New Mexico in Focus; 1008; Women in Science

A revolutionary breakthrough in the study of the human cell, UNM biologist Margaret Warner Washburn and her team of researchers unravel a scientific mystery that is caused for celebration. Are we closer to finding a cure for cancer? Find out next, on in focus. Hello, and thank you for joining us, I'm R. C. Choppa. Tonight we meet a woman who is making remarkable discoveries in the world of science and the study

of the cell. Internationally recognized UNM biologist Margaret Warner Washburn is not only a leader in the field of biology and genetics, but she is also vice chair of one of the strongest biology departments in the country. Yes, right here at UNM. Warner Washburn generates millions of dollars for research, that is one of the reasons she is actively pursued by the National Science Foundation and other universities. In a moment we'll be talking with Margaret, but first we want to show you a bit of what she does. What you're about to see is a short segment taken from a documentary that was recently produced about her research. Biology today is undergoing a revolution that will change the world. It is a revolution in how we understand life on an molecular level, deep within the cell. In November 1997, in a project funded by the National Science Foundation, Margaret Warner Washburn and her team of researchers at the University of New Mexico made a revolutionary

breakthrough, a breakthrough which might lead to a cure for cancer, controlled with aging and even a better beer. They unraveled the mystery of an ancient gene. Understanding the stationary phase of an organism would be extremely helpful from a clinical point of view. We know from studies of a number of different organisms that during stationary phase, the organisms are much more resistant to both the immune response and to antibiotics. If we get determined weaknesses that we can attack by understanding what genes are expressed during stationary phase, then potentially one might come up with effective therapies for treating organisms that are in their dormant stationary phase. Therefore, you could really induce a complete cure. Understanding us now is Margaret Warner Washburn.

Margaret, thank you so much for joining us. Oh, you're welcome, Ersy. Can I call you Maggie? I know that's what you like, right? Sure. Maggie's fine. You just went out. There were a litany of questions that you say those were the important questions about the cell being in the stationary phase. Let me ask you first question. What regulates the cell? I mean, that's one of the questions. The big questions that you were asking. Well, there's no simple answer in it. The bottom line is that's what we'd like to know. And a long time ago, I used to talk about that, well, you can talk about cancer or how cells grow, that it's kind of like how you get a car from one place to the other, that's a combination of using the accelerator and having breaks. And within the cell, there are these proteins that do things. Some of them act like accelerators. They tell the cell go, do whatever it needs to do, divide, make things. And there are proteins that act as breaks, that say, stop growing. And so in normal growth, just as in normal driving, sometimes you use the accelerator, sometimes you use the brakes.

In stationary phase, it's more breaks than accelerator. And in most of the cells in our body, it's more breaks than accelerator. In cancer, what happens sometimes is that you'll have a change in the gene that affects how the protein works so that you get a stuck accelerator and breaks that don't work at the same time. So all the things are related when we're talking about cell growth. All the things that go wrong and end up causing cancer are things that, when they're working well, allow the cell to do what it has to do. So for the most part, the cell stays in a stationary phase until something happens that makes it change or move or... Right. So the cell's originally divide, I mean, in the beginning a cell will divide. And then it will stay in a stationary phase for a long period of time. And then, for instance, in our bodies, if we get a cut, then there's a change in the signals that tell the cells around the cut to start dividing to form new skin. So the stationary phase, would you say that's a phase where the cell is healthy?

The stationary phase is a perfectly normal part of life. Because as a matter of fact, most cells in the world are in stationary phase most of the time. And unfortunately, we don't know much about stationary phase. I think for a lot of reasons. But now with the new kinds of tools we have for looking at cells, we can learn a lot more about it. I see. And through your research, I know there was a cause for celebration. You found an ancient gene. Tell me about that. Tell me about what you have been able to find out. Well, science isn't easy. It's a continuing process. And we had found a gene that was very ancient. It was probably in, when you think of evolution, it was in the original cell. And because it stayed the same over millions or billions of years, that says it's probably important in what the cell has to do. That's the scientific argument that we would make.

