Paul Ewald: Can we domesticate germs?

Traducător: Maria Oprisescu Corector: Maria Tancu

What I'd like to do is just drag us all down into the gutter,

Ceea ce as dori să fac este să coborâm până la nivelul rigolelor,

and actually all the way down into the sewer

și chiar mai mult, în interiorul canalelor

because I want to talk about diarrhea.

pentru că vreau să vorbesc despre diaree.

And in particular, I want to talk about

Și în particular, aș vrea să discut despre

the design of diarrhea.

design-ul diareei.

And when evolutionary biologists talk about design,

Si atunci cand biologii evolutionisti vorbesc despre design,

they really mean design by natural selection.

de fapt vor sa spuna design prin selectie naturala

And that brings me to the title of the talk,

si asta ma aduce la titlul discutiei,

"Using Evolution to Design Disease Organisms Intelligently."

"Utilizarea evolutiei pentru proiectarea inteligenta a organismelor cauzale ale bolilor"

And I also have a little bit of a sort of smartass subtitle to this.

Si mai am un fel de subtitlu putin smecher la acesta.

But I'm not just doing this to be cute.

Dar nu fac asta doar ca sa fiu simpatic.

I really think that this subtitle explains

Chiar cred ca acest subtitlu explica

what somebody like me, who's sort of a Darwin wannabe,

cum cineva ca mine, care e un fel de aspirant Darwinist,

how they actually look at one's role in

cum arata de fapt in rolul unuia

sort of coming into this field of health sciences and medicine.

in acest domeniu al stiintelor medicale si medicinei.

It's really not a very friendly field for evolutionary biologists.

Nu este nu domeniu foarte prietenos pentru biologii evolutionisti.

You actually see a great potential,

De fapt vezi un potential imens,

but you see a lot of people who are sort of defending their turf,

dar vezi o multime de oameni care isi apara intr-un fel ograda,

and may actually be very resistant, when one tries

si pot opune rezistenta atunci cand cineva incearca

to introduce ideas.

sa introduca idei.

So, all of the talk today is going to deal with two general questions.

Asa ca, toata dicutia de azi va dezbate doua intrebari generale

One is that, why are some disease organisms more harmful?

Una este aceea de ce sunt sunt unele organisme ale bolilor mai periculoase decat altele,

And a very closely related question, which is,

si o intrebare strans legata de prima, care este,

how can we take control of this situation once we understand

cum putem prelua controlul asupra situatiei de indata ce intelegem

the answer to the first question?

raspunsul la prima intrebare?

How can we make the harmful organisms more mild?

Cum putem face organismele daunatoare mai bande?

And I'm going to be talking, to begin with, as I said,

Si voi vorbi, ca sa incep cu asta, dupa cum am spus,

about diarrheal disease organisms.

despre organisme cauzale ale bolilor diareice

And the focus when I'm talking about the diarrheal organisms,

Si accentul atunci cand vorbesc despre oranisme cauzale ale bolii diareice,

as well as the focus when I'm talking about any organisms

ca si atunci cand vorbesc despre orice organism

that cause acute infectious disease,

care cauzeaza o boala acuta infectioasa,

is to think about the problem from a germ's point of view,

este sa ne gandim la acesta problema din punctul de vedere al unui microb.

germ's-eye view.

Asa cum priveste un microb.

And in particular, to think about a fundamental idea

Si in mod particular sa ne gandim la idea fundamentala

which I think makes sense out of a tremendous amount of variation

care cred ca are sens dintr-o multitudine de variatii,

in the harmfulness of disease organisms.

de nocivitate a organismelor cauzatoare de boli.

And that idea is that from the germ's-eye point of view,

Si acea idee este ca din punctul de vedere al microbului,

disease organisms have to get from one host to another,

organismele cauzatoare de boli trebuie sa ajunga de la o gazda la alta,

and often they have to rely on the well-being of the host

si ca adesea trebuie sa se bazeze pe bunastarea gazdei

to move them to another host.

ca sa se deplaseze la alta gazda.

But not always.

Dar nu întotdeauna.

Sometimes, you get disease organisms

Uneori ai parte de organisme cauzatoare de boli

that don't rely on host mobility at all for transmission.

care nu se bazeaza de loc pe mobilitatea gazdei pentru transmitere.

And when you have that, then evolutionary theory tells us

Si cand asa sta cazul, teoria evolutionista ne spune

that natural selection will favor the more exploitative,

ca selectia naturala va favoriza organismul cel mai abuziv,

more predator-like organisms.

care are caracteristicile unui pradator.

So, natural selection will favor organisms

Deci selectia naturala va favoriza organisme care,

that are more likely to cause damage.

cel mai probabil, vor cauza daune.

If instead transmission to another host requires host mobility,

Daca in schimb transmiterea la alta gazda necesita mobilitatea gazdei,

then we expect that the winners of the competition

atunci ne asteptam ca organismele mai blande

will be the milder organisms.

sa fie castigatorii competitiei.

