Wednesday, September 26, 2007

Hybrids and helium
[This is the pre-edited version of my Lab Report column for the October issue of Prospect.]

It’s not obvious that, when the Human Fertilisation and Embryology Authority was established in 1991, anyone involved had much inkling of the murky waters it would be required to patrol. The HFEA was envisaged primarily as a body for regulating assisted conception, and so it seemed sensible to give it regulatory powers over human embryo research more generally. Sixteen years later, the HFEA is having to pronounce on issues that have little bearing on fertility and conception, but instead concerns biological research that some say is blurring the boundaries of what it means to be human.

So far, the HFEA has remained commendably aloof from the ill-founded fears that this research attracts. Its latest permissive ruling on the creation of human-animal cells is the outcome of sober and informed consideration of a sort that still threatens to elude the British government. It belies (in the UK, at least) the fashionable belief that Enlightenment ideals are in eclipse.

There are many different ways human and non-human components might be mixed in embryos. Some research requires human genetic material to be put into animal cells – for example, to create human embryonic stem cells without reliance on a very limited supply of human eggs. There are also arguments for putting animal genes into human cells, which could offer new ways to study the early stages of human development, and might even help assess embryo quality for assisted conception.

Certainly, there are dangers. For example, eviscerating an animal cell nucleus (where most DNA is housed) to make way for a human genome does not remove all the host’s genetic material. Such transfers, which produce so-called cytoplasmic hybrid (‘cybrid’) cells might, if used to make stem cells for medical implantation, run the risk of introducing animal diseases into human populations. Recent findings that genomes can be altered by ‘back-transfer’ from non-genetic material adds to the uncertainties.

But no one is intending at this stage to use cybrids for stem-cell treatments; they are strictly a research tool. The HFEA has decided that there is no ‘fundamental reason’ to prohibit them – recognizing, it seems, that protests about human dignity and unnaturalness impose misplaced criteria. It stresses that the ruling is not a universal green light, however, and that licensing will be made on a case-by-case basis – as they surely should be. The first such applications are already being considered, and are likely to be approved.

The ruling says nothing yet about other human-animal fusions, such as embryos with mixtures of human and animal cells (true chimeras) or hybrids made by fertilization of eggs with sperm of another species. These too may be useful in research, but carry a higher yuk factor. On current form, it seems we can count on the HFEA not to succumb to squeamishness, panic or the mendacious rhetoric of the slippery slope.


Was it vanity or bravery that prompted Craig Venter to allow his complete genome to be sequenced and made public? That probably depends on how you feel about Venter, whose company Celera controversially provided the privatized competition to the international Human Genome Project. Both those efforts constructed a composite genome from the DNA of several anonymous donors, and analysed only one of each pair of the 23 human chromosomes.

In contrast, Venter’s team has decoded both of his chromosomes, revealing the different versions of genes acquired from each parent. It is these variants, along with the way each is controlled within the genome and how they interact with the environment, that ultimately determines our physical characteristics. The analysis reveals other sources of difference between chromosomal ‘duplicates’, such as bits of genes that have bits inserted or cut out. This is, you might say, a study of how much we differ from ourselves – and it should help to undermine the simplistic notion that we’re each built from a single instruction manual that is merely read again and again from conception to the grave.

Venter bares all in a paper in the free-access electronic journal PLoS Biology, joining Jim Watson, a co-discoverer of the structure of DNA, as one of the first individuals to have had his personal genome sequenced. Some have complained that this ‘celebrity’ sequencing sends out the message that personalized genomics will be reserved for the rich and privileged. But no one yet really knows whether such knowledge will prove a benefit or a burden – Venter has discovered a possible genetic propensity towards Alzheimer’s and cardiovascular diseases. The legal and ethical aspects of access to the information are a minefield. Venter himself says that his motive is partly to stimulate efforts to make sequencing cheaper. But right now, he has become in one sense the best-known man on the planet.


The moon has always been a source of myth, and now we have some modern ones. Many people will swear blind, without the slightest justification, that the Apollo missions gave us Teflon and the instant fruit drink Tang. New calls for a moon base are routinely supported now with the claim that we can mine the lunar surface for nuclear-fusion fuel in the form of helium-3, a rare commodity on Earth. BBC’s Horizon bought the idea, and it’s been paraded in front of the US House of Representatives. But as physicist Frank Close pointed out recently, there is no sound basis to it. None of the large fusion projects uses helium-3 at all, and the suggestion that it would be a cleaner fuel simply doesn’t work, at least without a total reactor redesign. That’s not even to mention the cost of it all. But no straw is too flimsy that advocates of human spaceflight will fail to grasp it.


JimmyGiro said...

I remember when Horizon was a science program.

Does anybody watch it any more, being that it is neither fat nor lean ?

Jason Bobe said...

Thanks for making the much needed distinction between haploid and diploid genome sequencing. There is still a lot of confusion on this point in the popular press, most often in the form of saying that Venter's diploid genome contains 3 billion base pairs (rather than 6 billion base pairs).