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8-Humans: Update on stem cell and embryo reseach

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                                  PART I
-------------------------------- GENET-news -------------------------------

TITLE:  'She-male' embryos created in lab
SOURCE: New Scientist, UK, by Shaoni Bhattacharya
DATE:   Jul 3, 2003

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'She-male' embryos created in lab

The revelation of experiments in which human embryos with both female and
male cells were created has been condemned as "flawed" and "revolting" by
both fertility scientists and anti-abortion groups.

US researcher Norbert Gleicher and colleagues took cells from three-day-
old human male embryos and added them to female embryos, creating what is
called a chimera. Gleicher, who unveiled the work at the European Society
of Human Reproduction and Embryology's annual conference in Madrid, says
the experiments were to test a theoretical alternative to gene therapy.

Gene therapy aims to repair genetic defects by using vectors, usually
viruses, to ferry new DNA into a patient's cells. But the technique has
been troubled by safety fears. Gleicher suggests that embryos carrying
genetic defects might be cured by injecting early embryonic cells, called
blastomeres, which carry healthy versions of the genes. This could even
prevent the need to destroy embryos with faulty genes, he claims.

But Alan Trounson, fertility expert and IVF pioneer at Monash IVF in
Melbourne, Australia is scathing. "It seems to me completely flawed," he
says. "You can't have half of Huntington's disease."

Lynn Fraser, chair of ESHRE's international scientific committee agrees.
In chimeric individuals, the "bad genes" would "all still be there", she
says. Naturally-conceived human chimeras can exist but the distribution
of the cells containing the different genetic profiles is far from uniform.

Trounson adds that the work is damaging to the image of fertility
science: "It could cause some harm because it would be difficult to argue
why that experiment was done to patients." Gleicher's study is the second
from the conference to cause a furore, following a report of work
assessing the potential of ovarian tissue from aborted fetuses to provide
eggs for IVF.

Feasible or ethical

Gleicher, at the Center for Human Reproduction in New York, and his team
extracted blastomeres from 16 human male embryos. They added one, two or
three of the male cells to each of 21 female embryos.

The embryos were then followed to the blastocyst stage, which occurs five
to six days after fertilisation. Male cells were used because the Y
chromosome is an easy marker to track in the developing embryos.

"Twelve of the 21 embryos reached what we considered to be perfectly
normal blastocysts," says Gleicher. But four of the female embryos
stopped developing after the transplantation, while five become "abnormal

"This study was meant in principle to determine whether the [genetic
repair] concept is possible," says Gleicher. "It is not meant to support
in any way that the clinical application of this kind of concept at the
present time is either feasible or ethically acceptable."

However, he says a patent has been filed for the concept and adds: "We
believe further investigation is warranted."

                                  PART II
-------------------------------- GENET-news -------------------------------

TITLE:  Playing God: Eggs from foetuses, artificial wombs, dead men's sperm
        - it's not only the religious right who object to such 'advances'
SOURCE: The Guardian, UK, by Hilary and Steven Rose,3604,990046,00.html
DATE:   Jul 3, 2003

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Playing God: Eggs from foetuses, artificial wombs, dead men's sperm -
it's not only the religious right who object to such 'advances'

The promised age of genetics - or at least the age of genetic promises -
has surely arrived. Scarcely a week goes by without some further claim of
hitherto undreamed-of prospects for providing children for the childless.
>From the Raelian clones to artificial wombs and the marriage of harvested
eggs and sperm from dead adults or aborted foetuses, geneticists and a
newly emerging tribe of reproductive technologists seem to be coming
closer to "playing God". Anything goes in this technologically
sophisticated western world where consumers are king and queen and, with
each newly extravagant claim, the capacity to shock is weakened.

So, collecting the ovaries from four-month-old female foetuses and
stimulating them in vitro to develop to the stage where mature eggs can
be harvested seems but one small further step down a path long ago
embarked upon.

Of course, the possibility is still "only theoretical". Other biologists
will point to the hazards of the approach, such as potential genetic
problems and birth deformities, and seek to kick discussion of the
development into the long grass. But the reassurance may well mask an
intense research effort to realise the theoretical possibility.

Few share the belief that scientific progress automatically generates
social progress. Whatever the biological possibilities, the advance may
carry such huge risks that the outcome may be unacceptable for anything
other than the most restricted use.

