Lab report

Mandelbrot’s insight into financial crises; how stem cells develop; counting genomes
November 17, 2010

If bankers had heeded Benoît Mandelbrot’s discovery in the 1960s that economic fluctuations and the risks they entail are not governed by bell-curve statistics, they might not have been caught off-guard by the credit crunch. In his seminal 1982 book The Fractal Geometry of Nature, the Polish-born mathematician, who died in October aged 85, argued that fractals describe everything from cracks to the crazy convulsions of the markets.

Fractal objects look the same at different magnifications—forking branch tips, for example, echo the whole tree—so you cannot gauge any size scale by shape alone: they are “scale-free.” The mathematical fractal pictured above, discovered by Mandelbrot, has borders at which you see ever more fine detail (including tiny repetitions of the whole object) as you zoom in. His work established a geometric language for understanding structures and processes that once seemed irreducibly complex, such as fracture or turbulent fluid flow.

He defended pugnaciously his claims to have been first to come up with certain ideas, and he made enemies easily. In 1998 I saw him give an incoherent talk in which he wielded transparencies of graphs like legal deeds of entitlement, flashing them up just long enough to file his case. But that was just his style, and doesn’t detract from his significance in directing scientists to patterns that have no natural scale—now recognised to feature in areas ranging from cosmology to population dynamics.

HOW DO STEM CELLS DEVELOP?

The cloud hanging over stem-cell research, after the rogue ruling by a US judge in August stopped federal funding for research on human embryonic stem cells, hinges on an eccentric reading of old legislation. Whether congress will clarify the matter is now unclear after the Republican gains in the midterms. This situation adds urgency to the quest to create stem cells by reprogramming mature cells that have already “differentiated” into specific tissue types, potentially obviating the need to destroy embryos. Understanding how stem cells in the early embryo become differentiated—and how this might be reversed—is the burning question, reflected at two big stem-cell meetings in October at the Royal Society in London and Rockefeller University in New York.

Mature cells can be returned to a stem cell’s “pluripotent” status (able to form all tissue types) by moving the nucleus, which contains the chromosomes, into an unfertilised egg cell—basically the technique used to clone Dolly the sheep. But that’s cumbersome, which was why the discovery in 2007 that cells can be reprogrammed by adding a cocktail of four genes, ferried by viruses, excited such interest. Unfortunately, last July it was found that such induced pluripotent cells don’t entirely forget their specialised lineage and so don’t achieve full “stem cell” capability. Working out why they don’t might not only be central to the clinical use of stem cells, for example to regenerate damaged nerves or brain tissue, but also holds the answer to fundamental questions about how our genes make us. We know that some genes are chemically “silenced” as cells specialise, and those messages must be erased in reprogramming; researchers now aim to identify the proteins responsible, as some of them explained at the recent meetings. Meanwhile, a Boston-based team have devised a new reprogramming approach that uses RNA—the intermediary molecule that translates genetic information into proteins—rather than genes carried on viruses, thus avoiding cells’ antiviral responses that limit the efficiency of the latter method. Researchers may lament the ethical constraints that make all this work necessary, but the biological questions it forces us to confront are profound.

SO MANY GENOMES

The 1000 Genomes project, an international consortium that in fact aims to sequence many thousands of human genomes, has released its first findings in a blaze of publicity. So far it has totted up around 179 (rather sketchy) genomes, and genomic segments for hundreds more. By cataloguing the gene variants within and across populations, we should gain a better understanding of how certain mutations confer inheritable susceptibility to disease. This link is considerably more subtle than was generally advertised during the Human Genome project. Yet a survey by Nature estimates there are already around 2,700 human genomes sequenced worldwide, and there will be more than 30,000 by the end of 2011. Judging by past experience, advances in sequencing technology will make that forecast an underestimate. But, as with stem cell research, promises of medical benefits should be greeted with caution; the more immediate effect will be a better understanding of what makes us who we are.