eBriefing

Microbes in the City

Microbes in the City
Reported by
Alan Dove

Posted March 16, 2016

Presented By

New York University

The New York Academy of Sciences

Overview

At the New York Academy of Sciences, researchers often discuss microscopic natural phenomena in full view of a vast cityscape of towering skyscrapers. The meeting on June 19, 2015, blended these seemingly disparate worlds. The Microbes in the City: Mapping the Urban Genome symposium, sponsored by the Academy and New York University, featured a diverse group—microbiologists, entomologists, engineers, and architects—who came together to discuss the microbiomes of the human-built environment.

The first session provided an overview of the burgeoning field of microbiomics, which uses high-throughput DNA sequencing techniques to study the huge population of unculturable microbes that previously eluded detection. These microbial ecosystems vary from person to person and place to place, and influence both normal human metabolism and disease pathogenesis.

Two sessions on the urban metagenome—a term describing genetic material recovered from environmental samples—surveyed efforts to identify novel pathogens before they emerge in humans, to understand hospital-acquired infections, and to probe the distinctive microbial ecosystems of buildings, subways, and sewers. The final presentation covered the fascinating but under-studied microbiology of insect pests.

The meeting closed with a panel discussion that covered the need for careful communication about research that may frighten the uninformed. The panelists also discussed the evolving regulatory framework for handling microbial data and microbiota-based products.

Use the tabs above to find a meeting report and multimedia from this event.

Presentations available from:
Eric Alm, PhD (Massachusetts Institute of Technology)
Jane Carlton, PhD (New York University)
Jack Gilbert, PhD (Argonne National Laboratory)
Jo Handelsman, PhD (White House Office of Science and Technology Policy)
Curtis Huttenhower, PhD (Harvard T.H. Chan School of Public Health)
W. Ian Lipkin, MD (Columbia University)
Christopher Mason, PhD (Weill Cornell Medical College)
Rachel Poretsky, PhD (University of Illinois at Chicago)
Moderator: Laurie Garrett (Council on Foreign Relations)


This symposium was made possible with support from

  • New York University

eBriefing Sponsor

  • Alfred P. Sloan Foundaton

This eBriefing was made possible with support from the Alfred P. Sloan Foundation via grant number G‐2015‐14187.


How to cite this eBriefing

The New York Academy of Sciences. Microbes in the City: Mapping the Urban Genome. Academy eBriefings. 2016. Available at: www.nyas.org/UrbanGenome2015-eB

Genomic Analysis of Microbial Communities: What Have We Learned?


Jo Handelsman (White House Office of Science and Technology Policy)
  • 00:01
    1. Introduction and history; Phylogenetics; Metagenomics
  • 08:26
    2. Discoveries from metagenomics and microbiome analyses
  • 21:22
    3. Outstanding questions; What is community robustness?; Can we manipulate the microbiome?
  • 27:16
    4. White House plan on the microbiom

The Changing Face of Pathogen Discovery


W. Ian Lipkin (Columbia University)
  • 00:01
    1. Introduction; Pathogen discovery; Zoonotic diseases and international transit
  • 05:25
    2. Estimating the zoonotic viral pool; Viral diversity in a population
  • 11:00
    3. Hepatitis C animal models; Kawasaki disease; Stillbirth research
  • 18:38
    4. Infections triggering chronic diseases; Exposure to infection during pregnanc

The Built Environment Microbiome: Health and Disease


Jack Gilbert (Argonne National Laboratory)
  • 00:01
    1. Introduction; Microbial signatures
  • 02:34
    2. Home microbiome study; Mapping microbial highways
  • 09:05
    3. Importance of microbial diversity; Ecosystems in buildings; Hospital stud

Using Metagenomics to Map Transmission of Species, Strains, and Genes


Eric Alm (Massachusetts Institute of Technology)
  • 00:01
    1. Introduction to tracking the gut microbiome; C. diff pathogenesis
  • 04:00
    2. Engineering microbial transmission to cure C. diff infection
  • 08:58
    3. Tracking transmission communities; Horizontal gene transfer
  • 12:45
    4. Transfer of regulatory regions across species (horizontal regulatory transfer

From Microbes to Molecules: Detailing Function in Integrated Multi'omics


Curtis Huttenhower (Harvard T.H. Chan School of Public Health)
  • 00:01
    1. Introduction; Function in integrated 'omics
  • 06:10
    2. Applications of assembly-independent metagenome profiling and other methods; How unique are meta'omic fingerprints?
  • 12:15
    3. Core human microbiome; Tools for functional profiling of the microbiome
  • 22:21
    4. Microbes in transit systems; HMP2 - Microbiome in diseas

Multi-kingdom Diversity of Subways and Cities with Metagenomics


Christopher Mason (Weill Cornell Medical College)
  • 00:01
    1. Introduction; Where do microbes come from?; Hopes and fears associated with microbiota
  • 06:44
    2. MYC Pathomap project - a city-scale metagenomics
  • 11:21
    3. Results across the five boroughs
  • 20:32
    4. Conclusion

Don't Forget the Protists! Characterizing Microbial Eukaryotes in New York City


Jane Carlton (New York University)
  • 00:01
    1. Introduction; Trichomonads, a zoonotic protist lineage
  • 04:10
    2. Surveilling Trichomonas vaginalis in NYC; Mapping the NYC Microbiome
  • 11:15
    3. Methods for sewage processing and sampling
  • 15:32
    4. Result

Wastewater Effluent Impacts on an Urban River Microbiome


Rachel Poretsky (University of Illinois at Chicago)
  • 00:01
    1. Introduction; Wastewater and treatment in Chicago; Data from Chicago River samples
  • 09:15
    2. Metagenomic data
  • 15:35
    3. Measuring the success of upcoming treatment plans; Conclusion

Panel: Ethical, Legal and Social Issues of Metagenomics


Moderator: Laurie Garrett (Council on Foreign Relations)
  • 00:01
    1. Introduction; Communicating scientific findings to the public; Funding and permission
  • 09:50
    2. Data reliability and standards; Legal considerations
  • 15:43
    3. What are the end goals? Microbiome of the built environment
  • 27:15
    4. Q and A sessio

Journal Articles

Ackelsberg J, Rakeman J, Hughes S, et al. Lack of evidence for plague or anthrax on the New York City subway. Cell Syst. 2015;1(1):4-5.

