Thursday, December 13, 2007

Surfers and stem cells
[This is the pre-edited version of my Lab Report column for the January issue of Prospect.]

Just when you thought that the Dancing Wu Li Masters and the Tao of Physics had finally been left in the 1970s, along comes a surfer living on the Hawaiian island of Maui who claims to have a simple theory of everything which shows that the universe is an ‘exceptionally beautiful shape’. Garrett Lisi has a physics PhD but no university affiliation, and lists his three most important things as physics, love and surfing – “and no, those aren’t in order.”

But Lisi is no semi-mystic drawing charming but ultimately unedifying analogies. He is being taken seriously by the theoretical physics community, and has been invited to the high-powered Perimeter Institute in Waterloo, Canada, where leading physicist Lee Smolin has called his work “fabulous.”

One thing rather fabulous is that it is almost comprehensible, at least by the standards of modern fundamental physics. Lisi himself admits that, in comparison to string theory, the main contender for a theory of everything, he uses only “baby mathematics.” That’s not to say it’s easy, though.

A theory of everything must unify the theory of general relativity, which describes gravity and the structure of spacetime on large scales, with quantum theory, which describes how fundamental particles behave at the subatomic scale. To put it another way, gravity must be mixed into the so-called Standard Model of particle physics, which explains the interactions between all known fundamental particles – quarks, electrons, photons and so forth.

Physicists typically attempt unification by using symmetry. To put it crudely, suppose there are two particles that look the same except that they spin in opposite directions. These can be ‘unified’ into a single particle by appreciating that they can be interconverted by reflection in a mirror – a symmetry operation.

The idea is that the proliferation of particles and forces in today’s universe happened in a series of ‘symmetry-breaking’ steps, just as lowering a square’s symmetry to rectangular creates two distinct pairs of sides from four identical ones. This is already known to be true of some forces and particles, but not all of them.

Lisi claims that the primordial symmetry is a pattern called E8, known to mathematicians for over a century but fully understood only recently; it is rather like a multi-dimensional polyhedron with 248 ‘corners’. He has shown that all the known particles, plus descriptions of gravity, can be mapped onto the corners of E8. So a bit of it looks like the Standard Model, while a bit looks like gravity and spacetime. Twenty of the ‘corners’ remain empty, corresponding to hypothetical particles not yet known: the E8 model thus predicts their existence. It’s rather like the way nineteenth-century chemists found a pattern that brought coherence and order to the chemical elements – the periodic table – while noting that it had gaps, predicting elements that were later found.

Is E8 really the answer to everything? Physicists are reserving judgement, for Lisi’s paper, which is not yet peer-reviewed or published, is just a sketch – not a theory, and barely even a model. Mathematical physicist Peter Woit is unsure about the whole approach, saying that playing with symmetry just defers the question of what breaks it to make the world we know. But the trick worked before in the 1950s, when Murray Gell-Mann predicted a new particle by mapping a group of known ones onto a symmetry group called SU(3).

Lisi’s surfer-dude persona is fun, but so what, really? The real point is that his suggestion invigorates a field that, wandering in the thickets of string theory, sorely needs it.

*****

Stem-cell researchers in Shoukhrat Mitalipov’s team at the Oregon Health and Science University might be forgiven a little chagrin. No sooner had they reported the breakthrough that has eluded the field for years than they were trumped by two reports seeming to offer an even more attractive way of making human stem cells. Having sung the praises of Mitalipov’s achievement, Ian Wilmut, the University of Edinburgh cloning pioneer who created Dolly the sheep, announced that he was ditching their approach in favour of the new one.

Stem cells are the all-purpose cells present in the very early stages of embryo growth that can develop into just about any type of specialized tissue cells. The ‘traditional’ strategy for making them with DNA matched to the eventual recipient involves stripping the genetic material from an unfertilized egg and replacing it with donor DNA, and then prompting the egg to grow into a blastocyst, the initial stage of an embryo, from which stem cells can be extracted. This is called somatic cell nuclear transfer (SCNT), and is the method used in animal cloning. It works for sheep, dogs and mice, but there had previously been no success for humans or other primates.

On 14 November last year, Mitalipov and colleagues reported stem cells made by SCNT from rhesus macaques that could develop into other cell types. But a week later, teams based at the universities of Kyoto and Wisconsin-Madison independently reported the creation of human stem cells from ordinary skin cells, by treating them with proteins that reprogrammed them. In effect, the proteins switch the gene circuits from a ‘skin cell’ to a ‘stem cell’ setting. This reversal of normal developmental pathways is extraordinary.

The two teams used different cocktails of proteins to do the reprogramming – the Wisconsin team manage to avoid an agent that carries a cancer risk – showing that there is some scope for optimising the mix. Best of all, the method avoids the creation and destruction of embryos that has dogged the ethics of stem-cell research. But Mitalipov insists that starting with eggs is still best, and he has now started collaborating with a team in Newcastle licensed to work with human embryos. After years of frustrating effort, suddenly all options seem open.

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