Microbes and Men 1974 Episode 02 A Germ Is Life

three mom not much more than century ago epidemics of typhoid cholera and other fevers decimated cities towns villages whole communities then the average life expectancy was brutally short just 40 years you were fortunate indeed if you lived beyond childhood large families were the only means of ensuring any family at all only hundred years ago human survival depended on this alone disease was mystery the remedies near witchcraft hope lay in fervent prayer until out of this background of total ignorance of the true causes or nature of infection there emerged man whose intuitive belief in single observation was to change everything putting an experiment with piece of copper wire and battery now on his table at the time there happened to be magnetized needle as he connected the wire to the battery he suddenly saw the needle move by chance you may say but chance only favors the mind that is prepared that discovery was barely 20 years old before it had its application in the wonders of the electric telegraph and so gentlemen new idea or discovery is like child it awakens hope but no more but let it be cultivated let it grow and then you will see what it will become louis pasteur newly appointed professor of science at leel university was the son of tanner from arbois in southeastern france his father joseph was man of stern moral principle who every sunday would proudly pin to his best frock coat the legion of honor that he'd won as former sergeant major in napoleon's army from him louis derived his patriotism his simple christian faith his belief in discipline and hard work the old man was immensely proud of him but not even he as he walked by himself along the country lanes on sundays could have anticipated that before the boy was 30 he too would have been admitted to the legion of honor for by then young louis had made important discoveries in chemistry that had put him at once in the forefront of french scientists those close to him were expecting even greater things his wife marie claimed that he would either make no name for himself at all or one that would rank was none less than newton or galileo the council wants us to take on the testing of manures for the entire district hope you refused did not but the work it will entail if the faculty is to justify itself in the eyes of the community it must be seen to be of service but you you have little enough time for your research as it is luanne that's what matters most who's to say that buddy science and the application of science go together they belong to each other as the fruit to the tree it was his strength and perhaps his weakness that pasteur was always so eager to put his knowledge to practical use for the benefit of france so he came at once when asked by the son of local manufacturer of alcohol to look into the problems of fermentation this bed looks healthier yes sir an unhealthy one has great scum around the top we're emptying one over here cesar grey scum around the edge typical of vat going lactic and the smell completely different almost acid the manufacture of alcohol by adding yeast to pulp sugar beet was long established process but from time to time it went wrong and no one knew why at this time all fermentations were held to be purely chemical processes despite the fact that in some of them the yeasts had clearly been seen as minute living organisms you can see them quite clearly have look can you see some of them budding that's how they grow and reproduce themselves that's what causes the fermentation and was always told that fermentation took place when yeast were dying not growing yes that is what the textbooks say and some chemists likely big will hear of nothing else but they're wrong in fermentation the yeasts are not dying but growing but the other vets there's fermentation going on there even if the wrong sword and there the yeasts aren't growing suppose yeast isn't the only thing that causes fermentation supposing something else has got into the vets something living causes its own fermentation pasteur had noticed beside the yeasts and the bad vats shimmering little rods it was because chemists like libby could not observe them that they argued that lactic fermentation could take place without minute living organisms it was therefore purely chemical process and the presence of yeasts in some fermentation was purely incidental but pasteur felt now that he could show that the yeasts and little rods were each entirely responsible as living organisms for their own fermentation it's gone in heaven but you'll be back here by six in the morning anyway you must get some sleep they're growing and reproducing murray my little organisms are producing lactic acid as when milk ferments and goes sour really can't accept his ideas nothing fits them whose ideas lee biggs i'm quite sure he's wrong it's not just chemical process he came nearer to the truth in lamppoon he once wrote than he ever came in his serious writings something liebig published as joke would find it funny don't know that should tell you it's slightly indecent find it hard to imagine an indecency of yeast cell well he had the idea that yeast cells were minute animals shaped like distilling apparatus they eat sugar and eject alcohol from their anus and carbon dioxide from their genitals yes but is that all well don't find it all together obscenely or particularly funny but he could almost be right what have you got to do to