It started more than 200 years ago with cowpox, a weak cousin to the deadly
smallpox virus.
Doctors purposely infected people with the cow disease to protect them from
the scourge.

Centuries later, the basic concept behind vaccines has not changed. Most are
versions of the very bacteria or viruses that we want to avoid.

Henry Daniell thinks there is a better way.

The University of Central Florida researcher is working on a new kind of
vaccine that is grown inside plant cells, crushed into powder and swallowed
as a capsule.
He recently had success in animal tests of his vaccine for bubonic plague.

"What we have developed is a totally new platform; it's a revolutionary
approach,'' said Daniell, who receives funding from the National Institutes
of Health and others for his research.

Often given as shots, vaccines work by stimulating the body's natural
defenses. The immune system attacks the invader and becomes resilient to
future infections.

Vaccines have tamed many diseases that once killed and maimed
indiscriminately such as measles, diphtheria and polio. But most are
expensive and hard to manufacture. In rare cases, the vaccines themselves
cause the disease or severe reactions.

That's why Daniell and others are working on new types that reduce the risks
and expense. The need has become more urgent in recent years amid fear of
bioterrorism and natural outbreaks such as bird flu.

Daniell's approach relies on selected genes from the bacteria or viruses -
not the whole pathogens. At a basic level, genes are the recipes for
proteins. Researchers have found that the immune system can be provoked by
just a few proteins from the invader.

Consider the experimental vaccine for bubonic plague. Though uncommon today,
the plague has killed millions throughout history to earn its nickname: the
Black Death. There are still cases every year in parts of Africa and Asia.

In the United States, health officials are more concerned about plague as a
weapon of bioterrorism. That's why Daniell was able to get the US Army to
help with his recent tests on mice.

In creating the vaccine, Daniell chose a few genes from the plague bacteria
and spliced them into the genetic blueprint for the lettuce.

Then he grew the genetically modified plants. Because they hold the genes,
the lettuce also creates the proteins that could rev up the immune system.

Some of the mice ate a compound of the crushed lettuce leaves.

Others received injections of another plague vaccine. The rest of the
animals were not immunised at all. Then Army researchers exposed the animals
to the dangerous bacteria.

The mice that took Daniell's oral vaccine survived. But all of the
non-immunised animals died, along with most of the mice that had the
injectable vaccine. Daniell and his colleagues published the results of the
test in the journal Infection and Immunity.

"What we're seeing here is that the oral vaccine can be very effective,''
said Daniell, a UCF professor of molecular biology.

"It's also a very cheap way to create a vaccine - by altering plant cells
and creating a pill. If you have to vaccinate millions of people in a
bioattack, it's much easier to hand them a pill than to give out shots.''

He is among only a few vaccine researchers worldwide using lettuce, though
others are experimenting with potatoes and different food crops. Daniell
said he is focusing on the plant because it is inexpensive and easy to grow.
His lab uses an ordinary variety of lettuce that is similar to what you
might find on your salad plate.

"Lettuce is eaten almost everywhere in the world. It's very common, and it's
very feasible to modify it genetically,'' Daniell said.

"Plus, it produces nice, green leaves that lend themselves to drying and
powdering.''

Sound too good to be true? For now, it is.

Many hurdles remain for vaccines based on the genetic components of
disease-causing pathogens, said Darren Higgins, an associate professor of
microbiology and immunology at Harvard University.

For starters, scientists don't always know what genes are sufficient to
provoke an immune response, Higgins said. Then they still have to find
ways - such as the lettuce leaves - to give people just the right dose of
DNA or its proteins.

"The issue is how do you deliver it in a way that's going to be effective
and yet where you're not going to have any toxicity,'' said Higgins, also a
founder of a biotechnology company that is working on the approach.

Daniell said his team has had success in tests of similar vaccines for
malaria and cholera. He thinks it's just a matter of time before it's
refined.

"I am confident this platform will be validated and someday, people will
have the opportunity to get cheap and effective vaccines,'' he said.
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