So, if the pathogen doesn't need the host to be healthy and active,

Astfel, daca agentii patogeni nu au nevoie ca gaza sa fie sanatoasa si activa,

and actual selection favors pathogens

atunci selectia reala favorizeza agentii patogeni

that take advantage of those hosts,

care profita de aceste gazde,

the winners in the competition are those that exploit the hosts

castigatorii in competitie sunt aceia care exploateaza gazdele

for their own reproductive success.

pentru propriul succes reproductiv.

But if the host needs to be mobile in order to transmit the pathogen,

Dar daca gazda trebuie sa fie mobila pentru a transmite agentii patogeni,

then it's the benign ones that tend to be the winners.

atunci agentii inofensivi, benigni, au tendinta de a iesi invingatori.

So, I'm going to begin by applying this idea to diarrheal diseases.

Asa ca o sa incep prin aplicarea aceastei idei la bolile diareice.

Diarrheal disease organisms get transmitted in basically three ways.

Organismele care cauzeza boli diareice sunt transmise in principiu in trei moduri.

They can be transmitted from person-to-person contact,

Pot fi transmise prin contact personal, persoana-persoana,

person-to-food-then-to-person contact,

contact prin mancare, persoana-mancare-persoana,

when somebody eats contaminated food,

atunci cand cineva mananca mancare contaminata.

or they can be transmitted through the water.

Sau pot fi transmise prin intermediul apei.

And when they're transmitted through the water,

Si atunci cand sunt transmisi prin intermediul apei,

unlike the first two modes of transmission,

spre deosebire de primele doua metode de transmitere,

these pathogens don't rely on a healthy host for transmission.

acesti agenti patogeni nu se bazeaza pe o gazda sanatoasa pentru transmitere.

A person can be sick in bed and still infect tens, even hundreds

O persoana poate fi bolnava la pat si totusi poate infecta zeci, poate sute

of other individuals.

de alti indivizi.

To sort of illustrate that, this diagram emphasizes that

Pentru a ilustra asta, aceasta diagrama subliniaza ca

if you've got a sick person in bed,

daca ai o persoana bolnava in pat,

somebody's going to be taking out the contaminated materials.

cineva va ridica materialele contaminate.

They're going to wash those contaminated materials,

Cineva va spala acele materiale contaminate,

and then the water may move into sources of drinking water.

si apa se poate scurge in surse de apa potabila.

People will come in to those places where you've got

Vor veni oameni in acele locuri unde avem

contaminated drinking water,

apa potabila contaminata,

bring things back to the family,

pot duce lucruri contaminate la famillile lor,

may drink right at that point.

sau pot bea apa pe loc.

The whole point is that a person who can't move

Ceea ce vreau sa spun este ca o persoana care nu se poate misca,

can still infect many other individuals.

poate totusi sa infecteze multi alti indivizi.

And so, the theory tells us that

Asa ca teoria ne spune ca

when diarrheal disease organisms are transported by water,

atunci cand organismele cauzatoare de diaree sunt transportate de apa,

we expect them to be more predator-like, more harmful.

ne asteptam ca ele sa fie mai periculoase, in stilul unui pradator.

And you can test these ideas.

Aceste idei se pot testa.

So, one way you can test is just look at all diarrheal bacteria,

O modalitate de testare este sa privim la toate bacteriile cauzatoare de diaree,

and see whether or not the ones that tend to be

si sa vedem daca acele bacterii care tind sa fie

more transmitted by water, tend to be more harmful.

transmise prin apa, au tendinta de a fi mai periculoase.

And the answer is -- yep, they are.

Si raspunsul este - - da, sunt.

Now I put those names in there just for the bacteria buffs,

Deci, pun aici aceste nume pentru impatimitii bacteriilor

but the main point here is that --

dar punctul principal este acela

(Laughter)

Rasete

there's a lot of them here, I can tell --

vad ca sunt multi impatimiti aici -

the main point here is that those data points

principalul punct aici este acela ca toate aceste date

all show a very strong, positive association between

arata o asociere foarte puternica, pozitiva, intre

the degree to which a disease organism is transmitted by water,

gradul in care un organism cauzator de boala este transmis prin apa,

and how harmful they are,

si cat de periculoase sunt,

how much death they cause per untreated infection.

rata moralitatii pentru fiecare infectie netratata.

So this suggests we're on the right track.

Deci acest lucru sugereaza ca suntem pe drumul cel bun.

But this, to me, suggests that we really need

Dar acest lucru, mie imi sugereaza ca avem cu adevarat nevoie

to ask some additional questions.

sa punem cateva intrebari suplimentare.

Remember the second question that I raised at the outset was,

Aminititi-va ca a doua intrebare pe care am pus-o la inceput a fost

how can we use this knowledge

cum putem folosi aceste cunostinte

to make disease organisms evolve to be mild?

pentru a face organismele cauzatoare de boli sa evolueze pentru a fi mai blande?

