A PUBLICATION OF ASM | VOL 2 | ISSUE 2 | 2015
FOUNDATIONS OF MICROBIOLOGY Steven Specter P. 18
THE CUTTING EDGES MEASLES & RUBELLA OF CONTEMPORARY ELIMINATION: WHY NOW? DIAGNOSTICS Joseph Campos P. 34
Andrus & Cooper P. 42
2
2
FROM YESTERDAY’S FOUNDATIONS TO TODAY’S FRONTIERS, WHERE IS MICROBIOLOGY GOING?
CULTURES Staff
Board of Advisors UNITED STATES
BRUCE
Alberts
JASON Rao MONGOLIA
TULGAA
Khosbayar
KATY Stewart
EGYPT
ENAS
Newire
UNITED STATES
SANJANA
PETER Geoghan
Patel
PORTUGAL
DIOGO
Proenรงa
JENNA Jablonski PARAGUAY
For interactive features and more content, read Cultures on your browser, tablet, or phone. Visit asm.org/cultures
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
The Rise of Cultures
26
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
IN CONVERSATION
58
Cultures interviews Ellen Jo Baron
ON THE GROUND
66
Emerging careers in microbial science
QUESTIONS, COMMENTS, & CORRECTIONS PHOTOGRAPHY CREDIT ON PAGES 82 - 83
80
BY JASON RAO + TIM DONOHUE
ΖQ WKLV LVVXH ZH UHȾHFW XSRQ WKH IRXQGDWLRQDO discoveries as well as the emerging frontiers of the microbial sciences. 7KLV LV WLPHO\ 7KH $60 PDGH XS RI LQGLYLGXDOV WKDW VSDQ ERWK WKH ȴHOG DQG WKH HDUWK LV DFWLYHO\ UHȾHFWLQJ XSRQ LWV RULJLQV LWV DFFRODGHV LWV challenges, and its future. Driven by its core mission to promote and advance the microbial sciences, each of us is drawn to the Society, IRU WKH EHQHȴW RI DOO :KHWKHU LQ 1HZ 2UOHDQV 6DQDD 6DQ -XDQ Karachi, or Abuja, the 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. 2QFH IRUPHG WR IDFLOLWDWH PHHWLQJV VKDUH GLVFRYHULHV DQG VWUHQJWKHQ 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. The 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 PLFURELDO VFLHQWLVWV RQ DQG RÎ? the bench. From public policy to science communication, to global health and development, the ASM’s microscope peers LQWR D ČľRXULVKLQJ ZRUOG RI 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 6RFLHW\ ZLOO EHQHČ´W IURP WKHP ΖQ WKLV 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 ΖQWHUQDWLRQDO $Î?DLUV
:H LQYLWH \RX WR UHDG WKH ODWHVW DERXW WKH $60 )XWXUHV 3URMHFW E\ looking at http://www.asm.org/index.php/futures. There will be additional opportunities to hear about the ASM Futures Project at DVP LQ 1HZ 2UOHDQV 6HH \RX WKHUH 6HQG XV TXHVWLRQV DQG input about the ASM’s future by email: asmfuture@asmusa.org.
SNAPSHOT OF CULTURES
6,000+
reads online in over 75 countries
47
countries made contributions
111,916
copies mailed worldwide
Visit www.asm.org/cultures for additional content and interactive features! CULTURES Vol 2, Issue 1 Âť 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 1 8
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
MAX THEILER
Developed vaccine against yellow fever
1952
CHARLES LOUIS ALPHONSE LAVERAN
SELMAN ABRAHAM WAKSMAN
Discovered streptomycin, first antibiotic against tuberculosis
Connected protozoa with disease
1908 ILYA ILYICH MECHNIKOV + PAUL EHRLICH
1958
Cultivated polio virus in a test tube
Established foundation for the science of immunology
1958 1919
JULES BORDET
Discovered key principles of immunity
1960 1928
1930
1965
Discovered blood group antigens
JOSHUA LEDERBERG
Discovered that bacteria can mate and exchange genes
SIR FRANK MACFARLANE BURNET + SIR PETER BRIAN MEDAWAR
Predicted acquired immune tolerance
CHARLES JULES HENRI NICOLLE
Discovered transmission method of typhus
KARL LANDSTEINER
JOHN FRANKLIN ENDERS + FREDRICK CHAPMAN ROBBINS + THOMAS HUCKLE WELLER
FRANÇOIS JACOB + ANDRÉ LWOFF + JACQUES MONOD
Discovered bacteriophage infectivity mechanisms
CULTURES Vol 2, Issue 2 » Page 7
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
Page 8
1996
PETER C. DOHERTY + ROLF M. ZINKERNAGEL
Discovered cellmediated immune defense mechanisms
“The frontiers
1997 STANLEY B. PRUSINER
Discovered prions, a new biological principle of infection
that we face will likely be transcended using these foundational
2005
BARRY J. MARSHALL + J. ROBIN WARREN
Discovered link between Helicobacter pylori and stomach ulcers
2008 HARALD ZUR HAUSEN + FRANÇOISE BARRÉ-SINOUSSI + LUC MONTAGNIER
Discovered HIV
discoveries that have served us well for centuries, decades, or only a few years. These frontiers will be
2011
BRUCE A, BEUTLER AND JULES A. HOFFMANN
Discovered innate immunity activation
2011
RALPH M. STEINMAN
Discovered dendritic cells in adaptive immunity
the foundation for future generations.” – DR. STEVEN SPECTER R E A D M O R E O N PA G E 18
T O D AY
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 GR QRW" :K\ LV WKLV LPSRUWDQW" DR. DOL AN: TIDES has extraordinary potential to change what undergraduate STEM HGXFDWLRQ ORRNV OLNH 2QH SURJUDP 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 WKHLU YHU\ ȴUVW VHPHVWHU RQ FDPSXV in doing research connected to a faculty member’s ongoing work, and they earn credit for courses that are UHTXLUHG IRU WKHLU PDMRU 6R LQVWHDG 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
Page 10 Âť Happening Now
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: :H KDYH WR balance novelty with what we NQRZ LV HÎ?HFWLYH $V D QHZ program, the most important WKLQJ IRU 7Ζ'(6 LV Č´JXULQJ RXW ZKDW LV DOUHDG\ ZRUNLQJ :KDW assets are available? I spent D ORW RI P\ Č´UVW VL[ WR QLQH months on campus answering WKHVH TXHVWLRQV %XW WR PDNH experimental programs and novel teaching methods more possible in the future, there must be a OHYHO RI FUHDWLYLW\ DQG ČľH[LELOLW\ involved. Let me tell you, people are working really creatively, and they work with extraordinary energy and enthusiasm. Instead RI VD\LQJ ČŠ1R WKDW FDQQRW FRXQW for introductory lab credit; introductory lab needs to address X, Y, and Z,â€? people said, “How can we make this count for credit? How can we integrate this into the curriculum?â€? Sometimes we have to use things that we already know work, and sometimes we have to innovate. CULTURES: :KDW LPSDFWV DUH 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 ZH DUH KDYLQJ D SRVLWLYH HÎ?HFW on graduation rate, that we are KDYLQJ D SRVLWLYH HÎ?HFW RQ WKH number of science majors, and WKDW ZH DUH KDYLQJ D SRVLWLYH HÎ?HFW 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, ZKLFK LV DFWXDOO\ D GLÎ?HUHQW 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 WRSLFV LQ KLJK SURČ´OH MRXUQDOV For example, alumni from our FRI program coauthored a major publication in genetics recently.
CULTURES Vol 2, Issue 2 Âť Page 11
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?
Č´HOG :H DOVR UHDFK RXW WR KLJK school students to engage them in research, because that is where I think our strength OLHV DQG VRPHWKLQJ XQLTXH ZH FDQ RÎ?HU WR . VFKRROV ΖW LV important to think of it as a collaborative relationship that HQDEOHV XV WR EXLOG RÎ? HDFK 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 RÎ?HU :H DUH UHDOO\ YLHZLQJ WKLV 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 VSHFLČ´F WHFKQLTXHV DQG teaching methods that you would like to see incorporated in all levels of education across the United States?
VISIT US AT
:H DOUHDG\ 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 RI 1DWXUDO 6FLHQFHV SUHSDUHV 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 IURP GLÎ?HUHQW EDFNJURXQGV capabilities, experience, and interests. And we have a range RI SHRSOH ZKR WHDFK :KDW PLJKW work for one instructor, might not work for another. Everyone EULQJV WKHLU RZQ XQLTXH experiences to the table, and that needs to be considered. 2QH WKLQJ WKDW ZH QHHG WR emphasize is Carol Dweck’s “growth mindset,â€? 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.
Page 12 Âť Happening Now
CULTURES Vol 2, Issue 2 » Page 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 ZLWK :KDW DSSURDFKHV GR \RX think that these FRXQWULHV VSHFLȴFDOO\ 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 LV D WRXJK TXHVWLRQ 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: :KDW DGYLFH ZRXOG 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.
