What I'd like to do is just drag us all down into the gutter, and actually all the way down into the sewer because I want to talk about diarrhea. And in particular, I want to talk about the design of diarrhea. And when evolutionary biologists talk about design, they really mean design by natural selection. And that brings me to the title of the talk, "Using Evolution to Design Disease Organisms Intelligently." And I also have a little bit of a sort of smartass subtitle to this. But I'm not just doing this to be cute. I really think that this subtitle explains what somebody like me, who's sort of a Darwin wannabe, how they actually look at one's role in sort of coming into this field of health sciences and medicine. It's really not a very friendly field for evolutionary biologists. You actually see a great potential, but you see a lot of people who are sort of defending their turf, and may actually be very resistant, when one tries to introduce ideas.
Ceea ce as dori să fac este să coborâm până la nivelul rigolelor, și chiar mai mult, în interiorul canalelor pentru că vreau să vorbesc despre diaree. Și în particular, aș vrea să discut despre design-ul diareei. Si atunci cand biologii evolutionisti vorbesc despre design, de fapt vor sa spuna design prin selectie naturala si asta ma aduce la titlul discutiei, "Utilizarea evolutiei pentru proiectarea inteligenta a organismelor cauzale ale bolilor" Si mai am un fel de subtitlu putin smecher la acesta. Dar nu fac asta doar ca sa fiu simpatic. Chiar cred ca acest subtitlu explica cum cineva ca mine, care e un fel de aspirant Darwinist, cum arata de fapt in rolul unuia in acest domeniu al stiintelor medicale si medicinei. Nu este nu domeniu foarte prietenos pentru biologii evolutionisti. De fapt vezi un potential imens, dar vezi o multime de oameni care isi apara intr-un fel ograda, si pot opune rezistenta atunci cand cineva incearca sa introduca idei.
So, all of the talk today is going to deal with two general questions. One is that, why are some disease organisms more harmful? And a very closely related question, which is, how can we take control of this situation once we understand the answer to the first question? How can we make the harmful organisms more mild? And I'm going to be talking, to begin with, as I said, about diarrheal disease organisms. And the focus when I'm talking about the diarrheal organisms, as well as the focus when I'm talking about any organisms that cause acute infectious disease, is to think about the problem from a germ's point of view, germ's-eye view. And in particular, to think about a fundamental idea which I think makes sense out of a tremendous amount of variation in the harmfulness of disease organisms. And that idea is that from the germ's-eye point of view, disease organisms have to get from one host to another, and often they have to rely on the well-being of the host to move them to another host.
Asa ca, toata dicutia de azi va dezbate doua intrebari generale Una este aceea de ce sunt sunt unele organisme ale bolilor mai periculoase decat altele, si o intrebare strans legata de prima, care este, cum putem prelua controlul asupra situatiei de indata ce intelegem raspunsul la prima intrebare? Cum putem face organismele daunatoare mai bande? Si voi vorbi, ca sa incep cu asta, dupa cum am spus, despre organisme cauzale ale bolilor diareice Si accentul atunci cand vorbesc despre oranisme cauzale ale bolii diareice, ca si atunci cand vorbesc despre orice organism care cauzeaza o boala acuta infectioasa, este sa ne gandim la acesta problema din punctul de vedere al unui microb. Asa cum priveste un microb. Si in mod particular sa ne gandim la idea fundamentala care cred ca are sens dintr-o multitudine de variatii, de nocivitate a organismelor cauzatoare de boli. Si acea idee este ca din punctul de vedere al microbului, organismele cauzatoare de boli trebuie sa ajunga de la o gazda la alta, si ca adesea trebuie sa se bazeze pe bunastarea gazdei ca sa se deplaseze la alta gazda.
But not always. Sometimes, you get disease organisms that don't rely on host mobility at all for transmission. And when you have that, then evolutionary theory tells us that natural selection will favor the more exploitative, more predator-like organisms. So, natural selection will favor organisms that are more likely to cause damage. If instead transmission to another host requires host mobility, then we expect that the winners of the competition will be the milder organisms. So, if the pathogen doesn't need the host to be healthy and active, and actual selection favors pathogens that take advantage of those hosts, the winners in the competition are those that exploit the hosts for their own reproductive success. But if the host needs to be mobile in order to transmit the pathogen, then it's the benign ones that tend to be the winners.
