Merck Research Laboratories Designated as Milestones in Microbiology Site
The American Society for Microbiology Designates
Merck Research Laboratories
as a Milestones in Microbiology site
The ASM Milestones in Microbiology program recognizes institutions and the scientists who worked there that have made significant contributions toward advancing the science of microbiology.
Roger Perlmutter, President, Merck Research Laboratories, and Susan E. Sharp, President, American Society for Microbiology (photo courtesy of Merck Creative Studios)
The Milestones in Microbiology designation is made in recognition of Merck Research Laboratories’ strong and sustained legacy of anti-infective and vaccine research, and encompasses work accomplished in both the Rahway, NJ and West Point, PA facilities.
Milestones Site Dedication Ceremony
The plaques that will mark Merck Research Laboratories (MRL) as a Milestones in Microbiology site were unveiled on October 17, 2016, in a ceremony held in conjunction with the opening of Merck's 125th Anniversary celebration. Susan Sharp, President of ASM, presented the plaque on behalf of ASM. Roger Perlmutter, President of MRL, accepted the plaque on behalf of Merck.
(L-R) Roger Perlmutter, President, Merck Research Laboratories, Susan E. Sharp, President, American Society for Microbiology, Kenneth C. Frazier, CEO, Merck & Co. (photo courtesy of Merck Creative Studios)
Historical Background and Perspective
The Milestones designation is for Merck Research Laboratories’ strong and sustained legacy of anti-infective and vaccine research, and recognizes accomplishments in both the Rahway, NJ and West Point, PA facilities.
Pioneering Breakthroughs and Contributions – Since its opening in 1903, Merck’s Rahway facility has been the location for many therapeutic breakthroughs in the anti-infective space. Notably, scientists at Rahway conducted pioneering work in the development of
- Mefoxin® (cefoxitin),
- Mectizan® (ivermectin) and
- Cancidas® (caspofungin acetate) g. as well as other life-saving products
New Way to Conduct Inquiry: Formal Collaboration Between Academia and Industry – Merck worked with Selman Waksman (Rutgers University, New Jersey) to secure one of the earliest formal collaborations between a business and a university. This early example of effective, cooperative academic and industrial collaboration is still touted today, and this partnership and later collaboration with Mayo Clinic allowed Merck scientists to show that streptomycin was the chemotherapeutic medicine found to be effective for tuberculosis.
Large Scale Production of Penicillin – While Merck cannot claim the discovery of penicillin, the company developed one of the first methods for its large scale production. Prior to Merck’s involvement, academic scientists were producing penicillin in static cultures on nutrient media. This process was laborious and yielded limited quantities of the active ingredient for therapeutic purposes. Merck scientists and engineers worked to scale up and enhance the penicillin yields from these cultures. Using pilot plants, they generated several hundred liters of penicillium culture that by March 1942 had yielded enough penicillin for the first patient, and another 10 cases were treated by June 1942. Further work involving Merck working in collaboration with other pharmaceutical companies and government agencies succeeded in advancing and refining a method of deep tank fermentation that increased yields substantially and ultimately paved the way for the mass production of penicillin.
Streptomycin – In 1939, Professor Selman A. Waksman of Rutgers University and George W. Merck, Merck ’s then CEO, secured one of the first ever formal collaborations between a business and a university to further explore the potential for isolating and characterizing antimicrobial agents derived from actinomycetes species found in soil samples. This agreement provided Waksman with support from Merck’s chemists and access to extensive animal testing resources, as well as state of the art pilot plant facilities. This early example of effective, cooperative academic and industrial collaboration is still touted today and this partnership and later collaboration with Mayo Clinic allowed Merck scientists to show that streptomycin was the first chemotherapeutic medicine found to be effective for tuberculosis.
Natural Products Screening Program – Following the success of the Waksman collaboration, Merck invested in a natural products screening program that ultimately led to the identification of several new antibiotic medicines. These capabilities, based mainly in Rahway, enabled Merck researchers to culture organisms sampled from sites all over the world which were then evaluated for antimicrobial activity. In the 1970s, following a fifteen-year effort, Merck’s screening procedure resulted in the discovery of Mefoxin® (cefoxitin). Mefoxin was an important new addition to the physician’s armamentarium due to the increasing incidence of antimicrobial resistance. Unlike cephalosporins that were originally discovered in fungi, Mefoxin® (cefoxitin) was interestingly derived from cephamycin C, which is produced by Streptomyces lactamdurans. At the time, it was recognized as a major advance over clinically available beta-lactam antibiotics.
