Ear on Chicago; Abbott Laboratories

This is the sound of thousands of pills being sugar coated. Soon these same pills will be on the shelf of your local drug store. This is the story of Abbott Labs located in North Chicago about 35 miles from the loop. Here is manufactured more than 700 pharmaceuticals, including the well -known antibiotics such as penicillin. These drugs are administered to the patient in many forms. The most common being in pills are the medical profession prefers to call them tablets. It is the manufacturer of these tablets which will be the basis of this program. Behind each new drug that hits the headlines lies the patients of scientists and the boredom of routine. Much of scientific investigation is routine, testing and checking, recording day after day, year after year, just playing the percentages on a long term basis. Give the right man the freedom of ideas and movement, give him unlimited equipment sooner or later, great new

therapeutic drugs will be discovered. Our story opens in a research lab in room 200 on the second floor. Our guide is Dr. Marlon Leffler, Associate Director at the Research Department. We are standing now in one of the laboratories main labs where they conduct research. Dr. Leffler, could you tell us what this machine here is? We're going to talk about a flame potometer and I'm going to ask Bill Lennox to explain to you what it does and what it's for. This instrument called the flame potometer is used to determine the amount of sodium potassium or calcium in the solutions that we prepare here at the laboratory. The way it operates is sodium will impart a yellow color to a flame when burned. Potassium will impart a pink color to a flame when it is

burned. If we are determining sodium as you see running at present time, the yellow color of the flame is picked up by a photo tube which is set up to measure only yellow color and transmitted to a meter on the front of the instrument. The meter is now reading 70, which means that on sodium we have 4 .2 parts per million of sodium in the solution. To use this machine to test your finished products, we use it both to test the finished products and to follow our material in process. Thank you very much Mr. Lennox for describing this flame potometer to us and now I think we're ready to move on. Dr. Leffler, where will we go next? Now we're going into the microanalytical laboratory. The head of the

microanalytical laboratory is Mr. Elmer Schelberg. Mr. Schelberg, what are these instruments that we're standing in front of now? These are very sensitive microanalytical balances used for weighing minute quantities of material. Just how critical are they? Well, they're extremely sensitive. Shall we say that if we would take a piece of paper and tear it like this and I would weigh this paper on this balance and then place a pencil mark on that paper, I could weigh approximately one tenth of that pencil mark. Now this balance is estimated in gammas, which is rather difficult to point out in ounces or pumps. Well, I would like to try this experiment if you don't mind, weighing a pencil mark. Yes, I will perform this experiment for you. I will take this paper now and I will place it in the balance and I'll weigh this paper now, which will take several seconds

to weigh. Then I will take the paper off and place the pencil mark on here and replace the paper. What can you talk to us while you're weighing the paper? Yes, I can do that. Although the balances are extremely sensitive and I will have to move back from the balance to keep my face away from the balance so there will be no heat radiated to the balance. I'm now weighing the paper and very shortly I will have that weight. Now I'm going to take that paper off again and I will place the pencil mark on there, which I'm now doing. Put the paper back on the balance, close the doors, and start weighing the paper again with the pencil mark on it. With the pencil mark on it, that's right. Now I have the weight of that pencil mark, which is approximately 15 gammas. Now I could weigh one tenth, the sensitivity of this balance could weigh one tenth of that pencil mark. You say it's this,

excuse me, can you tell them what that figure would be with a number of zeroes in front of it? Well, I could do that in grams, which would be decimal five zeroes one. Grammas. Yeah, that's right. And to break it down into ounces as you said would be. Well, ounces, there are 28 .35 grams per ounce, which would be rather difficult to bring down. Well, that's a fantastically small risk. Yes, it is. These balances are extremely sensitive, not only as far as weighing the sample, but to heat measurement and so forth. And if I were to take this balance and move it out of this room, I could not use this balance for several hours due to the heat from my hands and moving the balance. Is that right? That's absolutely great. Extremely delicate, very strange, extremely sensitivity. Well, I'm Mr. Schellberg, I'd like to talk with you just a moment about another instrument which you have in the laboratory.