Now, this suggests that if you could just block waterborne transmission,

Acest lucru sugereaza ca daca am putea bloca tansmiterea pe calea apei,

you could cause disease organisms to shift from

am putea determina organismele cauzatoare de boli sa isi schimbe forma

the right-hand side of that graph to the left-hand side of the graph.

din partea dreapta spre partea stanga a graficului.

But it doesn't tell you how long.

Dar nu ne spune cat dureaza.

I mean, if this would require thousands of years,

Vreau sa spun, daca ar avea nevoie de mii de ani

then it's worthless in terms of controlling of these pathogens.

atunci este nefolositor in ceea ce priveste controlul acestor agenti patogeni.

But if it could occur in just a few years,

Dar daca s-ar putea petrece in cativa ani

then it might be a very important way to control

atunci ar putea fi o modalitate foarte importanta de control

some of the nasty problems that we haven't been able to control.

a unor probleme neplacute pe care nu le-am putut controla.

In other words, this suggests that we could

Cu alte cuvinte, aceasta sugereaza ca am putea

domesticate these organisms.

domestici aceste organisme

We could make them evolve to be not so harmful to us.

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,

Si asa, cum ma gandeam la asta, m-am axat pe acest organism,

which is the El Tor biotype of the organism called Vibrio cholerae.

care este biotipul El Tor al organismului numit Vibrio choleri.

And that is the species of organism that is responsible

Si acesta este specia organismului care este responsabil

for causing cholera.

pentru provocarea holerei.

And the reason I thought this is a really great organism to look at

Si motivul pentru care am crezut ca aceste este un organism cu adevarat maret de privit

is that we understand why it's so harmful.

este pentru ca intelgem de ce este atat de periculos.

It's harmful because it produces a toxin,

Este periculos pentru ca produce o toxina,

and that toxin is released when the organism

si acea toxina este eliberata cand organismul

gets into our intestinal tract.

ajunge in tractul nostru intestinal.

It causes fluid to flow from the cells that line our intestine

Determina lichidul sa curga de la celulele care delimiteaza intestinul

into the lumen, the internal chamber of our intestine,

in lumen, camera interna a intestinului nostru,

and then that fluid goes the only way it can, which is out the other end.

si apoi acel lichid merge in singura directie posibila, catre celalalt capat.

And it flushes out thousands of different other competitors

Si alunga mii de alti competitori diferiti

that would otherwise make life difficult for the Vibrios.

care altfel ar fi facut viata dificila organismelor vibrio.

So what happens, if you've got an organism,

Deci ce se intampla, daca ai un organism,

it produces a lot of toxin.

acesta produce o cantitate mare de toxina.

After a few days of infection you end up having --

Dupa cateva zile de infectie ajungi sa ai --

the fecal material really isn't so disgusting as we might imagine.

materiile fecale nu sunt chiar atat de dezgustatoare cum ne-am imagina.

It's sort of cloudy water.

E un fel de apa inorata.

And if you took a drop of that water,

Si daca ai lua un strop din acea apa,

you might find a million diarrheal organisms.

ai putea gasi un milion de organisme diareice.

If the organism produced a lot of toxin,

Daca organismul produce o cantitate mare de toxina,

you might find 10 million, or 100 million.

poti gasi 10 sau 100 de milioane de organisme.

If it didn't produce a lot of this toxin,

Daca nu produce o cantitate mare de toxina,

then you might find a smaller number.

atunci vei gasi un numar mai mic de organisme.

So the task is to try to figure out

Deci sarcina este sa incercam sa ne dam seama

how to determine whether or not you could get an organism like this

cum sa stabilim daca putem face sau nu, ca un organism ca acesta

to evolve towards mildness by blocking waterborne transmission,

sa evolueze spre o forma mai blanda, prin blocarea transmiterii pe calea apei,

thereby allowing the organism only to be transmitted

astfel permitand organismului sa fie transmis

by person-to-person contact,

doar prin contact direct (persoana-persoana),

or person-food-person contact --

sau prin contact cu mancarea infectata(persoana-mancare-persoana) ---

both of which would really require that people be

iar pentru ambele fiind necesar ca oamenii sa fie

mobile and fairly healthy for transmission.

mobili si destul de sanatosi pentru transmitere.

Now, I can think of some possible experiments.

Acum, ma pot gandi la cateva experimente posibile.

One would be to take a lot of different strains of this organism --

Unul ar fi sa iau o multime de tulpini diferite ale acestui organism --

some that produce a lot of toxins, some that produce a little --

unele care produc o multime de toxine, altele care produc putine ---

and take those strains and spew them out in different countries.

si sa iau acele tulpini si sa le imprastii in tari diferite.

Some countries that might have clean water supplies,

Unele tari care pot avea aprovizionare cu apa curata,

so that you can't get waterborne transmission:

asa incat sa nu pot avea transmitere pe calea apei:

you expect the organism to evolve to mildness there.

te astepti ca organismul sa evolueze aici catre o forma mai blanda.

