Miller School of Medicine researchers Teresa A. Zimmers, Ph.D., and Leonidas Koniaris, M.D., don’t seem like people who would publicly sound off on either side of the death penalty debate. They are much more comfortable in their lab than anywhere near the United States Supreme Court. But because of their scientific research on the effects of the drug cocktail used in lethal injections, they could help influence a decision in the country’s highest court about one of the nation’s most controversial subjects. In September the Supreme Court justices decided they will hear a Kentucky case in which a death row inmate is challenging the constitutionality of being put to death by lethal injection, a process many lawyers argue is a form of cruel and unusual punishment—in violation of the Eighth Amendment—because some inmates have been conscious while being put to death. Though this case could have lasting effects nationally depending on what the justices decide, it would not be the first time the high court has considered the UM research. Last year, in oral arguments in Hill v. McDonough, three of the justices quizzed Florida lawyers on flaws in the state’s protocol based upon research published in the journal The Lancet by Zimmers, Koniaris, and colleagues. The unanimous decision in that case enabled the current wave of litigation, including the first-ever consideration of whether lethal injection presents an unnecessary risk of pain and suffering. The initial and latest research conclude that some convicted murderers likely suffered unnecessarily because the procedure and drug mix used in Florida and 36 other states are flawed.

Americans have a conflicted view of the death penalty,” says Zimmers, research assistant professor of surgery at the Miller School and lead author of “Lethal Injection for Execution: Chemical Asphyxiation?” that appeared in the April issue of PLoS Medicine.

“Many who profess to believe in capital punishment,” she adds, “don’t want it to look too unpleasant and want to be reasonably assured that the person isn’t suffering egregiously.”

Through groundbreaking research, Zimmers, her husband Koniaris, and colleagues concluded that lethal injections, the most common form of government-sanctioned death for those condemned in the United States, were plagued by poor training of corrections employees and slipshod regulations that, in some states, came with no written rules, not even for dosage.

And worse, the three-drug protocol—used since 1977 and credited to Jay Chapman, Oklahoma’s then chief medical examiner—was flawed to a point where inmates could awaken during execution, experience pain, and likely die from asphyxiation.

“We think we have made the most compelling argument out there, and it’s based on solid scientific evidence which has been rigorously reviewed,” says Koniaris, an associate professor of surgery at Miller and the senior author of the PLoS article. “This is the best evidence showing there is a problem with the protocol design.”

The researchers suggested that the common protocol, the ultra-short acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, were intended to be lethal on their own and as a combination bring on anesthesia, then death from respiratory and cardiac arrest.

“Many people are familiar with their pets being put to sleep, and they think it’s the same thing,” says study co-author Jonathan Sheldon, a Virginia lawyer who specializes in legal defense of the condemned. “It ought to be simple, but the process seems unnecessarily complex and secretive.”

In addition to Koniaris, Zimmers, and Sheldon, the research team included three others from Miller: David A. Lubarsky, M.D.; Richard S. Weisman, Pharm.D.; and Linda Waterman, D.V.M. Francisco Lopez-Munoz, M.D., Ph.D., from the University of Alcala, Madrid, also contributed.

It is unclear which studies lawyers arguing the Kentucky case will use in the Supreme Court, but it is almost certain the University of Miami-led work will play a part. In a separate case in September, Lubarsky, professor and chairman of the Miller School’s Department of Anesthesiology, testified in a Tennessee death row case and chastised state officials for retaining the flawed lethal injection procedure though it had been causing problems in a number of states. The judge in that case ruled lethal injection cruel and unusual, halting executions in the state.

In Florida, where lethal injections have been under heavy scrutiny for the past year, the state Supreme Court is also considering the Kentucky case in the appeal of Mark Dean Schwab, the next inmate scheduled to die by the state.

