Buzzing off

The bizarre biological control which may save millions from malaria

A couple of weeks ago, I went up to Auckland for a few days, since my visit over Christmas had been shorter than I’d originally planned. While I was there, I visited the Auckland Museum, which had an exhibition on loan from Canada called Bloodsuckers. Among other things, the exhibition covered the extraordinary diversity of animals which feed by sucking the blood of other animals. I know a fair bit about weird and wonderful creatures, and had heard of vampire bats, mosquitoes, lice, ticks, lampreys, leeches and even the Galapagos vampire finch. But even I found some surprises, including blood-sucking moths, snails, kissing bugs and a catfish. I also found a book called the Illustrated Encyclopaedia of Dangerous Animals in the museum shop, so I’ve solved my nephew’s birthday present four months early.

Some of the animals covered in this exhibition prove the point I made last week, that nature comes up with creatures as outlandish as any human could imagine. Then, however, I was exploring trees which filled me with delight. Bloodsuckers leave me fluctuating between disgust and horror – even if there’s some fascination there as well. I remember the time that leeches got inside my clothing when I was walking through dense vegetation in India. I’ve got a strong stomach, but that really troubled me. As a child, I was terrified of vampire bats, largely because of their association with rabies, which has always frightened me far more than a disease like Ebola. And I still think that the lamprey has one of nature’s most horrific faces.

Of all the bloodsuckers, though, one stands out among all the others. Today, it’s the most dangerous by far, contributing to the deaths of hundreds of thousands of people every year. It should be the one we are most afraid of, that is, if we were most afraid of the things that are most likely to kill us – which we aren’t, as I’ve explained previously.

I’m talking, of course, of mosquitoes. These little buzzers carry an arsenal of deadly diseases. The worst are those which carry malaria, a disease which still kills around 600,000 people every year, most of them young children. The vast majority of those infected and killed are in sub-Saharan Africa.

Malaria was once a much more widespread problem. Although medications to treat the parasites causing the disease have helped, most malaria control has been about reducing mosquito populations and reducing the chance of people being bitten. For example, swamp drainage has reduced the habitat for the 70 or so species of Anopheles mosquitoes which carry the disease. This approach is effective because malaria mosquitoes don’t breed in containers like some other mosquitoes, such as the ones which carry dengue fever. Better housing and the use of bed nets also helps, because it means that people are less likely to get bitten at night, which is when the malaria mosquitoes are active.

In the 1950s, a period of extraordinary faith in the ability of science to solve the world’s problems, the World Health Organisation believed that we could eradicate malaria. Not only was there a wonder drug, chloroquine, which killed the malaria parasites, but there was a miracle pesticide, DDT, which controlled the mosquitoes.

In a little over a decade, though, this goal would be abandoned. Chloroquine and DDT lost their effectiveness, as both the malaria parasites and the mosquitoes developed resistance. I’ve written about this in more detail before, and how Rachel Carson warned about this resistance in her book Silent Spring. Here’s the link: Biting back - by Melanie Newfield - The Turnstone.

Since then, humanity has been in an arms race against malaria parasites and mosquitoes. We have tools we can use, but sometimes they stop working and we need to develop others, or use them in varying combinations. The dream of a simple solution to a complex problem remains a dream.

However, there are two new tools which promise hope in the battle against malaria. One is a form of biological control, the other involves gene technology. I’ll get to the gene technology tools next week, but first I want to talk about the biological control approaches. Originally, I thought that these would take a couple of paragraphs and then I’d talk about gene technology, but when I started turning over metaphorical stones, as I often do, I found something completely unexpected.

Biological control of mosquitoes involves bacteria known as Wolbachia¹. These are like no bacteria I’ve ever heard of. They are weird, really weird. It truly has taken a lot of work for me to understand them, and I’m a biologist.

The first thing that makes Wolbachia a little weird is that they live inside cells. In fact, the whole bacterial group they belong to lives only inside cells. Some of these bacteria infect humans, causing diseases like typhus and Rocky Mountain spotted fever (I just like the name of that one), while some infect our livestock. In humans and other mammals, they are spread by various kinds of bloodsuckers, particularly ticks. Because they live only inside cells, they are difficult to find and study – while many bacteria can be grown in a laboratory, these can’t.

