Curing disease is really a matter of outfoxing evolution. When we assault bacteria or viruses or cancer cells with drugs, they evolve ways of resisting those drugs. We attack, they counter-attack. Take malaria: the Plasmodium parasites that cause the disease have repeatedly evolved to resist our best anti-malarial drugs. The mosquitoes that carry the parasites have evolved to resist the insecticides we poison them with. And now, Victoria Barclay from Pennsylvania State University has found that some malaria vaccines could drive Plasmodium to become even deadlier than it is now.
Several malaria vaccines are in development, but none have been licensed yet. Barclay vaccinated mice with a protein that’s found in several of these vaccines, and then exposed them to Plasmodium. After a few generations, the parasite became more ‘virulent’ – that is, it caused more severe disease. And it did so via an evolutionary escape route that is rarely considered.
When bacteria start building cities, we’re in trouble. The normally free-floating cells can gather in large numbers and secrete a slimy matrix that they live within. These communities are called biofilms, and they grow wherever there is a surface to support them. Hospital catheters are prime real estate, but they’ll settle on everything from plumbing to oil refineries to ship hulls.
Within a biofilm, bacteria are extraordinarily durable. Antibacterial chemicals have a tough time reaching them within their slimy fortress. Even if they do, there’s always a batch of dormant cells that can persist through a chemical onslaught and restart the community. They’re involved in the majority of persistent hospital infections, and it’s easy to see why. You could bleach a biofilm for an hour and still fail to kill it. They’ve survived in pipes that are flushed with toxic chemicals for a week.
Since killing biofilms is a Sisyphean task, some scientists are trying to prevent them from forming at all. They’ve tried textured surfaces, chemical coats, and antibiotic-releasing layers. But Joanna Aizenberg has developed a new solution that goes well beyond what the competitors can do. Inspired by the flesh-eating pitcher plant, she created a material so slippery that biofilms simply cannot form upon it.
If wasps didn’t exist, picnics would be a lot more fun. But the next time you find yourself trying to dodge a flying, jam-seeking harpoon, think about this: without wasps, many of your ingredients might not exist at all. Irene Stefanini and Leonardo Dapporto from the University of Florence have found that the guts of wasps provide a safe winter refuge for yeast – specifically Saccharomyces cerevisiae, the fungus we use to make wine, beer and bread. And without those, picnics would be a lot less fun.
S.cerevisiase has been our companion for at least 9,000 years, not just as a tool of baking and brewing, but as a doyen of modern genetics. It has helped us to make tremendous scientific progress and drink ourselves into stupors, possibly at the same time. But despite its significance, we know very little about where the yeast came from, or how it lives in the wild.
The wild strains do grow on grapes and berries, but only found on ripe fruits rather than pristine ones. And they’re usually only found in warm summery conditions. So, where do they go in the intervening months, and how do they move around? They certainly can’t go airborne, so something must be carrying them.
Stefanini and Dapporto thought that wasps were good candidates. They’re active through the summer, when they often eat grapes. Fertilised females hibernate through the winter and start fresh colonies in the spring, feeding their new larvae with regurgitated food. In the digestive tracts of wasps, yeasts could get a ride from grape to grape, from one wasp generation to the next, and from autumn to spring.
The male Japanese rhino beetle wields a huge forked horn on his head. It looks like a jousting weapon, and the male uses it to pry and flip other males off a branch. But it’s also a billboard, a prominent and completely honest advertisement for the male’s quality.
The horns are extremely variable. Small males have pathetic nubbins on their heads, while big ones have unfeasibly large prongs that can grow to two-thirds of their body length. Doug Emlen from the University of Montana has found that the growth of the horns is intimately tied into molecules that reflect how well-nourished the beetles are. Not only that, but the horn is more sensitive to these molecules than any other body part. Well-fed beetles may have larger wings and bodies than poorly-fed ones, but they have much larger horns.
