of chromosomes.

Note: The chromosome copying and division process results in the shuffling and mixing of the sperm cell genes with respect to the parental chromosomes. Therefore, the four sperm cells produced from the single precursor sperm cell are all genetically different.

Oogenesis (the development of female eggs)

Starting from an immature egg cell precursor containing two sets of chromosomes (each one coming from a parent of the woman), oogenesis is the production (through a chromosome copying and division process) of one egg containing only one set of chromosomes. During this process two unused cells (polar bodies) each containing a single set[110] of unwanted chromosomes are produced. The first polar body is discarded before ovulation and the second within 11 hours following fertilisation. Only once the second polar body has been discarded is it considered that a "mature" egg exists.

Fertilisation (the process in which a female egg is combined with a male sperm cell)

Fertilisation begins when a sperm penetrates an oocyte (an immature egg) and ends about 24 hours later. As mentioned above, within 11 hours following fertilisation, the oocyte extrudes the second polar body with its excess chromosomes. The fusion of the oocyte and sperm nuclei containing their respective chromosomes marks the end of fertilisation.

C. NEW DEVELOPMENTS IN THE CREATION OF HUMAN SPERM, EGGS AND EMBRYOS

1. The creation of new eggs

1.1 The Creation of New Eggs from Embryonic Stem Cells

In May 2003, a team led by H Schöler of the University of Pennsylvania, USA, reported the production of egg-precursor-like cells from both male and female mouse embryonic stem (ES) cells.[111] In addition, the researchers indicated that these egg-precursor-like cells seemed to have begun dividing (although it remains to be shown whether their chromosomal number had halved).[112] The egg-precursor-like cells could also recruit adjacent cells to form structures similar to ovarian follicles (a large egg cell surrounded by smaller (non-egg) cells) that nurture the mouse eggs. The American team now plans to test whether these egg-like cells can be fertilised to give rise to mouse pups.[113]

The researchers also indicated that they had obtained embryos containing about 100 cells which they suggested were likely to be parthenotes[114] resulting from egg-precursor-like cells undergoing chemical or thermic activation.[115]

Theoretically,[116] this procedure could enable: Heterosexual couples in which the women were infertile to have children that were genetically their own. Men to obtain eggs containing their own genetic material which could be fertilised by sperm from other men or even from themselves.

Legislation in the UK

— Once Embryonic Stem Cells are obtained, the creation of eggs from these cells would not come under the jurisdiction of the HFEA.

— The fertilisation of such eggs would not be prohibited by the Human Fertilisation and Embryology Act (1990) provided a licence was obtained from the HFEA.

1.2 The Creation of New Eggs from the Association of Eggs stripped of their Chromosomes and the Nuclei of Adult Cells

Researchers at Cornell University in New York City, USA, announced in 2002 that they had injected human adult cell nuclei into human eggs donated during IVF which were stripped of their chromosomes, and discovered that these nuclei could subsequently be made to expel one half of their chromosomes.[117],[118]

It should be noted that earlier in its development, the immature egg is like any other normal cell, and has a full set of genetic instructions, and therefore has the capacity to discard half to become prepared for possible fertilisation. Furthermore an adult cell has a full set—so half has to be removed before fertilisation can occur.

Thus, the researchers first removed the nucleus containing the donor's genetic material from the egg, then injected a normal adult cell from ovarian tissue. And by using a small electrical current and/or chemicals, the scientists then harnessed the natural ability of the egg to activate the process whereby the adult cell's nucleus is split in half and one half of the chromosomes ejected.

Despite fertilising more than 150 of these human eggs, in only a handful of cases did any cell division, which might suggest fertilisation, occur.[119] Other teams have recently presented more research concerning this procedure.[120],[121]

Theoretically, this procedure could enable Heterosexual couples in which the women were infertile to have children that were genetically their own. Men to obtain eggs containing their own genetic material which could then be fertilised by sperm from other men or even from themselves.

Legislation in the UK

— The creation of eggs using this procedure would not come under the jurisdiction of the HFEA.

