2-Plants: Edible vaccines � more than a PR issue?

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TITLE:  Bioengineering for the mouths of babes
SOURCE: Redherring.com, USA, by Missy Globerman
        http://www.redherring.com/insider/2001/0119/
        tech-mag-90-vaccines011901.html
DATE:   January 19, 2001

------------------ archive: http://www.gene.ch/genet.html ------------------


===========================
"The first federal regulations for plant-based vaccines are now being 
hammered out, with Dr. Arntzen's help, and he hopes to get U.S. approval 
for two vaccines within two years."
                                  -----
"'But the potential of this produce is still anybody's guess, and remember 
that developing countries won't just grow these drugs in the woods. They 
will have to be licensed, regulated, controlled, and purchased from the 
Americans with the patent. '" � Dr. Dennis Lang, NIH
===========================



Bioengineering for the mouths of babes

This article is from the January 16, 2001, issue of Red Herring magazine.

Deep beneath a five-floor labyrinth of laboratories on the fringe of 
Cornell University's campus lurks a plant biologist who means to save 
children from the doctor's needle. "See that stuff inside," says Charles 
Arntzen, as he shows us a triple-stuffed British cookie, not unlike an 
Oreo, that he'd purchased the other day in London's Heathrow Airport. "In 
just a few years, my friend, that will be the dried concentrate powder of 
hepatitis B vaccine made from tomatoes, mushed into a tasty cr�me. A great 
snack for kids everywhere, wouldn't you say?"

Dr. Arntzen, 59, may be as popular with the Nobel Prize Committee as he 
will be with the kids if his bioengineered fruits and vegetables can ward 
off disease in countries too poor to refrigerate and store conventional 
vaccines. Granted, such vaccines are the core of preventative medicine, 
having already rid the world of smallpox and come close to ridding it of 
polio. Yet even now, one infant in five goes unvaccinated against a slew of 
other plagues, including diphtheria, tetanus, and measles. How different 
matters might be if you could load a canoe with vaccine-carrying bananas, 
potatoes, or tomatoes and paddle it down the Amazon or Congo River.


PRESCRIPTION FOOD

Perhaps if Monsanto had come out with such fruits of mercy before unveiling 
crops that make their own pesticides, the company would have disarmed 
critics of bioengineered food before they could build a head of steam. 
"It's very hard to be pro-infant mortality," Dr. Arntzen notes dryly.

Dr. Arntzen is alive to the problem of public perception. Having grown up 
on a farm in Minnesota, he still remembers his dairy-farmer neighbors 
fighting an earlier wonder food, margarine, hyping its supposed health 
hazards and getting Washington to pass laws to discourage its sale. Dr. 
Arntzen cringes at the memory, saying that the ingrained horror of 
technology has already slowed the development of vaccine technology. His 
first financial backer, Britain's Axis Genetics, went bankrupt last fall, 
in part because of political opposition to so-called Frankenfood.

Dr. Arntzen, a grandfatherly man with a bit of a paunch, did his 
undergraduate work at the University of Minnesota. His first love was 
rocks, and it was only after taking a break from college to marry his wife, 
Kathy, that he switched to molecular biology, graduating in 1965. He went 
on to earn a doctorate in cell physiology from Purdue University, then 
spent five years at the University of Illinois, punctuated by visiting 
professorships overseas. He became a globe-trotter, beginning in India, 
where he served in a U.S. government mission from 1976 to 1981 to teach 
villagers how to grow drought-resistant crops.

His eureka moment came in 1992, at a floating market just north of Bangkok. 
As Dr. Arntzen watched, a mother swabbed the lips of her crying baby with a 
bit of banana, and the baby stopped crying. "I knew at that point it would 
be totally logical to put something useful into that fruit," Dr. Arntzen 
remembers. "It's obvious children like it, and it's a sterile little 
syringe that every developing country can grow."

Dr. Arntzen got the insight because his mind was prepared. He had spent 
four years in the mid-'80s working in DuPont's program for bioengineered 
crops, assembling a medley of skills that won him an unusual double 
appointment: dean of the school of agriculture at Texas A&M University and 
adjunct professor of physiology at the University of Texas Medical School.

