IT HAPPENED in a quiet lab in New England. In the early hours of 10 October,
Jose Cibelli took a batch of human eggs, sucked out their DNA with a pipette,
and replaced it with DNA from an adult human being. Three days later, a few of
the embryos the Argentinian-born scientist created were still alive.
Thus was born the media frenzy about the 鈥渇irst human clones鈥� that raged
earlier this week. The embryos in question were mere pinpricks鈥攏o arms, no
legs, just bundles of up to six cells. Yet this was what some had hoped for and
others dreaded ever since Dolly the sheep was born in 1997.
Whether they really are the first cloned human embryos isn鈥檛 clear. South
Korean researchers claimed to have created a cloned embryo in 1998, and maverick
would-be cloners such as Clonaid, a company set up by the Raelian cult, also
claim to have carried out experiments. But the company behind the latest work,
Advanced Cell Technology of Worcester, Massachusetts, is the first to publish a
scientific paper on cloned human embryos (online in The Journal of
Regenerative Medicine).
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What鈥檚 certain is that the announcement couldn鈥檛 have come at a more delicate
moment for politicians. The US seems poised to bring in legislation that would
ban all forms of human cloning. That left ACT no choice but to rush out the
paper and launch a PR offensive.
The company stresses that its research is not about cloning people but
tackling the ravages of disease and old age. The embryos it has cloned are the
dawn of a new era in medicine in which people with Parkinson鈥檚, diabetes and a
multitude of other diseases will be patched up with spare-part tissues, ACT
says. Cells from these patients will be used to create cloned embryos to supply
embryonic stem cells. These will be grown into all manner of replacement
tissues, all perfect matches for the patient. Tissue rejection will become a
problem of the past.
It was a bold pitch that inevitably drew swift criticism from religious
groups and politicians. Within hours, pro-life groups were talking about
power-hungry cloners crossing moral Rubicons, George W. Bush was quoted as being
鈥�100 per cent opposed to any type of human cloning鈥�, and there were fears that
ACT鈥檚 research would lead to full reproductive cloning.
So who鈥檚 right? Are Cibelli鈥檚 embryos a recipe for miracle cures, or a
disastrous step towards reproductive cloning that should be banned as soon as
possible?
The surprise consensus among scientists is that they are neither. Nobody
doubts ACT is indeed hoping to transform medicine. But the company鈥檚
鈥渂reakthrough鈥� comes just as other scientists are abandoning the idea of ever
using cloned human embryos in the fight against disease. For months now, many
have been saying that even if they can get therapeutic cloning to work, the
technique would be hopelessly impractical and expensive.
Nothing ACT has done has changed this. In fact, just the opposite. Far from
confirming that therapeutic cloning is feasible, most scientists thinks the
creation of the first cloned human embryos shows just how nightmarishly
difficult it would be.
To create the embryos
(see graphic),
Cibelli had to use 71 eggs donated by
seven volunteers and carried out three failed rounds of experiments before he
generated his first cloned embryo. And even the fourth, 鈥渟uccessful鈥� round of
experiments was far from efficient.
In it, Cibelli took nuclei from skin cells, or from the cumulus cells that
surround growing eggs, and injected them into 19 denucleated eggs, only three of
which began to grow. One cloned embryo divided just once, to form a two-cell
bundle. Another divided twice, to form a four-cell bundle, and the third embryo
split again to form a six-cell clump. After that it too failed to grow.
To be a viable source of stem cells, a human embryo would have to develop to
the blastocyst stage鈥攁 mass of around 100 cells. None of the embryos got
anywhere near that stage. 鈥淚t鈥檚 disappointing,鈥� says Harry Griffin of the Roslin
Institute, which created Dolly. 鈥淭heir failure to create blastocysts and derive
stem cells raises questions about the value of their work.鈥�
Indeed, some think the scientists were crazy to publish before they had grown
embryos to the blastocyst stage. 鈥淢y fear is that this tiny step will inflame
the conservatives in Congress into slapping a ban on this technology before we
even know it鈥檚 feasible,鈥� says Tom Okarma, the chief executive of Geron, another
鈥渟tem cell鈥� company in Menlo Park, California.
Worse, according to Ian Wilmut, the creator of Dolly, the embryos were so
tiny they reveal almost nothing about the prospects of human clones developing
further in future experiments. Embryos cruise 鈥渙n autopilot鈥� through the first
two or three cell divisions, he says. Only then does the embryo鈥檚 genetic
material start to influence its development.
Despite this, ACT insists its work is a 鈥渕ilestone鈥�. In 11 of the 19 cloned
human embryos, it says, chromosomes took on the form only normally seen in a
fertilised egg鈥攁 vital sign, the company claims, that human adult cells
can be 鈥渞eprogrammed鈥� to become embryos again.
But even if researchers did manage to grow cloned human embryos to the
all-important blastocyst stage, many doubt it will make any difference. Cloning
is dead in the water because it requires an unfeasibly large number of eggs,
says Alan Trounson, whose team at Monash University in Melbourne first extracted
stem cells from cloned mouse embryos.
