Chemist Hans Clevers replaces worn-down body parts with organoids created outside the body

Dutch chemist Hans Clevers makes organoids (living organs outside the body) out of stem cells. If every human body part can be replaced by organoids, what defines a human?

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00:00:00 My name is Hans Clevers, I have been working in Utrecht for a long time.
00:00:03 First I worked at the teaching hospital...
00:00:08 and since 2002 my laboratory is at the KNAW Hubrecht Institute.
00:00:13 Over the years I have tried to answer the question
00:00:21 of how we succeed to become ourselves out of one singular cel,
00:00:26 the fertilized ovum.
00:00:28 This is the science of developmental biology,
00:00:33 it has taken us on a journey through many different fields of study.
00:00:37 We started as immunologists,
00:00:38 the study of the body's defence system.
00:00:41 We've occupied ourselves with frogs and fruit flies and worms.
00:00:44 For the past fifteen years we've primarily worked on adult stem cells,
00:00:49 we've done a lot on mice
00:00:51 and for the last couple of years, since we know more about how it works,
00:00:55 we've also done this with human stem cells.
00:00:58 That's quite a story, I'm going to split it into smaller parts.
00:01:06 But it's good you mentioned all of it. What is your field of study?
00:01:16 My field of study is medical biology,
00:01:20 everything that has to do with animals an humans,
00:01:24 how we come into existence, how we enduringly stay healthy,
00:01:27 but also how we become ill, and how we eventually repair damaged tissue.
00:01:33 What does you research concentrate on? What is your domain in this area?
00:01:45 We've never allowed ourselfs to be restricted by scientific disciplines.
00:01:51 We've frequently crossed borders,
00:01:55 but the unifying factor is technology, it has been a lot of DNA technology,
00:02:01 which went through an explosive growth since the '80.
00:02:04 Every time a technical step was taken, we could take up new questions.
00:02:09 That is actually what we do,
00:02:11 whether it concerns a fruit fly or a human, doesn't really matter to us.
00:02:16 And what is your speciality?
00:02:18 At the moment it is stem cells and cancer research,
00:02:22 in particular the link between the two. A cancer cell is actually a derailed stem cell.
00:02:28 Really, is it that simple?
00:02:30 Yes, well...
00:02:33 What does a stem cell, the way we sit here, do?
00:02:36 So not the stem cells that we are made out of very early on in our existence, three days after fertilization,these exist shortly,
00:02:43 then they dissapear.
00:02:45 But the way I sit here, every organ has it's own specialized stem cells.
00:02:51 What are these stem cells good at? They lay low when they are not needed, they don't devide themselves.
00:02:55 But when tissue is damaged, they renew the tissue,
00:03:02 they can resist a lot of radiation and abuse.
00:03:08 That's exactly like cancer cells, they can handle anyting, cystostatics, radiation,
00:03:14 they can sleep for years before becomming active again.
00:03:17 But they've lost the brake to stop once they should be done.
00:03:21 So the cancer cell is like a natural enemy for the stem cell?
00:03:24 It's the doctor Hyde... What are they called?
00:03:29 Dr. Jeckyll and Mr. Hyde.
00:03:32 It's the downside of having stem cells, they sometimes go astray,
00:03:39 and become our worst enemy.
00:03:42 So if you compare it to good and evil....?
00:03:46 That comes very close, we all struggle with aging.
00:03:51 Can we only live till we're eighty, or is there no limit to aging?
00:03:55 I'm convinced we've been designed to live for about eighty, ninety years.
00:03:59 That's plenty of time to bring children and grandchildren into the world.
00:04:05 But then it's time to step off the stage, evolution must be able to do it's work,
00:04:09 which means selected generations eventually need to dissapear.
00:04:13 We're not built to live longer than eighty to ninety years,
00:04:16 on average our stem cells are capable to repair our organs over that period of time,
00:04:23 but in the end they wil start making mistakes and finally we will all encounter cancer.
00:04:28 Yes, yes...
00:04:30 I can explain it simpler and shorter, but that's actually...
00:04:35 What isn't done very much, we study healthy stem cells, and how they aid in staying healthy over time,
00:04:43 as well as the malignant stem cells.
00:04:46 They are so much alike, from each one you learn about the other,
00:04:52 it works both ways. We simultaneously do cancer research and stem cell research.
00:04:56 Everytime we make progress in one field, we can translate it to the other field.
00:05:01 For example, how does a stemcell in the intestine regenerate?
00:05:04 A cancer cell turns out to use the exact same process as the normal cell, but has lost the off switch.
00:05:14 So it's the like the naughty child?
00:05:17 Yes, yet in my experience a child can be controlled,
00:05:24 but cancer cells have lost the ability to be controlled.
00:05:28 And then, what can you do?
00:05:31 Designing therapies to battle cancer is very complicated,
00:05:38 because almost any other disease comes from the outside.
00:05:42 Aids is a good example, unknown in 1980 and resolved by 1985.
00:05:48 An exernal disease-causing agent,
00:05:50 completely different from anyting in our body.
00:05:53 It's not that complicated to rapidly develop a few drugs
00:05:56 that at first may not be excellent but are quickly much better
00:05:58 at combatting the virus, but not you own cells.
00:06:02 A cancer cell is you, yourself.
00:06:06 Our genetic information consists of three billion letters, Gs As Ts and Cs.
00:06:11 It only takes three to four errors in those three billion letters for a normal cell to turn into a cancer cell,
00:06:19 that's a tiny difference, enough for the cell to keep growing, but very difficult to target with therapy.
00:06:26 If you aim a little too wide, you target every cell in the body,
00:06:31 you have to try to aim at those few little mistakes that distinguish the cancer cell from your normal cells.
00:06:38 That is a huge challenge.
00:06:40 Are you kind of like a cryptologist?