Just exactly what was that click and what did it do? This turned the automatic combustion unit on in preparation for burning an organic compound in the determination or for the determination of carbon and hydrogen. And what do you call this instrument? An automatic combustion unit and its purpose is what? Is to burn an organic compound and convert the sample from the carbon into carbon dioxide or the hydrogen to water, which we pick up on weighing tubes over here, and there are weight and from this weight we can determine the carbon and hydrogen in the compound. And that would be to measure the carbon in a finished product, for example? That would then tell the research man whether he had the right compound or not. Well, now we heard a second click just a second ago. What was that? That was the furnace is resetting himself now and there is a flushing crate going on and

you now heard the error turning on to pull off the tube prior to the next acid, preparation for the next acid. Well, Dr. Leffler, now we have seen the flameometer, the balances, and this electric furnace. How do they fit into the picture of research? The flame photometer, for instance, can be used in assaying one of our products such as our sweetening agent, calcium sucurille. Now in using the balances that you heard about and this carbon hydrogen furnace, these are very important things to the research man in developing such new things as the antibiotics that have become so important in medicine today. And I think that you would be interested now in going down to the antibiotic division to hear about the development of these new products. This is the

antibiotic division and we're going to talk to Dr. Alan Saunders just a moment. The sound you're hearing is that of a rotating machine which is shaking a great quantity of beakers filled with some kind of liquid about which I know very little but about which I intend to learn a great deal from Dr. Saunders. Could you tell us what this machine does, Dr? This machine is one of several that we have for growing cultures and rotating motion. We grow cultures of yeast, molds, or bacteria in this manner. Why do you shake them so? Shaking is necessary to incorporate oxygen from the air which is required for the growth of these organisms. What do you mean these organisms can grow and they're moving in such a fast rate of speed? Yes, they grow in these containers and reach maximum growth in about 72 hours. And if you didn't shake them they would die? Yes, that's right. Because they didn't get enough air? Yes. Well now what is the purpose for growing these organisms? These

organisms are grown for many purposes, primarily for the production of antibiotic products like penicillin, streptomycin, or any of the known products produced by fermentation procedures. I have never seen anything like this. I always understood that they grew these organisms on molds. Do you do that also? Yes, well actually we grow the molds in these containers. I see not on great large slabs like I've been led to believe. That has been done or was done first to grow them on slabs and then the process was converted to a so -called submerged culture which means growing in a liquid with agitation as you see these on the shaker. Well some of these organisms be used in some penicillin shot in the distant future. Conceivably the material here could be used in that fashion. These are more likely to be considered experimental and the results of the work in this shaker will be extrapolated to larger equipment where

the antibiotics to be used in hospitals actually produced. Well Dr. Leffler how do you grow the organism in a large scale? We use larger fermenters which are mechanical pieces of equipment that are something like the ones that you've just talked about in the shake flas and the next step in research is to go to a larger size five gallon fermenter and from there then we go to the plant for production of these antibiotics. In order to find out about the fermentation Department of Abbott Laboratories we've come to the office of Dr. Charles Brown. Here they grow penicillin. Now that probably sounds like a strange thing to say but that's just exactly what they do. They grow antibiotics such as penicillin. Dr. Brown would you take us through the steps of the growth of these antibiotics? The first steps in the production of the antibiotics occur in a

biological laboratory where we start with a few cells of the particular organism that is to be used and through suitable transfers we induce that organism to multiply. In other words increase in population to the point that finally we have sufficient numbers of cells to move into plant size equipment. The first step in the plant takes place in 500 gallon tanks where we have a diet that is suitable for the growth of the particular organism that is prepared by cooking operations so that there are no other microorganisms present. We then introduce the cells of the particular organism that we want to grow into this sterile medium and if we supply the correct temperature and air the organism will grow and when it grows it produces a specific chemical penicillin for instance. Now penicillin is not the organism itself but is what is produced by the organism. That is correct penicillin is a byproduct of the growth of this

organism. It is similar to let's say the carbon dioxide that you and I give off when we live or grow so that we are looking for a byproduct of a resulting product from the growth of this particular organism. Well what is the organism itself? The organism that produces penicillin is a mole, a green mole very similar to that which you've seen growing on the surface of a jar of jelly or you'll stay a loaf of bread. A very specific strain however are family in that it produces penicillin not all green moles produce antibiotics. Well where do you get the raw material to grow this mold? Well we have used two sources some of our antibiotic producing organisms have been delivered to us from various university groups however we have a very extensive research program whose sole purpose is to look for organisms that might produce interesting antibiotics and most of this program is based on the searching of soil samples ordinary dirt that is sent to us from all parts of the world organisms are

