I'm going to start with a little story. So, I grew up in this neighborhood. When I was 15 years old, I went from being what I think was a strapping young athlete, over four months, slowly wasting away until I was basically a famine victim with an unquenchable thirst. I had basically digested away my body. And this all came to a head when I was on a backpacking trip, my first one ever actually, on Old Rag Mountain in West Virginia, and was putting my face into puddles of water and drinking like a dog.
Počeću jednom kratkom pričom. Odrastao sam u susedstvu. Kada sam imao 15 godina, smatrao sam za sebe da sam robustan, mlad atletski građen tip ali tokom četiri meseca polako sam slabio i skoro da sam postao žrtva gladi sa osećajem neutoljive žeđi. Skoro sam "svario" svoje telo. Svega ovoga sam postao svestan kada sam otišao na "bekpek" putovanje, u stvari, na moje prvo takvo putovanje, na Old Rag planinu u Zapadnoj Virdžiniji i kada sam uranjao lice u barice vode i pio kao pas.
That night, I was taken into the emergency room and diagnosed as a type 1 diabetic in full-blown ketoacidosis. And I recovered, thanks to the miracles of modern medicine, insulin and other things, and gained all my weight back and more.
Te noći su me odveli u Hitnu pomoć i dijagnostikovali su mi dijabetes tip 1 sa potpunom ketoacidozom. I oporavio sam se, zahvaljujući čudima savremene medicine, insulinu i drugim stvarima i povratio sam svu svoju težinu, čak i više od toga.
And something festered inside me after this happened. What I thought about was, what caused the diabetes? You see, diabetes is an autoimmune disease where your body fights itself, and at the time people thought that somehow maybe exposure to a pathogen had triggered my immune system to fight the pathogen and then kill the cells that make insulin. And this is what I thought for a long period of time, and that's in fact what medicine and people have focused on quite a bit, the microbes that do bad things. And that's where I need my assistant here now. You may recognize her.
Posle ovoga nešto se skupljalo u meni. Razmišljao sam o tome šta je bio uzrok dijabetesu. Znate, dijabetes je autoimuno oboljenje gde se organizam bori sa sobom i jedno vreme su ljudi mislili da je nekako možda izloženost patogenu aktivirao moj imuni sistem da se bori sa patogenom, a zatim da uništi ćelije koje proizvode insulin. I ja sam dugo tako mislio, i to je, u stvari, ono na šta se medicina i ljudi prilično fokusiraju, a to je da mikrobi čine loše stvari. I sada mi treba moj pomoćnik. Možda je prepoznajete.
So, I went yesterday, I apologize, I skipped a few of the talks, and I went over to the National Academy of Sciences building, and they sell toys, giant microbes. And here we go! So you have caught flesh-eating disease if you caught that one. I gotta get back out my baseball ability here.
Juče sam išao, izvinite, preskočio sam nekoliko govora, i išao sam do Nacionalne akademije nauka gde su prodavali igračke, ogromne mikrobe. Evo, idemo! Ako ste uhvatili neku, dobićete bolest koja jede meso. Moram da povratim svoju veštinu za bejzbol.
(Laughter)
(Smeh)
So, unfortunately or not surprisingly, most of the microbes they sell at the National Academy building are pathogens. Everybody focuses on the things that kill us, and that's what I was focusing on. And it turns out that we are covered in a cloud of microbes, and those microbes actually do us good much of the time, rather than killing us. And so, we've known about this for some period of time. People have used microscopes to look at the microbes that cover us, I know you're not paying attention to me, but ...
Pa, na žalost, ali nije iznenađujuće, većina mikroba koje prodaju u Nacionalnoj akademiji su patogeni. Svi se fokusiraju na stvari koje nas uništavaju pa sam tako i ja. Ispostavlja se da smo prekriveni oblakom mikroba i oni nam uglavnom čine dobro, više nego što nas uništavaju. I tako, ovo nam je poznato već izvesno vreme. Ljudi koriste mikroskope da pogledaju mikrobe kojima smo prekriveni, znam da ne obraćate pažnju na mene, ali...
(Laughter)
(Smeh)
The microbes that cover us. And if you look at them in the microscope, you can see that we actually have 10 times as many cells of microbes on us as we have human cells. There's more mass in the microbes than the mass of our brain.
Ti mikrobi koji nas pokrivaju. I ako ih pogledate u mikroskopu možete videti da, u stvari, imamo 10 puta više ćelija mikroba nego što imamo ljudskih ćelija. Masa mikroba je veća od mase našeg mozga.