And so we found this gene, and it's very interesting. What we think it has to do is somehow allowing the cell to get a sense of itself in terms of what it's making and what it needs. So that's what we're working on. And the importance of this gene, we call it snooze because we found it in stationary phase cells. The importance of this gene is that, well, first of all, it lets us understand more about biology, but it's present in almost every type of organism on Earth, but we don't think it's in humans. So in that respect, it has some potential importance in terms of being able to target microorganisms but not humans, for example. Right. So what is it going to be able to tell us? One of the questions that the documentary talks about is that we might find a cure for cancer because of some of this research. And even a better beer.

Yeah. Is this real? Is this real? Well, as a scientist, I have to say that those kinds of, when I saw these ads, you know, it's just going to cure cancer, I mean, my heart stops, you know, because although that's exactly what I'd love to do. And part of the reason that I'm actually doing the science I'm doing is because my mother would always tell people that I was working on cancer, and I never was, you know? So I thought, well, what can I have got to do something? Like my mother's not going to change her line, I better change her. So anyway. In the long run, the snooze gene, that particular part of our research, probably won't have anything to do with cancer. It's more likely to have an impact on tuberculosis, cryptococcus, other types of infections that humans have. It may be very important in learning about how microorganisms survive in different environments. People warming could have some impact on whether organisms can survive, and this may have a relationship to it.

So, in this particular thing, it's probably not going to cure cancer. A better beer, I don't know that either, but it's possible we haven't looked into it. We tend not to use our lab strains to make beer. It kind of makes me nervous, and there are a lot of controls on using, you know, transformed strains for making things that people eat, so we don't do it. But in the long run, we may learn that kind of thing. Now, in terms of cancer, stationary phase absolutely will have an overall impact. Once we understand the signals and the mechanisms by which cells allow themselves to stop growing, stay for a long period of time, and then the things that happen to get them to start growing again, once we understand how that normally happens, I think it will give us some insight into cancer. In fact, most of the cancers that arise in solid tissues, like lung cancer, liver cancer, those sorts of things, arise in cells that were in a stationary phase state, so absolutely overall the general direction of studying stationary phase will have to do with cancer,

and maybe even aging, so I don't know, it's kind of exciting right now. So, are you at this point passing the baton, or are you going to continue this research? Or what? No, I'll keep the research going. My lab is going and funded, knock on wood, and I find the research very, very interesting. But in terms of my life, I really love doing the research, but I get to a point where now I do a lot of things at the national level in terms of being an advisor to the Director of the National Science Foundation on Equal Opportunity, or the NSF was interested in having me come and run a new program in fungal genetics and work on the genome project, and so I have a lot of other interests right now. So I hope to keep my lab going, but I'm kind of looking, you know, you get to this part in your life where you've, I've been a scientist for 20 years, and it's been an incredible journey,

I love it. So what's really exciting is that now I actually have a lot of different avenues that I could go. Right, so you just said you've been a scientist for 20 years, so that means that you haven't always wanted to be a scientist, not that I'm dating you or anything like that, but there was a time when you weren't, and I want to get to another piece of the documentary that shows how you actually became interested in science, so can we please roll that please? I had grown up in Iowa on horseback riding in the forest all the time, and never noticed anything that grew around me. It took a long time for me to become a biologist, I graduated, my undergraduate degree was in English, but when I was in Mexico, in the markets in Morocco, there were, there were good and dead-ass selling medicinal plants and seeds and things, and once I saw how people really could interact with their environment and became fascinated with biology.

So does that bring back any memories or was it, was it your visit to Mexico that propelled you into the study of biology? Absolutely, no question, there were, I was just talking to a student yesterday who came in, we were talking about things, and I was telling him that I had, you know, I feel like, I was born in Iowa, but I feel like I had a sort of rebirth in Mexico, because I was an English major and was interested in poetry, and my mother's from Mexico, so when I finished, well my father's German, so I learned German, I went to Austria as part of my undergraduate education, and I didn't understand a thing about the whole situation there, so I thought, oh, no, what am I going to do? So I came back, and when I finished school, I went to Mexico, and I had several things that I thought I was interested in, but I think going to the Museum of Anthropology in Mexico City, I saw the statue of Coatley-Qui, the mother of Coatley-Qui, and it's sort