Afshinnekoo E, Meydan C, Chowdhury S, et al. Geospatial resolution of human and bacterial diversity with city-scale metagenomics. Cell Syst. 2015;1(1):72-87.

Alivisatos AP, Blaser MJ, Brodie EL, et al. A unified initiative to harness Earth's microbiomes. Science. 2015;350(6260):507-8.

Andersson S, Sikora P, Karlberg ML, et al. It's a dirty job—a robust method for the purification and de novo genome assembly of Cryptosporidium from clinical material. J Microbiol Methods. 2015;113:10-2.

Booth W, Balvín O, Vargo EL, et al. Host association drives genetic divergence in the bed bug, Cimex lectularius. Mol Ecol. 2015;24(5):980-92.

Briese T, Kapoor A, Mishra N, et al. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. MBio. 2015;6(5):e01491-01415.

Burstein D, Amaro F, Zusman T, et al. Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires. Nat Genet. 2016. [Epub]

Carlton JM, Das A, Escalante AA. Genomics, population genetics and evolutionary history of Plasmodium vivax. Adv Parasitol. 2013;81:203-22.

Chunara R, Goldstein E, Patterson-Lomba O, Brownstein JS. Estimating influenza attack rates in the United States using a participatory cohort. Sci Rep. 2015;5:9540.

Conrad MD, Kissinger P, Schmidt N, et al. Genetic diversity of Trichomonas vaginalis reinfection in HIV-positive women. Sex Transm Infect. 2013;89(6):473-8.

Dominguez-Bello MG, Blaser MJ. Asthma: Undoing millions of years of coevolution in early life? Sci Transl Med. 2015;7(307):307fs39.

Ehrenberg R. Urban microbes come out of the shadows. Nature. 2015;522(7557):399-400.

Faust K, Lima-Mendez G, Lerat J-S, et al. Cross-biome comparison of microbial association networks. Front Microbiol. 2015;6:1200.

Goff J, Rowe A, Brownstein JS, Chunara R. Surveillance of acute respiratory infections using community-submitted symptoms and specimens for molecular diagnostic testing. PLoS Curr. 2015;7.

Gordon J, Gandhi P, Shekhawat G, et al. A simple novel device for air sampling by electrokinetic capture. Microbiome. 2015;3(1):79.

Hicks LA, Blaser MJ. Variability in antibiotic prescribing: an inconvenient truth. J Pediatric Infect Dis Soc. 2015;4(4):e136-8.

Hicks LA, Taylor TH Jr, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368(15):1461-2.

Kaminski J, Gibson MK, Franzosa EA, et al. High-specificity targeted functional profiling in microbial communities with ShortBRED. PLoS Comput Biol. 2015;11(12):e1004557.

Kapoor A, Kumar A, Simmonds P, et al. Virome analysis of transfusion recipients reveals a novel human virus that shares genomic features with hepaciviruses and pegiviruses. MBio. 2015;6(5):e01466-01415.

Kurylo CM, Alexander N, Dass RA, et al. Genome sequence and analysis of Escherichia coli MRE600, a colicinogenic, nonmotile strain that lacks RNase I and the type I methyltransferase, EcoKI. Genome Biol Evol. 2016. [Epub ahead of print]

Ma B, Wang H, Dsouza M, et al. Geographic patterns of co-occurrence network topological features for soil microbiota at continental scale in eastern China. ISME J. 2016. [Epub ahead of print]

Maritz JM, Land KM, Carlton JM, Hirt RP. What is the importance of zoonotic trichomonads for human health? Trends Parasitol. 2014;30(7):333-41.

Oh S, Caro-Quintero A, Tsementzi D, et al. Metagenomic insights into the evolution, function, and complexity of the planktonic microbial community of Lake Lanier, a temperate freshwater ecosystem. Appl Environ Microbiol. 2011;77(17):6000-11.

Poretsky R, Rodriguez-R LM, Luo C, et al. Strengths and limitations of 16S rRNA gene amplicon sequencing in revealing temporal microbial community dynamics. PLoS ONE. 2014;9(4):e93827.

Preheim SP, Perrotta AR, Friedman J, et al. Computational methods for high-throughput comparative analyses of natural microbial communities. Meth Enzymol. 2013;531:353-70.

Shade A, Jones SE, Caporaso JG, et al. Conditionally rare taxa disproportionately contribute to temporal changes in microbial diversity. MBio. 2014;5(4):e01371-14.

Sinha R, Abnet CC, White O, et al. The microbiome quality control project: baseline study design and future directions. Genome Biol. 2015;16:276.

Smolinski MS, Crawley AW, Baltrusaitis K, et al. Flu near you: crowdsourced symptom reporting spanning 2 influenza seasons. Am J Public Health. 2015;105(10):2124-30.

Stollman N, Smith M, Giovanelli A, et al. Frozen encapsulated stool in recurrent Clostridium difficile: exploring the role of pills in the treatment hierarchy of fecal microbiota transplant nonresponders. Am J Gastroenterol. 2015;110(4):600-1.

Tadin A, Tokarz R, Markotić A, Margaletić J, et al. Molecular survey of zoonotic agents in rodents and other small mammals in Croatia. Am J Trop Med Hyg. 2015. [Epub]

Tsementzi D, Poretsky R, Rodriguez-R LM, et al. Evaluation of metatranscriptomic protocols and application to the study of freshwater microbial communities. Environ Microbiol Rep. 2014;6(6):640-55.

Udikovic-Kolic N, Wichmann F, Broderick NA, Handelsman J. Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization. Proc Natl Acad Sci U S A. 2014;111(42):15202-7.

Vargo EL, Crissman JR, Booth W, et al. Hierarchical genetic analysis of German cockroach (Blattella germanica) populations from within buildings to across continents. PLoS ONE. 2014;9(7):e102321.

Wada-Katsumata A, Zurek L, Nalyanya G, et al. Gut bacteria mediate aggregation in the German cockroach. Proc Natl Acad Sci U S A. 2015;112(51):15678-83.

Wichmann F, Udikovic-Kolic N, Andrew S, Handelsman J. Diverse antibiotic resistance genes in dairy cow manure. MBio. 2014;5(2):e01017.


Websites

MetaSUB: Metagenomics & Metadesign of Subways & Urban Biomes
This project aims to bring a molecular view of cities to improve their design, use, and impact on health.

