0:00:02 > 0:00:04Death...
0:00:04 > 0:00:07sooner or later,
0:00:07 > 0:00:09we'll all have to face it.
0:00:09 > 0:00:11It's an inevitable part of life.
0:00:13 > 0:00:15But medicine is engaged in a never-ending battle
0:00:15 > 0:00:17to delay this final moment,
0:00:17 > 0:00:22and, today, a biomedical revolution is promising to extend our
0:00:22 > 0:00:26lifespan further than ever before and improve the quality of our lives
0:00:26 > 0:00:28in old age.
0:00:28 > 0:00:33With a Nobel Prize in physiology and a career spanning over four decades,
0:00:33 > 0:00:38cell biologist and geneticist Paul Nurse is uniquely placed to explore
0:00:38 > 0:00:40this fast-moving field of science.
0:00:41 > 0:00:45We are beginning to understand the complexities of how cells work and how
0:00:45 > 0:00:50that applies to how tissues and organs and bodies work.
0:00:50 > 0:00:51And critically,
0:00:51 > 0:00:55we can now imagine ways we can intervene with some of these complex
0:00:55 > 0:01:00- processes.- With the help of the BBC's archive,
0:01:00 > 0:01:03Paul is going to take us to the extreme frontiers of medicine...
0:01:04 > 0:01:09..where pioneers are experimenting with ground-breaking treatments...
0:01:09 > 0:01:14Gene editing holds enormous potential in the treatment of cancers, and that
0:01:14 > 0:01:16journey's really just beginning.
0:01:16 > 0:01:19..where controversial figures may be going too far...
0:01:19 > 0:01:23Why should I give up? I'm not the type to give up.
0:01:23 > 0:01:26..and where ethical dilemmas abound.
0:01:26 > 0:01:31We could start seeing the emergence of genetic haves and have-nots.
0:01:31 > 0:01:35For Paul, the big question is not just what science can do to fix our
0:01:35 > 0:01:37bodies and extend our lives
0:01:37 > 0:01:41but whether it's right to use all the tools and techniques available.
0:01:43 > 0:01:48If we don't keep society properly engaged and content with what we're
0:01:48 > 0:01:53doing, then we will not be able to use science to help humankind.
0:02:17 > 0:02:20We all hope to escape death for as long as possible.
0:02:27 > 0:02:29And thanks to modern medicine,
0:02:29 > 0:02:31we're now able to do this better than ever before.
0:02:33 > 0:02:38In fact, our lifespan is increasing by two-and-a-half years every decade,
0:02:38 > 0:02:43and a third of all babies born today can expect to live to 100 years.
0:02:43 > 0:02:46Modern medicine is transforming our lives.
0:02:46 > 0:02:49We're living longer, but it can come at a cost.
0:02:51 > 0:02:55Old age itself brings with it a range of debilitating illnesses.
0:02:56 > 0:03:02Many of the diseases of old age are a result of accumulating damage as
0:03:02 > 0:03:04we live longer and longer.
0:03:05 > 0:03:08Three diseases in particular have
0:03:08 > 0:03:11become the main killers in the developed world,
0:03:11 > 0:03:14cancer, heart disease and dementia...
0:03:15 > 0:03:19..and it turns out that conquering all three diseases may be possible
0:03:19 > 0:03:21with a single deceptively simple approach...
0:03:22 > 0:03:28..understanding the fundamental building block of our bodies, the cell.
0:03:28 > 0:03:32The cell is the basic unit of life. It's life's atom.
0:03:32 > 0:03:35We are all made up of billions of cells, and they are extraordinarily
0:03:35 > 0:03:39complicated. Many people think that CERN,
0:03:39 > 0:03:44the Large Hadron Collider in Geneva, is the most complicated machine
0:03:44 > 0:03:46known to man, but I tell you,
0:03:46 > 0:03:50that is trivial compared with every one of those cells,
0:03:50 > 0:03:53those billions of cells that makes up every one of us.
0:03:55 > 0:03:57Throughout his career,
0:03:57 > 0:04:01Paul Nurse has attempted to unlock the secrets of the cell and
0:04:01 > 0:04:03understand how it relates to illnesses.
0:04:03 > 0:04:06So, many of the diseases of old age -
0:04:06 > 0:04:09heart disease, dementia, cancer -
0:04:09 > 0:04:11can be traced back to cells.
0:04:11 > 0:04:16So, knowing how cells work is important for understanding disease,
0:04:16 > 0:04:20and knowing how we can fix cells provides us new ways of thinking of
0:04:20 > 0:04:21how we can cure disease.
0:04:23 > 0:04:25And by curing these illnesses,
0:04:25 > 0:04:29we should be able to extend our lives even further and make our
0:04:29 > 0:04:30old age a healthier experience.