00:06:43 We do a lot of DNA analysis,
00:06:47 other colleagues do this more in-depth, we mostly use it,
00:06:52 and it is indeed like decoding a book.
00:06:56 A book we now know has more than one code, maybe three or four or even many more.
00:07:02 Codes we didn't even suspect existed.
00:07:05 Interestingly physicists approximately know what they don't know,
00:07:08 the dark matter, eighty percent of the universe.
00:07:11 We don't know what we don't know,
00:07:14 every few years a new system is discovered, one we never needed to explain the way that things are.
00:07:20 A new principle emerges, which turns out to be half of biology's foundation, but we never missed it in our explanations.
00:07:28 This has already happend three or four times.
00:07:29 It's usually a code in the genetic information we hadn't seen.
00:07:36 So there many you don't know of yet?
00:07:40 There used to be talk of one or two percent serious code
00:07:44 and 98 percent "junk DNA".
00:07:47 By now we can probably understand about ten percent,
00:07:51 but in the other 80 percent there is undoubtedly much more hidden we still need to discover.
00:07:57 Let's get back to the stem cell research you do, what is that like?
00:08:07 The research or the stem cell?
00:08:10 The research of the stem cell. I have no...
00:08:16 You can't imagine... Let me try to explain how it's done.
00:08:21 Everyone knows, if you hurt yourself, if you have a scrape wound, it heals.
00:08:29 If you look at it with a microscope, you see many cells are dead or gone, and they are replaced.
00:08:37 After two to three weeks the skin is healed.
00:08:42 Most of our organs can do this,
00:08:44 we are still searching for stem cells in the heart,
00:08:46 it's unclear of they excist, there are even stem cells in our brain.
00:08:49 What a stem cell does, in theory,
00:08:52 many haven't been discovered yet,
00:08:53 but they can repair damaged cells, they can replace lost tissue.
00:09:09 So that's my definition, this field is quite young,
00:09:13 there are many dogma's that turned out to be wrong.
00:09:19 We try to stick to this: which cell, in a surtain organ, helps this organ to replace cells and tissue.
00:09:29 How do you recognize those cells?
00:09:31 Yes, then the next question is how to recognize them.
00:09:32 First off, they need to be able to multiply,
00:09:34 that is what they do when they are active.
00:09:36 That is is way to spot them.
00:09:38 the very strong convictions on how a stem cell should look were problematic for us,
00:09:46 they would be very rare, extreemly small,
00:09:50 they never or rarely multiplied, their offspring would multiply a lot.
00:09:57 So they were defined as cells that you would hardly be able to find.
00:10:02 Nowadays we can use many genetic tricks.
00:10:07 We can replace the genetic code in mice, while sitting behind a computer.
00:10:15 We can change or improve it.
00:10:17 That way we can make a mouse that has exactly the alteration in it's code we need.
00:10:22 For example, if we see a surtain type of cell,
00:10:28 in the mouse's intestine and we think it might be the intestine's stem cell,
00:10:33 that is how we started,
00:10:35 we can make a mouse who's stem cells lights up.
00:10:38 It's a hereditary trait stolen from fire flies
00:10:44 we write an email to the man in Califonia who discovered this,
00:10:48 he puts some of this DNA on a coffee filter, sends it to us by fedex,
00:10:53 we put in in a tube with water, and then we have the DNA code for giving off light.
00:10:58 We can place it in the mouse, it's not that simple,
00:11:02 but we do it in such a way that the cell will light up.
00:11:08 That makes it much simpler, we can easily spot them,
00:11:13 we can take them out of the mouse, because they light up and the other cells do not.
00:11:16 Back then we used a second trick,
00:11:20 from the outside, we can inject a three to four months old mouse with something
00:11:27 and we activate something else we built in,
00:11:30 then only the permanent cells can give themselves a colour.
00:11:35 They light up, but if they are no longer stem cells they won't light up anymore,
00:11:38 when we colour a cell, every cell that comes from that cell, will have the same colour.
00:11:48 so you can wait for a year, after a day you see one blue cell,
00:11:54 but after a year you see a whole part of the intestine had coloured blue,
00:11:58 that way you see the cell indeed is a stem cell,
00:12:03 you have formal evidence.
00:12:04 Those are the tricks we can use in mice.
00:12:10 And do you think that when a stem cell has multiplied, the new cell has stem cells?
00:12:15 Well, that was also a dogma,
00:12:17 once a stem cell multiplies it makes one new stem cell and a daughter cell,
00:12:20 the daughter cell goes futher through the system, but has a short life.
00:12:23 But we see this isn't true.
00:12:26 If you loose many stem cells, the remaining stem cells immediatly replenish the shortage.
00:12:32 And if you loose all of you stem cells, cells that were on their way out can turn back and become stem cell.
00:12:42 It's a very artificial system,
00:12:44 we didn't know this,
00:12:45 the dogma was that it didn't work this way,
00:12:47 it was a challenge to dismiss these convictions I had been taught since elementary school,
00:12:53 to look at those stem cells in a different way.
00:12:57 What is your field, what in you research makes you a front runner, what discoveries enjoy international interest?
00:13:28 If I look at the subjects I'm asked to speak about at conventions, it started about fifteen years ago,
00:13:36 by accident we discovered how colon cancer arises,
00:13:41 we became interested in the intestine's stem cells,
00:13:43 we discovered that in the '60 it was described as the most active stem cell in our body,
00:13:48 we thought this would make it the easiest to study, we just needed to find it.
00:13:52 That took a while, but when we found the intestenal stem cell,
00:13:57 we discovered nothing that was known about stem cells was actually true.
00:14:01 For example, I think this is what we are most know for,
00:14:05 a very powerful dogma was that a healthy cell,
00:14:09 put onto a petri dish with a culture medium would die after a few days.
00:14:19 The only cells that would grow well were cancer cells.