U.S. Centers for Disease Control and Prevention. Adult Obesity Facts.

UT BIOME
A project at the University of Texas at Austin to sequence the microbiome of the campus.

Organizers

Eric Alm, PhD

Massachusetts Institute of Technology
website | publications

Martin Blaser, MD

New York University
website | publications

Jane Carlton, PhD

New York University
website | publications

Elodie Ghedin, MSc, PhD

New York University
website | publications

Jack Gilbert, PhD

Argonne National Laboratory
website | publications

Christopher Mason, PhD

Weill Cornell Medical College
website | publications

Aristides A. N. Patrinos, PhD

New York University
website | publications

Claudio T. Silva, PhD

New York University
website

Melanie Brickman Stynes, MSc, PhD

The New York Academy of Sciences

Brooke Grindlinger, PhD

The New York Academy of Sciences


Keynote Speakers

Jo Handelsman, PhD

White House Office of Science and Technology Policy
website | publications

Jo Handelsman is the associate director for science at the White House Office of Science and Technology Policy, appointed by President Obama and confirmed by the Senate in June of 2014. Handelsman helps advise the president on the implications of science for the nation, on the ways in which science can inform U.S. policy, and on federal efforts in support of scientific research. Her own research focused on communication among bacteria that associate with soil, plants, and insects. She helped pioneer the field of metagenomics, bridging agricultural and medical services. Handelsman is also recognized for her research on science education and women and minorities in science. She received the Presidential Award for Excellence in Science Mentoring in 2011. Before joining OSTP Handelsman was the Howard Hughes Medical Institute Professor and Frederick Phineas Rose Professor in the Department of Molecular, Cellular and Developmental Biology at Yale University. She holds a PhD in molecular biology from the University of Wisconsin–Madison.

Curtis Huttenhower, PhD

Harvard T.H. Chan School of Public Health
website | publications

Curtis Huttenhower is an associate professor of computational biology and bioinformatics at the Harvard T. H. Chan School of Public Health and an associate member at the Broad Institute. He received his PhD from Princeton University, where he also performed his postdoctoral research at the Lewis-Sigler Institute. He was an analysis lead in the NIH Human Microbiome Project and currently coleads the "HMP2" Center for Characterizing the Gut Microbial Ecosystem in Inflammatory Bowel Disease. His lab focuses on computational methods for functional analysis of microbial communities, including systems biology reconstructions integrating metagenomic, metatranscriptomic, and other microbial community 'omics. It studies the human microbiome in autoimmune disease such as IBD and its potential as a diagnostic tool and point of therapeutic intervention.

W. Ian Lipkin, MD

Columbia University
website | publications

W. Ian Lipkin, the John Snow Professor of Epidemiology and a professor of neurology and pathology at Columbia University, is internationally recognized for the development of genetic methods for microbial surveillance and discovery. He directs the Center for Infection and Immunity at Columbia University and the NIH Center for Diagnostics and Discovery. He is a member of the Advisory Committee to the director of the NIH and to the scientific director of the Joint Research Laboratory for Pathogen Discovery in the Chinese Centers for Disease Control. His contributions include the first use of genetic methods to identify an infectious agent, the implication of West Nile virus as the cause of the encephalitis in North America in 1999, the invention of MassTag PCR and the first panmicrobial microarray, the first use of deep sequencing in pathogen discovery, and the molecular characterization of more than 600 viruses. He has been active in translating science to the public through print and digital media, including as chief scientific consultant for the film Contagion. He has been honored as a Pew Scholar in the Biomedical Sciences and as National Institutes of Health Kinyoun Lecturer and Oxford University Simonyi Lecturer. He is also a recipient of the Mendel Medal.

Coby Schal, PhD

North Carolina State University
website | publications

Coby Schal is the Blanton Whitmire Distinguished Professor of Entomology at North Carolina State University (NCSU). He holds a PhD in entomology from the University of Kansas and completed postdoctoral training in chemical ecology at the University of Massachusetts Amherst. Between 1984 and 1993, he was assistant and then associate professor of entomology at Rutgers University. Schal's research group takes an integrative approach to questions in fundamental insect biology and urban entomology, on topics including cockroach and bed bug pheromones, the roles of microbes in mediating insect behavior, the electrophysiological and molecular basis of sugar-aversion in cockroaches, and cockroach-produced allergens. Schal is a fellow of AAAS and the Entomological Society of America and a recipient of the Silverstein-Simeone Award from the International Society for Chemical Ecology and of the Holladay Medal (NCSU's highest faculty award).


Speakers

Eric Alm, PhD

Massachusetts Institute of Technology
website | publications

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Martin Blaser, MD

New York University
website | publications

Martin J. Blaser is the Muriel and George Singer Professor of Medicine, a professor of microbiology, and the director of the Human Microbiome Program at the NYU School of Medicine. He previously served as chair of the Department of Medicine at NYU. A physician and microbiologist, Blaser is interested in understanding the relationships we have with our persistently colonizing bacteria. His work has focused on human pathogens, including Campylobacter species and Helicobacter pylori, which are also model systems for understanding interactions of residential bacteria with their human hosts. Over the last decade, he has been studying the relationship of the human microbiome with health and with such diseases as asthma, obesity, diabetes, and allergies. Blaser has served as president of the Infectious Diseases Society of America, chair of the Board of Scientific Counselors of the National Cancer Institute, and chair of the Advisory Board for Clinical Research of the National Institutes of Health. He serves on the Scientific Advisory Board of the Doris Duke Charitable Foundation. He is elected to the Institute of Medicine and the American Academy for Arts and Sciences and holds 24 U.S. patents. He is the author of Missing Microbes, a book for general audiences.

Ilana Brito, PhD

Massachusetts Institute of Technology
website | publications

Ilana Brito is a postdoctoral associate in Eric Alm's lab at MIT, where she works on microbial transmission. Brito holds a BA in biology and government from Harvard University and a PhD in genetics from MIT. She completed an Earth Institute postdoctoral fellowship at Columbia University, studying microbial transmission, both pathogenic and friendly. While at Columbia University, she launched a large-scale project to examine the transmission of microbes. She is focused on understanding how microbes (and their genes) are transmitted among individuals and between individuals and their environments.

