The use of radioactive compounds as medicines is starting to have it’s moment in the sun. Currently over 60 of these radiopharmaceuticals are approved worldwide, primarily for the purpose of diagnosing and treating cancer. Billion dollar acquisitions have a funny way of getting investors excited, though the specialized nature of these compounds leaves many companies struggling to fill a “significant talent shortage.” Of course, the story of radioactivity in medicine didn’t begin with billion-dollar deals, it began with the curious case of uranium.

Our story begins in 1789, when the German chemist Martin Heinrich Klaproth decided to take a deeper look at what was essentially mining waste. A self taught expert in mineral analysis, Klaproth was busy doing analytical chemistry before it was cool. The hipsters among us may know him for his work on zirconium, but his early work on uranium is definitely one of his greatest hits. Klaproth had started some early work on the mineral torbernite, but eventually switched to working on a mineral that gold and silver miners knew well: pitchblende. This black substance typically meant that the gold and silver had been exhausted and that it was time to move elsewhere.

In what no doubt must drive a 6^th year analytical chemistry PhD student to the edge of sanity, Klaproth utilized the following protocol to isolate Uranium:
1) Dissolve pitchblende in nitric acid
2) Neutralize the solution with a strong base to produce a yellow precipitate
3) Heat this yellow precipitate with charcoal to obtain black powder
4) Claim you’ve discovered a new element, because you can’t separate anything else

Klaporth announced to the Royal Prussian Academy of Sciences on September 24, 1789:

“The number of known metals had been increased by one — from 17 to 18…. A few years ago we thrilled to hear of the discovery of the final planet by Sir William Herschel. He calls the new member of our solar system Uranus. I propose to borrow from the honor of that great discovery and call this new element Uranium.“

–Martin Heinrich Klaproth, as told in Lennard Bicknel’s The Deadly Element, the Story of Uranium

This announcement was a bold choice for a couple reasons:

• First, clout chasing a recent planetary discovery with a strong tie to butt jokes would not have been my go to naming strategy. I’ve also never discovered an element before so my opinions on elemental naming should be taken with a grain of radioactive salt.
  
• Second, Klaproth and I have something in common… not discovering uranium in it’s elemental form. It took until 1841 for Uranium metal to be isolated by the French chemist Eugène-Melchior Péligot. He ultimately showed Klaproth’s purification, in the oxygen rich atmosphere, produced Uranium Oxide rather than Uranium metal. This may seem like a real “well actually…” move on Péligot’s part but from a scientific street cred perspective its meaningful. It’s a bit like someone claiming they just bought the most recent iPhone only to discover later that they now own the most current iPhone charger. It’s a useful accessory but not exactly what was advertised.

Technicalities aside, uranium salts became a real topic of industrial interest in the nineteenth century thanks in large part to the glass industry but also in response to their perceived potential as medicines. While industrial chemistry in the nineteenth century was really coming into it’s own, medicine didn’t have the foggiest idea what caused diabetes. Physicians entertained notions such as “like cures like,” the central tenant being that “a disease can be cured by a substance that produces similar symptoms in healthy people.” Such ideas live on in questionable practices such as homeopathy, where such compounds are diluted to a just a faint memory. On the plus side overdoses on homeopathic medicines remain in short supply so at least we have that as a consolation prize.

In 1853, C. Le Conte showed small doses of orally administered uranium nitrate induced sugar secretion into the urine, an observation also made of diabetic patients. Clinicians had known for centuries that diabetics had a demanding thirst and produced copious amounts of urine that was sweet with sugar, but the mechanisms for this remained poorly understood. This discovery, paired with a belief in “like cures like,” led to the hot take that uranium nitrate may be an effective treatment for diabetes. Now for those saying things like “that’s not how diabetes works” or “what about the radiation?”, I hear you but you have to put this work in context. This predates the discovery of insulin by more than 60 years. Becquerel will not discover uranium emits radiation until 1896. Everyone is pretty much flying blind and in 1853, diabetes was almost universally fatal, so why not try something like this?

In this back drop, enters the physician Samuel West, with his 1895 publication in the British Medical Journal titled “The Treatment Of Diabetes Mellitus By Uranium Nitrate.” In this rather meandering pair of case reports, West administers a solution of water and uranium nitrate to just 2 patients, starting with a low dose of just 1-2 grains (100 mg) and then gradually escalating to as much as 20 grains (1.3 grams) 3x per day. As one might imagine this resulted in some rather unpleasant gastrointestinal issues (eg indigestion, diarrhea) that ultimately led patients to discontinue. West insists taking the mixture after a meal helps address these issues. He is ultimately struck by dramatic reductions in thirst, urination, and sugar in urine. All these data points indicated to West that the patients diabetes was improving, though one is right to wonder if urination frequency was the most clinically meaningful endpoint for diabetics in 1895.

In 1896, West publishes his follow up with another 5 cases showing “the same general improvement… though not to the same degree.” This study would be laughably weak today, but at the time these results were sufficient for some drug makers to take action. Some began exploring oral formulations of uranium nitrate that would be more palatable. Oppenheimer, Sons & Co of London for example marketed it’s uranium nitrate palatinoids “as combining the benefits of uranium, which ‘has been recently recommended in the treatment of diabetes by Dr S West’ without the ‘repugnant flavour’ of his treatment.” Prior to the discovery of insulin some 6 different uranium salts were in use for the the treatment of diabetes, joining the ranks of other toxic options such as arsenic salts and more benign choices like sodium bicarbonate. The most colorful formulation by far was a Bordeaux wine known as Vin Urané Pesqui which contained just a soupçon of uranium nitrate. It was widely used in the early twentieth century as a treatment for diabetes. In the wine’s monograph, Le Diabète, Son Traitement Par Le Vin Urané Pesqui the authors claimed:

“Statistics from medical specialists show that at least 10,000 diabetics die each year in France due to lack of treatment, even though they could be cured by Vin Urané Pesqui“

– Le Diabète, Son Traitement Par Le Vin Urané Pesqui

Uranium nitrate as a treatment for diabetes ultimately fell out of fashion in favor of more effective therapies such as insulin. While extensively diluted uranium salts may still be in use amongst homeopaths, evidence of efficacy is generally lacking and currently no homeopathic medications are FDA approved. Uranium with its long half-life of hundreds of millions to billions of years, depending on the isotope, makes it a tough sell as an oral product today. Though uranium is a good source material for other radioactive isotopes that have medical applications.

That said if anyone has a bottle of Vin Urané Pesqui on their shelf I’d love to see it. I think I’ll pass on the wine tasting though… I’ve never been a fan of Bordeaux.

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This post was inspired by and significantly benefited from the work of Lucy Jane Santos. I highly recommend you read her latest book entitled Chain Reactions: The Hopeful History of Uranium.