Posted on behalf of Stu Hutson
A mother in Freiburg, Germany finds her three-year-old son comatose in a pool of his own vomit. She immediately begins CPR as his twin brother looks on. The ailing boy is rushed to the local university hospital where he is stabilized — his life ultimately saved by quick thinking. However, two and half hours later, his father returns home to find the twin brother dead.
Both boys’ bodies had dangerously high levels of codeine — the unintended consequence of a treatment for lingering colds. But what had caused the overdose? Had the boys been given too much, or did they lack the ability to process the drug? After this scene played out three years ago, investigators turned to genetic tests to help them find out who, if anyone, was liable for the deaths (Int. J. Legal. Med. 123, 387–394, 2009).
Pharmacogenetic tests, used to help predict how an individual will react to medication, are becoming increasingly common in medical settings. The tests, although still rare, can sometimes be used proactively to help predict what medication is most likely to be effective or whether a severe adverse reaction is likely to occur. They can also be used forensically to help determine what went wrong.
Such forensic use is popping up in legal proceedings and investigations around the globe — but the judicial system may not be ready for the new technology.
“I’ve been in a courtroom and listened to a toxicologist say, to my face, that pharmacogenetics is useless pseudoscience,” says Saeed Jortani, director of the Forensic Toxicology Laboratory at the University of Louisville in Kentucky. “If a so-called expert is this misinformed, it’s easy to see why there is a need to educate judges and other law experts about the current state of the technology.”
Jortani, along with Steven Wong of the Medical College of Wisconsin in Milwaukee, Dan Blinka of Marquette University in Milwaukee and 14 other genetic, forensic and legal experts, has authored an editorial calling for such efforts, saying that a new class of “personalized justice,” needs to be developed to deal with the era of personalized medicine (Pharmacogenomics 11, 731–737, 2010).
Several of the authors are currently advising investigations wherein genetic tests are being used to determine whether a genetic abnormality was implicit in a treatment-related death.
For example, Jeffery Jentzen, director of autopsy services at the University of Michigan–Ann Arbor, says he is currently investigating several cases nationwide involving morphine overdoses. Genetic tests for variations that indicate an inability to properly metabolize morphine can help determine whether people who died in a hospital had an adverse reaction or received too much of the drug.
Alleviating liability with this sort of investigation is not entirely new. For example, in 2000, researchers reported a case where genetic tests helped exonerate the parents of a nine-year-old boy who died of an overdose of Prozac as a result of a genetic deficiency (J. Child. Adolesc. Psychopharmacol. 10, 27–34, 2000).
Painful truths
The pharmacogenetic test used in the Freiburg case revealed that the boys carried copies of the CYP2D6 gene associated with normal codeine processing, and had, indeed, received too much of the drug. Ultimately, it was determined that their mother had not understood the dosing directions.
“Sometimes, just having a better medical understanding of what happened is the greatest benefit,” Jentzen says. “If only to prevent it from happening again.” Recently, Jortani used similar tests to help show that a teenager who had killed someone in a car accident while ‘driving under the influence’ was actually intoxicated as a result of an inability to metabolize diphenhydramine, a common ingredient in cold medicine. The fact was taken into account in the teenager’s sentencing.
Blinka says that similar genetic tests will probably become a common practice as a defense against criminal charges in the next several years. “‘My genetics made me do it,’ might be the next insanity plea,” he says. But the fact that such tests remain relatively rare provides a different kind of legal trouble for doctors and pharmaceutical companies, says Wong. Although he is not aware of any such court cases, Wong is concerned that the lawyers behind some class-action lawsuits might try to insinuate that doctors of patients who suffered adverse reactions were negligent in not performing pharmacogenetic tests beforehand.
The standard of defense against such accusations would be that such genetic tests are not yet the ‘standard of care’, which is usually largely determined by recommendations by professional associations associated with a particular field of medicine.
However, determining the standard of care for genetic tests might not be quite as simple, says David Hunter of the Harvard School of Public Health in Boston.
For example, Hunter says, even though genetic testing for warfarin adverse reactions has been recommended by the US Food and Drug Administration, there are still numerous ongoing clinical trials that need to be resolved before a case can be made for such tests to become a standard of care.
An alternative example, he says, would be prescribing the HIV treatment Abacavir without a genetic screening. Doing so would be relatively reckless, because the screening has been shown to accurately predict a genetic predisposition to hypersensitivity that’s both common and very dangerous.
“This is new ground,” Hunter says. “The experts have a hard time agreeing on a lot of the specifics, so it shouldn’t be surprising that there’s going to be a challenge explaining this to laymen.”