It’s easy to see why scientists want to make vaccines for diseases like HIV and pneumonia. These illnesses kill a lot of people. Bert Jacobs, on the other hand, is developing a vaccine for a disease that no one ever catches—smallpox.

It might seem silly for a scientist to create a vaccine for a disease that was eliminated years ago. But after the terrorist attacks on September 11, 2001, the United States began preparing for any kind of terrorist activity, including bioterrorism, or germ warfare.

Smallpox could be used as a bioterror weapon. People today aren’t vaccinated against smallpox, but the virus still exists in laboratories. If a stolen lab sample was unleashed on the public, it could sicken millions of unprotected people.

Why don’t we just use the existing smallpox vaccine—the one that destroyed the disease to begin with? The current smallpox vaccine is made with vaccinia, a living virus that is related to smallpox. Unfortunately, vaccinia can make some people sick, especially children and people with weak immune systems.

These risks are rare. But even the “normal” side effects of the vaccine are pretty nasty. Some people develop a red welt and blistering. Some suffer flu-like symptoms such as fever and swollen glands.

Most vaccines used today are made with either killed viruses or parts of viruses (known as subunit vaccines). These are safer than live vaccines. Unfortunately, vaccinia does not work as a killed or subunit vaccine.

“So we’re stuck with a live vaccine for smallpox,” Jacobs says.

Developing a safer smallpox vaccine has become a national priority. But vaccine development takes a long, long time. Jacobs has a head start. He already has a good understanding of how vaccinia virus works in the body.

When Jacobs arrived at ASU more than 20 years ago, he never imagined that he would end up making vaccines. He certainly never imagined his work would be considered important for national security. He just wanted to do basic research on viruses, the kind of studies that add to our general knowledge.

“I’ve been interested in science ever since I can remember,” says Jacobs. “I want to know how living things work.”

After studying biology in college, Jacobs chose to focus on the interferon system. Interferon is one of your body’s main defenses against disease. It works kind of like a distress signal. When a virus invades your cells, they produce interferon. It tells healthy cells to produce an enzyme that fights the infection.

One way to study interferon is by studying how viruses get around it. Vaccinia is particularly good at getting around interferon. Jacobs decided to study vaccinia to learn its tricks.

Now he’s putting his knowledge to use. He is trying to engineer vaccinia to make the live vaccine safer. He is tackling the problem from two different angles. One way is by engineering the vaccine so that any problems can be treated easily with antibiotics.

The second approach is to make the virus weaker. The key lies in a gene called E3L. Jacobs discovered that vaccinia needs E3L to cause disease. So he is trying to develop a vaccine with E3L disabled.

“E3L is the gene we’ve been working on for 20 years,” says Jacobs. “It’s kept us going for a long time—a single gene!”