Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin (Translating Basic Research to the Clinic)

Author/Writer: Stephen J. Williams, Ph.D.

This will be a regular posting which I hope people will find interesting.  I wish to highlight the basic research which led to seminal breakthroughs in the medical field, brought on by the result of basic inquiry, thorough and detailed investigation, meticulously following the scientific method, and eventually leading to development of important medical therapies.

This month I would like to highlight the research of Dr. Barnett Rosenberg and his discovery of one of the most used and effective chemotherapeutics, cisplatin.

The compound cis-PtCl₂(NH₃)₂ (seen in the Figure ) was first described by M. Peyrone in 1845, and known for a long time as Peyrone’s salt.^[3] In 1965, Barnett Rosenberg, van Camp et al. of Michigan State University  had asked a simple question and noticed that electrical fields can inhibit the division and induce filamentous growth  of Escherichia coli (E. coli) bacteria. . Although bacterial cell growth continued, cell division was arrested, the bacteria growing as filaments up to 300 times their normal length.^[5]  However, Dr. Roenberg did not stop at this finding and meticulously accounting for each variable which might explain this finding, including altering the metal composistion of the electrodes.  Dr. Rosenberg thought of the possibility it was not the electric field perse, which caused the growth inhibition, but a chemical produced in the media by electrolysis.  Eventually he discovered that electrolysis of platinum electrodes generated a soluble platinum complex which inhibited binary fission in Escherichia coli (E. coli) bacteria.  In addition he isolated this platinum complex and discovered that ammonium ions were required as well, owing to the full chemical structure of cisplatin as seen above (the nitrogens moieties are bioactivated to cations). This finding led to the observation that cis PtCl₂(NH₃)₂ was indeed highly effective at regressing the mass of sarcomas in rats.^[8] Confirmation of this discovery, and extension of testing to other tumour cell lines launched the medicinal applications of cisplatin. Cisplatin was approved for use in testicular and ovarian cancers by the U.S. Food and Drug Administration on December 19, 1978.^[9]

• ^ Peyrone M. (1844). “Ueber die Einwirkung des Ammoniaks auf Platinchlorür”. Ann Chemie Pharm 51 (1): 1–29. doi:10.1002/jlac.18440510102.
• ^ ^{a b c} Stephen Trzaska (20 June 2005). “Cisplatin”. C&EN News 83 (25).
• ^ Rosenberg, B.; Van Camp, L.; Krigas, T. (1965). “Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode”. Nature 205 (4972): 698–699. doi:10.1038/205698a0. PMID 14287410.

Barnett Rosenberg

From Wikipedia, the free encyclopedia

Barnett Rosenberg (16 November 1926 – 8 August 2009) was an American chemist best known for the discovery of the anti-cancer drug cisplatin.^[1]

Rosenberg graduated from Brooklyn College in 1948 and obtained his PhD in Physics at New York University (NYU) in 1956. He joined Michigan State University in 1961 and worked there until 1997.

In 1965, Rosenberg and his colleagues proved that certain platinum-containing compounds inhibited cell division and then in 1969 showed that they cured solid tumors. The chemotherapy drug that eventually resulted from this work, cisplatin, obtained US Food and Drug Administration (FDA) approval in 1978 and went on to become a widely used anticancer drug. The initial discovery was quite serendipitous. Rosenberg was looking into the effects of an electric field on the growth of bacteria. He noticed that bacteria ceased to divide when placed in an electric field and eventually pinned down the cause of this phenomenon to the platinum electrode he was using.^[2]

He was awarded the Charles F. Kettering Prize in 1984 and the Harvey Prize in 1984. ^[3]

1. ^ Rosenberg, B.; Van Camp, L.; Krigas, T. (1965). “Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode”. Nature 205 (4972): 698–9. doi:10.1038/205698a0. PMID 14287410. edit
2. ^ Petsko, G. A. (2002). “A christmas carol”. Genome biology 3 (1): COMMENT1001. PMC 150444. PMID 11806819. edit
3. ^ http://visualsonline.cancer.gov/details.cfm?imageid=8173

Other posts of interest  in this site  include:

Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin

Otto Warburg, A Giant of Modern Cellular Biology

Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics