Thalidomide: From Tragedy to Triumph?

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Formerly hailed as “The tenderlion” of New York, the famous, bustling Times Square is home to a huge sky scraper known as the Conde Nast Builiding. Seventeen years ago, it was the office of Beth jacobson, a former pharmaceutical lawyer who in 1995, put her career on hold to take care of her husband who was diagnosed with multiple myeloma.

Jacobson is currently caught in a storm that began in the 1950’s when the drug Thalidomide (known as Poli Grapin in Pakistan) was introduced as a sedative that was phenomenal in curing the symptoms of morning sickness. It attracted thousands of pregnant women but their temporary comfort came at a tragic price: it was found that almost 10,000 children were born with deformities as a result of its use. The link between thalidomide and these defects was proved by a German Pediatrician Lenz in 1961.

After her husband’s diagnosis, Jacobson decided to take matters into her own hands as she tried to find a possible cure despite the fact that her expertise was on the legal and not scientific aspect of pharmacology. However, thanks to her ingenuity and keen medical sleuthing, she discovered that a researcher was using Thalidomide to treat children with leukemia and suspected it might be useful for her husband’s disease too.

How can a drug whose usage has been insinuated as “the biggest medical tragedies of modern times” possibly act as a cure for a fatal disease? The answer lies in the mechanism of action of thalidomide; the structure of thalidomide is such that it can bind to various proteins and cell receptors. This mechanism displayed its ugly side in the instance of it causing birth defects for it binds with a protein cereblon which is important in limb formation. In the treatment of multiple myeloma however, it proves to be effective in curbing the disease mainly by inhibiting a certain growth factor, interleukin 6 that is responsible for the spread of myelomic cells.

Even before Jacobson’s discovery, thalidomide was already proving effective in the treatment of leprosy. According to Wikipedia “In 1964, Jacob Sheskin, Professor at the Hadassah University Hospital and the chief staff and manager of Hansen Leper Hospital in Jerusalem, administered thalidomide to a critically ill patient with erythema nodosum leprosum (ENL), a painful skin condition and a complication of leprosy, in an attempt to relieve his pain in spite of the ban. The patient slept for hours, and was able to get out of bed without aid upon awakening. The result was followed by more favorable experiences and then by a clinical trial.” In 1998 it was re-introduced in the US for use in ENL.

At that time in 1995, Celegne was the only pharmaceutical company that held a license for the therapeutic use of Thalidomide. Jacobson approached them and asked for the drug to be supplied to her husband.

Ironically, the drug proved ineffective for her husband who died later, but another patient whp heard of the treatment, requested for the same and it worked wonderfully for him. Eventually a clinical trial was done that proved successful and in favour of thalidomide being used as treatment of multiple myeloma. In its annual report Celegne thanked Beth’s efforts but did not provide any monetary compensation despite and as according to her complaint that “t least 80 percent of Celgene’s annual revenue of $2.3 billion was derived from the sale of Thalidomide and related drugs to treat the disease.”

The wide mode of action of thalidomide suggests that its influences are vast and far-reaching. As if trying to make up for the horror and tragedy caused in 1950, thalidomide is proving beneficial in many areas of medicine. Some of these are being discovered recently. For example, in an experiment conducted by A. Abbas, H. Feroze and G.H.Hyman of The Aga Khan University, Pakistan and Brookdale University Hospital, NY, it has been discovered that thalidomide is an effective inhibitor of corneal angiogenesis (development of new blood vessels) in an alkali burn induced corneal neovascularization model in rabbits. It may thus prove effective in use

to prevent the negative effects of alkali burns. According to their report, this is a pretty important aspect as alkalis have the capability to damage not only the conjuctival surface but also the corneal stroma and endothelium. Usually, a corneal transplant is required as treatment however with the use of thalidomide these harmful injuries may be cured more quickly and cheaply.

Ultimately, despite its devastating history, thalidomide is emerging as a successful agent for the cure of myelomas, leprosy and many other diseases and injuries. It is yielding good fruit in many experiments conducted regarding its mode of action. Whether it can replace its tragic past and become a ‘wonder drug’ for the masses remains to be seen.