Jane Carlton, PhD

New York University
website | publications

Rumi Chunara, PhD

New York University
website | publications

Rumi Chunara is an assistant professor at New York University's School of Engineering and Global Institute of Public Health. She specializes in harnessing information from participatory tools, such as point-of-care diagnostics, mobile phones, and other Internet-enabled sensors and media. Chunara develops statistical methodology for using these observational data sources in population-level disease surveillance. She was previously an instructor at Harvard Medical School working on the Children's Hospital Informatics Program and HealthMap. Chunara holds a PhD from the Harvard-MIT Division of Health, Sciences and Technology and an ScM from MIT in electrical engineering and computer science. Chunara has clinical experiences in Kenya, Pakistan, and the U.S., and was selected as an MIT Technology Review Top 35 under 35 Innovator in 2014.

Jack Gilbert, PhD

Argonne National Laboratory
website | publications

Jack A. Gilbert earned his PhD from Unilever and Nottingham University, UK, and received postdoctoral training at Queens University, Canada. He subsequently worked at Plymouth Marine Laboratory, UK, at a senior scientist until his move to Argonne National Laboratory and the University of Chicago in 2010. Gilbert is group leader for microbial ecology at Argonne National Laboratory, associate professor in the Department of Ecology and Evolution and the Department of Surgery at the University of Chicago, associate director of the Institute of Genomic and Systems Biology, and senior scientist at the Marine Biological Laboratory. His research uses molecular analysis and sequencing tools to test fundamental hypotheses in microbial ecology. He is on the board of the Genomic Standards Consortium and is a section editor for PLoS ONE and a senior editor for the ISME Journal and for Environmental Microbiology. He leads the Earth Microbiome Project, the Home Microbiome Project, and the Hospital Microbiome Project and cofounded American Gut (www.americangut.org). In 2014 he was recognized on Crain's Business Chicago's 40 Under 40 List.

Juan Maestre, PhD

University of Texas at Austin
website | publications

Juan Maestre earned his PhD from the Autonomous University of Barcelona, Spain, and received postdoctoral training at the University of Texas at Austin's Civil, Architectural, and Environmental Engineering Department. His doctoral training integrated microbiology, air pollution, and biological treatment processes, and his postdoctoral training involved research in water treatment and indoor air quality. Maestre uses molecular biology and sequencing tools in combination with engineering approaches to study the intersection of biological processes and engineered systems. He has investigated environments ranging from rural homes to commercial buildings. He is co-lead on the "Mapping the UTBIOME" effort to engage the UT community in the collection and analysis of environmental and microbiome samples from across campus and from the surrounding urban area.

Christopher Mason, PhD

Weill Cornell Medical College
website | publications

Christopher E. Mason holds a PhD in genetics from Yale University and completed postdoctoral training at Yale Medical School, while also holding a fellowship at Yale Law School. In 2009, Mason founded his laboratory at Weill Cornell Medical College in the Department of Physiology and Biophysics and at the Institute for Computational Biomedicine, the Tri-Institutional Program on Computational Biology and Medicine, the Weill Cornell Cancer Center, and the Brain and Mind Research Institute. He is a recipient of the Hirschl-Weill-Caulier Career Scientist Award, the Vallee Foundation Young Investigator Award, the Center for Disease Control and Prevention Honor Award for Standardization of Clinical Testing, and the WorldQuant Foundation Research Scholar Award. He was named one of the "Brilliant Ten Scientists in the World" by Popular Science in 2014. His work has been featured on the covers of Nature Biotechnology, Nature Collections, Cell Systems, Neuron, Genome Biology and Evolution, and in the press in the Wall Street Journal, the New York Times, and other media outlets.

Rachel Poretsky, PhD

University of Illinois at Chicago
website | publications

Rachel Poretsky began her scientific career as a high school student in Brooklyn, which resulted in the only other time presenting research at the New York Academy of Sciences, in 1995 as the recipient of an Academy high school research award. Since then, she obtained a BS in biology from Brandeis University and a PhD in marine sciences from the University of Georgia. She was a postdoctoral researcher in geology and planetary sciences at Caltech and in environmental engineering at Georgia Tech. She currently studies the metagenomics and metatranscriptomics of microbial communities. She is an assistant professor in ecology and evolutionary biology at the University of Illinois at Chicago.


Moderator

Laurie Garrett

Council on Foreign Relations
website

Laurie Garrett is the senior fellow for global health at the Council on Foreign Relations. She is the only writer to have been awarded all three of the big Ps of journalism: the Peabody, the Polk, and the Pulitzer. Garrett is also the best-selling author of The Coming Plague: Newly Emerging Diseases in a World Out of Balance and Betrayal of Trust: The Collapse of Global Public Health. Her most recent book, I Heard the Sirens Scream: How Americans Responded to the 9/11 and Anthrax Attacks, received the 2011 E-Literature Award for best science writing. Garrett is an expert on global health with a particular focus on newly emerging and reemerging diseases, bioterrorism, and public health, and how these relate to foreign policy and national security. A member of the National Association of Science Writers, Garrett served as the organization's president in the mid-1990s. She currently serves on the advisory board for the Hideyo Noguchi Africa Prize and is a principal member of the Modernizing Foreign Assistance Network (MFAN). She chaired the Scientific Advisory Panel to the United Nations High Level Commission on HIV Prevention in collaboration with UNAIDS.


Panelists

Joel Ackelsberg, MD, MPH

NYC Department of Health and Mental Hygiene
publications

Jo Handelsman, PhD

White House Office of Science and Technology Policy
website | publications

Paula Olsiewski, PhD

Alfred P. Sloan Foundation
website | publications


Alan Dove

Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism and blogs at http://dovdox.com.

Sponsors

Platinum Sponsor

This symposium was made possible with support from

  • New York University

Academy Friend

Agilent Technologies

eBriefing Sponsor

  • Alfred P. Sloan Foundaton

This eBriefing was made possible with support from the Alfred P. Sloan Foundation via grant number G‐2015‐14187.

Speakers

Jo Handelsman, Keynote Speaker

White House Office of Science and Technology Policy

Ilana Brito

Massachusetts Institute of Technology

Martin Blaser

New York University

Rumi Chunara

New York University

Highlights

Modern DNA sequencing technologies have revealed a vast hidden world of unculturable microbes.

Antibiotics prompt weight gain in livestock and may have a similar effect in humans.