isolated from that soil and are tested in our research division to see whether they produce any antibiotic materials. You mean you could go out here in the backyard and dig up a bucket full of soil and find these organisms that would produce such antibiotics as penicillin in them? That is correct all soil contains thousands of microorganisms bacteria, moles, yeast and so on not all of those organisms however produced antibiotics so it's a matter of looking for the needle in the haystack looking for the few that might produce antibiotics and that's exactly what we do. Well you discovered penicillin and that was a very effective thing and of course it's still being produced but have you discovered anything since penicillin that is even more effective? Well we have had antibiotics discovered since the days of penicillin penicillin was one of the first and those that have come since penicillin have done jobs that penicillin can't do so that we have rounded out the picture if you will in combating the

various diseases of man. Well penicillin was the first great and most publicized antibiotic so why don't you tell us a story of penicillin Dr. Brown? The organism that produces penicillin was discovered by chance in the laboratory of Dr. Fleming in England. Dr. Fleming was a bacteriologist who was engaged in studying the growth habits of a particular strain of bacteria and one day quite by accident while he was examining the vessel on which he was growing these bacteria a few moles pores that is the reproductive stages of this particular organism fell on the surface of this this vessel and there grew when they grew the bacteria that were there failed to multiply so the Dr. Fleming noticed a clear zone of inhibition that is an area where the bacteria were not growing and the mole was growing and he deduced that perhaps the mole itself or something that the mole produced when it grew must have killed the bacteria. He therefore made a note of

this fact and some years later that fact was further investigated by chemist and they discovered that this mole in fact did produce a chemical that would inhibit or prevent the growth of bacteria. And this product was penicillin. This chemical product was penicillin. Where did its name come from? The mole that Dr. Fleming encountered as a contaminant was penicillium chrysogenum and hence the name penicillin was derived from the Latin term penicillium. Well have other antibiotics been manufactured in the same manner that penicillin has always been manufactured? That is correct the only thing we have done is to change the organism and change the diet on which the organism is grown. At this point the drugs are sent over to the production department and put into pill or tablet form but there is yet one more step in the research department about which we should speak at least briefly. That is the fact that they bring the

tablet back to what is known as the disintegration department to test and see how long it would take the pill to dissolve or disintegrate in the stomach. Here in the tablet disintegration laboratory we find that for the first time in our trip through the research department we see a tablet in its final stage. Now the group leader in this department is Fred Inns. Fred what are these machines doing? These machines are simulating or giving the same effect as the action of the stomach upon the medicine. And those juices through which those tablets are being put are they the same juices through which go through the stomach? They are essentially the same. The juices here are artificial gastric or intestinal juices. Well now they're disintegrating. Do you determine how long it takes a tablet to disintegrate in the stomach in this manner? Yes we do. The tablet is placed in a special basket and agitated inside the solution or in the solution. What's this particular

tablet? This particular tablet is one of our antibiotics. How long would it take to dissolve? Oh it may take from a half an hour to an hour and a half. Does it really take that long for some of them to dissolve in our stomachs? The reason for that is that some of the tablets must have a buffer which will tend to delay the action of the gastric juice so that the active ingredient in the medicine can then be absorbed into the system and give the effect that we desire. And of course sometimes the tablet will dissolve in a matter of seconds I suppose. That's right we do have some limits of tablets that must dissolve in less than one minute. We've come out of the development department of Abbott Laboratories the place where they produce the goods they make the pharmaceuticals and in this first stage is a giant mixer which mixes up the drugs I suppose we're going to talk about

that right now. The guide on our tour is Dr. Charles Brown. Dr. Brown tell us about this machine which is making quite a good deal of noise right now. This is the first step in the manufacture of our tablets. Here we are mixing the powders that will ultimately be compressed into the actual tablets. In order to give you a better description I'd like to introduce you to Mr. Jess Oins the department manager of tablet manufacturing. Mr. Oins can you tell us about this particular badge? Yes. The erythrosin tablets are mixed the powder are mixed in this large mixer about 800 pounds which will make 465 ,000 tablets. After it comes out of this mixer will be dried all the excess moisture dried out and it will be remixed before going to the tablet machine. When I'm Mr. Oins there's a lot of material in this giant mix master the strange mechanism which keeps turning over and over it looks

like flour being made into dough by some bakery and the machine looks like a machine that a bakery would use just how much or what is in this in this mixture. It's the drug plus the acceptance that are necessary to make a tablet. The main one is starch which makes the tablet break up when you swallow it. And the drug in this case is what? It's erythrosin. That's something like penicillinis but that's very similar to penicillin yes. Thank you very much. Now Dr. Brown where would be the next step that we would go? Logically we would go from here to our compressing room where we will compress a similar powder into the actual tablets. Let's go take a look at the compressing room. Well the machine you are hearing now is the machine in the final stage or one of the final