— The Fertilisation of such eggs would not be prohibited by the Human Fertilisation and Embryology Act (1990) provided a licence was obtained from the HFEA.

1.3 The Creation of New Eggs from the Association of Eggs stripped of their Chromosomes and the Nuclei of other Eggs

In theory it may be possible to insert the nucleus containing the chromosomes of a woman's egg into a donor egg which has been stripped of its chromosomes. The new egg formed in this way would then need to be fertilised by a man's sperm using in vitro fertilisation techniques. Any child born would inherit its nuclear DNA from the mother and the father. Very little research has been undertaken to investigate whether the theoretical promise of this procedure is real. It is not yet possible using this procedure to produce viable human embryos with the capacity to develop to term.[122]

Theoretically, this procedure could enable heterosexual couples in which the women were infertile to have children that were genetically their own.

Legislation in the UK

— The creation of eggs using this procedure would not come under the jurisdiction of the HFEA.

— The Fertilisation of such eggs would not be prohibited by the Human Fertilisation and Embryology Act (1990) provided a licence was obtained from the HFEA.

1.4 The Creation of New Eggs from the Association of Eggs stripped of their Chromosomes and the Nuclei of Sperm

It has also been suggested that a "male egg" could be created by stripping the chromosomes from a female donor's egg and replacing it with the nucleus containing the chromosomes from a sperm cell.[123] The new egg would then have DNA coming from a man and could be fertilised in-vitro by another sperm before being implanted in the womb of a surrogate mother.[124]

With mice, reports show the ability of mouse androgenetic embryos (containing two sets of male chromosomes) to be produced by in-vitro fertilisation and being able to develop to day 9.5 of gestation.[125]

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Theoretically, this procedure could enable a man to obtain eggs containing his genetic material which could then be fertilised by sperm from another man or even the same man.

Legislation in the UK

— The creation of eggs using this procedure would not come under the jurisdiction of the HFEA.

— The fertilisation of such eggs would not be prohibited by the Human Fertilisation and Embryology Act (1990) provided a licence was obtained from the HFEA.

2. THE CREATION OF NEW SPERM

The Creation of New Sperm from Embryonic Stem Cells

Researchers in Tokyo, Japan, have induced cultures of mouse embryonic stem (ES) cells down the developmental pathway that leads to sperm production. The scientists claimed that their cultures yielded male primordial germ cells, the earliest precursors of sperm. After being matured into sperm in the testes of adult mice, the cells seemed to be able to fertilise mouse eggs and begin dividing.[126] But the birth of healthy pups remains to be reported.[127],[128],[129]

Other researchers from Cambridge, Massachusetts, USA, have claimed to have derived spermatocytes, a later stage in sperm production, from mouse embryonic stem (ES) cells.[130] In December 2003, the same researchers were able to isolate sperm-like cells produced from mouse stem cells and injected them into unfertilized mouse eggs. One in five of the resulting embryos began to develop normally until the 100 cell stage.[131] However, no live births have yet been achieved.

nature02247_fs.html&dynoptions=doi1078941434.

Theoretically,[132] this procedure could enable Heterosexual couples in which the men were infertile to have children that were genetically their own.

Legislation in the UK

— The creation of sperm using this procedure would not come under the jurisdiction of the HFEA.

133

3. THE CREATION OF NEW EMBRYOS

3.1 The Creation of New Embryos from the Association of Eggs stripped of their Chromosomes and the Nuclei of Adult Cells

In February 1997, scientists in Scotland announced that a cloned lamb called Dolly had been created.[134] In this procedure, the nucleus which contains the chromosomes of an adult sheep cell was fused with an egg from another sheep which had been stripped of its chromosomes. The resulting entity was then made to develop into an embryo after being triggered by chemicals or electricity before being transferred into a surrogate sheep which gave birth to the lamb.

The Scottish experiment occurred after 277 nucleus fusions took place, whereby eight embryos were obtained giving only one viable lamb.

Since Dolly, researchers have cloned a number of large and small animals including sheep, goats, cows, mice, pigs, cats and rabbits.