Dar nu întotdeauna. Uneori ai parte de organisme cauzatoare de boli care nu se bazeaza de loc pe mobilitatea gazdei pentru transmitere. Si cand asa sta cazul, teoria evolutionista ne spune ca selectia naturala va favoriza organismul cel mai abuziv, care are caracteristicile unui pradator. Deci selectia naturala va favoriza organisme care, cel mai probabil, vor cauza daune. Daca in schimb transmiterea la alta gazda necesita mobilitatea gazdei, atunci ne asteptam ca organismele mai blande sa fie castigatorii competitiei. Astfel, daca agentii patogeni nu au nevoie ca gaza sa fie sanatoasa si activa, atunci selectia reala favorizeza agentii patogeni care profita de aceste gazde, castigatorii in competitie sunt aceia care exploateaza gazdele pentru propriul succes reproductiv. Dar daca gazda trebuie sa fie mobila pentru a transmite agentii patogeni, atunci agentii inofensivi, benigni, au tendinta de a iesi invingatori.
So, I'm going to begin by applying this idea to diarrheal diseases. Diarrheal disease organisms get transmitted in basically three ways. They can be transmitted from person-to-person contact, person-to-food-then-to-person contact, when somebody eats contaminated food, or they can be transmitted through the water. And when they're transmitted through the water, unlike the first two modes of transmission, these pathogens don't rely on a healthy host for transmission. A person can be sick in bed and still infect tens, even hundreds of other individuals. To sort of illustrate that, this diagram emphasizes that if you've got a sick person in bed, somebody's going to be taking out the contaminated materials. They're going to wash those contaminated materials, and then the water may move into sources of drinking water. People will come in to those places where you've got contaminated drinking water, bring things back to the family, may drink right at that point. The whole point is that a person who can't move can still infect many other individuals.
Asa ca o sa incep prin aplicarea aceastei idei la bolile diareice. Organismele care cauzeza boli diareice sunt transmise in principiu in trei moduri. Pot fi transmise prin contact personal, persoana-persoana, contact prin mancare, persoana-mancare-persoana, atunci cand cineva mananca mancare contaminata. Sau pot fi transmise prin intermediul apei. Si atunci cand sunt transmisi prin intermediul apei, spre deosebire de primele doua metode de transmitere, acesti agenti patogeni nu se bazeaza pe o gazda sanatoasa pentru transmitere. O persoana poate fi bolnava la pat si totusi poate infecta zeci, poate sute de alti indivizi. Pentru a ilustra asta, aceasta diagrama subliniaza ca daca ai o persoana bolnava in pat, cineva va ridica materialele contaminate. Cineva va spala acele materiale contaminate, si apa se poate scurge in surse de apa potabila. Vor veni oameni in acele locuri unde avem apa potabila contaminata, pot duce lucruri contaminate la famillile lor, sau pot bea apa pe loc. Ceea ce vreau sa spun este ca o persoana care nu se poate misca, poate totusi sa infecteze multi alti indivizi.
And so, the theory tells us that when diarrheal disease organisms are transported by water, we expect them to be more predator-like, more harmful. And you can test these ideas. So, one way you can test is just look at all diarrheal bacteria, and see whether or not the ones that tend to be more transmitted by water, tend to be more harmful. And the answer is -- yep, they are. Now I put those names in there just for the bacteria buffs, but the main point here is that -- (Laughter) there's a lot of them here, I can tell -- the main point here is that those data points all show a very strong, positive association between the degree to which a disease organism is transmitted by water, and how harmful they are, how much death they cause per untreated infection. So this suggests we're on the right track. But this, to me, suggests that we really need to ask some additional questions.
Asa ca teoria ne spune ca atunci cand organismele cauzatoare de diaree sunt transportate de apa, ne asteptam ca ele sa fie mai periculoase, in stilul unui pradator. Aceste idei se pot testa. O modalitate de testare este sa privim la toate bacteriile cauzatoare de diaree, si sa vedem daca acele bacterii care tind sa fie transmise prin apa, au tendinta de a fi mai periculoase. Si raspunsul este - - da, sunt. Deci, pun aici aceste nume pentru impatimitii bacteriilor dar punctul principal este acela Rasete vad ca sunt multi impatimiti aici - principalul punct aici este acela ca toate aceste date arata o asociere foarte puternica, pozitiva, intre gradul in care un organism cauzator de boala este transmis prin apa, si cat de periculoase sunt, rata moralitatii pentru fiecare infectie netratata. Deci acest lucru sugereaza ca suntem pe drumul cel bun. Dar acest lucru, mie imi sugereaza ca avem cu adevarat nevoie sa punem cateva intrebari suplimentare.
Remember the second question that I raised at the outset was, how can we use this knowledge to make disease organisms evolve to be mild? Now, this suggests that if you could just block waterborne transmission, you could cause disease organisms to shift from the right-hand side of that graph to the left-hand side of the graph. But it doesn't tell you how long. I mean, if this would require thousands of years, then it's worthless in terms of controlling of these pathogens. But if it could occur in just a few years, then it might be a very important way to control some of the nasty problems that we haven't been able to control. In other words, this suggests that we could domesticate these organisms. We could make them evolve to be not so harmful to us.
