Deleting Mad Cow Disease

Forget medicine. Scientists want to engineer cattle that won’t get sick in the first place

Over the past two decades, up to 1 million head of cattle around the world have been infected with mad cow disease. Although fewer than 200 people have died from the human version, known as variant Creutzfeldt-Jakob disease (vCJD), it´s likely that hundreds of thousands of people have eaten mad-cow-contaminated meat. And experts fear that thousands of those people may eventually come down with the lethal brain disease, which can take years or even decades to appear.

Instead of searching for a cure, several research teams are now in a race to stamp out the illness at its source, by genetically engineering cattle that are immune to it. The scientists, including Woo Suk Hwang, a stem-cell and cloning researcher at Seoul National University in South Korea, and Jim Robl, chief scientific officer at Hematech, a South Dakota biotech company, are leading the effort to create cattle with altered or missing prions, the mysterious proteins that play a key role in mad cow disease and vCJD.

Prions, which exist in almost all human and animal cells, are normally benign. Researchers have yet to nail down their exact role; they may aid in brain development or sleep, but no one is sure. What is known is that when prions mutate and take on new shapes, they become lethal to brain cells. These misshapen proteins then infect healthy ones, causing them to misfold too, and the whole process snowballs out of control.

There are four groups now working on ways to delete or alter prions from bovine DNA: Hwang´s and Robl´s, as well as Mark Westhusin´s at Texas A&M University and Will Eyestone´s at Virginia Tech University. Only one has managed to breed a modified animal. Hwang´s team announced this spring that it had begun testing a genetically altered calf. The animal is being exposed to mad cow disease, and scientists will watch whether it contracts the ailment. In cows, the early signs of the disease don´t appear for at least six months, so results won´t be available until next year at the earliest.

Hwang says he has made four other resistant calves using the same technique: He inserted into the cow´s DNA a modified gene to produce a kind of armored prion that won´t change shape even when infected by mutant proteins.

Robl, who in 1998 became the first to clone a cow, has a different approach. Rather than inserting a new gene into cow DNA, as Hwang did, he is trying to silence an existing gene, the one that produces prions in the first place. "You can´t infect prions that aren´t there," he reasons. Westhusin and Eyestone are using methods akin to Robl´s.

If someone does produce mad-cow-proof animals, the creatures could be enormously valuable. The disease has wreaked havoc worldwide. So far, 3.5 million cows have been euthanized in quarantine, and every year millions of animals are tested for the disease. The cost of these efforts runs into the billions of dollars.

But with success, scientists will face another issue: Will engineered cows prove acceptable to consumers? "The question is, will anyone want them?" Robl asks.
"I don´t know."