Disease surveillance could be improved if individuals could take their own clinical samples when sick.

In small, isolated villages people acquire and maintain distinctive local microbiomes.

Biology's dark matter

For years, it stood as one of the biggest mysteries in microbiology—the plate count anomaly. When researchers looked at environmental samples under the microscope, they frequently saw many more species of organisms than appeared on culture plates from the same samples. What were all those unculturable organisms doing, and how did they interact with each other?

With the advent of DNA sequencing and amplification technologies, scientists can finally probe this vast pool of biological dark matter, and the burgeoning field of microbiomics has revealed huge microbial diversity everywhere. The Academy's Microbes in the City meeting focused on one of the stranger discoveries of this field, the finding that even entirely artificial human-built environments teem with hidden life. Besides being fascinating to biologists, discoveries about these ubiquitous ecosystems are poised to revolutionize fields as diverse as health care, forensics, and architecture.

Collections of genes

Jo Handelsman of the White House Office of Science and Technology Policy began the meeting with a keynote address summarizing the history and current state of microbiomics. When polymerase chain reaction (PCR) amplification and gene sequencing technologies first became available, researchers applied the new techniques to sequence highly conserved ribosomal genes from environmental samples. That work prompted a reorganization of the entire tree of life into three domains: Bacteria, Archaea, and Eukarya. The overwhelming majority of Earth's biodiversity resides in the first two domains, both of which exist entirely at the microscopic scale.

While the taxonomic revision was clearly important, biologists wanted more. "Eventually we began to ask 'how do we get past just a list of the species and their relatedness to each other and begin to understand what's going on in these complicated communities?'" Handelsman said. Her team at Yale University and several others simultaneously began applying a new generation of high-speed DNA sequencing systems to sequence whole genomes from diverse microbial samples. Handelsman dubbed the technique "metagenomics," because it involved analyzing the genomes of entire populations rather than of individual organisms.

The metagenomic approach led investigators to look at ecosystems as collections of genes rather than as collections of organisms. For example, the gut microbiomes of obese and non-obese people show consistent differences in the abundance of genes for energy production and carbohydrate transport, regardless of the specific strains of organisms present. Similarly, genes for antibiotic resistance often appear in multiple species in different microbial ecosystems.

It's not just scientists who find microbiomes compelling: President Obama has taken an interest, and Handelsman described several White House efforts to support the field. The President's Budget for Fiscal Year 2016 includes $1.2 billion for studying antibiotic resistance, with an emphasis on using microbiome data to track resistance genes and to identify new sources of antibiotics.

The government also requested input from scientists, and received a huge number of suggestions about where the field should go next. "We need tools to be able to look at microbes and the chemicals they produce," said Handelsman, adding that more sophisticated mathematical models will also be essential for analyzing the deluge of microbiome data.

One pill makes you larger

Martin Blaser of New York University began his presentation with a familiar set of maps documenting the skyrocketing rates of obesity in the U.S., with the greatest and fastest weight gains in the southeastern states. Maps showing outpatient antibiotic prescriptions reveal a similar pattern; states where doctors hand out the most antibiotics have the highest obesity rates. "This is not a difference based on the rate of serious bacterial infections, this reflects culture and practice," Blaser said.

Rates of obesity (right) and antibiotic prescription (left) overlap geographically. (Images presented by Martin Blaser. Sources: Obesity data – U.S. CDC; Antibiotic-use data – Hicks et al. 2013.)

Though the observations do not prove causality, they do point to a possible mechanism for rising obesity. Farmers have known for decades that low doses of antibiotics cause animals to grow faster and fatter. This use of sub-therapeutic antibiotics as livestock growth promoters now accounts for over 70% of U.S. antibiotic use.

Blaser and his colleagues found that livestock-like antibiotic regimens and high-fat diets have additive effects in mice, prompting the animals that received both to get much fatter than controls. In a series of additional experiments, the researchers demonstrated that short courses of antibiotics at a crucial stage of early development—similar to what many children now experience—also led to weight gain and changes in gut microbiota in mice.

Going viral

Rumi Chunara of New York University shifted the focus from bacteria to viruses, describing her work on disease tracking. Chunara's group wants to improve influenza surveillance, which currently relies on reports from clinics. While those data are crucial for public health planning, they miss the bulk of flu cases in the community. "A lot of times if you have influenza or an acute respiratory infection, you might not go in to see your physician, so that data doesn't get captured," Chunara explained.

Collecting illness reports directly from individuals would be a more sensitive way to measure disease rates, but previous efforts to do so have fallen short. The Google Flu Trends tool, for example, relied on Internet search data to predict influenza rates, but search habits turned out to be a poor proxy for illness rates.

Chunara decided to take a direct approach instead, recruiting a broad sample of people through multiple media channels and then giving them clinical sampling kits. On experiencing flu symptoms, participants send the research team nasal swabs and saliva samples. The researchers test the samples for 17 common respiratory pathogens and tell participants which illness is present and which other pathogens have been detected in their area. The data correlate well with clinical surveillance results, and Chunara now hopes to expand the program to include foodborne illnesses.

It takes a village

Ilana Brito of the Massachusetts Institute of Technology gave a hot topic talk to close the first session. She has studied a different type of microbial transmission question: How do microbes move between people and their environments? In a large city such as New York, these transfers occur millions of times a day, making them difficult to track. Instead, Brito focused on a more tractable environment by visiting and sampling small, isolated villages in the Fiji Islands.

Brito enlisted 300 people from five villages and collected extensive data on their family structures, social contacts, and behaviors. She then performed two types of sequencing analyses on more than 500 samples from the people and their environments, tracking both gene and microorganism distribution. Comparing the data to sequences from Americans in the Human Microbiome Project, Brito found some genes were common to both cohorts, while others were unique to one group or the other.

Fijian gut microbiota contain more genes for breaking down plant fibers while American gut microbiota contain more for animal protein degradation, consistent with the different diets of the two groups. Individual villages within Fiji also show distinct microbial gene patterns. "It suggests that there are place-based ... mobile gene pools that might have specific functions for different populations even at the very, very local scale," Brito said.

Speakers

W. Ian Lipkin, Keynote Speaker

Columbia University

Jack Gilbert

Argonne National Laboratory

Eric Alm

Massachusetts Institute of Technology

Juan Maestre

University of Texas at Austin

Highlights

Surveying microbes in wildlife can identify potential human pathogens before diseases break out.

