So, embryonic stem cells are really incredible cells. They are our body's own repair kits, and they're pluripotent, which means they can morph into all of the cells in our bodies. Soon, we actually will be able to use stem cells to replace cells that are damaged or diseased.
Dakle, embrionalne matične ćelije su zaista neverovatne ćelije. To je prosto pribor za pomoć samom našem telu. Te ćelije su pluripotentne, što znači da se od njih mogu razviti sve ostale ćelije našeg tela. Uskoro ćemo moći da koristimo matične ćelije za zamenu oštećenih ili obolelih ćelija u telu.
But that's not what I want to talk to you about, because right now there are some really extraordinary things that we are doing with stem cells that are completely changing the way we look and model disease, our ability to understand why we get sick, and even develop drugs. I truly believe that stem cell research is going to allow our children to look at Alzheimer's and diabetes and other major diseases the way we view polio today, which is as a preventable disease.
Ali ne želim o tome da pričam, jer u ovom trenutku dolazimo do neverovatnih otkrića u razumevanju matičnih ćelija koja će potpuno promeniti način na koji izučavamo i modelujemo bolesti, način na koji shvatamo zašto se razboljevamo i način na koji pronalazimo lekove. Duboko verujem da će istraživanje matičnih ćelija omogućiti našoj deci da Alchajmerovu bolest ili dijabetes i ostale velike bolesti današnjice, doživljavaju onako kako mi shvatamo polio, kao bolest koju je moguće sprečiti.
So here we have this incredible field, which has enormous hope for humanity, but much like IVF over 35 years ago, until the birth of a healthy baby, Louise, this field has been under siege politically and financially. Critical research is being challenged instead of supported, and we saw that it was really essential to have private safe haven laboratories where this work could be advanced without interference. And so, in 2005, we started the New York Stem Cell Foundation Laboratory so that we would have a small organization that could do this work and support it.
Tako da pričamo o neverovatnim otkrićima, koja nose ogromnu nadu za ljudsku vrstu, ali kao što se primena veštačke oplodnje pre 35 godina borila sa političkim i finansijskim problemima do rođenja zdrave bebe, Luiz - slično se i sada dešava. Kritična istraživanja se dovode u pitanje umesto da dobiju podršku, pa smo shvatili da je neophodno da imamo privatne, zaštićene laboratorije i gde se može baviti ovim radom bez uplitanja sa strane. Tako smo 2005. osnovali Laboratoriju matičnih ćelija - Njujorška fondacija, kako bismo imali malu organizciju koja može podržati i odrađivati taj rad.
What we saw very quickly is the world of both medical research, but also developing drugs and treatments, is dominated by, as you would expect, large organizations, but in a new field, sometimes large organizations really have trouble getting out of their own way, and sometimes they can't ask the right questions, and there is an enormous gap that's just gotten larger between academic research on the one hand and pharmaceutical companies and biotechs that are responsible for delivering all of our drugs and many of our treatments, and so we knew that to really accelerate cures and therapies, we were going to have to address this with two things: new technologies and also a new research model. Because if you don't close that gap, you really are exactly where we are today. And that's what I want to focus on. We've spent the last couple of years pondering this, making a list of the different things that we had to do, and so we developed a new technology, It's software and hardware, that actually can generate thousands and thousands of genetically diverse stem cell lines to create a global array, essentially avatars of ourselves. And we did this because we think that it's actually going to allow us to realize the potential, the promise, of all of the sequencing of the human genome, but it's going to allow us, in doing that, to actually do clinical trials in a dish with human cells, not animal cells, to generate drugs and treatments that are much more effective, much safer, much faster, and at a much lower cost.
