Stopping "Cellular Suicide" Could Boost Production In Biotech Labs

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July 15, 1997FOR IMMEDIATE RELEASECONTACT: Phil Sneidermanprs@jhu.edu

STOPPING "CELLULAR SUICIDE" COULD BOOST PRODUCTION IN BIOTECH LABS

Every day, for reasons that are not clearly understood, somehuman cells commit suicide. Some cells, such as those that havebeen infected by a virus, kill themselves to preserve the healthof the body as a whole. Other self-destruct simply because theysense that a threat to their survival or merely somethingunfamiliar is lurking nearby.

This process, called apoptosis or programmed cell death, is anormal biological occurrence that can promote proper organdevelopment and help to prevent cancer. But it's unwelcome inmodern biotech labs, where scientists turn living cells intominiature pharmaceutical factories that produce proteins,enzymes, antibodies and viruses to help patients with an array ofillnesses. Apoptosis prompts many of these microscopic workers toput physiological "guns to their heads" after just a few days onthe job. Working closely with molecular biologists, Johns HopkinsUniversity engineer Michael J. Betenbaugh is trying to disablethese guns and allow the drug-making cells to lead longer, moreproductive lives.

"Ideally, we'd like to extend the lifetime of these cells andincrease their efficiency in making biotech products that savepeople's lives," says Betenbaugh, an associate professor in theDepartment of Chemical Engineering.

His research has important implications. If scientists find a wayto stop cellular suicide, they may be able to keep some cardiaccells from killing themselves after a heart attack. They may alsobe able to extend the life of artificial organs made from animaltissue.

The key is to halt apoptosis, which is often triggered by changesin a cell's environment. "It may be a viral infection, the lossof a key nutrient, radiation or a chemical toxin, all at sub-lethal levels," Betenbaugh explains. "These would not kill thecell by themselves. Nevertheless, the cell turns on thisphysiological chain of events that causes it to self-destruct."

In biotech labs, however, researchers want genetically engineeredcells to thrive and produce medicines for as long as possible, agoal that is thwarted by programmed cell death. To remove thisstumbling block, Betenbaugh installs "stop signals" at specificpoints along a cell's road toward self-destruction. To find thesesignals, he works with researchers led by J. Marie Hardwick, anassociate professor of molecular microbiology and immunology atThe Johns Hopkins School of Public Health. Hardwick's team ismapping out the genetic path that a cell follows toward self-destruction. In his own biotech lab, Betenbaugh uses thesefindings to figure out the best way to block the cell's progressalong this path.

"There is a point of no return as the cell goes through theprocess of killing itself," Betenbaugh explains. "But at somepoint you can stop it. I'm collaborating with the biologists whoare figuring out what those stop signals are. Then, as anengineer, my job is to apply those stop signals to the cell linesthat I'm developing."

One potential stop signal is membrane protein called bcl-2. Whenthis material is inserted during the genetic engineering of a newcell line, it appears to shut down the suicidal impulses,Betenbaugh says. He is also experimenting with chemicals thatmimic the effects of bcl-2 when added to cells that are alreadygrowing in the lab. "Maybe our cells see the signals that tellthem to commit suicide," Betenbaugh says. "But we can halt thatprocess before it hits the point of no return. Instead of dyingafter two days, our cells might live for six or seven days,making pharmaceuticals for a longer period of time."

In his initial experiments, Betenbaugh has more than doubled thelife-span of some biotech lab cells. Thus far, however, each ofthese hardier cells has not produced as much medicine as the onesthat died quickly. By trying new genetic and chemical strategies,the researcher seeks to improve the system significantly in thenear future. "We want to find the combination that will allowthese cells to work more efficiently and live longer," Betenbaughsays. "That's what this research is all about."

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