This ornament can’t be faked. It is impossible for a weak beetle to feign rude health by growing a larger horn, so females can rely on the size of the horns to judge a potential partner’s health. And with a body part that conspicuous, they don’t have to look very hard.
The growth of the horns depends on insulin and related molecules called insulin-like growth factors (IGFs). Most people know insulin as the substance that some diabetics have to take, but it and the IGFs are also major players in animal development. Their levels change depending on nutrition, stress and infections, and they control how fast different tissues can grow. They fine-tune the size of an animals’ body so that it’s appropriately sized for the environmental challenges it will face. If there’s plenty of food around, a bigger body will do well, and insulin and IGFs ensure that one is produced.
If every body part was equally responsive to insulin and IGFs, then every bit of an animal would grow at the same size. A big individual would just be a scaled-up version of a small one. But this doesn’t always happen. Some body parts ignore the signals and are much the same size in every individual – the genitals of many insects are a good example. Others, like the rhino beetle’s borns, are hypersensitive and grow huge, out of all proportion to the rest of their bearer’s anatomy.
Emlen studied the beetles’ horns by interfering with their insulin receptors, the molecules that insulin docks with. Without these receptors, insulin becomes a messages without a listener – it has no influence. Emlen silenced the receptors when the beetles were finishing up their larval careers, and ready to transform into adults. At this point, their body size is roughly set, but their adult body parts, like horns, wings and genitals, were still getting bigger.
The loss of insulin signals didn’t affect the beetles’ genitals – they were the same size as those of normal insects. It did, however, make their wings around 2 percent smaller. And it made their horns a whopping 16 percent smaller. This means that the horns are 8 times more sensitive to insulin than wings (which are representative of most other body parts).
Insulin and IGF help to set the size of many other exaggerated animal ornaments, including the antlers of red and fallow deer, the horns of dung beetles, and the giant claws of some crustaceans. You can understand why. These hormones have been coupling the growth of animals to environmental conditions for half a billion years. They form a widespread system, and an easy one to tweak. If a body part becomes subtly more sensitive to these signals, then – Bam! – it’s free to outpace the rest of the body in size.
Here’s the important thing: a change like that would necessarily produce body parts that honestly indicate their owner’s quality. Weak, starving individuals can’t produce big ornaments, because the size of those ornaments is tied to their insulin levels and their insulin levels are tied to their nutritional state. They can’t fake their way to showiness.
This is a subtly different explanation to the one that’s often put forward to explain the evolution of flashy animal ornaments – the handicap principle. It states that low-quality individuals can’t bear the cost of, say, a long tail or a magnificent set of antlers. They would be too conspicuous or heavy. They need strength and health to pull off. Cheats couldn’t bear the burden.
You can understand how the handicap principle would work for a signal that’s already exaggerated, but obviously, those signals didn’t start off that way. They would have had much humbler and smaller origins, when the costs of bearing them would have been low. So, at this early stage of evolution, why didn’t weak individuals cheat by producing larger ornaments?
Emlen’s rhino beetles provide an answer. The signals can’t be faked not because they’re a drain, but because they’re intimately tied into an individual’s physical condition. It’s not that cheaters can’t carry the burden of big ornaments. It’s that cheaters can’t exist.
Reference: Emlen, Warren, Johns, Dworkin & Lavine. 2012. A Mechanism of Extreme Growth and Reliable Signaling in Sexually Selected Ornaments and Weapons. Science http://dx.doi.org/10.1126/science.1224286
More on extreme body parts:
There are thousands of termite species, and many engage in chemical warfare. Some squirt noxious chemicals from nozzles on their heads. Others violently rupture their own bodies to release sticky immobilising fluids, sacrificing themselves for the good of their sisters. Their range of weapons is astounding, and Jan Sobotnik from the Academy of Sciences of the Czech Republic and Thomas Bourguignon from the Université Libre de Bruxelles have just found a new one.
They were studying the termite Neocapritermes taracua when he noticed that some workers have a pair of dark blue spots in the gap between their torsos and abdomens. When other termites attack their colony, the blue workers bite the intruders and burst, releasing a drop of fluid that soon becomes sticky gel. Watch it happen in the video below – the black dot in the middle of the droplet are intestines and other internal organs).