Aminititi-va ca a doua intrebare pe care am pus-o la inceput a fost cum putem folosi aceste cunostinte pentru a face organismele cauzatoare de boli sa evolueze pentru a fi mai blande? Acest lucru sugereaza ca daca am putea bloca tansmiterea pe calea apei, am putea determina organismele cauzatoare de boli sa isi schimbe forma din partea dreapta spre partea stanga a graficului. Dar nu ne spune cat dureaza. Vreau sa spun, daca ar avea nevoie de mii de ani atunci este nefolositor in ceea ce priveste controlul acestor agenti patogeni. Dar daca s-ar putea petrece in cativa ani atunci ar putea fi o modalitate foarte importanta de control a unor probleme neplacute pe care nu le-am putut controla. Cu alte cuvinte, aceasta sugereaza ca am putea domestici aceste organisme Le-am putea face sa evolueze pentru a nu mai fi asa de periculoase pentru noi.
And so, as I was thinking about this, I focused on this organism, which is the El Tor biotype of the organism called Vibrio cholerae. And that is the species of organism that is responsible for causing cholera. And the reason I thought this is a really great organism to look at is that we understand why it's so harmful. It's harmful because it produces a toxin, and that toxin is released when the organism gets into our intestinal tract. It causes fluid to flow from the cells that line our intestine into the lumen, the internal chamber of our intestine, and then that fluid goes the only way it can, which is out the other end. And it flushes out thousands of different other competitors that would otherwise make life difficult for the Vibrios.
Si asa, cum ma gandeam la asta, m-am axat pe acest organism, care este biotipul El Tor al organismului numit Vibrio choleri. Si acesta este specia organismului care este responsabil pentru provocarea holerei. Si motivul pentru care am crezut ca aceste este un organism cu adevarat maret de privit este pentru ca intelgem de ce este atat de periculos. Este periculos pentru ca produce o toxina, si acea toxina este eliberata cand organismul ajunge in tractul nostru intestinal. Determina lichidul sa curga de la celulele care delimiteaza intestinul in lumen, camera interna a intestinului nostru, si apoi acel lichid merge in singura directie posibila, catre celalalt capat. Si alunga mii de alti competitori diferiti care altfel ar fi facut viata dificila organismelor vibrio.
So what happens, if you've got an organism, it produces a lot of toxin. After a few days of infection you end up having -- the fecal material really isn't so disgusting as we might imagine. It's sort of cloudy water. And if you took a drop of that water, you might find a million diarrheal organisms. If the organism produced a lot of toxin, you might find 10 million, or 100 million. If it didn't produce a lot of this toxin, then you might find a smaller number. So the task is to try to figure out how to determine whether or not you could get an organism like this to evolve towards mildness by blocking waterborne transmission, thereby allowing the organism only to be transmitted by person-to-person contact, or person-food-person contact -- both of which would really require that people be mobile and fairly healthy for transmission.
Deci ce se intampla, daca ai un organism, acesta produce o cantitate mare de toxina. Dupa cateva zile de infectie ajungi sa ai -- materiile fecale nu sunt chiar atat de dezgustatoare cum ne-am imagina. E un fel de apa inorata. Si daca ai lua un strop din acea apa, ai putea gasi un milion de organisme diareice. Daca organismul produce o cantitate mare de toxina, poti gasi 10 sau 100 de milioane de organisme. Daca nu produce o cantitate mare de toxina, atunci vei gasi un numar mai mic de organisme. Deci sarcina este sa incercam sa ne dam seama cum sa stabilim daca putem face sau nu, ca un organism ca acesta sa evolueze spre o forma mai blanda, prin blocarea transmiterii pe calea apei, astfel permitand organismului sa fie transmis doar prin contact direct (persoana-persoana), sau prin contact cu mancarea infectata(persoana-mancare-persoana) --- iar pentru ambele fiind necesar ca oamenii sa fie mobili si destul de sanatosi pentru transmitere.
Now, I can think of some possible experiments. One would be to take a lot of different strains of this organism -- some that produce a lot of toxins, some that produce a little -- and take those strains and spew them out in different countries. Some countries that might have clean water supplies, so that you can't get waterborne transmission: you expect the organism to evolve to mildness there. Other countries, in which you've got a lot of waterborne transmission, there you expect these organisms to evolve towards a high level of harmfulness, right? There's a little ethical problem in this experiment. I was hoping to hear a few gasps at least. That makes me worry a little bit.