00:14:23 All the research on cells, outside of the body of humans or mice, has been on cancer cells.
00:14:31 Almost all discoveries within the biomedical science, are based on cancer cells.
00:14:35 Because you can endlessly multiply them.
00:14:38 How is that possible? I don't understand. How come healthy cells die after a few days, but cancer cells don't?
00:14:46 That was the observation, from the '60 people tried to cultivate cells
00:14:52 after a few attempts it turned out to be quite easy to keep tumor cells alive,
00:15:04 tumor cells look a lot like the tissue they originate from, they are like malignant stem cells.
00:15:12 That was a dogma, you would read is was impossible to keep healthy cells alive for more than a few days.
00:15:20 But when we made the stem cells visible in mice,
00:15:23 using the trick to let them light up, we could see that they split every day.
00:15:28 However, it was thought they multiplied just once a year.
00:15:31 We thought, if they split every day,
00:15:34 they will do this a thousand times in a the lifetime of a mouse, about three years.
00:15:40 We have to be able to recreate this in a lab.
00:15:43 If you understand it, nothing is impossible within biology.
00:15:47 Eventually it turned out to be quite simple, the hardest thing was convincing someone in my lab that we needed to do this.
00:15:55 Everyone was convinced it would be a waste of time and effort.
00:16:00 A japanese scientist, TOSHIRO SATO, started working on it, and accomplished it in a couple of months.
00:16:06 What did he do exactly?
00:16:07 What you need...
00:16:09 Can you briefly explain?
00:16:12 He extracted those luminous stem cells from the mice,
00:16:16 everyone knew this was possible,
00:16:18 what the cells need to grow in culture are the right nutrients.
00:16:22 Epo is what bicyle racers take, it activates the stem cells in you bone marrow,
00:16:27 they in turn make red bloodcells, so you can cycle faster.
00:16:29 We thought we needed substances like that, and we discovered which ones.
00:16:33 A combination of three substances was added to the stem cell and it never stoped growing.
00:16:39 It grows ten times bigger each week.
00:16:41 If we had saved all that tissue we could have filled the whole universe.
00:16:46 A physisist could calculate it...
00:16:50 It grows endlessly?
00:16:51 Yes, it grows endlessly, you can see it grow under a microscope.
00:16:56 We can film it if you like, it just never stopped.
00:17:00 The first mouse we used has been dead for three years, but the cells continue to grow.
00:17:05 So we thought it must have turned into cancerous cells...
00:17:09 Wait a moment, so you have found something that doesn't die?
00:17:16 Yes.
00:17:18 Isn't that sort of a code of life you have found? Eternal life?
00:17:26 Yes, well, let me finish the story, you'll be better able te understand.
00:17:35 The stem cell of the intestine was the most active,
00:17:39 so at first people told us it could not be the stem cell because it didn't fit the criteria.
00:17:46 It does grow the intestine, so it must be the stem cell.
00:17:52 It took a couple of years before people accepted this.
00:17:55 Then we thought, it splits so fast, we must be able to copy that.
00:17:58 It was thought to be impossible, healthy cells could not survive outside the body,
00:18:03 however it did turn out to be possible.
00:18:05 We became facinated with this possibility and thought, what about other tissue,
00:18:12 tissue that doesn't devide so quickly.
00:18:14 Your intestine devides every day, but not much happens in your liver.
00:18:18 Or in your pancreas, prostate or lungs.
00:18:23 But they can repair themselves, if you binge on alcohol,
00:18:28 your liver is damaged, your stem cells are activated and repair the damage.
00:18:32 TOSHI had the mice in front of him and tried it with their pancreas, and it also grew.
00:18:41 This was a stem cell that is usually very quiet,
00:18:44 one that is only temporarily active and then sort of goes to sleep again.
00:18:47 So that opened the floodgates, we could try it for all the organs, we just needed to find the right nutrients.
00:18:55 And soon we could do the liver, prostate, lungs, kidneys.
00:19:00 We can cultivate kidney cells out of the urine of children.
00:19:05 Kidney tumor cells, right out of a tube of urine.
00:19:09 Out of a bit of saliva we can cultivate lung cells.
00:19:11 I'm trying follow, it's going quite fast. So in the intestines you found something that could live outside of the body, and even continues to grow.
00:19:20 It makes miniature intestines, we thought, if we succeeded we would make a lump of stem cells.
00:19:27 But it turns out they form a miniature version of the intestines.
00:19:32 It is shaped like a ball with protrusions, you can shape it like a tube.
00:19:39 So we can make two centimeters of intestine out of one cell.
00:19:44 And all of it is under a microscope, we can film it.
00:19:47 I would like to see that!
00:19:50 You can really just do that?
00:19:52 Well... not me, but...
00:19:54 You said it can be filmed, so when we're at the lab...
00:19:58 You can see those miniature organs with your bare eyes,
00:20:02 but they don't have a blood supply, so their growth is limited,
00:20:06 they need to have oxygen and nutrients, and waste needs to be filtered out.
00:20:12 These things are called organoids,
00:20:16 the past couple of years a whole new field developed, I think we were one of the two founders, SASAI, whom I previously mentioned was the other.
00:20:25 So now we are trying to make the organoid more complete,
00:20:30 with blood vessels, white blood cells, gut flora for the intestines, to see if it will function the same.
00:20:39 It is a whole new technology.
00:20:42 It's the cell by cell construction of organs and maybe even more?
00:20:46 The main idea is, this is long term research, but we think it will be possible,
00:20:51 that we won't need organ transplantations anymore,
00:20:55 you can take tissue from a living donor, cultivate it to be much more,
00:21:02 then freeze it, you can freeze cells and keep them for years.
00:21:05 And when someone needs a new liver, and the liver's infrastructure is present,
00:21:10 but the cells are ill, in theory, and in animal testing,
00:21:15 you can place a couple of stem cells from a living voluntary donor, which you can keep in the freezer,
00:21:21 and a stemcell will repair the liver.