People carry unique microbiomes that colonize the built environments they visit.

Fecal transplants can rearrange people's gut microbiomes.

Samples taken around a university campus reveal distinctive microbial ecosystems.

The next pandemic

Ian Lipkin of Columbia University began the meeting's second session on a cautionary note. As tools for detecting and characterizing microbes have become more sensitive, researchers have inevitably stumbled across spurious linkages. Lipkin pointed to cases where viruses, vaccines, and even a laboratory contaminant appeared to correlate with various diseases, only to be proven irrelevant in later work. "For those of us who are doing this sort of pathogen discovery work ... you have to be responsible in the way you approach this," he said.

With appropriate skepticism, though, the ability to sequence entire microbial ecosystems provides unprecedented insight into pathogenesis and epidemiology. As recent outbreaks of West Nile virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) have demonstrated, this new capability has arrived just in time.

Rather than waiting to react to the next emerging disease, Lipkin and his colleagues are hoping to anticipate it by surveying likely reservoir hosts for new pathogens. It's a big job. Looking just at flying foxes (Pteropus giganteus) in Bangladesh, the team found 58 viruses in these bats' feces; 50 of them were new to science. "Our estimate is that there's a minimum of 320 000 viruses yet to be identified" on Earth, Lipkin said.

Closer to home, Lipkin's team also investigated the case of a woman in the New York area who became acutely ill immediately after Hurricane Sandy. After sequencing non-human DNA from infarcts that appeared on her scalp, the researchers identified a polyomavirus that had never been seen before. They still do not know where it came from, or whether it was the chief cause of her illness.

Many emerging infectious diseases are zoonotic, originating in animals and moving into people. Diseases highlighted in orange are zoonotic; diseases highlighted in white spread from person to person. (Image courtesy of Ian Lipkin)

Some of the team's discoveries are also helping scientists study previously known viruses. For example, Lipkin's lab has found viruses in dogs that are closely related to human hepatitis C virus, providing a new laboratory model for that disease.

Home is where the microbiome is

Jack Gilbert of Argonne National Laboratory presented his group's work on microbial distribution in homes and hospitals. Because every person brings a distinct microbiome wherever he or she goes, buildings hold enormous biodiversity. "The bacteria, the fungi, the archaea, the viruses, and the way we build these ecosystems could ... potentially have profound implications for everything from autism and Alzheimer's and Parkinson's ... to digest[ion]," Gilbert said.

To study these interactions, Gilbert and his colleagues enlisted volunteers who were moving from one house to another. The team sampled the houses and occupants before and after the move. Each family had a unique microbial fingerprint that colonized the new house within 24 hours, displacing the building's former microbiota. Furthermore, close family members shared more microbes with one another than with lodgers living in the same house, tracing a microbial map of relationships. Adding a pet such as a dog to the house dramatically increased the spread of microbes between individuals, so couples living with a dog became more microbially similar than were couples living without one.

Microbial transfers trace relationships between individuals and via the built environment. (Image courtesy of Jack Gilbert)

In another project, Gilbert is studying a large new hospital building in Chicago, monitoring environmental conditions within the building as well as its microbial distribution. The first surprise was how quickly the microbiome of the entire structure changed when the facility first opened. "As soon as the hospital opened, literally the very next day, the entire system shifted to an entirely new ecosystem state, and this new ecosystem state is an occupied building environment," Gilbert said. The researchers now hope to find ways to increase beneficial microbial populations while reducing harmful ones in the hospital.

The gift of feces

Eric Alm of the Massachusetts Institute of Technology began his talk with a description of one of the best-known examples of microbiome engineering—treatment of Clostridium difficile infections with fecal transplants. Antibiotics sometimes allow C. difficile to overrun patients' normal intestinal microbiomes, causing serious digestive problems. Transferring feces from healthy donors into these patients cures about 90% of these infections.

However, Alm and his colleagues found that the transplant patients' gut microbiota are distinct from both their original microbiota and those of their donors. "It looked nothing like either, it was just very distinct, and it was very difficult ... to predict which of these particular species were going to engraft," Alm said.

The researchers built computer models to predict which species and strains would take up residence after a fecal transplant. Most species contained three to five strains, which tended to engraft or vanish as a group; patients either retained all or none of the strains of that species. When a species persisted, it also tended to promote the acquisition of more strains of the same species later. "We're learning that transmission to some extent depends on whether you've already got something in your microbiome," Alm explained.

Individual genes revealed another level of activity. After finding that antibiotic-resistance genes travel between farm animals and human guts, Alm's team discovered that the promoter regions upstream of the genes were the most mobile parts. This transfer of regulatory regions can drive significant changes in phenotypes, possibly switching some bacteria between pathogenic and nonpathogenic forms.

Big microbes on campus

Juan Maestre of the University of Texas at Austin started his presentation with an ambitious vision of the future. Maestre described a world in which researchers could build a three-dimensional map tracking all the microbes and genes in a city in real time, with the information available to a highly educated population able to understand the meaning of the data. "There is a long road to get there, but in the meanwhile we can do something," Maestre said.

Maestre's project, UTBiome, focuses on the University of Texas campus in Austin, TX. The project includes several sampling campaigns that cover building renovations, creeks, laboratories, and other features of the area. With the aid of dozens of students using online forms and user-friendly sampling kits, Maestre has collected over 400 samples.

The program has illuminated several microbial phenomena on the campus, revealing, for example, the effects of aging sewer infrastructure on biofilms in creeks and dramatic changes in indoor air when people enter a room. The data are stored online but only downloadable by request. "We are trying to find ... the best way to put it in a way that scientists can access it and the general public can access it but nobody freaks out," Maestre said.

The researchers plan to study the microbiomes of local homes to compare apartments and detached homes. They will also study how different ventilation systems and building materials, as well as the presence of pets, affect the microbiomes of buildings.

Speakers

Curtis Huttenhower

Keynote Speaker

Harvard T.H. Chan School of Public Health

Christopher Mason

Weill Cornell Medical College

Jane Carlton

New York University

Rachel Poretsky

University of Illinois at Chicago

Highlights

Human microbiomes are distinct enough to identify individuals with up to 80% accuracy.

The microbiome of an urban subway resembles that of the skin of its riders.