of a fierce, terrible, terrifying, matron-lazed sculpture, well, I don't know, something about seeing her kind of shook my foundations, and then when I got to Oaxaca, that was the first time that I had been living in an area with an intact indigenous culture, and there was a sense of time and connection, and just history, and I spent a long time in Oaxaca just hearing people's stories, but it was the use of the plants to heal themselves, it was the women from Tawanda Peck taking their cloth down to the mollusk in the ocean, and agitating the mollusk in the mollusk spit off this purple dye, and so they were one of the very few groups to have purple as a color for a dye, you know, that's why they all the kings and princes had purple. So anyway, yes, round about, then every time I went and lived in Colombia for a year,

and there was a professor who'd been, I think, a Guggenheim fellow, and who was a botanist and ran the botanical garden in Boatta, and I used to go talk to him a lot, and it took a long time, but I got back into the sciences. By that time I was older, more motivated, I'd been really intimidated by school, I thought I hated school, I never wanted to go back, but it was this sense that I could plug into Western science and end up doing something in terms of being a bridge between the cultures that I love down in Central and South America, and Western science in terms of validating traditional science that propelled me and made it easy to go to school. So prior to your visit to Mexico, you had never seen that connection that people made with the environment and the plants until then, I mean, what kind of upbringing did you have in Iowa? Sick, huh?

No, I mean, I don't know, I had, you know, we had tamales and stuff, I don't know, I knew corn, I knew soybeans, I knew corn soybeans and oak trees, I don't know, I mean, I knew some things, but you know what, oh, I know, okay, there's a T.S. Eliot poem, T.S. Eliot wrote called Four Cortets, and it said that all of us should be explorers, and the end of all our explorations should be to come back to the place from which we began, and to see it for the first time, and it's the same, so now I go back to Iowa, it looks different to me, stationary phase is the same kind of thing to bring you back to science, that stationary phase is very familiar, and so I think people haven't thought it was interesting, and now we look at it again, and so all I can say, those experiences were really important, I think a lot of kids don't notice things when they're growing up, I think a lot of students never give themselves the opportunity to think about what it is they actually are passionate about in terms of learning, I think they probably, you know, we're in such a hurry to

get things out, we're in a hurry to get things out in the class, we're in a hurry to get our homework done, we're in a hurry to play Nintendo, we're in a hurry to go to the mall, and I think all of those things keep us from really getting to what's in our heart and where we need to go, and ultimately what kinds of contributions that we can make to the life around us. It sounds like your trip to Mexico was a real revelation for you in terms of getting back to your roots and understanding your roots, is that correct? Well it was, you know, I mean it was, right, see I hadn't realized I grew up with Forty-Counter Foster Brothers, and I hadn't realized that I was not identifiable as Hispanic when I was growing up, I mean I, you know, it didn't occur to me, and so when I went to my undergraduate institution I, it was at Stanford, and then that's where I found this whole thing out, and it was like well then who am I if I'm not, you know,

you know, a conscious granddaughter, and so yeah, getting back to Mexico was a real reaffirmation, and because there's so many things to learn there, there's so many things to learn there, I mean the people who go to Mexico and go, oh, the poverty, you know, but the thing that the people of Mexico have that I really found was that it was not a poverty of spirit. I mean I could talk to anybody about my science really, I mean because if they saw that I loved it, then they wanted to hear about it, you know, and so that's what I tried to bring in my classroom, and that's what I tried to bring into my lab, is a sense of really paying attention to finding a path with heart wherever you are, and in science it's sometimes a challenge, but you can find it, and I think you can surprise people because a lot of people aren't, you know, consciously trying to do this. Is it an exciting time to be in science right now, I know that in the 20th century physicists

were going through an explosion of knowledge, is biology the science of the 21st century? Didn't that only biology, it's biology, it's chemistry, it's computer sciences, I mean what's happened is that I think previously that the different disciplines were more isolated and what's happening, oh absolutely, biology is going through this amazing time where we're seeing things differently because of the new discoveries that people are making, but because we need different tools to analyze things, different ways to look at things, then you know, we start interacting more with chemists, with engineers, with computer scientists, with mathematicians, you know, I mean the sky's the limit, and New Mexico is a great place to be doing this. So are you getting a lot of offers, or not necessarily offers, but I guess support from organizations, you talked about the National Science Foundation, and I know that this documentary cost quite a bit from what I understand to make, and you had some incredible graphics

which I want to show in just a few minutes, but how were you able to do that, how were you able to get your, what your research is out into the community, into the science community, not only nationally, but internationally. Well, the National Science Foundation had a grant supplement that was available, and so they were trying to get people to communicate the research that NSF was paying for to the public. Okay, so Larry Walsh and Denise Wollen are here, and I'd known of the quality of their videos, and so I said, well, can we do this, and Larry and Denise got very excited about it, and so I said, well, let's go, and NSF got very excited about it, and we got about halfway through, and Larry said, you know, we have to have videos. And so through Ed Walters, we were able to get a contract from Los Alamos, they needed the video, they needed the animation for their science museum because they have to, they need to develop an exhibit on the Human Genome Project.