Page 14 Âť Happening Now
DR. DOL AN: Again, there is no one silver bullet, but I recall D 1REHO /DXUHDWH ΖVLGRU ΖVDDF 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 KRPH IURP VFKRRO Ȋ:KDW GLG
you learn in school today?â€? She would ask him “Did you ask any JRRG TXHVWLRQV"Č‹ $QG Ζ ZRXOG say that that is what science is: being curious and asking good TXHVWLRQV 6R Ζ DOZD\V HQFRXUDJH students at all levels – people at all levels – to just be curious and DVN JRRG TXHVWLRQV
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 WR VRFLDO FDSLWDO ZLWKLQ WKH VFLHQWLȴF FRPPXQLW\ HVSHFLDOO\ 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/).
CULTURES Vol 2, Issue 2 Âť Page 15
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.
Page 16
STEVEN SPECTER | PAGE 18 FOUNDATIONS OF MICROBIOLOGY
Dr. Specter of the University of South Florida chronicles microbiology’s key discoveries and advancements over the past 150 years, and how WKH\ KDYH GLUHFWHG WKH HYROXWLRQ RI WKH ȴHOG
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 2, Issue 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 maZm Zk^ ghp Ʈkfer ^lmZ[ebla^]' FZgr h_ ma^ foundational events are presented at http://micro.digitalproteus.com/history3.php and http://www.microbeworld.org/ history-of-microbiology.
CULTURES Vol 2, Issue 2 » 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 XQGHUVWRRG WKLV SULQFLSOH \HW RUJDQL]HG HÎ?RUWV WR NHHS 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 HVWDEOLVKHG WKH Č´UVW PXQLFLSDO ZDWHU system in a major American city. However, it was not until the work of Pasteur, establishing the microbial relationship to GLVHDVH WKDW HÎ?RUWV EHFDPH V\VWHPDWLF WR install water treatment and waste disposal V\VWHPV EURDGO\ 6DQLWDWLRQ HÎ?RUWV KDYH EHHQ PRUH HÎ?HFWLYH WKDQ YDFFLQHV DQG 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 (1818â&#x20AC;&#x201C;1865) introduced the concept of antisepsis in 1847 related to puerperal sepsis, but WKLV SUHGDWHG WKH ZRUN RI 3DVWHXU DQG FRQČľLFWHG ZLWK established practice. Despite reducing mortality to <1% in delivery wards, his work was derided. It was not XQWLO 2OLYHU :HQGHOO +ROPHV 6U SXEOLVKHG KLV WUHDWLVH on this topic in 1885 that antisepsis was accepted. 7KH VXFFHVVIXO DGRSWLRQ RI GLVLQIHFWLRQ WHFKQLTXHV FDQ be traced to Joseph Lister (1827â&#x20AC;&#x201C;1912), who pioneered antiseptic surgery in 1865 following the establishment of the germ theory of disease, leading to decreases in morbidity and mortality postsurgery.
Page 20 Âť Across the Divide Âť Specter
CASE STUDY B
IMMUNIT Y + IMMUNIZATION Î&#x2013;PPXQL]DWLRQ ZDV Č´UVW HVWDEOLVKHG E\ DQFLHQWV ZKR GLG QRW SRVVHVV D VFLHQWLČ´F XQGHUVWDQGLQJ RI WKHLU SUDFWLFHV EXW UHFRJQL]HG WKH EHQHČ´W RI WUHDWPHQW 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 E\ WKH HDUO\ V ZKHUH /DG\ 0RQWDJX Č´UVW OHDUQHG RI LW DQG EURXJKW LW EDFN WR (QJODQG 6XEVHTXHQWO\ LQ 1798, the English physician Edward Jenner (1749â&#x20AC;&#x201C;1823) actively immunized against smallpox by using cowpox, HVWDEOLVKLQJ WKH Č´UVW SULQFLSOHV RI PRGHUQ YDFFLQDWLRQ :KLOH KH GLG QRW XQGHUVWDQG WKH PLFURELRORJLFDO RU 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 WR /RXLV 3DVWHXU Č&#x201A; ZKR GHYHORSHG WKH Č´UVW vaccine through the attenuation of chicken cholera and then for humans by inactivation and inoculation of rabies virus. Many GLVHDVHV KDYH VXEVHTXHQWO\ EHHQ 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 2, Issue 2 Âť 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 Č&#x201A; LQ Č´UVW GHVFULEHG FHOOV WKHQ $QWRQ YDQ Leeuwenhoek (1632â&#x20AC;&#x201C;1723) in 1674 published a description of microorganisms, and in 1685 he demonstrated animalcules EDFWHULD LQ GHQWDO SODTXH 0XFK ODWHU WKH GLVFRYHU\ RI WKH electron microscope (Max Knoll and Ruska, 1931) and the ČľXRUHVFHQFH PLFURVFRSH 0DUYLQ 0LQVN\ SHUPLWWHG WKH LGHQWLČ´FDWLRQ RI VPDOOHU EDFWHULD DQG YLUXVHV H[SDQGLQJ greatly our recognition of microbes. )HUGLQDQG - &RKQ Č&#x201A; ZDV WKH Č´UVW WR SXEOLVK D FODVVLČ´FDWLRQ RI EDFWHULD LQ Č´UPO\ HVWDEOLVKLQJ WKH VFLHQFH of microbiology. However, no one advanced microbiology as Louis Pasteur did, renowned as the â&#x20AC;&#x153;Father of Microbiologyâ&#x20AC;? for a series of accomplishments in the latter half of the 19th century WKDW GHČ´QLWLYHO\ PRYHG PLFURELRORJ\ WRZDUG WKH PRGHUQ HUD +H GLVSURYHG WKH QRWLRQ RI VSRQWDQHRXV JHQHUDWLRQ Č´UPO\ HVWDEOLVKHG WKH JHUP WKHRU\ RI GLVHDVH GHYHORSHG WKH Č´UVW immunizations, coined the term virus, and developed a process, SDVWHXUL]DWLRQ WR SURWHFW PLON DQG RWKHU OLTXLGV QRWDEO\ ZLQH from spoiling because of microbial contamination. Robert Koch (1843â&#x20AC;&#x201C;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 RI .RFKČ&#x2021;V SRVWXODWHV IRXU SULQFLSOHV WKDW ZHUH UHTXLUHG WR GHČ´QLWLYHO\ LGHQWLI\ WKH HWLRORJLF DJHQW RI D GLVHDVH 7KHVH KDYH guided the determination of disease etiology for more than a century; although, with the sophisticated tools of today, we can QRZ LGHQWLI\ HWLRORJ\ ZLWKRXW IXOČ´OOLQJ .RFKČ&#x2021;V SRVWXODWHV
Page 22 Âť Across the Divide Âť Specter
CASE STUDY D
ANTIMICROBIAL AGENTS 3DXO (KUOLFK Č&#x201A; Č´UVW UHSRUWHG D successful treatment for syphilis in 1912, WKXV RSHQLQJ WKH Č´HOG RI DQWLPLFURELDO chemotherapy. This ultimately led to the discovery of penicillin by Sir Alexander Fleming (1881â&#x20AC;&#x201C;1955) in 1928 and the ability to commercialize the Č´UVW DQWLELRWLF WKURXJK WKH HÎ?RUWV RI Howard Florey (1898â&#x20AC;&#x201C;1968) and Ernst Alexander Fleming &KDLQ Č&#x201A; GXULQJ :RUOG :DU Î&#x2013;Î&#x2013; It is often noted that the war spurred this work as more soldiers died of infection that followed gunshots and other LQMXULHV :KLOH WKH FRPPHUFLDOL]DWLRQ RI SHQLFLOOLQ RSHQHG DQ HQWLUHO\ QHZ Č´HOG WKH ZRUN RI 6HOPDQ :DNVPDQ (1888â&#x20AC;&#x201C;1973) and colleagues really propelled antibiotics IRUZDUG EHFDXVH WKH\ ZHUH WKH Č´UVW WR SXUSRVHIXOO\ VHHN 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 GUXJV KDYH EHHQ DURXQG ORQJHU EHFDXVH TXLQLQH DV an antimalarial has been used since the 17th century. Modern antiparasitic drugs can be traced to the 1940s and WKH LQWURGXFWLRQ RI FKORURTXLQH IRU WUHDWPHQW RI PDODULD The antifungal drug amphotericin B was introduced in 1956 and several classes of antifungals have followed. 7KH Č´UVW DQWLYLUDO GUXJ DF\FORYLU ZDV GLVFRYHUHG LQ by Gertrude Elion (1918â&#x20AC;&#x201C;1999) for treatment of herpes YLUXVHV DQG WKLV GLVFRYHU\ RSHQHG D Č´HOG WKDW QRZ KDV KDG D KLJKO\ VLJQLČ´FDQW LPSDFW ZLWK WKH SUROLIHUDWLRQ RI DQWLYLUDO GUXJV WR WUHDW WKH KXPDQ LPPXQRGHČ´FLHQF\ 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 FXUUHQW VFLHQWLČ´F NQRZOHGJH
CULTURES Vol 2, Issue 2 Âť Page 23
CASE STUDY E
DIAGNOSTICS Diagnostic methods for the isolation DQG LGHQWLČ´FDWLRQ RI PLFUREHV EH\RQG microscopy is not an ancient art. The late 19th century saw the introduction of FXOWXUH WHFKQLTXHV IRU EDFWHULD -RVHSK Lister in 1878 reported on a method to isolate a pure bacterial culture from milk, and Martinus Beijerinck (1851â&#x20AC;&#x201C;1931) discovered an enrichment medium that allowed for the culture of bacteria in 1898. Ten years later, he discovered viruses E\ GHPRQVWUDWLQJ WKDW Č´OWHUDEOH DJHQWV 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 (1897â&#x20AC;&#x201C;1985), 7KRPDV :HOOHU Č&#x201A; DQG )UHGHULFN 5REELQV Č&#x201A; GHYHORSHG D WHFKQLTXH WR FXOWXUH SROLRYLUXV 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. KĂśhler (1946â&#x20AC;&#x201C;1995) and CĂŠsar Milstein (1927â&#x20AC;&#x201C;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 (1944â&#x20AC;&#x201C;) established the polymerase chain reaction, which allowed for rapid, highly VSHFLČ´F LGHQWLČ´FDWLRQ RI '1$ VHTXHQFHV DQG JUHDWO\ expanded our ability for rapid, accurate diagnosis. The PRVW UHFHQW EUHDNWKURXJK LV WKH VHTXHQFLQJ RI JHQRPHV 7KH Č´UVW EDFWHULXP VHTXHQFHG ZDV Haemophilus LQČľXHQ]DH, which was accomplished by J. Craig Ventner Č&#x201A; DQG FROOHDJXHV OHDGLQJ WR VHTXHQFLQJ WKH HQWLUH human genome.