Ono što smo ubrzo shvatili je da su i medicinska istraživanja i proces pronalaženja lekova i tretmana, pod apsolutnom dominacijom velikih organizacija, što biste i očekivali. Ali u novim granama nauke, ponekad te velike organizacije nerado odustaju od starog načina rada, pa nekada ne mogu da postave pravo pitanje i postoji ogromna praznina, koja postaje sve veća, između akademskog istraživanja sa jedne strane i farmaceutskih i biotehnoloških kompanija koje stoje iza proizvodnje velikog dela lekova i mnogih tretmana za naše lečenje. Znali smo da ako želimo zaista ubrzati pronalazak lekova i terapija, treba da razmislimo o ove dve stvari: o novim tehnologijama i o novim laboratorijskim modelima. Jer ukoliko ne prevaziđete tu prazninu, onda ćete se naći tu gde smo danas. O tome želim danas da pričam. Tokom proteklih par godina to smo detaljno analizirali i pravili smo listu stvari koje treba da uradimo. Tako smo razvili novu tehnologiju, odgovarajući softver i hardver, koji u prinicipu može da stvori hiljade i hiljade genetički različitih matičnih ćelija koje bi mogle da se koriste za stvaranje globalnog niza, pravih avatara nas samih. To smo uradili jer smatramo da će nam ta tehnologija omogućiti da iskoristimo potencijal, obećanje koje stoji iza sekvenciranja humanog genoma. Omogućiće nam da odradimo klinička istraživanja sa humanim ćelijama u posudi, dakle ne na životinjskim ćelijama, kako bismo došli do lekova i tretmana, koji su efektniji, sigurniji, brži i zahtevaju mnogo manje novca.
So let me put that in perspective for you and give you some context. This is an extremely new field. In 1998, human embryonic stem cells were first identified, and just nine years later, a group of scientists in Japan were able to take skin cells and reprogram them with very powerful viruses to create a kind of pluripotent stem cell called an induced pluripotent stem cell, or what we refer to as an IPS cell. This was really an extraordinary advance, because although these cells are not human embryonic stem cells, which still remain the gold standard, they are terrific to use for modeling disease and potentially for drug discovery.
Sada bih vam to predstavila u svetlu određenih saznanja. Ovo je zaista novo polje izučavanja. Humane matične ćelije su identifikovane 1998. i samo devet godina kasnije grupa naučnika u Japanu je uspela da od ćelija kože uz pomoć moćnih virusa napravi jednu vrstu pluripotentnih matičnih ćelija koje se nazivaju indukovane pluripotentne matične ćelije, a mi ih nazivamo iPM ćelije. Ovo je bilo otkriće koje pomera granice, bez obzira što te ćelije nisu humane matične ćelije, koje zaista jesu zlatni standard, one su odlično oruđe za modelovanje bolesti, i moguće čak i za otkrivanje lekova.
So a few months later, in 2008, one of our scientists built on that research. He took skin biopsies, this time from people who had a disease, ALS, or as you call it in the U.K., motor neuron disease. He turned them into the IPS cells that I've just told you about, and then he turned those IPS cells into the motor neurons that actually were dying in the disease. So basically what he did was to take a healthy cell and turn it into a sick cell, and he recapitulated the disease over and over again in the dish, and this was extraordinary, because it was the first time that we had a model of a disease from a living patient in living human cells. And as he watched the disease unfold, he was able to discover that actually the motor neurons were dying in the disease in a different way than the field had previously thought. There was another kind of cell that actually was sending out a toxin and contributing to the death of these motor neurons, and you simply couldn't see it until you had the human model.