Acum, ma pot gandi la cateva experimente posibile. Unul ar fi sa iau o multime de tulpini diferite ale acestui organism -- unele care produc o multime de toxine, altele care produc putine --- si sa iau acele tulpini si sa le imprastii in tari diferite. Unele tari care pot avea aprovizionare cu apa curata, asa incat sa nu pot avea transmitere pe calea apei: te astepti ca organismul sa evolueze aici catre o forma mai blanda. In alte tari, in care parte din plin de transmitere pe calea apei, aici te astepti ca aceste organisme sa evolueze catre un nivel inalt de nocivitate, nu? Este insa o mica problema etica in acest experiment. Speram sa aud un murmur cel putin. Acest lucru ma ingrijoreaza putin.
(Laughter)
Rasete
But anyhow, the laughter makes me feel a little bit better. And this ethical problem's a big problem. Just to emphasize this, this is what we're really talking about. Here's a girl who's almost dead. She got rehydration therapy, she perked up, within a few days she was looking like a completely different person. So, we don't want to run an experiment like that. But interestingly, just that thing happened in 1991. In 1991, this cholera organism got into Lima, Peru, and within two months it had spread to the neighboring areas. Now, I don't know how that happened, and I didn't have anything to do with it, I promise you. I don't think anybody knows, but I'm not averse to, once that's happened, to see whether or not the prediction that we would make, that I did make before, actually holds up. Did the organism evolve to mildness in a place like Chile, which has some of the most well protected water supplies in Latin America? And did it evolve to be more harmful in a place like Ecuador, which has some of the least well protected? And Peru's got something sort of in between.
Dar oricum, aceste rasete ma fac sa ma simt un pic mai bine. Si aceasta problema etica este o problema mare. Doar pentru a sublinia acest lucru, despre asta vorbim de fapt. Aici este o fata care este aproape moarta. A primit o terapie de rehidratare, s-a inviorat, in cateva zile arata ca o persoana complet diferita. Asa ca, nu vrem sa facem un experiment ca acela. Dar interesant, chiar acest lucru s-a intamplat in 1991. In 1991, acest organism cauzator de holera a intrat in Lima, Peru. si in doua luni s-a intins catre zonele invecinate. Acum, nu stiu cum s-a intamplat, si nici nu am avut nimic de a face cu asta, va promit. Nu cred ca stie cineva, dar nu sunt contra, o data ce s-a intamlat, sa vedem daca predictia pe care am face-o, pe care am facut-o inainte, de fapt sta in picioare. A evoluat organismul catre o forma mai blanda intr-un loc precum Chile, care are unele dintre cele mai bine protejate surse de apa din America Latina? Si a evoluat catre o forma mai periculoasa intr-un loc precum Ecuadorul, care are unele dintre sursele de apa cel mai putin protejate? Si in Peru susele sunt cam intre cele doua exemple.
And so, with funding from the Bosack-Kruger Foundation, I got a lot of strains from these different countries and we measured their toxin production in the lab. And we found that in Chile -- within two months of the invasion of Peru you had strains entering Chile -- and when you look at those strains, in the very far left-hand side of this graph, you see a lot of variation in the toxin production. Each dot corresponds to an islet from a different person -- a lot of variation on which natural selection can act. But the interesting point is, if you look over the 1990s, within a few years the organisms evolved to be more mild. They evolved to produce less toxin. And to just give you a sense of how important this might be, if we look in 1995, we find that there's only one case of cholera, on average, reported from Chile every two years.
Si asa, cu finantare de la fundatia Bozack-Kruger, Am luat o multime de tulpini din aceste tari diferite si le-am masurat productia de toxina in laborator. Si am gasit ca in Chile - in decursul a doua luni de la invazia din Peru au intrat tulpini in Chile -- si cand ne-am uitat la acele tulpini, in partea stanga a graficului, foarte indepartat, se vad o multime de variatii in producerea toxinei. Fiecarui punct ii corespunde o insulita de la o alta persoana -- o multime de variatii asupra carora poate actiona selectia naturala. Dar interesant este, daca ne uitam peste anii 1990, peste cativa ani organismele au evoluat catre o forma mai blanda. Au evoluat spre a produce o cantitate mai mica de toxina. Si doar ca sa va dau un indiciu despre cat de importat ar putea fi acest lucru, daca ne uitam in 1995, vedem ca acolo exista un singur caz de holera, in medie, raportat din Chile la fiecare doi ani.
So, it's controlled. That's how much we have in America, cholera that's acquired endemically, and we don't think we've got a problem here. They didn't -- they solved the problem in Chile. But, before we get too confident, we'd better look at some of those other countries, and make sure that this organism doesn't just always evolve toward mildness. Well, in Peru it didn't. And in Ecuador -- remember, this is the place where it has the highest potential waterborne transmission -- it looked like it got more harmful. In every case there's a lot of variation, but something about the environment the people are living in, and I think the only realistic explanation is that it's the degree of waterborne transmission, favored the harmful strains in one place, and mild strains in another.