Carbapenem Class Of Antibiotics – Primaxin® (imipenem/cilastatin) is the first member of the carbapenem class of antibiotics, which continues to be prescribed extensively in the U.S. and across the world. Carbapenems were an important discovery, as they are generally less susceptible to common mechanisms of antibiotic resistance than other beta-lactam molecules. The development of Primaxin® even today is considered one of the most arduous research efforts in Merck’s history to date. Screening of bacterial cultures identified a molecule, thienamycin, that had potent antibiotic properties. Unfortunately thienomycin was highly unstable. In 1974, the research teams at Rahway produced a sample pure enough to be chemically analyzed. This allowed the company’s chemists to develop and synthesize a stable derivative with similar antibiotic properties known as imipenem. Further experiments found that imipenem activity could be improved if it was administered with the dehydropeptidase inhibitor, cilastatin. The commercial manufacturing process for imipenem involved 16 defined steps at four locations, finishing in Rahway. The process was the first in Merck’s history and the most complex total chemical synthesis the industry had known.
River Blindness / Nobel Prize – Mectizan® (ivermectin): Research, performed predominantly in Rahway, led to the discovery and development of Mectizan® (ivermectin) for the treatment of onchocerciasis (also known as river blindness). River blindness is a parasitic infection by a parasitic worm Onchocerca volvulus that can cause intense itching, skin discoloration, rashes, and eye disease that can lead to permanent blindness. It is spread by the bites of infected black flies that breed in rapidly flowing rivers in the affected countries. The development of ivermectin coupled with Merck’s commitment to donate it worldwide (over 1 billion people treated to date), has led to the elimination of river blindness in several countries and significantly reduced the prevalence of this affliction worldwide by breaking the lifecycle of the causative parasite.
William C. Campbell, a retired Merck scientist who worked in Rahway, shared the 2015 Nobel Prize winner in Physiology or Medicine for the discovery of avermectin, which led to the development of Mectizan® (ivermectin).
Treatment for Fungal Infections – Cancidas® (caspofungin acetate): A 15-year process led Merck scientists to develop the first in class echinocandin antifungal agent, Cancidas® (caspofungin). Caspofungin is a semisynthetic derivative of pneumocandin B0, a naturally occurring molecule isolated from the fungus Glarea lozoyensis. Caspofungin is used today to treat opportunistic fungal infections of the genera Candida, Aspergillus, and Cryptococcus, particularly in patients who are immunocompromised. This medicine provided an important new option for patients, and by 2006, caspofungin had become the number one intravenous antifungal medicine worldwide.
WEST POINT FACILITY:
Vaccines – Merck’s West Point facility has been the location for pioneering work leading to the development of prophylactic vaccines for the protection of measles, mumps, rubella, hepatitis A, hepatitis B, pneumococcal disease and Human Papilloma Virus. In 1956, Maurice R. Hilleman became the director of virus and cell biology research at the Merck Institute, West Point, Pennsylvania. During his tenure, Hilleman and his team developed vaccines to prevent measles, mumps, hepatitis A, hepatitis B, meningitis, pneumonia, Haemophilus influenza bacteria and rubella. Notably, he cultivated mumps from a swab taken from his own daughter’s throat, using the culture as the basis of what became known as the Jeryl Lynn strain vaccine. Hilleman also succeeded in isolating and culturing other viruses, including the hepatitis A vaccine in culture. Additionally, Hilleman and his team developed a vaccine for hepatitis B by treating blood serum with pepsin, urea and formaldehyde; however, there were concerns about the purity of this vaccine during the HIV/AIDS epidemic. To address these concerns, Hilleman and his team developed an alternate hepatitis B vaccine using recombinant DNA technology. This was the first recombinant vaccine to be approved for widespread use. Today, Hilleman is recognized as one of the most influential contributors to modern day vaccinology.