HIV is an exceptional adversary. It is more diverse than any other virus, and it attacks the very immune cells that are meant to destroy it. If that wasn’t bad enough, it also has a stealth mode. The virus can smuggle its genes into those of long-lived white blood cells, and lie dormant for years. This “latent” form doesn’t cause disease, but it’s also invisible to the immune system and to anti-HIV drugs. This viral reservoir turns HIV infection into a life sentence.
When the virus awakens, it can trigger new bouts of infection – a risk that forces HIV patients to stay on treatments for life. It’s clear that if we’re going to cure HIV for good, we need some way of rousing these dormant viruses from their rest and eliminating them.
A team of US scientists led by David Margolis has found that vorinostat – a drug used to treat lymphoma – can do exactly that. It shocks HIV out of hiding. While other chemicals have disrupted dormant HIV within cells in a dish, this is the first time that any substance has done the same thing in actual people.
At this stage, Margolis’s study just proves the concept – it shows that disrupting HIV’s dormancy is possible, but not what happens afterwards. The idea is that the awakened viruses would either kill the cell, or alert the immune system to do the job. Drugs could then stop the fresh viruses from infecting healthy cells. If all the hidden viruses could be activated, it should be possible to completely drain the reservoir. For now, that’s still a very big if, but Margolis’s study is a step in the right direction.
HIV enters its dormant state by convincing our cells to hide its genes. It recruits an enzyme called histone deacetylase (HDAC), which ensures that its genes are tightly wrapped and cannot be activated. Vorinostat, however, is an HDAC inhibitor – it stops the enzyme from doing its job, and opens up the genes that it hides.
It had already proven its worth against HIV in the lab. Back in 2009, three groups of scientists (including Margolis’ team) showed that vorinostat could shock HIV out of cultured cells, producing detectable levels of viruses when they weren’t any before.
To see if the drug could do the same for patients, the team extracted white blood cells from 16 people with HIV, purified the “resting CD4 T-cells” that the virus hides in, and exposed them to vorinostat. Eleven of the patients showed higher levels of HIV RNA (the DNA-like molecule that encodes HIV’s genes) – a sign that the virus had woken up.
Eight of these patients agreed to take part in the next phase. Margolis gave them a low 200 milligram dose of vorinostat to check that they could tolerate it, followed by a higher 400 milligram dose a few weeks later. Within just six hours, he found that the level of viral RNA in their T-cells had gone up by almost 5 times.
These results are enough to raise a smile, if not an outright cheer. We still don’t know how extensively vorinostat can smoke HIV out of hiding, or what happens to the infected cells once this happens. At the doses used in the study, the amount of RNA might have gone up, but the number of actual viral particles in the patients’ blood did not. It’s unlikely that the drug made much of a dent on the reservoir of hidden viruses, so what dose should we use, and over what time?
Vorinostat’s actions were also very varied. It did nothing for 5 of the original 16 patients. For the 8 who actually got the drug, some produced 10 times as much viral RNA, while others had just 1.5 times more. And as you might expect, vorinostat comes with a host of side effects, and there are concerns that it could damage DNA. This study could be a jumping point for creating safer versions of the drug that are specifically designed to awaken latent HIV, but even then, you would still be trying to use potentially toxic drugs to cure a long-term disease that isn’t currently showing its face. The ethics of doing that aren’t clear.
Steven Deeks, an AIDS researcher from the University of California San Francisco, talks about these problems and more in an editorial that accompanies the new paper. But he also says that the importance of the study “cannot be overstated, as it provides a rationale for an entirely new approach to the management of HIV infection”.