One of the unanticipated consequences of the genetic revolution in a
highly individualised society is that it has helped foster a cultural
preoccupation with genetic origins. A secure loving home is the
foundation of any child's well-being. Yet the questions of who am I, who
are my "real" parents, are ones many much-loved adopted children still
ask. This longing is being recognised by a gradual shift in which it is
seen as desirable for sperm donors to lose their invisibility.
Legislation increasingly gives adopted children the right to know their
birth parents.

Such shifts acknowledge that the longing to know our genetic identity has
become more acute in the age of genetics. So consider the existential
crisis faced by a child who learns that she is the product of a
fertilised ovum harvested from a long-dead foetus and frozen sperm from
an unidentifiable source. We have some idea of the stakes by
extrapolating from the social research on IVF families. These are in many
ways far less existential and more interesting than the abstract debates
among ethicists would suggest.

The ethical reasoning used by families enables them to skilfully adjust
to the new possibilities opened up by the new technologies. But social
research has also documented the severe psychosocial and developmental
problems of IVF multiple births and generated ethical reflection about
the numbers of embryos to be implanted. In Britain, as in most European
countries, there are restrictions on the number of implanted embryos; but
in the US, one of the least regulated and technologically advanced
countries, there are none.

The varied pattern of regulation leads to reproductive tourism in which
well-heeled people from well-regulated countries go to less well-
regulated ones to buy services, whether to choose the sex of a child, use
pre-implantation genetic diagnostics, or ensure fertilisation by the
sperm of a dead partner. While it is probable that the children conceived
are likely to find themselves in a loving family, there is something
unnerving about the way that a number of would-be parents court the
media, exposing their intimate family life to such public scrutiny. (What
do the four boys think when their mother so publicly used sex selection
to make sure she didn't have another child like them?)

Genetics does more than make media headlines. It increasingly pervades
our lives, with massive financial support from the government and the
biotech industry. The Medical Research Council and the Wellcome Trust
investment of #66m into creating a British human genetic biobank remains
unchallenged, even though the expenditure has practically bankrupted the
MRC and foreclosed other biomedical research options.

The need for more and more reproductive technology because of increasing
problems in having children starts at the wrong end. Yes, it is true that
women are having children later because they have to establish their
careers first. Yes, it is true many men's sperm count is reduced. But
instead of working at the curative end, if we began with the preventive,
Britain would put serious money into affordable high-quality childcare so
that women who wanted them could have their babies younger.We need a
society that promotes reproductive health rather than expensive
technological fixes.

We are witnessing a process that increasingly turns a child into a
commodity, with product specification, quality control and rejection of
sub-standard products - the wrong sex, the wrong genes.

The process also harms the clinicians who, instead of being professionals
who give the best advice regardless of market considerations, become the
providers of biotechnical services to customers with effective demand
powers. Lady Warnock's quick dismissal of the ethical problems involved
in harvesting eggs from aborted foetuses on the grounds that she can't
see any difficulties for the mother, erases the human dignity claims of
the potential child. It is distressing to find a social philosopher who
has contributed so much to this debate forgetting the children.

In Britain the ethical debate is often characterised (not least by the
scientists themselves) as being between the right-to-life religious lobby
and the rational scientists who really care for the right to have a baby.
We live in one of the most secular countries in the world, so the
reprotechnologists can be sure of eventually pushing any innovation
through despite the ethical debates. The secular criticism has been
stifled by this split.

Reproductive tourism and its media coverage teaches a number of lessons.
One is that the serious press needs to be more responsible. The new
reproductive genetics and technologies open choices to people facing hard
negatives. Pages of sentimental press coverage following the self-
dramatising activities of a tiny minority get in the way of thinking
deeply about human genetics as one of the biggest challenges of the 21st

Hilary Rose is a sociologist, Steven Rose is a biologist. They are joint
editors of Alas Poor Darwin: Arguments Against Evolutionary Psychology.

                                  PART III
-------------------------------- GENET-news -------------------------------

TITLE:  Scientists Take A Step Nearer To Creating An Artificial Egg Using
        A Somatic Cell
SOURCE: European Society For Human Reproduction And Embryology
DATE:   Jul 2, 2003

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Scientists Take A Step Nearer To Creating An Artificial Egg Using A
Somatic Cell

Madrid, Spain -- Scientists believe that they are an important step
nearer to success in creating an artificial egg from the combination of
the nucleus of a somatic cell and an oocyte which has had its DNA-
carrying nucleus removed, a conference of international fertility experts
heard today (July 1).

