Benjamin Rush and the story of Calomel: Lessons for Today about Gadolinium

George Santayana is credited for saying the original variant of the quote: "Those who do not learn from history are doomed to repeat it." In some ways the story of Calomel ( a mercury-based drug) and gadolinium-based contrast agents (gadolinium-based ofcourse), share some properties. I do not intend to represent those shared qualities, as all of the truth; but they are some, starting with that they are both heavy metal-based drugs that were (Calomel) and are (GBCAs) highly touted in their day/present day. It is also worth adding Salvarsan in, as it is a heavy-metal based drug developed around 1910 (arsenic-based) to treat syphillis. Maybe though the relationship between these heavy-metal drugs and GBCAs should be better thought of in terms of Mark Twain's observation on history: History doesn't repeat itself, but it often rhymes... but perhaps appropriately enough for a controversial article like this, it is not clear Mark Twain actually said this.

It is worthwhile for the reader to consult accounts of the life of Benjamin Rush. His peak period of practicing medicine in the USA was 1770-1800 and practiced in Philadelphia. He was the most famous physician in the USA at the time, and had the highest international recognition of American physicians. He focused on purging as the principle medical treatment, for essentially everything. So he focused on blood-letting (which is ok), but also the purging of the GI tract, and his favorite agent was Calomel (not ok). Mercury purgatives had been in use for at least a few centuries prior to Benjamin Rush. He espoused 'heroic doses' of Calomel that resulted in massive diarrhea, and he was enthused by the volume of diarrhea. Yet the severe adverse effects, especially massive bone destruction, emphasizing facial bones, was somehow entirely ignored, and massive fatal GI hemorrhage, also completely overlooked. Despite all this, the practice of administering heroic doses of Calomel carried on in the USA til atleast 1850 (ceased earlier in Europe). There were few dissenting voices, pointing out the adverse events, but for many years they were largely ignored and ridiculed. The focus was on the enthusiastic observation of massive diarrhea. In the cold light of the modern medical eye, 100s of thousands, maybe millions of patients died horrible painful deaths or suffered severe and irreversible damage from this medical practice of Calomel administration. At the time these injuries were ignored.

Does this sound familiar?

Let me start by repeating what I have often said: 1. GBCAs are useful for the investigation of a great number of disease, 2. despite the fact that some Gd is retained in essentially everyone who receives a GBCA, it is a small minority who get sick, and truly sick, from GBCAs, BUT i) we need to figure out who gets GDD, ii) we have learn how to prevent it from occurring, and iii) we need to develop effective comprehensive treatments for the disease.

So, with Calomel, essentially no one benefitted from it, 100s of thousands died or became irreversibly permanently damaged, whereas with GBCAs, many patients have benefited (probably 50 million individuals of 300 million doses - I never forget the problem of overuse in imaging), and possibly 5,000 - 10,000 individuals seriously injured (large absolute number, but only 0.01 % of the total). So the cost/benefit ratios are very different between Calomel and GBCAs.

I have considered it an artifact of the history of medical practice, that remarkably somehow physicians ignored the serious injuries they were causing; earlier than the 1950's (when Salvarsan was in use) or the 1800's and earlier (with Calomel). So I do find it remarkable that a sizable number of modern-day physicians do not recognize the existence of GDD. The explanations I have expounded on in earlier blogs, so I won't repeat them here. So I can explain it, but still find it remarkable; as a lesser example of the willful ignorance of the dangers of Calomel in the early 1800s.

I also find it somehow funny that physicians and radiologists who criticize my writings on GDD, may also be blissfully unaware that atleast 320 of the approximately 370 peer-reviewed papers I have written have focused on the value of GBCAs, and also 8 major text-books - much more than even the most famous or published of the critics. So I am well aware of the value that GBCAs can contribute to an MR study. I am not a Johnny-come-lately trying to achieve fame, by ruining everyone else's GBCA party. I have to remind them of the well regarded quote from Sir William Osler: Doctors, Listen to your patients, they are telling you the diagnosis. I suspect most if not all of the naysayers have never actually spoken to patients about issues they have had with GBCAs or any other radiology agent (eg, iodine-based agents). As with everything else in life, those who are the most vociferous and self-confident in their pronouncements are generally the ones who have the least knowledge. Knowledge and experience, when one pays attention to observations, have a way of making an individual cautious, and recognize that may be the patient is right, even in the face of orthodox medical knowledge.

The final point in this blog, and that I also find humor in, but is unfortunately tragic for patients, is the observation on truths that Arthur Schopenhauer described: All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.

We have now entered stage 2. I am looking forward to the day, maybe two years from now, that the nay-sayers will say: I knew it all along, it just was never said in the correct way for me to believe it.