Frank A. Wollheim
Lund, Sweden (Spring 2017)
There were no signs of genius to impress us in any of the medical students at Lund in the fall of 1950, and certainly not in Torsten Almen. He seemed rather ordinary, somewhat shy and stuttering; and it was a well kept secret that he was a good pianist and an accomplished oboist. He came from Ystad, a medieval city on the south coast of Sweden where his father was the regimental medical officer, known among recruits for his rod of iron; and we assumed that Torsten had been victim of a dominating father. But in the end he became the most illustrious graduate of our class. (Fig. 1).
In 1959 Torsten decided to take up diagnostic radiology. His main interest being angiography, he worked on patients during the day and experimented with liver angiography on dogs at night. But he became increasingly upset by how painful it was for patients to be injected with iodine contrast media (1). He had noted that flushing catheters with saline was painless; and he remembered how it hurt when he was splashed in the eye with salty sea water when swimming on the Swedish west coast, yet how the brackish water outside his home town of Ystad caused no pain. Could high osmolality be the culprit?
Torsten bought books on organic and colloidal chemistry; and concluded that transforming the contrast media into non-ionized but water soluble derivatives by modifying the structure might solve the pain problem. But the experts in the drug industry in Sweden and abroad showed no interest in his idea.
|Fig. 2. The notarized sketch of 1968|
In 1967 after defending his PhD thesis Torsten joined Mary Wiedeman at Temple University and studied the microcirculation of bat wings. Here again osmotoxicity seemed to be the problem. One day at a convention in Miami he happened to walk past a public notary office. On an impulse he rushed to his hotel room and made a sketch summarizing his ideas on non-ionized contrast media (fig. 2). The following day, 20 March 1968, he went to the sheriff and had his document notarized. The sheriff commented “Well young man, my lack of education does not allow me to appreciate your work”. Torsten replied “Don’t apologize, educated people do not appreciate it either”. The sheriff realized that he was dealing with a smart young man, wished him good luck and advised him to stay out of prison.
Torsten tried to publish a paper on his invention but after it was rejected by all radiology journals it was printed well out of sight of most colleagues (2). Finally he was approached by Dr. Holterman, head of research at Nyegaard & Co, a small company in Oslo. A contract was signed on 17 May 1968. Torsten became a member of the Nyegaard research team working on improving the water solubility of the contrast agent. He made several suggestions to the sceptical company chemists, who tested but one: to add hydroxyl containing side chains to the third non-iodinized carbon atom of the benzene ring. The first success with water solubility was noted in November of that year, but that compound turned out to be toxic. A year later, after testing some eighty other derivatives “agent 16” showed promise and was eventually developed into metrizamide (Amipaque) and marketed in 1974. As predicted its injection was completely painless. This breakthrough transformed Nyegaard into one of the largest companies in Norway, now named Nycomed. A further product, iohexol, was marketed as Omnipaque in 1985. It is still widely used for angiography and MRI and is on the World Health Organization’s list of essential medicines. It is also used as a sensitive and reliable test of glomerular function.
When Torsten Almén was awarded the Big Fernström Prize he illustrated his prize lecture with his oboe. He was a man with a sense for the humanities, and in the end it was his concern for humane treatment that led to a great scientific discovery.
- Nyman U, Ekberg O, Aspelin P. Torsten Almén (1931-2016): the father of non-ionic contrast media. Acta Radiologica 2016;57:1072-1078
- Almén T. Contrast agent design. Some aspects on the synthesis of water soluble contrast agents of low osmolality. J Theor Biol 1969;24:216–226.
FRANK A. WOLLHEIM, is an Emeritus professor in the Department of Rheumatology at Lund University.