Merck halts natural products research

Bad news: Merck has decided to close down its natural product research facilities. This means the end of CIBE (Centro de Investigación Básica de España) — or Spanish Center for Biological Research — located in Madrid, Spain. Since its creation in 1954, this center has been dedicated to the discovery of new compounds of therapeutical potential produced by microbes. These efforts led to the development of several useful medicines, including antibiotics (fosfomycin, cefoxitin, thienamycin), cholesterol-lowering drugs (lovastatin), and antifungal agents (caspofungin). In May 2006, Merck researchers hit the news with the discovery of platensimycin, a natural product belonging to a new class of antibiotics.

According to Chemical & Engineering News, the high costs are behind the decision to eliminate natural products research. Merck spokesman Ian R. McConnell explains to C&EN:

"The investment involved in finding these chemicals in the environment is significant. The products that came out of our effort have been significant as well, but that was over a 50-year period"

Sad, but true. Many thousands of natural samples need to be screened in order to detect a bunch of potentially useful compounds, most of which will never become a marketed drug. Turning a promising natural product into a useful medicine takes much effort and time (over 10 years) and, hence, money. So, perhaps it is understandable that most pharmaceutical companies dedicate only a very small fraction of their resources, if any, to natural product drug discovery.

However, even with that little dedication, many medicines in the market have a natural origin, being based in substances originally isolated from plants, microbes, etc. Can we imagine the possible results of investing in natural product research as many resources as those dedicated to chemical synthesis?

Natural compounds often have bizarre, complicated chemical structures and exert their biological effects through unexpected mechanisms. They are the result of an on-going combinatorial chemistry performed by organisms since the origin of life.

Are chemists that good?



Related links

A) About job cuts at Merck:

• Merck cuts sales jobs and halts natural products research. Chemical & Engineering News (May 7, 2008).
• Merck bails on natural products. In the Pipeline (May 8, 2008).
• At Merck, some layoffs are made by PowerPoint. Pharmalot (May 8, 2008).
• Layoffs by PowerPoint? BioJobBlog (May 8, 2008).

B) About CIBE:

• Centro de Investigación Básica de España (CIBE). Merck Sharp & Dohme de España [in Spanish].
• Ten years of CIBE symposia, 1989-1998 (by Sagrario Mochales, CIBE) [pdf]. Int. Microbiol. (1998) 1, 251-254.
• Forty years of screening programmes for antibiotics (by S. Mochales). Microbiología (1994) 10, 331-342.
• Declaraciones de Fernando Peláez, director del CIBE, durante la presentación del BIO-Europe Spring (Marzo 2008) [video, in Spanish].
• Este pueblo puede salvar a España del colesterol (incluye una entrevista a Sagrario Mochales, "la científica olvidada"). ElMundo.es (16 Dic. 2007) [in Spanish].
• El tesoro de la selva tropical llega a Madrid. ElPaís.com (14 Jun. 1995) [in Spanish].

C) About natural products in drug discovery:

• Natural products to drugs: natural product-derived compounds in clinical trials. Nat. Prod. Rep. (2008) 25, 475-516.
• Natural products: chemical instruments to apprehend biological symphony. Org. Biomol. Chem. (2008) 6, 424-432.
• Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. (2007) 70, 461-477.
• New aspects of natural products in drug discovery. Trends Microbiol. (2007) 15, 279-289.
• The value of natural products to future pharmaceutical discovery. Nat. Prod. Rep. (2007) 24, 1225-1244.
• Natural product drug discovery: the times have never been better. Chem. Biol. (2007) 14, 1098-1104.
• The historical delivery of antibiotics from microbial natural products--can history repeat? (By Fernando Peláez, CIBE). Biochem. Pharmacol. (2006) 71, 981-990.
• Drug discovery from natural sources. AAPS Journal (2006) 8, E239-E253.
• Antibacterial natural products in medicinal chemistry--exodus or revival? Angew. Chem. Int. Ed. Engl. (2006) 45, 5072-5129.
• The renaissance of natural products as drug candidates. Science (2005) 310, 451-453.
• The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov. (2005) 4, 206-220.
• Rediscovering natural products. Chemical & Engineering News (Oct. 13, 2003).

Image credits:
Digital Atlas of Actinomycetes. Copyright: Society for Actinomycetes Japan. Contributor: S. Mochales. This strain produces β-lactam antibiotics, thienamycins. It has the color of cattleya orchids.

Read the rest of the article >>>

Twisted Picks 2: Science, Poverty and Medicine

This is my second edition of Twisted Picks.