Deci, este sub control. Atat avem si in America, holera dobandita pe cale endemica, si nu credem ca avem o problema aici. Nici ei nu au crezut - au rezolvat problema in Chile. Dar, inainte sa devenim prea inrezatori, mai bine ne-am uita la alte cateva tari, sa ne asiguram ca acest organism nu evolueaza intodeauna catre o forma mai blanda. Ei bine, in Peru nu a facut-o. Si in Euador -- va amintiti, este locul care are cel mai mare potential de trasnsmitere pe calea apei -- se pare ca a devenit mai periculos. In fiecare caz exista multa variatie, dar ceva din mediul in care traiesc oameni, si cred ca singura explicatie realista este aceea ca, gradul de trasnsmitere pe calea apei, a favorizat tulpinile periculoase intr-un loc si pe cele mai blande in alt loc.
So, this is very encouraging, it suggests that something that we might want to do anyhow, if we had enough money, could actually give us a much bigger bang for the buck. It would make these organisms evolve to mildness, so that even though people might be getting infected, they'd be infected with mild strains. It wouldn't be causing severe disease. But there's another really interesting aspect of this, and this is that if you could control the evolution of virulence, evolution of harmfulness, then you should be able to control antibiotic resistance. And the idea is very simple. If you've got a harmful organism, a high proportion of the people are going to be symptomatic, a high proportion of the people are going to be going to get antibiotics. You've got a lot of pressure favoring antibiotic resistance, so you get increased virulence leading to the evolution of increased antibiotic resistance. And once you get increased antibiotic resistance, the antibiotics aren't knocking out the harmful strains anymore. So, you've got a higher level of virulence.
Asa ca, este foarte incurajator, sugereaza ca ceva ce am fi vrut sa facem oricum, daca am fi avut suficienti bani, de fapt, s-ar putea dovedi foarte rentabil. Ar face ca aceste organisme sa evolueze catre o forma mai blanda, si asa ca, chiar daca s-ar infecta oameni, ar fi infectati cu tulpini blande. Nu ar cauza boli grave. Dar mai este un alt aspect chiar interesant al aceste probleme, si acela este ca daca ai putea controla evolutia virulentei, evolutia nocivitatii, atunci ai putea controla rezistenta la antibiotice. Si ideea este foarte simpla. Daca ai un organism periculos, o mare parte a populatiei va avea simptome, o mare parte a populatiei va lua antibiotice. Exista multa presiune in favoarea rezistentei la antibiotice, deci avem parte de o virulenta crescuta care duce la evolutia unei rezistente crescute la antibiotice. Si o data ce avem o rezistenta crescuta la antibiotice, Antibioticele nu mai distrug tulpinile nocive. Deci, avem un nivel crescut de virulenta.
So, you get this vicious cycle. The goal is to turn this around. If you could cause an evolutionary decrease in virulence by cleaning up the water supply, you should be able to get an evolutionary decrease in antibiotic resistance. So, we can go to the same countries and look and see. Did Chile avoid the problem of antibiotic resistance, whereas did Ecuador actually have the beginnings of the problem? If we look in the beginning of the 1990s, we see, again, a lot of variation. In this case, on the Y-axis, we've just got a measure of antibiotic sensitivity -- and I won't go into that. But we've got a lot of variation in antibiotic sensitivity in Chile, Peru and Ecuador, and no trend across the years. But if we look at the end of the 1990s, just half a decade later, we see that in Ecuador they started having a resistance problem. Antibiotic sensitivity was going down. And in Chile, you still had antibiotic sensitivity.
Deci, avem acest cerc vicios. Scopul este sa transformam acest lucru. Daca am putea cauza o scadere evolutiva a virulentei prin curatarea sursei de apa, ar trebui sa putem obtine o scadere evolutiva a rezistentei la antibiotice. Deci, putem merge in acelasi tari si sa vedem. A evitat Chile problema rezistentei la antibiotice, unde a inceput de fapt problema in Ecuador? Daca ne uitam la inceputul anilor 90, din nou vedem variatie. In acest caz, pe axa Y, tocmai am masurat sensibilitatea la antibiotice -- si nu o sa intru in problema asta. Dar avem multa variatie privind sensibilitatea la antibiotice in Chile, Peru si Ecuador si nici o tendinta dealungul anilor. Dar daca ne uitam la sfarsitul anilor 90, doar o jumatate de deceniu mai tarziu, vedem ca in Ecuador au inceput sa aiba o problema de rezistenta. Sensibilitatea la antibiotice scadea. Si in Chile avem inca sensibilitate la antibiotice.
