University of Cambridge, UK

A zoologist traces flu across the globe.

In winter, everybody recognizes a stuffy nose, a fever and an achy body as influenza. But experts still grapple with where the flu virus goes during the summer. One theory has it that flu lays low, holding out until the following season in a small number of asymptomatic people. Another idea — that flu strains tend to become extinct locally but shift around geographically — carries more weight. A recent paper by Derek Smith of the University of Cambridge, UK, and his colleagues helped nail the latter hypothesis by plotting the results of antigen-binding assays and genetic sequencing of more than ten thousand viruses on a map (C. A. Russell et al. Science 320, 340–346; 2008).

The researchers call this approach 'antigenic cartography'. Their antigenic time charts contain data crunched from the portion of the World Health Organization's enormous 'Global Influenza Surveillance Network' database that details strains classified as 'H3N2' between 2002 and 2007. First, they confirm flu's source–sink dynamics by showing that winter flu strains are more closely related to (and thus more likely to have evolved from) strains found elsewhere than to last season's local contagion. Second, the team pinned down H3N2's spread. Temperate regions are regularly seeded by strains from east and southeast Asia, where many strains circulate continuously and asynchronously in a pattern probably driven by varying climatic conditions.

These findings suggest that close surveillance of emerging strains in east and southeast Asia could enable us to predict those that will later affect the rest of the world. Yet it also poses a question: why do flu strains not return to this region after spending time (and thus evolving) elsewhere? Now that we know where new strains come from, we need to find out why they never go back.

Posted by Anna Petherick at 03:19 PM | Permalink | Comments (0) | TrackBacks (0)

University of Washington, Seattle, Washington

An evolutionary biologist considers the virulence of emerging infectious diseases.

When a pathogen — for example, HIV — emerges into the human population, it adapts to growth and transmission in human hosts. At the same time, its virulence (often measured by case mortality) typically changes as well. On the basis of theoretical arguments and examples such as the myxoma virus, conventional wisdom holds that if a disease is highly virulent at first, it will rapidly evolve reduced virulence so as to maximize transmissibility. The idea is that pathogens face a virulence–transmissibility trade-off: strains that kill or even incapacitate their hosts are unlikely to spread as broadly as those that keep their hosts alive and mobile.

One might think — and some have argued — that we can take comfort from such reasoning. By this logic, the 60% mortality rate seen in human cases of H5N1 avian influenza should rapidly attenuate were a human pandemic to occur. But in the inaugural issue of Evolutionary Applications, Bull and Ebert refute this thinking using a clear, simple mathematical model (J. J. Bull & D. Ebert Evol. Appl. 1, 172–182; 2008).

As someone working on the dynamics of emerging infectious diseases, I find this paper fascinating and sobering in equal measure. The gist of its argument is that trade-off models may not apply well to emerging infectious diseases, precisely because they are still emerging. When a disease first enters a new host, it can be far from the optimum point on the virulence–transmissibility trade-off curve. Its early evolutionary trajectory may be contingent on mutation supply and thus very hard to predict: virulence might decline, but could also initially rise.

The implications are clear. We need to invest now in disease surveillance, public-health infrastructure and pandemic planning. We cannot count on evolution to do our work for us.

Posted by Anna Petherick at 03:18 PM | Permalink | Comments (2) | TrackBacks (0)

Imperial College London

A population geneticist looks back in time in search of human origins.

When and where anatomically modern humans evolved is arguably one of the most fundamental scientific questions. The issue also has philosophical and possibly even moral implications because it influences our definition of humanity. But I became involved in the subject for much more prosaic reasons. I was trying to make sense of the distributions among human populations of different versions of genes that imbue resistance to infectious diseases. It struck me that attempting to do this without a clear understanding of humans' past demography was bound to end in a muddle.

Despite decades of research, the origin of modern humans is still hotly debated. In a recent paper, Laurent Excoffier and his colleagues provide the first formal statistical evaluation of the likelihood for the various schemes that have been proposed (N. J. R. Fagundes et al. Proc. Natl Acad. Sci. USA 104, 17614–17619; 2007). They conclude that a recent expansion from a single African origin is better supported by the current geographical spread of human genes than a multi-regional scenario. The multi-regional hypothesis proposes that modern humans hybridized with archaic humans, such as Homo erectus, as they spread.

