Science in Action: Antibiotics (1950)

thank you one usually thinks of the treatment of wounds and other things with antibiotics or the modern wonder drugs or something which is relatively recent actually that's not the case because the history on this goes back some 2,500 years through the early days in China at that time we find that although the principal was not understood that people were using such things as moldy soy bean curds the treat boils and other infection and surprisingly enough the treatment was often successful and it was successful because of the mold which was going on they soybean curd now the doctor applying these on the infection now that was 2,500 years ago early China coming back to the present and went out the library to find out something else about this field of antibiotics picked up the most recent text in this field it's a new revised edition of a book just offered press entitled anti biotics written by two university of california scientists doctors Robertson Pratt and John Gouffran i will make a long story senior author of this volume and stanley he is the professor of pharmacognosy plant physiology at the University of California's School of Pharmacy dr. Robertson Pratt what once again the lines now Joe Carroll it's nice to be back at you thank you well what's the antibiotic field is getting to be really something these days the antibiotics to seem likely to become our most important weapons against many diseases and actually as more and more of them are discovered seems quite likely that in time we may actually be able to control most of the infectious disease that plagued mankind with them well perhaps the first thing we should do then is find out just as just what is an antibody yes well a derivation of the word of course anti against biotic from the root meaning life something that's detrimental to as the term antibiotic is used in pharmacy and in medicine however it has a very specific connotation and is used to describe a chemical substance which is elaborated by one microorganism and which when present even in very dilute concentrations is able to kill or inhibit the growth of other microorganisms the antibiotics are biosynthetic but I mean that they are elaborated by a living organism in the course of its nowise function well I one thing I'm wondering about we used to hear quite a bit about the sulfa drugs recently of course anti biotics will now what is the relationship between these two while the sulfa drugs are strictly synthetic chemical has been made in a laboratory by human chemist they have a peculiar way of working i have a diagram here you might get a look at sulfa drugs act by interfering with metabolism of the pathogen of the pathogenic organism let's consider this as a complex molecule of a substance that is essential for the life of an organism this substance is composed of five simpler constituent now it so happens that the sulfa drugs are so similar in form to one of the constituents of this complex compound that at first the organisms are unable to discriminate between the two and they incorporate the sulfa drug into this essential product but of course this is no longer the same product and in due course the organism finds but it can't use this product in its normal life functions and so across it died amazon that's fine for the sulfur's but now how about the antibody well that's a debatable point but many of the antibiotics probably act in essentially the same way but by interfering with other essential compound let's go back again to the soybean curtsied we looked at now but earlier there is the culture of this material is growing here and here is the same materializer with fear not in culture well they take some of this now and I'll just get a little bit of it and put around the microscope here and then turn on the lamp we will see that this has a very beautiful arrangement one of the penicillium proof and so called because of the fringe life arrangement it looks like a painters brush of course and that's quite characteristic of that yes and as this growth of course growing on the soybean curd that secretes the chemical penicillin which diffuses into the curd and from that of us in the wound of the patient thought it would be a very unwise procedure for us to try to dr. ourselves in this way because such a product is extremely crude and contains many impurity some of which might be rather detrimental here is some penicillin in the purified crystalline form in which it is used today now let me put some of this under the microscope for you uh now if you look at this you'll notice that the field is covered with some very beautiful crystals which are crystals of the purified penicillin as the organism is grown commercially it looks something like tapioca the large sort and is one of the if the only sort fungus as a matter of fact the only mole which is source at the present time are they useful antibiotic there are many produced by other molds but most of them are too toxic Oh step over here behind the lab break down here were these various products to originate for example here's the penicillin Courtin it comes from a mole that was the first 1i sir hadn't another group the accent over my seeds which has a group of intermediate between the molds and the last group the bacteria now we've had a lot of these new ones come in here what's the story on that well a kid of my teeth have been the most fruitful source of antibiotics producing such thing to streptomycin nuria mice and terramycin borrow my speeding to read from ice and magnum ison whole host of them we shouldn't have caught ignore the bacteria although they don't produce so many antibiotics very useful we do get bacitracin virus ricin and polymyxin from the bacteria which are extremely useful a characteristic of course is their selective toxicity of these drugs i think you have no choice after that would bring out this point on this in other words with disinfectants the thing that they do is to kill all of the microbes and when we get over here the antibiotics we find that some of them kill certain