Nekoliko meseci kasnije u 2008. jedan od naših naučnika je nastavio sa tim istraživanjem. Uzeo je uzorke biopsija kože, ovog puta od ljudi koji su bolovali od ALS-a ili kako je u Britaniji poznata - bolest motornih neurona. Potom je od njih napravio iPM ćelije o kojima sam vam upravo pričala, a onda je ove iPM ćelije, pretvorio u motorne neurone, koji su i sami umirali od te bolesti. Tako da je on u principu od zdrave ćelije napravio bolesnu ćeliju i uspeo je da reprodukuje nebrojeno puta bolest u laboratorijskoj posudi. To je vanserijsko otkriće, jer smo po prvi put imali u rukama model bolesti, od živog pacijenta i živih humanih ćelija. Dok je posmatrao tok bolesti, došao je do zaključka da u stvari motorni neuroni umiru u ovoj bolesti na drugačiji način u odnosu na ono što se pre toga mislilo. Postojao je još jedan tip ćelija koje su izlučivale otrov koji je doprinosio smrti tih motornih neurona, a to niste mogli da uvidite, dok niste baratali sa humanim modelom.
So you could really say that researchers trying to understand the cause of disease without being able to have human stem cell models were much like investigators trying to figure out what had gone terribly wrong in a plane crash without having a black box, or a flight recorder. They could hypothesize about what had gone wrong, but they really had no way of knowing what led to the terrible events. And stem cells really have given us the black box for diseases, and it's an unprecedented window. It really is extraordinary, because you can recapitulate many, many diseases in a dish, you can see what begins to go wrong in the cellular conversation well before you would ever see symptoms appear in a patient. And this opens up the ability, which hopefully will become something that is routine in the near term, of using human cells to test for drugs.
Tako da slobodno možete reći da su oni istraživači koji pokušavaju da razumeju uzrok bolesti, a da pri tome nemaju model od humanih matičnih ćelija, prilično nalik istraživačima koji pokušavaju da shvate šta se loše desilo u avionskoj nesreći, a da pri tome nemaju crnu kutiju ili snimak leta. Oni mogu da postave hipoteze o tome šta se loše desilo, ali nikako ne mogu zasigurno znati šta je dovelo do tih strašnih događaja. Matične ćelije zaista jesu crne kutije raznih bolesti, a to je neopisivo značajan prozor. To je vanserijski značajno jer možete da imitirate mnoge, mnoge bolesti u laboratoriji, možete uvideti šta se pogrešno dešava u komunikaciji između ćelija mnogo pre nego što uvidite same simptome kod pacijenta. Ovo otvara mogućnost koja će, nadamo se, uskoro postati rutinska stvar - mogućnost upotrebe humanih ćelija za potrebe testiranja lekova.
Right now, the way we test for drugs is pretty problematic. To bring a successful drug to market, it takes, on average, 13 years — that's one drug — with a sunk cost of 4 billion dollars, and only one percent of the drugs that start down that road are actually going to get there. You can't imagine other businesses that you would think of going into that have these kind of numbers. It's a terrible business model. But it is really a worse social model because of what's involved and the cost to all of us. So the way we develop drugs now is by testing promising compounds on -- We didn't have disease modeling with human cells, so we'd been testing them on cells of mice or other creatures or cells that we engineer, but they don't have the characteristics of the diseases that we're actually trying to cure. You know, we're not mice, and you can't go into a living person with an illness and just pull out a few brain cells or cardiac cells and then start fooling around in a lab to test for, you know, a promising drug. But what you can do with human stem cells, now, is actually create avatars, and you can create the cells, whether it's the live motor neurons or the beating cardiac cells or liver cells or other kinds of cells, and you can test for drugs, promising compounds, on the actual cells that you're trying to affect, and this is now, and it's absolutely extraordinary, and you're going to know at the beginning, the very early stages of doing your assay development and your testing, you're not going to have to wait 13 years until you've brought a drug to market, only to find out that actually it doesn't work, or even worse, harms people.
