C U LT U R E S | V O LU M E 2 | I S S U E 2 | 2 0 1 5
AMERICAN SOCIETY FOR MICROBIOLOGY
1752 N Street NW, Washington, DC 20036 www.asm.org/cultures | cultures@asmusa.org
A PUBLICATION OF ASM | VOL 2 | ISSUE 2 | 2015
HAPPENING NOW
FOUNDATIONS OF MICROBIOLOGY
IN CONVERSATION
Erin Dolan P. XX
Steven Specter P. XX
Ellen Jo Baron P. XX
2
2
FROM YESTERDAY’S FOUNDATIONS TO TODAY’S FRONTIERS, WHERE IS MICROBIOLOGY GOING?
Page 1 » Across the Divide » XXX
CULTURES Staff
Board of Advisors UNITED STATES
BRUCE
Alberts
JASON Rao MONGOLIA
TULGAA
Khosbayar
KATY Stewart
EGYPT
ENAS
Newire
UNITED STATES
PETER Geoghan
SANJANA
Patel
PORTUGAL
DIOGO
Proenรงa
JENNA Jablonski For interactive features and more content, read Cultures on your browser, tablet, or phone. Visit asm.org/cultures
PARAGUAY
LAURA
Acevedo Ugarriza
UNITED STATES
VAUGHAN
Turekian
UNITED STATES
NATHAN
Wolfe
In this Issue LETTER FROM THE EDITOR
4
HAPPENING NOW
10
Cultures interviews Erin Dolan
ACROSS THE DIVIDE Foundations of Microbiology: Our Legacy and Gateway to New Frontiers
18
Steven Specter
26
The Rise of Cultures Bob Tupper
The Cutting Edges of Contemporary Diagnostics
34
Joseph Campos
Measles and Rubella Elimination: Why Now?
42
Jon Kim Andrus & Louis Z. Cooper
Tackling Antibiotic Resistance: What Do We Know and What Do We Need to Know?
50
Ramanan Laxminarayan
58
IN CONVERSATION Cultures interviews Ellen Jo Baron
ON THE GROUND
66
Emerging careers in microbial science
QUESTIONS, COMMENTS, & CORRECTIONS PHOTOGRAPHY CREDIT ON PAGES 82 - 83
Page 3
80
BY JASON RAO + TIM DONOHUE
In this issue we reflect upon the foundational discoveries as well as the emerging frontiers of the microbial sciences. This is timely. The ASM, made up of individuals that span both the field and the earth, is actively reflecting upon its origins, its accolades, its challenges, and its future. Driven by its core mission to promote and advance the microbial sciences, each of us is drawn to the Society, for the benefit of all. Whether in Louisiana, Sanaa, San Juan, Karachi, or Abuja, ASM members share a passion for discovery, for advancement, and for education, through science. Much has changed since the ASM formed more than 100 years ago, and with these changes come challenges and opportunities. Once formed to facilitate meetings, share discoveries, and strengthen the voice of the individual, professional societies remain a powerful platform to do so, and much more. Technology has changed the way we communicate with each other, has changed the way we meet with one another, and, in many ways, has made the world a much smaller place, changing the pace of science and our lives tremendously. In turn, the ASM has grown to over 40,000 members, with a respected voice in public policy. ASM is an advocate for discovery research, a home for clinical science, a respected expert for educational programming, a networker with various industries, and an umbrella for global partnerships with members in 160+ countries. This is not a destination, but a new beginning for an even more remarkable future journey. Page 4
Currently, representatives from across the ASM are convening as part of a Futures Project to think about its future, and put in place the framework to not only continue our tradition of excellence, but also to realize the aspirations of its members to truly advance microbial sciences for the improvement of all in a new era of science. The science itself is changing at an unprecedented rate, with microbes on the front lines of meeting the greatest challenges we share in energy, environment, health, food, and even security. As such, new career paths are forming every day for microbial scientists, on and off the bench. From public policy to science communication, to global health and development, the ASM’s microscope peers into a flourishing world of professional practice with no end to its potential. Young people in every corner of the globe are coming to the ASM to advance their science, their career, and their society. In turn, the Society will benefit from them. In this way, every member must not only ask what the ASM is doing for them, but also what they are doing for the ASM.
FROM LEFT TO RIGHT /
Tim Donohue (ASM President), Nancy Sansalone (ASM’s Interim Executive Director), Jason Rao (Director for International Affairs).
We invite you to read the latest about the ASM Futures Project by looking at http://www.asm.org/index.php/futures. There will be additional opportunities to hear about the ASM Futures Project at asm2015 in New Orleans. See you there! Send us questions and input about ASM’s future by email: asmfuture@asmusa.org.
SNAPSHOT OF CULTURES
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Visit www.asm.org/cultures for additional content and interactive features! CULTURES Vol Page 2, Issue 5 1 » Page 5
MICROBIOLOGY + IMMUNOLOGY NOBEL L AUREATES
“Today’s scientists at the frontier of microbiology stand on the shoulders of generations of giants, both well-known and more obscure. While the evolution of microbiology has spanned about 1,000 years, progress over the past 150 years has been astounding.” – DR. STEVEN SPECTER R E A D M O R E O N PA G E 18
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MICROBIOLOGY MILESTONES
1939
PRESENTED BY DATE AWARDED THE NOBEL PRIZE
1901
GERHARD DOMAGK
Discovered first commercial antibiotic, Prontosil
1945
EMIL ADOLF VON BEHRING
Developed serum therapies for diphtheria
SIR ALEXANDER FLEMING + ERNST BORIS CHAIN + HOWARD WALTER FLOREY
Discovered penicillin
1902
SIR RONALD ROSS
Discovered malaria vector
1951 1905
1907
ROBERT KOCH
Discovered infectivity of tuberculosis
1952
CHARLES LOUIS ALPHONSE LAVERAN
SELMAN ABRAHAM WAKSMAN
Discovered streptomycin, first antibiotic against tuberculosis
Connected protozoa with disease
1908
1958
ILYA ILYICH MECHNIKOV + PAUL EHRLICH
1958 JULES BORDET
Discovered key principles of immunity
1960 1928
1930
JOHN FRANKLIN ENDERS + FREDRICK CHAPMAN ROBBINS + THOMAS HUCKLE WELLER
Cultivated polio virus in a test tube
Established foundation for the science of immunology
1919
MAX THEILER
Developed vaccine against yellow fever
CHARLES JULES HENRI NICOLLE
JOSHUA LEDERBERG
Discovered that bacteria can mate and exchange genes
SIR FRANK MACFARLANE BURNET + SIR PETER BRIAN MEDAWAR
Predicted acquired immune tolerance
Discovered transmission method of typhus
1965
KARL LANDSTEINER
FRANÇOIS JACOB + ANDRÉ LWOFF + JACQUES MONOD
Discovered bacteriophage infectivity mechanisms
Discovered blood group antigens
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1966
1969
PEYTON ROUS
Discovered tumorinducing viruses
1984 NIELS K. JERNE + GEORGES J.F. KÖHLER + CÉSAR MILSTEIN
Developed key theories on the immune system & discovered monoclonal antibodies
MAX DELBRÜCK + ALFRED D. HERSHEY + SALVADOR E. LURIA
Discovered the replication mechanism and genetic structure of viruses
1987
1972 GERALD M. EDELMAN + RODNEY R. PORTER
SUSUMU TONEGAWA
Discovered mechanism that produces antibody diversity
Discovered the chemical structure of antibodies
1988 1975
GERTRUDE B. ELION + GEORGE H. HITCHINGS + SIR JAMES W. BLACK
DAVID BALTIMORE + RENATO DULBECCO + HOWARD MARTIN TEMIN
Discovered important principles for drug treatment, including chemotherapy
Discovered reverse transcriptase and interaction between tumor viruses and genetic material of cell
1976
BARUCH SAMUEL “BARRY” BLUMBERG + DANIEL CARLETON GAJDUSEK
1989
Identified and invented vaccine for Hepatitis B showed Kuru is trans missible to chimpanzees, first human prion disease
Discovered first human oncogenes and retroviral oncogenes
1990 1977
1980
J. MICHAEL BISHOP + HAROLD E. VARMUS
JOSEPH E. MURRAY + E. DONNALL THOMAS
Developed cell and organ transplantation
ROSALYN YALOW
Developed the radioimmunoassay (RIA) technique
1993
BARUJ BENACERRAF + JEAN DAUSSET + GEORGE D. SNELL
KARY B. MULLIS
Invented polymerase chain reaction
Discovered major histocompatibility complex genes, immunogenetics
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1996
PETER C. DOHERTY + ROLF M. ZINKERNAGEL
Discovered cellmediated immune defense mechanisms
“The frontiers
1997
that we face
STANLEY B. PRUSINER
Discovered prions, a new biological principle of infection
will likely be transcended using these foundational
2005
BARRY J. MARSHALL + J. ROBIN WARREN
Discovered link between Helicobacter pylori and stomach ulcers
discoveries that have served us well for centuries,
2008 HARALD ZUR HAUSEN + FRANÇOISE BARRÉ-SINOUSSI + LUC MONTAGNIER
Discovered HIV
decades, or only a few years. These frontiers will be
2011
the foundation
BRUCE A, BEUTLER AND JULES A. HOFFMANN
for future
Discovered innate immunity activation
2011
generations.”
RALPH M. STEINMAN
Discovered dendritic cells in adaptive immunity
T O D AY Page 9
– DR. STEVEN SPECTER R E A D M O R E O N PA G E 18
H A P P E N I N G N O W:
E R I N
DO L A N
The Texas Institute for Discovery Education in Science (TIDES) in the College of Natural Sciences (CNS) aims to catalyze, support, and showcase innovative, evidence-based undergraduate science education. TIDES was proposed in the CNS 2013 Strategic Plan (as the Texas Center for Science Discovery) as a way to continue and enhance the college’s leading role in Science, Technology, Engineering, and Mathematics (STEM) education.
CULTURES: How does the Texas Institute for Discovery Education in Science (TIDES) prepare young scientists for life after their studies in ways that traditional programs do not? Why is this important? DR. DOL AN: TIDES has extraordinary potential to change what undergraduate STEM education looks like. One program housed under TIDES, the Freshman Research Initiative (FRI), is actually what attracted me to the position of director of TIDES. FRI is a program I have been
watching for about a decade since it was launched. The program is revolutionary because it engages freshmen, from their very first semester on campus, in doing research connected to a faculty member’s ongoing work, and they earn credit for courses that are required for their major. So, instead of, for example, doing your standard introductory biology course or your standard introductory chemistry course, you can do your research in chemistry or biology and earn that introductory laboratory credit. It is life
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changing, because the students get to see what science really is, and how science is really done. CULTURES: How do you create novel teaching methods and experimental programs like TIDES? DR. DOL AN: We have to balance novelty with what we know is effective. As a new program, the most important thing for TIDES is figuring out what is already working. What assets are available? I spent a lot of my first 6 to 9 months on campus answering these questions. But to make experimental programs and novel teaching methods more possible in the future, there must be a level of creativity and flexibility involved. Let me tell you, people are working really creatively, and they work with extraordinary energy and enthusiasm. Instead of saying, “No, that cannot count for introductory lab credit; introductory lab needs to address X, Y, and Z,” people said, “How can we make this count for credit? How can we integrate this into the curriculum?” Sometimes we have to use things that we already know work, and sometimes we have to innovate. CULTURES: What impacts are you seeing from undergraduates taking an increased role in research at UT Austin, and how can this be applied to other universities and institutions?