microbes others weakened some of the microbes and finally there are some antibiotics it show no affection or another yes they are very discriminating in their action this is one reason why antibiotics should not be used indiscriminately I'll say for the common cold for example because they each one is a able to do a specific job and it shouldn't be you shouldn't try to make it do a job that's not capable I know all of us have had the experience of going to the reptilian doctor's office and they're feeling that we have to have an antibiotic we've heard about all these things we say doc may I have one he says no no wow the doctor is actually serving in your best interest in taxation shouldn't argue with them because the doctor knows which diseases which organisms can be controlled by antibodies he also knows that if he uses an antibiotic when it isn't really called for he may sensitize you so that some future time when you have a really serious infection calling for an antibiotic it wouldn't be possible to use it what's up over here and see how some of these various right now activity penicillin of course is the first one that was discovered and it works on streptococcal infections most wound infections and most bacterial pneumonias and that is what this narrow spectrum antibodies what do you mean I actually of course it looks at the penicillin covers quite as territory here and does it is useful in many diseases but it turns out that most of these are caused by a relatively small group of organisms and then switch tents we call it a narrow spectrum antibiotic the next major antibiotic discovered after penicillin was streptomycin which comes from one of your into my seat and has a slightly broader spectrum if you wish but it's still relatively limited in its usefulness and today is used mostly for urinary infections is effective in plague and particularly interesting is capable of controlling some of the very persistent tuberculosis organism know about these broad spectrum antibiotics well these antibiotics or you my sins terramycin for my seat and Magnemite and others that aren't shown here have a much wider range of activity in that they can in not only inhibit the growth of bacteria but some viruses some few viruses some work as a useful in such things as whooping cough undulant fever some of the dysentery some boil from pneumonias they're particularly useful in typhoid and typhus certificate with some of our boys encountered in the South Pacific uh some few virus diseases because of this wide range we call them a broad-spectrum antibiotics well of course a lot of these things you come from the soil and a sport now I go out in my backyard and I dig up some soil I bring in you I know this has a new antibody are you going through I thought for general health I picked up a sample from Golden Gate Park dad like bringing the lab mrs. truck this is dr. Harrell becoming science or mrs. tuck is working on some soil samples now this sample was carefully weighed out and then it's placed into a dilution bottle of this sort and you noticed that you gets a rather muddy a turbid solution now actually the soil is so loaded with organism that if try to culture these directly we wouldn't be able to see the forest for the trees there'd be so many colonies that were show well so we're going to dilute this and that's what she's doing now should take a small amount of this puts it into a relatively large amount of water and gets a much more dilute suspension which will be useful for our subsequent work now how many times would she do that well it depends on the type of soil and not of organic matter in it so on but we generally run from the delusion of one to ten thousand up to one in a hundred million uh you notice that she tilts this plate to get a uniform suspension of the distribution of the suspension over the entire surface and she would run through several of these she's making a second one now now these organisms actually are relatively slow growing and after she completes this useless pipette which he can suck up the solution and you notice again into the plate and she will tilt this plate but it's essential that we get uniform distribution of the suspension over the circle know the interesting thing into here is that the soil instead of being a reservoir of disease that's been considered and pass actually is a potential resource for these handle yes very true thousands of years men have been searching for remedies to cure their ills and to excuse a pond in many instances they lay the kuro laye literally at their feet in the soil now these will grow rather slowly they'll have to be placed in the incubator but we have some colonies here someplace which were poured out two days ago like to show you some of these you notice this the plate here which has a quite a dense growth you can see a number of individual colonies everything on you could well studied out of court no it's pretty difficult on a fight like the which ones would you I mean which one would you pick now for study on it well no normally we would look for one of the actinomycete uh because we know that's the best bet but specifically we would look for colonies which is surrounded by clear areas and we have marked one on one of the plate this would seem show that this organism is producing a substance which is preventing the growth of other organisms here by now you would take that out and set it up on another plate down yes we would pull out the colony of that organism and it could be streaked out on a petri plate uh we would get something of this sort well I notice that doesn't go all the way to the top does that to indicate now that's being real well you see this is our soil organism across the top here and we have cross street with various disease-causing germs now you're exactly right this organism which grows right up to the top is inhibited markedly it is not inhibited whereas these which grow only some distant are inhibited by the material defusing bomb this soil organism know the amazing thing to me about this is that what you demonstrate here very very