Page 24 Âť Across the Divide Âť Specter
SUMMARY
7KH Č´HOG RI JHQRPLFV LV FRQVLGHUHG WKH IRUHIURQW RI 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 (1976â&#x20AC;&#x201C;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 (GXFDWLRQ Č&#x201A; $VVRFLDWH 'HDQ IRU 6WXGHQW $Î?DLUV Č&#x201A; 2014), and Associate Dean for Alumni Relations (2014â&#x20AC;&#x201C;present) at the USF MCOM. He has written more than 175 publications and has edited a dozen books. He is Chairman â&#x20AC;&#x201C; Clinical Virology Symposium (1985â&#x20AC;&#x201C;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 (2005â&#x20AC;&#x201C;2014) and is Chair, ASM International Board (2014â&#x20AC;&#x201C;presesnt).
CULTURES Vol 2, Issue 2 Âť Page 25
THE RISE OF CULTURES BOB TUPPER
When we chose the title for hnk Ʈklm [hhd% Drinking In the Culture, we intended the double entendre of absorbing a social Zmfhlia^k^ pabe^ jnZưg` [^^k' 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 2, Issue 2 » Page 27
1R RQH NQRZV KRZ WKH Č´UVW EHHU KDSSHQHG 6RPHRQH PD\ KDYH OHIW some grains out in the rain long enough for natural microorganisms to take a turn. Modern palates would cringe at what probably resulted, EXW WR WKH SHUVRQ FXULRXV HQRXJK WR WDNH WKDW Č´UVW VZLJ LW PXVW KDYH been nothing short of miraculous. :H GR NQRZ WKDW WKHUH LV D YHU\ JRRG FKDQFH WKDW FLYLOL]DWLRQ LWVHOI EHJDQ EHFDXVH RI EHHU :LOG JUDLQV ZHUHQČ&#x2021;W WKDW KDUG WR Č´QG IRU KXQWHU gatherers, 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 d Lactobacillus. Low alcohol and refreshing, it is traditionally served â&#x20AC;&#x153;mit SchĂźss,â&#x20AC;? with ZRRGUXÎ? JUHHQ RU UDVSEHUU\ ČľDYRUHG VXJDU V\UXS
Page 28 Âť Across the Divide Âť Tupper
The earliest recipes for beer date to 4300 BCE. Ancient societies used beer for payment, as medicine, and for ritual purposes â&#x20AC;&#x201C; as one could argue we still do. Brewing was traditionally part of the regular household tasks, like baking. At least as early as WKH 9LNLQJV 1RUVH KRPHEUHZHUV learned that, if they used a wooden stick to stir a brew, then stirred the next batch with the same stick, the â&#x20AC;&#x153;magicâ&#x20AC;? would pass on. Some of these intricately carved â&#x20AC;&#x153;yeast logsâ&#x20AC;? are still in use today; in their crevices, they preserve strains of yeast that originated hundreds of years ago.
B EER > WAT ER â&#x20AC;&#x153;PART OF THE D E MAND F OR BE E R GRE W F ROM THE FACT THAT BE E R WAS OFTEN SAFER TO D RINK THAN WATE R.
In the Middle Ages, monasteries also brewed. There is evidence WKDW :HOWHQEXUJ $EEH\ PD\ KDYH been making beer as early as the 7th century, and hops were cultivated near the monastery RI :HLKHQVWHSKDQ QRW ORQJ WKHUHDIWHU :HLKHQVWHSKDQ ZDV GHČ´QLWHO\ EUHZLQJ E\ Î&#x2013;W LV now owned by the State of Bavaria and is the oldest continuously operating brewery in the world.
THE D IF F E RE NCE WAS ESPECIALLY MARKED ON OCE AN VOYAGE S: AS L ATE AS THE MID19 T H CENTURY, THE IMMIGRANT F OUND E R OF WASHINGTONâ&#x20AC;&#x2122;S HEURICH BREWERY NOTED THAT THOSE WHO DRANK HIS BEER ON THE ATL ANTIC
By the time of Englandâ&#x20AC;&#x2122;s Magna Carta in 1215, commercial breweries and pubs had grown numerous enough to need regulating, but the regulations didnâ&#x20AC;&#x2122;t slow their growth. By 1300, London alone had 1,300 â&#x20AC;&#x153;brewshopsâ&#x20AC;? slaking the thirst of a population that had not yet reached 40,000. Part of the demand grew from the fact
CROSSING SURVIVE D, WHILE THOSE WHO D RANK F ROM THE SHIPâ&#x20AC;&#x2122;S WATE R BARRE LS D IE D.â&#x20AC;? â&#x20AC;&#x201C; BOB TUPPER
WKDW EHHU ZDV RIWHQ VDIHU WR GULQN WKDQ ZDWHU 7KH GLÎ?HUHQFH ZDV especially marked on ocean voyages: as late as the mid-19th century, WKH LPPLJUDQW IRXQGHU RI :DVKLQJWRQČ&#x2021;V +HXULFK EUHZHU\ QRWHG WKDW those who drank his beer on the Atlantic crossing survived, while those who drank from the shipâ&#x20AC;&#x2122;s water barrels died. )RU FHQWXULHV EHHU KDV UHČľHFWHG FKDQJHV LQ VRFLHW\ DQG WHFKQRORJ\ %UDQG LGHQWLW\ H[LVWHG ORQJ EHIRUH %DVV VFRRSHG XS WKH Č´UVW 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, VKDULQJ WHFKQLTXHV discoveries, and even yeast strains in a collegiality that advanced both brewing and culture. German guilds employed â&#x20AC;&#x153;hefners,â&#x20AC;? specialists whose job was to manage the transfer of â&#x20AC;&#x153;Zeugâ&#x20AC;? (German for, more or OHVV Č&#x160;VWXÎ?Č&#x2039; IURP RQH batch to the next. After Louis Pasteurâ&#x20AC;&#x2122;s discovery that â&#x20AC;&#x153;special fermentsâ&#x20AC;? produced beer and wine â&#x20AC;&#x201C; and that these products FRXOG EH SXULČ´HG E\ heating â&#x20AC;&#x201C; brewers across Europe corresponded ZLWK KLP DQG RQH DQRWKHU LQ WKHLU TXHVW WR SURGXFH FRQVLVWHQWO\ KLJK TXDOLW\ EHHU Î&#x2013;Q (PLO &KULVWLDQ +DQVHQ DW &DUOVEHUJ %UHZHU\ published a method for propagating pure brewerâ&#x20AC;&#x2122;s yeast, using yeasts from Munichâ&#x20AC;&#x2122;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 ZRUNHUV LQWR VWXÎ?\ IDFWRULHV DQG VPRNH Č´OOHG FLWLHV EUHZLQJ IRU 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 world’s oldest brewery in operation for nearly a millennium.
ABOVE /
7KH 6XQ 1HYHU 6HWV ΖQGLD 3DOH $OH ZDV ȴUVW UHFRJQL]HG DV 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.
CULTURES Vol 2, Issue 2 » Page 31
U.S. PRESIDENTS WHO WERE HOME BREWERS
GEORGE WASHINGTON
T H O M A S J EF F ER S ON
SAMUEL ADAMS
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 â&#x20AC;&#x153;India Pale Ales.â&#x20AC;? (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 GLG EUHZ DV GLG :DVKLQJWRQ and Jefferson. It didnâ&#x20AC;&#x2122;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 EHHU FXOWXUH $IWHU :RUOG :DU Î&#x2013;Î&#x2013; PDVVLYH EUHZHULHV producing lowest-commondenominator beer at rockbottom cost overwhelmed local brewers. Throughout the world, big brewers such as Heineken, Carlsberg, and the ancestors of InBev gobbled up small breweries
by the thousands. By the 1980s, the United States was down to a few dozen breweries. In the dismally conformist 1950s, Jack Kerouac and many others planted seeds for the cultural rebellion of the 1960s. Similarly, in the 1970s, as the United States spiraled toward brewing oblivion, -DFN 0F$XOLÎ?HČ&#x2021;V 1HZ $OELRQ %UHZHU\ EHFDPH WKH Č´UVW RI D ZDYH 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 Î&#x2013;QQRYDWRU 2YHU LQGHSHQGHQW EUHZHULHV QRZ SRXU VWULNLQJO\ inventive potions along with traditional, classic styles of beer. The opportunity for microbiological creativity has never been greater. 1RZ IDPLOLHV JDWKHU LQ WKH SDUNLQJ ORWV RI UXUDO PLFUREUHZHU\ taphouses and beer lovers pack craft beer showplaces into the QLJKW LQ HYHU\ PDMRU FLW\ LQ WKH :HVWHUQ ZRUOG 7RGD\ PD\ EH WKH EHVW WLPH HYHU WR Č´QG QHZ EHHUV PDNH QHZ IULHQGV DQG WUXO\ 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, DCâ&#x20AC;&#x2122;s legendary Brickskeller. Bob and Ellie are publishing their book Drinking In the Culture: Tuppersâ&#x20AC;&#x2122; Guide to Exploring Great Beers in Europe, a European travel guide for beer lovers, in June 2015; information at CulturAlePress.com.
CULTURES Vol 2, Issue 2 Âť Page 33
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
CULTURES Vol 2, Issue 2 » Page 35
The other day, as I drove my son home from school, I was thinking about how much my own laboratory has changed over WKH SDVW GHFDGH :RXOGQČ&#x2021;W \RX NQRZ LW RQH RI .DW\Č&#x2021;V UHFHQW KLWV began playing on the radio, accompanied by loud singing from the back seat. The song was titled â&#x20AC;&#x153;Dark Horse,â&#x20AC;? and, just to DFTXDLQW \RX ZLWK WKH PXVLF WKDW DSSHDOV WR \RXQJ ER\V WKHVH 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.
â&#x20AC;&#x153;T H E
Katy sang â&#x20AC;&#x153;So you wanna play with magic? Boy you should know whatcha falling for.â&#x20AC;? 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 LED US TO A PERFECT STORM â&#x20AC;&#x201C; A PL AC E IN WHICH THE COMBINATION OF RAPID AND 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 THE WAYS IN WHICH WE DIAGNOSE INFE C T I O N S.â&#x20AC;?
-JOSEPH CAMPOS
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 WKRVH ZLWK JURZWK 7KH VDPH HTXLSPHQW DOVR enables suspicious colonies to be subcultured WR IUHVK PHGLD RU LQRFXODWHG WR LGHQWLČ´FDWLRQ susceptibility test panels without a human touching the culture plate. It is theoretically possible for todayâ&#x20AC;&#x2122;s microbiology technologist to complete a dayâ&#x20AC;&#x2122;s work while wearing pajamas, VLSSLQJ FRÎ?HH DQG UHOD[LQJ LQ D UHFOLQHU DW KRPH
As amazing as that sounds, there is another WRWDOO\ GLÎ?HUHQW NLQG RI PDJLF PDNLQJ LQURDGV LQWR laboratories around the world. It is the magic of matrix-assisted ODVHU GHVRUSWLRQ LRQL]DWLRQČ&#x201A;WLPH RI ČľLJKW 0$/'Î&#x2013; 72) WKDW HQDEOHV LVRODWHV WR EH LGHQWLČ´HG YLD SURWHRPLFV LQ D PDWWHU RI PLQXWHV DW an extremely low cost. Yes, there is an up-front investment to the Page 36 Âť Across the Divide Âť Campos
WXQH RI D VL[ Č´JXUH QXPEHU RI GROODUV WR SXUFKDVH WKH QHFHVVDU\ PDVV spectrometer, but, in high-volume laboratories, the return on that investment is achieved in a relatively short time through not purchasing FRQYHQWLRQDO LGHQWLČ´FDWLRQ WHVWV In another part of â&#x20AC;&#x153;Dark Horseâ&#x20AC;? Katy Perry chants â&#x20AC;&#x153;Are you ready for, ready for, a perfect storm, perfect storm. â&#x20AC;&#x2DC;Cause once youâ&#x20AC;&#x2122;re mine, once youâ&#x20AC;&#x2122;re mine. Thereâ&#x20AC;&#x2122;s no going back.â&#x20AC;? The magic of molecular testing has led us to a perfect storm â&#x20AC;&#x201C; 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 DFLG VHTXHQFHV ZKHWKHU WKURXJK DPSOLI\LQJ NQRZQ WDUJHWV RU VHTXHQFLQJ XQNQRZQ WDUJHWV KDV DOUHDG\ KDG D KXJH LPSDFW RQ PDQ\ laboratories. It stands to reason that for physicians and patients who KDYH EHQHČ´WWHG IURP PROHFXODU WHVWLQJ WKHUH LV QR JRLQJ EDFN 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 WR GHWHFW VLQJOH WDUJHWV XQLTXH WR LQGLYLGXDO PLFURRUJDQLVPV 1RW PXFK ODWHU FDPH WKH DELOLW\ WR TXDQWLWDWH WKRVH WDUJHWV VR WKDW WKH HÉ?FDF\ RI DQWLPLFURELDO WKHUDS\ FRXOG EH TXLFNO\ DQG DFFXUDWHO\ DVVHVVHG 7KH QH[W 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 UHFRJQL]H GR]HQV RI GLÎ?HUHQW PLFURRUJDQLVPV in a single reaction mixture.
â&#x20AC;&#x153;â&#x20AC;&#x2DC;SO YOU WANNA PL AY WITH MAGIC? BOY YOU SHOULD KNOW WHATCHA FALLING F OR.â&#x20AC;&#x2122; IN A SENSE, 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.â&#x20AC;?
So have we reached the end of the microbiology -JOSEPH CAMPOS, PDJLF" )DU IURP LW 7KH DYDLODELOLW\ RI KLJKO\ automated, â&#x20AC;&#x153;sample to resultâ&#x20AC;? testing platforms QUOTING KAT Y PERRY is bringing molecular assays to the masses, all DURXQG WKH JOREH Î&#x2013;VRWKHUPDO DPSOLČ´FDWLRQ is now a reality that obviates the need for expensive thermocyclers, and these assays will soon threaten the RQFH XQWRXFKDEOH GRPLQDQFH RI 3&5 :LWKLQ WKH SDVW IHZ PRQWKV WKH Č´UVW &OLQLFDO /DERUDWRU\ Î&#x2013;PSURYHPHQW $PHQGPHQWV &/Î&#x2013;$ ZDLYHG molecular platform and assays were cleared for use in the United CULTURES Vol 2, Issue 2 Âť Page 37
THE EVOLUTION OF THE PCR MACHINE:
A DIAGNOSTIC TOOL
PRO/PETTE 1980s The pro/pette was a prototype that would later b ecom e a part of th e fi r s t PCR machine. It had the ability to manipulate small volumes of liquid on a m icrotiter p la te.
MR. CYCLE, THERMAL CYCLER 1984 - 1985 To use the first automated PCR ma ch i n e, s c i e n t i s t s h a d t o s t a n d at the lab bench for several hours as they moved samples between water baths of varying temperatures and were required to inject new enzymes each cycle.
DNA THERMAL CYCLER 1
DNA THERMAL CYCLER 480
1987
1990
The DNA Thermal Cycler 1 w as the f irst com mer ci a l instrum ent, with a ca p a ci ty of 48 samples.
The DNA Thermal Cycler 480 was the first PCR ma ch i n e wi t h a c a p a c i t y of 96 samples.
SON OF CYCLE, THERMAL CYCLER 1985 - 1986 T h e Son of Cycle in cor p or a ted two important innovations that made the PCR m ac h i n e mor e au tom atic. It used T a q DNA P o ly merase, no long er r equi r i n g th e a d dition of f res h en z y mes after each denaturation step. I t also included semi con ductor el ements f or heating a n d cooli n g t h e sam ple- hold i n g b lock , el imi nating the nee d to tr a n s fer th e sa m ples between w a ter b a th s .
BABY BLUE 1986 T h e B a by B l u e wa s t h e fi r s t s i n g l e i n s t r u m e n t to integrate the software cycling controller with the th er m a l c yc l i n g bl o c k .
REAL-TIME MACHINES (RT-PCR) 1996 R eal- tim e PCR m a ch i n es h i t the market, allowing for a targeted DN A m olecule to be detected as the r ea cti on pro cesses in real time, r a th er th a n being d etect ed a t th e end of the reaction. Today, m any d if f erent m a ch i n e types exist and are able to process up to 384 samples at o nc e and run up to 40 cy cles in under 10 m i n utes .
