THE moral controversy over stem cell research seemed to have been put to rest with the engineering of induced pluripotent stem cells (iPSCs), which do not require the destruction of embryos. But news of the creation of cloned human embryonic stem cells (New ĐÓ°ÉÔ­´´, 8 October, p 6) sets the stage for renewed ethical debate.

A research team at The New York Stem Cell Foundation Laboratory fused unfertilised human eggs with skin cells, effectively creating an embryo containing personalised stem cells for the donor of the skin cells – albeit stem cells of no clinical use because they have three sets of chromosomes rather than two.

What are we to make of this? It is the moral lens we choose which determines our conclusion.

One lens is consequentialism, which would argue that the research is acceptable because it moves us closer to long-anticipated treatments. On the other hand, those who argue that an embryo is entitled to the respect befitting a person would find its destruction morally unacceptable despite the potential benefits.

Others may see it as a moral step too far to create embryos only to destroy them, instead of the more palatable route of using surplus embryos from IVF.

Then there is the yuck factor and its close cousin, “it’s unnatural”. The creation of chimeras using animal eggs caused a fury. The embryos created in New York, while totally human, are also mutants and are sure to do the same.

Further moral questions arise over the fact that the egg donors were paid. This raises concerns about commodification and exploitation similar to those voiced in response to proposals to allow the sale of organs.

Finally, one might ask whether the work brings us closer to human cloning. The embryos are not viable; no one can spirit one out of the lab and implant it. But if they were viable, would we be on the proverbial slippery slope?

“If the embryos were viable, would that put us on the proverbial slippery slope to human cloning?”

On this at least we can be clear. There is a logical difference between therapeutic and reproductive cloning and the existence of the former would not set the stage for acceptance of the latter. There is simply no connection.

As a healthcare lawyer and bioethicist, I find it curious that nobody is
asking this question, for we have surely entered a new era of transplant surgery
where hands, faces and even sex organs could be donated to strangers in need,
just as hearts, kidneys and livers are donated now. Clint Hallam’s famous hand
transplant in Lyons in September 1998 was soon followed by news that an American
team in Louisville had transplanted a hand, and intends to transplant 10 more in
the near future.

If the hand transplants prove successful, even the faces of the dead could
some day grace living recipients who have suffered catastrophic burn injuries.
Only last autumn Nicolo Scuderi, a surgeon based in Rome, applied for permission
to transplant penises as part of three sex-change operations.

These transplants raise a serious policy question. The success of mainstream
transplant surgery has spawned a vexing problem—the ever-widening gap
between the number of people in need of “the gift of life” and those suitable
and willing to be organ donors. As of 2 June, there were 63 635 people on the
waiting list in the US with a new name added every 16 minutes. When people hear
about face and penis transplants, could the “yuck factor” deter them from
filling out donor cards, thus making a bad situation worse?

By now, you’d think we would have a good idea of how the public feels. But we
don’t. I could find no empirical data in the literature, no responses from the
public to carefully crafted questionnaires assessing their reaction to
transplants of hands, arms, faces and penises. Perhaps most experts think no new
emotions will be stirred. If so, they may be wrong at our peril.

Our hands, second only to our faces, introduce us to the world. We shake
hands when we meet others and gesture to express our emotions. We caress those
we love. The idea of a transplanted hand—bringing with it the essence of
the person whose hand it once was—is a staple of horror films or science
fiction. And face transplants are even more likely to carry with them a sense of
the hijacking of someone’s personal identity.

Of course, such feelings are irrational. Unless the facial bones are
transplanted as well, recipients are unlikely to look like the donor. But
medical pioneers and policy makers ought to deal with people’s emotions as they
are, not as they would like them to be. What’s more, unlike all existing
transplants, hand and face transplants will result in obvious disfigurement of
the donor’s corpse.

Liz Reed, regional director of Kentucky Organ Donor Affiliates, has the job
of finding the 10 hands that the Louisville team. In many countries, including
the US, families of dead potential donors have the final say. To minimise the
impact of hand transplants on donation of vital organs, Reed says she will only
ask families for hands after they have been approached for organs and other
tissues. Clearly, this is a prudent policy, but it may not help much if people
turn against organ donation before they die and tell their families of their
change of view.

In many places round the world, people prefer open-casket funerals.
Ironically, the makers of the artificial hand that was recently replaced by a
real one by the Louisville team are now offering their services to the families
of donors. Indeed, they have already fashioned one hand for a corpse. Artificial
hands may be going out of fashion for the living, but not, it seems, for the
dead.

In the two years since the world first learnt about the cloning of Dolly the
sheep, this area of science has made huge progress. Not just sheep, but mice and
cows have now been cloned from adult cells. The talk now, however, is not about
cloning to reproduce a later-born “identical twin”. The focus of ethics and
public policy has shifted from an alarmist and rather fanciful preoccupation
with human reproductive cloning to an emphasis on “therapeutic cloning” for cell
and tissue replacement and repair.