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CHOMA Symposium 2016
Title: Foundations to Frontiers: The Molecular Revolution
Date: Sunday, June 19, 2016
Time: 2:45 pm – 5:15 pm
Location: Westin Boston Waterfront Hotel; Grand Ballroom B
Conveners: Joan W. Bennett; Rutgers, The State University of New Jersey
Lin-Jun MA; University of Massachusetts, Amherst
Every branch of the microbial sciences and clinical medicine has been transformed by our ability to exploit scientific insights into the molecular workings of life. This section will invite FIVE distinguished scientists who have made significant contributions to recent biology, including molecular cloning, DNA sequencing, and gene editing. Hearing stories from these scientists directly regarding why they chose their career paths, how they made their discoveries, and what they think about the economic, ethical and social implications of their research, will be extremely valuable for the next generation microbiologists.
- The Ignition of BLAST
- Stephen Altschul; NIH, Bethesda, MD
- From the Lac Operon to Science and Social Justice Teaching
- Jonathan Beckwith; Harvard University Medical School, Boston, MA
- Microbial Genomics: The Early Years
- Claire M. Fraser; University of Maryland, Baltimore, MD
- Origins of Genomics and Semi-synthetic Genes
- Joachim Messing; Rutgers, The State University of New Jersey, Piscataway, NJ
- Following Carl Woese into the Natural Microbial World: The Beginnings of Metagenomics
- Norman R. Pace; University of Colorado, Boulder, CO
History of Microbiology at ASM Microbe 2016
The Center for the History of Microbiology/ASM Archives (CHOMA) Committee is pleased to announce its schedule of ASM MICROBE 2016 meeting events:
- History of Microbiology Lecture: Alexander Fleming and the Beginnings of Biofilm Research
- Symposium: Foundations to Frontiers: The Molecular Revolution
- CHOMA History Exhibit: Two-part Exhibit: Significant Events in Microbiology and the Founding of Journal of Bacteriology, 1916
Annual History of Microbiology Lecture 2016
Annual History of Microbiology Lecture
Title: Alexander Fleming and the Beginnings of Biofilm Research
Lecturer: Michael J. Hanophy
St. Joseph's College, Brooklyn, NY
Date: Saturday, June 18, 2016
Time: 2:45 pm – 3:45 pm
Location: Boston Convention & Exhibition Center (BCEC); Meeting Room 257A
Conveners: James A. Poupard; Chair, Center for the History of Microbiology/ASM Archives
Douglas E. Eveleigh; Rutgers, The State University of New Jersey
The 2016 History of Microbiology Lecture discusses the early work of Alexander Fleming on wound infections and what we would now call biofilm research. The history of bacteriology had been, in many ways, a history of the study of pure culture until significant research into the area of biofilms began in earnest in the 1990s. However, although the term “biofilm” did not appear in a publication until as late as 1977, the study of microbial communities attached to surfaces goes back to the earliest days of microbiology. Van Leeuwenhoek himself noted the abundance and diversity of microbes in dental plaque, while research in the 1940s by Heukelekian and Heller was among the first studies to note real differences between growth in a film and planktonic growth. Some of the earliest work on biofilms, particularly medically significant biofilms, was actually carried out by a young Alexander Fleming, long before his Nobel prize-winning work on penicillin. A review of the literature shows that Fleming authored or co-authored ten papers between 1914 and 1920 specifically on the mechanisms and treatment of infection. Among these papers are studies of the mixed flora found on soldiers’ uniforms and in different types of wounds and reports on innovative techniques that Fleming developed that allowed him to study biofilm populations. As a result of this work, Alexander Fleming was among the first to extensively characterize the diverse populations in biofilms and to recognize that organisms in a biofilm are often much more resistant to antimicrobial compounds than organisms growing planktonically. The Annual History of Microbiology Lecture is sponsored each year by the Center for the History of Microbiology/ASM Archives (CHOMA) to present topics in the history of microbiology and show how they have impacted and continue to influence the field of microbiology. The Lectures demonstrate that history is a critical factor for understanding the current and future directions of the science.
ASM MICROBE 2016
June 16-20, 2016
History Exhibit 2016
History of Microbiology Exhibit - Two-part Exhibit: Significant Events in Microbiology and the Founding of Journal of Bacteriology, 1916
Visit the History of Microbiology Exhibit to view images and documents from the Center for the History of Microbiology/ASM Archives collection and interact with the ASM Archivist!
Location: Boston Convention and Exhibition Center, Level 1 Northwest Lobby A
ASM MICROBE 2016
June 16-20, 2016