1996
Hands-on work: An old method of Č´OOLQJ WXEHV 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 non-laboratory 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 VLJQLČ´FDQW UHDOORFDWLRQ RI WHVWLQJ UHYHQXH There still remains at least one more untapped source of laboratory magic and that is the use of high-throughput, nextJHQHUDWLRQ '1$ 51$ VHTXHQFLQJ QRW RQO\ IRU WKH GLDJQRVLV RI infectious diseases, but also for the recognition of virulence factor and antimicrobial resistance genetic markers. The costs RI VHTXHQFLQJ UHDJHQWV DQG HTXLSPHQW DUH VWLOO YHU\ KLJK DQG WKH DVVD\V DUH TXLWH FXPEHUVRPH DQG WLPH FRQVXPLQJ EXW WKDW was also the state of PCR testing not that long ago. Technological advances and the automation of complex procedures are LQHYLWDEOH DQG ZLOO RFFXU LQ WKH QHDU IXWXUH Î&#x2013; DP FRQČ´GHQW WKDW
Page 40 Âť Across the Divide Âť Campos
VHTXHQFLQJ DVVD\V ZLOO EH IRXQG LQ PDLQVWUHDP ODERUDWRULHV and will become the preferred method for diagnosis of certain LQIHFWLRQV 6HTXHQFLQJ WHFKQRORJ\ ZLOO DOVR RSHQ WKH JDWH WR microbiome analyses of individual patients â&#x20AC;&#x201C; 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 DQG 3&5 DVVD\V DUH QHJDWLYH 7KH VHTXHQFLQJ RI PLFURELDO QXFOHLF acids from the same specimens can still provide actionable LQIRUPDWLRQ 2QFH ZH EHJLQ XWLOL]LQJ SHUKDSV WKH PRVW SRZHUIXO magic yet to salvage a diagnosis from specimens that used to be XVHOHVV LW PD\ EH WLPH WR KXP D GLÎ?HUHQW .DW\ 3HUU\ KLW 7KH VRQJ LV Č&#x160;:LGH $ZDNH Č&#x2039; DQG LQ LW VKH VLQJV Č&#x160;Î&#x2013; ZLVK Î&#x2013; NQHZ WKHQ ZKDW Î&#x2013; NQRZ now.â&#x20AC;? I predict that a lot of us will have the same feeling as the PLFURELRORJ\ PDJLF NHHSV ČľRZLQJ
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 Childrenâ&#x20AC;&#x2122;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 centerâ&#x20AC;&#x2122;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. Dr. Campos currently serves as ASMâ&#x20AC;&#x2122;s Secretary (2007-present).
CULTURES Vol 2, Issue 2 Âť Page 41
MEASLES AND RUBELLA ELIMINATION:
WHY NOW? JON KIM ANDRUS, M.D. LOUIS Z. COOPER, M.D.
Measles means “miserable” 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 AĮA?REÌA TAJJõELRACP=RA@ QRP=RACEAQ 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 JA@ CJM>=J AĮMPRQ RM AP=@E?=RA QK=JJNMU
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As the theme of this special issue implies, â&#x20AC;&#x153;foundationsâ&#x20AC;? provide WKH Č&#x160;VWXÎ?Č&#x2039; RU V\VWHPV DQG FDSDFLW\ XSRQ ZKLFK WR EXLOG VXFFHVVIXO 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 :HVWHUQ +HPLVSKHUH 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 WKDW OHDYHV D FKLOG ZLWK D OLIHWLPH RI VXÎ?HULQJ IURP DQ\ FRPELQDWLRQ of intellectual disability, autism, blindness, deafness, and cardiac GHIHFWV Î&#x2013;Q WKDW VHQVH LW LV YHU\ VLPLODU WR WKH FRQVHTXHQFHV RI 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 VDIH DQG HÎ?HFWLYH YDFFLQHV DQG FDQ DFWXDOO\ EH HOLPLQDWHG )URP 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 VLJQLČ´FDQW RXWEUHDNV LQ GHYHORSHG QDWLRQV PRVW UHFHQWO\ LQ 3RODQG and Japan, with at least 50 reported cases of infants being born with congenital rubella syndrome in each country. 2QH UHDVRQ ZK\ PRUH LV QRW EHLQJ GRQH WR HOLPLQDWH FRQJHQLWDO UXEHOOD V\QGURPH LV WKDW WKH GLVHDVH EXUGHQ LV GLÉ?FXOW WR PHDVXUH As a result, the political commitment to eliminate this disease is undermined. Babies born with damaged central nervous systems DUH QRW OLQNHG WR Č´UVW WULPHVWHU UXEHOOD LQIHFWLRQ 7R FRPSRXQG 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 â&#x20AC;&#x153;pushâ&#x20AC;? 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 Âť Across the Divide Âť 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 FRVWV RI DɞLFWHG 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 HHFWLYHO\ WR HPHUJLQJ LQIHFWLRQV DQG RWKHU
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national security threats. Measles, rubella, and congenital rubella syndrome elimination becomes the litmus test for any particular FRXQWU\Č&#x2021;V FDSDFLW\ WR UHVSRQG HÎ?HFWLYHO\ WR HPHUJLQJ GLVHDVH 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 VXFFHHG 6XFK LV WKH FDVH ZLWK (EROD LQ :HVW $IULFD 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 SURJUDP 9DFFLQDWLRQ PXVW EH FRXSOHG ZLWK KLJK TXDOLW\ VXUYHLOODQFH for early detection of new cases to prevent large outbreaks and to direct focused vaccination strategies. Success can be better assured ZLWK HÎ?HFWLYH OHDGHUVKLS DQG PDQDJHPHQW DW DOO OHYHOV RI WKH 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 DFWLYLWLHV DQG LQFOXGH DVVXUHG YDFFLQH VXSSO\ VXÉ?FLHQWO\ WUDLQHG DQG
Measles Elimination Campaigns: A health worker in Bossangoa, Central African Republic, prepares a vaccine dose.
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H[SHULHQFHG KXPDQ UHVRXUFHV HÎ?HFWLYH FRPPXQLFDWLRQ DQG VRFLDO PRELOL]DWLRQ VWUDWHJLHV DQG DGHTXDWH ORJLVWLFV DQG FROG FKDLQ Many experts would argue that rubella, congenital rubella syndrome, and measles are easier to eliminate than polio. But certainly their HOLPLQDWLRQ ZRXOG JUHDWO\ EHQHČ´W IURP HQJDJLQJ DQG LQWHJUDWLQJ 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. $V RXWOLQHG LQ WKH *OREDO 9DFFLQH $FWLRQ 3ODQ *9$3 RI WKH :RUOG +HDOWK 2UJDQL]DWLRQ DFKLHYLQJ PHDVOHV UXEHOOD DQG FRQJHQLWDO 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 DOO FKLOGUHQ 2I WKH Č´YH VSHFLČ´F JRDOV WZR FRYHU WKH HUDGLFDWLRQ RI polio and the elimination of measles, rubella, and congenital rubella syndrome by 2020. Global, regional, and national buy-in for GVAP was GHPRQVWUDWHG E\ LWV DSSURYDO E\ WKH :RUOG +HDOWK $VVHPEO\ LQ The accomplishments of the public/private partnership led by the 3DQ $PHULFDQ +HDOWK 2UJDQL]DWLRQ DQG JOREDOO\ E\ WKH 0HDVOHV DQG Rubella Initiative, document that elimination and even eradication are feasible. Although it would be naĂŻve to believe the goal is easy, LWV PHDVXUDEOH EHQHČ´WV PRUDO KXPDQLWDULDQ HFRQRPLF DQG SROLWLFDO 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):D91â&#x20AC;&#x201C;D96. $QGUXV -. &DVWLOOR 6RORU]DQR & GH 2OLYHLUD / 'DQRYDUR +ROOLGD\ 0& Strengthening surveillance: confronting infectious diseases in developing countries. Vaccine 29(Suppl 4):D126â&#x20AC;&#x201C;D130. $QGUXV -. $JXLOHUD ; 2OLYD 2 $OGLJKLHUL 6 *OREDO KHDOWK VHFXULW\ 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, VHUYLQJ DV D 'LVWULFW 0HGLFDO 2É?FHU LQ Malawi and has since held positions in the U.S. Centers for Disease Control and Preventionâ&#x20AC;&#x2122;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 (2001â&#x20AC;&#x201C;2002) of the American Academy of Pediatrics (AAP). As current chair of the International Pediatric Association Technical Advisory Group RQ Î&#x2013;PPXQL]DWLRQ 'U &RRSHUČ&#x2021;V HÎ?RUWV 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 TAPA ÐPQR ELRPM@S?A@ RM RPA=R ELBA?REMSQ 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 WKH HHFWV ZLOO EH VXVWDLQHG DIWHU 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). WKRXJKW WR EH GLɝFXOW FRQWH[WV 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 » Across the Divide » Laxminarayan
