A Worm and Fuzzy Feeling for Cornell Researchers

Don’t squash that caterpillar. It might help save your life.

Scientists at Cornell University have developed two new technologies that cause insects to produce huge amounts of raw pharmaceutical protein in their larvae--and that, in turn, can be used to manufacture drugs to treat such things as leukemia and hepatitis.

The “bugs to drugs” program, as Cornell officials call it, could have wide applications in everything from pharmaceuticals to insecticides. And it all came about because Patrick Hughes was fascinated by the eating habits of caterpillars.

Hughes, a researcher at the Boyce Thompson Institute for Plant Research at Cornell, noticed that the insects got their footing along the edges of plant leaves, rather than on the flat surfaces, as they nibbled away. So he built a small box with scores of small pillars, sort of like Popsicle sticks, and dumped in a bunch of insects.

When he added food, the insects did just what he had observed in nature. They clomped on to the tops of the sticks. The result was hundreds of insects packed in a very small area.

Thus was born a recently patented system called HERD, for high-efficiency rearing device.

“The technology is so clever,” says H. Alan Wood, a virologist at the institute who immediately recognized its potential. “What it means is you can pack them in at very high density.”

That intrigued Wood, who had developed a system for infecting insects with a virus and thus producing protein that can be used to manufacture drugs. Insect larvae are especially suited for a wide range of drugs, Wood says, because they can produce a complex protein that cannot be grown in the most common way.

“The simplest and best and cheapest way to produce protein is bacterial,” says Lee Compton, a molecular biologist and president of AgriVirion Inc. of New York, which was formed to take advantage of the work of Wood and Hughes.

“However, there are huge numbers of proteins, including most of the really important ones, that cannot be made in bacteria or yeast for a variety of reasons. They just don’t have the systems necessary to make these complex proteins.”

But the desired proteins can be produced in insects infected with the appropriate virus. The virus kills the insect and, in the process, produces the desired protein. Scientists have worked for more than a decade to find some way to do that economically, but have had disappointing results.

The standard procedure today is to grow the protein in insect cell cultures in stainless steel tanks.

A quicker method would be to infect the insect directly, thus causing the larvae to produce the protein, but a gene in viruses prohibits the insects from becoming infected if they eat it, Compton says. Thus, the virus had to be injected into the insects, which proved too costly and too time-consuming.

But through genetic engineering, Wood removed the protective gene, and insects that ate the virus became infected.

The marriage of Wood’s and Hughes’ technologies should make the production of the protein far more efficient.

“Now we grow 1,000 insects in a little box that is 6 inches by 6 inches and just spray in an aerosol containing the virus. They eat it and become infected and produce the protein,” Compton says.

“We are turning little insects into protein factories,” Wood adds.

Not everyone buys into the approach. Peter Snow, who runs a protein experiment program at Caltech, says other researchers have achieved similar results, but he doubts it will revolutionize the world of pharmacology. One drawback, he says, is that the protein produced in insect larvae would be contaminated with “stuff” that would have to be removed “downstream.”

By using cell culture, he says, you can “eliminate a lot of the extraneous materials” and end up with a purer protein.

But the Cornell scientists insist their work will lead to cheaper, better protein that can be refined into drugs, and they see other applications as well.

The caterpillar used in the experiments is the Trichoplusiani, also known as the cabbage looper, a notorious agricultural pest. The virus spreads through the caterpillar within 24 hours and “literally turns the insect to liquid,” Hughes says.

The virus then loses its punch, ending its impact on the environment, according to Compton. Thus the research also has potential for developing new insecticides.

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Lee Dye can be reached via e-mail at leedye@compuserve.com