The UM-led research made worldwide headlines but it had simple roots. Sheldon, a former Peace Corps volunteer, had been hearing about lethal injections where inmates woke up from the lethal injection anesthesia to experience pain. The legal challenges resulting from problematic executions then were based upon scant scientific data. Sheldon, who had known Koniaris since elementary school, sought out the scientist. Koniaris assembled the UM team, and in 2005 the group authored the initial article in The Lancet that raised troubling questions about the largely secretive lethal injection process. As such, the research often included an uphill battle for records.

“Interestingly, the states that do the most executions, Texas and Virginia, are the ones that were least forthcoming with information,” says Zimmers. “There is a sense that there is a concerted attempt to hide what’s going on.”

The researchers reviewed cases from North Carolina and California, the two states that release information on executions. They also analyzed data from clinical, lab, and veterinary animal studies.

“When we started this research my only goal was to provide hard evidence about the reality of what is done. I had no strong ideological commitment for or against lethal injections,” says Lubarsky. “I hoped that publication of what we found would stimulate our society to take a fresh look at exactly how we carry out corporal punishment.”

Their most recent study was nothing short of eye opening. It showed that in 43 of 49 lethal injection cases, inmates may not have had enough thiopental to ensure they were unconscious.

In PLoS, the researchers wrote: “Given that neither thiopental nor potassium chloride can be constructed reliably to be the agent of death in lethal injection, death in at least some inmates might have been due to respiratory cessation from the use of pancuronium bromide.”

Additionally, because pancuronium bromide is effective even when delivered subcutaneously or intramuscularly, “pancuronium is likely the sole agent of death when IV catheter misplacement or blowout impairs systemic delivery of the other two drugs. In such cases death by suffocation would occur in a paralyzed inmate fully aware of the progressive suffocation and potassium-induced sensation of burning.”

Nationally, federal judges in many jurisdictions have noted the research, and it likely has contributed to stays of execution in states such as California, Ohio, New Jersey, and Maryland. At one point as many as 14 of the 37 lethal injection states were taking a second look at the process, including Florida where a hold was put on executions last year.

It was the botched death of Angel Diaz that led to the temporary moratorium in Florida. Diaz, 55, was convicted of killing a bar manager during a 1979 holdup. At the December 13, 2006 execution, the death team incorrectly inserted needles into the skin of Diaz’s arm, instead of his veins, causing him to take 34 minutes to die, about twice the normal time. There are reports he shuddered and grimaced in pain for over 20 minutes and required a rare second dose of chemicals to die.

“I have the vision of this being a Keystone Cop type of affair in the death chamber where you’ve got people who basically don’t know what they’re doing and as a result you end up with IVs not put in correctly and the possibility of drugs not mixed correctly, not administered correctly,” explains study contributor Weisman, research associate professor of pediatrics and director of the Florida Poison Information Center/Miami.

Lethal injections would obviously be more efficient if done by or in the presence of doctors, but most seem to agree with the American Medical Association’s mandate that participating in any way affronts the oath to “do no harm.”

Zimmers believes that some people find lethal injections acceptable because they think it is humane “because the practitioners of lethal injections use drugs and IVs. But the protocol is not based upon any experimental or clinical data and it actually contradicts veterinary practice. The conventional view of lethal injection as an invariably painless, peaceful death is simply wrong,” she says.

In an editorial accompanying the article, PLoS’s editors stated the research “will further strengthen the constitutional case for the abandonment of execution in the U.S.” But clearly, from the dozens of harsh e-mails to PLoS, some supporters of capital punishment believe that for the condemned, pain is inconsequential.

The significant response to the article “is unusual for a scientific journal,” says Larry Peiperl, M.D., a senior editor at PLoS. “What struck me from the responses is that people are terribly angry and wanting revenge. From the terrible crimes committed I can see where they are coming from, but as a society we should consider if revenge is the right motive for state-sponsored killing.”

Says study co-author Weisman: “The issue is not the severity of the crime or if you believe in the death penalty. Prisoners sentenced to death should have a right to be executed humanely. The same people who are ignoring the possibility that lethal injections may be extremely painful, would be appalled if you put people to death by throwing them out of a building or setting them on fire. They’d cry how inhumane that was. I fear lethal injections may be just as inhumane.”