Ellen Roche was a 24 year old technician at Johns Hopkins Asthma and Allergy Center, where she heard of a trial recruiting healthy volunteers to help doctors discover the reflex that protects the lungs of healthy people against asthma attacks. The researchers would provoke a mild asthma attack by having her inhale hexamethonium, a medication used for treating high blood pressure in the 1950s and 1960s. She signed up for the study and quickly developed a cough, though the researcher administering the trial chalked it up to a common cold. Her condition worsened over the next week. Doctors put her on a ventilator. Ellen Roche’s lung tissue dissolved and her blood pressure plummeted. Then, her kidneys began to fail. She died on June 2, 2001, a month after entering the study.
Medical officers from the trial now admit that the hexamethonium was either solely responsible or played a contributory role to her illness, but that doesn’t make accepting her death any better. In fact, to make things worse, participants learned the FDA did not even approve of the drug after the trial. In their consent forms, they merely referred to it as a “medication” instead of clearly indicating that it was experimental or listing the risks. Keep reading for facts about clinical trials that won’t horribly wrong.
Since chimpanzees share more than 99% of DNA with humans, and mice share more than 98%, they are susceptible to many similar health problems as humans like cancer, diabetes, and heart disease. Researchers are legally and morally obligated to ensure the health and well-being of the animals in their care. They never set out to harm them; animal testing is essential in drug approval. Animal trials have helped scientists learn about disease stages and how to treat or even cure them. Currently, animal use is even a mandated part of drug development. Current federal laws in the U.S. require proof of safety and effectiveness in animal trials before they move into human trials. In our last entry, we’ll look at a clinical trial where successful animal testing didn’t translate to safe human testing.
Theralizuman is also as TGN1412, CD28-SuperMAB, and TAB08. Thomas Hunig developed it at the University of Wurzburg in 2006. The purpose of the drug was originally to treat B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis by binding to receptors on the T-cell. The six human participants were assumed that the worst symptoms they’d experience were likely a headache and nausea, but the trial soon spiraled into one of the most infamous medical trials in British history. Shortly after receiving their doses, all patients began experiencing severe pain and vomiting uncontrollably. One patient lost his fingers and toes, another had to have this foot partially amputated. The trial is “the Elephant Man Trial” because one patient’s head swelled up so much that his girlfriend teased him about looking like an elephant.
Doctors now know to call the symptoms men experienced cytokine storm. It is where their temperatures soared, their organs failed, and some of their bodies swelled past recognition. One of the participants, Rob Oldfield, had fluid seeping into his lungs and had to breathe through a mask. Ryan Wilson spent four months in the hospital and battled pneumonia, septicaemia and dry gangrene. His father had warned him the night before the trial: “Don’t do it. Your body is a temple.” The volunteers still suffer from weakened immune systems and other side effects.
Though knowing what went wrong with the trial is difficult, there are a few theories about why it was so ill-fated. One theory claims that the period of drug injection was to blame. Researchers spent over an hour and a half injecting the drug carefully into the animals. However, injecting the entire dosage into the human participants took a mere six minutes. Another theory suggests that animal testing did not translate to human testing accurately because it was done on a macaque instead of a bonobo, so the animal-to-human DNA match was only 94% instead of 98%.
Oddly, one source said that the first infusion in six patients was five hundred times smaller than that found safe in the animal studies, but the volunteers still suffered life-threatening organ failure. Clearly, a disconnect between animal and human studies happened here, resulting in a hugely unfortunate incident for those involved. Parexel, the drug company that ran the clinic where the trial was carried out, was found to have acted within all proper protocols. However, a final report did indicate that the trial had not adequately considered the safe dosage for humans. The company that developed the drug, TeGenero Immuno Therapeutics went bankrupt later that year.