Because they are hard to find, Wolbachia were considered to be ‘rare and inconsequential’ bacteria which infected a few types of insects. If you wanted to study them, you’d probably have struggled to get funding, since it would have been hard to justify any direct benefit. But in the 1990s, with the development of techniques which could look directly at DNA, they were found in many kinds of insects, as well as ticks, spiders, scorpions and certain worms. Scientists now think that at least half of insect species can be infected by Wolbachia bacteria.

Wolbachia don’t infect humans or other mammals, and they’re not spread by vectors. This is where things start to get weird. They are known as reproductive parasites, because they particularly infect the reproductive organs of insects. They are transmitted from ovary to egg, from mother to offspring, generation to generation.

Even that isn’t the weirdest part. The really weird part is that they manipulate the reproduction of infected insects in a variety of ways which benefit the Wolbachia.

Here’s one example: they can give some kinds of female insects the ability to reproduce without males. This increases the spread of Wolbachia, because the female insects produce female offspring, which are also infected and can pass the Wolbachia on to their offspring. If males were produced, they couldn’t pass on Wolbachia.

Here’s another: Wolbachia can turn genetic males of some kinds of insect into females. Not only that, but females capable of reproducing – but only more females. They’ve still got the male chromosomes though. Scientists have experimented with treating these apparent females with antibiotics to eliminate the Wolbachia, and found that the offspring are then all male².

Neither of these are going to help us control malaria, but some of the other ways Wolbachia bacteria affect insects might. Some kinds of Wolbachia, including some found in malaria mosquitoes, are capable of inducing a kind of egg-sperm incompatability, where crossing infected males with uninfected females results in death of the offspring at a very early stage of development. This is theoretically useful for controlling malaria, because if large numbers of infected male mosquitoes were introduced to an area, they could reduce the ability of the uninfected mosquitoes to breed, and therefore reduce the number of mosquitoes. There are difficulties with this, however. It’s difficult to produce large numbers of infected males without producing a few infected females. Infected males can breed with infected females, resulting in an infected population of mosquitoes no longer susceptible to control.

So, it’s back to the arms race again, where as soon as we have a new way to control mosquitoes, they’ve got a way around it.

But there’s something else Wolbachia can do which might prove even more useful to us. There’s relatively recent evidence that insects infected with Wolbachia may be more resistant to infection by other microbes. This has been observed in a number of mosquitoes and for a number of diseases. There are Wolbachia bacteria which can protect the yellow fever mosquito from infection with viruses such as dengue fever. There are also those which protect some species of malaria mosquitoes from infection with malaria parasites. By protecting the mosquitoes, the Wolbachia could protect us.

These weird, wonderful bacteria provide real hope for a new way of protecting us from mosquito-transmitted diseases, but it’s not a simple solution. The approach has been tested with yellow fever mosquitoes in parts of Australia, Malaysia and Brazil. While initial results have been promising, it’s not yet clear whether repeated releases of infected mosquitoes will be required, and whether the disease resistance in the mosquitoes will last. Perhaps it will work for a while, and then the mosquitoes, or the diseases, will find a way around it.

Malaria, and the mosquitoes which transmit it, are a much more complex problem. It’s not simply a case of finding a kind of Wolbachia which has the right effect in mosquitoes, because there are different kinds of mosquito transmitting different kinds of malaria parasite in different places. Complex problems seldom, if ever, have simple solutions. But another tool which might help alleviate the suffering of millions is something to feel hopeful about.

Image credit: Melanie Newfield

1. I’ve searched around, and I can’t find a common name. I can’t even find an abbreviation. Everything I’ve read, even non-technical publications, refer to Wolbachia, with the italics indicating that it’s a scientific name. So, I apologise for using the name here, but I can’t find an alternative.

2. Just to be on the safe side, I’ve been downloading all the papers I used for this article onto my own computer, because quite a few of them are on US government websites and contain words which the current administration/ coup leaders object to.