Other countries, in which you've got a lot of waterborne transmission,

In alte tari, in care parte din plin de transmitere pe calea apei,

there you expect these organisms to evolve

aici te astepti ca aceste organisme sa evolueze

towards a high level of harmfulness, right?

catre un nivel inalt de nocivitate, nu?

There's a little ethical problem in this experiment.

Este insa o mica problema etica in acest experiment.

I was hoping to hear a few gasps at least.

Speram sa aud un murmur cel putin.

That makes me worry a little bit.

Acest lucru ma ingrijoreaza putin.

(Laughter)

Rasete

But anyhow, the laughter makes me feel a little bit better.

Dar oricum, aceste rasete ma fac sa ma simt un pic mai bine.

And this ethical problem's a big problem.

Si aceasta problema etica este o problema mare.

Just to emphasize this, this is what we're really talking about.

Doar pentru a sublinia acest lucru, despre asta vorbim de fapt.

Here's a girl who's almost dead.

Aici este o fata care este aproape moarta.

She got rehydration therapy, she perked up,

A primit o terapie de rehidratare, s-a inviorat,

within a few days she was looking like a completely different person.

in cateva zile arata ca o persoana complet diferita.

So, we don't want to run an experiment like that.

Asa ca, nu vrem sa facem un experiment ca acela.

But interestingly, just that thing happened in 1991.

Dar interesant, chiar acest lucru s-a intamplat in 1991.

In 1991, this cholera organism got into Lima, Peru,

In 1991, acest organism cauzator de holera a intrat in Lima, Peru.

and within two months it had spread to the neighboring areas.

si in doua luni s-a intins catre zonele invecinate.

Now, I don't know how that happened,

Acum, nu stiu cum s-a intamplat,

and I didn't have anything to do with it, I promise you.

si nici nu am avut nimic de a face cu asta, va promit.

I don't think anybody knows,

Nu cred ca stie cineva,

but I'm not averse to, once that's happened,

dar nu sunt contra, o data ce s-a intamlat,

to see whether or not the prediction that we would make,

sa vedem daca predictia pe care am face-o,

that I did make before, actually holds up.

pe care am facut-o inainte, de fapt sta in picioare.

Did the organism evolve to mildness in a place like Chile,

A evoluat organismul catre o forma mai blanda intr-un loc precum Chile,

which has some of the most well protected water supplies

care are unele dintre cele mai bine protejate surse de apa

in Latin America?

din America Latina?

And did it evolve to be more harmful in a place like Ecuador,

Si a evoluat catre o forma mai periculoasa intr-un loc precum Ecuadorul,

which has some of the least well protected?

care are unele dintre sursele de apa cel mai putin protejate?

And Peru's got something sort of in between.

Si in Peru susele sunt cam intre cele doua exemple.

And so, with funding from the Bosack-Kruger Foundation,

Si asa, cu finantare de la fundatia Bozack-Kruger,

I got a lot of strains from these different countries

Am luat o multime de tulpini din aceste tari diferite

and we measured their toxin production in the lab.

si le-am masurat productia de toxina in laborator.

And we found that in Chile -- within two months of the invasion of Peru

Si am gasit ca in Chile - in decursul a doua luni de la invazia din Peru

you had strains entering Chile --

au intrat tulpini in Chile --

and when you look at those strains,

si cand ne-am uitat la acele tulpini,

in the very far left-hand side of this graph,

in partea stanga a graficului, foarte indepartat,

you see a lot of variation in the toxin production.

se vad o multime de variatii in producerea toxinei.

Each dot corresponds to an islet from a different person --

Fiecarui punct ii corespunde o insulita de la o alta persoana --

a lot of variation on which natural selection can act.

o multime de variatii asupra carora poate actiona selectia naturala.

But the interesting point is, if you look over the 1990s,

Dar interesant este, daca ne uitam peste anii 1990,

within a few years the organisms evolved to be more mild.

peste cativa ani organismele au evoluat catre o forma mai blanda.

They evolved to produce less toxin.

Au evoluat spre a produce o cantitate mai mica de toxina.

And to just give you a sense of how important this might be,

Si doar ca sa va dau un indiciu despre cat de importat ar putea fi acest lucru,

if we look in 1995, we find that there's only one case of cholera,

daca ne uitam in 1995, vedem ca acolo exista un singur caz de holera,

on average, reported from Chile every two years.

in medie, raportat din Chile la fiecare doi ani.

So, it's controlled.

Deci, este sub control.

That's how much we have in America,

Atat avem si in America,

cholera that's acquired endemically,

holera dobandita pe cale endemica,

and we don't think we've got a problem here.

si nu credem ca avem o problema aici.

They didn't -- they solved the problem in Chile.

Nici ei nu au crezut - au rezolvat problema in Chile.