So they needed these things, and we could work together, and so it turned out beautifully, and then can, and me helped, and you know, the biology department, and everybody's been helping. It's great. Right, and I want to show our viewers some of those graphics, because they are pretty amazing. Can we see some of those graphics? Well, what are we looking at here? Well, is this a graphic? No, this is not, this is not a graphic, I guess, but this is, what were you talking about? This is a jellyfish, and one of the things that we use is a protein called green fluorescent protein, to find out where proteins are in living cells. You know, before this, and microscopist looked at things in dead cells, but we can use things in living cells, so this is showing how we make the green fluorescent protein. We actually do it at the level of changing DNA sequence. So they're talking about, at this point, a plasma that we've constructed that has a protein linked to the green fluorescent protein is in the nucleus now, and it's going to be transcribed. That means it's going to, from the DNA, there will be an RNA sequence that you see going

out of the nuclear pore, and it's coming into the cytoplasm. Those little things that you see rolling along that big, the RNA, are ribosomes that's making a protein. The protein comes out, and it's made of two parts. One, your protein, the other part is the green fluorescent protein. Your protein directs where that thing's going to go in the cell. Then you can hit it with UV light, and there you go, you see where the protein is. This is really remarkable because it's allowed us to watch how cells divide, and it gives us an enormous insight into how things work. Now this is what you see under the microscope. Is this what we're looking at here? No, no. I know these are graphics, but is this something similar? Are we just... This is all too small. This is all too small. Oh, too small to see. Oh yeah. Let me think. I'm always telling my students to tell me how big things are, but all these things are too small to see at the level of the light microscope. You could see possibly some of this DNA thing at the level of the atomic force electron microscope.

But, no, you wouldn't see this, but this is what's happening. Basically, the technology is being developed in engineering and chemistry in various places to actually be able to see this kind of thing. So, the revolution in biology is a development of lots of different kinds of tools that allow us to see these kinds of things from different directions so that we can really understand how things work, and what we've come to understand is that shapes are really important because you have to understand that in the cell, all these molecules are blind. They don't have eyes, so they're just kind of going around feeling things, and they have to find something that is just the right shape to be able to do their job. It's a miracle. It is. I swear, I can't even tell you. It's just the most amazing honor to be a scientist, to even be able to ask these kinds of questions. I mean, I just, you know, it's a very special honor. Right.

And that's having that feeling about being in science. You're also wanting to get other people interested in as well. I understand that you're trying to at least recruit younger students, women, Hispanics, anybody who was interested in science, is that one of your goals now? Sure. No, I think, well, bottom line I think people should do what they love, and that's what I, my larger goal, I don't care if it's philosophy, I don't care if it's, you know, political science or English or Spanish or whatever, just do something that actually matters to you. But yes, in terms of the sciences, we have enormously important problems to solve. I think a lot of students get interested in the sciences because of some health problem when other family members have or they like lizards or something. And in that case, I do like to help them. I think it's very important that we have diversity in science. I think it's, there are some big science projects now that are not diverse to my mind. And I think it's hurting them in the long run.

I think it's really important, we can't have, you know, 200 different people with the same solution. We have to have 200 different solutions and be able to take a little bit from each one of those. And that's why it's really important, and that's why we went to make the video was to present this information so that people can start having voices that are, you know, so they know a little bit more about what they're saying, what they're asking, and what they can do. There are so many different things that our students can do now with the training that we can give them right here in the biology department. And that's your goal for the future. Thank you so much, man. You're welcome. If you would like to contact us here at Infocus, you can reach us on our website at www.pbs.org-kennemy or at our email address at infocusatkennemy1.umnm.edu. That's our program for this week.

Thank you for joining us. Thank you very much.