A History of Clinical Research…An Interesting, Amusing and Sometimes Horrifying Sampling of Events

The history of clinical trials is a sordid one that, thank goodness, now yields positively remarkable life altering and many times lifesaving results.

The beginning of the evolution of clinical trials dates back to well before biblical times, in 562 BC. The ruler of Babylon believed that his people would remain better nourished and more physically fit if they stuck to a strict diet of meat and wine. Certain resistant royals who poo-pooed this proclamation were permitted to exist on only legumes and water instead. This vegetarian diet, as you might imagine, produced healthier results.

Although there is no record of actual application, it is said that the author of the “Canon of Medicine” suggested, in 1025 AD, that “two contrary types suffering from the natural state of the same disease” should be studied.

In 1537, a famous surgeon treating wounded soldiers on the battlefield conducted a clinical trial quite by accident when he ran out of certain conventional treatments and tested some makeshift medicine on the next group of unfortunate men…who actually ended up being more fortunate.

Possibly more famously, in 1747, a ship surgeon treated groups of scurvy patients differently and discovered that citrus was effective. Limes, the cheapest of the lot, prevailed as the scurvy treatment of choice.

Then, things as they relate to clinical trials started to become a little more – shall we say – clinical. The first evidence of placebo use within a clinical study was recorded in 1800. This was during research of treatment of rheumatism patients. In 1943, the United Kingdom’s Medical Research Council conducted the first double blind controlled clinical trial while researching patulin for use with the common cold. Then in 1946, the first controlled trial used streptomycin in tuberculosis clinical trials. These quickly became a universally used clinical trial model.

In the 1920s, a researcher stumbled upon penicillin while attempting to discover an antiseptic. While there were difficulties during testing, efforts were revitalized during WWII and penicillin was mass produced after the attack on Pearl Harbor.

Many clinical trials began at the start of The Great Depression in 1929 and continued until the end of WWII in 1945. This surge in clinical trials brought about a world of change as well as a world that knew it all needed careful review. And so, the history of clinical research goes hand in hand with the evolution of its regulation…which was a rocky and sometimes even astonishing and appalling road…

Early regulation began with the creation of the U.S. Bureau of Chemistry, which was formed in an effort to prevent the use of transportation of dirty, decomposed and putrid (their word) food substances. In 1927, this review board and governing body morphed into the Food, Drug and Insecticide Organization and, in 1930, into the Food and Drug Administration with which we are familiar today.

In 1902, new standards in immunology were instituted when the Biologics Control Act required pharmaceutical companies to become licensed before they could produce vaccines and antitoxins.

In 1906, the Pure Food and Drug Act that required alcohol and drugs including cocaine, heroin and cannabis to include accurate labeling, was established to protect the public from unsafe “medicines”. My, we HAVE come a long way. Later, this act was used to place restrictions on certain unsafe products. For example, Coca-Cola, which contained cocaine and was marketed as a medicinal drink in the 1890s, was forced to switch from cocaine to caffeine in 1903. Wow. 

1938 was the year that the Federal Food, Drug and Cosmetic Act authorized factory inspections and granted Food and Drug Administration control over quality standards.

The Nuremberg Code, guidelines for ethical human experimentation, was created in 1947 in reaction to Nazi Germany experiments. These experiments, such as injecting blue dye into brown eyes to see if eye color could be changed, poisoning and involuntary sterilization – just to name a few – were conducted in prison camps on unwilling prisoners.

In 1951, the Durham-Humphrey Amendment, co-sponsored by later Vice President Hubert Humphrey, required a doctor prescription for drugs that were sold.

In 1956, thalidomide was marketed after it was tested only on rodents, causing tens of thousands of children to be born malformed. In 1962, the Kefauver-Harris Amendment, which requires drug manufacturers to prove safety and efficacy before approval, was a direct reaction to the thalidomide tragedy. Today, after proper clinical testing, thalidomide is safely used in cancer treatment.

The horrific Tuskegee Study of Untreated Syphilis, conducted by the U.S. Public Health Service and the Tuskegee Institute, followed 600 black males, 399 of which had syphilis. In exchange for their participation in this clinical study, they were promised free meals, medical care and burial insurance. None were told they had syphilis; only that they were being treated for blood related issues. These men were never treated for their symptoms, even when penicillin was found to be a proven treatment and they were never told they could opt out.

This madness was ended in 1972 by a whistleblower, but not before the deaths of 128 mean and the contraction of 40 wives and 19 unborn children….All of which led to the National Research Act of 1974 which addressed long-needed guidelines for how human subjects should be treated, including being protected from harm, ensuring that every effort is taken to secure their well-being and to treat people equally and with respect.

In 1983, Congress made changes to federal laws and, through the Orphan Drug Act, financially encouraged the development of treatments for rare conditions and disorders. This resulted in clinical study, review and Food and Drug Administration approval of 41 drugs within 25 years.

The Genome Project, resulting in genetic testing which identified the predisposition to certain illnesses and diseases, was launched in 1990. In 1997, the Food and Drug Administration Modernization Act increased patient access to experimental drugs and medical devices and accelerated drug approval time constraints. And 2001 marked the start of stem cell research regulation review.

Today, clinical testing is light years safer, far better regulated and more advanced than ever before; and its results are astounding.