So, it looks like Chile dodged two bullets. They got the organism to evolve to mildness, and they got no development of antibiotic resistance. Now, these ideas should apply across the board, as long as you can figure out why some organisms evolved to virulence. And I want to give you just one more example, because we've talked a little bit about malaria. And the example I want to deal with is, or the idea I want to deal with, the question is, what can we do to try to get the malarial organism to evolve to mildness? Now, malaria's transmitted by a mosquito, and normally if you're infected with malaria, and you're feeling sick, it makes it even easier for the mosquito to bite you.
Deci, se pare ca Chile a nimerit doua dintr-o lovitura. Oranismul a evoluat catre o forma mai usoara, si nu au inregistrat nici o evolutie in ceea ce priveste rezistenta la antibiotice. Acum, aceste idei ar trebui aplicate pe toata suprafata tablei, atat timp cat na dam seama de ce unele organisme au evoluat in virulenta. Si vreau sa va dau mai dau un singur exemplu, pentru ca am vorbit putin despre malarie. Si exemplul de care vreau sa ma ocup este, sau ideea de care vreau sa ma ocup, intrebarea este, ce putem face sa incercam sa determinam organismul cauzator de malarie sa evolueze catre o forma mai blanda? Acum, malaria este transmisa de un tantar, si in mod normal daca esti infectat cu malarie si te simti rau, devine si mai usor pentru tantar sa te muste.
And you can show, just by looking at data from literature, that vector-borne diseases are more harmful than non-vector-borne diseases. But I think there's a really fascinating example of what one can do experimentally to try to actually demonstrate this. In the case of waterborne transmission, we'd like to clean up the water supplies, see whether or not we can get those organisms to evolve towards mildness. In the case of malaria, what we'd like to do is mosquito-proof houses. And the logic's a little more subtle here. If you mosquito-proof houses, when people get sick, they're sitting in bed -- or in mosquito-proof hospitals, they're sitting in a hospital bed -- and the mosquitoes can't get to them.
Si putem arata, doar uitandu-ne la datele din literatura de specialitate, ca bolile cu transmitere vectoriala sunt mai daunatoare decat bolile fara transmitere vectoriala. Dar cred ca aici avem un exemplu cu adevarat fascinant de ce poate face cineva pe cale experimentala ca sa incerce sa demonstreze de fapt acest lucru. In cazul transmiterii pe calea apei, am vrea sa curatam alimentarea cu apa, sa vedem daca acele organisme evolueaza catre o forma mai blanda sau nu. In cazul malariei, ceea ce am dori este sa facem case in care nu pot patrunde tantarii. Si logica este putin mai subtila aici. Daca avem case in care nu pot patrunde tantarii, cand oamenii se imbolnavesc, stau in pat -- sau in spitale in care nu pot patrunde tantarii, stau intr-un pat de spital -- si tantarii nu pot ajunge la ei.
So, if you're a harmful variant in a place where you've got mosquito-proof housing, then you're a loser. The only pathogens that get transmitted are the ones that are infecting people that feel healthy enough to walk outside and get mosquito bites. So, if you were to mosquito proof houses, you should be able to get these organisms to evolve to mildness. And there's a really wonderful experiment that was done that suggests that we really should go ahead and do this. And that experiment was done in Northern Alabama. Just to give you a little perspective on this, I've given you a star at the intellectual center of the United States, which is right there in Louisville, Kentucky. And this really cool experiment was done about 200 miles south of there, in Northern Alabama, by the Tennessee Valley Authority. They had dammed up the Tennessee River. They'd caused the water to back up, they needed electric, hydroelectric power. And when you get stagnant water, you get mosquitoes. They found in the late '30s -- 10 years after they'd made these dams -- that the people in Northern Alabama were infected with malaria, about a third to half of them were infected with malaria.
Deci, dace esti o varietate daunatoare intr-un loc in care avem case in care nu pot patrunde tantari, atunci esti un perdant. Singurii agenti patogeni care sunt transmisi sunt aceia care infecteaza oameni care se simt suficient de sanatosi sa iasa afara si sa fie intepati de tantari. Deci, daca am fi in acele case in care nu pot patrunde tantari, ar trebui sa putem obtinem ca acele organisme sa evolueze catre o forma mai blanda. Si exista un experiment cu adevarat minunat care a fost facut care sugereaza ca ar trebui sa continuam si sa facem asta. Si acest experiment a fost facut in Alabama de nord. Doar ca sa va ofer o omagine de ansamblu, v-am pus o stea in centrul intelectual al Statelor Unite, care este chiar acolo in Louisville, Kentucky. Si acest experiment cu adevarat grozav a fost facut la aproape 200 de mile in sud de acolo, in Alabama de nord, de catre Tennessee Valley Authority. Au indiguit raul Tennessee. Au fortat apa sa se retraga, aveau nevoie de curent electric, produs de hidrocentrale. Si atunci cand ai apa statatoare, ai tantari. Au descoperit la sfarsitul anilor 30 -- 10 ani dupa ce au construit aceste baraje -- ca oamenii din Alabama de nord erau infectati cu malarie, cam o treime, pana la o jumatate dintre ei erau infectati cu malarie.