Dr Peter Nagy, from Reproductive Biology Associates, Atlanta,
collaborating with the University of Connecticut, USA, told the European
Society of Human Reproduction and Embryology annual conference that
former approaches to haploidisation[1] using a fully mature oocyte and a
resting (interphase) somatic cell had caused misaligned chromosomes
during cell division. However, he was confident from his team's latest
experiments that this difficulty could be overcome, even though their new
approach also ran into some problems.

"We decided to initiate haploidisation at an earlier stage in the
oocyte's cell cycle, when it was still immature, but this time using a
somatic cell in its active (metaphase or G2/M) stage. Essentially, we
took the control of the first nuclear division away from the oocyte and
gave it to the somatic cell," he said.

The US-Brazilian research team[2] , working with mouse cells, removed the
nucleus of the immature oocyte, then transformed the somatic cell from
its diploid (46 chromosome or 2n) stage to its next (4n) stage and
transferred it to the immature enucleated oocyte (ooplast).

"What we expected by doing this was that the DNA in the somatic cell
would condense into chromosomes inside the somatic cell - not in the
ooplast - and that the somatic cell would direct the chromosome alignment
and initial spindle formation, which would then be normal. The nucleus of
the somatic cell, at its second stage of division and correctly
assembled, would then undergo chromosome segregation in the ooplast,
resulting in twice its diploid nuclear content during in-vitro
maturation. As a result of an artificial activation, a second round of
chromosome segregation provides the haploid (23 chromosome) normal oocyte
content. This is a novel strategy that cannot be used with a mature
ooplast because mature ooplasts can support only one round of chromosome

However, the researchers found that there were still some misaligned
chromosomes and problems with the integrity of the spindle - the
chromosomes' 'holding' mechanism. But, they are confident that these will
be overcome.

"This initial set of experiments shows that it is possible to induce
haploidisation with our approach," said Dr Nagy. "This is the first time
that this has been tried so we are still learning. Now we have to check
how frequently the chromosomal problems occur and whether there is an
easy solution or whether it is a fundamental difficulty."

But, even in a worst case scenario, he said, it does not mean that they
were back to the drawing board because his team was already developing
new techniques to overcome the problem.

"I'm really confident - not simply optimistic - that haploidisation will
work and if everything goes well we will be able to obtain artificial
gametes in one or two years. Even if we encounter more problems it should
still be possible within three to five years."

Haploidisation is not cloning because it is the production of a
reconstituted egg (which can then be fertilised by the sperm) in a
situation where a woman has no eggs of her own. One of the woman's own
somatic cells would be the source of the chromosome-carrying nucleus,
which would be transferred into a donated 'shelled-out' oocyte.


[1] Haploid: a cell with only one set of chromosomes - in humans 23. Only
the egg and sperm are haploid.

[2] University of Connecticut, Animal Science, Storrs, USA; Reproductive
Biology Associates, Atlanta, USA; Clinical e Centro de Pesquisa em
Reprodugco Humana Roger Abdelmassih, Sco Paulo, Brazil.

                                  PART IV
-------------------------------- GENET-news -------------------------------

TITLE:  Era of 'unborn mother' looms as scientists use aborted foetuses to
        grow human eggs
SOURCE: The Independent, UK, by Steve Connor
DATE:   Jul 1, 2003

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Era of 'unborn mother' looms as scientists use aborted foetuses to grow
human eggs

Almost every day a scientific or medical development seems to bring new
promise and controversy to mankind; none more so, perhaps, than in the
field of human fertility.

A quarter of a century ago the first test-tube baby, Louise Brown, was
born. Now scientists have raised another startling prospect - "unborn

The notion that children can derive from human matter that has not itself
been born sounds the stuff of science fiction. Yet it has moved a step
closer with research showing that it is possible to extract ovarian
tissue from aborted foetuses for in-vitro fertilisation (IVF) treatment.

Scientists announced yesterday that they have been able to remove
immature ovaries from four-month-old foetuses. The theory is that they
can then be stimulated in the test tube to go through the later stages of
development before the creation of fully mature eggs.

But such a scenario raises grave ethical questions about the possibility
of creating children whose biological mothers were never born. When a
high-powered committee of British ethicists considered this possibility
in the early 1990s it took the view that any child created by such a
procedure would not be able to come to terms with the idea of deriving
from aborted foetal tissue.

However, it is clear that the increase in demand for a supply of healthy
human eggs - which are not easy to "harvest" from even the most fertile
women - is causing several groups of scientists around the world to
explore the possibility of using aborted foetuses.

