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Even a Worm Will Turn

This worm is born to travel. It begins life in human lymph, only to seep out of the lymphatic vessels into the grimy fluid that bathes our organs. From there, it drifts into the blood stream. During the day, it keeps to deep veins. Once darkness falls, it migrates up to the skinny veins just under the skin.

Then one lucky night, a mosquito will find the sleeping human and feast on its blood. The worm will end up in the insect’s gut and, eventually, in its muscles. It will reach adolescence there, and then travel to the mosquito’s head, stinger and, finally, to the next person the insect bites. From the blood stream, the worm will find its way back to the lymph to mate and, after such a long journey, retire. It will stay there for six to eight years, the rest of its life, and pump out millions of new little worms to embark on the same cross-species adventure.

Unfortunately, the health of these worms, called parasitic filarial nematodes, is in direct conflict with that of their human hosts. The worms slowly accumulate inside of people, eventually clogging lymph nodes and causing the extreme swelling, discoloration and deformity known as elephantiasis. More than 120 million people in 72 countries are infected with the disease, formally called lymphatic filariasis, leaving some 40 million incapacitated.

There is no cure, but there is a potent treatment called ivermectin. The drug paralyzes juvenile worms swimming in blood, making them much more vulnerable to attack by the human immune system. But ivermectin has little effect on the long-living adult worms in the lymph. To target those, doctors rely on two other drugs, diethylcarbamazine and albendazole.

A woman with elephantiasis
A few million years ago, Jamaica was home to one of the strangest boxers in the animal kingdom – a flightless bird called Xenicibis xympithecus that could batter its enemies with club-shaped wings. Xenicibis is a large, extinct, flightless ibis. It was discovered by Storrs Olson from the Smithsonian Institution, who found some partial remains in a Jamaican cave in 1977. When Olson eventually saw the bird’s wing bones, he was baffled. They were so “utterly strange” that he thought the animal must have been suffering from some inexplicable disease. Since then, Olson has found more remains including an almost complete skeleton. Now, he and his partner Nicholas Longrich from Yale University, have a very different view of the wing. They think it was a club. Weapons like clubs and bats have large weighted ends to deliver heavy impacts, and long handles to increase the speed of the swing. That’s exactly what you see in Xenicibis’s wing. Its hand bone (the metacarpal) was massive, curved and inflated – perfect for inflicting strong blows. It sat at the end of a long ‘handle’, made up of the wrist and the forearm – perfect for creating a fast swing. The metacarpal is also hollow, just like many baseball bats are, allowing it to produce a stronger blow without adding too much weight. And its joints allowed it to swing its wing out very quickly, and extend it as far as possible, giving it speed and reach. The bones are telling, but did Xenicibis really punch with its wing? It’s hard to be sure, especially because there are few modern birds with similar bones to compare against. However, Longrich and Olson have found some compelling evidence that the bird struck heavy blows with its wings At least two specimens of Xenicibis had arm bones that had broken and healed. The first had broken its upper arm (humerus) in two and the bones hadn’t knitted together properly. The second had fractured its hand, and a massive callus had grown over the front edge. These birds struck something with enough force to injure themselves. Xenicibis might have used its wings to clobber enemies in defence. Unlike its living cousins, this ibis couldn’t fly. Many island birds lose the ability to fly because they aren’t threatened by any land predators. As a result, their wings become small and stunted, as in the kiwi or the flightless cormorant of the Galapagos. But prehistoric Jamaica had no shortage of predators, including a boa, an extinct monkey, and several birds of prey. Defence would have been important. Alternatively, the bird could have boxed with its rivals. Longrich and Olson note that a couple of flightless birds have similar (but far less extreme) forearms, including the steamer duck and the extinct Rodriguez Island Solitaire. And both of these species occasionally use (or used) their wings in to beat other individuals in fights. In fact, many birds use their wings as weapons (including some ibises). Some even have special adaptations for combat. Waterfowl in particular, such as geese, ducks and swans, have a wide variety of spurs, spikes and bony knobs on their wrists. They use these weapons in battle and conflicts can be very violent (although there’s some debate about whether swans can actually break a person’s arm). Xenicibis just expanded on a theme that’s common in the bird world and took it to an evolutionary extreme. Reference: Proc Roy Soc B http://dx.doi.org/10.1098/rspb.2010.2117 If the citation link isn't working, read why here More on bird wings:

In the past decade or so, several large pharmaceutical companies have worked with the World Health Organization and the Gates Foundation to widely distribute these drugs for free in developing countries. “In certain areas of the world, these compounds have been incredibly effective at reducing transmission,” says Tilde Carlow, a parasitologist at New England Biolabs.

But the drugs are not ideal. First problem: In some parts of Africa, many people are also infected with a different parasite, called the loa loa worm, that can cause adverse reactions to diethylcarbamazine and ivermectin.

Then there’s the more controversial issue of ivermectin resistance, which would play out like this: Some worms carry genetic glitches that just happen to help them evade the drug. Over time their descendants will thrive, eventually making ivermectin useless. Widespread resistance has already happened in worms living inside of farm animals, which have been exposed to the drug much longer than humans have. “So there’s a lot of caution and concern that when you’re using this drug in these massive drug campaigns for humans something similar is going to happen,” Carlow says.

A study published last year gave the first evidence that ivermectin resistance is indeed happening in people. The researchers focused on Onchocerca volvulus, a worm that causes another nasty tropical disease called onchocerciasis, or “river blindness.” Some 25 percent of infected people in Ghana — where ivermectin is used heavily — carry worms that respond poorly to the drug, the study found. Researchers are still hotly debating the extent of the resistance, and the speed of its potential spread, Carlow says. “But the implications are huge.”

Which is all to explain why, for the past 28 years, Carlow and her colleagues have been trying to develop new ways to eliminate these parasites. Because of their complicated life cycles, the worms are extremely tricky to grow in the lab (it involves gerbils and mosquitos). But the genomic revolution of the past few years has uncovered a lot of information about the worms’ genes and those of a closely related species, Caenorhabditis elegans, which is easy to keep alive and ubiquitous in genetic research.

Why is it helpful to decode their genomes? “It helps us explore what these worms are made of, and find their Achilles’ heel,” Carlow says. For example, by looking at the genetic code, scientists discovered that one parasite carries around a bacteria called Wolbachia that somehow helps the worms survive. That opened up a whole new line of attack against the worms: antibacterial drugs. More recently, Carlow’s lab has identified two compounds that target a crucial enzyme inside of Wolbachia. When that’s knocked down, so is the bacteria, and so is the wayfaring worm.

This post was originally published on The Last Word on Nothing