Reference: Archin, Liberty, Kashuba, Choudhary, Kuruc, Crooks, Parker, Anderson, Kearney, Strain, Richman, Hudgens, Bosch, Coffin, Eron, Hazudas & Margolis. 2012. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature http://dx.doi.org/10.1038/nature11286
Image by Dr. A. Harrison; Dr. P. Feorino
More on HIV:
Earlier this year, I wrote about a new study showing that polar bears split off from brown bears around 600,000 years ago – already making them four times older than previously thought. Now, a new study pushes the date of that split back even further, to between 4 and 5 million years ago. The exact date is probably going to shift again in the future, and if anything, it’s the least interesting bit of the new paper.
Webb Miller, Stephan Schuster and Charlotte Lindqvist have taken a whirlwind look at the history of the polar bear. For a start, they sequenced its genome – that detail would be the centrepiece of other papers, but gets mentioned halfway through this one. They started looking at the genetic changes that have made polar bears lords of the Arctic, and they reconstructed the bears’ population history across the many climate upheavals it must have lived through. Finally, they found evidence that polar bears carry a lot of brown bear DNA in their genome (and vice versa) – a sure sign that the two species repeatedly bred with each other after diverging, in much the same way that our ancestors had sex with Neanderthals and other ancient humans.
I’ve written about the study for The Scientist. Head over there for the full story.
Photo by Alan Wilson
Some folks just can’t help being loud in bed, but noisy liaisons can lead to a swift death… at least for a housefly. In a German cowshed, Natterer’s bats eavesdrop on mating flies, homing in on their distinctive sexual buzzes.
Based on some old papers, Stefan Greif form the Max Planck Institute for Ornithology knew that Natterer’s bats shelter in cowsheds and sometimes feed on the flies within. What he didn’t know was how the bats catch insects that they shouldn’t be able to find. They hunt with sonar, releasing high-pitched squeaks and visualising the world in the returning echoes. Normally, the echoes rebounding from the flies would be masked by those bouncing off the rough, textured surface of the shed’s ceiling. The flies should be invisible.
And they mostly are. Greif filmed thousands of flies walking on the shed’s ceiling, and not a single one of them was ever targeted by a bat. That changed as soon as they started having sex. Greif found that a quarter of mating flies are attacked by bats. Just over half of the attacks were successful and in almost all of these, the bat swallowed both partners.
An old friend of mine found and forwarded an email that I had written on 22nd August, 2006. I sent it to a group of close university mates, telling them about this new science blog that I had created.
It makes me almost embarrassingly sentimental to read this, but hopefully it might help those of you who are in the same situation. Here is me, six years ago, working at a cancer charity, miles away from being a professional science writer, looking for opportunities, and taking a step. Also, note that 6 years ago, I knew even less than the little I know now, so if anything in this seems even remotely prescient, it’s probably best to interpret it as naivety that looks good in hindsight.
The bit where I say “Hopefully, I’ll be able to write a new one every week” cracks me up.
Subject: Shameless self-publicity
Over the last three years, I’ve written three non-work science articles and all three have won runner-up prizes in the Daily Telegraph’s Young Science Writer competition. Which is cool, because it makes me think that I might be able to do this full-time.
So, following kind encouragement from Alice and various friends, I’ve decided to put more effort into this science writing malarkey, stop waiting for others to publish my stuff, and do it myself. To this end, I’ve set up my own blog – go mighty Interweb, go!
The plan is to fill it with feature-length science-related articles on whatever takes my fancy. It’s been live for a week and has three articles thus far, and hopefully, I’ll be able to write a new one every week. It’s an outlet for me to flex a couple of interests – science and writing – and get some good practice in combining the two. It’s also a chance for me to write without worrying about the usual constraints of accessibility, journalistic styles, finding stories that haven’t been covered yet etc. It’s just me, writing for the sake of it, about stuff wot I find fascinating, in the discursive narrative style that I feel most comfortable with.
So come on in, have a read, leave some comments if you wish. If you like it, come back often, or better yet, tell a friend. At best, you might find out something interesting. At worst, you’ll be terribly bored and curse me for wasting your time, but you’ll ramp up my hits and maybe WordPress will send me a muffin. Or some such.