We are literally a teeming ecosystem of microorganisms. And unfortunately, if you want to learn about the microorganisms, just looking at them in a microscope is not sufficient. And so we just heard about the DNA sequencing. It turns out that one of the best ways to look at microbes and to understand them is to look at their DNA. And that's what I've been doing for 20 years, using DNA sequencing, collecting samples from various places, including the human body, reading the DNA sequence and then using that DNA sequencing to tell us about the microbes that are in a particular place.
Mi smo bukvalno ekosistem koji vrvi od mikroorganizama. I nažalost, ako želite da saznate nešto o mikroorganizmima, nije dovoljno da ih samo gledate na mikroskopu. Upravo smo čuli o sekvenciranju DNK. Ispostavlja se da je najbolji način da posmatramo mikrobe i da ih razumemo, taj da pratimo njihov DNK. To upravo i radim već 20 godina, koristim sekvenciranje DNK, sakupljam primerke sa raznih mesta, uključujući i ljudsko telo, zatim čitam DNK nizove i koristim to da saznam o mikrobima koji su na određenom mestu.
And what's amazing, when you use this technology, for example, looking at humans, we're not just covered in a sea of microbes. There are thousands upon thousands of different kinds of microbes on us. We have millions of genes of microbes in our human microbiome covering us. And so this microbial diversity differs between people, and what people have been thinking about in the last 10, maybe 15 years is, maybe these microbes, this microbial cloud in and on us, and the variation between us, may be responsible for some of the health and illness differences between us.
I ono što je neverovatno kad koristite ovu tehnologiju na primer, posmatrajući ljude, nije da smo samo prekriveni morem mikroba. Ima na hiljade i hiljade različitih vrsta mikroba na nama. Milioni gena mikroba nas pokrivaju u našem ljudskom mikrobiomu. Tako, diverzitet mikroba se razlikuje od čoveka do čoveka i ono o čemu ljudi razmišljaju u zadnjih 10 godina, možda i 15, da su ovi mikrobi, ovaj oblak od mikroba oko nas i varijacije među nama, možda odgovorne za razlike u zdravlju i u bolestima kod ljudi.
And that comes back to the diabetes story I was telling you. It turns out that people now think that one of the triggers for type 1 diabetes is not fighting a pathogen, but is in fact trying to -- miscommunicating with the microbes that live in and on you. And somehow maybe the microbial community that's in and on me got off, and then this triggered some sort of immune response and led to me killing the cells that make insulin in my body.
Evo vraćam se na priču koju sam vam pričao o dijabetesu. Ispada da ljudi sada misle da jedan od okidača za dijabetes tipa 1 nije borba sa patogenom, nego, u stvari, pokušaj pogrešne komunikacije sa mikrobima koji žive u nama i na nama. I možda je nekako ta zajednica mikroba nestala sa mene i to je pokrenulo neku vrstu odgovora imunosistema što je dovelo do uništavanja ćelija koje proizvode insulin u mom telu.
And so what I want to tell you about for a few minutes is, what people have learned using DNA sequencing techniques in particular, to study the microbial cloud that lives in and on us. And I want to tell you a story about a personal project. My first personal experience with studying the microbes on the human body actually came from a talk that I gave, right around the corner from here at Georgetown.
Ono o čemu želim da vam pričam nekoliko minuta je, šta su ljudi saznali, posebno koristeći tehniku sekvenciranja DNK za proučavanje oblaka mikroba koji žive u nama i na nama. Želim da vam ispričam priču o jednom ličnom projektu. Moje prvo lično iskustvo u vezi sa proučavanjem mikroba na ljudskom telu potiče, u stvari, iz jednog govora koji sam održao ovde, blizu, u Džordžtaunu.
I gave a talk, and a family friend who happened to be the Dean of Georgetown Medical School was at the talk, and came up to me afterwards saying, they were doing a study of ileal transplants in people. And they wanted to look at the microbes after the transplants.
Ja sam govorio i jedan porodični prijatelj, koji je slučajno bio dekan Medicinske škole u Džordžtaunu, je bio tamo i posle je došao do mene da mi kaže da rade studiju o transplantaciji ileuma kod ljudi. I hteli su da vide mikrobe posle transplantacije.
And so I started a collaboration with this person, Michael Zasloff and Thomas Fishbein, to look at the microbes that colonized these ilea after they were transplanted into a recipient. And I can tell you all the details about the microbial study that we did there, but the reason I want to tell you this story is something really striking that they did at the beginning of this project. They take the donor ileum, which is filled with microbes from a donor and they have a recipient who might have a problem with their microbial community, say Crohn's disease, and they sterilized the donor ileum. Cleaned out all the microbes, and then put it in the recipient. They did this because this was common practice in medicine, even though it was obvious that this was not a good idea.
