NEB Podcast #58 -
Transcript
Interviewers: Lydia Morrison, Marketing Communications Writer & Podcast Host, New England Biolabs, Inc.
Interviewee: Jo Handelsman, Director of the Wisconsin Institute for Discovery at the University of Wisconsin, Madison
Lydia Morrison:
Welcome to the Lessons from Lab & Life podcast, brought to you by New England Biolabs. I'm your host, Lydia Morrison, and I hope this episode offers you some new perspective. Today I'm joined by Dr. Jo Handelsman, Director of the Wisconsin Institute for Discovery at the University of Wisconsin-Madison, where she's a member of the Department of Plant Pathology. Jo was selected as this year's Don Comb Memorial Lecturer, an award in honor of NEB's late founder Donald Comb. Joe's expertise in microbiome research secured her a role as a scientific advisor to President Barack Obama during his term in office. And her work promoting diversity in STEM fields through changes in the classroom is truly inspirational. I'm so excited to have Jo Handelsman with us today. Jo, thanks so much for joining me.
Jo Handelsman:
Thanks for having me.
Lydia Morrison:
So I was hoping that you could tell our listeners what microbiomes are and why they're so important.
Jo Handelsman:
Microbiome in general means all the microorganisms in an environment. So every environment on earth has its own microbiome. So there's a soil microbiome, which is all the microorganisms in the soil. There's a human gut microbiome, which is all the bacteria, fungi, viruses, maybe nematodes that live in our gut. So it just is a comprehensive word to describe a total microbial community.
Lydia Morrison:
And why are they so important?
Jo Handelsman:
In almost every environment that's been looked at, it turns out that the microbiome is what determines the nature of that environment. And so we know that in the environment, the outside environment microbes run a lot of the geochemical cycles that make the earth work. So carbon cycles, nitrogen cycles, phosphorous cycles, and so that's really important for processing all the elements that are around us in the air and in the soil and in water. We also know that human health is defined a lot by the microbiome and that I think was probably the biggest surprise of the last decade or decade and a half, was every time we look at the role of the microbiome in fill in the blank, whether it's Parkinson's disease or autism or depression or IBS or Crohn's disease, we find that the microbiome plays a role in it. And it certainly in many of those diseases, it's not the only factor, but it can be a very critical factor that perhaps suggests a mechanism for treatment.
Lydia Morrison:
Thank you so much for that explanation. I think that's really helpful for our listeners to understand that these communities live in us and in almost every other place on the earth and probably beyond the earth. What is a model microbial community and how do these models help enable your work?
Jo Handelsman:
Well, the microbiomes that we're interested in are very complex. So one that we're interested in my lab is the root microbiome, which are all the microorganisms that live on a plant root, and that'll usually be hundreds of organisms. We're also interested in the human gut microbiome, which is also hundreds of organisms and the soil microbiome, which is thousands of different species of organisms. So the complexity of these environments is much greater than what we've been tackling for most of the history of microbiology during which we most often have studied one organism at a time in pure culture. And so my approach was maybe we could find something intermediate between the single organism approach, one organism in the lab, and the natural environment where there are thousands potentially of different species. And so my lab constructed a model microbiome or model microbial community that has three members who are representative of the root community.
And the hope with a model is that it gives you the simplicity to be able to dissect it very rapidly and with really powerful tools, but it also gives you some relevance to the real world. And in our model, we call it The Hitchhikers Of the Rhizosphere or for short THOR, THOR seems to be very relevant to the real world because many of the characteristics have been recapitulated from the field to the lab. And there are so many interactions among the three members that it suggests to us that it really is relevant constellation of organisms. The idea is to figure out the principles of microbial community function, what makes them stable, what happens when you disrupt them, how do they deal with invaders?
How do they deal with changes, perturbations due to temperature or chemicals? And then are those principles that we derive applicable to the real world communities? And so it truly is an experiment. We don't know that everything we learn in the laboratory will translate to the real world, but no model is perfect, whether it's little white mice in the lab or model plants or they're about a dozen different really great models. None of them reflects reality and all of biology, but the amount that we've learned from them is simply staggering. And we think that communities can benefit the same way from a model community.