00:21:25 It would take a while, but you could use stem cells to make someone repair his own damaged liver.
00:21:33 So that would be possible?
00:21:34 We can already do it in mice.
00:21:37 To be allowed to test it in humans is very complicated and the logistics... it would not be cheap.
00:21:43 But the proof of principle exists, we've supplied it, as have others.
00:21:50 So is it's just a matter of time?
00:21:50 Yes, and a large number of funds.
00:21:56 To translate such an insight into a therapy, you'll need corporations, it's not possible in an academic setting.
00:22:05 Yes, but it is possible, you've proved it...
00:22:09 The most important thing we've proved is that
00:22:13 the way people thought stem cells looked,
00:22:17 that they were undetectable, is all wrong.
00:22:20 They are easily detectable, if you search well and know what to look for.
00:22:24 We've clarified many things, but with our mice, the luminated ones, other laboratories have found other stem cells.
00:22:33 In the inner ear for example, if you lose those you become deaf.
00:22:37 Tasting buds on the tongue, a lab in the United States... all the same type of stem cells.
00:22:43 So that was the first, find the stem cells, if you know what they look like, you can learn to manipulate them.
00:22:49 The second thing is we countered the belief that it would be impossible to multiply them outside of the body.
00:22:55 The third thing is, they actually make a miniature version of the organ, we were surprised about this as well.
00:23:01 It is very interesting to see how they do this, we can see that they do it,
00:23:05 and we pretend we discovered it all.
00:23:08 We just give them a nudge in the right direction and they start to make the organ, but we have no idea how.
00:23:13 What happed to you when you saw that?
00:23:18 Well the first time...
00:23:20 People often talk of their eureka moment, it's the same,
00:23:23 the belief that something is correct grows,
00:23:25 Toshiro, the Japanese colleague,
00:23:28 when he came in he had ruined a piece of equipment.
00:23:31 His colleagues were temporarily not very fond of him, he became a bit isolated.
00:23:35 I hadn't talked to him much.
00:23:36 One day I walked into the lab, and asked him if the cells were growing, and he replied "Yes!"
00:23:41 And I asked him for how long they'd been growing, and he told me for about three months!
00:23:45 I asked him why he didn't tell me, he replied "You didn't ask."
00:23:49 I looked throught the microscope, I could see the cells were healthy, it was just beautiful!
00:23:57 I still have the images...
00:23:59 How big were they?
00:24:01 Large under the microscope, but about two, three milimiters in real life.
00:24:05 But if you've studied cells before, you can just see it, they were very healthy.
00:24:09 The cells had been growing for three months, while they should have been dead after a day.
00:24:15 Could you believe it?
00:24:16 Yes, immediatly. That wasn't a problem.
00:24:19 What did you do?
00:24:22 I told the others in the laboratory of course.
00:24:25 TOSHI deserved to have a different position in the lab.
00:24:29 And we tried to show as many people as possible.
00:24:34 In a scientific career... Then it's locked down, you have the evidence. You must celebrate this, I assume?
00:24:49 Yes, but you know it's not finished yet.
00:24:51 You need to build the story.
00:24:54 You need to convince other colleagues, that was the hardest.
00:25:01 We tried to publish our paper, and encountered many difficulties.
00:25:08 The first was people thought they already knew how it was done,
00:25:09 that is wasn't possible,
00:25:12 so it wasn't exactly new, and it wasn't deemed possible.
00:25:16 It took one an a half years to get the paper published.
00:25:21 Then people read the paper and think, yeah, they might have done it, but still have their doubts.
00:25:28 It takes a couple more years before others try to do it themselves, it's not simple,
00:25:32 you need to have a numbre of things in order.
00:25:34 For the past three or four years people are starting te realize it is in fact quite easy,
00:25:40 you need some experience, but you can do it with any organ.
00:25:46 It is possible with any organ, you did it with the intestines, those cells were easy to find. But you can do it with any of your body's organs?
00:25:59 Outside of the body? -Outside of the body.
00:26:01 We usually first try it with mice, then with humans.
00:26:07 Humans are a bit more complicated, it grows a little slower compaired to the tissue of mice.
00:26:11 But so far we've succeeded with every organ we tried.
00:26:15 The criterium is they need to be able to grow for at least a year.
00:26:19 And at the end of the year they need to be normal.
00:26:22 You can read the DNA material, the fear is there will be a mutation, a cancer.
00:26:28 You can regognize those, but we never find them.
00:26:31 The cells really stay healthy, it's like you literally took them out of a body.
00:26:36 So in you lab, you have department with living tissue...
00:26:45 Human living tissue, yes.
00:26:48 And is that personal or not?
00:26:53 To us, no. They are just cells.
00:26:56 But it has a lot to do with ethics of course.
00:26:57 we get all the human tissue from hospitals.
00:27:02 We deal with many regulations, informed consent, medical ethical committees are involved.
00:27:08 We are constucting large bio banks, we can do it with healthy tissue, but also with many forms of unhealthy tissue.
00:27:15 Interessting to research, interesting for the development of medication.
00:27:20 But what we are expanding on at the moment is using someone's sick cells to find the best personal medicine.
00:27:30 We're doing this for cystic fibrosis, there are a couple of drugs, that are very expensive, and it is unclear who will respond well to it.
00:27:36 All the patients want it, there is nothing else.
00:27:40 We now have a test that can see it this drug, that costs half a million a year, for eighty years, if it works their life expectancy is normal.
00:27:51 In our lab we can see, within a week, which drug will or will not work for you.
00:27:57 We're doing this, a great number of patients can't try these drugs, their insurance will not pay for it.
00:28:07 But when can prove it will work for the patient, then the insurance will cover it.
00:28:12 Now there are a few children walking around with the results of our organoid tests.
