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Sunday, Sept. 30, 2001

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Recognizing the role of insects in the progress of science and medicine

Staff writer

The British archaeologist Howard Carter was excavating in the Valley of the Kings in 1922 when he found a wall bearing the seal of Tutankhamen from the 14th century B.C. He made a small hole and peered through. From his journal:

"It was some time before one could see, the hot air causing the candle to flicker, but as soon as one's eyes became accustomed to the glimmer of the light the interior of the chamber gradually loomed before one, with its strange and wonderful medley of extraordinary and beautiful objects heaped upon one another. And everywhere, the glint of gold."

In his 1992 book, "The Making of a Fly," the British geneticist Peter Lawrence describes how the thousands of genes in a fruit fly turn on and off, interacting to form an embryo, a larva, an adult fly. Although his book is about the genetics of animal design, Lawrence prefaces it with Carter's account of the discovery of the tomb of the boy king. It might seem ludicrous, even pretentious, to compare a 25-mm fly with the most spectacular archaeological find of all time, but work on that little fly, Drosophila melanogaster, has yielded a treasure trove of developments in biotechnology, medicine, evolutionary biology and genetics that make King Tut's baubles seem like so many grains of sand in the desert.

The fruit fly has long been used to study genetics -- the science of inheritance and variation -- because its fast growth and reproduction time allow inherited changes to be easily tracked through generations. Indeed, the science of genetics itself was born as a result of the breakthrough work on Drosophila by an American biologist, Thomas Hunt Morgan.

In 1908, Morgan discovered a mutant in one of the culture bottles he used for breeding the flies. Unlike normal, red-eyed fruit flies, the mutant lacked eye pigment and had white eyes. Morgan's experiments had massive importance -- they showed for the first time that information determining the characteristics of organisms resides on chromosomes. (Helpfully, as biology high school students know, Drosophila has giant chromosomes in its salivary glands.) Originally an opponent of Darwinism, Morgan converted and accepted natural selection after the importance of his work sank in. He was awarded the Nobel Prize for physiology or medicine in 1933.

The discovery that the "blueprint of life" is contained in the chromosomes of cells led to a race to find out the material it was written in. This turned out to be DNA, whose structure was elucidated in 1953. Then in 2000, nearly a century after Morgan unknowingly discovered a gene (for white eyes), the entire sequence of the fruit fly genome (about 13,601 genes) was published in the journal Science.

Scientists have now sequenced the entire human genome too, discovering in the process that we carry about 60 percent of Drosophila genes -- including those that cause certain cancers and kidney diseases, as well as Alzheimer's. Obviously, the medical potential is immense.

Matthew Freeman, of the Medical Research Council in Cambridge, England, uses Drosophila to uncover the molecular causes of cancer.

"Medicine over the coming century is going to be based around understanding the underlying biology of the body and the cells that make up the body," he says. "The fruit fly can lead to that understanding -- it will be the absolute and necessary underpinning of the medical research of the future."

And God created parasitoids?

What else can we learn from the study of insects? The question is similar to one put to the renowned English population geneticist J.B.S. Haldane (1892-1964). What can we learn about the Creator from a study of the natural world, he was famously asked. "That He has an inordinate fondness for beetles," replied Haldane, alluding to the fact that of all the known species of animals, around 90 percent of them (numbering some 5 million) are insects -- and most of those are beetles.

Darwin cited the existence of parasitoids as one of the reasons why he couldn't believe in a beneficial god. These creatures -- insects in the wasp family -- use exquisitely sensitive, needlelike ovipositors to lay their eggs in the bodies of other insects. The eggs hatch, feed and develop within the living tissue of their unwitting hosts, eventually killing them.

As well as helping Darwin overcome his religious beliefs, insects have had crucial roles in deepening our understanding of zoology. In the last few decades, two key research areas have grown from work on insects: the evolution of sociality and an evolutionary force known as sperm competition. Both concepts have had fundamental repercussions for evolutionary theory, and both influence humans.

Selfish insects

First, sociality. Until the 1960s, it was thought that animals behaved according to "the good of the species," with individual animals acting in the best interests of the continuation of their species. For a long time, this was the only way of explaining why most ants in a colony, for example, don't reproduce, but work to help the queen ant reproduce. It was an Oxford entomologist and evolutionary biologist, William Hamilton, who in the 1960s hit upon the correct explanation.

Ant society is a sisterhood: All worker ants are sisters. Not only that, but an ant worker is more closely related to her sisters than she would be to her own offspring. (The same is true for bees and wasps.) Thus the best way for a worker to pass her genes on to the next generation is to support her mother, the queen, as she produces more children. That's why worker ants defend the nest against enemies, gather food and care for the eggs laid by their mother. With this radical new analysis, what had seemed to be altruistic behavior on the part of the ant workers actually turned out to be in their own best genetic self-interest.