Sewage contains a huge assortment of protists, bacteria, and viruses.

Even treated sewage causes profound changes in a river's microbiome.

Genes that fit

Curtis Huttenhower of the Harvard T.H. Chan School of Public Health started the meeting's third session with a keynote presentation on his group's approach to microbial metagenomics. His goal is to understand not only which microbial genes are present in different environments but also how the genes function and interact with their hosts and environments. He and his colleagues have built computerized phylogenetic analysis tools to do so.

There is no shortage of data to use in these programs; the group loads genome sequences from the database of the National Center for Biotechnology Information, where researchers around the world deposit their results. "We're currently getting on the order of a thousand new microbial genomes per month," Huttenhower said. His group has used that data to place genes into families that associate with particular clades of microbes.

In another project, the group looked at specific microbial genes and genetic markers to measure the diversity of individuals' microbiota. "Combinations of microbial genetic elements do tend to be quite unique to individuals and persistent over time," Huttenhower said. The technique can identify individuals with about 25% accuracy from a skin or mouth sample, and with up to 80% accuracy using a combination of microbial markers from the gut.

The human microbiome is best viewed as a collection of genes, not as a collection of species. (Image courtesy of Curtis Huttenhower)

Although individual microbial signatures vary, the researchers could identify a core microbiota consisting of particular genes that most people carry. The species of bacteria carrying those genes differ from one person to the next, however, suggesting that gut niches recruit specific functions without regard to which species provide them.

Huttenhower is also leading a study in the Boston subway system, sampling surfaces on trains and in stations across several lines. Two themes have emerged in that study: the surfaces around people are coated with their skin microbiota, and the microbial constituents of different surfaces depends heavily on the adhesion properties of the underlying materials.

Written on the subway walls

Christopher Mason of Weill Cornell Medical College is also analyzing the microbiomes of a subway system—New York's. To cover this enormous transit network, he deputized ordinary citizens as microbe samplers by providing them with a smartphone application and user-friendly sampling kits. The lab received 1427 samples, from locations across the 600-plus miles of the subway's rail lines and stations.

Half of the resulting DNA sequences come from unknown organisms. "These are things that we touch literally every day that we don't know what they are," Mason said, adding that "I would call this a kind of job security."

Like Boston's transit system, New York's subway looks a lot like skin at the microbial level. The Bronx had the most biodiversity, with Brooklyn second. One station, however, stood out. At South Ferry on Manhattan's southern tip, the researchers found 10 species not seen anywhere else in the subway system. That station flooded in 2012 during Hurricane Sandy, and some of the distinctive sequences matched species previously associated with fish. "What happened on the walls [was] an ocean or marine environment that was left behind," Mason said.

The samples from across the subway system also contained human skin cells and DNA, which revealed local ethnic differences. More Asian-associated markers appeared in Chinatown, while in northern Manhattan around Harlem there was more African DNA. "For all kingdoms, [there's] a molecular echo that's left behind of the DNA that was transiting through that system," Mason said.

Sex and the sewer

Jane Carlton of New York University took the discussion into the sewer, but she got there indirectly. Initially, her group wanted to study Trichomonas vaginalis, the most common sexually transmitted pathogen. In an effort to determine the genetic diversity of T. vaginalis in New York City, Carlton and her colleagues worked with public health clinics to collect vaginal swab samples. That project was a success, but the team could only sample one trichomonad in a relatively small number of individuals. To broaden their analysis to other trichomonads and expand it citywide, they looked at sewage.

Trichomonads are a diverse group of organisms, including many pathogens. (Image courtesy of Jane Carlton)

The NYC sewer system pumps 1.5 billion gallons of waste through some seven thousand miles of pipes each day. Carlton's group started by sampling a much smaller system, the on-site sewage treatment plant at the Visionaire, a recently constructed luxury condominium. The plant's aerated sewage tank "is full of cockroaches, which is great, because cockroaches have trichomonads in them," Carlton said.

After developing their analytical techniques in the Visionaire plant, the investigators collaborated with the NYC Department of Environmental Protection to sample the citywide system. Those specimens contained diverse taxa of protists, including T. vaginalis and other trichomonads. The team is now trying to work backward through the pipelines to map protists to their sources. Carlton closed with a call for more standardized protocols and analytical techniques across microbiome studies. "In my dream I'd love that we could compare our data with ... sewage data in [other cities]," she said.

Going with the flow

Rachel Poretsky of the University of Illinois at Chicago also studies a sewer, but one that doubles as a navigable waterway—the Chicago River. "It's estimated that the Chicago River flow is about 70% wastewater effluent," she said. Although the effluent is mostly treated, heavy rainfall sometimes overloads the city's combined sewer system and forces authorities to open floodgates, dumping potentially contaminated effluent into Lake Michigan.

Poretsky sampled the river at points upstream and downstream of the major waste treatment plants and near combined sewer overflows. To look at how the discharge from the plants affects aquatic microbes, she and her colleagues performed both ribosomal DNA sequencing and metagenomic analyses. "In terms of community composition, the river is distinct before effluent input and after," she said, adding that the overall biodiversity of the samples declines downstream of the treatment plants. The metagenomic analyses also revealed that the sewage plants deliver numerous antibiotic-resistance genes to the river's microbiome.

Chicago is the only major city in the U.S. whose sewage plants treat, but do not fully disinfect, sewage. That situation is about to change, at least for most of the city's plants. Under pressure from the U.S. Environmental Protection Agency, Chicago is now adding a disinfection step at its smaller sewage facilities, and Poretsky's team is poised to study the effects of this change. The group is already performing laboratory-scale experiments to predict the effects of different disinfection regimens. "What'll be interesting is when we start looking at the metagenomic data and determining ... if the same sorts of patterns hold in the environment," Poretsky said.

Speakers

Coby Schal

Keynote Speaker

North Carolina State University

Laurie Garrett

Moderator

Council on Foreign Relations

Joel Ackelsberg, Panelist

NYC Department of Health and Mental Hygiene

Jo Handelsman, Panelist

White House Office of Science and Technology Policy

Paula Olsiewski, Panelist

Alfred P. Sloan Foundation

Highlights

Bedbugs' intestinal microbiota resembles the microbiota of human skin, with a few distinctive differences.

Microbes on swine farms acquire resistance to the antibiotics fed to the pigs.

The roach gut microbiome produces compounds that attract other roaches.

