The Niche

Cloning by reprogramming?

“Now we have the technology that can make a cloned child” reads the headline of the most-read article in the Independent right now. But the article does not actually break any news, nor does it use the common method of cloning; rather it discusses a well-understood implication of that recent reprogramming breakthroughs might yield yet another weird way of making a baby.

If a technician wanted to do this, here’s how it would work: First, cells would be gathered from an existing human, probably through a skin biopsy. Second, these cells would be reprogrammed to an embryonic like state. (Current techniques to do this require engineered viruses to insert copies of genes into the reprogrammed cells. This makes the cells’ behavior less predictable and more prone to form tumours, but many scientists believe that new reprogramming techniques will soon be available that don’t require genetic modification.) Next, the reprogrammed cells would be merged with an early stage embryo, created by sperm fusing with egg in a laboratory dish. The “chimeric” embryo would be cultured for a few days and then implanted into a woman. If a baby was born, he or she would contain cells from two genetic individuals: the embryo and the human who supplied the cells. The baby would have three parents: two who gave the gametes for the embryo, one who gave the cells from a biopsy. (Such an individual would not be a clone. However, it is feasible that the chimeric embryo could be manipulated such that the original embryo only forms placenta and the reprogrammed cells form the body. This has been accomplished with mixtures mouse embryonic stem cells and mouse embryos, but not with mixtures of reprogrammed mouse cells and mouse embryos. )

The results of some quick internet research suggests that using human iPS cells this way would not be allowed: In the UK, creating or using embryos outside the body requires a special license from the government, so I’d guess that permission would need to happen proactively. The US lacks legislation on reproductive cloning, though some individual states ban it. Australia distinguishes between research embryos (created through technical manipulation or by mixing genes from three or more people) and reproductive embryos (created through fusion of sperm and egg) and allows only reproductive embryos to used to create an embryo. A document dated to 2004 from Japan banned, among other things, the creation of chimeric human-human embryos for research.

Technically, inserting reprogrammed cells in an embryo does not produce a clone, as the Independent article implies, but a chimera. Scientists purposely and frequently produce mouse chimeras via this technique in order to prove that cells have been truly reprogrammed. (Truly reprogrammed cells can contribute to all the tissues in the body, including gametes.) Human chimeras happen naturally with some transplants and even during some pregnancies when cells from different embryos mix. ( See our commentary on a theological argument for chimeras .)

The expert quoted in the Independent article is Bob Lanza, chief scientific officer of Advance Cell Technology. I called him up and asked if he was putting reprogrammed human cells into human embryos.

“Oh no no no,” he gasped. He said the reporter was following up on a commentary he published in Science last year, where he urged ethicists to consider ethical implications of reprogrammed cells, called induced pluripotent stem (iPS) cells.

He said he didn’t know anyone trying to do create humans this way, but that the possibility should be considered. “You can easily imagine where an infertile couple may desperately want a child that has its own genes,” he said, adding that right now attempts would not be safe for the child because of the need to genetically modify the cells.

When chimeric embryos are made, chance plays a big role in determining which cells grow into which parts of the body. Reprogrammed cells might contribute to many tissues or to very few. There are techniques in mice such that cells mixed in with an embryo contribute more heavily to the mouse pup, but they require potentially harmful manipulation of the embryos, and the most rigorous has yet to produce a live mouse.

Still, the ability to make people who are genetic hodgepodges has plenty of ethical implications, many truly scary. (If a skin sample was taken without your consent and used to make a child, what are your obligations to the child? What if the iPS cells did not contribute to, say, the child’s brain or gametes? If a donor’s iPS cells did contribute to a child’s gametes, then the donor would be the physical grandparent but genetic parent of that child’s children.)

Other possibilities, not mentioned in the article, center on using reprogrammed human cells to make viable sperm and eggs, but so far attempts at getting human embryonic stem cells have failed, and many scientists think this is a long way off.

In this week’s Nature, an editorial describes a man who was born female underwent hormone treatment and some gender-reassignment surgery. Thomas, whose wife is unable to bear children, decided to become pregnant himself. The editorial states that “our visceral concept of what is natural will continue to evolve as technology does” and please for “rational consideration of deeper and more important ethical issues.”

It is possible that reprogramming will mean that couples and people who never considered the possibility of having children will, one day, be able to do so. This advice will continue to apply.


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