U ovom momentu, način na koji ispitujemo lekove je prilično problematičan. Da bi lek izašao na tržište, danas je u proseku potrebno 13 godina - a to je samo jedan lek, u sam proces se uloži oko 4 milijarde dolara, a samo 1% lekova koji uđu u sistem provere izađu na tržište. Ne možete zamisliti ni jedan posao koji biste spremno započeli, ukoliko raspolažete ovim brojkama. To je loš poslovni model. U suštini, to je još lošiji socijalni model, usled onoga što je u to uključeno i cene koju za to plaćamo. Danas pronalazimo lekove tako što testiramo jedinjenja koja obećavaju na ... nismo raspolagali modelima bolesti od humanih ćelija, tako da smo ih testirali na ćelijama miševa ili drugih stvorenja ili ćelija koje mi napravimo, ali one ne ispoljavaju osobine bolesti koje pokušavamo da izlečimo. Znate, nismo miševi, a ne možete prosto iz osobe koja boluje uzeti nekoliko ćelija mozga ili ćelija srca i onda pokušati u laboratoriji da isprobate delovanje obećavajućeg leka. Ali ono što vam matične ćelije danas omogućavaju je da stvorite avatare, možete stvoriti ćelije bilo da su u pitanju živi motorni neuroni ili ćelije srca koje pulsiraju ili ćelije jetre ili drugi tipovi ćelija i možete testirati lekove, obećavajuća jedinjenja na pravim ćelijama na koje i želite da utičete. Ovo je zaista važno jer ćete na samom početku mnogo znati, u vrlo ranim stadijumima razvoja vašeg eksperimenta i testiranja, nećete morati da čekate 13 godina dok lek ne izađe na tržište, da saznate da u stvari ne odrađuje posao ili još gore, da nanosi štetu ljudima.
But it isn't really enough just to look at the cells from a few people or a small group of people, because we have to step back. We've got to look at the big picture. Look around this room. We are all different, and a disease that I might have, if I had Alzheimer's disease or Parkinson's disease, it probably would affect me differently than if one of you had that disease, and if we both had Parkinson's disease, and we took the same medication, but we had different genetic makeup, we probably would have a different result, and it could well be that a drug that worked wonderfully for me was actually ineffective for you, and similarly, it could be that a drug that is harmful for you is safe for me, and, you know, this seems totally obvious, but unfortunately it is not the way that the pharmaceutical industry has been developing drugs because, until now, it hasn't had the tools.
Zaista nije dovoljno da samo analizirate ćelije koje su izolovane iz nekoliko ljudi ili grupe ljudi, ovde treba da zastanemo. Moramo sagledati širu sliku. Pogledaje okolo. Svi smo različiti, bolest od koje ja možda patim, ako bih imala Alchajmerovu ili Parkinsonovu bolest, verovatno bi drugačije uticala na mene nego na vas, i ukoliko bismo oboje patili od Parkinsonove bolesti, i uzimali iste lekove, ali pri tome imamo drugačiji genetički materijal, verovatno bismo pokazali različiti rezultat. Lako bi moglo da se desi da lek koji ima odličan uticaj na mene, uopšte ne deluje na vas i isto tako moglo bi se desiti da lek koji je loš za vas dobro deluje na mene. To deluje potpuno očigledno ali nažalost, to nije način na koji farmaceutska industrija razvija lekove jer su do sada za to nedostajala sredstva.
And so we need to move away from this one-size-fits-all model. The way we've been developing drugs is essentially like going into a shoe store, no one asks you what size you are, or if you're going dancing or hiking. They just say, "Well, you have feet, here are your shoes." It doesn't work with shoes, and our bodies are many times more complicated than just our feet. So we really have to change this.
Trebalo bi da zaboravimo na filozofiju "jedna veličina odgovara svima". Prosto način na koji smo do sada pronalazili lekove podseća na kupovinu cipela u prodavnici u kojoj vas niko ne pita za broj koji nosite, niti ih zanima da li idete na ples ili planinarenje. Samo bi rekli: "Pa, vi imate stopala, evo vam cipele." To ne funkcioniše sa cipelama, a naša tela su mnogo komplikovanija u odnosu na naša stopala. Tako da zaista moramo promeniti ovo.