This shows you the positions of some of these dams. OK, so the Tennessee Valley Authority was in a little bit of a bind. There wasn't DDT, there wasn't chloroquines: what do they do? Well, they decided to mosquito proof every house in Northern Alabama. So they did. They divided Northern Alabama into 11 zones, and within three years, about 100 dollars per house, they mosquito proofed every house. And these are the data. Every row across here represents one of those 11 zones. And the asterisks represent the time at which the mosquito proofing was complete. And so what you can see is that just the mosquito-proofed housing, and nothing else, caused the eradication of malaria. And this was, incidentally, published in 1949, in the leading textbook of malaria, called "Boyd's Malariology." But almost no malaria experts even know it exists. This is important, because it tells us that if you have moderate biting densities, you can eradicate malaria by mosquito proofing houses.
Aici vedeti pozitia unora dintre aceste baraje. OK, asa ca Tennessee Valley Authority era la ananghie. Nu era DDT, nu era clorochina, ce sa faca? Ei bine, au hotarat sa izoleze fiecare casa din Alabama de nord impotriva tantarilor. Si asa au facut. Au impartit Alabama de nord in 11 zone. si in trei ani, cu aproximativ 100 de dolari per casa, au izolat fiecare casa impotriva tantarilor. Si acestea sunt datele. Fiecare rand de aici reprezinta una din acele 11 zone. Si asterixurile reprezinta momentul la care s-a incheiat izolarea caselor impotriva tantarilor. Si ceea ce vedem este ca doar izolarea caselor impotriva tantarilor, si nimic altceva, a dus la eradicarea malariei. Si acest lucru a fost intamplator publicat in 1949, in cartea de capatai a malariei, intitulata "Boyd's Malariology" (Malariaologia lui Boyd) Dar aproape nici un expert in malarie nici macar nu stie ca exista. Acest lucru este important, pentru ca ne spune ca daca avem o densitate moderata a intapaturilor, putem eradica malaria prin izolarea caselor impotriva tantarilor.
Now, I would suggest that you could do this in a lot of places. Like, you know, just as you get into the malaria zone, sub-Saharan Africa. But as you move to really intense biting rate areas, like Nigeria, you're certainly not going to eradicate. But that's when you should be favoring evolution towards mildness. So to me, it's an experiment that's waiting to happen, and if it confirms the prediction, then we should have a very powerful tool. In a way, much more powerful than the kind of tools we're looking at, because most of what's being done today is to rely on things like anti-malarial drugs. And we know that, although it's great to make those anti-malarial drugs available at really low cost and high frequency, we know that when you make them highly available you're going to get resistance to those drugs. And so it's a short-term solution. This is a long-term solution.
Acum, as sugera ca se poate face asta in multe locuri. Asa cum stiti, chiar cum intrii in zona cu malarie, in Africa sub-sahariana. Dar cum ne miscam catre zone cu o rata crescuta de intepaturi, cum e Nigeria, cu siguranta nu o sa eradicam malaria. Dar asta este cand ar trebui sa favorizam evolutia catre o forma mai usoara. Asa ca pentru mine este un experiment care asteapta sa se intample, si daca confirma predictia, atunci ar trebui sa avem un instrument foarte puternic. Intr-un fel, mult mai puternic decat tipul de unelte la care ne uitam, pentru ca cea mai mare parte din ceea ce se face azi este sa ne bazam pe lucruri cum ar fi medicamentele anti-malarie. Si stim ca, desi este un lucru mare sa punem foarte frecvent dispozitie acele medicamente anti-malarie la costuri cu adevarat mici, stim ca atunci cand le faci extem de diponibile urmeaza sa intampini rezistenta la acele medicamente. Si deci este o solutie pe termen scurt. Aceasta este o solutie pe permen lung.
What I'm suggesting here is that we could get evolution working in the direction we want it to go, rather than always having to battle evolution as a problem that stymies our efforts to control the pathogen, for example with anti-malarial drugs. So, this table I've given just to emphasize that I've only talked about two examples. But as I said earlier, this kind of logic applies across the board for infectious diseases, and it ought to. Because when we're dealing with infectious diseases, we're dealing with living systems. We're dealing with living systems; we're dealing with systems that evolve. And so if you do something with those systems, they're going to evolve one way or another. And all I'm saying is that we need to figure out how they'll evolve, so that -- we need to adjust our interventions to get the most bang for the intervention buck, so that we can get these organisms to evolve in the direction we want them to go.