Moreover, scientists in South Korea have extracted and grown stem cells from cloned early human embryos using a modified version of the technique used to clone Dolly the sheep. The researchers carried out their work using 247 unfertilised eggs donated by 16 women by removing the genetic material from 176 of them, choosing those at the most suitable stage of development. They then replaced the genetic material with the genetic material from cumulus cells (cells that surround a developing egg), taken from each of the same egg donor women, so that each clone was an exact genetic copy of the women. In this experiment 30 cloned human embryos were obtained reaching the 100 cell stage. From 20 of these embryos, stem cells were extracted from which the scientists managed to grow one human embryo stem cell line. The researchers also showed that these stem cells could grow into different embryo tissues in the laboratory.[135].

Theoretically, this procedure could enable men or women to create embryos which would be identical twins of themselves.

Legislation in the UK

The creation of embryos using this procedure would be prohibited by the Human Reproductive Cloning Act 2001.[136]

3.2 The Creation of New Embryos from the Association of Fertilised Eggs stripped of their Chromosomes and the Nuclei of other Fertilised Eggs

In October 2003, researchers from China and USA were reported to have accomplished a procedure similar to cloning. They, first of all, fertilised the eggs of five infertile women with their husbands' sperm through IVF, creating one-cell embryos and, in addition, fertilised the eggs of a fertile woman with sperm from anonymous donors.

The scientists then transferred the "pronuclei" (the combined set of maternal and paternal chromosomes) of the one-cell embryos resulting from the infertile women into the one-cell embryos created with the eggs of the fertile woman whose own pronuclei had been removed. Finally, these eggs were put back into the wombs of the infertile women, whereby one 30 year old woman became pregnant with triplets.

After a month of pregnancy, one of the fetuses was selectively terminated to increase the chances of survival for the other two. But after 24 weeks of pregnancy, one of the remaining fetuses was delivered prematurely because of ruptured membranes and died of "respiratory distress". As a result of a "silent infection" triggered by the miscarriage, the last remaining fetus was delivered stillborn at 29 weeks gestation. The researchers say that there is no evidence to suggest that the technique itself was the problem.[137]

Theoretically, this procedure could enable heterosexual couples in which the women were infertile to have children that were genetically their own.

Legislation in the UK

The creation of embryos using this procedure would be prohibited by the Human Reproductive Cloning Act 2001.[138]

3.3 The Creation of New Genetic Human-Human Chimeric[139] Embryos

The potential for cells from two different embryos to fuse and become a combination of individuals is well known in nature where genetic human-human chimeras can occur naturally when twin dizygotic embryos fuse in the womb a few days after conception. The resulting babies contain genetic material from both embryos. If the embryos are of different sexes, the babies are often noticed to resemble boys but have characteristics of both sexes.[140]

For example, scientists from the Human Genetics Unit of the University of Edinburgh in Scotland presented the case in 1998 of a boy who was genetically derived from two human persons. He was formed when two eggs, fertilised by two different sperm, fused into one embryo inside his mother's womb. He was an unremarkable baby. But as a toddler, doctors discovered that he was a hermaphrodite. Indeed, what was originally diagnosed as an undescended testis turned out to be an ovary, a fallopian tube and part of a uterus. Further investigation revealed that some parts of his body were genetically female but the rest, which contained a different combination of his parents' genes, was male.[141]

A further example was reported in 1995 by the same researchers from Edinburgh University who described another boy who was partially parthenogenetic.[142] In other words, cells from his blood and certain other tissues contained none of his father's chromosomes. Instead, they featured a duplicated set of one half of his mother's.[143] Although it is not unknown for an egg to start developing without being fertilised, it is believed that fully parthenogenetic human embryos cannot develop to term. The scientists suggested that the partially parthenogenetic boy owed his unusual genetic constitution to an egg that spontaneously divided into two cells, one of which was fertilised. The second cell then copied its maternal chromosomes, allowing the resulting chimera to form a viable embryo.[144]