But, before we get too confident, we'd better look at some of those other countries,

Dar, inainte sa devenim prea inrezatori, mai bine ne-am uita la alte cateva tari,

and make sure that this organism doesn't just always evolve toward mildness.

sa ne asiguram ca acest organism nu evolueaza intodeauna catre o forma mai blanda.

Well, in Peru it didn't.

Ei bine, in Peru nu a facut-o.

And in Ecuador -- remember, this is the place where it has

Si in Euador -- va amintiti, este locul care are

the highest potential waterborne transmission --

cel mai mare potential de trasnsmitere pe calea apei --

it looked like it got more harmful.

se pare ca a devenit mai periculos.

In every case there's a lot of variation,

In fiecare caz exista multa variatie,

but something about the environment the people are living in,

dar ceva din mediul in care traiesc oameni,

and I think the only realistic explanation is that it's

si cred ca singura explicatie realista este aceea ca,

the degree of waterborne transmission,

gradul de trasnsmitere pe calea apei,

favored the harmful strains in one place, and mild strains in another.

a favorizat tulpinile periculoase intr-un loc si pe cele mai blande in alt loc.

So, this is very encouraging,

Asa ca, este foarte incurajator,

it suggests that something that we might want to do anyhow,

sugereaza ca ceva ce am fi vrut sa facem oricum,

if we had enough money, could actually give us a much bigger bang for the buck.

daca am fi avut suficienti bani, de fapt, s-ar putea dovedi foarte rentabil.

It would make these organisms evolve to mildness,

Ar face ca aceste organisme sa evolueze catre o forma mai blanda,

so that even though people might be getting infected,

si asa ca, chiar daca s-ar infecta oameni,

they'd be infected with mild strains.

ar fi infectati cu tulpini blande.

It wouldn't be causing severe disease.

Nu ar cauza boli grave.

But there's another really interesting aspect of this,

Dar mai este un alt aspect chiar interesant al aceste probleme,

and this is that if you could control the evolution of virulence,

si acela este ca daca ai putea controla evolutia virulentei,

evolution of harmfulness,

evolutia nocivitatii,

then you should be able to control antibiotic resistance.

atunci ai putea controla rezistenta la antibiotice.

And the idea is very simple.

Si ideea este foarte simpla.

If you've got a harmful organism,

Daca ai un organism periculos,

a high proportion of the people are going to be symptomatic,

o mare parte a populatiei va avea simptome,

a high proportion of the people are going to be going to get antibiotics.

o mare parte a populatiei va lua antibiotice.

You've got a lot of pressure favoring antibiotic resistance,

Exista multa presiune in favoarea rezistentei la antibiotice,

so you get increased virulence leading to

deci avem parte de o virulenta crescuta care duce la

the evolution of increased antibiotic resistance.

evolutia unei rezistente crescute la antibiotice.

And once you get increased antibiotic resistance,

Si o data ce avem o rezistenta crescuta la antibiotice,

the antibiotics aren't knocking out the harmful strains anymore.

Antibioticele nu mai distrug tulpinile nocive.

So, you've got a higher level of virulence.

Deci, avem un nivel crescut de virulenta.

So, you get this vicious cycle.

Deci, avem acest cerc vicios.

The goal is to turn this around.

Scopul este sa transformam acest lucru.

If you could cause an evolutionary decrease in virulence

Daca am putea cauza o scadere evolutiva a virulentei

by cleaning up the water supply,

prin curatarea sursei de apa,

you should be able to get an evolutionary decrease

ar trebui sa putem obtine o scadere evolutiva

in antibiotic resistance.

a rezistentei la antibiotice.

So, we can go to the same countries and look and see.

Deci, putem merge in acelasi tari si sa vedem.

Did Chile avoid the problem of antibiotic resistance,

A evitat Chile problema rezistentei la antibiotice,

whereas did Ecuador actually have the beginnings of the problem?

unde a inceput de fapt problema in Ecuador?

If we look in the beginning of the 1990s,

Daca ne uitam la inceputul anilor 90,

we see, again, a lot of variation.

din nou vedem variatie.

In this case, on the Y-axis, we've just got a measure of antibiotic sensitivity --

In acest caz, pe axa Y, tocmai am masurat sensibilitatea la antibiotice --

and I won't go into that.

si nu o sa intru in problema asta.

But we've got a lot of variation in antibiotic sensitivity in Chile,

Dar avem multa variatie privind sensibilitatea la antibiotice in Chile,

Peru and Ecuador, and no trend across the years.

Peru si Ecuador si nici o tendinta dealungul anilor.

But if we look at the end of the 1990s, just half a decade later,

Dar daca ne uitam la sfarsitul anilor 90, doar o jumatate de deceniu mai tarziu,

we see that in Ecuador they started having a resistance problem.

vedem ca in Ecuador au inceput sa aiba o problema de rezistenta.

Antibiotic sensitivity was going down.

Sensibilitatea la antibiotice scadea.