not fail treatment with the more readily available first- and VHFRQG OLQH DQWLELRWLFV :KDW ZH GR QRW NQRZ LV KRZ WR FRQYH\ 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, WKH\ DUH RYHUXVHG DQG EHFRPH LQHHFWLYH 7KH VRFLDOO\ DSSURSULDWH 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
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 IXQFWLRQV DQG UHVLVWDQFH IDFWRUV 'HYHORSPHQW HÎ?RUWV 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 RI FROLVWLQ D GUXJ Č´UVW LQWURGXFHG LQ the 1950s, can reduce toxicity and LPSURYH HÉ?FDF\ Today, bacterial infections like pneumonia and gonorrhea, which could be treated with penicillin for SHQQLHV D GRVH UHTXLUH DQWLELRWLFV 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 â&#x20AC;&#x153;THE COMING CRISIS moved onto chronic diseases where IN ANTIBIOTICSâ&#x20AC;? IN there is much more money to be SEPTEMBER 2014. made. But that does not make sense. VIEW IT AT Shouldnâ&#x20AC;&#x2122;t pharmaceutical companies be interested in selling antibiotics in a http://ow.ly/MHcvW 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 CULTURES Vol 2, Issue 2 Âť Page 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 ZLOO EH KDUG WR Č´QG DQG PRUH H[SHQVLYH WR EULQJ WR PDUNHW LQ WKH VDPH 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. 2I FRXUVH WKHUH DUH WKRVH ZKR PD\ QRW EH DEOH WR DÎ?RUG WKH QHZ antibiotics, but the same is true for expensive gene therapy or cancer GUXJV DQG ZH VKRXOG Č´QG ZD\V RI ensuring that no one dies because of a lack of access to medicines that WKH\ FDQQRW DÎ?RUG 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 )OHPLQJČ&#x2021;V Č´UVW SXEOLVKHG DUWLFOH RQ 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 WR Č´QG XV D QHZ DQWLELRWLF" 1R RQH ZRXOG DUJXH WKDW ZH VKRXOG VXEVLGL]H WKH GLVFRYHU\ RI QHZ 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 Âť Across the Divide Âť 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 XVHG LQ RXU KRVSLWDOV DQG FRPPXQLW\ EXW DQ LQYHVWPHQW LQ Č´OOLQJ LQ 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 KHOSHG FUHDWH WKH $Î?RUGDEOH Medicines Facility for malaria, a QRYHO Č´QDQFLQJ PHFKDQLVP WR GHOD\ 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 SKUDVH WKH\ XVH LV Č&#x160;VNLS WHFKQRORJLHV Č&#x2039; :KDW GR \RX WKLQN RI WKDW" :H NQRZ WKDW LW LV D ORDGHG TXHVWLRQ EHFDXVH LW is not always easy in resource-constrained settings to just GURS GRZQ WKH HTXLSPHQW %XW ZKDW GR \RX WKLQN LV WKH most important focus in doing clinical microbiology in developed settings? ELLEN: 7KDW LV D EULOOLDQW TXHVWLRQ Î&#x2013; KDG QHYHU WKRXJKW 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 WKDW \RX Č´QG LQ GHYHORSLQJ FRXQWULHV Î&#x2013; ZLOO JLYH \RX VRUW RI a strange example with Cambodia, the country with which I am most familiar. In Cambodia, our nongovernmental RUJDQL]DWLRQ 1*2 VXSSRUWV VHYHQ ODERUDWRULHV DOO of which diagnose diseases that are not on the list for big donor projects. Big donor projects often include HIV, TB, and malaria. â&#x20AC;&#x153;The Big Threeâ&#x20AC;? are well taken care of, and new technologies such as the Cepheid GeneXpert for TB, rapid enzyme amino acid lateral ČľRZV IRU PDODULD DUH RXW WKHUH $ ORW RI HÎ?RUW LV EHLQJ SODFHG 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 â&#x20AC;&#x201C; those kinds of things Č&#x201A; WKDW SUREDEO\ DÎ?HFW PRUH SHRSOH overall than the three that I mentioned â&#x20AC;&#x201C; nobody is paying attention to making little tiny cutting-edge diagnostics IRU WKRVH 6R RXU 1*2 IRFXVHV RQ 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 RU ZKHUH WKH\ DUH QRW DÎ?RUGDEOH Î&#x2013; am sure there is a Kiestra giant total laboratory automation system for doing microbiological cultures, but that would probably cost more than the entire countryâ&#x20AC;&#x2122;s budget for health care just to purchase one instrument.) JASON: 2QH WKLQJ ZH WKRXJKW ZRXOG EH UHDOO\ LQWHUHVWLQJ WR DVN \RX VLQFH \RX KDYH VXFK D XQLTXH SHUVSHFWLYH KDYLQJ ZRUNHG LQ WKH developing and resource-limited setting for decades â&#x20AC;&#x201C; is it getting EHWWHU" 2U LV LW MXVW DQ RQJRLQJ FKDOOHQJH ZH UHDOO\ QHHG WR GHGLFDWH ourselves to? ELLEN: I think schools are getting better. I have visited some very DPD]LQJ VFKRROV DURXQG WKH ZRUOG WKDW DUH EHLQJ VXSSRUWHG E\ 1*2V and the teachers are dedicated, and they are bringing in more and more students. 2XU ODERUDWRULHV LQ &DPERGLD DUH JHWWLQJ EHWWHU IRU VXUH $V D PDWWHU RI fact, we are stopping all of our laboratoriesâ&#x20AC;&#x2122; or most of our laboratoriesâ&#x20AC;&#x2122; GHYHORSLQJ DFWLYLWLHV LQ &DPERGLD :H DUH FRQFHQWUDWLQJ DOO RI RXU resources, money, and people on medical school education, and changing medical training, because physicians have not been able to NHHS XS ZLWK ODERUDWRULHV :H DUH QRZ DKHDG RI WKH SK\VLFLDQVČ&#x2021; DELOLW\ Page 60 Âť In Conversation
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: 7KHUH DUH IHZ GLÎ?HUHQFHV WKH\ DUH SUHWW\ PXFK WKH VDPH LQ PDQ\ VHQVHV 7KH RQO\ NH\ GLÎ?HUHQFH LV DFFHVV WR UHVRXUFHV For example, students everywhere rely on the Internet. However, students at Stanford certainly have more and better access to the Internet. The students overseas may not have access to the Internet as easily â&#x20AC;&#x201C; 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 VSHFLDO DERXW &DPERGLD :KDW ZDV LW WKDW GUHZ \RX WKHUH RULJLQDOO\ and why did you choose to drill down there and make such a big GLÎ?HUHQFH" Č&#x201A; ZKLFK \RX FHUWDLQO\ KDYH ELLEN: I have to credit two people with that: Jim McLaughlin, now WKH &(2 RI '0'3 DQG 3DW +RJDQ FXUUHQWO\ D PLFURELRORJLVW ZLWK CULTURES Vol 2, Issue 2 Âť Page 61
My Major Accomplishments â&#x20AC;˘ 1983 - Fho^] mh GR< and joined group of clinical micro lab director pioneers, unofficially led by Dr. Henry Isenberg. Henry got me involved in :LF chnkgZel !Zl ^]bmhk"% books, and local and gZmbhgZe :LF community leadership. â&#x20AC;˘ 1984 - Dr. Finegold offered me the opportunity to coauthor the major textbook Bailey and Scottâ&#x20AC;&#x2122;s Diagnostic Microbiology with him, thus beginning
3Č´]HU Î&#x2013;Q ERWK ZHUH ZRUNLQJ on global health in Cambodia, Jim as D &'& FRQVXOWDQW DQG 3DW DV D 3Č´]HU fellow working in the microbiology laboratory at the Angkor Hospital. $W WKH WLPH Î&#x2013; ZDV JLYLQJ D :+2 OHFWXUH in Malaysia, and, having two friends in &DPERGLD Î&#x2013; DVNHG P\VHOI Č&#x160;:K\ GRQČ&#x2021;W Î&#x2013; just stop there on my way home from .XDOD /XPSXU"Č&#x2039; 6R Î&#x2013; GLG :KHQ Î&#x2013; VDZ what was going on there, I realized that the way microbiology was being WDXJKW ZDV QRW IXOČ´OOLQJ WKH QHHGV RI the Cambodian people, and that the :+2 ZRUNVKRS Î&#x2013; ZDV JLYLQJ ZRXOG QRW IXOČ´OO WKRVH QHHGV HLWKHU
a 12-year history of writing that book. â&#x20AC;˘ 1990 - Began writing and editing the ASM Manual of Clinical Microbiology. I worked with Dr. Pat FnkkZr hg maZm [hhd _hk three editions. â&#x20AC;˘ 1996 - Became World Health Organization expert trainer, leading and teaching WHO courses with John Stelling, who ]^o^ehi^] PAHG>M' â&#x20AC;˘ 2007 - Took sabbatical and developed the Basic ;^g\amhi Fb\kh ?ehp\aZkm training program. â&#x20AC;˘ 2008 - <h_hng]^] =F=I pbma Cbf F\EZn`aebg' â&#x20AC;˘ 2008 - Started working Zm <^ia^b]% a^eibg` mh develop rapid, nearpatient molecular diagnostic tests that are changing the world.