Probiotic products have proliferated despite a paucity of evidence to show that they are beneficial.

The other superbugs

Coby Schal of North Carolina State University gave the meeting's final keynote presentation, which focused on urban insect pests. "The insect gut is quite capable of moving microbiota from one place to another," Schal said. In a city, there are plenty of places to move those microbiota and plenty of insects to do it.

The island of Manhattan, for example, has only 59 square kilometers of land area, but its skyscrapers and apartment buildings encompass 172 square kilometers of built space, representing an enormous artificial environment. Despite humans' best efforts, that environment hosts huge populations of insects. Schal and his colleagues focus on three of the most numerous species: bedbugs (Cimex lectularius), German cockroaches (Blatella germanica), and American cockroaches (Periplaneta americana). These species occupy distinct urban niches—bedrooms (bedbugs), kitchens (German cockroaches), and sewers and residences (American cockroaches).

In the U.S., "there are no natural populations of either the German cockroach or the bedbug—they live with people," Schal explained. American cockroaches, in contrast, are natives of the country's caves but also thrive in sewers. All three insects are major urban pests. Cockroach feces contain potent allergens that have been linked to elevated asthma rates in roach-infested low-income housing, while bedbugs provoke anxiety, sleeplessness, and extremely expensive pest control interventions.

The three species have strikingly different microbiota, reflecting their distinct lifestyles. Bedbugs feed exclusively on human blood, an essentially sterile diet, so most of their bacteria come from their hosts' skin. However, 63% of the species in the bedbug microbiota are in the Wolbachia genus. While Wolbachia is a parasite in many insects, it appears to function as an essential commensal organism in bedbugs, allowing the insects to metabolize B vitamins.

German cockroaches eat microbially rich diets, providing them with diverse microbiota. Schal and his colleagues found numerous antibiotic-resistance genes in the microbiomes of roaches that infest swine farms in North Carolina. The resistance genes closely matched the types of antibiotics fed to the pigs as growth promoters, and the roaches may help move the genes between the animals and people. "We have not been able to follow up on this, because after we did this study there was lots of media about this, and [pork producers] completely disallowed us from going back to these farms," Schal said.

In cities, American cockroaches specialize in sewer life. To date, the only study of the microbiome of a field population of these roaches focused on insects in a natural cave. That work revealed a surprisingly depauperate microbiota. Schal hopes to study sewer roaches soon to see if their microbiomes are more diverse.

To determine the functions of insect microbiomes, Schal compared feces from microbially sterile German cockroaches and from nonsterile controls. Roaches preferred to aggregate near the nonsterile feces, "suggesting that bacteria associated with these feces are producing agents ... that cause these cockroaches to aggregate," Schal said. His team found several volatile carboxilic acid compounds in the nonsterile feces that were not in the sterile feces. A purified cocktail of these compounds proved to be a powerful roach attractant.

Besides looking at the effects of microbes on pests, the researchers are now doing the reverse, examining how large infestations change the microbiomes of homes. An infestation of ten thousand insects—not uncommon in some types of housing—consumes and generates large quantities of organic material that should alter the local microbiome. To measure this effect, Schal plans to analyze the microbiomes of infested homes before and after extermination efforts.

Selective media

Laurie Garrett of the Council on Foreign Relations led a panel discussion to end the meeting. Garrett began by asking panelist Joel Ackelsberg about the experience of explaining nuanced microbiome data to the public. Ackelsberg was the public face of the New York City Department of Health and Mental Hygiene when researchers published the first data surveying subway microbiomes. That project included some findings that could be considered frightening when taken out of context, and indeed city newspapers were quick to trumpet some of the more striking results, such as the identification of potential Bacillus anthracis (anthrax) sequences on trains.

Ackelsberg emphasized the importance of transparency in such situations. "If we're not transparent with what we know and what we don't know and what we are doing in order to learn more, not only is it bad risk communication, but I think the public sees through it very quickly," he said, adding that "we all live one bad quote away from the abyss when we're in the public [eye]."

Garrett next asked Jo Handelsman about the White House's position on the potential use of microbiome evidence in court. Handelsman began by explaining that with the exception of DNA testing, no forensic technique has been held to truly rigorous standards. Crime scene investigators match bite marks and hair, for example, by eye, and experts commonly score matches and mismatches inconsistently. "It's a little bit hard to hold the microbial forensics that we know must be coming down the pike to some high standard of science when there's currently very little in forensics that can even be called science," Handelsman said, echoing the conclusion of a 2009 National Academy of Sciences report on the field.

Paula Olsiewski talked about the role of the Sloan Foundation, which currently funds far more research on the microbiology of the built environment than the U.S. government does. Garrett asked whether researchers are expected to get informed consent from cities or building owners. Olsiewski explained that while there are no rigorously defined standards yet, she makes a point of meeting with researchers seeking Sloan funding to discuss how they will interact with property owners. She added that the research could help improve architecture: "We're inadvertently designing ecosystems; maybe with some of what we learn we can design them so that they're better for us."

Audience members asked panelists about the relative contributions of both antibiotic use on farms and human overprescription in the growing problem of antibiotic resistance. "The microbes that are in us are a lot more likely to affect us and become pathogens, [but antibiotic] use on farms as you know is vastly higher," Handelsman said, explaining that the available evidence does not show which use drives more clinically relevant antibiotic resistance.

Handelsman also addressed the question of regulating the rapidly growing probiotics industry. "The market has already gotten ahead of the regulation, no question about it; the claims on many of the probiotics are unfounded," she said. It is unclear, she added, whether the U.S. Food and Drug Administration will be able to implement new regulations before the end of the Obama administration, particularly because the agency still lacks a permanent commissioner.

Is antibiotic overprescription causing some of the rise in obesity rates?

How distinctive are microbiomes in different human communities?

What factors predispose pathogens to leap from animals to humans, and can we anticipate future pandemics via improved tracking?

To what extent does the microbiome of a hospital affect patient outcomes?

What are the best strategies for explaining the results of microbiome research without frightening the public?

What determines the genes that accumulate in a given microbiome, and how is the preponderance of certain genes related to their functions?

Can microbial analysis be made accurate enough to be used in forensics?

What effect does treated sewage have on the microbiota of a river?

Which drives more clinical antibiotic resistance: agricultural antibiotic use or medical overprescription?