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==History==
===Development===
Thalidomide was thought to have been developed by [[Germany|German]] pharmaceutical company [[Grünenthal]] in [[Stolberg (Rhineland)]] near [[Aachen]] although this has recently been challenged by Dr Martin W Johnson, director of the Thalidomide Trust in the UK<ref>http://www.timesonline.co.uk/tol/life_and_style/health/article5683577.ece</ref>. It is thought that thalidomide was developed by the Nazis as an antidote to nerve gas such as sarin.

It was sold from 1957 to 1961 in almost 100 countries under at least 40 names, including Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, and Softenon. Thalidomide was chiefly sold and prescribed during the late 1950s and early 1960s to [[pregnant]] women, as an [[antiemetic]] to combat [[morning sickness]] and as an aid to help them sleep. Before its release, inadequate tests were performed to assess the drug's safety, with catastrophic results for the children of women who had taken thalidomide during their pregnancies.

===Birth defects===
From 1956 to 1962, over 9000 children in Africa and Europe were born with severe malformities, including [[phocomelia]], because their mothers had taken thalidomide during pregnancy.<ref name =Bren> 
The Australian obstetrician [[William McBride (doctor)|William McBride]] discovered the link between birth defects and the drug, and was awarded a medal and prize money by the prestigious L'Institut de la Vie in Paris.<ref>[http://embryology.med.unsw.edu.au/Defect/page5i.htm Report of Thalidomide at University of New South Wales.] See also main [[William McBride (doctor)|William McBride]] article.</ref>

The impact in the United States was minimized when [[Frances Oldham Kelsey]] refused FDA-approval for an application from [[Marion Merrell Dow|Richardson Merrell]] to market it saying it needed more study.  Richardson Merrell gave the tablets to doctors with the understanding that it was still under investigation. 17 children in the U.S. were born with the defects.<ref>[http://www.medic8.com/medicines/Thalidomide.html Thalidomide - medic8.com - Retrieved August 25, 2008]</ref>

In 1962, the [[United States Congress]] enacted laws requiring tests for safety during pregnancy before a drug can receive approval for sale in the U.S.<ref name =Burkholz>{{cite news | first =Herbert | last =Burkholz | title = Giving Thalidomide a Second Chance | url =http://www.fda.gov/fdac/features/1997/697_thal.html | format = | work =FDA Consumer | publisher =US [[Food and Drug Administration]] | date =[[1997-09-01]] | accessdate =2006-09-21 }}</ref> Other countries enacted similar legislation, and thalidomide was not prescribed or sold for decades.

However, it was soon found that it was only one particular [[optical isomer]] of thalidomide which caused the teratogenicity. The pair of [[enantiomers]], although mirror images of each other, cause different effects<ref>Chemistry 2, published by Cambridge University Press 2001. ISBN 0-521-79882-5</ref> (see [[Thalidomide#Teratogenic_mechanism|''Teratogenic mechanism'']] section for details).

===Revived interest===
Researchers, however, continued to work with the drug. Soon after its banishment, an Israeli doctor discovered anti-inflammatory effects of thalidomide and began to look for uses of the medication despite its [[teratogenic]] effects. 

In 1964 Israeli physician Jacob Sheskin was trying to help a critically ill French patient with erythema nodosum leprosum&nbsp;(ENL), a painful complication of [[leprosy]]. He searched his small hospital for anything to help his patient stop aching long enough to sleep. He found a bottle of thalidomide tablets, and remembered that it had been effective in helping mentally ill patients sleep, and also that it was banned. Sheskin administered two tablets of thalidomide, and 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. Dr. Sheskin's drug of last resort revolutionized the care of leprosy and led to the closing of most leprosy hospitals.<ref name =Silverman>{{cite journal |last= Silverman, MD |first= William |authorlink= |coauthors= |date= [[2002-04-22]]|title=The Schizophrenic Career of a "Monster Drug" |journal=Pediatrics |volume= 110 |issue= 2 |pages= 404–406 |id= |url=http://pediatrics.aappublications.org/cgi/content/full/110/2/404 |accessdate= 2006-09-21|doi=10.1542/peds.110.2.404|pmid=12165600 }}</ref>