So, I took a sabbatical from Stanford in 2007 and developed a training SURJUDP WKH ČľRZFKDUW SURJUDP ZKLFK is now used widely as a microbiology mentoring program. Foundation Merieux, which supports the developing worldâ&#x20AC;&#x2122;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. $IWHU Î&#x2013; Č´QLVKHG JLYLQJ WKLV ZHHN ORQJ workshop to local microbiologists, they said, â&#x20AC;&#x153;You cannot just leave now; you have to stay and help us LPSOHPHQW DOO WKLV VWXÎ? Č&#x2039; /RQJ VWRU\ short, with initial funding from the Global Fund, we started our own 1*2 WKH 'LDJQRVWLF 0LFURELRORJ\ 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 /DRV DQG &DPERGLD DV D FRQVHTXHQFH RI WKH XQH[SORGHG GHYLFHV IURP WKH 9LHWQDP :DU" Î&#x2013; NQRZ WKDW WKDW FDPSDLJQ 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 ZRUN ZLWK WKHUH EHOLHYH WKDW ZH VKRXOG FRQFHQWUDWH RXU HÎ?RUWV RQ EORRG 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 ČľXLG FXOWXUHV DQG WKDW VRUW RI WKLQJ DQG OHVVHU RQ WKH RWKHU WKLQJV %XW LI 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: Î&#x2013; FDOOHG \RX WKH TXHHQ RI PLFURELRORJ\ ZKLFK E\ WKH ZD\ LV true. This brings us to you being on the frontiers as well. You mentioned \RXU WUDLQLQJ SDFNDJH VR KXPEO\ :H DUH ZHOO DZDUH RI LWV LPSDFW around the world because we train literally thousands of people a year through the Laboratory Capacity program with your package â&#x20AC;&#x201C; with the Microbiology Mentoring package, we call it. Certainly, that is already \RXU OHJDF\ %XW ZKDW GR \RX VWLOO KDYH \HW WR GR" :KDW DUH \RX VWLOO SDVVLRQDWH DERXW DFKLHYLQJ" :KDW DUH \RX UHDOO\ KRSLQJ WR GR QRZ" ELLEN: Î&#x2013; DP KRSLQJ WR GR PRUH WUDLQLQJ DFWXDOO\ :KHQ Î&#x2013; VWRS ZRUNLQJ so much for Cepheid, which will come at the end of this year â&#x20AC;&#x201C; I will go to part-time. I am hoping to get back into the medical school training arena. Right now, Stanford is doing something called the Č&#x160;ČľLSSHG FODVVURRPČ&#x2039; ZKLFK D ORW RI PHGLFDO VFKRROV KDYH GRQH RU DUH 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 CULTURES Vol 2, Issue 2 Âť Page 63
Page 64 Âť In Conversation
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 VLWXDWLRQ DQG ZKHQ \RX DUH QRW WKHUH QRERG\ JHWV LW :H DUH JRLQJ WR EH GRLQJ WKDW DW &HSKHLG :H DUH PDNLQJ YLGHRV WKDW SHRSOH FDQ DFFHVV DW DQ\ WLPH :H DUH JRLQJ WR EH GRLQJ WKDW DW 6WDQIRUG DQG SRVVLEO\ with ASMâ&#x20AC;&#x2122;s training modules. JASON: :HOO Î&#x2013; FDQ WKLQN RI QRWKLQJ PRUH LPSDFWIXO (GXFDWLRQ FXUULFXOD ULJKW QRZ FRXOG UHDOO\ XVH \RXU KHOS :KDW DGYLFH ZRXOG \RX JLYH WR young people who are interested in a career in microbiology as they head into science or even into development? ELLEN: Î&#x2013; ZRXOG VD\ WKH\ QHHG WR OHDUQ WKH LQIRUPDWLRQ DERXW WKH Č´HOG 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. /HDUQ LW DV ZHOO DV \RX FDQ :ULWH SXEOLVK DQG WKHQ EH DEOH WR VSHDN 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 7HFKQLFDO $Î?DLUV DW &HSKHLG LQ 6XQQ\YDOH &$ 'U %DURQ LV YHU\ DFWLYH LQ WKH Č´HOG RI GLDJQRVWLF PLFURELRORJ\ DV D V\PSRVLXP SUHVHQWHU 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. Dr. Baron is an ASM International Board member.
CULTURES Vol 2, Issue 2 Âť Page 65
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Page 66 » On the Ground
MARY WOOLLEY For almost 25 years now, I have been the president and CEO of 1DRD@QBG} LDQHB@ SGD M@SHNMsR K@QFDRS MNS ENQ OQNÂ&#x;S @CUNB@BX @KKH@MBD 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
+RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" Iâ&#x20AC;&#x2122;m no microbiologist, but Iâ&#x20AC;&#x2122;m told that further development in the area RI VHTXHQFLQJ DQG PLFURVFRS\ ZLOO SURYLGH WKH DELOLW\ WR GR VHTXHQFLQJ LQ WKH Č´HOG DQG WR DQDO\]H VDPSOHV instantly. I think of how many lives ZLOO EH VDYHG DQG HQKDQFHG Î&#x2013; ORRN WR PLFURELRORJLVWV WR HÎ?HFWLYHO\ 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 EHFRPH HÎ?HFWLYH YRLFHV IRU UHVHDUFK to the nonscience public: the media, HOHFWHG DQG DSSRLQWHG RÉ?FLDOV DQG nonscientists everywhere, across the family holiday dinner table or on the VRFFHU Č´HOG RU WKH Î&#x2013;QWHUQHW
CULTURES Vol 2, Issue 2 Âť Page 67
JESSICA MEIR Astronauts support the overarching NASA mission of DWOKNQ@SHNM @MC RBHDMSHÂ&#x;B HMMNU@SHNM ANSG HM RO@BD @MC 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
KXPDQ ERG\ WR XWLOL]LQJ WKH XQLTXH microgravity environment to provide insight into processes in cell signaling or protein structure. As astronauts, we DUH IRUWXQDWH WR VHUYH DV ERWK VFLHQWLČ´F operators and test subjects to perform such experiments in space and collect data for the cadre of investigators back on the ground. :KDW LV WKH EHVW SDUW RI \RXU MRE"
:KDW UROH GRHV PLFURELRORJ\ SOD\ LQ \RXU FXUUHQW SURIHVVLRQ" The biological sciences are an essential component of the space program, IURP XQGHUVWDQGLQJ WKH HÎ?HFWV 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 RIWHQ DSSHDU DV WKH IDFH RI 1$6$ the scientists, engineers, support personnel, and entire team on the ground enable us to advance the presence of humans in space and to
Page 68 Âť On the Ground
FROM TOP TO BOTTOM
Flight training at Navy Pensacola. %DU KHDGHG JRRVH ȵLJKW WUDLQLQJ 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. +RZ GR \RX VHH WKH ȴHOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" 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 » Page 69
J O N K AY E A curiosity for what makes the geosphereâ&#x20AC;&#x201C;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 AQHMFHMF LX LHBQNAHNKNFX DWODQSHRD @MC RBHDMSHÂ&#x;B @OOQN@BG to bear on bioterrorism policy making. PROGRAM DIRECTOR / MARINE MICROBIOLOGY INITIATIVE AT THE GORDON & BETTY MOORE FOUNDATION / ASM FUTURES MEMBER
+RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" :H DUH DUULYLQJ DW SURIRXQG FODULW\ DERXW WKH GHSWK to which our world is microbial, and has been for billions of years. Developing new technologies, DGDSWLQJ DSSURDFKHV XVHG LQ RWKHU Č´HOGV DQG LQFUHDVLQJ WKH SHUPHDELOLW\ EHWZHHQ VFLHQWLČ´F disciplines will continue to push open doors in unexpected ways for the microbiological sciences. As the philosopher Donna Haraway summed up, â&#x20AC;&#x153;â&#x20AC;Śwe are in a knot of species coshaping one another in layers of reciprocating complexity all the way down,â&#x20AC;? and when we unravel this knot, we will perceive HTXLYDOHQW DPRXQWV RI WKH ORVV RI RXU KXPDQ LGHQWLW\ and the gain of a fantastical array of microbial friends.
Page 70 Âť On the Ground
L A U R A B O WAT E R I started my career as a microbiologist working in a laboratory where LX QDRD@QBG @CCDC SN SGD RBHDMSHÂ&#x;B TMCDQRS@MCHMF NE LHBQNAH@K 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 T O 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. +RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" 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 WLPH UHPDLQV RXWVLGH RXU Č&#x160;Č´HOG RI YLVLRQ Č&#x2039; At the same time, we will seek to exploit WKH SRWHQWLDO WKDW PLFUREHV RÎ?HU WR improve every aspect of our lives, from promoting health, combating disease,
ensuring food security, to combating global challenges. :KDW LV WKH EHVW SDUW RI \RXU MRE" 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.