Ceea ce sugerez este ca putem obtine ca evolutia sa lucreze in directia in care vrem, si sa nu mai fim nevoiti sa luptam cu ea de fiecare data lucru care ne ingreuneaza eforturile de a controla agentul patogen, cum este exemplul cu medicamentele anti-malarie. Deci, am facut acest table doar ca sa subliniez ca am vorbit doar despre doua exemple. Dar asa cum am zis mai devreme, aceast tip de logica se aplica pentru toata tabla pentru bolile infectioase, asa cum ar trebui sa o faca. Pentru ca atunci cand ne ocupam de boli infectioase, avem de-a face cu sisteme vii; Avem de-a face cu sisteme vii; Avem de-a face cu sisteme care evolueaza. Si deci daca faci ceva cu acele sisteme, Ele vor evolua intr-un fel sau altul. Si tot ce spun este ca avem nevoie sa ne dam seama cum vor evolua, astfel incat -- avem nevoie sa ne ajustam interventiile pentru a obţine cele mai bune rezultate pentru intervenţiile facute, astfel incat sa facem aceste organisme sa evolueze in directia dorita.
So, I don't really have time to talk about those things, but I did want to put them up there, just to give you a sense that there really are solutions to controlling the evolution of harmfulness of some of the nasty pathogens that we're confronted with. And this links up with a lot of the other ideas that have been talked about. So, for example, earlier today there was discussion of, how do you really lower sexual transmission of HIV? What this emphasizes is that we need to figure out how it will work. Will it maybe get lowered if we alter the economy of the area? It may get lowered if we intervene in ways that encourage people to stay more faithful to partners, and so on.
Asa ca, nu prea am timp sa vorbesc despre aceste lucruri, dar am vrut sa le pun aici, doar pentru a vă oferi certitudinea că exista intr-adevăr solutii pentru a controla evolutia nocivitatii unora dintre cei mai rai agenti patogeni cu care ne confruntam. Si asta se leaga cu o multime de alte idei despre care s-a vorbit. Deci, spre exemplu, mai devreme au fost dezbateri despre, cum scadem rata de transmitere a virusului HIV? Ceea ce subliniaza acest lucru este ca trebuie sa ne dam seama cum va functiona. Poate va scadea daca modificam economia zonei? Poate scadea daca intervenim in moduri in care incurajeaza oamenii sa ramana mai fideli partenerilor, si asa mai departe.
But the key thing is to figure out how to lower it, because if we lower it, we'll get an evolutionary change in the virus. And the data really do support this: that you actually do get the virus evolving towards mildness. And that will just add to the effectiveness of our control efforts. So the other thing I really like about this, besides the fact that it brings a whole new dimension into the study of control of disease, is that often the kinds of interventions that you want, that it indicates should be done, are the kinds of interventions that people want anyhow. But people just haven't been able to justify the cost.
Dar elementul cheie este sa ne dam seama cum sa o scadem, pentru ca daca o scadem, vom obtine o schimbare in evolutia virusului. Si datele sustin acest lucru: ca intr-adevar obti ca virusul sa evolueze catre o forma mai blanda. Si asta se va adauga efectivitatii eforturilor noastre de control. Si celalalt lucru care mi-a placut la asta, in afara faptului ca aduce o dimeniune cu totul noua in studiul privind controlul bolilor, este ca adesea tipurile de interventii pe care le vrei, care sunt indicate ca trebuie facute, sunt tipurile de interventii pe care oamenii le vor oricum. Dar oamenii pur si simplu nu au putut justifica costul.
So, this is the kind of thing I'm talking about. If we know that we're going to get extra bang for the buck from providing clean water, then I think that we can say, let's push the effort into that aspect of the control, so that we can actually solve the problem, even though, if you just look at the frequency of infection, you would suggest that you can't solve the problem well enough just by cleaning up water supply. Anyhow, I'll end that there, and thank you very much.
Deci, acesta este genul de lucruri despre care vorbesc. Daca stim ca urmeaza sa merite sa furnizam apa curata, atunci cred ca putem spune, haideti sa facem eforturi in privinta aspectului controlului, ca sa putem rezolva de fapt problema, chiar daca, daca ne uitam doar la frecventa infectiei, ai putea sugera ca nu poti rezolva suficient de bine problema doar prin curatarea aprovizionarii cu apa. Oricum, voi incheia aici si va multumesc foarte mult.
(Applause)
Aplauze