The Voice
How Did Clinical Trials Come About?
For patients with lung cancer, one treatment option may be a clinical trial. Clinical trials provide valuable insights on how people respond to new treatments or treatment combinations. But how did clinical trials come to be?
It’s taken a long time to arrive at clinical trials in the form that they are today. According to an article inthe journal, Perspectives in Clinical Research, the first record that we have of something resembling a clinical trial comes from The Bible. In The Book of Daniel, King Nebuchadnezzar ordered his soldiers to drink only wine and eat only meat, believing that this would make them the strongest. However, several noblemen objected, as they preferred to eat vegetables. The King allowed them ten days to eat only legumes and water, then compared their performance to that of his meat-eating soldiers. He found that they performed better than the soldiers on his diet, and they were allowed to continue their vegetarian diet.
The first theoretical application of a clinical trial in the medical world comes from Avicenna, an 11th century Islamic philosopher and poet. In his Canon of Medicine, he describes how a clinical trial should be run: the subjects should not be suffering from unusual complications, and the remedies should be used as they normally would be. Avicenna also advised physicians to test if the results are reproducible. Although he wrote about how to conduct a clinical trial, Avicenna’s writings seem very theoretical, as there is no corresponding record of actual clinical trials that he carried out.
One of the first recorded medical tests that resembled a clinical trial took place not because it was carefully planned and based on deep theory, but out of necessity. In 1537, the famous French surgeon Ambroise Pare was serving with the French army during the War of Spanish Succession. Pare was trying to treat wounded soldiers with boiling oil to sanitize their wounds. However, he did not have enough oil for the wounded. So, he came up with a mix of egg yolks, roses and turpentine to use on some of the soldiers. In his writing, he confessed to being nervous about this improvised treatment, and unable to sleep well because he feared the men were in pain. However, when he checked on patients early the next morning, he found that the egg mixture had not adversely affected the soldiers’ wounds, and that these soldiers had slept more soundly than those treated with the conventional treatment.
One of the first recorded intentional clinical trials was carried out by Scottish physician, James Lind while treating scurvy in sailors in 1747. He ran the trial as a controlled experiment and made sure that the sailors were all kept in the same conditions and fed in the same way. He then tried six different treatments, ranging from seawater, and cider to various elixirs, the recommended treatment of the day, and a diet of oranges and lemons for two of the soldiers. Two soldiers tried each treatment option, and Lind found that the sailors treated with oranges and lemons improved the most. He published his results in a Treatise on Scurvy in 1753.
Between 1753 and the middle of the 19th century, clinical trials continued to evolve and become more complex, with additional features like placebo treatments, “blind” studies (where neither the physician nor the subject know whether they are receiving an active treatment or part of the control group) and truly randomized assignment of treatments.
It is not widely known who performed the first clinical trial related to cancer. But, according to the Yale School of Medicine, the first clinical trial of chemotherapy came out of military-related studies. As World War II was beginning, the US government had asked Yale to study nitrogen mustard, which had been used as part of chemical warfare in World War I. Two younger pharmacology professors, Louis S. Goodman and Alfred Gilman, began their research in 1942. They noticed that nitrogen mustard destroyed lymph tissue and bone marrow and theorized that it could be used to treat tumors. They experimented first on mice and rabbits, and had promising results, before trying the treatment on a terminal cancer patient with lymphosarcoma. The 48-year-old patient initially saw his tumors regress, and the results (though not long-lasting) were considered promising enough that the study was expanded to 67 patients.
The National Cancer Institute states that the first major clinical trial that studied lung cancer in a large population started in 1993. The trial studied the effect of screening for lung cancer and other types of cancer such as prostate cancer, colorectal cancer and ovarian cancer. The National Cancer institute also lists the National Lung Screening Trial, which studied two ways of diagnosing lung cancer, as one of the first landmark lung cancer clinical trials.
Sources
Evolution of Clinical Research: A History Before and Beyond James Lind | NIH
From the field of battle, an early strike at cancer | Yale School of Medicine
Celebrating Clinical Trials Day 2021: The Evolution of Clinical Research | PharPoint Research
Milestones in Cancer Research and Discovery | NCI National Cancer Institute