Medical researchers from Israel and the Netherlands have now gone further
than any previous attempt at experimenting with ovarian tissue from human
foetuses. They artificially stimulate fluid-filled sacs or follicles
within surgically removed ovaries to undergo several stages of development.

Normally an egg develops within the follicle as it goes through four
developmental phases - the primordial, primary, secondary and pre-
ovulatory stages - before it is released from the ovary into the
Fallopian tubes.

The scientists said they had managed to culture foetal ovaries in test
tubes to enter the start of the secondary stage. This is when the ovarian
follicles begin to produce the female sex hormones necessary to develop
and mature the eggs.

Tal Biron-Shental, a gynaecologist from Meir Hospital-Sapir Medical
Centre in Kfar Saba, released the findings of the study at the annual
meeting of the European Society for Human Reproduction and Embryology in

Dr Biron-Shental said that the researchers obtained ovarian tissue from
seven aborted foetuses aged between 22 and 33 weeks and managed to keep
slices of the ovaries alive for four weeks, long enough for the follicles
to develop to the stage when they began to produce the female hormone

"We didn't have mature oocytes, we had follicles that changed from
primordial follicles and survived. We had E2 [oestradiol] secretion which
means that we had more secondary follicles which means there was a
development," Dr Biron-Shental said.

"This is the first report showing survival of second and third trimester
human foetal ovarian follicles in culture with E2 production. E2 was
probably secreted from the few secondary follicles in the cultured
slices," she told the meeting.

The study in Israel was run with the veterinary department of Utrecht
University, which supplied some of the culture medium for the test-tube
development of the ovarian tissue. Full ethical approval was obtained
prior to the study being carried out, the scientists confirmed.

"The local ethical committee of our medical centre approved the study and
informed consent was obtained from the mothers," Dr Biron-Shental said.
"We had different kinds of aborted foetuses with all kinds of
malformations. Of course we could not use normal foetuses for such
experiments because it is controversial enough," she explained.

However, there was one exception. "We had one aborted foetus that was
completely abnormal and the abortion took place because the mother of the
foetus had severe psychiatric problems. There are a lot of ethical
questions on this point. Since it is still preliminary results we don't
have all the answers for those ethical questions," she added.

Asked how long it would be before she was able to produce fully mature
eggs from foetal ovaries, Dr Biron-Shental said: "It will still take a
long time. I don't know exactly.

"We have an end goal and we continue to culture follicles from aborted
foetuses. We have tried to improve the culture media and to prolong the
culture period. We hope to get better results and more follicles," she
said. "I am fully aware of the controversy about this, but probably, in
some places, it will be ethically acceptable."

Anti-abortion groups were quick to denounce the research yesterday. Nuala
Scarisbrick of the organisation Life said the study was morally
repugnant. "Who would want to know that their mother was an aborted
baby?" she said.

Frangoise Shenfield, an ethicist at University College London and a
former member of the Human Fertilisation and Embryology Authority, also
voiced concerns about where this sort of research was leading.

"I would be very troubled by this not only for ethical reasons but for
psychological reasons, because what is the public going to think about
where the eggs come from?" Dr Shenfield said.

A spokeswoman for the HFEA said that the use of ovarian tissue from
foetuses was considered by a committee of ethicists in 1994, which led
the authority to decide that it would be difficult for a child to come to
terms with the idea that it had been created from aborted foetal material
because of prevailing social attitudes.

"The authority does not consider the use of tissue from this source to be
acceptable for infertility treatment. But the authority does allow the
use of foetal material to produce eggs for research provided that it is
taken only with full, explicit consent," she said.

Roger Gosden, a leading fertility specialist working at the Jones
Institute in Norfolk, Virginia, said the ethical issues centre on the
issue of informed consent - the foetus cannot give its consent.

Dr Gosden also questioned whether the research was necessary because he
had demonstrated that it is possible to obtain ovarian tissue from adult
women with the aim of culturing the follicles in vitro to produce mature eggs.

"I would say that we don't need to use foetal material. The only
advantage in doing so is that there are a huge number of eggs there, but
obviously we have to be very sensitive to ethical issues," he said.

"We should be able to study foetal ovaries for research purposes, but
it's the application in reproduction that I have concerns about," he added.

Experiments with mice have shown that it is possible to mature foetal
eggs fully, fertilise them in a test tube, implant them into an adult
mouse and produce healthy offspring. Some scientists hope to be able to
do the same with human material.


European NGO Network on Genetic Engineering

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D - 38116 Braunschweig

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