The Oxford evolutionary biologist Richard Dawkins, describing a mass of ants he saw in Panama, puts it with typical eloquence in his 1986 book, "The Blind Watchmaker":

"I never did see the queen, but somewhere inside that boiling ball she was the central data bank, the repository of the master DNA of the whole colony. Those gasping soldiers were prepared to die for the queen, not because they loved their mother, not because they had been drilled in the ideals of patriotism, but simply because their brains and their jaws were built by genes stamped from the same master die carried by the queen herself."

Because Hamilton's breakthrough meant that behaviors that had previously appeared aberrant could now be correctly interpreted, it had huge implications for the study of behavior. Since then, the concept of the selfish gene -- the idea that evolution acts to increase gene frequencies -- has spread to every part of biology, from viruses to humans.

The mating game

The study of insects led to a second research breakthrough: the formulation of an evolutionary concept that transformed the field of sexual selection.

(Be warned: Some things insects do during sex almost need an X rating, or at least a parental guidance sticker.)

Darwin realized that sex is a powerful evolutionary force, so much so that he coined a term for it: sexual selection. Just as natural selection favors adaptations that help animals survive -- such as long necks in giraffes so they can reach leaves high in trees -- sexual selection favors adaptations that help animals have sex. More precisely, adaptations to ensure their genes get through to the next generation -- even if this means growing body parts or adopting behaviors that would be opposed by natural selection.

A classic example is the peacock's tail. It takes a lot of a male's energy to grow and carry around such a huge, colorful tail. It's also dangerous, because it makes him more easily caught by predators. Natural selection alone would act to reduce tail size. But despite the costs, all male peacocks have such tails because peahens like to mate with colorfully tailed peacocks. (Why they like to is another long story, but it's thought that such extravagant and colorful ornaments are signals of a male's genetic quality.)

Darwin went no further than this (the adaptations animals have for courtship), but it still took about 100 years for his ideas on sexual selection to be fully accepted, since in this, as in so much else, he was well ahead of his time. In fact it wasn't until 1970 that a young man, now a professor at the University of Liverpool, took the theory of sexual selection to its logical conclusion.

Geoff Parker was working on an animal perhaps less charismatic than peacocks: dung flies. While watching flies fighting and copulating on soft dung pats, fresh from the cow, Parker noticed that females would copulate with several different males in quick succession. Males fight for control of the pat, which females visit to lay their eggs. Parker realized that it's not enough to beat other males to the female, like the peacock with the showiest tail: Males have to ensure that it is their sperm, and not that of another male, that fertilizes the female's eggs. This is the evolutionary force that Parker called sperm competition.

"Rampant female mating leads to competition not before but after copulation; not among bodies but among sperm" is how Lynn Margulis and Dorion Sagan put it, in their book "Mystery Dance."

Parker's work on dung flies started the ball rolling, but some of the clearest examples of the selective power of sperm competition came from research on dragonflies and damselflies. Jonathan Waage, at Brown University, Rhode Island, discovered that the penis of the damselfly had horns on it, like the horns on a ram. Waage showed that the male uses his barbed penis like a pipe cleaner, to scrape out sperm left by a previous partner, before inseminating his own.

Penis variety in insects puts the most elaborate Swiss Army Knife to shame. There are knives, whips and inflatable beach balls, all functioning to displace rival sperm. Earwigs have two penises, because, says Yoshitaka Kamimura at Tokyo Metropolitan University, one sometimes breaks off inside the female during copulation.

The unprepossessing fruit fly, Drosophila, has adaptations as bizarre as any other insects.

Female fruit flies satisfy the conditions for sperm competition: That is, they store sperm from several males at once. Rather than scoop out rival male's sperm, the male's trick is to introduce sperm so large that it displaces that of other males. Hence the sperm of Drosophila melanogaster is about the length of the male's body, 300 times longer than a human sperm. Meanwhile, Drosophila bifurca produces sperm 58 mm long -- 20 times longer than its body. (The sperm is tightly coiled inside the male.) That's equivalent to a human male producing a sperm about 35 meters long.

The list of extraordinary adaptations goes on and on.

"Insects are the evolutionary biologist's god-send," said Mike Siva-Jothy, an entomologist at the University of Sheffield in England. "There is more diversity in a single order of insects than in most other classes of organism. They have been here so long and are so specious that every imaginable, and probably unimaginable, adaptation is present in one insect or other."

And the fruit fly, one tiny insect found flying around kitchen tables around the world, has told us more about life, growth and death than King Tut and the ancient Egyptians -- who thought they knew the secrets of life -- could have ever dreamed of.

You can e-mail Rowan Hooper at rowan@japantimes.co.jp

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