Lydia Morrison:
Yeah, that's really interesting. Certainly value to scientific models for the study of complex interactions, and certainly there's much more complexity occurring in nature. Speaking of relevant applications, how do microbial communities play a role in the spread or the evolution of infectious disease?
Jo Handelsman:
Communities are very important for infectious disease because usually infectious disease is due to one or very small number of organisms. The vast majority of organisms in our environment and in our bodies and on our surfaces are not pathogenic. They are usually beneficial or just maybe neutral. And so in the process of colonizing the environment, they often will crowd out the bad pathogens that could be there. So a normal microbiome is really critical for keeping pathogens at bay, but they're also important for providing a stable environment with all the right chemicals and functions that we need. So whether it's a plant that gets nutrients from its microbiome or the human gut where the right microbes will suppress symptoms of depression, will alter the outcome of Parkinson's, seem to play a role even in Alzheimer's disease, that's all important, not because they are preventing one single pathogen from invading, but because they're forming a constellation that leads to health.
Lydia Morrison:
That's so interesting. And really I can't wait to see how that research comes to fruition in terms of treatment for those diseases and how that's able to support community health and public health moving forward. It's really important work. Could you tell us about the Tiny Earth Chemistry Hub and how microbial communities play a role in the discovery of new antibiotics as well?
Jo Handelsman:
The Tiny Earth initiative across the world is actually started as a teaching initiative combined with having a major research goal. And the research goal was to discover new antibiotics because we're rapidly losing the use of many of our antibiotics because pathogens are becoming resistant to them. And so we need new antibiotics to treat a lot of bacterial infectious disease, but at the same time, we need to offer undergraduates better experiences early in college so that they find the joy and the thrill and the excitement of science early on before they take, no offense to my colleagues, but a lot of boring classes that often turn them off from science. And what's been found is that research courses introduced in the first or second year of college can help students sustain their interest in science through courses that are, for example, the weed out courses as professors like to call them, where they're almost proud of the fact that a third of the students aren't going to make it through and aren't going to survive in that discipline, which is a real problem.
I mean, can you imagine if English courses led to people never reading again? If English professors were proud of the fact that most of their students were never going to pick up a book? I mean, it's crazy, but that's what we do in a lot of science disciplines. And so we see the research course as an antidote to that effect, but it has to be early because if you wait until junior year of college, for example, the damage is done and students have often departed, we lose about 60 or more percent of our students who start intending to major in science. By the time they graduate, they're graduating in another discipline. And it's not because they're weeded out due to incompetence or lack of talent. They have the same grade distribution in their science courses as the students who stay. They've just simply been discouraged from remaining in that field.
So Tiny Earth is one of many attempts across the country to excite students about science by having them do research early in their college career. And so we've combined a social and medical crisis, which is the loss of antibiotics and the fact that the industry, the pharmaceutical industry is not searching for new antibiotics. And so in actually a moment of frustration, I said, "Well, darn it, if the pharmaceutical industry isn't going to look for new antibiotics, the undergraduates of the world can do it." And so the students who take this course dig up a soil sample from a place of interest to them, they culture bacteria from that sample, and then they test the organisms that they grow in the lab for the ability to inhibit pathogens or organisms that are closely related to pathogens. We don't always want the students working with the bad pathogens and they almost invariably find antibiotics.
And what we don't know until we have a chemical structure is whether those are new antibiotics. And that's what the Tiny Earth Chemistry Hub does, is we take the student discovery and do the rest of the work, which is the chemistry to determine the nature, the chemical that is responsible for killing the pathogen or other organism that is being killed. So it's part of a much larger network of colleges, instructors and many, many thousands of students who are working to discover antibiotic producing organisms. And then we're trying to find out if those organisms are producing new compounds.
