Program Four: "Creators of the Future"

Resistance Fighters (Part 9 of 10)

As antibiotics lose their ability to control infectious diseases, scientists are busy looking for new, more effective drugs from the soil of a park in Vancouver to the radioactive environment of Chernobyl.



{Title: Resistance Fighters}

Narrator, Lillian Lehman: San Francisco, one of the world's most beautiful cities, we are its master builders. Humanity, the product of over one hundred thousand years of evolution. The most capable, powerful life form on Earth. Or are we? Far tinier then the point of a sewing needle, is another life form, a community of minute living things surrounds us. The product of almost four billion years of evolution. They greatly out number us, and their collective weight exceeds that of all animals, and plants combined. Microbes. The trillions of microscopic bacteria, viruses, protozoa, and fungi, that are everywhere around, and inside us. Most are beneficial to us, a few are not. All have amazing powers we are just beginning to recognize. This bacterium can survive a thousand times the nuclear radiation that would kill a human. This virus is responsible for the colors of many tulips. Microbes like these generate half the oxygen that we take in, with every breath. The power of microbes is largely untapped, now they promise new ways to fight disease, alleviate hunger, and clean up pollution. They promise to change our world.

Narrator, Lillian Lehman: Microbes are commonly associated with illness. It's easy to forget that they are front line warriors in the fight against disease. Molds are fungi, that look like microscopic plants. This mold changed medical history.

John B. Kennedy, from old news reel: Industrial monument to the miracle drug, mass production Penicillin plant in Terre Haute Indiana, one of many where the life saving medicine is now being manufactured wholesale. Tons of mold like that you've seen on spoiled foods are processed by rapid fermentation. The Penicillin.

Narrator, Lillian Lehman: Penicillin gave doctors a magic bullet. Suddenly they could cure people of infections that had claimed countless lives, for centuries. Discovered in nineteen twenty eight, by Scottish microbiologist Alexander Fleming. Penicillin was the first microbial product to cure human disease. The first mass produced antibiotic. Like all living things, microbes compete with one another for what they need. Among their chemical weapons are antibiotics. They use them offensively, and defensively. Microbes have had billion of years to prefect their chemical interactions. All that practice has made them the most brilliant chemists on Earth. When we discovered their powerful antibiotic creation, we became over confident. We assume these miracle drugs would serve us, and our children indefinitely. We were wrong. Now there's a serious problem, antibiotic resistance. Around the world we are loosing our ability to cure infections. Vancouver Canada. Julian Davies is a scientist, teacher, and entrepreneur, whose microbial research could save thousands of lives.

Scientist, Julian Davies: Most antibiotics we have at the moment, we've been using for almost fifty years. And in fifty years time, microbes have learned how to live with them. There are microbes, that are found in hospitals that are causing severe infections in human beings, that are resistant to every antibiotic that we know. They cannot be treated.

Narrator, Lillian Lehman:
Tuberculosis, long considered under control in the developed world, is returning. So are many other illnesses we thought antibiotics could cure. Even though antibiotics work in different ways, microbes are outsmarting them one by one. Disease causing bacteria colonize living tissue. Penicillin kills the bacteria by weakening their cell walls. When the walls collapse, the bacteria die. The patient's disease symptoms subside. Microbes reproduce by dividing in two, replicating themselves exactly each time. But mutations, the random genetic changes in all living things, have more impact among microbes because they reproduce so rapidly. As often as every twelve minutes. When a mutation enables a microbe to fend off an antibiotic attack, all the better for the new, stronger microbe, and all the worse for us. As antibiotics kill off the susceptible microbes, the resistant ones can multiply quickly without competition. So the more antibiotics we use, the more the playing field is cleared for antibiotic resistant bacteria.

Scientist, Julian Davies: People ask for antibiotics when they shouldn't need antibiotics. Doctors prescribe antibiotics when they should not. As much as thirty, forty percent of prescriptions Written by family physicians are inappropriate. You don't give antibiotics for a cold.

Narrator, Lillian Lehman: Antibiotic resistance has reached crisis proportions. Around the world, thousands of people are dying of infections that existing antibiotics can't touch.

Scientist, Julian Davies: We have to remember here that no matter what we do, microbes will become resistant to antibiotics, it is inevitable. What we can aim for all the time, is to slow this process down.

Narrator, Lillian Lehman: Nothing will stop microbes from mutating. It's their nature to change.

Scientist, Julian Davies: So the question is what are we gonna do about this? The obvious answer is, we need new antibiotics. The question then is, where do we find the new antibiotics?

Narrator, Lillian Lehman: The microbial community is everywhere, largely unexplored. It contains many undiscovered antibiotics. So Davies searches close to home.

Scientist, Julian Davies: Oh, look I've found a feather, I'm gonna stick it in my hat. Right here. Yeah, sure.

Unknown man: Looks like, it would make a great spot, to take a soil sample.