This result may seem unsurprising because most genetic evidence points to an African origin some 60,000 years ago with no or negligible hybridization with archaic humans. However, there is a twist. By far the best supporting evidence for hybridization between modern and archaic humans has been the observation that, looking back, the amount of time it takes to reach the most recent common ancestor of some genes largely predates the age of our species. The extensive simulations in this paper debunk that argument by demonstrating that such cases can arise if modern humans had a recent and single African origin.

Posted by Anna Petherick at 12:51 PM | Permalink | Comments (2) | TrackBacks (0)

University of Colorado, Boulder

A biologist looks to 'click chemistry' for better three-dimensional tissue models.

A hot topic in organic chemistry is the development of ways to neatly home in on a particular chemical group and cause a reaction to proceed extremely efficiently under mild conditions. Such highly optimized reactions have been grouped under the term 'click chemistry'. A commonly cited example involves functional groups called azides and alkynes, which react to form triazoles with the aid of a copper catalyst.

Click chemistry has all sorts of uses, although few are in biology because the technique relies on toxic metal catalysts. However, Carolyn Bertozzi and her colleagues at the University of California, Berkeley, and the nearby Lawrence Berkeley National Laboratory recently demonstrated copper-free click chemistry in a living system (J. M. Baskin et al. Proc. Natl Acad. Sci. USA 104, 16793–16797; 2007). These authors selectively — and rapidly — labelled cell-surface polysaccharides with with triazole bound to a fluorescent probe. The technique allows real-time imaging of cell surface molecules that are otherwise impossible to achieve.

This research throws open the door for a host of new applications for click chemistry. As a tissue engineer, I am particularly excited about exploiting it to make better gels for three-dimensional cell culture.

Physiological processes are routinely guided by interactions between cells and their tissue environment. Thus, a major hurdle in tissue regeneration is knowing which biochemical signals must be recapitulated in cell culture, and how to present them at the appropriate time and place. Copper-free click chemistry could allow scientists to synthesize materials that deliver these signals at times that are governed by the physiological conditions in which the material resides. Next on my wish list is the ability to control the spatial organization of these reactions.

Posted by Anna Petherick at 12:43 PM | Permalink | Comments (0) | TrackBacks (0)

Harvard Medical School, Boston, Massachusetts

An immunologist muses about inflammation through cell interactions.

I spend my lab hours trying to understand what prompts T cells — a type of white blood cell — to specialize. Some T cells produce soluble molecules that rattle the immune system into an inflamed state; other cells generate molecules that calm the system back down.

Upon infection, cells such as macrophages — another type of white blood cell — produce soluble molecules called interleukins that direct the fate of the responding T cells. An emerging curiosity in the field is which interleukins make certain T cells become pro-inflammatory, and which cause other T cells to become anti-inflammatory. This decision is crucial for determining whether an immune response induces or suppresses inflammation.

Recently, investigators have turned their attention towards an interleukin known as IL-27. This is produced by activated macrophages and was initially thought to induce IFN, a signalling molecule that activates macrophages even more.

But work by Nico Giraldi and his colleagues at Genentech in South San Francisco, and other groups, has recast IL-27 as a molecule that primarily directs T cells to suppress inflammation. In a paper published in March, Giraldi's team confirmed that IL-27 acts in this way because it causes CD4+ and CD8+ T cells to make the anti-inflammatory IL-10, and does not work through an alternative pathway (M. Batten et al. J. Immunol. 180, 2752–2756; 2008). Mice with Listeria infections or autoimmune tissue inflammation in their brains and spinal cords generated fewer IL-10-producing T cells when they lacked an IL-27 receptor. Whether an analogous interaction occurs in humans is not known, but, if it does occur, this research could become medically useful.

Posted by Maxine Clarke at 09:19 AM | Permalink | Comments (0) | TrackBacks (0)