prove him wrong i'd never prove my case must abolish his i'll publish my work on lactic fermentation that's the battle to be won first yes shall read paper on lactic acid to the leel scientific society the academy will have to wait until we get to paris we're leaving leo didn't tell you no wrote to duma the color is shadow of its former self mary i've offered to become director of administration and scientific studies there's little doubt that the offer will be accepted but with all your work on fermentations did that needn't be interrupted francis premier science college to which owe so much is losing its good name and the least can do is offer my services it's question of duty duty to whom to france our country you have other duties this conflict of duties was to dog pastor all his life when he and his family arrived in paris they had three children by now he had already published what we recognize today as the first manifesto of the germ theory paper demonstrating that when milk went sour it was not just chemical process of decomposition but change brought about by the action of minute living organisms in an age when students at the ecole normale were taught that chemistry explained all and men like liebig held sway it was shattering disclosure pasteur's next move was eagerly awaited by everyone at the ecole especially his old friend and teacher professor bio professor so now we have the finest mind and sounds touch safety away upstairs and yet all they can give him for our laboratory is couple of rooms in the attic offered to share my laboratory space with him but he declined pastor prefers to work alone it's probably my pipe to put him off he can't stand smoking suppose they think that since lauren died from the damp cellar they gave him they'd better give pastor an ethic they gave him nothing pastor found those rooms himself officially he's not even entitled to laboratory louis pasteur well officially he's here as director of scientific studies and administration you complain about the food the mutton stew is inedible when was student here we were grateful for the privilege we didn't send protests to our elders and bitters now take note that stew will be placed on your table every monday until you learn to show proper spirit of appreciation dismiss and take that with you discipline respect for authority to pester the ex-sergeant major son upholding the social order was patriotic duty and patriotism was to color his whole career at present often visited by his mentor bo he was still working to finally discredit liebig and the chemical theory of fermentation why not dead things breaking down to do this pasteur was intending to produce fermentation under conditions where his opponents would say it was not possible because liebig still insists that ferments are the breaking down of albumin so i've got to show that can grow yeast in liquid that doesn't even contain any albumin succeed these outdated chemical theories will be finished for good if the turning of sugar into alcohol was the result of the breaking down of albumen as lee being maintained and the yeast just set it off then it should follow that if there were no albumen to break down the yeast would do nothing pasta knew this to be wrong he knew that yeast would grow and produce fermentation as long as they had something to feed on so in his incubator small cupboard high up in one of the outhouses he placed flasks containing no albumin at all just sugar ammonia and some mineral salts to which specks of yeast had been added down at arbois his nine-year-old daughter jean was staying with her grandfather long way from louis and his flasks they were just beginning to harvest the vintage it was early that year it had been good summer hot summer in the village there'd been one or two cases of typhoid leaving louis attending his experiments and administrative duties murray left paris and went down to arbor where jean had been taken ill oblivious of the seriousness of shan's illness and completely preoccupied with discrediting liebig he at last experienced success flask containing no albumin or organic material to break down had become cloudy showing that the yeast had multiplied exactly as he'd hoped they would the chemical theory of fermentation was disposed of at last in september 1859 jean died of typhoid pasteur wrote to his father cannot keep my thoughts from my poor little girl so good so happy in her life which this fatal year has taken from us let us think now of those that remain and try as much as lies in our power to keep from them the bitterness of life now with young assistant and larger laboratory pasteur was determined to inquire more deeply into this new order of life where did these minute creatures come from if they could find their way so easily into so many substances the obvious place to look first was the air so he and his assistant set up pump to draw air through the window and trap everything it contained on wad of gun cotton the gun cotton would then be dissolved in alcohol and the resulting suspension examined under the microscope pasteur was already aware that many other scientists preferred to believe that germs appeared spontaneously synthesized out of decaying organic matter this completely undermined pasteur's belief that germs could one day be controlled what he saw under his microscope confirmed that they did indeed come from the air in every sample there were hundreds of organized living bodies here were the organisms