DR. DOL AN: Data show that we are having a positive effect on graduation rate, that we are having a positive effect on the number of science majors, and that we are having a positive effect on the number of students that are graduating in general, for both science and nonscience majors. But what is CHECK OUT less easy to CNS.UTEXAS.EDU/TIDES measure is TO LEARN MORE the change in ABOUT TIDES AND culture. The THEIR PROGRAMS University of Texas is embracing an intertwining of research and teaching. As a result, students are empowered to contribute to what is happening at the university. They are not just the consumers; they are collaborators, as well. They are actively involved in the work that is happening at the university. In broader terms, for example, we have engineering students, or students in the geosciences, which is actually a different organizational unit than where TIDES is housed, who are getting faculty to explore starting similar programs in their units. Students are feeling really empowered. In more concrete terms, we have students who are authors of publications on a range of topics in high-profile journals. For example, alumni from our FRI program co authored a major publication in genetics recently.
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CULTURES: Your work at UT Austin focuses heavily on STEM education at the undergraduate level and beyond. To ensure that students are better prepared when they set foot on the UT campus, what are some lessons that you would like to share with educators working in K-12?
field. We also reach out to high school students to engage them in research, because that is where I think our strength lies and something unique we can offer to K-12 schools. It is important to think of it as collaborative relationship that enables us to build off each other’s strengths.
DR. DOL AN: I worked a lot in K-12 before transitioning to undergraduate science education, and I know that the kneejerk reaction is to think of K-12 and university relations as a one-way street, with K-12 learning from what higher education has to offer. We are really viewing this as a two-way conversation; we can learn just as much from our K-12 partners as they can learn from us.
CULTURES: Are there any specific techniques and teaching methods that you would like to see incorporated in all levels of education across the United States?
VISIT US AT
We already have some TO ACCESS THE avenues AUDIO INTERVIEW through WITH ERIN DOL AN which we are engaging K-12 AND OTHER BONUS students and CONTENT. teachers. For example, the UTeach program in our College of Natural Sciences prepares STEM majors to be secondary STEM teachers, and supports them when they go into the
ASM.ORG/CULTURES
DR. DOL AN: I gave up looking for that silver bullet a few years ago. There are a range of approaches that need to be used because we have a range of learners; learners come from different backgrounds, capabilities, experience, and interests. And we have a range of people who teach. What might work for one instructor, might not work for another. Everyone brings their own unique experiences to the table, and that needs to be considered. One thing that we need to emphasize is Carol Dweck’s “growth mindset,” which says that everyone can get better with practice and feedback – and that includes students and instructors, whether it is students learning science or instructors changing their teaching.
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Page CULTURES 13 » Across Vol 2, Issue the Divide 2 » Page » XXX 13
CULTURES: In 2012 the Program for International Student Assessment (PISA) reported that several Asian countries dominate the top three and top six scores in science and mathematics testing. This has been known in the U.S. for a long time, and it is something that we have tried to compete with. What approaches do you think that these countries, specifically China, are taking that are placing them at the forefront of STEM education, and what can we learn from what they are doing? DR. DOL AN: That is a tough question. To me, it is not about teaching approaches – it is about culture. The countries that are really at the top of the PISAs, or just STEM scores, place emphasis on academics and education. Culturally, education and teaching are highly valued by those communities. Being a principal, being a teacher, or being a professor is a highly valued position in those societies. It is also considered important that students spend time doing their schoolwork, and I think that that
value is rare in the other parts of the world. I do not think there is an easy answer of how to replicate that elsewhere; I think it is a cultural issue that we are going to have to grapple with. CULTURES: What advice would you give young students looking to pursue a career in science?
“THAT IS WHAT SCIENCE IS: BEING CURIOUS AND ASKING GOOD QUESTIONS. SO, I ALWAYS ENCOURAGE STUDENTS AT ALL LEVELS – PEOPLE AT ALL LEVELS – TO JUST BE CURIOUS AND ASK GOOD QUESTIONS.” – ERIN DOLAN, PH.D.
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DR. DOL AN: Again, there is no one silver bullet, but I recall a Nobel Laureate, Isidor Isaac Rabi, who discovered nuclear magnetic resonance, and he explains the reason he became a scientist was because his mother would not ask him when he got home from school, “What did
you learn in school today?” She would ask him “Did you ask any good questions?” And I would say that that is what science is: being curious and asking good questions. So, I always encourage students at all levels – people at all levels – to just be curious and ask good questions.
ERIN DOL AN, PH.D. EXECUTIVE DIRECTOR, TIDES AT UT AUSTIN Erin Dolan earned a B.A. in Biology at Wellesley College and a Ph.D. in Neuroscience at the University of California at San Francisco. She has held tenure-track and tenured faculty positions at Virginia Tech and the University of Georgia, where she also held the position of Senior Scholar in Biology Education. Dolan is the founding director of the Texas Institute for Discovery Education in Sciences (TIDES; https://cns.utexas. edu/tides) in the College of Natural Sciences at The University of Texas at Austin. Her research group studies scalable ways of engaging high school and undergraduate students in science research, mentoring of undergraduate researchers, and research as a mechanism for undergraduates to gain access to social capital within the scientific community, especially for students from backgrounds that are underrepresented in the sciences. She is Principal Investigator of the Course-based Undergraduate Research Experiences Network (CUREnet: http://curenet.cns.utexas.edu/), and Editor-in-Chief of the biology education journal, CBE – Life Sciences Education (http://www.lifescied.org/).
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Microbial science relies heavily on the innovative discoveries and remarkable inventions of yesterday. Though there is much left to uncover, we are only able to understand where we are and where we will go by knowing what got us here.
In this section, we bridge the gaps between foundations and frontiers.
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STEVEN SPECTER | PAGE 18 FOUNDATIONS OF MICROBIOLOGY
Dr. Specter of the University of Florida chronicles microbiology’s key discoveries and advancements over the past 150 years, and how they have directed the evolution of the discipline.
BOB TUPPER | PAGE 26 THE HISTORY OF BEER MAKING
Brewing beer is one of the oldest applications of microbiology in human history. The inventor of Tuppers’ Hop Pocket Ale explains the history of beer making, from its ancient roots to the present day.
JOE CAMPOS | PAGE 34 CUTTING EDGE DIAGNOSTICS
A recent explosion of new technology has transformed clinical microbiology. The Director of the Microbiology Laboratory at Children’s National Medical Center takes readers on a journey along the cutting edge of molecular diagnostics.
JON ANDRUS + LOUIS COOPER | PAGE 42 THE FUTURE OF MEASLES & RUBELLA
The Executive Vice President of Sabin Vaccine Institute and the founder of the Rubella Project join forces to examine current vaccine use and share what can be done to eradicate preventable diseases once and for all.
RAMANAN L AXMINARAYAN | PAGE 50 FRONTIERS OF ANTIMICROBIAL RESISTANCE
Economist Ramanan Laxminarayan addresses the danger of antimicrobial resistance and the unknowns that make it such a complex problem.
CULTURES Vol Page 2, Issue 17 2 » Page 17
FOUNDATIONS OF MICROBIOLOGY:
OUR LEGACY AND GATEWAY TO NEW FRONTIERS
STEVEN SPECTER, PH.D.
Page 18 » Across the Divide » Specter
The foundations of microbiology include the study of microbes and our host responses (immunology) to microorganisms. This base was developed by renowned physicians and scientists, as well as by less well recognized individuals, as their contributions were smaller but equally important in advancing microbiology (See page 6 for timeline of noted scientists). Today’s scientists at the frontier of microbiology stand on the shoulders of generations of giants both well-known and more obscure. Some examples of the contributions that established microbiology and immunology as vital disciplines follow. The development of understanding of our immune system, the recognition of microbes as the causes of disease, the methods to detect them, the advent of best practices for sanitation, as well as vaccine and antimicrobial drug discovery form these foundations. While the evolution of microbiology has spanned about 1,000 years, progress over the past 150 years has been astounding. Thus, we stand at the frontier of greater things to evolve based on the principles that are now firmly established. Many of the foundational events are presented at http://micro.digitalproteus.com/history3.php and http://www.microbeworld.org/ history-of-microbiology.
CULTURES Vol Page 2, Issue 19 2 Âť Page 19
CASE STUDY A
SANITATION, DISINFECTION, + ANTISEPSIS Recognition that sanitation was important for public health and the control of disease can be traced to the Babylonians, who established a relationship between contaminated water and disease approximately 7,000 years ago. The Egyptians, Greeks, and Romans all understood this principle, yet organized efforts to keep cities clean did not begin until the 1790s. Following an epidemic of yellow fever in 1793, in Philadelphia, PA, the Select and Common Councils of Philadelphia established a health department and, in 1801, established the first municipal water system in a major American city. However, it was not until the work of Pasteur, establishing the microbial relationship to disease, that efforts became systematic to install water treatment and waste disposal systems broadly. Sanitation efforts have been more effective than vaccines and Louis Pasteur antimicrobial drugs in limiting disease. This is most evident in Syria where poor sanitation due to civil war has led to a rise in diseases such as cholera and polio. Ignaz Semmelweis (1818–1865) introduced the concept of antisepsis in 1847 related to puerperal sepsis, but this predated the work of Pasteur and conflicted with established practice. Despite reducing mortality to <1% in delivery wards, his work was derided. It was not until Oliver Wendell Holmes, Sr. published his treatise on this topic in 1885 that antisepsis was accepted. The successful adoption of disinfection techniques can be traced to Joseph Lister (1827–1912), who pioneered antiseptic surgery in 1865 following the establishment of the germ theory of disease, leading to decreases in morbidity and mortality postsurgery.
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CASE STUDY B
IMMUNIT Y + IMMUNIZATION Immunization was first established by ancients who did not possess a scientific understanding of their practices but recognized the benefit of treatment and, in a crude form, established the intersection of microbiology and immunology. The Chinese, in about 1,000 A.D., introduced the practice of placing pus from smallpox lesions of mild cases under the skin to protect against life-threatening disease, a practice later known as variolization. This practice spread to Turkey by the early 1700s, where Lady Montagu first learned of it and brought it back to England. Subsequently, in 1798, the English physician Edward Jenner (1749–1823) actively immunized against smallpox by using cowpox, establishing the first principles of modern vaccination. While he did not understand the microbiological or immunological principles underlying the disease, this initial use of vaccination demonstrates the integral relationship between microbiology and immunology and explains why their foundations are intertwined. The active pursuit of vaccine development is attributed to Louis Pasteur (1822–1895), who developed the first vaccine through the attenuation of chicken cholera and then for humans by inactivation and inoculation of rabies virus. Many diseases have subsequently been controlled or eliminated through immunization programs. Yet, many diseases remain uncontrolled, and the frontiers of microbiology have many challenges yet to unravel regarding prophylaxis.