quickly had to be going through some 100,000 times to discover just say terramycin or streptomycin alone that's correct and these have come from soil samples gathered from all over the world the Philippines the Orient and everyplace else see because there's only a small part of the actual procedure as you've said when a useful antibiotic or potentially useful one is found there are some ten or a dozen Pacific test that it has to go through before can be released for human medication how about some of these end products in the antibiotic industrial ear so much about b12 and some of the other well are a number of byproducts actually the antibiotics industry has caused a decrease in the cost of some other medicinal vitamin b12 for example is very important in the treatment of certain type of anemia and it extremely costly now it's produced as a by-product from the fermentation of by streptomyces in the production of streptomycin there are also other aspects of the antibiotic industry to aid in the productive growth acceleration small amounts added to the feed or stimulate the growth of young animals well we have some chickens are there I think Rachel's demonstrate that try to pull these cool grass roots both these are the same age and this one has been on a diet which inserted an antibody you know the difference in size is much larger whereas this Lou I don't seem to be very capable handling is the smaller one here has been on just a normal diet there's quite a bit difference in size now this works very well on chickens but it doesn't necessarily work on other animals recently in Steinhart aquarium we conducted some tests using salmon and adding antibiotics for the food we found that see everything happened that we didn't expect to happen so finally we had to take the we had to take a salmon off the antibody it didn't work for them where is it did work of that occurring one point yeah our own bed you brought that up because parents might be inclined to try this on their children if they thought they weren't growing rapidly enough it doesn't work that way actually they have been used in a few case of premature infants prevent early weight loss but on infants born at normal term or an older children as totally without effect and might actually be harmful by sensitizing the patient or the child fell it at a later time a drug couldn't be used when needed certainly this growth factor is very important but the germ killing factor is the thing is we're primarily interested in yes that's very true the use of penicillin alone as Kurt era reduced the case potato fatality rate in pneumococcal pneumonia from 75 to 85 percent of pre antibiotic years to less than ten percent certain time and in certain blood infection septicemia in the light likewise case fatality rates have declined a less than ten percent of the antibiotics sir prescriptions written as prescriptions written today more than twenty-five percent of the prescription business in pharmacy of the United States is for anabolic product well I'm wondering about with all these various antibiotics available hot as a physician know that he should use this one and not this one well good question the first step is to find out what the organism is and then to determine its sensitivity to the specific antibiotics this culture that you're holding is a type of thing that might be sent in by a physician for determination the first step would be to carefully remove this plug industry goes injuries the material out on the plate right so this play contains blood so that is to provide the organism of the nutritional environment than one of that it had in the host now this will have to be incubated for a few hours before anything would be pain but I out here a site which was streaked out yesterday showing the showing the type of thing that you might expect you notice growth along the clear areas those are important are they yes you notice there's long how long some of those streaks are these clear areas showing that the organism has actually destroyed the blood in that area and that's what it would do any case of septicemia well now with these rays shotgunner broad-spectrum antibiotics that work on a variety of things why is it necessary to know just what is involved by way of the germ yes the reason is that some of these antibiotics may be able to partially inhibit the organism without completely controlling it and you may then want to go to another antibiotic in order to actually cure the infection of if you've used wrong antibiotic space well you haven't kill the organism you may have so altered its parents that subsequent identification is practically impossible there boys only safe procedure is preliminary identification and later sensitivity testing well I see Polly's on this plate and they all look alike no guarantees only one type of notice that they're all clusters of little round colonies is showing that this is a Staphylococcus the next thing of course would make sure would be to take out of smears I have made a smear on a slide if you look at this under the microscope you'll see these clusters of colonies that I referred to go now following this we would want to determine its sensitivity to the different antibiotics and for that purpose we would set up a series of tubes of nutrient broth containing the organism and containing different concentrations of different antibiotics where the organism grows the antibiotic is not aspect as the tube is quite turban such as in these now whether tube is clear it indicates that there hasn't been much any growth and in this case things that we have two antibiotics which are effective and these two would then be was penicillin and this is streptomycin which are able to control the growth of this bug then the clinical laboratory would send the report back to the doctor who sent in this original specimen and he would know what antibody to prescribe in natick ok all this takes only a matter of 24 to 36 hours well one thing that we vary quite a bit about is this giving up to antibiotics at the same time what's well not well that's used because