Tomorrowland (16 page)

In an attempt to fight back, scientists are now heading down a radically new road and breeding a radically new breed of mosquito — the world’s first genetically altered insect destined to be released into the wild. Better or worse, we’re crossing a line. Which means that the mosquito we’re about to release is a hybrid
descendent of two of Pliny’s mythic lineages — both a fantastical creature and a pesticide — and both at once.

2.

The modern war against insect-borne disease dates back to 1897, when British scientist Ronald Ross discovered that malaria was spread by mosquitoes. He was also the first to propose reducing or eliminating the world’s mosquito population as a way of controlling the disease. But it wasn’t until early WWII forays into chemical warfare — leading to the discovery of insecticides ferocious enough to take on the insects — that his idea became truly possible.

Since that point, the fight against mosquito-vectored ailments has been a chemical battle. Scientists developed drugs that were useful against these diseases and insecticides that were useful against the mosquitoes that transmitted these diseases. For a time, it looked like we were winning this fight. Unfortunately, in the past thirty years, the rules have changed. Mother Nature interceded and evolution occurred. We’re now fighting insects that are resistant to our pesticides and diseases that are resistant to our drugs.

A number of these diseases are considered the deadliest on earth. Today, principally in Africa and Asia, dengue fever annually infects more than 50 million people and kills 500,000. Malaria infects about 400 million and kills more than a million — most of them kids. More disturbingly, the combination of pesticide and drug immunities, along with the rise of global transportation and climate change, has resulted in mosquito-vectored ailments appearing in places where they have not been seen before. In 2003, in the US, dengue fever appeared for the second time in Hawaii and the first time in the Gulf states, and the following summer there were 4,000 reported cases of West Nile and 300 deaths. Malaria has so far failed to make serious inroads into the
country, but in the slightly purple words of the Malaria Foundation International, “a plague is coming back, and we have only ourselves to blame.”

To address these concerns, during the past fifteen years, scientists have been trying to move beyond the chemical paradigm and toward a genetic one. The dream has been to build a
transgenic mosquito
, a genetically modified insect unable to transmit illness. This new insect would then be introduced in the wild, thus supplanting disease carriers with a harmless imposter. Seven teams, both in America and in Europe, have been working on the project — and that work is heading for prime time.

It is now possible to walk into any number of molecular biology labs and peer through a microscope at a mosquito unlike any other in history. The magnified insect shows a feature not found in the wild: a pair of bright, fluorescent green eyes — the telltale sign of successful genetic modification. These eyes are proof that one of the most scientifically advanced cures for disease ever conceived is feasible. They are also proof that, if we are not exceptionally careful, we could do irreparable damage to our ecosystems or, worse, create new, more devastating ailments currently unknown to science. One thing is certain: The bioengineered mosquito hangs precariously off the cutting edge of genetic research — how we proceed matters plenty.

3.

Before we can talk about how to proceed, it’s helpful to understand how we got here — a story that starts with the relationship between malaria and mosquitoes. Of the 2,500 kinds of mosquitoes in the world, no more than a tiny minority evolved to feed on humans. But evolve they did. And as these mosquitoes were learning to live off humans, malaria — the most prolific of mosquito-borne diseases — was learning to live off both.

Most mammals and quite a few birds are susceptible to the
disease. Up to now, all of the transgenic research has been done with malaria’s avian or rodent varieties, but the parasite spreads the same in every species. Transmission begins when a hungry female mosquito (only the female feeds on blood) drinks her dinner from an infected animal, along the way ingesting the malaria parasite. In a few days, the parasite travels into the mosquito’s mid-gut, where it develops sexually reproductive cells that mate and mature and release thousands of malaria sporozoites. In turn, these cells make their way into the mosquito’s circulatory system, eventually taking up residence in their salivary gland. The whole cycle takes about ten days. Afterward, the next time that mosquito bites into something, malaria goes along for the ride.

