Four years ago, Maddie Mason decided to explore New York City’s subway in a way most of its daily 5 million riders would not think of: she licked the handrails on her way down the stairs. As a toddler who had just started exploring the world with her tongue, Maddie’s attitude that Sunday morning was not particularly shocking to her parents. On the contrary, it was somewhat of an inspiring moment for her father. Instead of just worrying about the potential health consequences of his daughters’ curiosity, Dr. Christopher Mason, a geneticist and researcher at Cornell University, looked at the big picture and asked himself a simple question: could someone really tell what Maddie just licked into her body?
The short answer is no – but it took two years for Dr. Mason to prove it by the numbers. After the licking incident, he started a project to map the organisms lurking in New York City’s subways. Over 18 months, his team collected samples from benches, floors and, yes, handrails, to analyze DNA from 466 stations in the city. The results, published last year in the journal Cell, showed that 48% of all the genetic material they found belonged to unknown organisms — creatures not yet discovered or catalogued. “Some people estimate our planet has 10 million species; others, that it has over 100 million. Yet, science only has around 25 thousand known genomes to compare our findings to”, says Dr.Mason. “There is just so much we don’t know”.
Most of these unknown creatures are invisible to the eye, but have a huge impact in our lives. They include fungi, viruses, and bacteria that interact with each other and form their own microscopic ecosystem, known as the microbiome. In the past decade, scientists studying the microbiomes of the human body discovered that they play key roles in our system – from lactose intolerance to cancer resistance. Now, Dr. Mason is applying the same techniques that allowed scientists to study the microbiomes of our guts to better understanding our cities: metagenomics analysis.
Instead of the traditional DNA analysis, in which scientists isolate material from a single individual, metagenomics allows them to analyze complex samples containing many individuals and species. The field grew in the past decade with the advances of DNA sequencing technologies combined with the power of bioinformatics. In other words, when Dr. Mason analyzed New York City, he threw whatever got caught in the swabbing process – fungal spores, human hair, bacteria – in the same sequencing machine. Powerful computer algorithms then compared the results with genetic databases, allowing him to come up with the percentage of unknown species in the subway. The process also generates a blueprint of the system showing which species, or even genes, are more abundant.
Initially, scientists used metagenomics to study organisms that couldn’t be cultivated in the lab, like bacteria that don’t grow on a petri dish and must be observed in their natural environment. Gradually, the technique became a tool for studying complex interactions between living organisms and their microbiomes, such as humans and their gut bacteria. Now, pioneers like Dr. Mason are applying the technique to our cities and asking themselves two fairly simple questions: what can we learn from our invisible neighbors and how can they affect us?
Scientists began by using metagenomics as a way to detect dangerous microorganisms in urban areas, such as bacteria resistant to antibiotics. After a year collecting fecal, soil and water samples from two communities in South America, a team led by researchers at the Washington University School of Medicine found evidence on how antibiotic resistant bacteria can spread (and survive) in the environment. These types of bacteria — resistant to most available medication — are a worldwide concern that, in the US alone, claims over 20,000 lives every year. Many of the resistant bacteria share common resistance genes, called resistosomes. With metagenomics analysis, the scientists could see how abundant these genes were in different locations in Peru and El Salvador.
The Washington University results showed resistant bacteria can be found in unsuspected places, such as in water samples already filtered at local sewage treatment stations. “We discovered that some of these genes can survive the filtering system, even if the bacteria dies”, says Dr. Erica Pehrsson, from the Washington University School of Medicine, one of the co-authors of the paper in Nature. Ultimately, as the wastewater is discharged into the ocean and used to irrigate parks and farms, these genes are released back into the environment and can be incorporated by other bacteria. This process, called horizontal gene transfer, is one of the mechanisms bacteria use to adapt to antibiotics. It could not only be happening in poor shantytown communities, but also in big American metropolises.
To investigate the spread of resistant bacteria and other microorganisms in urban environments, researchers at the Massachusetts Institute of Technology have spent the past year analyzing the microbiomes in the local Boston sewage. Now, as the program is expanding, they have partnered with the Massachusetts Department of Public Health to correlate information on prescribed antibiotics and the number of resistant bacteria found in the sewage. The results could show if there is a relation between medication and resistosome spread, helping the development of better health policies.
The sewage project is part of the Underworlds, an initiative to study microorganisms as a way to better understand and plan our cities. Ultimately, the goal is to develop a technology that could constantly monitor different microbiomes and measure health aspects of an entire community. The concept is similar to air quality monitoring, but instead of analyzing levels of CO2 or pollutants, researchers would be assessing the growth of different types of microorganisms. A neighborhood with a high concentration of antibiotic in the sewage, for example, could signal the start of an infection outbreak in the area.
“The most obvious first application is infectious disease surveillance, and the prediction of viral outbreaks (…) like flu”, says Dr Carlo Ratti, director of MIT’s Senseable City Lab and of the Underworlds project. The Zika virus, for example, could probably have been detected earlier if there was such a system in Brazil. Scientists believe that the virus arrived with a tourist during the 2014 World Cup, but was only noticed almost a year later.
Now, a group at Fiocruz, the leading health research institution in Brazil, is interested in how microbiome analysis could identify future outbreaks. They believe they could detect traces of the Aedes aegypti mosquito, the vector of Zika, and also material from infected individuals, such as saliva or nasal fluids. To test the hypothesis, the researchers swabbed nine different subway stations in Rio de Janeiro before, during and after the 2016 Olympic Games. By the end of November, they will have gathered over 1302 samples, all of which will be sequenced in New York.
The Brazilian Olympic research is part of a bigger project coordinated by Dr. Masons’ lab. With a grant from the Gates Foundation, he founded MetaSub, an international consortium to expand the New York subway project to 67 cities in 33 countries. The goal is to create a global “DNA map” of busy areas. “This could become a measure of the cities’ health, just like counting the number of trees or monitoring pollution”, says Dr Mason. Research is still at the early stages, but the applications include not only monitoring resistant bacteria and virus outbreaks, but also potentially detecting early signs of biological terrorist attacks or even using the data as a new type of population census, as microbiome analysis in places like subways contain a lot of human DNA. By understanding microbiomes, we might be able to learn more about the invisible ecosystems that surround us.