There was a very sad example of this in the last decade. There's a wonderful drug, and a class of drugs actually, but the particular drug was Vioxx, and for people who were suffering from severe arthritis pain, the drug was an absolute lifesaver, but unfortunately, for another subset of those people, they suffered pretty severe heart side effects, and for a subset of those people, the side effects were so severe, the cardiac side effects, that they were fatal. But imagine a different scenario, where we could have had an array, a genetically diverse array, of cardiac cells, and we could have actually tested that drug, Vioxx, in petri dishes, and figured out, well, okay, people with this genetic type are going to have cardiac side effects, people with these genetic subgroups or genetic shoes sizes, about 25,000 of them, are not going to have any problems. The people for whom it was a lifesaver could have still taken their medicine. The people for whom it was a disaster, or fatal, would never have been given it, and you can imagine a very different outcome for the company, who had to withdraw the drug.
Desilo se nešto veoma tužno u poslednjoj deceniji, a oslikava upravo to. Postoji odličan lek, grupa lekova u stvari, ali ovaj specifičan lek je Vioks. Ljudima koji su patili od teškog hroničnog bola izazvanog artritisom, lek je spasio život, ali nažalost, kod jedne grupe ljudi lek je doveo do teških komplikacija u radu srca. Kod podgrupe tih ljudi ti sporedni efekti su bili zaista ozbiljni, ometanje rada srca je dovelo do fatalnog ishoda. Ali zamislite drugačiji scenario, gde bismo imali čitav niz uzoraka, genetički različit niz uzoraka ćelija srca, gde bismo mogli da zaista proverimo delovanje leka Vioksa u samim petri-šoljama i uvidimo da bi ljudi sa ovim genima patili od kontraindikacija, ali ljudi tačno određene genetske podgrupe ili genetičke veličine cipela i to oko 25 000 njih, ne bi doživelo nikakav problem. Ljudi kojima bi lek spasao život, bi i dalje mogli da primene lek. Oni ljudi za koje bi kontraindikacije bile neprihvatljive ili fatalne nikada ne bi ni dobili lek. Sada možete zamisliti potpuno drugačiji rezultat za samu kompaniju koja je morala da povuče lek sa tržišta.
So that is terrific, and we thought, all right, as we're trying to solve this problem, clearly we have to think about genetics, we have to think about human testing, but there's a fundamental problem, because right now, stem cell lines, as extraordinary as they are, and lines are just groups of cells, they are made by hand, one at a time, and it takes a couple of months. This is not scalable, and also when you do things by hand, even in the best laboratories, you have variations in techniques, and you need to know, if you're making a drug, that the Aspirin you're going to take out of the bottle on Monday is the same as the Aspirin that's going to come out of the bottle on Wednesday. So we looked at this, and we thought, okay, artisanal is wonderful in, you know, your clothing and your bread and crafts, but artisanal really isn't going to work in stem cells, so we have to deal with this.
To je odlično, pomislili smo, u redu, ako pokušavamo da rešimo ovaj problem jasno je da moramo da razmišljamo o genetici, moramo razmišljati o humanim modelima bolesti, ali tu postoji i osnovni problem jer su u ovom momentu, bez obzira koliko su zadivljujuće, matične ćelije i linije tih ćelija su samo grupe ćelija, koje je neko ručno napravio, jednu po jednu, a za to je neophodno nekoliko meseci. Ta brzina produkcije se ne može povećavati, a isto tako kada radite ručno stvari čak i u najboljim laboratorijama, dolazi do varijacija u tehnikama, a neophodno je da znate, ukoliko proizvodite lek, da je aspirin koji ste uzeli iz boce u ponedeljak, isti kao i aspirin koji će se naći u toj boci u sredu. Razmislili smo o tome i zaključili da je ručni rad zaista divna stvar u proizvodnji odeće, hleba i predmeta, ali ručni rad neće biti primenljiv u radu sa matičnim ćelijama. Morali smo da rešimo to.