First Pick: Poverty and human development

The Council of Science Editors organized a Global Theme Issue on Poverty and Human Development on October 22, 2007. More than 200 science and health journals participated:

• PLoS Journals: Poverty Collection
• Nature: Poverty and Human development
• PNAS: Poverty and Hunger Special Feature
• Full list of articles published in the journals participating in the CSE Global Theme Issue
  

Second Pick: Pharma companies and medical literature

As read in ScienceDaily, Influence of drug companies on medical literature (Sep. 28, 2007):

"Drug companies control or shape multiple steps in the research, analysis, writing, and publication of a large proportion of the medical literature, and they do so behind the scenes, according to a policy paper recently published in PLoS Medicine"

The mentioned paper is entitled Ghost management: How much of the medical literature is shaped behind the scenes by the pharmaceutical industry?, and is authored by Sergio Sismondo at PLoS Med 4(9): e286. In his own words:

"There are many reports of medical journal articles being researched and written by or on behalf of pharmaceutical companies, and then published under the name of academics who had played little role earlier in the research and writing process [2–14]. In extreme cases, drug companies pay for trials by contract research organizations (CROs), analyze the data in-house, have professionals write manuscripts, ask academics to serve as authors of those manuscripts, and pay communication companies to shepherd them through publication in the best journals. The resulting articles affect the conclusions found in the medical literature, and are used in promoting drugs to doctors"

An interesting discussion can be read in the responses to the article.



And Third Pick: Yes, it's a cruel world

A Favorite Quote of 2007 chosen by Clifford Mintz at BioJobBlog, and pronounced by Christopher Begley, chairman and chief executive of Hospira Inc.:

"Quite simply, life-saving drugs are irrelevant if they are not affordable"

Quite simply, he's right. Unfortunately.

Read the rest of the article >>>

Finding a needle in the ocean

The deep ocean may be similar to a rainforest in terms of the range of existing microbes and their genetic diversity. The resulting biochemical diversity might provide us with novel natural drugs and enzymes for cleaner industrial processes. The following clips are available for download from Out of the Blue, a DVD on marine microbes produced by Panache Productions with support from the NERC BlueMicrobe knowledge transfer network. The interviewed researchers are Alan Bull and Jem Stach, from the Universities of Kent and Newcastle (UK), respectively. For bioprospecting, the researchers use a combination of molecular techniques, bioinformatics, novel culturing strategies and screening approaches. In addition to potential pharmaceutical and biotechnological applications, these efforts will broaden our knowledge of microbial ecology and evolution (scarce knowledge, by the way).



*******************************************************
This post is a contribution to Microbial Week, a collection of posts highlighting the many roles of microbes in deep-sea or marine environments. The event is organized by Christina Kellogg and the guys at Deep-Sea News.
*******************************************************

Read the rest of the article >>>

Yondelis: from the seas to the pharmacy

Yondelis (trabectedin, ecteinascidin-743, ET-743) is an anticancer natural product isolated from a marine organism, the tunicate Ecteinascidia turbinata. The compound was initially extracted from the naturally growing and farmed tunicate, but now it's manufactured by semi-synthesis from a structurally-related metabolite produced by the bacterium Pseudomonas fluorescens. It is likely that the actual producer of Yondelis is not the tunicate itself but some unknown, symbiotic bacteria living in close relationship to the tunicate. The drug is being developed by PharmaMar, a Spanish biopharmaceutical company subsidiary of the Zeltia Group. For several years, Yondelis has being studied in clinical trials for treatment of several cancer types.

This morning, finally, good news: the European Medicines Agency has recommended Yondelis be approved by the European Comission, which means that the drug should be available to treat soft tissue sarcomas by the end of the year. I want to cite the words of José María Fernández Sousa (president of Zeltia), taken from the PharmaMar press release:

“This is excellent news. Firstly for the patients and their families, since a new therapeutic option is now available. Also for the PharmaMar and Zeltia employees who have devoted long years of effort and dedication in pursuit of this challenge. It is also excellent news for Spanish science as well as for the investigators from all over the world who have participated in the clinical trials and believed in the therapeutic potential of compounds of marine origin.”

I completely agree with him. Yondelis is the first anticancer drug developed and produced by a Spanish biopharmaceutical company. Hope more are coming.

(Image: left, a cluster of Ecteinascidia turbinata, photo courtesy of PharmaMar; right, structure of Yondelis)

Read the rest of the article >>>