Artificial human-human embryonic chimeras were only first reported in July 2003. In this case, a team of scientists from the USA indicated that they had made such chimeras by taking cells from three-day-old male embryos consisting of around eight primitive cells and inserting them into 21 female embryos at the same stage of development. The resulting embryos were part male, part female and could potentially have developed into an apparently healthy foetus. The chimera obtained in this way would then have four genetic parents. After three days, the male cells appeared to be evenly distributed in 12 of the chimeras. However, the embryos were destroyed soon after. The research has been submitted for publication.[145],[146]

Theoretically, this procedure could enable the formation of an embryo with any number of genetic "parents".

Legislation in the UK

The creation of human chimeras is considered to be illegal in the UK since the Human Fertilisation and Embryology Act (1990) states in Article 3 (3) (d) that:

"A licence cannot authorise replacing a nucleus of a cell of an embryo with a nucleus taken from a cell of any person, embryo or subsequent development of an embryo."

However, the exact wording of Article 3 (3) (d) covers the "replacing of a nucleus of a cell of an embryo" and not the cell as such as described in the American research.

3.4 The Creation of New Embryos from the Association of Eggs with the Nuclei of Adult Cells

Dr Orly Lacham-Kaplan, a reproductive biologist at the Monash Institute of Reproduction and Development in Melbourne, Australia, was reported in 2001 to have injected adult mouse male cells into mouse eggs that still contained two sets of chromosomes.[147]

Unlike sperm, an adult cell has two sets of chromosomes. To overcome this problem, the team exploited the cellular machinery that is used by an unfertilised egg to eject a spare set of chromosomes when it encounters sperm. Indeed, during normal fertilisation, two sets of chromosomes in an egg are separated and one set is ejected in a package that biologists call the polar body, leaving a single set to combine with another set from the sperm.

Thus, after "fertilisation" of the mouse egg by the adult male cell, the Australian scientists used chemicals to persuade the egg to carry out the steps typical of normal fertilisation: it released its spare set of chromosomes into a polar body; only this time the adult body cell also expelled its spare set into a second polar body.

In this way the researchers ended up with two polar bodies and a fertilised egg, with one set of chromosomes from the mother and the second from the adult cell which is similar to an embryo derived from fertilisation by sperm.

The embryos went on to develop relatively normally for a few days in the laboratory and the team was considering transferring the embryos into the womb of surrogate mice.[148],[149] However, whether the resulting embryos were viable remains to be shown.[150]

This procedure would enable:

— Couples in which the men have no sperm or sperm-making cells to have children that were genetically their own.

— Lesbian couples to create their own female embryos that would be genetically their own.

— A single women to create her own female embryo, the chromosomes of which would only come from herself. Note: This embryo would not be her clone.

Legislation in the UK

Following the ruling of R (Quintavalle) v Secretary of State for the Health of the 13 March 2003[151] it is very likely that the production of embryos using this procedure would be possible provided a licence was obtained from the HFEA.

3.5 The Creation of New Embryos from the Association of Eggs with half the Genetic Material from an Adult Cells

Scientist in the USA have created a procedure for any adult cell in a person's body to be used to fertilise a woman's egg. The procedure involves taking half the genetic material from an adult cell and injecting it into a woman's egg resulting in an embryo which contains half of the mother's chromosomes and half of the cell donor's chromosomes. The method is already being tested on human eggs. Indeed, US scientists together with a UK scientist (Mohammed Teranissi of the Assisted Gynaecology Research centre in London) are now trying to produce viable human embryos after the process, known as haploidisation, proved successful in experiments on mice.[152]

This procedure would enable lesbian couples to have a baby that shares both their genes. Indeed, a lesbian couple from the UK has already indicated that they want their names put forward for any medical trial of the technique.[153]

Legislation in the UK

Following the ruling of R (Quintavalle) v Secretary of State for the Health of the 13 March 2003[154] it is very likely that the production of embryos using this procedure would be possible provided a licence was obtained from the HFEA.

3.6 The Creation of New Embryos from the Association of Eggs with the Nuclei of other Eggs

In April 2004, scientist in Japan were reported to have fertilise a mouse egg with the genetic material from another mouse egg to give a mouse with two sets of chromosomes from two female mice, rather than one from the mother and one from the father as in a fertilised embryo. This was the first time that the procedure was successful in mammals.

To do this, the researchers injected the genetic material from immature mouse eggs into mature eggs with their own set of chromosomes. They then "activated" the combined eggs, prompting them to start growing as embryos. And by blocking the expression of a key gene which affected imprinting in the immature mouse eggs, the researchers increased the activity of another gene which manufactures a protein responsible for regulating growth in the developing foetus. Imprinting means that some genes are working in maternal DNA but switched off in paternal DNA, or vice versa. But as a result of this modification, just two out of 598 mice embryos made it to full term.[155],[156]

This procedure would enable lesbian couples to have a baby that shares both their genes.

Legislation in the UK

Following the ruling of R (Quintavalle) v Secretary of State for the Health of the 13 March 2003[157] it is very likely that the production of embryos using this procedure would be possible provided a licence was obtained from the HFEA.

3.7 The Creation of New Embryos through the Association of Eggs stripped of their Chromosomes and two Sperm Nuclei

Scientists from the organisation Advanced Cell Technology have speculated in November 2001 that it may be possible to transfer two sperm nuclei from a man's sperm into a donated egg stripped of its own nucleus which is then activated to give an embryo.[158]

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QID_NOT_SET&stored_search=&FIRSTIN

Theoretically, this procedure could enable:

— Homosexual men in to obtain embryos that were genetically their own.

— Single men to obtain embryos containing only their own genetic material.

Legislation in the UK

Following the ruling of R (Quintavalle) v Secretary of State for the Health of the 13 March 2003[160] it is very likely that the production of embryos using this procedure would be possible provided a licence was obtained from the HFEA.

3.8 The Creation of New Embryos through Parthenogenesis

Parthenogenesis, from the Greek word for "virgin birth", is a procedure which tricks a female egg into becoming an embryo on its own as though it had been fertilised by sperm. This happens naturally with female aphids, turkeys, certain forms of female reptiles[161] and some larger animals such as lizards. Parthenogenesis has also been artificially induced in frogs and snakes, although it quite often results in abnormal development[162].

Eggs halve their genetic complement (going from 46 (diploid) to 23 chromosomes (haploid)) relatively late in their maturation cycle, so if early activation is done by stimulating eggs that are still diploid to divide, a full set of genes is retained. Alternatively, it is possible to stimulate a haploid egg with 23 chromosomes to replicate its genetic material, resulting in a full genetic complement of 46 chromosomes.[163]

Using chemicals that mimic a sperm's arrival, scientists in recent years have triggered parthenogenesis in the eggs of a few mammals, including rabbits and mice, but the resulting embryos have never developed beyond the early foetus stage.[164]

Researchers in Los Angeles, USA, were reported in 2001 to have used chemical manipulation to trick unfertilised mouse eggs to develop into "embryos" with a full complement of two sets of chromosomes coming from the mother's chromosomes. Of 60 such embryos transferred into the reproductive tracts of female mice, 12 of them survived to the 13th day of gestation and were found to be developmentally normal.[165]

In the same year of 2001 scientists were also reported to have undertaken a similar experiment on 77 monkey eggs which were exposed to chemicals designed to make them think they had been fertilised by sperm. Only 28 of the eggs started dividing like embryos, with four continuing the development up to the about the 100 cell stage. The researchers retrieved from one of these parthenotes what appeared to be stem cells from which a cell line was produced which has been growing for over two years.[166],[167],[168]

With respect to human parthenogenesis, scientists working with the company Advanced Cell Technology (ACT) in Massachusetts, USA, were reported in November 2001 to have used chemicals to stimulate human eggs to grow into embryo-like balls of about 100 cells. In this first creation of human parthenotes, the stimulus was applied before the eggs underwent the normal ejection of half their chromosomes, which typically occurs at the time of fertilisation to accommodate the sperm's DNA.