Lydia Morrison:
How ingenious. And I hate to think of you being frustrated, but at the same time, I'm a little bit glad that you were on that occasion because I think that's such a wonderful application of the ingenuity of undergraduates and to be able to kindle that passion and curiosity for science in students because I totally understand that the path to advanced degrees in science is tough, and it feels like a struggle. I think when you're in it and it's hard to think that there are so many people who are discouraged from continuing to follow that career path because professors might take pride in the difficulty of their course in sort of low numbers of success through their teachings. So that's really inspiring to hear. I know that you're a big advocate of achieving diversity in STEM education, and I've seen some of your writing suggesting that the structure of classrooms is partially discouraging students from historically excluded communities from pursuing further education and careers in STEM fields. Could you speak to what you're currently seeing happening in classrooms and where changes could be beneficial to help drive diversity in STEM forward?
Jo Handelsman:
Well, I think it's worth talking first about why we need diversity. And first of all, we need to provide access to all groups to careers in STEM. And that's just a fairness issue. But sadly, that 60% of students who leave majors in STEM during college are disproportionately underrepresented groups. Black, Latinx, essentially any group that you look at that has been a minority in science in the past, it gets more discouraged than white men who are the former majority. And so that's the first thing is that we know that the way we've been teaching discourages the very people that we should be giving extra encouragement to. The other reason is something selfish to science, and that's a very big part of Tiny Earth. And that's that the more different kinds of people with different experiences, different minds, different geographic locations that we bring into science, the more creative our science.
And that's been shown in lots of experiments that more diverse groups at almost any measure of diversity, are much more creative and innovative and come up with better solutions to problems than less diverse groups. And so, one of the advantages in Tiny Earth is that we work with very diverse communities all over the world. We're in 31 different countries, and the students bring different experience, different knowledge, different values to the work that they do. On top of it, we know that undergraduate students are some of the most creative students that we can bring into the lab. And the reason I think that might be true is that they're not as bound by the dogma that constrains people who have been learning science for decades and are so inculcated with all the dogma that has been laid down over decades and decades of developing science that they kind of forget that there might another way to interpret data out there.
And early in my career, I learned from one of my first graduate students how absolutely wrong I could be about the result of an experiment I thought he had contamination in his plates, which are just unwanted bacteria. And it turned out he had a pretty major discovery. And the same thing happens in Tiny Earth classrooms where students who have kind of the naive approach that isn't constrained by all of the knowledge that the rest of us have accumulated are free to think in completely different ways. And in fact, the first semester I taught Tiny Earth, one of my students went to the shelf of media that we used to grow bacteria, and she said, "Oh, can I use that one?" And it was one called PDA, which is potato dextrose auger. And that came from my background in a plant pathology department. We use it all the time with fungi in plant pathology, but it's not typically used for bacteria.
And she found out that she got twice as many antibiotic producers as the other students in the class. And since then, every year that Tiny Earth has been taught some other instructor reports exactly the same finding that the students who use PDA get more antibiotic producers. And it was very funny when I talked at a meeting that had a lot of old pharmaceutical chemists, people who had spent most of their career discovering antibiotics, one of them said, "Well, why are you going to find things that I didn't find?" Because they had done very comprehensive, they think, surveys. And I said, "Well, we use PDA media for one thing." And one of them said, "What's PDA?"
Not a single person in the room knew what PDA was. So I said, "That's the kind of thing. Our students aren't constrained by the habits of science, and they try new things and they make discoveries as a result." So that's part of why diversity is so important. It's about why research courses are so important. Students have the freedom to express their individuality in designing experiments, but we need to do more than that 'cause we know that there's more than just research courses that we can do to change classroom environments. We have lots of ways of making classrooms more welcoming to formally excluded groups, and we need to pay attention to those mechanisms that will attract them to science.