CULTURES Vol Page 2, Issue 21 2 » Page 21
CASE STUDY C
MICROSCOPY + THE DISCOVERY OF MICROBES The compound microscope was developed by Dutch inventors in about 1595, enabling the search for microbes. The value of this tool was established when Robert Hook (1635–1703) in 1665 first described cells, then Anton van Leeuwenhoek (1632–1723) in 1674 published a description of microorganisms, and in 1685 he demonstrated animalcules (bacteria) in dental plaque. Much later, the discovery of the electron microscope (Max Knoll and Ruska, 1931) and the fluorescence microscope (Marvin Minsky, 1957) permitted the identification of smaller bacteria and viruses, expanding greatly our recognition of microbes. Ferdinand J. Cohn (1828–1898) was the first to publish a classification of bacteria in 1875, firmly establishing the science of microbiology. However, no one advanced microbiology as Louis Pasteur did, renowned as the “Father of Microbiology” for a series of accomplishments in the latter half of the 19th century that definitively moved microbiology toward the modern era. He disproved the notion of spontaneous generation, firmly established the germ theory of disease, developed the first immunizations, coined the term virus, and developed a process, pasteurization, to protect milk and other liquids, notably wine, from spoiling because of microbial contamination. Robert Koch (1843–1910) was another giant, who made several seminal contributions to the development of microbiology. He determined that Mycobacterium tuberculosis was the cause of tuberculosis and contributed to our understanding of more than a dozen other human and animal diseases. His most notable Robert Koch impact on microbiology was through the development of Koch’s postulates, four principles that were required to definitively identify the etiologic agent of a disease. These have guided the determination of disease etiology for more than a century; although, with the sophisticated tools of today, we can now identify etiology without fulfilling Koch’s postulates.
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CASE STUDY D
ANTIMICROBIAL AGENTS Paul Ehrlich (1854–1915) first reported a successful treatment for syphilis in 1912, thus opening the field of antimicrobial chemotherapy. This ultimately led to the discovery of penicillin by Sir Alexander Fleming (1881–1955) in 1928 and the ability to commercialize the first antibiotic through the efforts of Howard Florey (1898–1968) and Ernst Alexander Fleming Chain (1906–1979) during World War II. It is often noted that the war spurred this work as more soldiers died of infection that followed gunshots and other injuries. While the commercialization of penicillin opened an entirely new field, the work of Selman Waksman (1888–1973) and colleagues really propelled antibiotics forward, because they were the first to purposefully seek out new microorganisms that could secrete antibiotics. They succeeded in 1944 in discovering streptomycin. Since then, antimicrobial drugs have proliferated with the advent of numerous antimicrobial drugs. Antiparasitic drugs have been around longer, because quinine as an antimalarial has been used since the 17th century. Modern antiparasitic drugs can be traced to the 1940s and the introduction of chloroquine for treatment of malaria. The antifungal drug Amphotericin B was introduced in 1956 and several classes of antifungals have followed. The first antiviral drug, acyclovir, was discovered in 1974, by Gertrude Elion (1918–1999) for treatment of herpes viruses, and this discovery opened a field that now has had a highly significant impact with the proliferation of antiviral drugs to treat the human immunodeficiency virus. Concerns about antimicrobial resistance have compelled a search for newer drugs and ways to prevent or treat diseases with microbial etiologies. This is a frontier that needs to push beyond the boundaries of our current scientific knowledge.
CULTURES Vol Page 2, Issue 23 2 » Page 23
CASE STUDY E
DIAGNOSTICS Diagnostic methods for the isolation and identification of microbes beyond microscopy is not an ancient art. The late 19th century saw the introduction of culture techniques for bacteria. Joseph Lister in 1878 reported on a method to isolate a pure bacterial culture from milk, and Martinus Beijerinck (1851–1931) discovered an enrichment medium that allowed for the culture of bacteria in 1898. Ten years later, he discovered viruses by demonstrating that filterable agents Louis Pasteur experimenting (viruses) were responsible for the disease in his laboratory of tobacco leaves and established a method to separate viruses from larger microorganisms, showing that they were not soluble substances and could transmit infections because they could reproduce when transmitted to a new host. John Enders (1897–1985), Thomas Weller (1915–2008), and Frederick Robbins (1916–2003) developed a technique to culture poliovirus in 1949, which ultimately led to the attenuated polio vaccine and a tool that others applied to the isolation of other viruses. Georges J. F. Köhler (1946–1995) and César Milstein (1927–2002) in 1975 reported their discovery of hybridomas, cells that produced monoclonal antibodies, which became valuable tools for diagnostics and therapeutics. Molecular biology has led the most recent advances. In 1986, Kary Mullis (1944–) established the polymerase chain reaction, which allowed for rapid, highly specific identification of DNA sequences and greatly expanded our ability for rapid, accurate diagnosis. The most recent breakthrough is the sequencing of genomes. The first bacterium sequenced was Haemophilus influenzae, which was accomplished by J. Craig Ventner (1946–) and colleagues, leading to sequencing the entire human genome.
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SUMMARY
The field of genomics is considered the forefront of science and we can expect geometric growth in our understanding and control of microbes using the current tools and others under development. The frontiers that we face will likely be transcended using these foundational discoveries that have served us well for centuries, decades, or only a few years. These frontiers will be the foundation for future generations.
STEVEN SPECTER, PH.D. Dr. Steven Specter is Professor, Department of Molecular Medicine, and the Associate Dean for Alumni Relations at the University of South Florida College of Medicine. Dr. Specter received a B.A. in Biology (1969) and a Ph.D. in Microbiology and Immunology (1975) from Temple University, Philadelphia, PA. He was a Postdoctoral fellow at the Albert Einstein Medical Center, Philadelphia, in Experimental Immunology, and Director of Clinical Virology at the same institution (1976–1979). Dr. Specter became Assistant Professor of Medical Microbiology and Immunology at the University of South Florida Morsani College of Medicine (USF MCOM), Tampa, FL, 1979, and Professor in 1991. He was Associate Dean for Pre-Clinical Education (1998–2001), Associate Dean for Student Affairs (2001– 2014), and Associate Dean for Alumni Relations (2014–present) at the USF MCOM. He has written more than 175 publications and has edited a dozen books. He is Chairman – Clinical Virology Symposium (1985–present). He has received 2 outstanding teaching awards (1991, 1996), the Theodore and Vanette Askonas-Ashford Distinguished Scholar Award by USF (1997), Professorial Excellence Program Award (1998), and the PASCV Diagnostic Virology Award (2004). Dr. Specter was Chair, American Society for Microbiology Laboratory Capacity Building Committee (2005–2014) and is Chair, ASM International Board (2014–presesnt).
CULTURES Vol Page 2, Issue 25 2 » Page 25
THE RISE OF CULTURES BOB TUPPER
When we chose the title for our first book, Drinking In the Culture, we intended the double entendre of absorbing a social atmosphere while quaffing beer. In fact, we’re realizing that it’s a triple entendre. The myriad yeasts and bacteria that have shaped beer for millennia have also played an integral part in shaping the histories of most of the world’s societies. While we focus on Western brewing culture in this article, it’s worth remembering that indigenous brews are common on all the world’s populated continents.
CULTURES Vol Page 2, Issue 27 2 » Page 27
No one knows how the first beer happened. Someone may have left some grains out in the rain long enough for natural microorganisms to take a turn. Modern palates would cringe at what probably resulted, but to the person curious enough to take that first swig, it must have been nothing short of miraculous. We do know that there is a very good chance that civilization itself began because of beer. Wild grains weren’t that hard to find for huntergatherers, but the rich grains for brewing beer needed tending. People stopped wandering and started farming. Agriculture, and the food surpluses it produced, allowed people to move beyond subsistence living and become teachers, policemen, carpenters, artists, scientists... and brewers. In short, those cultures brought about culture.
The iconic Berliner Weisse, an astringently tart beer brewed from barley malt and wheat using a blend of traditional German Weizen beer yeast and Lactobacillus. Low alcohol and refreshing, it is traditionally served “mit Schüss,” with woodruff (green) or raspberry flavored sugar syrup.
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The earliest recipes for beer date to 4300 BCE. Ancient societies used beer for payment, as medicine, and for ritual purposes – as one could argue we still do. Brewing was traditionally part of the regular household tasks, like baking. At least as early as the Vikings, Norse homebrewers learned that, if they used a wooden stick to stir a brew, then stirred the next batch with the same stick, the “magic” would pass on. Some of these intricately carved “yeast logs” are still in use today; in their crevices, they preserve strains of yeast that originated hundreds of years ago. In the Middle Ages, monasteries also brewed. There is evidence that Weltenburg Abbey may have been making beer as early as the 7th century, and hops were cultivated near the monastery of Weihenstephan not long thereafter. Weihenstephan was definitely brewing by 1040. It is now owned by the State of Bavaria and is the oldest continuously operating brewery in the world.
B EER > WAT ER “PART OF THE D E MAND F OR BE E R GRE W F ROM THE FACT THAT BE E R WAS OF TE N SAF E R TO D RINK THAN WATE R. THE D IF F E RE NCE WAS E SPE CIALLY MARKE D ON OCE AN VOYAGE S: AS L ATE AS THE MID19 T H CE NTURY, THE IMMIGRANT F OUND E R OF WASHINGTON’S HE URICH BRE WE RY NOTE D THAT THOSE WHO D RANK HIS BE E R ON THE ATL ANTIC
By the time of England’s Magna Carta in 1215, commercial breweries and pubs had grown numerous enough to need regulating, but the regulations didn’t slow their growth. By 1300, London alone had 1,300 “brewshops” slaking the thirst of a population that had not yet reached 40,000. Part of the demand grew from the fact Page 29
CROSSING SURVIVE D, WHILE THOSE WHO D RANK F ROM THE SHIP’S WATE R BARRE LS D IE D.” – BOB TUPPE R
that beer was often safer to drink than water. The difference was especially marked on ocean voyages: as late as the mid-19th century, the immigrant founder of Washington’s Heurich brewery noted that those who drank his beer on the Atlantic crossing survived, while those who drank from the ship’s water barrels died. For centuries, beer has reflected changes in society and technology. Brand identity existed long before Bass scooped up the first trademark in 1876. Rivalry between brewing companies could be almost as intense as the competition between nations that gave the world eight world wars between 1688 and 1989. The brewers themselves, however, were often friends, sharing techniques, discoveries, and even yeast strains in a collegiality that advanced both brewing and culture. German guilds employed “hefners,” specialists whose job was to manage the transfer of “Zeug” (German for, more or less, “stuff”) from one batch to the next. After Louis Pasteur’s discovery that “special ferments” produced beer and wine – and that these products could be purified by heating – brewers across Europe corresponded with him and one another in their quest to produce consistently highquality beer. In 1888, Emil Christian Hansen at Carlsberg Brewery published a method for propagating pure brewer’s yeast, using yeasts from Munich’s Spaten brewery. Saccharomyces carlsbergensis became the world standard for lager beer. Brewing companies grew in skill and ambition as economies became more sophisticated. As the Industrial Revolution concentrated workers into stuffy factories and smoke-filled cities, brewing for the thirsty hands became big business. The railroads that made
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Microbial Master: Pasteur set the tone for modern medicine and industrial fermented beverages.