0:04:32 > 0:04:36Today, our ability to understand and manipulate the cell is creating
0:04:36 > 0:04:40extraordinary new opportunities to tackle age-related diseases.
0:04:53 > 0:04:59Half of us will be diagnosed with cancer at some point in our lives,
0:04:59 > 0:05:03and there is one risk factor that is bigger than all others...
0:05:03 > 0:05:04age.
0:05:05 > 0:05:10Cancer is caused by genetic damage, and that genetic damage accumulates
0:05:10 > 0:05:14over the years, and when enough genes become damaged,
0:05:14 > 0:05:16then the cells go out of control,
0:05:16 > 0:05:19they divide in an uncontrolled manner, and that forms a tumour.
0:05:22 > 0:05:26So, in theory, curing cancer should be straightforward.
0:05:26 > 0:05:30All you need to do is fix those faulty genes.
0:05:30 > 0:05:32It's a technique known as gene therapy.
0:05:33 > 0:05:35But although it may sound simple,
0:05:35 > 0:05:39it is, in fact, one of the greatest challenges in modern medicine...
0:05:40 > 0:05:43..and one fraught with ethical dilemmas.
0:05:47 > 0:05:51The very first attempts at gene therapy in the 1990s didn't involve
0:05:51 > 0:05:55cancer patients but young children who were born with a genetic disease.
0:05:58 > 0:06:02One of them was four-year-old Ashi DeSilva.
0:06:02 > 0:06:06She had a faulty gene that meant her immune system didn't work properly.
0:06:06 > 0:06:10Ashi had a disease called ADA deficiency.
0:06:10 > 0:06:14She never left the house except to go to the hospital or to the doctor.
0:06:14 > 0:06:17She was just kept in quarantine because she was constantly sick.
0:06:19 > 0:06:25In 1990, French Anderson and his team extracted blood from Ashi.
0:06:25 > 0:06:29Then they took a healthy immune-system gene from a donor and put it into
0:06:29 > 0:06:31her white blood cells in the lab.
0:06:32 > 0:06:34The cells with the new, healthy gene
0:06:34 > 0:06:37were then reinjected into Ashi's bloodstream.
0:06:38 > 0:06:41Then they waited to see if the genetically modified
0:06:41 > 0:06:43white blood cells would work.
0:06:43 > 0:06:45Within six months,
0:06:45 > 0:06:49her family began to realise that she wasn't sick at all any more,
0:06:49 > 0:06:53that she was starting to do all the things that normal kids do,
0:06:53 > 0:06:57and what tipped it over for the parents was in the spring,
0:06:57 > 0:07:00so about six months after she started therapy,
0:07:00 > 0:07:02the whole family came down with the flu...
0:07:02 > 0:07:06and the first one up and playing was Ashi.
0:07:06 > 0:07:09And the parents could not believe THEY were sick in bed
0:07:09 > 0:07:13and their immune-deficient child was up playing around.
0:07:16 > 0:07:20Ashi's gene-therapy treatment was successful,
0:07:20 > 0:07:21but it wasn't perfect.
0:07:23 > 0:07:27Her body still created its own blood cells with the defective gene,
0:07:27 > 0:07:30so Ashi needs regular injections of healthy genes for the rest of her life.
0:07:34 > 0:07:36French wanted to find a way to cure
0:07:36 > 0:07:39someone with a disease like this for ever.
0:07:41 > 0:07:44He thought he might be able to achieve this by injecting the
0:07:44 > 0:07:47healthy genes directly into a foetus in the womb.
0:07:51 > 0:07:54In theory, if the genes made it into the foetal cells,
0:07:54 > 0:07:59the child would go on to create cells with healthy genes for ever.
0:07:59 > 0:08:00It would be cured.
0:08:02 > 0:08:04It seemed the perfect solution,
0:08:04 > 0:08:07and in 1998, he decided to make it public.
0:08:10 > 0:08:14We brought this to the government regulatory committees, basically,
0:08:14 > 0:08:20three years before we anticipate being ready to actually do a clinical protocol.
0:08:20 > 0:08:23And as expected...
0:08:24 > 0:08:27..there was considerable interest in this topic.
0:08:28 > 0:08:31As we did not expect,
0:08:31 > 0:08:34there was a considerable amount of hysteria about this topic.
0:08:36 > 0:08:40The cause of the hysteria was down to the fact that some of the cells
0:08:40 > 0:08:45in an early embryo will turn into egg or sperm cells, and if the new gene
0:08:45 > 0:08:49accidentally ends up in these, it will affect what's called the "germ line".
0:08:51 > 0:08:55We need to think carefully about changes to genes that end up being
0:08:55 > 0:08:59inherited from one generation to another, because that doesn't simply
0:08:59 > 0:09:03affect the individual you're trying to treat for disease
0:09:03 > 0:09:05but will affect subsequent generations, as well.