CULTURES Vol 2, Issue 2 Âť Page 71
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 ) / A S M C O M M I T T E E F O R S U S TA I N A B L E D E V E LO P M E N T C H A I R
:KDW UROH GRHV PLFURELRORJ\ SOD\ LQ \RXU FXUUHQW SURIHVVLRQ" My understanding of microbiology KHOSV PH WR GHYHORS HÎ?HFWLYH 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.
:KDW VWHSV KDYH \RX WDNHQ WR JHW WR ZKHUH \RX DUH" 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
Page 72 Âť On the Ground
â&#x20AC;&#x153;â&#x20AC;? Microbiology will continue to become more international and more One Health oriented.
9LVLW WR D OLYH ELUG PDUNHW LQ -DNDUWD DV SDUW RI WKH $YLDQ Î&#x2013;QČľXHQ]D 3URJUDP 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 five years. Six years ago, I transitioned to USAID because I wanted to work overseas and work in the development field. :KDW LV WKH EHVW SDUW RI \RXU MRE" Î&#x2013; ORYH ZRUNLQJ LQ WKH Č´HOG KHOSLQJ JRYHUQPHQWV WR GHYHORS DQG LPSOHPHQW LQIHFWLRXV disease prevention and control programs, and also working at the community level ZKHUH WKH HÎ?RUWV WR SUHYHQW DQG WUHDW LQIHFWLRXV GLVHDVH VXFK DV 7% DQG LQČľXHQ]D have a major impact on peopleâ&#x20AC;&#x2122;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. +RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" 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 2QH +HDOWK RULHQWHG ZLWK KXPDQ KHDOWK DQG DQLPDO KHDOWK FRQWLQXLQJ WR EHFRPH PRUH integrated â&#x20AC;&#x201C; this is critical for issues of zoonotic diseases and antimicrobial resistance. CULTURES Vol 2, Issue 2 Âť Page 73
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
:KDW VWHSV KDYH \RX WDNHQ WR JHW WR ZKHUH \RX DUH" 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 P\ ZRUN H[SHULHQFH DW D ELRORJLFDO Č´HOG station and environmental monitoring and assessment program. :KDW LV WKH EHVW SDUW RI \RXU MRE" 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.
+RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" 1RZ WKDW PROHFXODU ELRORJ\ DQG stable isotope geochemistry tools DUH DYDLODEOH ZH FDQ Č´QDOO\ EHJLQ WR unravel the mysteries of the unknown RI WKH VRLO HFRV\VWHP :H ZLOO 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.
Page 74 Âť On the Ground
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 GD@KSG B@QD ONKHBX ENQ 2DM@SNQ $CV@QC *DMMDCX CDB@CD K@SDQ ( Â&#x;MC myself working for the leadership at the Department of State on data and transparency; Iâ&#x20AC;&#x2122;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
:KDW VWHSV KDYH \RX WDNHQ WR JHW WR ZKHUH \RX DUH" I began with a passion for applying the technical skills I learned through P\ GRFWRUDWH DW 2[IRUG WR DGGUHVV the most pressing societal challenges. Î&#x2013; Č´QG WKH PRVW H[FLWLQJ ZRUN RIWHQ exists at the intersection of two or
PRUH Č´HOGV VXFK DV VFLHQFH DQG 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. +RZ GR \RX VHH WKH Č´HOG RI PLFURELRORJ\ FKDQJLQJ LQ WKH QH[W \HDUV" $V ZLWK PDQ\ RWKHU Č´HOGV Î&#x2013; WKLQN WKH 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 KIDS’ EDITION. That’s right, pull out your crayons 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 (K-4). 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.
CULTURES Vol 2, Issue 2 » Page 77
“Ferdinand Cohn”
“Rosalind Franklin”
“E.Coli grocery store”
FROM THE ASM IMAGE ARCHIVE: SEE THESE IMAGES & MORE BY FOLLOWING
@
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”
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 DIRECTOR / SUSTAINABLE AGRICULTURE TANZANIA Featured on page 86 of Volume 2, Issue 1 of Cultures.
Page 80 » Questions, Comments, & Corrections
S, S, & ONS CORRECTION: On page 58, in Volume 2, Issue 1 of Cultures:
You’re never too young to start enjoying Cultures!
DO YOU HAVE SOMETHING TO SAY TO CULTURES? We’d love to hear from you! Was there an article you particularly enjoyed? Or something you want to read more about? Maybe you saw a mistake (hey, we’re human)! Reach out to us at cultures@asmusa.org.
WE INCORRECTLY L ABELED INFORMATION ON THE CHART AS FAHRENHEIT INSTEAD OF CELSIUS.
The views and opinions expressed in this publication are those of the individual authors and do not necessarily represent RU UHȵHFW WKH YLHZV RI the American Society for Microbiology.
Photography + Art Credit Page 5: Courtesy of Tim Donohue Page 8: &RXUWHV\ RI &+20$ Kolmer, John A. Serum Diagnosis by Complement Fixation with Special Reference to Syphilis. The 3ULQFLSOHV 7HFKQLTXH DQG &OLQLFDO Applications. 1928 Page 9: &RXUWHV\ RI &+20$ Gorham, Frederick P. A Laboratory Course in Bacteriology for the Use of Medical, Agricultural, and Industrial Students. 1901 Page 13: Marsha Miller, Director of Photography, UT-Austin Page 14: Brett Buchanan Page 18: Courtesy of the Center for the History of Microbiology/ $60 $UFKLYHV &+20$ .ROPHU John A. Serum Diagnosis by Complement Fixation, with special reference to syphilis. The 3ULQFLSOHV 7HFKQLTXH DQG &OLQLFDO Applications. 1928 Page 20: â&#x20AC;&#x153;French Biologist /RXLV 3DVWHXUČ&#x2039; E\ )HOL[ 1DGDU :LNLPHGLD &RPPRQV LV OLFHQVHG under CC-BY-SA 3.0 Page 21: Robert Hookeâ&#x20AC;&#x2122;s microscope from Scheme I of his 1665 â&#x20AC;&#x153;Micrographiaâ&#x20AC;? is licensed under CC-BY-SA 3.0. 2Q SHUPDQHQW GLVSOD\ LQ Č&#x160;7KH Evolution of the Microscopeâ&#x20AC;? H[KLELW DW WKH 1DWLRQDO 0XVHXP of Health and Medicine, in :DVKLQJWRQ '& Page 22: â&#x20AC;&#x153;Robert Kochâ&#x20AC;? by :LOKHOP )HFKQHU :LNLPHGLD Commons is licensed under CC-BY-SA 3.0. Page 23: â&#x20AC;&#x153;Alexander Fleming, who is credited with discovering penicillin in 1928â&#x20AC;? by Calibuon / :LNLPHGLD &RPPRQV LV OLFHQVHG under CC-BY-SA 3.0.
Page 24: â&#x20AC;&#x153;Pasteur experimenting in his laboratoryâ&#x20AC;? by Tungsten / :LNLPHGLD &RPPRQV LV OLFHQVHG under CC-BY-SA 3.0. Page 26: â&#x20AC;&#x153;Do you actually _drink_ WKH VWXÎ?"Č&#x2039; E\ 'DQLHO LV OLFHQVHG XQGHU && %< 1& 6$ Page 28: Courtesy of Bob Tupper Page 29: â&#x20AC;&#x153;Dr. J.C. Ayer and Co.â&#x20AC;? by Miami U. Libraries 'LJLWDO &ROOHFWLRQV :LNLPHGLD Commons is licensed under CC-BY-SA 3.0. Page 32: â&#x20AC;&#x153;Published 1914â&#x20AC;? / :LNLPHGLD &RPPRQV LV OLFHQVHG under CC-BY-SA 3.0. Page 32: Č&#x160;:DVKLQJWRQČ&#x2039; E\ + Rousseau (graphic designer), E. 7KRPDV HQJUDYHU :LNLPHGLD Commons is licensed under CC-BY-SA 3.0. Page 32: â&#x20AC;&#x153;Appletonsâ&#x20AC;&#x2122; Adams 6DPXHOČ&#x2039; E\ -DFTXHV 5HLFK :LNLPHGLD &RPPRQV LV OLFHQVHG under CC-BY-SA 3.0. Page 34: Č&#x160;1HLJKERUKRRG Diagnostic Testingâ&#x20AC;? illustration by Tim Skirven. Page 38: â&#x20AC;&#x153;pro/pette, Prototypeâ&#x20AC;? E\ WKH 6PLWKVRQLDQ 1DWLRQDO Museum of American History LV OLFHQVHG XQGHU && %< 1& http://americanhistory.si.edu/ collections/search/object/ nmah_1165104 Page 38: â&#x20AC;&#x153;Mr. Cycle, Thermal Cyclerâ&#x20AC;? by the Smithsonian from Roche Molecular Systems, Inc, WKURXJK 7KRPDV - :KLWH LV OLFHQVHG XQGHU && %< 1& http://americanhistory.si.edu/ collections/search/object/ nmah_1000862
Page 82 Âť Citations & Art Credit
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CULTURES Vol 2, Issue 2 Âť Page 83
Acknowledgments LIZ ROSE CHMELA TIM DONOHUE
AT TENTION:
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CULTURES |
VOLUME 2 |
ISSUE 2 |
2015
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