00:28:21 That is a wonderful application.
00:28:26 And it is easier than giving the stem cells to the patient.
00:28:30 we've shown we can take stem cells from a cystic fibrosis patients, hereditary disease, DNA error.
00:28:37 We can repair it using the CRISPR-Cas9 technique.
00:28:44 You can repair it from behind you computer, we already did this three years ago.
00:28:49 We cultivated stem cells for two patients, found repaired the error.
00:28:54 Then checked the whole DNA sequence.
00:28:59 We now have those cells.
00:29:01 If we would return the cells to the patients, the illness would be cured.
00:29:06 We still have a long way to go, doing this is not allowed yet.
00:29:09 But is is promising for the future.
00:29:11 If it would be allowed, this is what would happen?
00:29:12 It depends, not every organ is easily transplanted using stem cells.
00:29:17 The liver would be easy,
00:29:18 the lungs would be more difficult.
00:29:20 However we think this is the best way to attack hereditary disseases.
00:29:28 Repairing stem cells outside of the body.
00:29:31 I'm still stuck in you lab, where you've collected cells and issue that won't die. It's facinating, isn't it?
00:29:47 Well, we already knew, stem cells can keep our tissue intact for a long period of time.
00:29:58 What we've shown is you can take stem cells and multiply them outside of the body.
00:30:05 And in theory you could endlessly renew organs.
00:30:11 Like replacing parts on a car.
00:30:17 Over time we'll be able to do it for every organ,
00:30:21 In the end the question is, what will stand inbetween us and eternal life.
00:30:28 For me, that's our brain.
00:30:31 Where all your emotions and memories are stored.
00:30:37 You can't replace that with stem cells.
00:30:40 But you don't know yet?
00:30:42 There are science fiction writers...
00:30:45 There isn't that much information stored in your brain.
00:30:48 I think a large USB memory stick or hard drive could store it.
00:30:53 When we know how our brain works,
00:30:58 you could download everything, get a new brain and upload it again.
00:31:03 Sciencefiction...I think it would be very complicated ethically.
00:31:09 I understand, but if everything if made up of stem cells...
00:31:17 And is replacable...
00:31:19 What is interesting, we used to be taught you're born with a fixed amount of brain cells,
00:31:27 which are made in your first year.
00:31:32 But now some parts of the brain, like the hippocampus, have stem cells.
00:31:37 The memory department, keeps making new cells, keeps storing new memories.
00:31:45 No one knows what the relationship is, but it's the primary location of human brain stem cells.
00:31:54 Large parts of the brain probably don't have stem cells.
00:31:58 So what you have is what you've got.
00:32:01 So in the worst case, you're really stupid?
00:32:08 If you don't have a brain? You must be.
00:32:11 You wouldn't be able to do much...
00:32:13 The brain is quite important for controlling the body.
00:32:17 I've asked this before, but we didn't get to it. It sounds like you are occupied with the code of life.
00:32:27 Yes, yes. In my opinion the border of the individual being becomes a bit vague.
00:32:36 It generates many ethical questions.
00:32:40 If you think about species, my DNA code is mine, but it's not very different from yours,
00:32:47 and even less different from my parents'.
00:32:50 The DNA code is what makes our species.
00:32:54 Passed down from generation to generation. It hasn't been changed much for over three thousand years.
00:32:59 My body is just the carrier, the DNA gets passed on.
00:33:04 With our technology it's not just the code which is abstract, but parts of my body...
00:33:10 I just told you about that mouse. It died three years ago, but it's stem cells keep growing.
00:33:17 So the end of the life of most organ, turns out not to be so definite.
00:33:26 What does that mean?
00:33:29 Medically, it means you can keep people healthy for a longer time.
00:33:35 If you contemplate what you really are, I arrive at the things that are in my head.
00:33:45 Not much else about me is unique. My DNA code.
00:33:51 But in my body everything can be replaced. Like we now know how to do.
00:34:06 I think that's exeptional.
00:34:10 In biology, my life is just information.
00:34:17 The information stored in my brain,
00:34:22 and the information in my DNA. Given to me through evolution.
00:34:27 But my matter is completely replacable.
00:34:31 So you're a piece of information.
00:34:36 Do you understand?
00:34:38 Yes, I do. We're a code that can be programmed.
00:34:49 Yes.
00:34:54 The code can be programmed. We've known this for a long time.
00:34:56 There is great amount of resistance, ethical obstacles.
00:35:00 But we've know for a long time.
00:35:01 We only know a small part of the code,
00:35:03 but in biology, discovering something can be hard,
00:35:09 but it is always easy to understand.
00:35:12 If you understand the principle, you can apply it. You can do it in the lab.
00:35:17 I'm convinced that we can understand and copy everything nature does.
00:35:24 We can even change it, but in the distant future.
00:35:29 But it won't become more abstract or complicated.
00:35:31 We learn more and more, but we always still comprehend it.
00:35:40 I feel that is different in physics and mathematics.
00:35:43 The further you go, the less comprehendable it becomes.
00:35:48 In biology, you can always explain things.
00:35:51 You explain it very well. It's really facinating,
00:35:57 your body is your vehicle, broken parts can be replaced. Like car parts.
00:36:18 It sounds like science fiction. But is isn't.
00:36:21 We regularly do organ transplantations, but not often enough.
00:36:27 We've been doing blood transfusions for eighty years or so.
00:36:32 This is more complex, but it is not different.
00:36:37 I am diabetic. My pancreas has sort of stopped working. Can that be solved?
00:36:50 You're probably a type 1 diabetic, so you don't have any beta cells.
00:36:56 There a huge field of research on making new beta cells. Cells that make insulin.
00:37:03 For some reason it works up to the last step, but then something is missing.
00:37:14 You could do it with your cells.
00:37:17 We could do it in my lab, with cells from your pancreas. Also, we could use a trick, using your skin cells, turning them into pancreas cells.