sometimes an organism which may not be vulnerable to a frontal attack or only parsley so by one antibiotic may have an Achilles heel that will succumb to a second and also to reduce toxicity some of these antibiotics do have toxic properties we have some fish that we've been working with in this connection ah which probably show some of these symptoms these fish have received a half a milligram of streptomycin and be the half a milligram of die haider you notice that they're pretty sick most of them some of these are beginning to recover but they're pretty sick now that's because of the toxicity of those drugs well in this case these fish have received the same total amount but only half of each drug and that way you haven't done it that way we could we keep the full antibiotic activity but cut down on a toxicity of the drug and this same practice the supplies in human medication well seems to me that when we use the antibiotics what we're actually doing is is making a microbe look for us in other words of buying one against another that's right like all living organisms including man himself organized the microbes have to have not only food but space in order to live and to grow and to reproduce and the bacteria in the world of microorganisms do this best way they can to defend their right they secrete chemical substances which are capable of making a environment untenable for their sort of reddit the chemical warfare among the night so to say actually you realize there's so many antibiotics that a dictionary has come out now listening more than a thousand antibiotics of elves in this one volume some 300 of which have been chemically identified think it's very hopeful for the future because the the many of these haven't yet been tested that's a great deal may come from well one thing we're speaking a little bit earlier is the effective antibiotics are on the general longevity picture in other words life expectancy on this chart here notice it from 1940 are a little bit earlier when the Janet body was discard it's bright an upswing there now what's the gas well that's life expectancy at birth in the United States has been increasing for the last hundred years or so and going up in 1900 due largely to improve methods and sanitation healthcare diagnosis but there is two rather sharper increase since nineteen forty when antibiotics were first introduced I think this can be put in a more dramatic way by pointing out that in 1901 about this period here finalist figures of the Census Bureau are the children born in this year twenty five percent of them died for attaining age of 25 but it is predicted on the basis of statistics that are the children born in 1948 that before that the group has been depleted by twenty-five percent the remaining 75% will be nearly 60 years of a this tremendous and of course there the antibiotics have entered this picture largely then on recently responsible but I have contributed to it the social economic aspects of this in future is certainly something either tremendous there will be on us guilty well doctor I don't want to thank you for coming to talk action to tell us about the battle of the micro and chemical warfare in these group I'll be back in just a moment where the animal of the week our atom of the week is a hellbender it's a giant salamander and factually largest element of the lives in the United States and it occurs only in the eastern part of the country and you'll notice what the distribution is patch up in here down through here in the central part of the United States and over in this section in here and there's another type that lives here actually we have two different types not too much concerned with that at the present time but let's take this down look in the tank where we have the hellbender notice he's swimming down there regulo thought i'd like to have you notice first of all that he has this Ridge the fool why she fooled along the side of the body knots very important in the respiration of the animal when he's young he has gills but the youth loses those later this fall to skin has a lot of blood vessels close to the surface so that quite often you will see these animals rotating the body like this and that is it to enable them to pick up more oxygen of the water that's the hellbender and it's the guy a salamander of the Eastern party United States I normally hides in the bottom of ponds and pools during the daytime and usually more active at night during october november the females will lay about old 300 to 450 eggs it looks like a string of beads and occasionally several females would use the same nest very very interesting salamander this is the dying solemn and Eastern 49 states 27 inches maximum length actually it's mild compared with the largest member of this family and which is also the largest salamander in the world that comes from Japan looks very much like this Rob Dempster's bringing one in here right now I'm gonna ask them just put it right down on the getting right over here how does this go you have to be careful these because they have been known to bite I'll train him around here see if i can let us see these there folks all the head notice the spotting coloration this is vaughn because they according to some authorities they reach a length of five feet sometimes even seven feet very difficult to hold on to and one thing about this is good deed in fact if so good to eat that the japanese government has declared this to be a protected animal no one is permitted to take them except for scientific purposes and for exhibition this is the japanese giant salamander a relative of the Eastern hellbender which occurs united states of course this is the largest salamander in the world one's full grown this is just a little patient we have here now well now favre are animals of the week on an X program on science in action hope you find it be with us back actually you've just seen another in a fascinating television series science in action science in action is produced by the California Academy of Sciences under the supervision of dr. robert c Miller