This malarial life cycle was mostly understood by the early portion of the twentieth century, but our attempt to remake insects into allies in the war against insects dates to the 1930s and work done by the late Barbara McClintock. In 1983, McClintock won a Nobel Prize in medicine for her discovery of short chains of DNA called “transposable elements” or, more commonly, “jumping genes.” A jumping gene is so named because the proteins it encodes can splice open a chromosome, jump inside, and then sew the whole deal back together again. This discovery makes it possible to piggyback other, more helpful DNA — such as DNA that would be useful in the fight against malaria — on a jumping gene and use this gene to insert the mutation into a foreign genome.

At least that was the theory. It took a half century for theory to become practice. But, in 1981, biologist Gerald Rubin discovered a jumping gene in the fruit fly
Drosophilia melanogaster
. He named it “P.” A year later, working with embryologist Allan Spradling, Rubin used P as a Trojan horse to build the world’s first genetically modified insect. “It was a huge accomplishment,” says Peter Atkinson, an entomologist at the University of California, Riverside and one of the scientists leading the quest for transgenic mosquitos. “They took a gene that gives eyes a reddish
color, attached it to P, and then inserted the whole thing into a fruit fly. That fly’s offspring were born with reddish eyes, and their offspring as well. The trait was stable and heritable.”

Unfortunately, being able to manipulate fruit flies, while scientifically exciting, was not real-world important. Fruit flies neither carry disease nor pollinate crops and, other than being research tools, have little economic or social impact on our lives. Still, there was hope that P would be found in other insects and, once found, would be useful in manipulating genes in the fight against insect-borne diseases. “The eighties were pretty much a wild goose chase down this road,” recounts Atkinson. “Entomologists thought P was going to be this great breakthrough, but all that got published were negative results.”

By the early 1990s, it was pretty clear that P was finished. Scientists began looking for other jumping genes, Atkinson among them. In 1996–97, working with University of Maryland molecular geneticist David O’Brochta, he found one in houseflies — dubbed Hermes, for the speedy Greek messenger. The hope was that Hermes would be workable in a way that P wasn’t, and, the following year, hope was vindicated: Anthony James, an insect geneticist at the University of California, Irvine, used the gene to modify a mosquito that transmits yellow fever.

But this was only the beginning of the battle.

Fruit flies are the workhorse of modern genetics. As such, we have a long list of fruit fly traits that have been identified and cultivated in the lab. Eye color, for example. In their work with fruit flies, Spradling and Rubin had only to look for a change in eye color — what’s called a genetic marker — to see if their experiments were successful. But no such marker existed in mosquitos. Thus, the only way to figure out if a jumping gene had done its job was to breed potential transgenics by the boatload, dissect the results, and use a microscope to see if the inserted DNA had taken hold. For the long-haul work of fighting malaria, this process was too arduous to be economically viable. Plus, dissection killed the mosquito being studied, which — even if she did
contain the inserted DNA — put a serious damper on her future breeding abilities.

In the late 1980s, to get over these hurdles, scientists began looking for an easily identifiable genetic marker that could be attached to jumping genes. In the early 1990s, researchers at Columbia University began experimenting with a Puget Sound jellyfish that glowed fluorescent green when exposed to UV light. Turns out, the protein that created the glow could be inserted into other species without killing them. Then, in 2000, Peter Atkinson attached this Day-Glo protein to Hermes, and suddenly the use of genetically altered mosquitoes to fight mosquito-borne ailments became a much more viable proposition.

A few years later, with Atkinson’s Day-Glo marker guiding the work, Johns Hopkins geneticist Marcelo Jacobs-Lorena found a small peptide that binds to receptors in the mosquito’s gut — the same spot where the malaria parasite normally attaches itself. He next engineered a gene that expressed this peptide and inserted it into mosquitos. In these new transgenics, with vulnerable receptor sites blocked by the peptide, the parasite dies before it can reproduce and infect anything else. It was a major breakthrough. Jacobs-Lorena had turned a mosquito into an insecticide.

Unfortunately, that insecticide can still adapt — and that leads to an entirely different set of problems.

