Stripping Down Science (14 page)

King and his colleagues therefore suspected that this might be causing the babies' immune systems to develop what is known as ‘tolerance' to malaria. Tolerance is a process by which the immune system normally learns what it should befriend (and ignore) and what it should attack. If the malaria parasite is present when the baby is developing, the team reasoned, the baby's immune system might be fooled into thinking that the parasite is a normal part of the body and so ignore it.

In keeping with this theory, when the team mixed malaria antigens with white blood cells from babies whose mothers were infected with malaria at the time of delivery, the babies' cells reacted only very weakly. But white cells from babies who were not born to infected mothers, on the other hand, showed vigorous reactions and pumped out large
amounts of inflammatory hormones.

This suggests, say the team, that if a mother is infected with malaria when she is pregnant, the baby's immune system is misled into becoming tolerant to the parasite rather than attacking it. This could have serious implications for the development of a successful vaccine, because the children who are most at risk are those who are already tolerant to malaria and therefore won't make a very powerful immune response to a vaccine.

So why are children under six months less affected? This is because babies are initially protected from malaria by antibodies which are present in breast milk and are also added to the baby from the mother's bloodstream during the final phase of pregnancy. These antibodies persist in the baby's circulation for about six months, but once they are gone the child becomes vulnerable. And if the child is one that has developed tolerance to malaria, then it will develop far more severe malaria disease with a correspondingly increased risk of dying.

A saving grace is that researchers at least now know about this previously unappreciated part of the malarial parasitic puzzle. But as yet, the world is still waiting for an effective vaccine for one of the most common killers.

We often think of snow as a paragon of purity; it can transform even an ugly industrial landscape into a soothing sight that's easy on the eye. But snow's pristine image is something of a myth, because beneath its sparkling exterior lurks a dirty secret, the full scale of which is only now becoming apparent.

Analysing samples of freshly fallen snow collected from a range of locations around the world, Louisiana State University scientist Brent Christner and his colleagues
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found that the snow contained large numbers of bacteria which, it turned out, had quite literally come down in the last shower. Why were these bacteria turning up in pristine snow? Well, the results suggest that they were most likely hitching a ride around the world in snow clouds, and to help them to do that they've evolved a clever way to manipulate the formation of ice crystals.

When water-soaked air rises up into the
atmosphere, it cools until it eventually reaches a temperature at which the water can no longer remain as a vapour and so it begins to form droplets of water or ice. The droplets usually gather around particles of soot, pollen, dirt and even dandruff, which provide surfaces called nucleation sites on which the water can condense. But these structures only condense water efficiently at very low temperatures, below minus 10 degrees Celcius, and this is where the cloud-riding bacteria come in. The surfaces of their cells are peppered with a large protein which contains chemical groups that love to latch onto water molecules.

These chemical groups are arranged at just the right spacing and orientation so that they mimic the crystal structure of ice. Once water molecules have locked on, as soon as the temperature dips just below zero, they're already in the ideal arrangement for freezing, which means that ice can form around the bacterium at much higher temperatures than it would do normally.

So why should a bacterium want to seal itself into the middle of a microbial ice cube? Probably because these bugs, called
Pseudomonas syringae
, are a family of plant pathogens that use
frost to make a forced entry into the leaves and stems of their hosts. By triggering the formation of ice on a plant's surfaces, the bacteria can use the jagged crystals to punch holes into the tissue. This microbial equivalent of a ramraid allows the bacteria to penetrate the plant and soak up nutrients. This trick was first discovered in the 1970s, and very quickly researchers realised that if the bacteria were mixed with water and sprayed onto a near-naked ski-run they could produce a perfectly passable piste under the right conditions. In fact, they're marketed today as ‘Snomax', although they come freeze-dried, rather than ready frozen.

But what are they doing in clouds? Well, although these bugs are found everywhere in nature, until recently no one had appreciated how they were getting around. Now scientists suspect that strong winds blow them from plants up into the air and carry them for tens or even hundreds of kilometres. Then, as they go, they use their clever chemistry to trigger clouds to form around them and descend with the ensuing shower onto a new patch of greenery below. So where this piece of science is concerned, it seems that it never rains until it pours.

A question that's been circulating for over 100 years is where do the heart's own blood vessels – the two coronary arteries – come from? These vessels follow a characteristic path from the aorta, the body's main artery, around the two sides of the heart, branching as they go to supply each part of the muscle. Owing to this pattern, embryologists and anatomists thought that these arteries grew out from the aorta and across the heart's surface as the organ was developing. But this turns out to be a blood-vessel-bustingly-big myth, because new research has shown that the coronaries actually come from a large vein outside the heart. This matters because if we can now work out what the signals are that control the process, it might be possible in the future to reactivate them and so make broken hearts mend themselves.