LEFT PAGE /
Weihenstephan Taps: The worldâ&#x20AC;&#x2122;s oldest brewery in operation for nearly a millennium.
ABOVE /
The Sun Never Sets: India Pale Ale was first recognized as a hoppy brew enjoyed by British civil servants in India. Samuel Adams: Honoring its historic namesake, Sam Adams Brewery has produced numerous award-winning brews in just over three decades.
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U.S. PRESIDENTS WHO WERE HOME BREWERS
GEO R G E WA S HI N G TON
T H O M A S J EF F ER S ON
S A M UEL A DA M S
heavy industry practical also allowed brewers in cities such as Burton on Trent to sell throughout Britain and beyond. Strong ales followed the British Flag to India, where by the late 18th century civil servants sipped extravagantly hopped “India Pale Ales.” (The troops preferred porter.) As with literature, industry, and even political trends, the brewing culture in America largely paralleled that of Europe. Sam Adams really did brew, as did Washington and Jefferson. It didn’t take long for commercial brewing to take hold here. As in England, railways allowed regional brewers to reach a national market. Anheuser Busch established a network of ice houses that allowed it to ship refrigerated beer long distances from its St. Louis brewery. The close link between brewing and lifestyle almost destroyed the best of beer culture. After World War II, massive breweries producing lowest-commondenominator beer at rockbottom cost overwhelmed local brewers. Throughout the world, big brewers such as Heineken, Carlsberg, and the ancestors of InBev gobbled up small breweries
by the thousands. By the 1980s, the United States was down to a few dozen breweries. In the dismally conformist 1950s, Jack Kerouac and many others planted seeds for the cultural rebellion of the 1960s. Similarly, in the 1970s, as the United States spiraled toward brewing oblivion, Jack McAuliffe’s New Albion Brewery became the first of a wave of small breweries that appealed to niche markets rather than masses. Similar pioneers over the past few decades have helped save Britain, Scandinavia, and even Italy from malty monotony. Today, as with so many social trends, the United States is the Great Innovator. Over 3,000 independent breweries now pour strikingly inventive potions along with traditional, classic styles of beer. The opportunity for microbiological creativity has never been greater. Now families gather in the parking lots of rural microbrewery taphouses and beer lovers pack craft beer showplaces into the night in every major city in the Western world. Today may be the best time ever to find new beers, make new friends, and truly Drink In the Culture.
BOB TUPPER Robert Tupper, Jr., has been a history and government teacher for over 45 years. In 1979, he and his wife Ellie (a senior production editor at ASM) began taking notes on beer; their database now numbers over 26,000. Bob has conducted beer tastings and lectures for over 30 years, including a regular series at Washington, DC’s legendary Brickskeller. Bob and Ellie are publishing their book Drinking In the Culture: Tuppers’ Guide to Exploring Great Beers in Europe, a European travel guide for beer lovers, in June 2015; information at CulturAlePress.com.
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THE CUTTING EDGES OF CONTEMPORARY DIAGNOSTICS JOSEPH CAMPOS, PH.D.
OPEN
LAW OFFICES
My seven-year-old son is a big fan of popular music and he loves Katy Perry songs in particular. I realize there are readers of Cultures magazine who may not be familiar with Ms. Perry’s music. I would probably number among them were it not for my son’s musical interests. Furthermore, you may be asking yourself, what does this have to do with cutting edge laboratory testing?
WELL, HERE’S THE CONNECTION
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The other day, as I drove my son home from school, I was thinking about how much my own laboratory has changed over the past decade. Wouldn’t you know it, one of Katy’s recent hits began playing on the radio, accompanied by loud singing from the back seat. The song was titled “Dark Horse,” and, just to acquaint you with the music that appeals to young boys these days, this song has a very catchy ancient Egyptian musical accompaniment. As I listened, I heard Katy repeat a line several times that I realized is a remarkably appropriate comment about microbiology testing today.
“T H E
Katy sang “So you wanna play with magic? Boy you should know whatcha falling for.” In a sense, we clinical microbiologists have fallen for several forms of magic that we are now playing with for infectious disease testing. The magic of which she croons is no more intoxicating to her fans than are the advances in microbiology testing that have turned us into moths unable to escape the allure of a burning light bulb. MAG I C O F
MO L E C U L A R T E S T I N G HAS L E D U S TO A PE R FE CT S TO R M – A PL AC E I N WH I C H T H E CO M BI N AT I O N OF R A PI D A N D HIG H LY ACC U R AT E T E S T R E S U LT S H A S R E VOLU T I O N I Z E D T H E WAY S I N WH I C H WE DIAG N O S E INFE C T I O N S.”
-J O S E PH C A M PO S
During the past ten years, we have witnessed an unprecedented explosion of new technology in clinical microbiology. The time we used to spend peering through a microscope or manually manipulating culture plates is being replaced by digital imaging and automated processes complete with smart incubators that examine cultures and separate those with no growth from those with growth. The same equipment also enables suspicious colonies to be subcultured to fresh media or inoculated to identification/ susceptibility test panels without a human touching the culture plate. It is theoretically possible for today’s microbiology technologist to complete a day’s work while wearing pajamas, sipping coffee, and relaxing in a recliner at home.
As amazing as that sounds, there is another totally different kind of magic making inroads into laboratories around the world. It is the magic of matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) that enables isolates to be identified via proteomics in a matter of minutes at an extremely low cost. Yes, there is an up-front investment to the Page 36 » Across the Divide » Campos
tune of a six-figure number of dollars to purchase the necessary mass spectrometer, but, in high-volume laboratories, the return on that investment is achieved in a relatively short time through not purchasing conventional identification tests. In another part of “Dark Horse” Katy Perry chants “Are you ready for, ready for, a perfect storm, perfect storm. ‘Cause once you’re mine, once you’re mine. There’s no going back.” The magic of molecular testing has led us to a perfect storm – a place in which the combination of rapid and highly accurate test results has revolutionized the ways in which we diagnose infections. The recognition of signature nucleic acid sequences, whether through amplifying known targets or sequencing unknown targets, has already had a huge impact on many laboratories. It stands to reason that for physicians and patients who have benefitted from molecular testing, there is no going back. Truly astounding is the rapidity with which molecular diagnostics has evolved. It began before the turn of the century with the thermocycler-based PCR, which was leveraged to detect single targets unique to individual microorganisms. Not much later came the ability to quantitate those targets so that the efficacy of antimicrobial therapy could be quickly and accurately assessed. The next milestone was adapting PCR technology to detect multiple targets simultaneously. This is where many laboratories are today, choosing from an ever-increasing number of testing platforms and reagent test kits that can recognize dozens of different microorganisms in a single reaction mixture.
“‘SO YOU WANNA PL AY WITH MAGIC? BOY YOU SHOULD KNOW WHATCHA FALLING F OR.’ IN A SE NSE, WE CLINICAL MICROBIOLOGISTS HAVE FALLE N F OR SE VE RAL F ORMS OF MAGIC THAT WE ARE NOW PL AYING WITH F OR INF E CTIOUS D ISE ASE TE STING.”
So have we reached the end of the microbiology -JOSE PH CAMPOS, magic? Far from it! The availability of highly automated, “sample to result” testing platforms Q UOTING KAT Y PE RRY is bringing molecular assays to the masses, all around the globe. Isothermal amplification is now a reality that obviates the need for expensive thermocyclers, and these assays will soon threaten the once untouchable dominance of PCR. Within the past few months, the first Clinical Laboratory Improvement Amendments (CLIA)-waived molecular platform and assays were cleared for use in the United Page CULTURES 37 » Across Vol 2, Issue the Divide 2 » Page » XXX 37
THE EVOLUTION OF THE PCR MACHINE:
A DIAGNOSTIC TOOL
PRO/PETTE 1980s The pro/pette w a s a prototype that wo uld la ter b ecome a part of th e fi r s t P CR machine. It h a d th e ab i lity to m anipula te s ma ll v olumes of liqui d on a microtiter p la te.
DNA THERMAL CYCLER 1 1987 T he D N A Therma l C y cler 1 w as the f irst commer ci a l instrum ent, with a ca p a ci ty of 4 8 samp les .
MR. CYCLE, THERMAL CYCLER 1984 - 1985 To us e th e f i r s t a u t o ma t e d P C R ma ch i n e, s c i e nt i s t s h a d t o s t a nd a t th e l a b be nc h f o r s e v e r a l h our s a s t h e y mo v e d s a m p l e s b etw een wa t e r ba t h s o f v a r yi ng temp er a tur e s a nd we r e r e qu i r e d t o i nj ect ne w e n zyme s e a c h c yc l e .
DNA THERMAL CYCLER 480 1990 T h e D N A T h e r ma l C yc l e r 48 0 wa s t h e f i r s t P C R ma ch i ne wi t h a c a p a c i t y o f 9 6 s a mp l e s .
SON OF CYCLE, THERMAL CYCLER
BABY BLUE 1986
1 9 8 5 - 1 98 6 T h e Son of Cycle incor p or a ted t wo i mportant innov a ti ons th a t made the PCR mach i ne mor e au tomatic. It used T a q DNA P o ly merase, no longer r equi r i ng th e addition of f re s h enz y mes aft er each d enatur a ti on s tep . I t al so includ ed semi conductor el ements f or heating a nd cooli ng t h e sample- holdi ng b lock , el imi nating the need to tr a ns fer th e samples between w a ter b a th s .
T h e B a by B l u e wa s t h e fi r s t s i ng l e i ns t r u me nt to i nteg r a t e t h e s o f t wa r e cy cli n g c o nt r o l l e r wi t h t h e th er ma l c yc l i ng bl o c k .
REAL-TIME MACHINES (RT-PCR) 1996
1996 R eal- time PCR ma ch i nes h i t t h e mark et, allow i ng for a targeted DNA molecule to be d etected as the r ea cti on pro cesses in real ti me, r a th er th a n being detect ed a t th e e nd of the reactio n. Toda y , many d if f erent ma ch i ne ty p es exist and ar e a b le to pro cess up to 384 s a mp les a t o nce and run up to 40 cy cles in under 10 mi nutes . Page 39
Hands on work: An old method of filling tubes with culture media using a funnel.