4.

One of the main lessons learned in the pesticide wars of the last century was that mosquitoes and malaria are both nimble mutants. Therefore, while everyone acknowledges Jacobs-Lorena’s achievement, everyone knows it’s not enough to win the war. “In order to ensure success,” notes Anthony James, “we need to build a transgenic mosquito that kills malarial parasites in a number of different ways — it’s the only way to stay a few steps ahead of evolution.”

This work is also under way. For example, Jacobs-Lorena blocks the receptor that the parasite binds to inside the insect’s mid-gut, but James has found a way to block the parasite’s ability to bind to a mosquito’s salivary glands. Meanwhile, at the University of California, Riverside, Alexander Raikhel has taken a very different approach — he’s figured out how to boost a mosquito’s immune system so it turns on every time there’s a chance the insect can get malaria — thus killing the disease before it has the ability to spread.

Yet, even if we can outfox evolution and find a way to completely kill malaria in the lab, researchers still need to make this work in the real world. The transgenics that Jacobs-Lorena has created have the same life span and produce the same number of offspring as normal mosquitoes. “This means,” he says, “that in laboratory conditions there’s no fitness cost to building mosquitoes with an immunity to malaria. But there could be a fitness cost in the wild, and to really control the disease, we have to find a way to make our transgenic insects have more offspring than wild mosquitoes.”

This isn’t the only issue. Another problem is that we still need to make the switch from mosquitoes that carry animal malaria to mosquitoes that carry human malaria — a feat not as easy as it sounds. Not only are the mosquitoes that carry human malaria much harder to breed in captivity, there are also key differences between animal models and human models. The same gene that blocks malaria in mice, for example, does not work in humans, although Jacobs-Lorena believes he’s found a different gene to accomplish this task.

But once that task is accomplished, containment becomes an even greater concern. As there’s no way to build transgenics with a human form of malaria immunity without first breeding insects with the human form of malaria, much of this work has been moved to Level-3 biocontainment facilities — the kind that come with electronic passkeys, multiple airlocks, and drainage systems that dump waste water into a heating chamber that boils off any remnant of disease.

And this Fort Knox approach better work. Escaped mosquitos could easily lead to disease outbreaks, but more alarming is the fact that jumping genes not only hop around genomes — they also hop from species to species. An escaped transgenic could interbreed with wild populations and produce something that we’ve never seen before — something even more deadly than what we have today.

And even if unintentional escape can be prevented, eventually we’re going to have to release these transgenics into the wild (a Key West pilot project is already heading down this road). The downside here is that we know very little about how mosquitoes live in the wild. We don’t completely understand how they breed — meaning everything from how they select certain mates to why they choose to lay their eggs in one puddle rather than another. Nor do we know how seasons affect population size or how wide a territory certain populations inhabit or, critically, how and why genes travel through given populations. Thus, what we really don’t know is the full list of dangers involved in tinkering with this balance.

Mosquito-borne ailments are among the most devastating and successful diseases on earth. The chemical paradigm of the last century produced a disease immune to our drugs and an insect immune to our pesticides. Could we produce a Frankenstein mosquito carrying super-malaria? “There’s just no way to know exactly what will happen in ten thousand generations of mosquitoes,” says Atkinson. But it looks like we are about to find out.

So here we are, some two thousand years post-Pliny. A line has been crossed and another is about to fall, and the next time someone sets out to catalog the entire contents of the world, they will need to create a whole new mythic category: The very first man-made creature to venture into the wild.

The Great Galactic Gold Rush

THE BIRTH OF THE ASTEROID MINING INDUSTRY

The first time I met XPRIZE founder Peter Diamandis — the story that opens this book — he told me about the possibilities of asteroid mining, arguing that the very first trillionaire on Earth was going to be the person who figured out how to mine the sky. It was, without question, one of the zaniest things anyone had said to me. For a science writer, asteroid mining sat somewhere between “cold fusion” and “cloak of invisibility” on the list of things not likely to happen anytime soon.