Tako sam počeo saradnju sa ovim osobama, sa Majklom Zaslofim i Tomasom Fišbajnom, da proučimo mikrobe koji su zaposeli ileum posle transplantacije na primaoca. Mogu da vam pričam o svim detaljima ove mikrobijalne studije koju smo radili, ali razlog zbog čega želim da vam ispričam ovu priču je nešto zaista upečatljivo što su činili na početku ovog projekta. Uzeli su ileum pun mikroba od davaoca i imali su primaoca koji bi mogao imati problem sa njihovom mikrobijalnom zajednicom, recimo sa Kronovom bolešću i zato su sterilisali ileum davaoca. Očistili su sve mikrobe i presadili ileum u primaoca. Učinili su ovo jer je to bila uobičajna praksa u medicini, iako je bilo očigledno da to nije dobra ideja.
And fortunately, in the course of this project, the transplant surgeons and the other people decided, forget common practice. We have to switch. So they actually switched to leaving some of the microbial community in the ileum. They leave the microbes with the donor, and theoretically that might help the people who are receiving this ileal transplant.
I srećom, tokom ovog projekta, hirurzi koji su vršili presađivanje, a i drugi ljudi, odlučili su da zaborave na uobičajenu praksu. Morali su da promene nešto. U stvari, ostavili su malo mikrobijalne zajednice na ileumu. Ostavili su mikrobe davaoca, i teoretski, ovo je moglo da pomogne onima koji primaju ovaj transplantat ileuma.
And so, people -- this is a study that I did now. In the last few years there's been a great expansion in using DNA technology to study the microbes in and on people. There's something called the Human Microbiome Project that's going on in the United States, and MetaHIT going on in Europe, and a lot of other projects.
I tako, ljudi - ovo je studija koju sam zaista radio. U poslednjih nekoliko godina postoji velika ekspanzija upotrebe DNK tehnologije za proučavanje mikroba u ljudima. Postoji nešto što se zove Projekat ljudskog mikrobioma koji se sprovodi u SAD i projekat MetaHIT u Evropi i mnogo drugih projekata.
And when people have done a variety of studies, they have learned things such as, when a baby is born, during vaginal delivery you get colonized by the microbes from your mother. There are risk factors associated with cesarean sections, some of those risk factors may be due to mis-colonization when you carve a baby out of its mother rather than being delivered through the birth canal. And a variety of other studies have shown that the microbial community that lives in and on us helps in development of the immune system, helps in fighting off pathogens, helps in our metabolism, and determining our metabolic rate, probably determines our odor, and may even shape our behavior in a variety of ways.
I kada se uradi mnoštvo studija, ljudi su shvatili, na primer, kada se beba rodi, tokom vaginalnog porođaja, kolonije mikroba se prenose sa majke na dete. Postoje faktori rizika kod carskog reza, neki od tih faktora rizika mogu nastati zbog odsustva prenošenja kolonija kada se beba vadi iz majke, a ne rađa se preko porođajnog kanala. Mnoštvo drugih studija je pokazalo da mikrobijalne zajednice sa kojima živimo pomažu u razvoju imunosistema, pomažu da se izborimo sa patogenima, pomažu u metabolizmu i određuju vreme razmene materije, verovatno određuju naš miris, možda čak i oblikuju naše ponašanje na razne načine.
And so, these studies have documented or suggested out of a variety of important functions for the microbial community, this cloud, the non-pathogens that live in and on us. And one area that I think is very interesting, which many of you may have now that we've thrown microbes into the crowd, is something that I would call "germophobia." So people are really into cleanliness, right? We have antibiotics in our kitchen counters, people are washing every part of them all of the time, we pump antibiotics into our food, into our communities, we take antibiotics excessively.
Dakle, ove studije su dokumentovale ili nagovestile raznovrsne, važne uloge mikrobijalnih zajednica, ovog oblaka, ne-patogena, sa kojima živimo. I mislim da je jedno područje veoma zanimljivo, možda vam je i poznato, sad kad smo izbacili mikrobe u masu, a ja volim da ga zovem "klicofobijom" Ljudi su zaista za čistoću, zar ne? Imamo antibiotike na radnim površinama u kuhinji, ljudi stalno peru svaki deo svog tela, ubacujemo antibiotike u hranu, u naše zajednice, prekomerno uzimamo antibiotike.
And killing pathogens is a good thing if you're sick, but we should understand that when we pump chemicals and antibiotics into our world, that we're also killing the cloud of microbes that live in and on us. And excessive use of antibiotics, in particular in children, has been shown to be associated with, again, risk factors for obesity, for autoimmune diseases, for a variety of problems that are probably due to disruption of the microbial community.
