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Part of the work is done in offices, with computers, but the vital part remains handwork.

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We work in various laboratories...

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This lab, I will open it...

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Is entirely devoted to cultivating human tissue, the tiny organs.

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The environment is completely sterile, hence the lab coats...

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(interviewer) The organoids? Can we see them in this lab?

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Yes, although I am not sure if we can see them right now... shall we just go in?

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(interviewer) Yes please

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Do you have something, an organoid, that we can see on the microscope?

10
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(student) Yes

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The cells are kept cool, so as to limit their growth, the cabinets are dust-free.

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They are actually borrowed technique from space travel sciences.

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The air is being filtered, because the bacteria in it fall on the cultures and kill them.

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You can also see the gloves, lab coats...

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This is a kind of modern Petri dish, actually 12 small Petri dishes on a plate.

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They contain the nutrients, like carbohydrates and fats, and the grow factors we add.

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If you do that correctly you see the organoids growing. We split them manually so that they continue growing.

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This splitting is carried out every week, right?

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(student) Yes.

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These are kidney organoids?

21
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Yes, tiny kidneys.

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(interviewer) Is this a potential kidney?

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So far it is just kidney cells, a kidney is an incredibly complex organ.

24
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It has multiple layers of cells

25
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We have just started this... have you figured out yet what type this is?

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(student) This is mainly the functional tube part of the kidney.

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The other part is still in development, we are still working on that.

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This is nevertheless an important part of the kidney, and we can cultivate it quite well.

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A kidney is very complex, we probably have to cultivate several components independently.

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When we put everything together, my prediction would be...

31
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That nature works in a way that instigates the spontaenous generation of a kidney.

32
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We are not there yet, but the great thing is, we can cultivate these cells from urine.

33
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There are always kidney cells in urine. You can use the urine from patients and healthy persons.

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(interviewer) So this is alive?

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This is growing, yes, but it is now cooling down slowly.

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However, at a temperature of about 37 degrees celsius, you can witness the cell division.

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Tomorrow this organoid is probably too big, so we then have to fragmentize it.

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So it will fragmentize, but thereafter reorganise itself, become an organoid, and grow again.

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There is no end to this process. If we know the initial conditions, which are different for every organ...

40
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It is a bit trial-and-error to come to know the conditions, but you can repeat this endlessly.

41
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You can do it 2-3 times a week. Some organoids grow in tenfold measure, so if you do that for a year...

42
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You will have a universe full of intestines, or prostates, perhaps something you would not like...

43
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We all learned that there is a limit to cell division. Normal cell division has a limit...

44
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Because we think that endless growth equals cancer. This appears not to be the case.

45
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How old is this culture?

46
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(student) This one is 4 months old.

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Growing continuously.

48
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(interviewer) But how big is this culture in reality?

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(student) This is about one milimeter, actually.

50
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You can see them with the naked eye.

51
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If you dare to lift the cover... bacteria and dust will fall in the dish, that is really bad.

52
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You can see little globules, that is where these structures are in, there's a little condense so a bit hard to see...

53
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(interviewer) You are holding a small box with life!

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(student) That's right.

55
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(student) So I have to look trough the microscope as I usually do?

56
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Here are thin slices of organoid tissue, packed on small glass.

57
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There is not that much to see, but there is a variety of ways, colour tagging methods...

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To make a variety of things visible in the tissue.

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This is classic stuff, what happens in a hospital, for example.

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Purple is a general colour, different tints of purple reveal inflammations, normal tissue, viruses, and so on.

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(interviewer) Can you identify these things as well?

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For intestines - this is from a mouse, I can in this case, but pathologists know hundreds of diseases...

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I have to look up things and consult others. Also, mice are not humans, so its different.

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This is very important in a lab: music. There are endless discussions...

65
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Music on? Music off? What kind of music? We now have two labs: one without and one with music.

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This is also quite standard. With the help of an electromagnetic field and a fluid...

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You can transfer tiny bits of DNA from the one side of the device to the other.

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Bigger pieces tend to transfer slower, that is how we separate bits of DNA.

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Think of typical images of forensic DNA research.

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Producing a lot of DNA, cutting it into pieces, and comparing the pattern to the DNA of the potential culprit.

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It is just basic molecular biology.

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(interviewer) You do not have to show everything, only the things vital for your reserach.

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This is the molecular biologist's essential tool. They are property like a pistol, or violin. It does the work.

74
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P20. You set it, and basically what you do is extracting and injecting fluids.

75
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That is the way to design every step in the DNA.

76
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It happens always in this kind of tube.

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If I want to cut the DNA, I add an enzyme, precisely on one location, which cuts it.

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Then you have two pieces, which I can mix, add, you name it.

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This is the core of molecular biology.

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This is the microscope and we see the organoid sample on the screen. You see lasers, cabinets, and so on...

81
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Biologists never build their own devices. Physicists do. We work with industry and usually buy devices.

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This is beautiful. Can you turn it?

83
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This is the size of a normal liver.

84
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Every red area is one cell. You can see the nuclei.

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Blue is a nucleus, purple is the boundary of the cells.

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In all of these cells, there is at least one nucleus.

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It is a bit difficult to see... can you see all the nuclei?

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(student) It is difficult. Unfortunately, we don't really see the boundaries between the cells.

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The flipside is beautiful, with the nuclei...

90
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A liver has two cell types: we colour them red and green, and we see this liver generates them both.

91
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(interviewer) But you add these colours.

92
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Yes, but the possibilities are endless. It depends on what is informative.

93
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The student tries to make much more tissue in three dimensoins. He uses a nylon threads...

94
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The nylon meshwork apparently enhances the growth of the tissues quite well.

95
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Together we thought of implementing the meshwork in patients, but made from biodegradables.

96
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It may support this particular tissue structure. We ordered it, we hope that it works out for us.

97
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What you see is a plug, it is only half a centimeter big, we could implement it in a liver.

98
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Probably it will grow quite easily from there. We see that happening in mice already.