In ACT's human parthenogenesis experiments, 22 eggs were exposed to chemical activation. After five days of growing in culture dishes, six eggs had developed into what appeared to be embryos, but none clearly contained the so-called inner-cell mass that yields stem cells.[169] But related research suggests the goal of obtaining stem cells from human parthenotes is achievable. Indeed, in 2003 researchers from the biotech company Stemron in Maryland, USA, indicated that they had grown parthenogenetic human embryos to the about the 100 cell stage from which stem cells were obtained.[170],[171] And a statement from Advanced Cell Technology in December 2003 also indicated that they had managed to coax five out of eight human eggs into becoming 100 cell embryos through parthenogenesis.[172]

10&RESULTFORMAT=&fulltext=Wininger&searchid=1061994378613699549&stored699search=&FIRSTINDEX= 0&volume-21&issue=2&journalcode=stemcells

Theoretically, this procedure could enable a single woman to create her own female embryo, the chromosomes of which would only come from herself. Note: This embryo would not be her clone.

Legislation in the UK

The Human Fertilisation and Embryology Authority (HFEA) of the UK has granted a licence to the Roslin Institute, on 10 June 2003, to enable researchers to create human embryos through parthenogenesis from donated human eggs.[173]

D. CONCLUSION

The complex and grave ethical problems raised by the new procedures in this report emphasise the urgent need for more discussions and consultations amongst the wider public. And in this regard, it is unfortunate that one of these new procedures (parthenogenesis) has already been given a licence by the HFEA without any serious or appropriate ethical debate taking place either in the UK parliament or amongst the general public.

Hence, out of respect for democratic values and the views of the general public, it is suggested that a moratorium should be enforced on parthenogenesis and the other new possible procedures presented in this report until the HFEA has adequately consulted with the wider society and has ensured that the general public is sufficiently aware of the relevant ethical and medical[174] issues being considered.

If no appropriate programme to engage the general public is undertaken with respect to these new procedures, then the crucial trust the public has for the HFEA would, inevitably, be undermined. The Authority would then be seen as making decisions on behalf, but without the informed consent, of the general public. Questions could then arise about the level of power entrusted to the HFEA which is, after all, only a quasi-autonomous non-governmental organisation made up of 18 appointed members.

106 See: R (Quintavalle) v Secretary of State for Health, http://www.lawreports.co.uk/hlpcmarc0.1.htm Back

107 See: R (Quintavalle) v Secretary of State for Health, http://www.lawreports.co.uk/hlpcmarc0.1.htm Back

108 HFEA 10 June 2003, HFEA grants Roslin Institute's first licence for human embryo research, http://www.hfea.gov.uk/forMedia/archived/10062003.htm Back

109 Note: Chimeric foetuses have also been included in this study. Back

110 The chromosomes of the first polar body are each made up of two sister chromatides. Note: The chromosome copying and division process results in the shuffling and mixing of the egg genes with respect to the parental chromosomes. Back

111 Hubner, K et al. Derivation of Oocytes from Mouse Embryonic Stem Cells, Science 300, 1251-1256 (2003). Back

112 Dennis, C, Developmental biology: Synthetic sex cells, Nature 424, 364-366 (24 July 2003). Back

113 Roger Highfield, Science Editor, Scientists can make human eggs from male embryos, The Telegraph, 2 May 2003. Back

114 Resulting from parthenogenesis, from the Greek word for "virgin birth", is a procedure which tricks a female egg into becoming an embryo on its own as though it had been fertilised by sperm. Back

115 Hubner, K et al. Derivation of Oocytes from Mouse Embryonic Stem Cells, Science 300, 1251-1256 (2003). Back

116 The noted theoretical possibilities would only be realisable if adult stem cells are shown to be as versatile as embryonic stem cells. Back

117 Palermo, G D, Takeuchi, T and Rosenwaks, Z Reprod Biomed Online 4, 237-242 (2001). Back