00:37:26 You can instruct them to produce hormones.
00:37:29 But what we can't do yet, is the final step. We can't place them back.
00:37:39 When you start making beta cells, they'll be destroyed.
00:37:45 For some reason you immune system thinks of the beta cell as it's enemy.
00:37:49 So that is a second obstacle, protecting the cells from your immune system.
00:37:55 You need to keep the immune system away from the cell,
00:37:58 or change the cell so it won't be seen as an enemy.
00:38:04 I don't know how to do it, but you say eventually it will be possible.
00:38:07 Not at the moment. But when I see how easy it is to make other tissue It'll just be a matter of time.
00:38:14 A lot of time?
00:38:18 Predicting science is always hard.
00:38:21 I think it really just takes one more discovery. It could be tomorrow.
00:38:30 But maybe they're not thinking of the right thing, of the right thing isn't available yet.
00:38:36 It might take ten years.
00:38:38 What do you dream of?
00:38:39 Regarding my own work...
00:38:43 Doesn't matter, about anything...
00:38:45 I hope to continue doing this for a long time, that's my biggest dream.
00:38:52 That I can experience from up close,
00:38:55 how biological science is exploding into a wealth of knowledge,
00:39:01 we wouldn't have dreamed of thirty years ago.
00:39:03 And that I can contribute.
00:39:06 I don't feel like I have to solve a big problem all by myself,
00:39:11 I'm part of an international community, with my lab.
00:39:16 To be able to help to take some of these steps, that's the dream.
00:39:20 That's what you're already doing!
00:39:22 Yes, maybe.
00:39:25 So then it's not really a dream anymore.
00:39:27 Well I must admit, thirty years ago, when I just started, while I was studying,
00:39:32 I was always going somewhere.
00:39:36 A family, a home, children. The kids need to go to school...
00:39:43 In my work I haven't had that feeling, for the past fifteen years.
00:39:46 I want to keep things the way they are. In my lab things have become easier, more succesful.
00:39:57 Isn't there something, something you know is possible, something you want to achieve?
00:40:05 Maybe I need to tell you how we work.
00:40:08 Many people thing scientist pose a question, then formulate an answer, a hypothesis.
00:40:21 And see if it's correct. But in our field, that doesn't work at all.
00:40:30 In reality we are like historians.
00:40:32 We try to find out how evolution overcame obstacles.
00:40:36 If a fish is swiming in water, and want to come to land. You can come up with many solutions.
00:40:45 The fish needs feet and lungs.
00:40:47 But I could've come up with completely different things.
00:40:51 I can't just imagine the way it happened, like Einstein.
00:40:55 I need to look at what evolution did.
00:40:58 It is a search for the solutions evolution came up with, by coincidence.
00:41:09 They might not be the best solutions, but they work.
00:41:12 Then it's embedded in DNA and every living being carries the solution.
00:41:17 It's completely random.
00:41:22 You ask a question, you don't know it it's the right one.
00:41:27 If you can even answer it using the current technology.
00:41:31 I think it is arrogant to think you can just figure out, what happened thirty five million years ago, somewhere on this planet.
00:41:41 Something that changed us from the way we were thirty five million years ago.
00:41:46 What works much better, is studying a system, like the intestine,
00:41:53 poking it left and right,
00:41:57 you must precisely measure and observe,
00:42:00 keep an open mind, just collect observations,
00:42:08 at a certain moment you'll see a pattern, this is dangerous,
00:42:11 those patterns usually don't exist, like in aboriginal art,
00:42:14 those patterns don't exist, you make them up.
00:42:17 cause and effect, typically associated, we automatically turn it into a story.
00:42:23 This caused that...
00:42:25 When you start thinking like that, you need to prove it.
00:42:30 I go wrong there all the time, people in my lab as well.
00:42:33 Keep observing until you discover a natural law.
00:42:40 Then you test it, but many people don't do this.
00:42:46 It's very hard to design a test that challenges your own hypothesis.
00:42:56 That's another problem.
00:42:58 If you're wrong, this is usually the case, you let the idea go and start to observe again.
00:43:05 Then people tend to make the idea more and more complex,
00:43:10 until it doesn't explain anything anymore.
00:43:13 This way many people reach a dead end.
00:43:16 For myself and in my lab I try to keep an open mind.
00:43:20 Attach importance to something that is at odds with what you observe.
00:43:31 You're inclined to see confirmation, and ignore contradictions.
00:43:36 That is very difficult for the human mind, to let things go.
00:43:43 We don't know how it works and take a step back.
00:43:45 Isn't that also evolution? Confirmation after confirmation...
00:43:53 Yes, well... INAUDIBLE.
00:44:02 Returning to the way we work, we ask very superficial questions, like how does this work,
00:44:13 you talk about it, read about it and as long as you design a good system,
00:44:20 in our case often with mice that have new traits, so we can clearly see something and study it.
00:44:27 Then a moment comes and you know how something works.
00:44:32 At that point you switch from being intuitive, the first fase is completely intuitive and associative,
00:44:38 you feed off of things you remember.
00:44:48 Then you recognize a pattern, you want to see if it's correct, and you test it.
00:44:55 How do you call that quality, this ability to see connections?
00:45:01 I'm not sure how it's described.
00:45:03 I feel like a scientist needs to have productive intuition.
00:45:11 It isn't imagination.
00:45:13 No, it's intuitive and subconscious thinking and relating.
00:45:20 Then you need luck, you need the associations you come up with to be productive.
00:45:27 I think for an artist the process is the same, but what you creatively come up with doesn't have to fit into reality.
00:45:42 If you're not creative you can't do this.
00:45:44 You need to use unexpected angles, memories, conversations an observation.
00:45:55 We talk about this a lot, everyone has their own way,
00:46:01 but often ideas often come from your subconscious mind.