The new discovery was made by a scientist at the Howard Hughes Memorial Institute in
America called Kristy Red-Horse.
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By using a genetic label to trace, in mice, the movements of the cells that become blood vessels around the heart, she was able to show that the coronary arteries were springing up from a very unusual source, nowhere near the aorta. Instead, the first thing that happens, she found, is that very early during development a cluster of cells migrates onto the rear surface of the developing heart from a large vein passing behind it called the sinus venosus, which carries blood in the embryo back to the developing heart.

These cells, which are known as endothelial cells and normally form the inner linings of blood vessels, then migrate around and plumb themselves into the heart's main outflow tract – the future aorta – which is situated in the centre at the top of the developing organ. From there, the cells make their way down the left side and the front of the heart, laying the foundations for what will become the future left coronary arteries. The cells also travel along a strip down the back of the heart to form the right coronary artery. As they move over the organ's surface, the cells invade the
muscle tissue, producing capillaries to deliver the oxygenated blood flowing along the arteries to the actively beating cells. They also give rise to veins to return the spent blood to the heart's right atrium so that it can be reoxygenated by the lungs.

That all sounds relatively straightforward, but a key question is where do these artery-producing cells come from in the first place, and what directs them to achieve this impressive feat of cardiac plumbing? The answers to these questions might hold the key to growing new blood vessels to bypass coronaries clogged by cholesterol in patients with heart disease.

By carefully examining the sinus venosus, Kristy Red-Horse and her colleagues were able to spot the place where the cells were originating from the lining of this vein. After they appeared, rather like miniature moles, the cells burrowed through the wall of the sinus venosus to emerge onto the rear surface of the heart. This seems to occur in response to a chemical signal produced by the adjacent developing heart tissue, because when pieces of either the sinus venosus or the heart tissue were cultured in a dish in isolation, no vessel-forming cells appeared. But when the two were brought close together, coronary critical
mass was achieved and the cells began to grow and spread.

What makes this happen, and the nature of the other signals that guide the artery-producing cells across the heart surface, isn't known yet. But the researchers did find that the endothelial cells leaving the sinus venosus all turned off various genes that are associated with vein tissue and then, as soon as they entered the heart tissue, turned on a different combination of genes that are normally expressed in arteries.

This shows that vein cells can effectively be reprogrammed to build arteries and that the heart muscle must produce signals to direct and control this process. Now the race is on to work out what they are. As one of the team, Mark Krasnow, puts it, ‘If we can learn how to reprogram cells to build a new coronary artery just like the original, bypass grafts could last the rest of a lifetime.'

FACT BOX

Heart disease and repair

Heart disease kills about one person in every three, making it the most common cause of death worldwide. Heart attacks happen when the blood vessels that supply the heart muscle – the coronary arteries – become blocked, usually through a build-up of a fatty substance called atheroma. One way to deal with this problem is to carry out a bypass operation, where a piece of blood vessel – usually a muscular vein from the leg called the long saphenous vein – is used to route blood around the blocked part of the vessel, restoring flow downstream.

Although this sort of surgery is still occasionally performed, these days doctors are more likely to carry out a procedure called angioplasty and stenting. This involves the threading of a thin tube into one of the arteries in the leg and from there up to the heart and into the blocked coronary artery. Using X-rays, the tip of the tube is positioned over the blockage and a small balloon inflated for
a few seconds to open up the narrowed area. To prevent the vessel closing up again, a tiny metal cage called a stent is then inserted into the treated spot to prop open the artery walls.

These treatments have revolutionised the management of coronary artery disease, but unfortunately they are less useful for patients who have already had a heart attack, which has led to the death of a patch of heart muscle. In humans, the damaged area never recovers its pumping ability and is instead replaced with fibrous scar tissue, which can lead to heart failure and the formation of blood clots.

Not all species behave like this though. In fact, some, like the tiny zebra fish, can regenerate a sizeable chunk of their heart if it is damaged, leading scientists to wonder if it might be possible to recapitulate the trick in humans. But how these animals were doing this remained an unsolved cardiac conundrum, at least until very recently.

One idea was that the fish had some kind of stem cell lurking in their heart tissue, ready to spring into action and regenerate new muscle
if anything went wrong. This turns out not to be true, however, because Barcelona-based researcher Chris Jopling and Howard Hughes Medical Institute scientist Kazu Kikuchi
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have found that heart muscle cells themselves have the necessary know-how to carry out even fairly significant cardiac DIY. The researchers showed this by genetically tagging a group of fish with a coloured protein to label up just the heart muscle cells. They then removed 20% of the ventricle tissue and watched to see what happened. If the heart muscle cells grew and divided to replace the lost tissue, then the repair should comprise cells all carrying the coloured genetic marker. But if an unlabelled stem cell was responsible, then the repair would also be unlabelled and the new muscle cells would be colourless.