Dobro je uništavati patogene kad ste bolesni, ali bi trebalo da shvatimo da, kada unosimo hemikalije i antibiotike u naš svet, takođe uništavamo oblak mikroba sa kojima živimo. Prekomerna upotreba antibiotika, naročito kod dece, može biti faktor rizika za gojaznost, za autoimune bolesti, za različite probleme prouzrokovane razbijanjem mikrobijalne zajednice.
So the microbial community can go wrong whether we want it to or not, or we can kill it with antibiotics, but what can we do to restore it? I'm sure many people here have heard about probiotics. Probiotics are one thing that you can try and do to restore the microbial community that is in and on you. And they definitely have been shown to be effective in some cases. There's a project going on at UC Davis where people are using probiotics to try and treat, prevent, necrotizing enterocolitis in premature infants. Premature infants have real problems with their microbial community. And it may be that probiotics can help prevent the development of this horrible necrotizing enterocolitis in these premature infants.
Može doći do devijacije mikrobijalne zajednice hteli to ili ne ili ih možemo uništiti antibioticima, ali šta možemo učiniti da ih vratimo? Siguran sam da su mnogi čuli za probiotike. Možete pokušati da vratite mikrobijalne zajednice uz pomoć probiotika. U nekim slučajevima su se definitivno pokazali efikasnim. Na Dejvis Univerzitetu u Koloradu u toku je projekat gde ljudi koriste probiotike za lečenje, prevenciju nekrotičnog enterokolitisa kod prevremeno rođene dece. Prevremeno rođena deca zaista imaju problem sa mikrobijalnom zajednicom. Moguće je da probiotik pomaže u prevenciji razvoja ovog užasnog nekrotičnog enterokolitisa kod prevremeno rođenih.
But probiotics are sort of a very, very simple solution. Most of the pills that you can take or the yogurts that you can eat have one or two species in them, maybe five species in them, and the human community is thousands upon thousands of species. So what can we do to restore our microbial community when we have thousands and thousands of species on us?
Ali probiotici su samo mali deo rešenja. Većina tableta koje uzimate ili jogurt koji pijete sadrži samo jednu ili dve vrste probiotika ili možda pet, a u čoveku postoje na hiljade vrsta. Stoga, šta možemo učiniti da vratimo mikrobijalnu zajednicu kad ih imamo na hiljade vrsta?
Well, one thing that animals seem to do is, they eat poo -- coprophagia. And it turns out that many veterinarians, old school veterinarians in particular, have been doing something called "poo tea," not booty, but poo tea, to treat colic and other ailments in horses and cows and things like that, where you make tea from the poo from a healthy individual animal and you feed it to a sick animal. Although, unless you have a fistulated cow with a big hole in its side, and you can put your hand into its rumen, it's hard to imagine that the delivery of microbes directly into the mouth and through the entire top of the digestive tract is the best delivery system, so you may have heard in people they are now doing fecal transplants, where rather than delivering a couple of probiotic microbes through the mouth, they are delivering a community of probiotics, a community of microbes from a healthy donor, through the other end.
Pa, izgleda da životinje jedu kaku -- koprofagija. Izgleda da mnogi veterinari, naročito iskusni, prave nešto što bi nazvali "čaj od izmeta", da bi lečlii bol u stomaku i druge bolesti kod konja i krava i slično, gde se pravi čaj od izmeta zdrave životinje i time se hrani bolesna životinja. Mada, kada je kod krave burag otvoren i možete da stavite ruku unutra teško je zamisliti da "isporuka" mikroba direktno u usta i kroz ceo gornji deo sistema za varenje najbolji način za ubacivanje mikroba, pa ste možda čuli da se kod ljudi sada radi transplantacija fecesa, što je bolje nego ubacivanje par probiotskih mikroba preko usta. Sada se ubacuju zajednice probiotika, zajednice mikroba uzetih od zdravog davaoca, ali s drugog kraja.
And this has turned out to be very effective in fighting certain intransigent infectious diseases like Clostridium difficile infections that can stay with people for years and years and years. Transplants of the feces, of the microbes from the feces, from a healthy donor has actually been shown to cure systemic C. dif infections in some people.
Ispostavilo se da je ovaj način veoma efikasan u borbi protiv određenih upornih zaraznih bolesti, kao što je infekcija gram pozitivnim bakterijama Clostridium difficele koja može trajati godinama. Transplantacija fecesa, mikroba iz fecesa, od zdravog davaoca, pokazala se kao lek za infekciju ljudi zaraženih Clostridium diff. bakterijom.