that like his yeasts could transform whatever they fed upon he was about to demolish yet another of the old guards bastions understand he's trying to discredit the doctrine of spontaneous generation it's maze he'll never find his way out of when louis says it's essential that people realize that the lice they see crawling on bad meat have not been spawned by the meat itself but by other lives every scientist knows that perhaps but with these almost invisible creatures that louis has been finding it's difficult to convince people that these organisms don't just spring into being by themselves by chance that's the doctrine that he can't believe advise you to wipe your spoon well i've lived long enough without ever having done so my void and if i'm carried off now by one of your germs we'll let 82 why shouldn't have much cause for complaint for my part typhoid could be carried by germ admittedly most of us seem to have pretty strong built-in resistance to these organisms and the chances are remote sir but if the one in the thousands has happened to you already we do not take risks anymore in this family forgive me forgive me forgot can we please shall we talk about something more cheerful yes yes all right the death of his first child and his anxiety for the others was constant reminder of the significance his work might one day have and there you are we boil up broth of organic matter in the flask until the heat has destroyed everything living that it contains so it's completely sterile but the vapor from the boiling does not only sterilize the interior walls it also forces out the air now if we remove the flame from the flask and allow the liquid to cool the vapor condenses and is replaced by air it will come right through from the red hot tube where everything contained in it will have been burned and when the flask is cold we cut it off from the rest of the apparatus here and seal it again so we're left with flask containing air but air robbed of everything living in it will it spontaneously give rise to organisms now of course not that will remain pure for years know know but louis it's all been done before and now push and the others have come up with new objection what new objection when you heat the air you say you have killed the germs they say you have killed the life force it was seemingly impossible but how could he devise way of robbing the air of germs and then allowing it into contact with the broth without interfering with it in any way always resourceful he created with the help of colleague and glassblower novel an ingenious form of flask its neck drawn out like swans boil an infusion in that until the germs are killed and the air driven out then leave it to cool no heating this time of the air that has got into it we don't even need to seal the entrance yet ladies and gentlemen that flask will remain pure for years how do you explain that you partisans of spontaneous generation organic matter exposed to ordinary unheated air will you say that by boiling the infusion have destroyed some mysterious genetic power if so let me cut the neck of the flask there now ladies and gentlemen can assure you that in two days time that liquid will be cloudy will you now say that the genetic power has simply been waiting for the swan next removal to manifest itself no the truth is that before broke the neck of the flask the dust from the air was trapped in the curve of the neck here remove the curved neck and you have removed the trap and the dust now has clear passage down into the liquid as further proof i'll take another flask containing similar infusion and shake it so that the liquid now makes contact with the trapped dust and it too will begin to alter for if only one tiny organism makes contact with the liquid it needs to feed on it will multiply rapidly and thus cloud the liquid the partisans of spontaneous generation were unimpressed so pasteur chose another more spectacular way to prove his point that if the air was free of germs an infusion would suffer no change we've got broken one there hold on send that one back yes mr pistol with number of flasks in each of which some broth had been boiled the air driven out and then resealed he set off for the countryside around his hometown of arbois he'd already opened some of the flasks in the streets of paris and not surprisingly the broth had soon gone bad after exposure to the city germs but in the country the air would be purer and according to pasteur's theory fewer would go bad here among the vineyards the flasks were opened and immediately resealed out of 20 eight remained clear to prove his case further he now took his flasks to even purer air with his assistant and mule and an italian guide he ascended to an alpine glacier here he hoped there'd be little contamination from vegetation and little if any dust the time was not made any easier by the italian guide's inability to understand french much less science he seemed obviously determined to keep as far from these lunatics as possible why must he go so fast the slightest knock can break those flasks well he doesn't understand sir well doesn't he realize what's at stake he thinks we're mad be careful sir there's vacuum in every flask here's gently all 20 of the flasks had remained intact now in breaking the seal pester had to be certain that nothing would contaminate them that he or his assistant or the guide had brought there themselves but here at last pasteur was to put to the test his theory