And in Chile, you still had antibiotic sensitivity.

Si in Chile avem inca sensibilitate la antibiotice.

So, it looks like Chile dodged two bullets.

Deci, se pare ca Chile a nimerit doua dintr-o lovitura.

They got the organism to evolve to mildness,

Oranismul a evoluat catre o forma mai usoara,

and they got no development of antibiotic resistance.

si nu au inregistrat nici o evolutie in ceea ce priveste rezistenta la antibiotice.

Now, these ideas should apply across the board,

Acum, aceste idei ar trebui aplicate pe toata suprafata tablei,

as long as you can figure out why some organisms evolved to virulence.

atat timp cat na dam seama de ce unele organisme au evoluat in virulenta.

And I want to give you just one more example,

Si vreau sa va dau mai dau un singur exemplu,

because we've talked a little bit about malaria.

pentru ca am vorbit putin despre malarie.

And the example I want to deal with is,

Si exemplul de care vreau sa ma ocup este,

or the idea I want to deal with, the question is,

sau ideea de care vreau sa ma ocup, intrebarea este,

what can we do to try to get the malarial organism to evolve to mildness?

ce putem face sa incercam sa determinam organismul cauzator de malarie sa evolueze catre o forma mai blanda?

Now, malaria's transmitted by a mosquito,

Acum, malaria este transmisa de un tantar,

and normally if you're infected with malaria, and you're feeling sick,

si in mod normal daca esti infectat cu malarie si te simti rau,

it makes it even easier for the mosquito to bite you.

devine si mai usor pentru tantar sa te muste.

And you can show, just by looking at data from literature,

Si putem arata, doar uitandu-ne la datele din literatura de specialitate,

that vector-borne diseases are more harmful

ca bolile cu transmitere vectoriala sunt mai daunatoare

than non-vector-borne diseases.

decat bolile fara transmitere vectoriala.

But I think there's a really fascinating example

Dar cred ca aici avem un exemplu cu adevarat fascinant

of what one can do experimentally to try to actually demonstrate this.

de ce poate face cineva pe cale experimentala ca sa incerce sa demonstreze de fapt acest lucru.

In the case of waterborne transmission,

In cazul transmiterii pe calea apei,

we'd like to clean up the water supplies,

am vrea sa curatam alimentarea cu apa,

see whether or not we can get those organisms to evolve towards mildness.

sa vedem daca acele organisme evolueaza catre o forma mai blanda sau nu.

In the case of malaria, what we'd like to do is mosquito-proof houses.

In cazul malariei, ceea ce am dori este sa facem case in care nu pot patrunde tantarii.

And the logic's a little more subtle here.

Si logica este putin mai subtila aici.

If you mosquito-proof houses,

Daca avem case in care nu pot patrunde tantarii,

when people get sick, they're sitting in bed --

cand oamenii se imbolnavesc, stau in pat --

or in mosquito-proof hospitals, they're sitting in a hospital bed --

sau in spitale in care nu pot patrunde tantarii, stau intr-un pat de spital --

and the mosquitoes can't get to them.

si tantarii nu pot ajunge la ei.

So, if you're a harmful variant

Deci, dace esti o varietate daunatoare

in a place where you've got mosquito-proof housing, then you're a loser.

intr-un loc in care avem case in care nu pot patrunde tantari, atunci esti un perdant.

The only pathogens that get transmitted

Singurii agenti patogeni care sunt transmisi

are the ones that are infecting people that feel healthy enough

sunt aceia care infecteaza oameni care se simt suficient de sanatosi

to walk outside and get mosquito bites.

sa iasa afara si sa fie intepati de tantari.

So, if you were to mosquito proof houses,

Deci, daca am fi in acele case in care nu pot patrunde tantari,

you should be able to get these organisms to evolve to mildness.

ar trebui sa putem obtinem ca acele organisme sa evolueze catre o forma mai blanda.

And there's a really wonderful experiment that was done

Si exista un experiment cu adevarat minunat care a fost facut

that suggests that we really should go ahead and do this.

care sugereaza ca ar trebui sa continuam si sa facem asta.

And that experiment was done in Northern Alabama.

Si acest experiment a fost facut in Alabama de nord.

Just to give you a little perspective on this,

Doar ca sa va ofer o omagine de ansamblu,

I've given you a star at the intellectual center of the United States,

v-am pus o stea in centrul intelectual al Statelor Unite,

which is right there in Louisville, Kentucky.

care este chiar acolo in Louisville, Kentucky.

And this really cool experiment was done

Si acest experiment cu adevarat grozav a fost facut

about 200 miles south of there, in Northern Alabama,

la aproape 200 de mile in sud de acolo, in Alabama de nord,

by the Tennessee Valley Authority.

de catre Tennessee Valley Authority.

They had dammed up the Tennessee River.

Au indiguit raul Tennessee.

They'd caused the water to back up,

Au fortat apa sa se retraga,

they needed electric, hydroelectric power.

aveau nevoie de curent electric, produs de hidrocentrale.