But even with that, there still was another big hurdle, and that actually brings us back to the mapping of the human genome, because we're all different. We know from the sequencing of the human genome that it's shown us all of the A's, C's, G's and T's that make up our genetic code, but that code, by itself, our DNA, is like looking at the ones and zeroes of the computer code without having a computer that can read it. It's like having an app without having a smartphone. We needed to have a way of bringing the biology to that incredible data, and the way to do that was to find a stand-in, a biological stand-in, that could contain all of the genetic information, but have it be arrayed in such a way as it could be read together and actually create this incredible avatar. We need to have stem cells from all the genetic sub-types that represent who we are.
Čak i kada bismo to rešili, preostajao bi nam je još jedan veliki problem, problem koji nas vraća na mapiranje humanog genoma, jer smo mi svi različiti. Iz sekvenciranja ljudskog genoma znamo da je sastavljen od A, C, G i T slova, koja čine naš genetski kod, ali taj kod sam po sebi, naša DNK, je isto što i zapis gomile nula i jedinica u računarskom kodu, bez računara koji taj kod može da pročita. To bi bilo kao da imate aplikaciju, a nemate pametni telefon da je primenite. Neophodan nam je proces koji će primeniti biološka znanja na tu ogromnu količinu podataka, a način da se to uradi jeste da nađete zamenu, biološku zamenu koja u sebi sadrži sve te genetičke informacije, ali koje su na takav način poređane i utisnute da mogu biti istovremeno pročitane i na taj način formiraju ovaj neverovatan avatar. Nephodne su matične ćelije napravljene od svih genetičkih pod-tipova, koje prezentuju našu sliku.
So this is what we've built. It's an automated robotic technology. It has the capacity to produce thousands and thousands of stem cell lines. It's genetically arrayed. It has massively parallel processing capability, and it's going to change the way drugs are discovered, we hope, and I think eventually what's going to happen is that we're going to want to re-screen drugs, on arrays like this, that already exist, all of the drugs that currently exist, and in the future, you're going to be taking drugs and treatments that have been tested for side effects on all of the relevant cells, on brain cells and heart cells and liver cells.
Zato samo napravili ovo. Ovo je automatska, robotizovana tehnologija. Poseduje kapacitet proizvodnje hiljada i hiljada različitih linija matičnih ćelija. A pričamo o genetičkom čipu. Karakteriše ga enormna mogućnost paralelnog procesovanja podataka, i promeniće način na koji pronalazimo lekove, nadamo se. Mislim da će upravo to dovesti do ponovnog testitranja svih lekova, na ovakvim biološkim uzorcima, lekova koji već postoje, svih lekova koji su trenutno u upotrebi, tako da ćete u budućnosti koristiti lekove čiji su mehanizmi delovanja i nuspojave delovanja provereni na odgovarajućem tipu ćelija, na ćelijama mozga, srca, jetre.
It really has brought us to the threshold of personalized medicine. It's here now, and in our family, my son has type 1 diabetes, which is still an incurable disease, and I lost my parents to heart disease and cancer, but I think that my story probably sounds familiar to you, because probably a version of it is your story. At some point in our lives, all of us, or people we care about, become patients, and that's why I think that stem cell research is incredibly important for all of us. Thank you. (Applause) (Applause)
Ovo nas je stvarno dovelo do samog praga razvoja personalizovane medicine. To se u ovom momentu dešava, u mojoj porodici, moj sin boluje od dijabetesa tipa 1, to je i dalje neizlečiva bolest, a moji roditelji su umrli od bolesti srca i raka i ubeđena sam da svi delimo slične priče, i vaša priča podseća na moju. U jednom trenutku u svojim životima, svi mi ili ljudi do kojih nam je stalo, postajemo pacijenti i baš zato smatram da je istraživanje matičnih ćelija neverovatno važno za sve nas. Hvala vam. (Aplauz) (Aplauz)