00:46:06 You need some sort of censorship...
00:46:08 When do you get these ideas, when you're sleeping...
00:46:12 It often happend to me while I was running, while working out. Now it often happens...
00:46:17 Can you tell me how that works?
00:46:19 If you run fast you're not really thinking anymore.
00:46:22 But most of the time, after working out, you just get an idea.
00:46:30 Then you think it must be wrong, seven years ago we saw this...
00:46:35 I can feel it isn't right somehow, but I don't know why.
00:46:40 In my lab there is always someone else who feels the same.
00:46:43 And when you discuss it you think, seven years ago, darn I always knew.
00:46:51 And then you abandon the idea and start over.
00:46:55 It is productive creativity, you let things from your subconscience surface,
00:47:04 it can't be too much or too little.
00:47:13 You need to find a balance.
00:47:15 And you need a switch, you need to know when it's enough.
00:47:21 You take what seems right and start testing the idea.
00:47:25 At that moment the lab changes, everyone starts planning what to do.
00:47:32 Then within a week you know whether or not is't correct.
00:47:36 You know when everything you predict, works.
00:47:40 At the first try.
00:47:42 In that moment, what do you feel?
00:47:45 The whole lab becomes stoked, it's a lot of fun.
00:47:51 The advantage of having dutch people in you team, is that you experience it as a group.
00:47:58 In the United States people kept it for themselves, it was your personal succes.
00:48:05 I think that's the strength of our lab, everybody teams up, we work though the whole process together.
00:48:18 That is something you can learn.
00:48:22 I'm an experienced scientist, especially experienced in that process.
00:48:26 Turning that switch when you have enough and getting it out.
00:48:40 Can you try, as a scientist, to make a prediction?
00:48:46 You usually don't do this, but for this program,
00:48:51 the mind of the universe, we're looking for prospects, what can we expect from science in the future?
00:49:14 I can try.
00:49:18 What I know for certain, I'm not sure how long it will take,
00:49:30 but we will know exactly how our body constructs itself, and how it sustains itself.
00:49:35 That means we'll be able to repair any unhealthy organ, pobably using your own cells.
00:49:46 We'll be able to use your cells, outside of you body, to determine what drug is best for you.
00:49:54 Maybe even design better drugs.
00:49:57 Eventually, this leads to great ethical challenges,
00:50:05 we'll probably be able to optimize every individual's genetic code.
00:50:11 You can delete hereditary diseases, which isn't a major ethical problem.
00:50:19 But you could also change people's appearance, we can already do this, but we don't want to.
00:50:30 I think in the near future, we'll understand many hereditary traits
00:50:37 and we'll be able to manipulate them.
00:50:43 I
00:50:45 t's possible, but will it really happen...
00:50:49 It's not up to us.
00:50:52 I would like you to tell me about the aboriginal art, about the other things you study.
00:51:19 What is the opposite of your research?
00:51:25 The opposite of my work has always been sports.
00:51:29 And I've always read a great deal, I'm not good at doing nothing.
00:51:38 But recently I've become interested in the art of painting,
00:51:43 especially in Australian aboriginal art.
00:51:49 The history behind it this art came into existence like an explosion.
00:52:00 The aboriginals who had been painting on tree bark for fourty thousand years, suddenly had modern painting tools,
00:52:08 and started a huge art movement within fifteen years.
00:52:17 They create symbolic painting, usually big and colourful.
00:52:24 Patterns, depicting their genesis,
00:52:30 or maps showing where water was or where ceremonies where held.
00:52:36 When I look at it, I don't see what the story is, it is too strange.
00:52:46 But I can see the patterns,
00:52:48 how the painting brings about all kinds of associations in my mind.
00:52:56 It works exactly the same when we look at a image through a microscope.
00:53:01 Or a set of numbers.
00:53:03 And all kinds of patterns surface in our mind, and we have to wonder if they are in fact real patterns.
00:53:12 Does it fit into the whole of the painting, or the tissue?
00:53:17 I use the same creative processes... It's nice that it doesn't have to lead to a discovery.
00:53:28 You don't need to score, you can just enjoy it.
00:53:31 But it's very similar.
00:53:35 You look for a genetic code in their culture.
00:53:40 Yes, a code.
00:53:45 The genetic code is the start of everything in biology, it sets everything in motion.
00:53:52 You also find that in the art.
00:53:55 There literally is a code, using ancient symbols.
00:54:01 Of which I am now trying to understand the meaning.
00:54:06 It is a funny resemblance. What was it like, when first saw such a painting?
00:54:12 I was familiar with similar art from New Mexico, Native American art.
00:54:24 About five years ago, when I saw a painting that is currently in Amsterdam.
00:54:36 I became interested and discovered it was like the counterpart of what I do during the day.
00:54:46 You immediatly feel engaged, it's different from other art.
00:55:00 What does that say about art and science?
00:55:04 Art and science are much more related than most people think.
00:55:10 You can hear it in the words we use: passion, talent, enthusiasm.
00:55:16 Artists and scientists are facinated with the human being, our surroundings, our planet.
00:55:27 They ask and answer questions. They investigate and describe the world.
00:55:33 ninety percent of that process is the same,
00:55:38 the big difference is, an artist creates something unique,in any shape or form
00:55:48 But we produce the correct description of what the planet had created through evolution.
00:55:58 Although we can be creative, we are restricted by the truth.
00:56:07 It's not about what could be possible.
00:56:09 I think that's the big difference between art and science.
00:56:13 If we succeed to replace anything in our body, once it stops working, we can live forever. Right? What is stopping us?
00:56:24 There is one part of our body that can't be replaced, our brain.
00:56:29 I think, who I am, is in my brain.
00:56:37 It holds my emotions, my memories, me.
00:56:40 The way I see it every other part of you body is replaceable.
00:56:43 Is that your spirit?