that there were places where the air was completely free of germs if this proved so it would destroy for good the doctrine of spontaneous generation for by that doctrine living matter should arise in his flasks no matter where they were unsealed in fact out of twenty flasks only one on reopening was found to be contaminated but just as this appeared to prove that changes in organic matter could only be produced by the action of germs from the air pasteur made the starting discovery that some microbes were of fundamentally different kind have look at that would you tell me what you see little rods moving about in chains string of bodies on river yeah what else do you see well nothing that haven't seen many times before once you look closely at the edge of the drop where the fluid comes into contact with the air it's the organisms have shriveled up and died now the center of the drop they thrive miss you well those minute animal organisms are living without air indeed air kills them it's the last link in the chain they can live anywhere they can do anything there is no air milk dead animals if left to rot totally disappear even the bones go in the end devoured by microbes deep in the body of substance protected from oxygen they go about their job that's how it all works how what works the whole system of creation don't you see roland in these infinitely small creatures god has placed extraordinary powers of decay and destruction without them the world would be filled with garbage there will be no decay no change no life for everything that is needed for the renewal of life is taken by these tiny animals from the decomposing dead is there nothing to be done the tumor is very deep seated and you really can't operate i'd advise against it in the strongest terms but can you we can yes but the devil don't switch the only thing left look if we operate we may remove the tumor or most of at least but if she doesn't die of shock she's very weak already she inevitably succumbed to blood poisoning spent my life diagnosing diseases have no means of curing my medicine or surgery we're helpless look so alert for six weeks camille's condition continued to worsen during that time pasteur hardly ever left her once again he was discovering that he was still no nearer to understanding the processes of human disease in the very month that camille died september 1865 an epidemic of cholera reached paris that was soon claiming two hundred victims day few weeks earlier ignat semelveice had died in vienna his theories about germs largely ignored treatments were still crude ice wet blankets were wrapped around the patients to reduce fever and to combat the miasma the mysterious factor in the air believed to bring on the disease sulphur was burned shocked by his daughter's death pasteur turned his attention directly to the cause of disease is this the best that could be done for these poor people leeches any better suggestions i'm not doctor perhaps should have been how does it spread it's poisonous agent in the air must be like the ones find in my fermentations we must find it and isolate it by sucking air from the cholera ward through the ventilator he hoped to trap the microbe for just as he was convinced that for every fermentation particular microorganism was at work pasteur now believed that for every disease specific microbe was similarly responsible how's it going well monsieur well i'll take over for bit now with all the germs from the ward we condense into the tube how are we going to recognize the cholera germ isn't it possible that it's too small to be seen yes it is but if only we could isolate one organism from the air that's identical to one in the blood of color victim sadly he was unaware that already an englishman had observed that water was the key to the transmission of cholera in any event just to sort out the myriad organisms they found in the air from the ward was hopeless task defeated here by the complexity of human disease pasteur gladly returned to helping french industry for time the diseases of silkworms were to occupy him but once again his personal life caught him back to his true destiny his daughter cecile fell ill with typhoid fever how would you save yourself feel dragged you from your work under false pretenses she's so much recovered dearest cecile and all my silkworms they're sick and laz what fraud you are too much cecile had seemingly recovered but two days later she had relapse like her sister she was another victim of one of the diseases that passed her was still no nearer understanding it was the fourth death in the family within few years for even before camille's death his father had died too proud in the knowledge that his son was becoming national hero not only the vineyards of arbor but the whole of french industry was benefiting from his son studies of the maladies of fermentation thought you were lying down have to be at the academy at 2 30. but you weren't feeling well you you were shivering at lunch it's past and anyway if members of the academy are waiting for me to deliver celebrations paper can't let them down they're not progressing very fast down there are they well at least they've started but think that they'd prefer to spend millions on new opera house rather than on my laboratory well you got your way in the end it'll be finished by the spring in germany they've built palaces for medical studies the ones in berlin and bond cost four millions each and france is catching up