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  • One of the most extraordinary scientific discoveries of this century

  • was made by a doctor-turned-scientist working in Japan.

  • Shinya Yamanaka had been involved in the field of stem cells

  • for ten years

  • when his experiments changed the way we understand human biology.

  • Shinya Yamanaka is a medical doctor and a scientist.

  • He was interested in finding a way

  • to treat patients with incurable spinal cord injuries.

  • I was an orthopaedic surgeon,

  • so I didn't do any stem cell research at that time.

  • It was 20 years ago.

  • But I had many difficult patients

  • suffering from spinal cord injuries,

  • and there are no treatment methods for those patients.

  • That's why I became interested in basic research.

  • Because I thought that by doing basic research,

  • one day I may be able to treat and help those patients.

  • Shinya Yamanaka's desire to help his patients

  • led to a brilliant experiment.

  • This took us beyond the limits of our knowledge

  • and revealed something really extraordinary.

  • There are two types of stem cells.

  • Adult or tissue stem cells make cells in their own tissues.

  • Blood stem cells make blood, muscle stem cells, muscle and so on.

  • There is another type of stem cell, the embryonic stem cell.

  • These cells are called pluripotent

  • because as well as making copies of themselves,

  • they can become any of the types of cell that make up the human body.

  • So the point about the adult tissue stem cells is

  • that these are dedicated cells

  • for repairing and maintaining specific tissue.

  • The embryonic stem cells represent a very early stage in development

  • when there is no muscle or blood or bone.

  • There's nothing else really, just them.

  • Development starts with the early embryo and these pluripotent founder cells

  • and things become more and more restricted and channelled.

  • That's how the body is built, and it would be chaos

  • if cell types could start turning into one another.

  • Shinya already knew from earlier experiments on cloning

  • that development could be reversed, that a specialized cell,

  • which scientists call differentiated,

  • can produce embryonic cells.

  • But no one knew how this process worked. To find out,

  • Shinya looked for clues inside the cell.

  • I knew that eggs

  • or embryonic stem cells have factors

  • that can convert skin cells back to an embryonic state.

  • That's why we decided to search for such factors.

  • Scientists had no idea

  • what these factors were or how many would be needed.

  • Shinya went back to basics,

  • examining the biology that gives cells their individual identities.

  • We already knew that each cell in our body

  • contains something that determines what sort of tissue the cell becomes,

  • its cell identity.

  • These are the genes in the nucleus.

  • The nucleus in each of our cells contains 23 pairs of chromosomes

  • made up of long strands of DNA.

  • This is divided into sections or genes

  • that direct the cell to make particular proteins.

  • These proteins, which scientists sometimes call factors,

  • are what give the cells their different identities.

  • All of our cells contain the same genes,

  • but in a skin cell only the genes that make skin proteins are turned on.

  • The active genes are always in the unwound open areas of the chromosome.

  • All the other genes that would make a liver, a heart or an embryonic cell

  • are turned off.

  • They are tightly wrapped up and locked away.

  • The remarkable thing that Shinya Yamanaka did

  • was to question whether a cell had to stay differentiated.

  • Might it be possible to make an already specialised cell

  • turn back into an embryonic stem cell in the laboratory?

  • He wondered if the same proteins that keep embryonic stem cells pluripotent

  • might be able to reprogramme

  • the specialised identity of a differentiated cell.

  • He started with a list of over 100 possibles.

  • He didn't know if they operated alone or in combination,

  • which would mean over a million possible variations.

  • Using an off-the-shelf computer programme,

  • Shinya Yamanaka was able to ascertain the 24 most likely candidates.

  • It took years of work.

  • The next step was to narrow down factors,

  • from 24 factors to whatever was required,

  • and we found that

  • 4 out of the 24 factors were essential.

  • He took a combination of four factors

  • that normally only act together in the embryonic stem cell

  • and inserted them into a skin cell.

  • In a process we don't fully understand, the chromosomes began to unwind.

  • Shinya's factors could now attach to the genes

  • that make embryonic stem cell proteins.

  • The proteins, called Oct4, Sox2, Klf4 and C-Myc,

  • overwhelmed the competing message from the skin genes,

  • fooling the cell into thinking it was in an embryonic environment.

  • As these reprogrammed cells replicate,

  • they become more and more like embryonic stem cells

  • until eventually, they are indistinguishable.

  • From this state it can now be used to produce any cell in the body.

  • What I discovered was that

  • we can convert skin cells back to an embryonic state,

  • so we can make stem cells from skin cells.

  • All we have to do is add

  • three or four factors into skin cells. That's all we need.

  • From ES cells, embryonic stem cells,

  • we can make all the cells that exist in the body.

  • However, we have to destroy embryos

  • in order to generate ES cells.

  • But with our technology

  • we don't have to use embryos any more.

  • We can make ES like stem cells

  • directly from skin cells.

  • Shinya Yamanaka had made a new type of pluripotent cell,

  • called induced pluripotent stem cells or iPS cells.

  • He first made his discovery studying mice,

  • then quickly showed that it also worked for human cells.

  • This was an extraordinary discovery.

  • Shinya Yamanaka had proven that he could turn a skin cell backwards in time

  • and then forwards into any other cell.

  • In fact, it didn't just work with skin.

  • He could turn any differentiated cell into an iPS cell.

  • This generated headline news and astonished scientists

  • all over the world.

  • My reaction was, first of all, that this was

  • one of the most profound scientific developments

  • in our lifetime.

  • It completely turned upside down

  • everything we've been taught about development.

  • We have always been taught

  • that development was irreversible, everything was a one-way street.

  • But in fact that's not true.

  • Our notions about development

  • were clearly wrong. It isn't as fixed as we thought it was.

  • It means that we have to be

  • more open in our thinking about what is biologically possible.

  • Only Shinya Yamanaka imagined that it might be possible

  • to reprogramme a differentiated cell with just a handful of proteins.

  • Other scientists were quickly able to reproduce Shinya's findings.

  • The first step is to remove

  • the medium we used to culture our skin cells.

  • Now we are adding a new medium containing the reprogramming factors.

  • In a couple of weeks, we should have iPS cells in this dish.

  • So as a result of the skin cells being infected,

  • what you have after a few days is these nice colonies of cells.

  • Here you can see two clear examples.

  • They have ES cell morphology,

  • but we also know that they have acquired this embryonic stem cell status.

  • The way is now wide open for stem cell medicine.

  • Induced pluripotent stem cells, or iPS cells, are a whole new kind of cell.

  • They can provide better ways of tackling disease

  • and, potentially, of regenerating the body.

  • One major difference

  • between iPS cells and embryonic stem cells

  • is that iPS cells can be generated

  • from individual patients.

  • That means they are genetically identical

  • to the individual patient, and that means if we generate, for example,

  • cells for transplantation from iPS cells,

  • they will not be rejected.

  • They will not be recognised by the patient's immune system.

  • Here, for the first time, we see a perspective

  • for deriving specialised cells from, for example, the patient's skin

  • and changing them into brain cells, into insulin-producing cells,

  • or into heart cells

  • which can then be used to supply this individual patient

  • without the risk of transplant rejection.

  • The way reprogramming works to make iPS cells is still mysterious.

  • Although it's technically easy, it doesn't always work completely

  • and can produce cells with unexpected changes in their genes.

  • Scientists are now investigating how to produce perfect iPS cells

  • that could be safe to use for treating patients.

  • And although iPS cells provide a way

  • of making pluripotent cells without using human embryos,

  • which allays an important ethical concern,

  • they themselves have raised entirely new issues.