And when you get stagnant water, you get mosquitoes.

Si atunci cand ai apa statatoare, ai tantari.

They found in the late '30s -- 10 years after they'd made these dams --

Au descoperit la sfarsitul anilor 30 -- 10 ani dupa ce au construit aceste baraje --

that the people in Northern Alabama were infected with malaria,

ca oamenii din Alabama de nord erau infectati cu malarie,

about a third to half of them were infected with malaria.

cam o treime, pana la o jumatate dintre ei erau infectati cu malarie.

This shows you the positions of some of these dams.

Aici vedeti pozitia unora dintre aceste baraje.

OK, so the Tennessee Valley Authority was in a little bit of a bind.

OK, asa ca Tennessee Valley Authority era la ananghie.

There wasn't DDT, there wasn't chloroquines: what do they do?

Nu era DDT, nu era clorochina, ce sa faca?

Well, they decided to mosquito proof every house in Northern Alabama.

Ei bine, au hotarat sa izoleze fiecare casa din Alabama de nord impotriva tantarilor.

So they did. They divided Northern Alabama into 11 zones,

Si asa au facut. Au impartit Alabama de nord in 11 zone.

and within three years, about 100 dollars per house,

si in trei ani, cu aproximativ 100 de dolari per casa,

they mosquito proofed every house.

au izolat fiecare casa impotriva tantarilor.

And these are the data.

Si acestea sunt datele.

Every row across here represents one of those 11 zones.

Fiecare rand de aici reprezinta una din acele 11 zone.

And the asterisks represent the time at which

Si asterixurile reprezinta momentul la care

the mosquito proofing was complete.

s-a incheiat izolarea caselor impotriva tantarilor.

And so what you can see is that

Si ceea ce vedem este ca

just the mosquito-proofed housing, and nothing else,

doar izolarea caselor impotriva tantarilor, si nimic altceva,

caused the eradication of malaria.

a dus la eradicarea malariei.

And this was, incidentally, published in 1949,

Si acest lucru a fost intamplator publicat in 1949,

in the leading textbook of malaria, called "Boyd's Malariology."

in cartea de capatai a malariei, intitulata "Boyd's Malariology" (Malariaologia lui Boyd)

But almost no malaria experts even know it exists.

Dar aproape nici un expert in malarie nici macar nu stie ca exista.

This is important,

Acest lucru este important,

because it tells us that if you have moderate biting densities,

pentru ca ne spune ca daca avem o densitate moderata a intapaturilor,

you can eradicate malaria by mosquito proofing houses.

putem eradica malaria prin izolarea caselor impotriva tantarilor.

Now, I would suggest that you could do this in a lot of places.

Acum, as sugera ca se poate face asta in multe locuri.

Like, you know, just as you get into the malaria zone,

Asa cum stiti, chiar cum intrii in zona cu malarie,

sub-Saharan Africa.

in Africa sub-sahariana.

But as you move to really intense biting rate areas, like Nigeria,

Dar cum ne miscam catre zone cu o rata crescuta de intepaturi, cum e Nigeria,

you're certainly not going to eradicate.

cu siguranta nu o sa eradicam malaria.

But that's when you should be favoring evolution towards mildness.

Dar asta este cand ar trebui sa favorizam evolutia catre o forma mai usoara.

So to me, it's an experiment that's waiting to happen,

Asa ca pentru mine este un experiment care asteapta sa se intample,

and if it confirms the prediction, then

si daca confirma predictia, atunci

we should have a very powerful tool.

ar trebui sa avem un instrument foarte puternic.

In a way, much more powerful than the kind of tools we're looking at,

Intr-un fel, mult mai puternic decat tipul de unelte la care ne uitam,

because most of what's being done today is

pentru ca cea mai mare parte din ceea ce se face azi este

to rely on things like anti-malarial drugs.

sa ne bazam pe lucruri cum ar fi medicamentele anti-malarie.

And we know that, although it's great to make those

Si stim ca, desi este un lucru mare sa punem foarte frecvent dispozitie acele

anti-malarial drugs available at really low cost and high frequency,

medicamente anti-malarie la costuri cu adevarat mici,

we know that when you make them highly available

stim ca atunci cand le faci extem de diponibile

you're going to get resistance to those drugs.

urmeaza sa intampini rezistenta la acele medicamente.

And so it's a short-term solution.

Si deci este o solutie pe termen scurt.

This is a long-term solution.

Aceasta este o solutie pe permen lung.

What I'm suggesting here is that we could get evolution

Ceea ce sugerez este ca putem obtine ca evolutia

working in the direction we want it to go,

sa lucreze in directia in care vrem,

rather than always having to battle evolution as a problem

si sa nu mai fim nevoiti sa luptam cu ea de fiecare data

that stymies our efforts to control the pathogen,

lucru care ne ingreuneaza eforturile de a controla agentul patogen,

for example with anti-malarial drugs.

cum este exemplul cu medicamentele anti-malarie.