france has not yet begun louie you're not well curious tingling sensation look rest this afternoon i'll send note to the academy promised celebrate would deliver his paper and deliver it will i'll be back about five when he delivered his lecture pasteur had returned home tired at nine o'clock that evening after light dinner he'd gone early to bed i'm afraid there's very little hope dying buster don't believe it hemoplegia he's paralyzed down the left side and he's almost lost the power of speech he comes and goes one moment he can speak and actually can't it's more singular paralysis from stroke is usually instant and complete must relieve the pressure think sick should be enough mm-hmm is this the best that can be done for these poor people any better suggestions i'm not doctor perhaps should have been in my life diagnosing diseases have no means of curing made some more surgery we're helpless pasteur's stroke was to leave him partly paralyzed but it wasn't only his illness that clouded his career at this time mentally and physically he was forced to live quietly fermentations were still the only studies in which he achieved practical results and it was for this work that he was elected by one vote in 1873 to the academy of medicine he was by now not the only man to sense connection between fermentation putrefaction and disease but the opposition remained unconvinced every clinician whose experience extends beyond the somewhat limited field of the laboratory bench knows that the disease process is infinitely complex every practicing doctor knows that real success in treatment depends on treating the patient about the disease yet merced has not the slightest hesitation in attributing typhoid typhus tuberculosis septicemia all to the name of bacteria what simple pathology what startling diagnosis mr chairman may yet again draw the attention of my esteemed colleague to the results first published by the vain are now confirmed by myself in long series of experiments we injected animals with the blood of other animals who died of disease invariably these animals sickened and died even though the blood had been diluted to one part in million what does that prove the blood may well contain germs or whatever you wish to call them but it might just as well contain something else that is responsible for carrying the disease thus to say as the experimenters do that by striking dead the bacteria you can halt the process of disease is mere fantasy really do protest gentlemen gentlemen we're fortunate to have among us the only man who has fully investigated the role of germs on putrefaction and fermentation i'd like him to give us his opinion hadn't intended to speak and haven't studied the diseases that you were discussing but in all the fermentations that have studied lactic acid in milk butyric acid butter and recently that of beer have been caused by organized living beings but disease monsieur disease well in the case of beer which is all can talk of the correlation between disease and the presence of organisms is certain and indisputable pasteur had made the world aware of microbes he'd held out the promise of controlling them and conquering disease but neither he nor anyone else could prove that the microbe and only the microbe was the cause of infection the crucial advance when it came did not come from pasta or from any of the great centers of learning in remote country area of east prussia the local doctor was district medical officer robert his patients were scattered community of farmers their sickness provided him with modest income but it was their livestock that interested him most especially when dead he had single consuming interest in one particular disease anthrax it was ravaging the district and year after year it would reappear in the same pastures without any apparent sauce well you might as well bury it hardly worth our trouble doctor the trench will be reopened before the night's out and the car gets stolen from me before you do just take that blood sample what do you want that for it's just theory have coch had read that in the blood of sheep killed by anthrax some weird thread-like organisms always seem to be present he had himself found these twisting threads but were they the killers possibly but it could just as easily be something else in the blood he decided to find out his primitive laboratory was curtained off corner of his consulting room his microscope his wife's birthday gift for her husband's strange hobby his daughter's pet mice were to be the experimental subjects coch was the first to demonstrate their usefulness as laboratory animals using sliver of wood to inject them with the disease starting with the infected blood of the dead sheep he began series of injections passing the infection from one animal to another in each passage of the infection he used the blood of the animal that had previously died methodically he carried out autopsies on each of the dead animals the blood and body tissue all showed clear symptoms of the disease the spleen for example was always enlarged but more important for coch after as many as 20 consecutive passages he could always find the twisting threads in the blood and tissue fluids he noted that these bacilli invariably multiplied but in essence had got no further than other researchers how was he to show that the germ alone caused the disease when each slide sample showed many other organisms from the dead mice any of which could have been equally