In the summer of 1982, six individuals found themselves in emergency rooms in the San Jose, California, area with odd symptoms. Although these patients were young adults, they were “frozen” as if they had advanced Parkinson’s disease, a degenerative disorder that limits movement and typically affects older individuals. In these mysterious cases, the movement restriction resulted in complete paralysis. When the neurologist Bill Langston met his first patient, George Carillo, he saw a young man propped up in bed with his arms in an awkward position as if he had suddenly frozen while making a gesture. When Langston held George’s arms out in front of him and let go, they stayed in that position.
Doctors had no clues about the cause of George’s condition and no way to obtain a medical history. A week later, someone gave George a pencil and paper to see whether he could move his fingers. George finally wrote his name and, after a half hour, a few more sentences:
I’m not sure what is happening to me. I only know I can’t function normally. I can’t move right. I know what I want to do. It just won’t come out right. (Langston & Palfreman, 1995, p. 19)
George then wrote that his girlfriend was also experiencing the same symptoms. When asked whether they had taken any medication, he wrote, “heroin.” Over the next several days, four additional heroin users exhibited the same paralysis symptoms. Although heroin is associated with many health risks, becoming frozen was not one of them. This prompted a press conference warning the public to go to the hospital immediately if they developed paralysis symptoms following heroin use.
Behind the Scenes
When the police searched George’s apartment, they found what appeared to be heroin. As Langston and his colleagues waited for the lab results on the identity of the substance, they decided to give the frozen patients the drug L-DOPA (L-3, 4-dihydroxyphenylalanine). The drug is used to treat Parkinson’s disease by increasing levels of dopamine in patients experiencing deficits in this essential neurotransmitter. Within only a few hours, the frozen patients regained their movement—and emotionally conveyed what it was like to be trapped in their motionless bodies.
The lab results revealed that the samples were a “designer” analogue of the narcotic pain medicine Demerol (meperidine). The toxic substance in the “heroin” was 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Although MPTP had less severe effects in rats than in humans, it became evident in subsequent research with monkeys that MPTP attacked the cells of the substantia nigra (a brain area that produces dopamine), producing a form of Parkinson’s disease. Ironically, the MPTP tragedy prompted research in primates that led to the production of a clinically relevant model for Parkinson’s disease (Chiueh et al., 1984; Porras, Li, & Bezard, 2012).
But was l-DOPA a cure-all for the San Jose frozen patients? Unfortunately, l-DOPA worked for only about a year before patients became sensitized to it, exhibiting increased involuntary movements as well as hallucinations. At this point, the work of the Swedish neuroscientist Anders Björklund, who had experimented with the transplantation of rodent fetal cells in the substantia nigra as a treatment for Parkinson’s disease, came to the attention of the investigators.
Typically, researchers focus on rat and nonhuman primate models before moving to clinical studies of human patients. In this case, research provided evidence that the transplantation of developing dopaminergic neurons from a fetus into an adult host brain of the same species increases the chances of the cells surviving and maturing into dopamine-producing cells in the adult host brain (Björklund et al., 2003). Because the San Jose patients were still young, researchers believed they might be candidates for Björklund’s fetal transplant surgery. If the treatment succeeded in these patients, it was possible that their brains would be responsive enough to the new dopamine-producing brain tissue that they would be cured of drug-induced Parkinson’s disease.
George Carillo was the first patient to travel to Sweden for this experimental surgery. Every two weeks, Langston evaluated George. Subtle improvements became apparent approximately a year following the surgery. Several months later, George was walking with a natural arm swing, and more natural facial expressions began to return (see Figure 7A). With such encouraging results, two more patients underwent the surgery with comparable improvements. Langston reported that George enjoyed relief from Parkinson’s symptoms until his death in 2011 (personal communication, July 11, 2012).
Although the fetal transplant surgery appeared to successfully treat the symptoms of these patients, subsequent clinical trials demonstrated individual differences in the patients’ recovery rates (Barker, Barrett, Mason, & Bjorklund, 2013). Moreover, ethical questions about the use of fetal tissue led to political controversy. For these reasons, researchers have also considered the use of existing lines of human stem cells and fetal cells of animals such as pigs for this type of surgery (Bjorklund et al., 2003).