Scientist, Julian Davies: Oh under, by that tree? Oh yeah, let's have a look there. So here I am, essentially in downtown Vancouver, Stanley Park, the center of Vancouver. This is not an exotic environment, although some people might think so. But here is some soil. It's a bag of soil, we collected just down the road. Right by an old Douglas fir stump. That may have been cut down many years ago, the stump is old, but that soil is typical of that typical stump. That's what's interesting. And if we go somewhere else, next to another kind of tree, we find another kind of soil.

Unkown man: I don't think we need the worm.

Unknown woman: No.

Scientist, Julian Davies: And why is it another kind of soil? Because the microbial population is totally different. And we would expect them to generate different antibiotics. A variety of different products.

Narrator, Lillian Lehman: Most of the microbes in Davies' soil samples can't be grown in the lab. Separated from their tiny communities they die.

Scientist, Julian Davies: I wonder where, where do you think we should go from here? In a hand full of soil, there may be five to ten thousand different microbial species. And they live there as a community. They don't grow singly, like they do in the lab. They're not growing on little petri plates with nutrients. They need the community in order to grow. In fact, ninety nine point nine percent of the microbes from the environment cannot be grown in the lab. So the question is, how do we get at them?

Narrator, Lillian Lehman: Davies is using a new approach to find antibiotics from microbes that won't grow in the lab. He heads the University of British Columbia's Microbiology Department, and is also the president of a new company on campus called TerraGen. Davies and his colleagues are removing the microbes' DNA, the genetic codes that contain all the instructions for the microorganism's internal processes.

Scientist, Julian Davies: We take the genetic material that we isolate from a soil, or some known non-cultivatable source of microbes. And we take that genetic information, and we introduce it into what we call a "surrogate host." We introduce that information into other microbes, that we can grow. We are manipulating DNA. We're taking DNA from one organism, and we're putting it into another organism. And we're asking that the second organism, the recipient organism, can use that DNA to provide us with novel products.

Narrator, Lillian Lehman: Microbes are no strangers to accepting each other's DNA. In nature, they do it all the time.

Scientist, Julian Davies: Microbes have incredible abilities to exchange genetic information. So a microbe can be resistant to an antibiotic, and transfer the ability, to be resistant to that antibiotic, to another microbe.

{Sounds of metal banging.}

Narrator, Lillian Lehman: Sharing genes is a fact of life in the microbial world. Let's see that again. {Tape rewinding sounds} Tiny fragments of DNA called plasmids are transferred from one microbe to another. A single plasmid can pass on many different genetic traits, including antibiotic resistance. TerraGen takes small fragments of DNA, rather like plasmids, from microbes that can't be grown in the lab, and implants them in microbes that can. Genetically altered microbes are grown in cultures by a robot. Small paper disks are saturated with the chemicals the microbes produce. The disks are placed in colonies of harmful bacteria. Already it appears TerraGen has found an antibiotic.

Scientist, Julian Davies: It is an important pathogen in hospitals.

Unknown woman: We've got this very nice zone of clearing where bacterial growth has been inhibited, around this disk. So we know we've got an active antibiotic here.

Narrator, Lillian Lehman: The clear circle means the harmful bacteria are being killed by the antibiotic.

Unkown woman: What's really exciting to us about this one, now, is that it's also showing activity against staphylococcus aureus, one of the bacteria that's been causing a lot of problems in hospitals these days. Many of the strains that you find in hospitals are resistant to almost all drugs. We're going to carry on with the purification of this one. And we're really hoping that it might be TerraGen first new antibiotic.

Narrator, Lillian Lehman: A promising start, but new antibiotics take years to reach the pharmacy shelf. The need is urgent, and the search is on around the world. {Fades to black, then somber classical music plays.} Kiev, Ukraine, in the former soviet union. Berkeley, California microbiologist Jennie Hunter-Cevera has come here to find new antibiotics among some of the heartiest microbes on Earth. Ukraine's Institute of Microbiology appears unsophisticated by western standards. Many of the methods employed here, and much of the equipment, are not leading edge. But the institute's scientists are well trained in classical biology.

Scientist, Jennie Hunter-Cevera: What this program offers is a chance to link two very different sciences, sort of the classics with the modern, and actually have more mileage in combining those two sciences.

Narrator, Lillian Lehman: Genetic engineering is beyond the capabilities of this laboratory. But there is a unique, and forbidding source of genetically altered microbes nearby. Chernobyl's reactor number four. On April twenty six, nineteen eighty six, it exploded. A toxic plume of radioactivity spread across one hundred thousand, square miles. It was a monumental catastrophe. At least fifteen thousand people have died as a result of the accident. Yuri Gleba is the director of the Ukrainian Institute, and also works for an American company. He and Hunter-Cevera are on their way to the reactor complex. They are mounting a unique and potentially dangerous antibiotic safari in radioactive soil.

Scientist, Yuri Gleba: The whole Chernobyl area is a huge petri dish, yes? It's a huge experimental dish where you have, uh, experiments going on at a very high rate.

Scientist, Hunter-Cevera: There's a toxic effect from radiation where organisms will either be killed instantly because they can't deal with it, or some that have evolved over time, will be able to handle it, but they too will now be changed in the way they function. And that's what we're going to be looking at, are these little changes that might end up in, in new chemicals that could be of value to antibiotics.

