Searching For Pharmaceutical Proteins, Insect Researchers Just Say 'Grow'

"These are valuable proteins, and they can't be produced this well anyother way," said H. Alan Wood, a virologist at BTI.  "Essentially, this isa protein factory.  We are using insects to raise raw pharmaceuticalproteins.  In effect, we are turning insects into little protein factories."

Originally, the researchers were exploring ways to safely combatagricultural pests through biological means, but in their research theylearned that the proteins from these nearly dead pests could directlybenefit humanity.  Recombinant baculoviruses have been used before todevelop a panorama of pharmaceutical proteins but were made using theinsect cell culture method, a time-consuming, and expensive  process.

Scientists can harvest the beneficial protein from the infected larvae oflepidoptera -- moths and caterpillars.  Genetically engineeredbaculoviruses, which are viruses shaped like rods, attack the inside of thelarvae, initiate a wholesale, metabolic change and kill the insect.

"The baculovirus literally turns the insect to liquid," said Patrick R.Hughes, BTI researcher. "Right before the insect dies, we harvest theprotein, and the protein can be refined into pharmaceuticals."

The virus spreads through the caterpillar within 24 hours, but the bugcontinues to grow, spreading virus through the caterpillar's body for threedays.  Just prior to the fourth day, or the fifth larval stage, theproteins being grown in the bug are ready for harvest.  Hughes says the bugnever reaches pupation, and if the protein is not harvested from thecaterpillar during this crucial larval stage, the proteins are destroyed.

Farming the pharmaceuticals becomes easy using a recently patented systemcalled HeRD -- the high-efficiency rearing device.  Developed at BTI, HeRDcan raise thousands of insects all at once to produce protein, thusreducing the expense.  Using the HeRD system, the BTI researchers aregrowing caterpillars -- Trichoplusia ni -- a pest best known as the cabbagelooper, which feeds on cabbage, cotton and crucifers.

But the insects are living on the edge.  "Patrick [Hughes] is a veryobservant man and because he's observant, he came up with a brilliant idea-- the HeRD system," Wood said.  What Hughes observed is that insectsprefer getting their footing on the edges of surfaces, not directly on flatsurfaces.  Hughes developed a box full of close-spaced pillars -- pillarsshaped like small popsicle sticks -- and puts the insects in the box. Healso put food in the box.  The insects are reared on the pillars in thebox, making it easy to infect them with baculovirus and then harvest theproteins.

In the past 18 months, researchers report that recombinant baculovirus havebeen used for vaccine production.  Some of the diseases that can be foughtinclude human papillomavirus, human T-cell leukemia virus, hepatitis-Cvirus, Norwalk virus, rotavirus, porcine parvovirus and African swine fevervirus.  BTI researchers do not directly study these diseases.

Producing proteins through insects was seen as an alternative to raisingproteins in cell culture, Hughes said.  For a while, it appeared as ifraising the proteins in cell culture was less expensive, but rearingproteins in insects is substantially less expensive than cell cultures."We don't have the many technical barriers we had before," he said.

Hughes and Wood have published their presentation, "Recombinant ViralInsecticides: Delivery of Environmentally Safe and Cost-EffectiveProducts," in the July 24, 1997, edition of the journal Entomophaga, thepublication of the International Organization for Biological Control ofNoxious Animals and Plants.

In addition to pharmaceuticals, the researchers said that the technologiesinvolved could be used for other purposes, like manufacturing inexpensiveviral insecticides as alternatives to pesticides.  Wood and Hughes saidthat with more than 30,000 chemical pesticide registrations being canceledin the past eight years, there is a need to develop natural and geneticbaculoviruses. The researchers believe that to make these insecticidescommercially viable, methods like HeRD will need to be employed to bringcosts down.

BTI, the Boyce Thompson Institute for Plant Research Inc., is the largestnon-profit, independent plant research facility in the world. It wasfounded in 1924, by Col. William Boyce Thompson in Yonkers, N.Y.  Thepurpose of the institute was to find ways to meet the food and health needsof an increasing world population.  BTI moved to the Cornell campus in1978.