So, this table I've given just to emphasize

Deci, am facut acest table doar ca sa subliniez

that I've only talked about two examples.

ca am vorbit doar despre doua exemple.

But as I said earlier, this kind of logic applies across the board

Dar asa cum am zis mai devreme, aceast tip de logica se aplica pentru toata tabla

for infectious diseases, and it ought to.

pentru bolile infectioase, asa cum ar trebui sa o faca.

Because when we're dealing with infectious diseases, we're dealing with living systems.

Pentru ca atunci cand ne ocupam de boli infectioase, avem de-a face cu sisteme vii;

We're dealing with living systems;

Avem de-a face cu sisteme vii;

we're dealing with systems that evolve.

Avem de-a face cu sisteme care evolueaza.

And so if you do something with those systems,

Si deci daca faci ceva cu acele sisteme,

they're going to evolve one way or another.

Ele vor evolua intr-un fel sau altul.

And all I'm saying is that we need to figure out how they'll evolve,

Si tot ce spun este ca avem nevoie sa ne dam seama cum vor evolua,

so that -- we need to adjust our interventions

astfel incat -- avem nevoie sa ne ajustam interventiile

to get the most bang for the intervention buck,

pentru a obţine cele mai bune rezultate pentru intervenţiile facute,

so that we can get these organisms to evolve in the direction we want them to go.

astfel incat sa facem aceste organisme sa evolueze in directia dorita.

So, I don't really have time to talk about those things,

Asa ca, nu prea am timp sa vorbesc despre aceste lucruri,

but I did want to put them up there,

dar am vrut sa le pun aici,

just to give you a sense that there really are solutions

doar pentru a vă oferi certitudinea că exista intr-adevăr solutii

to controlling the evolution of harmfulness

pentru a controla evolutia nocivitatii

of some of the nasty pathogens that we're confronted with.

unora dintre cei mai rai agenti patogeni cu care ne confruntam.

And this links up with a lot of the other ideas that have been talked about.

Si asta se leaga cu o multime de alte idei despre care s-a vorbit.

So, for example, earlier today there was discussion of,

Deci, spre exemplu, mai devreme au fost dezbateri despre,

how do you really lower sexual transmission of HIV?

cum scadem rata de transmitere a virusului HIV?

What this emphasizes is that we need to figure out how it will work.

Ceea ce subliniaza acest lucru este ca trebuie sa ne dam seama cum va functiona.

Will it maybe get lowered if we alter the economy of the area?

Poate va scadea daca modificam economia zonei?

It may get lowered if we intervene in ways that

Poate scadea daca intervenim in moduri in care

encourage people to stay more faithful to partners, and so on.

incurajeaza oamenii sa ramana mai fideli partenerilor, si asa mai departe.

But the key thing is to figure out how to lower it,

Dar elementul cheie este sa ne dam seama cum sa o scadem,

because if we lower it, we'll get an evolutionary change in the virus.

pentru ca daca o scadem, vom obtine o schimbare in evolutia virusului.

And the data really do support this:

Si datele sustin acest lucru:

that you actually do get the virus evolving towards mildness.

ca intr-adevar obti ca virusul sa evolueze catre o forma mai blanda.

And that will just add to the effectiveness of our control efforts.

Si asta se va adauga efectivitatii eforturilor noastre de control.

So the other thing I really like about this,

Si celalalt lucru care mi-a placut la asta,

besides the fact that it brings a whole new dimension

in afara faptului ca aduce o dimeniune cu totul noua

into the study of control of disease,

in studiul privind controlul bolilor,

is that often the kinds of interventions that you want,

este ca adesea tipurile de interventii pe care le vrei,

that it indicates should be done,

care sunt indicate ca trebuie facute,

are the kinds of interventions that people want anyhow.

sunt tipurile de interventii pe care oamenii le vor oricum.

But people just haven't been able to justify the cost.

Dar oamenii pur si simplu nu au putut justifica costul.

So, this is the kind of thing I'm talking about.

Deci, acesta este genul de lucruri despre care vorbesc.

If we know that we're going to get extra bang for the buck from providing clean water,

Daca stim ca urmeaza sa merite sa furnizam apa curata,

then I think that we can say,

atunci cred ca putem spune,

let's push the effort into that aspect of the control,

haideti sa facem eforturi in privinta aspectului controlului,

so that we can actually solve the problem,

ca sa putem rezolva de fapt problema,

even though, if you just look at the frequency of infection,

chiar daca, daca ne uitam doar la frecventa infectiei,

you would suggest that you can't solve the problem well enough

ai putea sugera ca nu poti rezolva suficient de bine problema

just by cleaning up water supply.

doar prin curatarea aprovizionarii cu apa.

Anyhow, I'll end that there, and thank you very much.

Oricum, voi incheia aici si va multumesc foarte mult.

(Applause)

Aplauze