States by the FDA. To non-U.S. laboratorians reading this article, this development permits molecular testing to be performed in nonlaboratory settings such as hospital emergency departments, pharmacies, and even retail stores. Accordingly, I forecast that within the next two to three years the testing marketplace will experience major economic disruption. Testing presently performed in hospital and commercial reference laboratories will be conducted in thousands upon thousands of nontraditional sites resulting in a significant reallocation of testing revenue. There still remains at least one more untapped source of laboratory magic and that is the use of high-throughput, nextgeneration DNA/RNA sequencing, not only for the diagnosis of infectious diseases, but also for the recognition of virulence factor and antimicrobial resistance genetic markers. The costs of sequencing reagents and equipment are still very high and the assays are quite cumbersome and time consuming, but that was also the state of PCR testing not that long ago. Technological advances and the automation of complex procedures are inevitable and will occur in the near future. I am confident that
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sequencing assays will be found in mainstream laboratories and will become the preferred method for diagnosis of certain infections. Sequencing technology will also open the gate to microbiome analyses of individual patients – a mode of testing that shows huge potential for increasing our understanding of human disease. In conclusion, consider the patient who has a life-threatening illness that appears to be infectious, but a multitude of cultures and PCR assays are negative. The sequencing of microbial nucleic acids from the same specimens can still provide actionable information. Once we begin utilizing perhaps the most powerful magic yet to salvage a diagnosis from specimens that used to be useless, it may be time to hum a different Katy Perry hit. The song is “Wide Awake,” and in it she sings “I wish I knew then what I know now.” I predict that a lot of us will have the same feeling as the microbiology magic keeps flowing.
JOSEPH MICHAEL CAMPOS, PH.D. Dr. Joseph Campos is the Interim Chief of the Division of Laboratory Medicine, as well as Director of the Microbiology Laboratory, the Molecular Diagnostics Laboratory, and the Section of Laboratory Informatics at Children’s National Medical Center where he has worked since September 1985. In these roles, Dr. Campos oversees the activities of all of the clinical laboratories, the laboratory diagnosis and management of infectious diseases in children, as well as the operation of the medical center’s laboratory information system. Dr. Campos is also a tenured professor in the Departments of Pediatrics, Pathology, and Microbiology/Immunology/ Tropical Medicine at the George Washington University Medical Center where he participates in the teaching of medical students, residents, and fellows.
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MEASLES AND RUBELLA ELIMINATION:
WHY NOW?
JON KIM ANDRUS, M.D. LOUIS Z. COOPER, M.D.
Measles means â&#x20AC;&#x153;miserableâ&#x20AC;? in Latin. Measles can also kill. Fortunately, there is ample evidence that this disease, as well as rubella and congenital rubella syndrome, can be eliminated with effective, well-integrated strategies.1 Putting science into practice is essential for saving lives. It will never be enough to invent the vaccine and let it sit on the shelf. More importantly, the vaccine must be administered to those who need it most. Such was the vision of Albert Sabin who invented the oral polio vaccine, and D.A. Henderson, who led global efforts to eradicate smallpox.
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As the theme of this special issue implies, “foundations” provide the “stuff” or systems and capacity upon which to build successful national immunization programs. Success not only breeds more success, the foundation of what leads to success should be used to spring board to additional successes. Indeed, this was the experience in the Americas when smallpox, then polio, then measles, and rubella and congenital rubella syndrome were eliminated from the Western Hemisphere.2 Failure to eliminate measles, rubella, and congenital rubella syndrome will kill and maim future generations of children. In particular, congenital rubella syndrome is a devastating disease that leaves a child with a lifetime of suffering from any combination of intellectual disability, autism, blindness, deafness, and cardiac defects. In that sense, it is very similar to the consequences of paralytic polio. Globally, public health authorities have estimated that almost 300 children are born each day with some form of congenital rubella syndrome, a disaster not only for the child, but also for families, especially for families living in poverty. Most of this disease burden now comes from developing countries. Congenital rubella syndrome is totally preventable by the administration of safe and effective vaccines, and can actually be eliminated. From a humanitarian perspective it is upsetting that more is not being done to administer these vaccines. Most of this disease burden now comes from developing countries. However, there have been significant outbreaks in developed nations, most recently in Poland and Japan, with at least 50 reported cases of infants being born with congenital rubella syndrome in each country. One reason why more is not being done to eliminate congenital rubella syndrome is that the disease burden is difficult to measure. As a result, the political commitment to eliminate this disease is undermined. Babies born with damaged central nervous systems are not linked to first trimester rubella infection. To compound this issue, the infection in mothers may even be asymptomatic. In addition, some public health professionals have hypothetical concerns that introducing rubella vaccine in children may contribute to an increased risk of women of childbearing age becoming infected and thus cause more harm than good. In other words, vaccinating children would “push” or displace the virus into older populations, especially women of childbearing age, thereby increasing the risk of delivering babies with congenital rubella syndrome. However, there is no evidence to support this hypothesis. Page 44 » Across the Divide » Andrus & Cooper
“” The outbreak
in Ecuador in 2011 from an imported “European” measles virus likely cost the country millions of dollars to contain and stop transmission.
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A key lesson learned from the Americas was the role of economic studies in galvanizing the political commitment to eliminate congenital rubella syndrome. In country after country, the data demonstrated that, for every dollar invested in congenital rubella syndrome elimination, 12 to 13 dollars were saved in the medical treatment costs of afflicted children. These kinds of data made it a “nobrainer” for Ministers of Health and Finance to decide to embrace the rubella and congenital rubella elimination strategies. Protecting the Next Generation: A young girl receives a measles vaccine in Bossangoa, Central African Republic.
Measles outbreaks are not cheap. The United States declared itself measles, rubella, and congenital rubella syndrome free, but it continues to have recurring and expensive outbreaks of measles imported from Europe and other parts of the world. Health authorities in the United States are rightfully alarmed that the costs of containing these outbreaks and preventing spread nationally are substantial. Such costs consume local public health budgets and overwhelm already fully stretched public health authorities. Developing countries pay too. The outbreak in Ecuador in 2011 from an imported “European” measles virus likely cost the country millions of dollars to contain and stop transmission. Disease is only a plane ride away.3 The lack of success in eliminating measles, rubella, and congenital rubella syndrome may likely predict how countries are going to fail to respond effectively to emerging infections and other
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national security threats. Measles, rubella, and congenital rubella syndrome elimination becomes the litmus test for any particular country’s capacity to respond effectively to emerging disease threats. Countries that have achieved the elimination targets will likely respond reasonably well to new emerging threats, and countries that have not fared so well with these targets will not likely succeed. Such is the case with Ebola in West Africa. The fundamental strategies to eliminate measles, rubella, and congenital rubella syndrome are straightforward.1 The keys include rapid reduction of the pool of people susceptible to infection by mass campaigns using combined measles- and rubella-containing vaccines and building a sustained, strong routine immunization program. Vaccination must be coupled with high-quality surveillance for early detection of new cases to prevent large outbreaks and to direct focused vaccination strategies. Success can be better assured with effective leadership and management at all levels of the immunization program, the highest level of political commitment and government ownership with broad private support. Plans of action must ultimately drill down to the microneighborhood level of activities, and include assured vaccine supply, sufficiently trained and
Measles Elimination Campaigns: A health worker in Bossangoa, Central African Republic, prepares a vaccine dose.
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experienced human resources, effective communication and social mobilization strategies, and adequate logistics and cold chain. Many experts would argue that rubella, congenital rubella syndrome, and measles are easier to eliminate than polio. But certainly their elimination would greatly benefit from engaging and integrating with the polio infrastructure that has been built around the world, with a renewed commitment to strengthening routine immunization programs as well. Indeed, this could be a great and lasting legacy of polio eradication. As outlined in the Global Vaccine Action Plan (GVAP) of the World Health Organization, achieving measles, rubella, and congenital rubella syndrome elimination is possible. The discussions around the Decade of Vaccines led to the development of the GVAP, which serves as a roadmap for making immunization services available for all children. Of the five specific goals, two cover the eradication of polio and the elimination of measles, rubella, and congenital rubella syndrome by 2020. Global, regional, and national buy-in for GVAP was demonstrated by its approval by the World Health Assembly in 2012. The accomplishments of the public/private partnership led by the Pan American Health Organization, and globally by the Measles and Rubella Initiative, document that elimination and even eradication are feasible. Although it would be naïve to believe the goal is easy, its measurable benefits, moral/humanitarian, economic, and political, can also bring a positive boost for national security against emerging biological threats and for global morale.
REFERENCES 1. Andrus JK, de Quadros CA, Castillo-Solorzano C, Roses Periago M, Henderson DA. 2011. Measles and rubella eradication in the Americas. Vaccine 29(Suppl 4):D91–D96. 2. Andrus JK, Castillo Solorzano C, de Oliveira L, Danovaro-Holliday MC. 2011. Strengthening surveillance: confronting infectious diseases in developing countries. Vaccine 29(Suppl 4):D126–D130. 3. Andrus JK, Aguilera X, Oliva O, Aldighieri S. 2010. Global health security and the International Health Regulations. BMC Pub Health 10(Suppl 1):S2. Available at: http://www.biomedcentral.com/1471-2458/10/S1/S2.
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JON KIM ANDRUS, M.D. Dr. Jon Andrus joined the Sabin Vaccine Institute in October 2014 where he serves as Executive Vice President and Director of the Vaccine Advocacy and Education program. Dr. Andrus is a Professor in the Department of Global Health at the George Washington University (GWU). He also holds faculty appointments at the University of California, San Francisco, and the Johns Hopkins University Bloomberg School of Public Health. He began his global health career as a Peace Corps volunteer, serving as a District Medical Officer in Malawi and has since held positions in the U.S. Centers for Disease Control and Prevention’s Global Immunization Division, as Head, Vaccinology and Immunization Program at the Institute for Global Health at the Universities of California at San Francisco and Berkeley, and as Director of the Global Health MPH Program at GWU.
LOUIS Z. COOPER, M.D. Dr. Louis Z. Cooper is Professor Emeritus of Pediatrics at Columbia University and Past President (2001–2002) of the American Academy of Pediatrics (AAP). As current chair of the International Pediatric Association Technical Advisory Group on Immunization, Dr. Cooper’s efforts focus on global eradication of measles and rubella, protecting public trust in immunization through improved communication, expanded research on the safety of immunization, and equitable global distribution of vaccines.
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TACKLING ANTIBIOTIC RESISTANCE: WHAT DO WE KNOW
AND
WHAT
DO WE NEED TO KNOW? RAMANAN L AXMINARAYAN
By now, anyone who has not heard that our antibiotics no longer work as well as they used to probably has not picked up a newspaper or magazine in years. “Why?” you may ask. Rewind to when antibiotics were first introduced to treat infectious diseases just 72 years ago. They were miracle drugs that were able to travel through the body and kill living bacterial cells while leaving human cells unharmed. Even back then, Alexander Fleming, who discovered penicillin as a result of an experiment gone bad, predicted that, over time, the constant selection pressure created by the use of penicillin and other antibiotics would give rise to new strains that would be untreatable with the use of antibiotics. Resistance had emerged even before he had collected on his Nobel Prize and has been increasing ever since.