Now what these transplants, these fecal transplants, or the poo tea suggest to me, and many other people have come up with this same idea, is that the microbial community in and on us, it's an organ. We should view it as a functioning organ, part of ourselves. We should treat it carefully and with respect, and we do not want to mess with it, say by C-sections or by antibiotics or excessive cleanliness, without some real good justification.
Ove fekalne transplantacije ili čaj od izmeta, pokazalo se, a i mnogi misle slično, da je mikrobijalna zajednica - jedan organ. Trebalo bi da ga smatramo funkcionalnim organom, delom nas samih. Trebalo bi da ga lečimo pažljivo i sa poštovanjem, ne bi trebalo da se zafrkavamo s tim, recimo carskim rezom antibioticma, preteranom čistoćom, bez nekog zaista dobrog opravdanja.
And what the DNA sequencing technologies are allowing people to do now is do detailed studies of, say, 100 patients who have Crohn's disease and 100 people who don't have Crohn's disease. Or 100 people who took antibiotics when they were little, and 100 people who did not take antibiotics. And we can now start to compare the community of microbes and their genes and see if there are differences. And eventually we may be able to understand if they're not just correlative differences, but causative. Studies in model systems like mouse and other animals are also helping do this, but people are now using these technologies because they've gotten very cheap, to study the microbes in and on a variety of people.
Tehnologija sekvenciranja DNK sada omogućava ljudima da detaljno prouče, recimo, 100 pacijenata sa Kronovom bolešću i 100 ljudi bez te bolest. Ili 100 ljudi koji su uzimali antibiotike kada su bili mali i 100 ljudi koji nisu uzimali antibiotike. I sada možemo početi upoređivanje zajednice mikroba i njihovih gena, da vidimo ima li razlike. I na kraju moći ćemo da shvatimo da razlike nisu samo korelativne već i uzročne. Proučavanje miša ili nekih drugih životinja takođe pomaže, ali ljudi sad koriste ove tehnologije jer je proučavanje mikroba na mnoštvu ljudi postalo veoma jeftino.
So, in wrapping up, what I want to tell you about is, I didn't tell you a part of the story of coming down with diabetes. It turns out that my father was an M.D., actually studied hormones. I told him many times that I was tired, thirsty, not feeling very good. And he shrugged it off, I think he either thought I was just complaining a lot, or it was the typical M.D. "nothing can be wrong with my children." We even went to the International Society of Endocrinology meeting as family in Quebec. And I was getting up every five minutes to pee, and drinking everybody's water at the table, and I think they all thought I was a druggie.
Pa, da zaokružim, ono o čemu hoću da vam pričam, a nisam još ispričao, je deo priče o tome kako sam dobio dijabetes. Moj otac je bio doktor medicine u stvari, proučavao je hormone. Mnogo puta sam mu rekao da sam umoran, žedan, da se ne osećam baš dobro. Samo je slegao ramenima misleći da se previše žalim ili je to bilo ono tipično doktorsko: "Mojoj deci ništa ne fali". Išli smo porodično na susret Međunarodnog udruženja endokrinologa u Kvebek. Svakih pet minuta sam ustajao da piškim i svu vodu sa stola sam popio i mislim da su me smatrali za narkosa.
(Laughter)
(Smeh)
But the reason I'm telling you this is that the medical community, my father as an example, sometimes doesn't see what's right in front of their eyes. The microbial cloud, it is right in front of us. We can't see it most of the time. It's invisible. They're microbes. They're tiny. But we can see them through their DNA, we can see them through the effects that they have on people.
Ovo vam govorim jer medicinari, kao moj otac na primer, ponekad ne vide šta imaju ispred sebe. Mikrobijalni oblak je upravo ispred nas. Uglavnom ga ne vidimo. Nevidljiv je. Mikrobi su majušni. Ali ih vidimo kroz DNK i kroz uticaj koji imaju na ljude.
And what we need now is to start thinking about this microbial community in the context of everything in human medicine. It doesn't mean that it affects every part of us, but it might. What we need is a full field guide to the microbes that live in and on people, so that we can understand what they're doing to our lives. We are them. They are us.
Sada nam je potrebno da počnemo razmišljati o mikrobijalnoj zajednici u kontekstu celokupne medicine. Ne znači da utiče na sve u nama, ali mogao bi. Treba nam sveobuhvatan vodič za mikrobe sa kojima živimo, da bismo razumeli kako utiču na naš život. Mi smo oni. Oni su mi.
Thank you.
Hvala.
(Applause)
(Aplauz)