Lydia Morrison:
Thank you. Couldn't be more right. And it sounds like the difference in perspectives is so powerful as well as sort of the youthful naivete. It's great to see students even younger than undergraduates ask questions and demonstrate curiosity. And it's wonderful to hear that that is being kindled in undergraduates as well. And hopefully some of those individuals go on to feel welcome in the field and to continue asking those questions and coming up with those ideas that perhaps more restricted views wouldn't allow for. So you served as the Associate Director for Science at the White House Office of Science and Technology Policy for three years. What was it like to be a science advisor to President Obama?
Jo Handelsman:
It was incredibly exciting. Some of the time it was fun, sometimes it was miserable, but it was always exciting. President Obama values science and really enjoys science. And so it was a real privilege to work with a president who cared about science and wanted to understand scientific facts, scientific concepts and arguments. So teaching him was one of the great delights of my life, was explaining science to someone who was eager to learn and really excited about the content. And he was particularly interested in microbiology, which as a microbiologist kind of mattered. It was really thrilling to be at the center of developing policy for the country or even in some cases, the world, which is really a privilege that most scientists never experience.
But it also could be enormously frustrating because policy is based initially on facts and arguments and logic, and that's what scientists like. But then it moves into the political sphere, and that's when there are other factors that have to be considered besides just the right science. And there are always considerations that kind of pollute the arguments from a scientist standpoint, but are absolutely important and legitimate for getting anything done in government. And so there is always that level of frustration when the policy doesn't develop the way the scientists expect because of compromise and having to make decisions that are based partly on politics and partly on science.
Lydia Morrison:
Well, thank you so much for your service. And nothing's quite so rewarding without the challenges, right? So I'm sure that you cherish that time that you were able to spend there, and certainly I think we, the people, appreciate the time that you have given. Finally, before I let you go, you recently published a book entitled A World Without Soil: The Past, Present, and Precarious Future of the Earth Beneath Our Feet. Can you share what the book is about and what motivated you to write it?
Jo Handelsman:
When I was in the White House, I initiated a soil project or soil initiative to try to increase our knowledge of soil and to develop a strategic plan for maintaining our soil in the United States. I was kind of shocked to find out that the United States was one of very few countries that doesn't have a strategic plan for protecting soil. And soil is one of our most vulnerable and fragile resources that we're losing at a very high rate across the world. It's not just the United States, many, many countries are. And we're in a very unsustainable situation right now that in probably about 60 years, if we keep going the way we are, it's hard to imagine how we'll be able to grow crops in much of the world. And so I really wanted to have a plan for sustainability of soil, and there just wasn't enough time because I was there at the end of the second term for President Obama.
It wasn't enough time to develop a full strategic plan. And so a group of representatives of many federal agencies who all had an investment in soil got together and developed a framework for a strategic plan. And we hoped that that leads to a long-term United States strategic plan. But I didn't feel like I had made that much change for soil, and I didn't really enact policies that would protect the soil when I was in the White House. Other things went much better than the soil initiative or soil policy. So I decided I wasn't done when I left the White House. And so the book was my answer to not being done. I decided, okay, if I couldn't change policy at the White House level, then I could inform the public a very broad public, I hope, about the precarious future of soil and why we need to pay better attention to the health of our soil and the loss of soil, which is happening at a very high rate all around us all the time.
Lydia Morrison:
Well, that is both inspiring and terrifying to think that in such a short amount of time, we might be in a position where we're unable to grow enough food to feed the world, which is already in a precarious position to begin with. So thank you so much for your work on that, and thank you for your continued drive to educate the public and to understand what is happening in our soil, what we can learn from the soil, what we can learn from these microbiomes, and how we can use that knowledge to help protect our planet and continue to enjoy living here.
Jo Handelsman:
Thank you for having me to talk about these really important issues to me. It's nice to hear that they're important to you as well.
Lydia Morrison:
Thanks so much for taking the time to be with us today.
Jo Handelsman:
Thank you.
Lydia Morrison:
Thanks for joining us for this episode of The Lessons from Lab & Life Podcast. Join us next time for the final episode in our molecular cloning series in which we'll discuss the seamless DNA assembly method called NE Builder with New England Biolabs Production Scientist, Lindsey Spiegelman.