00:56:45 You could call it that. Not a religious spirit, but it's me.
00:56:53 That's up here. I am my brain,
00:56:56 I'm convinced of that.
00:56:58 If I replace my brain, the hardware,
00:57:03 everything that is stored up there would be gone.
00:57:07 I'm not my brain's matter, it's the information in my brain.
00:57:18 Stem cell scientists won't solve that problem.
00:57:24 It's like software?
00:57:26 Yes, data, stored in your brain.
00:57:33 An operating system?
00:57:38 It's more like a hard disc.
00:57:40 Everything you've seen, learnt and experienced is stored in your brain.
00:57:46 Together, that is who you are.
00:57:53 It works like a computer, your brain is the hardware that is fed with external data.
00:58:04 Images, experiences, emotions.
00:58:07 That isn't something tangible you can transplant.
00:58:13 I think it is fine, it's not my goal to become one hundred twenty years old.
00:58:20 I think humans are built to live eighty to ninety years.
00:58:25 Yes, but we can replace everything...
00:58:32 The most common age related disease is cancer,
00:58:35 we'll eventually conquer this.
00:58:40 The stem cells make a mistake when rewriting the code,
00:58:45 if the mistake is in an unfornunate place, it becomes a cancer cell.
00:58:48 That's a disease you need to get rid of.
00:58:51 The wear and tear on bones needs to be solved.
00:58:57 In the end you can't replace the brain.
00:59:01 After puberty, your brain cells don't renew.
00:59:11 It doesn't work that way in a computer either.
00:59:16 If the brain is damaged, for example by a stroke, you can't just place stem cells and make it work again.
00:59:26 You can do it with any other organ, but not with the brain.
00:59:28 Becaus vital information is lost.
00:59:36 Does anything scare you?
00:59:40 No, not really.
00:59:45 When you're working on something do you ever get scared by the possibilities?
00:59:52 No, I don't think I've ever been scared.
00:59:56 But we're very aware, that when we take steps in our research,
01:00:03 it has implications we can't always foresee.
01:00:09 It has become an important step to us,
01:00:14 after overcomming a technological obstacle we ask ourselves, do we want this, what do we want to use it for.
01:00:22 That is not something a debate by myself, of with my colleagues.
01:00:26 The debate takes place in society.
01:00:29 But I'm never afraid of things we discover, because we are a product of nature.
01:00:35 When we discover something, it is natural.
01:00:38 It's not something to be afraid of.
01:00:41 Well, nature can be frightening.
01:00:43 That's true. But we can't be more frightening than nature.
01:00:51 If I assume everything you have discovered is true, aren't there other parties interested in that knowledge?
01:01:06 The knowledge is so precious, yet so explosive.
01:01:18 Does that bother you? Is the knowledge protected, is it safe?
01:01:25 Do you mean in the wrong hands...
01:01:29 I can think of Dr. Frankensteins that would be interested...
01:01:34 It is possible, with the work of some of my colleagues.
01:01:41 As we speak there are experiments mixing human stem cells with an animal's embryo, with a mouse or a pig
01:01:49 You get an individual that is part human and part mouse.
01:01:55 It is allowed on mice in England. Up to about two third of the mouse's pregnancy,
01:02:00 then it has to be terminated.
01:02:03 But that little mouse, after fourteen days, is part mouse and part human.
01:02:10 I don't do those kinds of experiments, I wouldn't want to.
01:02:14 But in England they are allowed.
01:02:17 In that direction, you can imagine quite scary things.
01:02:23 At the moment, something governments are backing,
01:02:28 if you have diabetes and you want a new pancreas
01:02:33 there are experiments farming pigs, pigs don't have a pancreas,
01:02:43 but are given human stem cells right after fertilization.
01:02:48 That way you get a pig with a human pancreas, and some other random human cells.
01:02:57 In Japan and Spain they are working on farms with pigs,
01:03:04 that can give people with diabetes a new pancreas.
01:03:10 The farming of organs, it's happening right now.
01:03:16 What do you find inspiring?
01:03:20 Looking at when I come up with an idea, it's either after an intense workout, or at conventions.
01:03:41 I travel al lot, when it's not my turn to speak at a convention, I sit at the back of the room,
01:03:47 many things happen around you, and out of nowhere an idea pops up.
01:04:03 Or while I'm on an airplane, not really focussed on anything, ideas tend to come up.
01:04:24 Have you even had an idea while looking at the aboriginal art?
01:04:30 No, no...
01:04:34 Can you imagine it happening?
01:04:36 No.
01:04:40 When I look at the aboriginal art, I can feel the same things happening in my mind, the same enjoyment.
01:04:59 But I don't think the answers to my questions can be found in the aboriginal art.
01:05:04 It's the same pattern, it might be some kind of exercise.
01:05:14 But I don't think the answers are concealed within the art.
01:05:18 In your field of study, what is the magic word?
01:05:24 I don't understand...
01:05:26 What is the magic word for your field of study?
01:05:31 The magic word? I would think the discovery.
01:05:38 To have an insight no one has had before.
01:05:46 But there is no magic formula.
01:05:52 Beautiful, to discover something no one has seen before.
01:06:00 Maybe someone did see it, but didn't recognize it. That's also a possibility.
01:06:06 Well, in our work, evolution is history.
01:06:11 I've found an image, a drawing of stem cells, from 1888.
01:06:19 With an arrow, and a letter S,
01:06:26 I thought it stood for stem cell, but it meant small cell.
01:06:35 We watched the intestines for twenty years and couldn't find the stem cells until they lighted up.
01:06:40 And this man already saw them 150 years ago.
01:06:48 In 1960, a Canadese scientist spotted them again and predicted everything we've discovered.
01:07:02 We read about this afterwards,
01:07:05 everything was already known, it just needed to be proved.
01:07:12 These cells have been dicoverd three times, but now we were able to show what they are and what they can do.
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