To be sure, discussion of the so-called “spare parts” potential of human
cloning has not escaped sensationalist treatment. Tales of organ farms and
headless clones stuffed into cupboards—awaiting the need of their
forebears for new hearts, livers or kidneys—have provoked some anxiety.
But the real story is every bit as fascinating and far less alarming.

We may, for example, be able to produce cells and tissue for therapeutic use
by a technique known as somatic cell nuclear transfer: taking the nucleus from a
differentiated cell, such as a skin cell, and inserting it into an egg cell that
has had its nucleus removed. Even without cloning, appropriate growth factors
can be used on isolated embryo stem cells to produce immunologically compatible
cells or tissues for treating, say, degenerative diseases of the heart, liver,
kidney or brain and damaged bone.

Legislators were quick to appreciate the huge potential of human cloning at
the cellular level. In Britain, the House of Commons Select Committee on Science
and Technology issued a report on 18 March 1997, barely a month after the
announcement of Dolly’s birth. Ian Wilmut, who leads the team that produced
Dolly, and Harold Varmus, director of the US National Institutes of Health, were
asked to describe the promise of therapeutic cloning to a Senate subcommittee.
Three months later, the US National Bioethics Advisory Commission issued a
report recommending a five-year ban on human reproductive cloning by somatic
cell nuclear transfer that would result in the birth of a cloned child. It did
not seek to regulate private-sector research into human cloning at the cellular
level (This Week, 7 June 1997, p 13).

The most thorough and impressive public policy examination of cloning has
come from Britain. In December 1998, a joint working group representing the
Human Fertilisation and Embryology Authority and the Human Genetics Advisory
Commission issued its report Cloning Issues in Reproduction, Science and
Medicine (This Week, 12 December 1998, p 5). After a three-month public
consultation, the group recommended that human reproductive cloning should be
prohibited. And it said that regulations would have to be changed in order to
allow human embryo research involving cell nuclear transfer technology that does
not result in the birth of a human clone.

The joint committee decided that therapeutic cloning, with its potentially
beneficial applications, should be allowed to go ahead. But because the
consultation process had revealed widespread public unease with the term
“cloning”, the working group thought it wise not to use the term “therapeutic
cloning” but to refer instead to cell nuclear replacement.

In the early days of public discussion on cloning, when the emphasis was
still on human reproductive cloning, the tone in the US was mainly religious.
Theologians were everywhere in the media, and their call “not to play God” was
echoed in Congress. In Britain the discussions were largely secular. When
scientists speak of the benefits that cloning or any other novel technology
offers, they are using the language of “consequentialist” ethics, weighing the
benefits and the harms. Such language is now far more prevalent in both the US
and Britain than the “thou shalt not…” kind of pronouncement.

The change of focus from reproductive cloning to therapeutic or spare-part
cloning has brought a return to consequentialist ways among ethicists and policy
makers. This in no way diminishes the moral anxiety of those who disapprove of
cloning humans and using the resulting embryos to derive tissues and organs.
With thinking now directed towards the promise of medical benefits, the
consequentialist arguments seem to be coming up trumps.

Unlike the Struldbrugs, however, the promise of replaceable organs and
tissues won’t allow us to live for ever. While they might not be “such stuff as
dreams are made on”, embryonic stem cells—found only in early
embryos—are able to differentiate into every type of human cell. They are
the quintessential spare part. And what they promise for the future is
extraordinary: the replacement of missing or damaged cells, tissues and perhaps
even organs. They offer the potential to “cure” conditions such as diabetes,
Parkinson’s disease, heart disease and some cancers.

At first glance, it may seem odd that Geron, whose interests are primarily in
ageing, diseases of old age and cell death, is committed now to research at the
other end of the human life span. But the focus of the company’s research has
been telomeres. These are the bits at the ends of our chromosomes. They are like
the tips of shoelaces, because each time one of our cells divides its telomeres
are worn down a bit. Eventually, they disappear altogether and the cell
dies.

Another Geron-sponsored research project showed that the enzyme telomerase
can keep telomeres from shrinking, and so allow cells to live on, perhaps indefinitely
(In Brief, 24 January, p 23).

But what has this got to do with embryos? Telomerase is active in embryos
while cells are rapidly dividing. Once embryonic stem cells have
differentiated—into nerve, heart and skin cells, for example—the
telomerase vanishes and the clock begins to tick toward cell death. It may well
be that the telomerase found in cancer cells allows them to divide and multiply
indefinitely, and that embryonic stem cells, once transplanted, would be more
likely to become cancerous. Will our cellular creations spin out of control?

