Scientists create first-ever ‘biological pacemaker’ in pig hearts

Cardiologists have transplanted genes into the hearts of pigs with heart arrhythmias and genetically reprogrammed their defective heart cells into beating again, creating what they’re calling a “biological pacemaker,” according to a study published Wednesday.

The scientists, from the Cedars-Sinai Heart Institute in Los Angeles, say they hope their work will eventually lead to clinical trials for the genetic reprogramming of heart cells in humans with heart rhythm disorders who are unable to use electronic pacemakers.

"It is possible that one day, we might be able to save lives by replacing hardware with an injection of genes,” Dr. Eugenio Cingolani, director of the Heart Institute’s Cardiogenetics-Familial Arrhythmia Clinic and who worked on the research, told reporters in a phone call on Tuesday.

An estimated 300,000 Americans are fitted with pacemakers each year in order to control their heart arrhythmias, but babies who are still in the womb and develop heart rhythm disorders, for example, can’t be fitted with pacemakers, which must be implanted surgically. And some adults who have received electronic pacemakers can develop infections from the devices, so the possibility of an easily injectable, noninvasive means of regulating the heartbeat could allow such patients to heal.

After spending 12 years developing this research, the scientists successfully injected a gene called Tbx18 into one of the heart chambers of a group of seven pigs. The pigs all had what’s called “complete heart block,” a disorder in which the sino-atrial node of the heart becomes disconnected from the heart’s pumping chambers. Normally, the sino-atrial node regulates the pace of the heartbeat, somewhat like a metronome, but when it’s blocked, the heart rate slows down.

When the scientists injected the Tbx18 gene into the pigs' hearts through a catheter — another group of five pigs with complete heart block received a placebo injection — the pigs that received the gene had significantly faster heart rates than the control group by the second day. The faster heart rate lasted for two weeks, and mimicked the normal changes in heart rate resulting from circadian rhythms and physical activity.

The study was published in the journal Science Translational Medicine.

All 12 of the pigs were implanted with a “backup” electronic pacemaker before the injection experiment. The pigs that received the placebo needed to rely on the backup pacemaker between 8 and 40 percent of the time during the two-week period, while the pigs receiving the gene relied on it less than 1 percent of the time, according to the study.

That’s because the gene converted ordinary heart cells, of which pigs have billions, into specialized sino-atrial node cells, of which pigs have only a few thousand, the scientists said.

“In essence, we create a new sino-atrial node in a part of the heart that ordinarily spreads the [electrical] impulse, but does not originate it,” said Dr. Eduardo Marbán, director of the Cedars-Sinai Heart Institute, who led the research team. “The newly created node then takes over as a functional pacemaker, bypassing the need for implanted electronics and hardware.”

He explained that they had converted the regular heart cells into another, more specialized type of heart cell through what’s called somatic reprogramming, a method of injecting genes into a cell that transform it into an embryonic-stem-cell-like state. Japanese scientist Shinya Yamanaka, who developed the process, won the Nobel Prize in 2012 for his discovery.

The scientists tested the genetic modification on pigs because the animals have hearts that are similar to those of humans; heart valves from pigs are sometimes used to replace defective valves in humans.

The scientists said they still have much more research and testing to do before they can test their research on humans, but they are aiming to begin clinical trials within three years.

They said they’d originally hoped to use the Tbx18 gene injection as a sort of “bridge” to allow heart rhythm disorder patients to survive without an electronic pacemaker for long enough to heal infections or other problems.

“If proven to work in these disease settings, the technique could eventually become a realistic alternative to regular pacemakers in a broader spectrum of patients,” Cingolani said.

He added that, rather than having surgery to implant a device that may have to be replaced or could cause infections, “patients may someday be able to undergo a single gene injection and be cured of the slow heart rhythm forever.”