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Changing behavior is our best bet to reduce the threat of resistance. A recent Lancet Infectious Diseases study showed that, in a set of six premier U.S. hospitals, one-third of antibiotic prescriptions were given in instances where there was no sign of infection. Campaigns have been shown to work in reducing the demand for antibiotics. Annual mass media campaigns in Belgium reduced antibiotic prescriptions by 36% between 1999 to 2000 and 2006 to 2007. It is unclear whether such campaigns could work in low- and middle-income countries and if the effects will be sustained after the campaigns have come to an end. However, behavior change problems have been encountered Scanning electron micrograph before in contexts as varied as of methicillin-resistant smoking in public places, drunk Staphylococcus aureus surrounded by debris (above) driving, and driving without and killing and escaping from a wearing a seatbelt. Those were human white blood cell (below). thought to be difficult contexts in which to change behavior, but, in each instance, change was accomplished through a lengthy process of social education. In the case of antibiotic use, we have gaps in our understanding of how to nudge doctors to prescribe less and patients to demand fewer antibiotics. The actual level of resistance is highly variable across time and geography. Much of what we know about resistance levels around the world comes from tertiary hospitals that are likely to cater to the sickest patients and therefore present the greatest level of resistance. If we inadvertently convey an incorrect message that most antibiotics are no longer working, we run the risk of physicians prescribing unnecessary antibiotics to reduce the chance that a patient does Page 52 Âť Across the Divide Âť Laxminarayan
not fail treatment with the more readily available first- and second-line antibiotics. What we do not know is how to convey the treatment of resistance, without inadvertently making the problem worse by pushing doctors and patients into using unnecessarily powerful antibiotics. A third unknown relates to how to price antibiotics. If priced too high, they become inaccessible to those who need them. If priced too low, they are overused and become ineffective. The socially appropriate price of antibiotics has to be considered in arriving at a socially optimal policy for antibiotic pricing.
TOP: Images from Fleming’s original penicillin article in 1929. BOTTOM: Laxminarayan gives a TED Talk in September 2014.
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“The CDC conservatively estimates that at least 23,000 people died of drug-resistant infections last year in the U.S. alone. Meanwhile, few companies are in the antibiotics business, having moved onto chronic diseases where there is much more money to be made.” – RAMANAN L AXMINARAYAN
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A fourth unknown relates to the focus on new drug development. Although all agree that new antibiotic classes are needed, there is much that could be done by way of innovation involving combination therapies, such as amoxicillin-clavulanate, that target both essential functions and resistance factors. Development efforts could repurpose old drugs to optimize dosing levels and the duration and route of administration and leverage pharmacokinetics and pharmacodynamics to identify promising combination drug therapies. For example, optimizing the dosing of colistin, a drug first introduced in the 1950s, can reduce toxicity and improve efficacy. Today, bacterial infections like pneumonia and gonorrhea, which could be treated with penicillin for pennies a dose, require antibiotics that cost hundreds of dollars. The CHECK OUT CDC conservatively estimates that at least 23,000 people died of drugRAMANAN resistant infections last year in the L AXMINARAYAN U.S. alone. Meanwhile, few companies GIVING A TED TALK are in the antibiotics business, having “THE COMING CRISIS moved onto chronic diseases where IN ANTIBIOTICS” IN there is much more money to be SEPTEMBER 2014. made. But that does not make sense. VIEW IT AT Shouldn’t pharmaceutical companies be interested in selling antibiotics in a HT TP://BIT.LY/1DSLPI2 world with more resistance and where people are dying of infectious diseases? After all, if payers or individuals would pay tens of thousands of dollars for a new cancer drug that extends life by two months, they should be able to pay a few hundred dollars for a new antibiotic that can extend life by decades? Turns out that few payers would approve such an expensive antibiotic because of fear that it would be overused and bankrupt them. The most expensive antibiotic that Medicare will pay for is Synercid at a cost of $236 per injection. In comparison, the most expensive cancer drugs cost over $50,000 per month and extend life by just a few months. Another issue is Page CULTURES 55 » Across Vol 2, Issue the Divide 2 » Page » XXX 55
that only a trained oncologist can prescribe anticancer drugs, but any GP (general practitioner) can prescribe antibiotics. It is the medicine that most doctors think they know how to use but that few appreciate the value of. It is unclear why we should expect new antibiotics to be cheap. After all, we have exhausted the lowest hanging fruit of antibiotics that were easily, even serendipitously discovered. Inevitably, newer antibiotics will be hard to find and more expensive to bring to market, in the same way that oil costs a lot more money now than thirty years ago. This, by itself, is not a bad thing. Just as the rising price of oil is a signal to us that we should not count on oil lasting forever, the rising price of new antibiotics is a signal that we should be more careful about how we use the drugs we have. Of course, there are those who may not be able to afford the new antibiotics, but the same is true for expensive gene therapy or cancer drugs, and we should find ways of ensuring that no one dies because of a lack of access to medicines that they cannot afford. In 2014, the federal Biomedical Advanced Research and Development Authority (BARDA) agreed to pay GlaxoSmithKline $200 million for work on new antibiotics, with no guarantee of success. It is unclear if this either Fleming’s first published article on solves the problem of a depleted the discovery of penicillin in 1929. pipeline or of incentivizing conservation. Even if there were a new antibiotic as a result of the process, what incentive would anyone have for conserving the ones we have if we thought the government was going to step in each time to find us a new antibiotic? No one would argue that we should subsidize the discovery of new oil wells to keep the price of oil low. So why would we make that argument in the case of antibiotics? Instead, the government should Page 56 » Across the Divide » Laxminarayan
aim to make sure that reimbursement through Medicare and Medicaid is appropriate to the cost of new antibiotics, make sure that those new drugs are used appropriately when taxpayers pay for them, and get out of the way. Despite these unknowns, we know enough to slow down the rate at which antibiotic resistance has emerged and spread. Lack of evidence should not be a reason to improve how antibiotics are used in our hospitals and community, but an investment in filling in these gaps in our understanding is a clear need.
RAMANAN L AXMINARAYAN Ramanan Laxminarayan is director and senior fellow at the Center for Disease Dynamics, Economics & Policy, and senior research scholar and lecturer at Princeton University. Through his work on the Extending the Cure Project in the United States and the Global Antibiotic Resistance Partnership, he has worked to improve the understanding of drug resistance as a problem of managing a shared global resource. Laxminarayan is a series editor of the Disease Control Priorities in Developing Countries, 3rd edition. Laxminarayan has worked with the World Health Organization (WHO) and the World Bank on evaluating malaria treatment policy, vaccination strategies, the economic burden of tuberculosis, and control of noncommunicable diseases. He has served on a number of advisory committees at WHO, the Centers for Disease Control and Prevention, and the Institute of Medicine. In 2003 to 2004, he served on the National Academy of Science/Institute of Medicine Committee on the Economics of Antimalarial Drugs and subsequently helped create the Affordable Medicines Facility for malaria, a novel financing mechanism to delay resistance and improve access to antimalarial drugs. In 2012, he created the Immunization Technical Support Unit in India, which has been credited with helping to rapidly improve immunization coverage in that country.
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WITH
Dr. Ellen Jo Baron INTERVIEWED BY EDITOR-IN-CHIEF JASON RAO & PETER GEOGHAN
Cultures chats with a leading expert in clinical microbiology to discuss how the field has changed and where it is headed next.
JASON: You are known for working on both ends of the foundations and frontiers in microbiology, for your work with DMDP (Diagnostic Microbiology Development Program) in the least developed settings around the world, to your role at Cepheid, where you are working on cuttingedge diagnostics. A lot of people talk about bringing those cutting-edge diagnostics to the developing setting, and the phrase they use is “skip technologies.” What do you think of that? We know that it is a loaded question, because it is not always easy in resource-constrained settings to just drop down the equipment. But what do you think is the most important focus in doing clinical microbiology in developed settings? ELLEN: That is a brilliant question. I had never thought about it that way. In regard to microbiology, we have a problem, because the cutting-edge technologies are not available for all of the basic microbiological diagnostic needs that you find in developing countries. I will give you sort of a strange example with Cambodia, the country with which I am most familiar. In Cambodia, our nongovernmental organization (NGO) supports seven laboratories, all of which diagnose diseases that are not on the list for big donor projects. Big donor projects often include HIV, TB, and malaria. “The Big Three” are well taken care of, and new technologies such as the Cepheid GeneXpert for TB, rapid enzyme amino acid lateral flows for malaria are out there. A lot of effort is being placed on getting point-of-care or near-patient testing for HIV, and we have a new bunch of products out there for that purpose.
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But pneumonia, sepsis, urinary tract infections, wound infections, burn wound infections – those kinds of things – that probably affect more people overall than the three that I mentioned – nobody is paying attention to making little tiny cutting-edge diagnostics for those. So, our NGO focuses on basic microbiology training to allow laboratories to diagnose bacterial infection in the blood or salmonella or cholera in the feces. Ultimately, I think you can have both by targeting cutting-edge technology where it is appropriate. But, at this point, we still need basic microbiology where it is appropriate, and where there are no cutting-edge technologies or where they are not affordable. (I am sure there is a Kiestra giant total laboratory automation system for doing microbiological cultures, but that would probably cost more than the entire country’s budget for health care just to purchase one instrument.) JASON: One thing we thought would be really interesting to ask you, since you have such a unique perspective having worked in the developing and resource-limited setting for decades – is it getting better? Or is it just an ongoing challenge we really need to dedicate ourselves to? ELLEN: I think schools are getting better. I have visited some very amazing schools around the world that are being supported by NGOs, and the teachers are dedicated, and they are bringing in more and more students. Our laboratories in Cambodia are getting better for sure. As a matter of fact, we are stopping all of our laboratories’ or most of our laboratories’ developing activities in Cambodia. We are concentrating all of our resources, money, and people on medical school education, and changing medical training, because physicians have not been able to keep up with laboratories. We are now ahead of the physicians’ ability to correctly order tests and read the results. So, we need now to go to the medical schools and teach them. JASON: And what is your impression between teaching students at Stanford and teaching young people in Cambodia? ELLEN: There are few differences; they are pretty much the same in many senses. The only key difference is access to resources. For example, students everywhere rely on the Internet. However, Page 60 » In Conversation
students at Stanford certainly have more and better access to the Internet. The students overseas may not have access to the Internet as easily – sometimes they may not have it at all. JASON: You have admittedly traveled the world. You have gone deep into Africa, into Latin America, into India, but there is something special about Cambodia. What was it that drew you there originally, and why did you choose to drill down there and make such a big difference? – which you certainly have. ELLEN: I have to credit two people with that: Jim McLaughlin, now the CEO of DMDP, and Pat Hogan, currently a microbiologist with Pfizer. In 2007, both were working on global health in Cambodia, Jim as a CDC consultant and Pat as a Pfizer fellow working in the microbiology laboratory at the Angkor Hospital. At the time I was giving a WHO lecture in Malaysia, and, having two friends in Cambodia, I asked myself, “Why don’t I just stop there on my way home from Kuala Lumpur?” So I did. When I saw what was going on there, I realized that the way microbiology was being taught Page 61 » On the Ground
Maj o r A ccomp lish me nt s • 1983 - moved to NYC and integrated into active clinical micro pioneer group of lab directors, unofficially led by Dr. Henry Isenberg. Henry got me involved in ASM journals (as editor), books, and local and national ASM community leadership. • 1984 - Dr. Finegold offered me the opportunity to co-author the major textbook Bailey & Scott’s Diagnostic Microbiology
was not fulfilling the needs of the Cambodian people, and that the WHO workshop I was giving would not fulfill those needs either. So, I took a sabbatical from Stanford in 2007 and developed a training program, the flowchart program, which is now used widely as a microbiology mentoring program. Foundation Merieux, which supports the developing world’s health needs in French-speaking countries, agreed to sponsor me to do a workshop, since I had already developed the training program. I ended up delivering the workshop in Laos and Cambodia the next year.
with him. That began a 12 year history of writing that book. • 1990 - took on editing and writing chores for ASM Manual of Clinical Micro. Worked with Dr. Pat Murray on that book for 3 editions. • 1996 - became WHO expert trainer, leading to teaching WHO courses in many countries in developing world with John Stelling, who developed WHONET. • 2007 - took sabbatical and developed the Basic Benchtop Micro Flowchart training program. • 2008 - co-founded DMDP with Jim McLaughlin. • 2008 - started working at Cepheid. Helping to develop rapid, nearpatient molecular diagnostic tests that are changing the world.