Even though scientists have been working with mouse embryonic stem cells for
years, they still need to create scores of embryos to generate a single line of
usable cells. In humans this would be unworkable and unaffordable, says
Trounson. In Britain alone, there are 120,000 patients with Parkinson鈥檚 disease
and 200,000 with juvenile diabetes. You鈥檇 need anything up to 30 million eggs to
treat them all with therapeutic cloning.
Yet a woman cannot donate more than a dozen eggs a month鈥攁nd this is an
unpleasant and sometimes risky procedure, involving daily injections of powerful
hormones followed by surgery. ACT got its egg donors by advertising in local
newspapers and offering payments of $4000, the same amount given to women
who donate eggs for infertility treatments.
What鈥檚 more, it takes so long to generate stem cells that many patients with
serious diseases would die long before any of their cloned tissue was ready for
implanting. Working with ordinary human embryos, teams at the University of
Wisconsin and at Johns Hopkins University spent years generating just two viable
supplies of human embryonic stem cells. Repeating this process for individual
patients using the much trickier process of cloning embryos simply isn鈥檛
realistic. 鈥淭herapeutic cloning is not going to be a practical technique,鈥� says
Griffin.
This is why many teams are now abandoning work on therapeutic cloning in
favour of alternative ways of making compatible tissues for spare-part surgery.
Trounson鈥檚 team is focusing on two approaches that make eggs redundant. One idea
is to identify the chemical cues in eggs that tell adult cells to turn back into
embryos. Armed with these substances, scientists could in theory turn any cell
into an embryo without needing an egg.
Another possibility is to take adult body cells and fuse them with embryonic
stem cells. Earlier this year scientists at PPL Therapeutics at the Roslin
Institute claimed to have used such an approach to turn skin cells back into
stem cells and then into heart muscle cells.
Even Geron, ACT鈥檚 bitter rival and one-time staunch advocate of therapeutic
cloning, has moved on. It is armed with its own supplies of non-cloned human
embryonic stem cells and says it has successfully converted them into heart,
nerve and liver cells. It hopes that stocks of these cells can provide
鈥渙ff-the-peg鈥� tissue suitable for many patients.
To overcome immune rejection, Geron intends to engineer the cells so that
they become immunologically 鈥渟ilent鈥�. It hopes to insert viral genes into the
cell to disable the proteosome, which generates the protein fragments on a
cell鈥檚 surface that make the cell and its contents visible to the immune system.
鈥淚f we can interrupt that throughout differentiation, we鈥檝e got the problem
licked,鈥� says Okarma.
The problem with these alternatives to therapeutic cloning is that it鈥檚 hard
to know how seriously to take them. Citing commercial confidentiality, neither
Geron nor PPL Therapeutics, two of the key players, have published any details,
leaving other researchers in the dark. And nothing on the horizon suggests these
companies are about to become more open about their stem cell work.
Unlike ACT. The company鈥檚 claims may have been criticised as premature and
their rush to print as hasty. But on one front they cannot be faulted: at least
they published their findings.
In addition to creating cloned embryos, Advanced Cell Technology also created
human embryos through parthenogenesis, the process that leads to 鈥渧irgin births鈥�
in some reptiles, birds and insects.
In parthenogenesis, an unfertilised egg develops as if fertilised. In
mammals, this sometimes occurs accidentally but the resulting embryos either die
or turn into ovarian tumours. It鈥檚 precisely because parthenogenic embryos don鈥檛
have the potential to become human that American companies like ACT are
interested in them. They hope the technique will escape a forthcoming US ban on
all human cloning.
ACT鈥檚 researchers exposed 22 human eggs to chemicals that kick-start
parthenogenesis. After two days, 20 of the resulting embryos had reached the
four-cell stage. By five days, six had developed into a ball of cells resembling
an early embryonic stage known as a blastocyst. 鈥淭hese are exciting preliminary
results,鈥� says Bob Lanza, vice-president of medical and scientific development
at ACT.
But none of the six embryos developed an inner cell mass, the part of a
blastocyst that develops into the body, rather than the placenta, and from which
stem cells are taken, according to the paper published by ACT. A patent
application seen by 快猫短视频
(6 October, p 14),
however, suggests that the company has gone much further with monkey cells,
managing to both extract parthenogenic stem cells and get them to specialise.
The company hopes tissues grown from human parthenogenic stem cells could be
used for implantation. A woman could donate her own eggs for this purpose. The
resulting stem cells wouldn鈥檛 be genetically identical to her own cells, as they
contain two duplicated sets of chromosomes instead of two different sets, but
tissues grown from them should not cause any problems with rejection. For men,
things would be trickier, but it might be possible to create an embryo by
injecting two nuclei from sperm into a denucleated egg.
But ACT has yet to prove that stem cells can be derived from human
parthenogenic embryos, let alone whether tissues made from them will be safe to
implant into people.
Michael Le Page