responsible it's useless somehow he had to grow the bacilli outside the living animal in some substance that was absolutely pure and free of other organisms something the germs could feed on yet at the same time something transparent so he could see what was happening out in the yard chasing chickens she's becoming regular gypsy i'd do my best to keep her clean i'm just going down to the butchers shan't belong we've got patient in half an hour from rad boomst but she just have to wait weren't you the mayor's wife unless she goes to brazil she has no choice but she pays but the animal must be healthy an ox or cow how can be sure it's sound beast wouldn't slaughter it for meat if it weren't what part of it do you want it's the idea of using the sterile clear fluid from within an ox's eye was startlingly original but now how could it be made to work thin drop of fresh beef aqueous humor is placed in ground out hollow on the slide and seated at the periphery with infected spleen cover slip is placed on the slide and as temperature indicator drop of tallow is placed on the inner surface it will melt if the temperature rises to 45 degrees temperature of 40 degrees is satisfactory for my experiment the preparation is sealed with oil to exclude bacteria from the atmosphere and although there was only small amount of air in the slide preparation experience shows that it is adequate petroleum lamp is used as heater and the microscope placed on stand just above it to minimize all temperature changes the apparatus is shielded from drafts and observations are made but can't you keep yourself clean for five minutes in the first two hours the bacilli become thicker then growth begins after three to four hours the bacilli elongate 10 to 20 fold they then bend and form network after several hours the individual threads appear like mass of wavy parallel glass threads soon they form knotted masses and it is impossible to follow individual threads shall bring you something in here you must eat no thank you dude i'm not hungry after 10 to 20 hours the contents of the more vigorously growing threads become finely granulated the granules enlarge and become light refracting spores spending night after night at his microscope was to meticulously check these first observations until he knew his drawings traced with enormous detail the entire life history of the bacillus even revealing the mystery of how it perpetuated itself emmy what is it what's the time it's dawn i've been working all night you must be tired hope it's worth it they have spores it explains almost everything the knowledge that the bacilli could give rise to seed-like spores went long way to explaining the peculiar perniciousness of anthrax making use of his new sterile medium he was able to inoculate animals with the spores alone free of all other organisms it invariably produced anthrax but only after three years repeated experimentation did write to his nearest authority on bacteriology ferdinand cohn professor of botany at breslau university esteemed professor after many failures have finally succeeded in elucidating the developmental cycle of bacillus anthracis would be most grateful if you as our foremost authority on bacteria would give me your criticism of my work since my demonstration material cannot be preserved seek your permission to demonstrate the critical experiments over period of several days he's already here down in the courtyard unpacking his material of necessity i've had to improvise you understand these slivers of wood are somewhat unorthodox but with practice tried first behind the ear but they managed to get the inoculum out now if you care to examine this slide gentlemen it shows the spleen of an animal injected yesterday you can observe the bacilli in the first stages of their elongation i'm going to show the entire elongation process including the moment when the indentations appear and the bacillus is about to divide so clear so pure used the aqueous humor of an ox's eye in ground out hollow in the slide gentlemen leave what you're doing and come at once gentlemen come along to dr cohen's room country doctor all alone miles from anywhere an amazing discovery you must hear him method's all his own but but so exact so precise come along at still lower temperatures the formation was correspondingly more languid below 18 degrees sporolation was rare and there were no spores at all below 15 degrees now this incidentally gives us our first practical preventive measure against the disease because here in germany soil temperatures depth of weight to 10 meters is below 15 degrees thus burying cadavers in trenches of this depth would lead to the destruction of the bacilli and render the cadavers now after scholarlation the threads disintegrate and the spores sink to the bottom now if you care to examine this slide gentlemen you have shamed us all dr and consider this the greatest advance yet made in the field of bacteriology indeed we've all suspected know have that every disease has its own specific germ ever since pastor first suggested the idea but no one has been able to prove it this work of yours has opened the next door shall go on go on yes please dr koch do please go on well having thus eliminated putrefactive bacteria as possible agent we're left with the inescapable conclusion that one type of bacillus can produce specific disease and this leads us naturally to the next step which is the conquering of all disease in man foreign you