To prove that he could engineer a plant to make a foreign protein, Dr. 
Arntzen began with a banana's genome and added DNA coding for an enzyme 
that turns blue in a particular reagent. He placed it into a seed, planted 
the seed, harvested the fruit, and put a piece of it into the reagent. The 
result was a blue banana. His next move was to make a banana manufacture an 
antigen -- a protein on the surface of a germ that the immune system can 
recognize and attack.

The work "involves a lot of patience," Dr. Arntzen notes. He pulls a petri 
dish off a cart, picks up a baby banana plant taking root in it, and shows 
it to me. It took his lab two and a half years to make that seedling, which 
produces an antigen from the hepatitis B virus. It will be eight more years 
before he gets a ripe banana. (To get more bananas of his earlier design is 
easy -- just take cuttings from the existing 10-foot-high plants.)

Besides needing to prove that a plant could make antigens on command, Dr. 
Arntzen also had to overturn the conventional wisdom that an oral vaccine 
requires a whole virus, not just one protein isolated from the virus. 
Trials in rodents cast doubt on this prejudice. Then, in 1997, Dr. Arntzen 
published his first human trial, involving a potato-borne antigen from 
strains of Escherichia coli that often cause food poisoning. All 11 
volunteers who ate the potato developed an immune response to the bacteria.


PRIMING THE PUMP

Dr. Arntzen has also broken new ground in understanding how the gut accepts 
vaccination. The process, involving what doctors call mucosal immunity, 
offers a great advantage: the proteins generate antibodies that hide in the 
body's mucous membranes, serving as the first line of defense against 
invaders. Although it works wonderfully in animal trials, researchers still 
need to show that it works perfectly in humans. Above all, doctors must be 
reassured that the vaccine will never be recognized merely as food, 
inducing tolerance for the antigen, and thus the germ.

Edible vaccines may well be safer than injectable ones because their 
manufacture has absolutely nothing to do with the germs that cause disease. 
"Remember when kids used to get sick from the flu shot? Aha! No more," he 
exults. "The proteins we isolate cannot actually cause the diseases" 
they're supposed to protect against. The first federal regulations for 
plant-based vaccines are now being hammered out, with Dr. Arntzen's help, 
and he hopes to get U.S. approval for two vaccines -- against hepatitis B 
and the Norwalk virus, cause of so-called traveler's diarrhea -- within two 
years. "It may really be more like five years," he says, "but I would never 
send this vaccine technology out to other countries without approval here 
first."

Dennis Lang, head of the National Institutes of Health's Institute of 
Allergy and Infectious Diseases, has known Dr. Arntzen since their days at 
DuPont. "A real innovator and a really smart guy, and someday when people 
are talking about edible vaccines around the dinner table, his name will 
surely be mentioned as one of the first pioneers of this technology," Dr. 
Lang says. "But the potential of this produce is still anybody's guess, and 
remember that developing countries won't just grow these drugs in the 
woods. They will have to be licensed, regulated, controlled, and purchased 
from the Americans with the patent."

So far the main technical problem has been assuring the dosage. Raw, 
unprocessed fruits and vegetables cannot deliver consistent amounts of 
vaccine, so the plan now is to puree, can, or dry the banana vaccines into 
chips. The tomatoes will be dried and reconstituted into sauce. The first 
vats of processed tomatoes can be seen already on Cornell's campus in its 
Food Science Department.

Dr. Arntzen is leaving Cornell's Boyce Thompson Institute for Plant 
Research, where he has been president, for yet another academic perch, at 
Arizona State University, in Tempe. There he will collaborate with Dow 
AgroSciences on the development of edible vaccines for livestock. As he and 
his wife plan their move to the bottom of a desert cliff in Arizona, he 
makes a point of learning to enjoy life outside the lab, in year-round sun. 
He gave his skis to the Salvation Army and bought a BMW Z3 convertible; now 
he buffs his golf game and listens daily to the song "Don't Worry, Be 
Happy."

"I think every so often about why I got into this line of work. I always 
remember first and foremost that I love food and working with food. Then I 
think of the dangers of the work." He ruminates for a moment. "The most 
dangerous thing we as scientists can now do about vaccines is to do 
nothing. The world cannot afford to let this development opportunity pass 
us by."



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