Building a Cure from the Ground Up:
Soil-Based Antibiotics and the Rising Threat of Antibiotic Resistance
At Eastern Connecticut State University, Dr. Barbara Murdoch is digging into what makes an antibiotic effective and how we can turn the tide on the worldwide problem of antibiotic resistance. As a professor of biology at Connecticut’s only public liberal arts university, Dr. Murdoch’s approach to her subject appeals equally to majors of study. Incorporating different facets of science and coupling them with non-science keeps students engaged, regardless of their field of study.
“Because antibiotic resistance is a global problem, you could take a student with no science background and they could be in the lab doing these experiments to learn more,” Dr. Murdoch says.
“At Eastern, I try to combine students’ interests with some of my expertise, and that means sometimes you have to go beyond your core program,” she says. “For projects like that, it’s really exciting because antibiotics and antibiotic resistance has such a global presence, but for me it’s also exciting to take someone who’s not a science student and show them what the lab is like and unlock that creativity in their mind.”
Dr. Murdoch believes unlocking curiosity and creativity is the key to retaining students in STEM courses. “Over the next ten years, the U.S. will have a shortfall of about 1 million students in the STEM fields. So, if you look at that problem, you have to ask yourself why that is,” she says. “One possible reason is that in science classes, the science may be presented to students in a way that bores them—they come to think that science is memorizing facts from a textbook and dishing those facts back out on an exam.”
The lab serves as a prime location to help students redefine their understanding of what science is all about. “If you want to excite students, you should get them in a lab doing hands-on research where they have to make decisions, rationalize those decisions, and think critically about what they’re doing,” she says. “Then, students can bring their curiosity and their drive and their desire to science, and it is no longer comprised of a bunch of facts you can’t relate to. Instead, it’s purposeful. You can be creative and satisfy your curiosity.”
Dr. Murdoch marks the beginning of her career in science in 1987, when she began studying blood stem cells in the lab of Dr. John Dick. Dr. Dick has gone on to become a world leader in blood stem cells and cancer research, and is currently the Program Director in Cancer Stem Cells at the Ontario Institute for Cancer Research. “For the rest of my career since then, I’ve been studying stem cells and I look at them from different types of tissue,” she says, “whether they come from your blood or your brain or certain areas that occur only when you’re first developing as an embryo.”
Her interest in studying antibiotics and antibiotic resistance began when she was doing her postdoctoral training at Yale University. “One of my mentors, Jo Handelsman, who has gone on to be named Associate Director for Science at the White House Office of Science and Technology Policy, developed a program with former postdoc Tiffany Tsang called the Small World Initiative,” says Dr. Murdoch. “The Small World Initiative had two main goals: one was to bring awareness to antibiotic resistance because it’s such a global problem and is threatening the lives of so many people; and the second was to try to increase the number of students that would stay in the sciences and actually complete their science degrees.”
“Interestingly, if you speak to people here in the U.S. about antibiotic resistance, maybe they don’t know specifically what it is, but most people can tell you about somebody they know that has had an infection that’s recurring and they can’t get rid of it. Or, maybe they’ve had loved ones die because of infections that they’ve sustained,” says Dr. Murdoch. The issue touches anyone who has ever needed an antibiotic, and yet the amount of attention paid to the growing issue of bacterial resistance is strangely lacking.
In 2014, Dr. Murdoch helped put together an exhibit to raise awareness about antibiotic resistance through the Small World Initiative with partners from the Institute for Life Sciences Collaboration. “We went to the United Nations headquarters in New York City to try to get other UN members to put antibiotic resistance as one of the most important goals to be worked on over the next 10 years, called the Sustainable Development Goals,” she says. “Fortunately, we were able to make a case for how serious this really is, not only in North America but also worldwide. So, now that is a focus globally to try to educate people.” The exhibit has been presented during the 2015–2016 academic year by undergraduate students at Connecticut universities and community colleges, and is supported by a grant to ECSU from the Connecticut Space Consortium.
“It’s tough not to be alarmist because we are going to see people die from bacterial infections—something we haven’t seen on a grand scale since antibiotics were discovered—but that is a reality and it’s really important to educate people, whether they’re scientists or non-scientists, and empower them to take steps to deter bacteria that are resistant to antibiotics,” says Dr. Murdoch.
So, what steps can we take to decrease our own influence on bacterial resistance to antibiotics?
One of the more common contributors to resistance is a patient who doesn’t fully cycle through the antibiotics they’re given. Often, patients will just take antibiotics until they feel better, rather than adhere to the full prescription schedule. This can leave bacteria strains in your system that have been exposed to the antibiotic but not eradicated, allowing it to develop resistances and then propagate.
One of the areas in which doctors have to be more vigilant is determining whether the patient has a bacterial or viral infection before prescribing antibiotics. According to Dr. Murdoch, “In the future, we’ll be able to be more sophisticated, and our technology can drive this sophistication, where we can do a molecular analysis to determine first, whether you have a bacterial infection, second, what strain of bacteria is it, so we can make sure that the antibiotic we give you will actually prevent the growth of that specific strain.”
Developing new antibiotics and methods for curbing the growth of bacteria isn’t about working with the same samples over and over. In fact, “only about 0.3 percent of soil-based bacteria have ever been cultured,” Dr. Murdoch explains, “meaning out of every one thousand bacteria you would find in the soil, only three of those could we actually grow in a dish in a lab.” That means all of the antibiotics ever developed based on bacteria found in soil have come from this minute sample size.
“If you’re missing greater than 99 percent of the species that are found in the soil, aren’t you really missing out on something?” she asks. “I mean, you’d want to interrogate more than 1 percent of a population, but how do you go about doing that?” In this instance, there are a couple ways. The first deals with a contraption that circumvents the issue of growing bacteria in a lab setting by planted isolated bacteria back into the soil, since the vast majority doesn’t hold up well after being removed from their natural environment.
Another potential answer lies in a field called metagenomics, a term coined by Dr. Jo Handelsman, which addresses this very issue. “Instead of trying to grow the bacteria you find in the soil, what you do is a genetic analysis,” she says. “What sort of genomes do I find, and what bacterial species do they come from? And that’s how we’ve been able to figure out that if you were to take a gram of soil, which is a very small amount, that there are tens of thousands of different strains of bacteria in that single gram.”
As scientists move into an era of ‘big data,’ they’re able to collect huge amounts of information and are trying to get computers to analyze it to pull out patterns in order to determine the viability of testing the patterns scientifically. Even in the 0.3 percent of soil-based bacteria that have been sampled, there are still millions and millions of bacteria to work with, so overcoming the sheer volume of test subjects relies on a huge amount of aggregate data.
“The point is that you have to be methodical,” explains Dr. Murdoch. “It’s a step-by-step progression and you learn how to zero in on which facts are important and how to not pay attention to what might be background noise.”