He found that patients with [[erythema nodosum]] leprosum, a painful skin condition associated with [[leprosy]], experienced relief of their pain by taking thalidomide. Further work conducted in 1991 by Dr. Gilla Kaplan at Rockefeller University in New York City showed that thalidomide worked in leprosy by inhibiting tumor necrosis factor alpha. Kaplan partnered with Celgene Corporation to further develop the potential for thalidomide.  Subsequent research has shown that it is effective in [[multiple myeloma]], and it was approved by the FDA for use in this [[malignancy]]. The FDA has also since approved the drug's use in the treatment of [[erythema nodosum]] leprosum.  There are studies underway to determine the drug's effects on [[arachnoiditis]] and several types of [[cancer]]s. However, [[physicians]] and patients alike must go through a special process to prescribe and receive thalidomide (S.T.E.P.S and RevAssist) to ensure no more children are born with birth defects traceable to the medication.  Celgene Corporation has also developed analogues to thalidomide, such as [[lenalidomide]], that are substantially more powerful and have fewer side effects - except for greater [[myelosuppression]].<ref>http://www.medscape.com/viewarticle/562417_3</ref>

===FDA approval===
On July 16, 1998, the FDA approved the use of thalidomide for the treatment of lesions associated with Erythema Nodosum Leprosum (ENL). Because of thalidomide’s potential for causing birth defects, the distribution of thalidomide was permitted only under tightly controlled conditions.  The FDA required that Celgene Corporation, which planned to market thalidomide under the brand name Thalomid, establish a System for Thalidomide Education and Prescribing Safety (S.T.E.P.S) oversight program.  The S.T.E.P.S program   includes limiting prescription and dispensing rights only to authorized prescribers and pharmacies, extensive patient education about the risks associated with thalidomide, periodic pregnancy tests, and a patient registry.<ref>[http://www.fda.gov/cder/news/thalinfo/ FDA, Center for Drug Evaluation and Research, July 16, 1998]</ref>

"On May 26, 2006, the U.S. Food and Drug Administration granted accelerated approval for thalidomide (Thalomid, Celgene Corporation) in combination with dexamethasone for the treatment of newly diagnosed [[multiple myeloma]] (MM) patients."<ref>[http://www.fda.gov/cder/Offices/OODP/whatsnew/thalidomide.htm FDA Approves Thalomid (thalidomide) to Treat Multiple Myeloma<!-- Bot generated title -->]</ref>  The FDA approval came seven years after the first reports of efficacy in the medical literature<ref name=Desikan>{{cite journal | last = Desikan | first = R | coauthors = N. Munsi, J. Zeldis et al.| title = Activity of thalidomide (THAL) in multiple myeloma (MM) confirmed in 180 patients with advanced disease | journal = Blood | volume = 94 | issue = Suppl. 1 | pages = 603a-603a | publisher = | year = 1999 | url = | doi = | id = | accessdate = }}</ref> and Celgene took advantage of "off-label" marketing opportunities to promote the drug in advance of its FDA approval for the myeloma indication.  Thalomid, as the drug is commercially known, sold over $300 million per year, while only approved for leprosy.<ref>[http://www.publicintegrity.org/rx/report.aspx?aid=722 Pushing Prescriptions - The Center for Public Integrity<!-- Bot generated title -->]</ref>

Thalidomide was and, as of 2009, still is an important advance in the treatment of multiple myeloma, ever since news of its efficacy appeared in the Desikan et al. report.<ref name =Desikan /> The drug has some bothersome side effects such as neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy for multiple myeloma. Thalidomide, along with another new drug, [[bortezomib]], is changing multiple myeloma treatment, such that [[Hematopoietic stem cell transplantation|stem cell transplant]]s may no longer be the standard treatment for this incurable malignancy.