After I finished giving this week-long workshop to local microbiologists, they said, “You cannot just leave now; you have to stay and help us implement all this stuff.” Long story short, with initial funding from the Global Fund, we started our own NGO, the Diagnostic Microbiology Development Program (DMDP) to carry on the work of supporting laboratories in Cambodia and many other resource-poor countries. PETER: Earlier in the interview you mentioned a few infectious diseases that result from wounds or injury. Is that a prevalent issue you have been dealing with in Laos and Cambodia as a consequence of the unexploded devices from the Vietnam War? I know that that campaign was so massive that they have, on average, hundreds of deaths yearly in Laos. ELLEN: Yes, it is still an issue, but we
do not see those patients. There is not much laboratory work involved in treating them, because they are treated empirically. They do not even come in unless their wound festers so poorly that they get systemically ill. The physicians are not really utilizing the microbiology laboratory capability. And the other partners we work with there believe that we should concentrate our efforts on blood cultures and meningitis and not even worry about such trivial things as diarrhea and pneumonia, wound infections, urinary tract infections, etc. They think we need to start with the really important things. So, we try to get our laboratories doing a really good job on blood cultures and spinal fluid cultures and that sort of thing and lesser on the other things. But if you were to look for and get those samples early on in the infection, before they get worse or are left untreated, you would see a ton of resistant Gram-negative bacteria and all kinds of terrible things. But unfortunately, the way the medical system is there, most of those patients do not get into medical care early enough, and they just get treated empirically, if at all, and lose their limb when it could have been saved. JASON: I called you the queen of microbiology, which by the way is true. This brings us to you being on the frontiers as well. You mentioned your training package so humbly. We are well aware of its impact around the world because we train literally thousands of people a year through the Laboratory Capacity program with your package – with the Microbiology Mentoring package, we call it. Certainly, that is already your legacy. But what do you still have yet to do? What are you still passionate about achieving? What are you really hoping to do now? ELLEN: I am hoping to do more training actually. When I stop working so much for Cepheid, which will come at the end of this year – I will go to part-time. I am hoping to get back into the medical school training area. Right now, Stanford is doing something called the “flipped classroom” which a lot of medical schools have done or are in the process of doing. The material is didactic online, the students see it on their own time, and then they come to class prepared to use it in problem solving and decision making in a group process. I want to develop that kind of didactic material into a format where it can be accessed over time in small pieces so it is not just a one-on-one situation and, when you are not there, nobody gets it. We are going to be doing that at Cepheid. We are making videos that people can access at any time. We are going to be doing that at Stanford, and possibly with ASM’s training modules. JASON: Well I can think of nothing more impactful. Education curricula right now could really use your help. What advice would you give to Page 63 » On the Ground
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young people who are interested in a career in microbiology as they head into science or even into development? ELLEN: I would say they need to learn the information about the field of study that they are going into very well. They should choose their area of specialty based on their passion for it. Do not do something that you do not love, because you will not do it as well. Make sure you are having fun with it; if it becomes work, you are not going to do as well with it. So, make sure that you do something you love, that you are passionate about, and that is fun for you to spend your time doing. And then, become credible in it. Really do your homework. Learn it as well as you can. Write, publish, and then be able to speak. You need to be able to sell those ideas, get other people excited and passionate about it. Public speaking, expressing yourself clearly, speaking slowly and distinctly, and being able to stand up in front of a group and talk easily and passionately about what it is you do. I think those are extremely important skills that young people need to prepare themselves with.
BIO
Ellen Jo Baron, Ph.D.
Ellen Jo Baron is Professor Emerita, Department of Pathology at the Stanford University Medical Center and the Executive Director of Technical Affairs at Cepheid in Sunnyvale, CA. Dr. Baron is very active in the field of diagnostic microbiology as a symposium presenter and author. For the World Health Organization, she codeveloped the program for antimicrobial resistance detection and basic microbiology, which she presented in a number of resource-poor countries from 1995â&#x20AC;&#x201C;1998 and again in 2005.
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MARY WOOLLEY For almost 25 years now, I have been the president and CEO of Research!America, the nation’s largest not-for-profit advocacy alliance working to make the research to improve health a higher national priority. We are based in Washington, D.C. My career in research began as the San Francisco project director for the then largest-ever NIH-funded clinical trial, the Multiple Risk Factor Intervention Trial (MRFIT), following which I was the CEO of the Medical Research Institute of San Francisco. PRESIDENT AND CEO / RESEARCH!AMERICA
How do you see the field of microbiology changing in the next 20 years? I’m no microbiologist, but I’m told that further development in the area of sequencing and microscopy will provide the ability to do sequencing in the field and to analyze samples instantly. I think of how many lives will be saved and enhanced! I look to microbiologists to effectively expand their work and collaborate with other scientists to combat antibiotic-resistant bacteria, one of the most challenging threats of today and years to come. Finally, I look to microbiologists to lead the way among their science-trained colleagues to become effective voices for research to the nonscience public: the media, elected and appointed officials, and nonscientists everywhere, across the family holiday dinner table or on the soccer field or the Internet.
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JESSICA MEIR Astronauts support the overarching NASA mission of exploration and scientific innovation both in space and back on Earth by serving as crewmembers on human space missions and sharing our experiences through outreach to students and the general public. Our job involves intense training and preparation on the ground to ensure that we will serve as a valuable observer, operator, test subject, handyman, and team player on platforms like the International Space Station, our planetâ&#x20AC;&#x2122;s orbiting laboratory. ASTRONAUT / NASA JOHNSON SPACE CENTER
human body, to utilizing the unique microgravity environment to provide insight into processes in cell signaling or protein structure. As astronauts, we are fortunate to serve as both scientific operators and test subjects to perform such experiments in space and collect data for the cadre of investigators back on the ground. What is the best part of your job?
What role does microbiology play in your current profession? The biological sciences are an essential component of the space program, from understanding the effects of the space environment on the
The best part of my job is the people with whom I have the pleasure to work, and the opportunities they provide. Although, as astronauts, we often appear as the face of NASA, the scientists, engineers, support personnel, and entire team on the ground enable us to advance the presence of humans in space and to
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TOP, GOING DOWN
Flight training at Navy Pensacola Bar-headed goose flight training prior to wind tunnel studies. Training in the spacesuit at the Neutral Buoyancy Lab
Photo credit: Andrew R. Morgan
Photo credit: Katie Kuker
further our knowledge of our planet, our solar system, and beyond. How do you see the field of microbiology changing in the next 20 years? Although advancing technologies allow us to expose and tinker with the most minuscule components of biological structure and function, I believe maintaining the big picture will be the key to progress in the next 20 years. Using systems biology type approaches to study biological systems as a whole, and incorporating all aspects of our environment and the impact of our changing climate and society through integrative and interdisciplinary research, will be essential to interpreting the results of even the most intricate and focused of investigations. CULTURES Vol 2, Issue 2 Âť Page 69 Page 69 Âť On the Ground
J O N K AY E A curiosity for what makes the geosphere–biosphere system tick has motivated my path, taking me from lakes to the deep sea and, after shifting from research to philanthropy, around the blue planet through the work of Moore Foundation grantees. I also invested time in Washington, D.C. to learn how the U.S. government ecosystem ticks by bringing my microbiology expertise and scientific approach to bear on bioterrorism policy making. P R O G R A M D I R E C T O R / M A R I N E M I C R O B I O LO G Y I N I T I AT I V E AT T H E G O R D O N & B E T T Y M O O R E F O U N D AT I O N
How do you see the field of microbiology changing in the next 20 years? We are arriving at profound clarity about the depth to which our world is microbial, and has been for billions of years. Developing new technologies, adapting approaches used in other fields, and increasing the permeability between scientific disciplines will continue to push open doors in unexpected ways for the microbiological sciences. As the philosopher Donna Haraway summed up, “…we are in a knot of species coshaping one another in layers of reciprocating complexity all the way down,” and when we unravel this knot, we will perceive equivalent amounts of the loss of our human identity and the gain of a fantastical array of microbial friends.
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L A U R A B O WAT E R I started my career as a microbiologist working in a laboratory where my research added to the scientific understanding of microbial physiology. My current roles are to research how scientists engage with the public and to facilitate and support scientists to interact with a wide variety of audiences to promote a mutual understanding of microbiology, science, and research with a variety of key stakeholders. E D I TO R I N C H I E F / M I C R O B I O LO G Y TO D AY
What steps have you taken to get to where you are? I have actively sought opportunities to break out of the laboratory environment to work in a cross-disciplinary way. This has enabled me to take on new challenges and develop new skills that have allowed me to move from laboratory researcher to researching the laboratory and communicating microbial science with a wider audience. How do you see the field of microbiology changing in the next 20 years? Our understanding of the microbial world will continue to expand as we exploit the new tools and technologies that will provide a greater knowledge of the diversity of microbial life that we know is out there but that, at the current time, remains outside our “field of vision.” At the same time, we will seek to exploit the potential that microbes offer to improve every aspect of our lives, from promoting health, combating disease,
ensuring food security, to combating global challenges. What is the best part of your job? My job allows me to constantly learn about the depth and breadth of knowledge that underpins our understanding of microbiology. At the same time, I have a variety of roles that allow me to inform and enthuse others about the wonders of science, especially the microbial world.