stages of the Abbott Laboratories manufacturer pharmaceutical tablets. There are about 30 such machines manufacturing tablets of all sizes shapes and colors. Right now I'm holding three various tablets in my hand. One is a brown vitamin tablet and other one is a cube shaped pink tablet and the third is a round white tablet so they can make them any size any shape and just about any color that they desire. About 30 of these machines and they look like some machine from the 20th century should look with long tubes going up, bringing the drugs down into the machine where punches pound out those tablets. Mr. Owens is still with us and I want to ask him how the machines are operated. The machine is operated by compression, the dried mixture of drugs or granulation. It's fed into the machine and just by direct pressure between two

punches the tablets are compressed and ejected from the machine. Now on the other side of the room I noticed down further that there were some women but we're putting the tablets in the bottles. Is that the final step for those particular tablets? Yes or those tablets are going directly into the bottles because they have to be protected from ordinary atmospheric conditions. This whole room is air condition so we do the all the final step in here. Mr. Owens why do they always put cotton in the tops of tablet bottles to prevent the tablet from shaking in the bottle during transit and breaking so that the tablet can't move in the bottle. Somebody told me that was to keep the air out. No that's not true. Well this is just about the last stage then in the production of tablets isn't it? We have one more to go to which will be the coating of tablets. This is the sugar

coating department. The place where the tablets get their bright color and the color a cover of sugar. Now Dr. Brown is with us once more and it's going to tell us just exactly what these machines do and how they do it. Here in this room the compressed tablets are placed in the drums of these rotating machines and on the tablets is distributed a coating solution. The coating solution may be the older sugar coating or most recently a newly developed plastic material is being applied to tablets. In the rotation of the tablets in the drum the solution is evenly distributed over the surface of the tablets and the circulating air dries that coating. Now you say that in your newer machines you're putting on a wax coating. You mean that someday we won't ever be able to use the expression sugar coating that is correct. Not all of our products are protected with this newer coating but someday we hope to completely eliminate the use of sugar coating.

Your pills will look your tablets I beg your pardon. Your tablets will look as bright and pretty but won't taste as sweet but they will be small or an easy to take and they'll dissolve quicker that is correct. Dr. Brown what's the next step? Let's take a look at capsule manufacturing. Second only to the manufacturer of tablets at Abbott Laboratories is the manufacturer of capsules which contain drugs. Now these capsules are made from gelatin right in front of us here is a young lady operating a machine which is filling these gelatin capsules with drugs. Mr. Owens would you tell us how these machines are operated? The machine takes the empty capsule, separates it into two parts, fills the powder into the larger part of the capsule, replaces the cap and with the uniform weight on all the

capsules as are filled. May I ask this young lady a question? We heard a loud buzz a moment ago. Could you tell us what that was? It was the vibrator from the powder hopper. The vibrator? The vibrator from the powder hopper. In other words that sends the powder into this hopper up here? Yes it does. I see. The powder which is in a large hopper above the machine which fills the powder into the capsules has a loud buzz to it which you hear at periodic times. Well this is a very important department of Abbott Laboratories. Is it not Mr. Owens? Yes it is. Second only as we mentioned a moment ago to that in the tablet department. Yes sir. Well we have the tablets manufactured and we have the capsules manufactured. Now the problem is to get them into bottles. We have come over here to the packaging department to talk to Mr. Oglesby who is the manager. They have a rather intricate way in which they count the tablets a certain number to a bottle. Sometimes a hundred and I

suppose sometimes more and sometimes fewer. Is that true? That's true. That's right. Now tell us a little bit about how this equipment works. The tablets are dipped out of a drum and placed into the filling hopper. The hopper is and tilted up shook until all the holes in the slide are filled. This is checked by two girls to ensure the proper con in each bottle. At which time the slide is pulled out over a set of funnels where the tablets are fed down into the bottles. Now if Mrs. Brown or Mrs. Smith called up the drugstore and said I didn't get a hundred capsules or a hundred tablets in my bottle would you finally get that complaint Mr. Oglesby? We sure would. First and foremost in the production of drugs is research and research at Abbott Labs is carried out in the science building. As you enter the science building you see a towering, impressive and symbolic mural and heroic figure

stretching skyward taking its substance from a tree. The tree is deep rooted in the symbols of science and surrounded at the base by the tools and men of research. It is these tools and these men who will combine to give us the wonder drugs of tomorrow. We wish to thank the scientists of Abbott Laboratories whose fine cooperation has made this program possible.