Narrator, Lillian Lehman: The Chernobyl nuclear plant, is at the center of a heavily contaminated, and completely evacuated circle eighteen miles in diameter.

Scientist, Yuri Gleba: We are about to enter this special zone. There are many other people who would like to enter, and they have to have special permit that says the purpose of the visit, and gives them permission.

Narrator, Lillian Lehman: These evacuatees have brought flowers for the graves of loved ones. Cancer causing radioactive dust is still a danger near the reactor, coveralls and masks will afford some protection.

Scientist, Hunter-Cevera: There's always a little fear and anxiety, but that's good, because that keeps you on your toes, and aware that you'll following all the safety guidelines.

Scientist, Yuri Gleba: What you see is the city of Pripyat, its an abandoned city, a total of a hundred thousand people, have been evacuated from this area. They were forced to leave everything they have had here. It has been empty sine that time, it has to stay empty for another hundred years. It's roughly a hundred, a hundred and twenty microrads.

Scientist, Hunter-Cevera: You can almost hear the sounds of ghosts, that were once there playing on the playground, serving dinner, going to bed. You can hear birds chirping, you can hear insects, you can see buds, and shouts coming out, but you know that life is gone forever, as it was.

Narrator, Lillian Lehman: Reactor number four. Thousands of workers encased it in a twelve story high concrete tomb. It has already begun to crack.

Scientist, Yuri Gleba: This is where so called Red Forest was, pine trees that have been killed, as there was a flash of radioactivity twelve years ago. Now it's regrowing. Its really not, not worth while that you go farther. Okay?

Narrator, Lillian Lehman: For the first days after the accident, the winds blew to the north west. Here the radioactivity is most intense.

Scientist, Yuri Gleba: Unlike other humans, or animals, plants can talk, so they, they stay here. They have to coupe with this situation, with this stressful ecological situation. Yeah this is, this is very unusual. Look at this. Needles here, they're much, much longer then normal. There was some physiological stresses that this plant went through. And maybe, more than that, some mutations. That are causing this. It's really very sick.

Narrator, Lillian Lehman: The microbes in the soil here, have probably under gone similar mutations, they may be producing new antibiotics.

Scientist, Hunter-Cevera: At Chernobyl we have to be very quick when we collect the soil samples. There is that unknown fear, as your collecting the sample, and watching the geiger counter go up in numbers.

Unknown man: Five, Oh.

Scientist, Hunter-Cevera: We got five.

Scientist, Yuri Gleba: Five.

Scientist, Hunter-Cevera: Oh my gosh, am I going to get any dose that might cause changes in me? We have to move fast, so we minimize the chance of exposure. So there is a little sort of anxiety. In one way your dying to know what's in that soil sample, that could be beneficial to man, and on the other hand your sitting there thinking, this could be very negative for me, and so, let me get out of here.

Narrator, Lillian Lehman: The Chernobyl samples now go to the Institute of Microbiology in Kiev, where the bacterial strains they contain will be cultured. Elena Kiprianova heads a research team there.

Scientist, Elena Kiprianova: We have a big selection of strains, and we keep them maintained here. These strains, in, under the mineral oil. That's all, how our collection, is kept in such tubes.

Narrator, Lillian Lehman: Even though most bacteria don't adapt well to life in test tubes, the Ukrainian scientists have successfully cultured more than eight thousand species from around the world.

Scientist, Elena Kiprianova: These strains were isolated from the samples which were taken in Chernobyl reactor. And these bacteria are very interesting. Are they the same as the microorganisms which live in Kiev, or in Ukraine, or are they, some different, because of the radiation? Indeed, the radiation changed their properties. Maybe there are some more biologically active microorganisms than the common bacteria which are living in the Ukrainian soil. Do you understand me?

Narrator, Lillian Lehman: Using traditional techniques, that Alexander Fleming might have employed, Chernobyl bacteria are cultivated in test tubes. The chemicals they leave behind in their nutrient solutions will be screened for new antibiotics in the United States.

Scientist, Hunter-Cevera: Yuri, and I have the sort of the same philosophy that, you only find what your look for in nature.

Scientist, Yuri Gleba: If you collect a sufficient number of, sufficiently unusual organisms, you are going to find what you are looking for. It has been proven in science many, many times. So, I don't see us as, being programmed for failure at all. I'm sure I will win. This trip to Chernobyl was a very emotional day for me. To try, to recall the events, and try to, analyze the consequences. This is something that changed the history. The history of many, many thousands, if not millions of people.

{Accordion music playing.}

Narrator, Lillian Lehman: Had the winds blown to the south the day the Chernobyl reactor exploded, the three million citizens of Kiev, eighty miles away, might have had to abandon their city. They were lucky. But the tragedy continues to haunt this struggling country. Will the Chernobyl antibiotic search derive a benefit from the worst nuclear accident in history? Perhaps. With so many species of microbes yet to be studied, we will find new antibiotics, and they'll work for a while until microbes change the rules of the game, again.

(Transcript provided by Tyler Anderson)



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