Safety questions are always an issue with new and unproved technologies. The
main ethical question raised by this breakthrough concerns the status of the
embryonic stem cells themselves. Of course, there are people who are not
troubled by embryo experimentation—after all, it is legal in Britain, with
constraints and under licence—but such work does provoke vigorous
protests. In the US, there has been a ban in place for four years on federal
funding for embryo research
(Editorial, 14 November, p 3).

Embryonic stem cells are indisputably derived from embryos or fetuses. The
contentious question is whether these cells retain the capacity to develop into
a human being. The scientists involved in the research say no. The stem cells,
they maintain, have been diverted from the path that leads to germ cells (which
will form eggs or sperm in the embryo) into becoming cells for therapy. Other
observers are not so sure. And this is no arcane moral question. Officials at
the US National Institutes of Health are now trying to decide whether scientists
who use embryonic stem cell cultures derived from others’ research can conduct
that research if it is federally funded.

And what about the ethics of keeping people alive until extreme old age by
replacing their parts as they wear out? As a goal in itself, this may not seem
problematic. But, as the stream of exciting, innovative and expensive treatments
continues to flow from the laboratory to the bedside, we—especially in the
US—have an obligation to address first principles first. In the US, these
include an obligation to confront the morally indefensible lack of access to
healthcare for millions or citizens who are uninsured or under-insured.

Of course, there are good reasons for choosing the gender of your baby, such
as preventing sex-linked genetic diseases being passed on. In 1989, Robert
Winston, a world leading infertility specialist, pioneered a sex selection
procedure at the Hammersmith Hospital, London, for just this reason. Eggs taken
from the mother-to-be are fertilised and allowed to divide. One or two cells are
then removed from the two to three-day-old embryo and tested. Embryos of the
“wrong sex”—usually male, because most sex-linked diseases are carried by
women and affect their sons—can then be discarded.

However, this has raised some big moral questions. The status of the embryo
is highly contentious. Some view it as a full human being, others see it as a
potential human being, and still others as a mere clump of cells. In Britain,
the Human Fertilisation and Embryology Authority (HFEA) has banned sex selection
of embryos for social purposes, but it remains legal if medically necessary.

And at least one British hospital, the privately run BUPA Roding Hospital in
Essex, plans to offer IVF followed by pre-implantation diagnosis (PID) of
embryos to overseas patients—for £8000.

Sex selection using IVF and PID is unlikely to become popular: on top of the
ethical doubts, it’s long, painful and expensive. This is not the case for a new
method. Last month, the privately run Genetics & IVF Institute in Fairfax,
Virginia, announced in the journal Human Reproduction (vol 13, p 2367)
that a technique for sorting sperm, developed by the US Department of
Agriculture for cattle, has been used in humans.

Because sperm with X chromosomes (those producing a girl) have about 2.8 per
cent more genetic material, they can be separated from sperm with Y chromosomes
(the male chromosome). The sperm are exposed to a fluorescent dye that binds to
DNA, and a machine sorts the cells depending on how brightly they glow under
laser light. The success rate when choosing a girl is about 85 per cent; for a
boy it is about 65 per cent.

The technique has many advantages. Instead of having embryos implanted, a
procedure with a high failure rate, women can be artificially inseminated with
the sorted sperm. And the moral status of sperm doesn’t provoke the same
controversy as that of embryos.

Winston and the HFEA, have expressed doubts about the safety of the sorting
process. Despite this, the technique is already available in the US, where there
is no regulation of reproductive technology apart from the odd state law and
voluntary guidelines developed by the industry.

What’s more, the IVF Institute has already found a willing partner in
Britain. The BUPA Roding Hospital has announced plans to send sperm to Virginia
by post, so that it can be sorted there and then returned to Britain for
artificial insemination. Even if this sperm sorting was done on British
soil—and not via the Royal Mail—it would not be illegal.

The HFEA’s remit covers only assisted conception that involves either IVF or
donated eggs or sperm. But sorted sperm belongs to the man who produced it. It
is not donated sperm, so it does not fall under the HFEA rules for donated
gametes. And because the wife of the couple will be artificially inseminated,
there is no need for IVF.

But although the HFEA would be cut out of the loop, if the sorting were done
in Britain, importing the sperm into Britain would require a licence that the
hospital may not get because of the HFEA’s reservations about sperm sorting.

Sperm sorting offers the prospect of cheap and easy sex selection. But is
choosing to have, say, male children any different from choosing to have tall or
intelligent or attractive children? With sex selection, we may be moving onto a
slippery slope, from a benign application of technology for strictly medical
reasons to a more sinister one.

It may be too late already. In an age in which technology moves easily across
borders, can any country’s laws prevent a slide into a world where children are
commodities?