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KENDRA CHITTENDEN I work for USAID to help develop and implement robust infectious disease prevention and control programs in developing countries and to strengthen science and technology (S&T) partnerships. SENIOR INFECTUIOUS DISEASE AND SCIENCE AND TECHNOLOGY ADVISOR / U.S. AGENCY FOR I N T E R N AT I O N A L D E V E LO P M E N T (U S A I D )
What role does microbiology play in your current profession? My understanding of microbiology helps me to develop effective infectious disease prevention and control programs and to work with universities and clinicians to develop relevant research projects for public health. Being a microbiologist helps me understand infectious disease risks, analyze data, and develop evidence-based programs. Having a degree in microbiology allows me to work as a colleague with the Ministries of Health and the academic sector, which is very valuable. Because I understand the challenges and obstacles that microbiologists and scientists face and the assets they can bring to development, I can help establish programs to overcome these obstacles to leverage the technical assets in developing countries.
What steps have you taken to get to where you are? After I earned my doctorate degree in Molecular Virology and Microbiology from the University of Pittsburgh School of Medicine, I was an American Society for Microbiology (ASM) Science and Technology Congressional fellow for one year. Following my fellowship, I stayed in DC and worked at a few
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“” Microbiology will continue to become more international and more One Health oriented.
Visit to a live bird market in Jakarta as part of the Avian Influenza Program. nongovernmental organizations (Federation of American Scientists, then CUBRC Center for International Science and Technology Advancement) where I began to do international work facilitating research collaborations. This led me to a civil service job at the State Department as a Team Leader for Bioengagement Programs for almost 5 years. Six years ago, I transitioned to USAID because I wanted to work overseas and work in the development field. What is the best part of your job? I love working in the field, helping governments to develop and implement infectious disease prevention and control programs, and also working at the community level where the efforts to prevent and treat infectious disease, such as TB and influenza, have a major impact on people’s health and livelihoods. Being able to work on S&T partnerships has been incredibly rewarding, and I greatly enjoy fostering international collaborations. S&T is a vital part of development. How do you see the field of microbiology changing in the next 20 years? Technology is a major game changer. Disease detection is becoming feasible at point of care and in rural communities, which allows us to detect emerging infectious diseases and potential outbreaks much earlier and to get more accurate estimates for infectious disease burden. Microbiology will continue to become more international and more One Health oriented, with human health and animal health continuing to become more integrated – this is critical for issues of zoonotic diseases and antimicrobial resistance. CULTURES Vol 2, Issue 2 » Page 73 Page 73 » On the Ground
DEBORAH A. NEHER I am a soil ecologist with research interests in developing biological indicators for environmental monitoring of agricultural, forest, and wetland soils. I view nature as a model and am a question-driven researcher using a population and community ecology approach. P R O F E S S O R A N D D E PA R TM E N T C H A I R / U N I V E R S I T Y O F V E R M O N T, D E PA R TM E N T O F P L A N T A N D S O I L S C I E N C E
What steps have you taken to get to where you are? Growing up on a family farm in northwestern Kansas stimulated my interest in nature. I chose Environmental Science as my undergraduate degree because it was all about big-picture and systems approaches. My current position as chair of a multidisciplinary department allows me to pull from my formal education in plant biology and my work experience at a biological field station and environmental monitoring and assessment program. What is the best part of your job? I love to travel, and research and speaking opportunities have taken me to all 50 states and 24 countries outside the United States. My job provides me with the challenge, independence, and variety of tasks that motivate me.
How do you see the field of microbiology changing in the next 20 years? Now that molecular biology and stable isotope geochemistry tools are available, we can finally begin to unravel the mysteries of the unknown 90% of the soil ecosystem. We will look at microbes as consortiums in their roles in plant rhizospheres and begin to link spatial assemblages of microbes within soil structure at the aggregate scale.
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LIBBIE PRESCOTT I consider myself a recovering scientist who takes on interesting challenges at the intersection of science, technology, and society. I started my policy career as an ASM Congressional Fellow working on health care policy for Senator Edward Kennedy. A decade later, I find myself working for the leadership at the Department of State on data and transparency; I’ve had many interesting career stops along the way. C O U N S E LO R & S T R AT E G I C A D V I S E R / O F F I C E O F T H E S C I E N C E & T E C H N O LO G Y A D V I S E R TO T H E S E C R E TA R Y O F S TAT E
What steps have you taken to get to where you are? I began with a passion for applying the technical skills I learned through my doctorate at Oxford to address the most pressing societal challenges. I find the most exciting work often exists at the intersection of two or
more fields such as science and international relations. To get there, I have been willing to take career risks when I see opportunities to have an impact. Building deep and diverse interests and networks across many disciplines has been critical for me to identify and explore novel ways of applying my technical expertise in policy and academia. How do you see the field of microbiology changing in the next 20 years? As with many other fields, I think the ease of access, storage, and sharing of all sorts of data will change our understanding and relationship to the microbial world. From a human health perspective, I think the insights coming out of initiatives like the Human Microbiome Project will elucidate the powerful role microbes play in maintaining human health as well as causing disease.
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THE NEXT ISSUE OF CULTURES WILL BE
A SPECIAL KID’S EDITION. That’s right, pull out your Crayola’s and junior chemistry set because the next issue will be full of microbiology-related activities you can do with the young person in your life! We’re looking to our readers to share some of their favorite science experiments and activities for tiny scientists (age 3-10). Just send an email to cultures@asmusa.org with a short description of the activity, what supplies are required, and your name and location if you’d like us to credit you in the next issue.
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“Ferdinand Cohn”
“Rosalind Franklin”
“E.Coli grocery store”
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FROM THE ASM IMAGE ARCHIVE: SEE THESE IMAGES & MORE BY FOLLOWING
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asmicrobiology ON INSTAGRAM
“Ruth Ella More, 1st African American to receive a Ph.D. in microbiology”
“Vaccination A Curse and a Menace to Liberty”
“Joseph Leidy”
“Diptheria Antitoxin Bottle” Page 79 » On the Ground
QUESTION COMMENT CORRECTI “I just received the parcel from the post office today. I am very happy! Thank you very much. Many greetings from Morogoro.”
JANET MARO
DIREC TO R / S US TA INAB LE AGR I C ULTUR E TA N Z ANIA Featured on page 86 of Volume 2, Issue 1 of Cultures.
Page 80 » Questions, Comments, & Corrections
DO YOU HAVE SOMETHING TO SAY TO CULTURES?
CORRECTION: ON PAGE 58 IN VOLUME 2, ISSUE 1, WE INCORRECTLY L ABELED INFORMATION ON THE CHART AS FAHRENHEIT INSTEAD OF CELSIUS.
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The views and opinions expressed in this publication are those of the individual authors and do not necessarily represent or reflect the views of the American Society for Microbiology.
Photography + Art Credit Page 18: Courtesy of the Center for the History of Microbiology/ ASM Archives (CHOMA). Kolmer, John A. Serum Diagnosis by Complement Fixation, with special reference to syphilis. The Principles, Technique and Clinical Applications. 1928 Page 20: “French Biologist Louis Pasteur” by Felix Nadar / Wikimedia Commons is licensed under CC-BY-SA 3.0 Page 21: Robert Hooke’s microscope from Scheme I of his 1665 “Micrographia” is licensed under CC-BY-SA 3.0. On permanent display in “The Evolution of the Microscope” exhibit at the National Museum of Health and Medicine, in Washington DC. Page 22: “Robert Koch” by Wilhelm Fechner / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 23: “Alexander Fleming, who is credited with discovering penicillin in 1928” by Calibuon / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 24: “Pasteur experimenting in his laboratory” by Tungsten / Wikimedia Commons is licensed under CC-BY-SA 3.0.
Page 32: “Published 1914” / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 32: “Washington” by H. Rousseau (graphic designer), E. Thomas (engraver) / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 32: “Appletons’ Adams Samuel” by Jacques Reich / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 34: “Neighborhood Diagnostic Testing” illustration by Tim Skirven. Page 38: “pro/pette, Prototype” by the Smithsonian National Museum of American History is licensed under CC-BY-NC. http://americanhistory.si.edu/ collections/search/object/ nmah_1165104 Page 38: “Mr. Cycle, Thermal Cycler” by the Smithsonian from Roche Molecular Systems, Inc, through Thomas J. White, is licensed under CC-BY-NC. http://americanhistory.si.edu/ collections/search/object/ nmah_1000862
Page 26: “Do you actually _drink_ the stuff?” by Daniel is licensed under CC BY-NC-SA 2.0.
Page 38: “Baby Blue Thermocycler” by the Science Museum London / Science and Society Picture Library / Wikimedia Commons is licensed under CC-BY-SA 3.0.
Page 29: “Dr. J.C. Ayer and Co.” by Miami U. Libraries - Digital Collections / Wikimedia Commons is licensed under CC-BY-SA 3.0.
Page 38: “Perkin-Elmer Cetus DNA Cycler PCR” by Scientific Support is licensed under CC-BY-NC.
Page 82 » Citations & Art Credit
Page 39: “Perkin Elmer DNA Thermal Cycler 480” is licensed under CC-BY. Page 39: “Son-of-Son-ofCycle, Thermal Cycler” by the Smithsonian National Museum of History is licensed under CC-BY-NC. http:// americanhistory.si.edu/ collections/search/object/ nmah_1165081 Page 39: “ViiA™ 7 RealTime PCR System” by Life Technologies is licensed under CC-BY-NC. Page 39: “Neighborhood Diagnostic Testing Part II” illustration by Tim Skirven. Page 40: Courtesy of CHOMA. Gorham, Frederick P. A Laboratory Course in Bacteriology for the Use of Medical, Agricultural, and Industrial Students. 1901 Page 42: “Transmission electron micrograph of rubella virus.” by CDC/Dr. Erskine Palmer / Wikimedia Commons is licensed under CC-BY-SA 3.0. Page 42 & 45: “Simian measles pneumonia - Case 287” by Philip Kane, MD is liscensed under CC BY-SA 2.0 Page 46: “Measles campaign 17” by Hdptcar is licensed under CC-BY-NC-SA 2.0. Page 47: “Measles campaign 09” by Hdptcacr is licensed under CC-BY-NC-SA 2.0.
Page 52: “Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteria” by NIAID is licensed under CC-BY 2.0. Page 52: “Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteria” by NIAID is licensed under CC-BY 2.0. Page 53: Courtesy of CHOMA “Shots of Pills” by Sparky is licensed under CC-BY-NC 2.0 Page 53: Courtesy of Abby Colson of CDDEP Page 56: Courtesy of CHOMA. The original penicillin article, 1929. Page 67: Courtesy of Libbie Prescott Page 68 – 69: Pictures courtesy of Jessica Meir Page 70: Courtesy of Jon Kaye Page 71: Courtesy of Laura Bowater Page 72: Courtesy of Kendra Chittenden Page 74: Courtesy of Deb Neher Page 75: Courtesy of Mary Woolley Page 78–79: Courtesy of ASM Page 84: © 2014 American Society for Microbiology Cover: Kara Miller / Made by We
Page 50: “Syringe with Clear Liquid” by Andre Rueda is licensed under CC-BY 2.0.
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FROM YESTERDAY’S FOUNDATIONS TO TODAY’S FRONTIERS, WHERE IS MICROBIOLOGY GOING?
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CULTURES |
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2015
AMERICAN SOCIETY FOR MICROBIOLOGY
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