0:09:07 > 0:09:09Many people seem to feel that...
0:09:10 > 0:09:12..our honest statement,
0:09:12 > 0:09:17that there might be a very low level of inadvertent germ-line gene
0:09:17 > 0:09:22transfer, might really be hiding that we're trying to get into the
0:09:22 > 0:09:25germ line, we're trying to redesign babies.
0:09:30 > 0:09:33The stage was set for a mighty ethical battle.
0:09:33 > 0:09:37French was convinced that foetal gene therapy could work and was
0:09:37 > 0:09:42responsible. Set against him were moralists and some scientists who
0:09:42 > 0:09:44feared it would lead to designer babies.
0:09:47 > 0:09:49But in the end, it all came to nothing.
0:09:52 > 0:09:56The difficult part of gene therapy had always been getting the healthy
0:09:56 > 0:09:57gene into a cell.
0:09:59 > 0:10:02French had used a virus.
0:10:02 > 0:10:06These viruses had been modified so that they wouldn't cause an infection
0:10:06 > 0:10:10as they transported the healthy genes inside the cells.
0:10:10 > 0:10:14In other clinical trials, these modified viruses also seemed to be working.
0:10:15 > 0:10:19But then, one gene-therapy trial in Philadelphia went dramatically wrong.
0:10:22 > 0:10:26Jesse Gelsinger had been injected with a modified cold virus as part of a
0:10:26 > 0:10:28gene therapy treatment, but the virus was
0:10:28 > 0:10:31not as safe as scientists had thought.
0:10:33 > 0:10:37Within a week, it had attacked all his major organs and he died.
0:10:44 > 0:10:46Jesse's tragic death changed everything.
0:10:47 > 0:10:51It was clearly far too early to think about using this potentially
0:10:51 > 0:10:53dangerous technique in the womb.
0:10:57 > 0:11:00A few years later, French Anderson's career was
0:11:00 > 0:11:03destroyed when he was jailed for sexual offences.
0:11:12 > 0:11:14The challenge of getting a
0:11:14 > 0:11:18healthy gene safely into a cell seemed insurmountable.
0:11:18 > 0:11:22But what if there was an altogether different way of doing gene therapy,
0:11:22 > 0:11:25one that didn't require a virus to carry new genes into the human body?
0:11:27 > 0:11:30It's an idea that has been central to Paul's career.
0:11:31 > 0:11:35He has spent most of his life studying yeast, and by working with
0:11:35 > 0:11:40this tiny, simple microorganism, he found a way to get a new gene into a cell.
0:11:41 > 0:11:43In 1981,
0:11:43 > 0:11:49we developed techniques that allowed us to introduce genes into yeast
0:11:49 > 0:11:54cells and to very precisely replace one gene with another.
0:11:54 > 0:11:57And that's actually the main reason I've worked on yeast for all
0:11:57 > 0:12:01these years, because I could do such precise experiments.
0:12:02 > 0:12:05This method would later be dubbed "gene editing".
0:12:05 > 0:12:07Just like early gene therapy,
0:12:07 > 0:12:11the purpose of gene editing is to modify genes.
0:12:11 > 0:12:15But the way the two methods work is fundamentally different.
0:12:17 > 0:12:20Early experiments with human cells were rather crude.
0:12:21 > 0:12:26Genes were added, they could integrate anywhere in the genome.
0:12:26 > 0:12:28They might or might not work,
0:12:28 > 0:12:31they might damage other genes where they'd integrated,
0:12:31 > 0:12:34and you really didn't know what was happening.
0:12:35 > 0:12:39Gene editing, on the other hand, is much more precise.
0:12:39 > 0:12:41It fixes the faulty gene by snipping
0:12:41 > 0:12:44it out and replacing it with the correct one.
0:12:46 > 0:12:49For example, if you have a damaged gene and you were just introducing
0:12:49 > 0:12:53genes randomly, you're still left with that damaged gene.
0:12:53 > 0:12:55But if you can gene-edit it,
0:12:55 > 0:12:58then you can replace that damaged gene with one that works perfectly.
0:13:01 > 0:13:04Doing this in yeast is relatively straightforward.
0:13:05 > 0:13:08What I've got here is an example of an experiment
0:13:08 > 0:13:11where we've done gene editing of yeast.
0:13:11 > 0:13:16We've put DNA into the yeast cell and transformed how it behaves.
0:13:18 > 0:13:22In this experiment, Paul took two yeast cells.
0:13:22 > 0:13:26He then gene-edited one of them to enable it to grow in a Petri dish
0:13:26 > 0:13:29containing particular types of nutrients.
0:13:30 > 0:13:32So, if you look here, you will see
0:13:32 > 0:13:35all these little sort of cream blobs here.
0:13:35 > 0:13:40Each of these contain about 100 million yeast cells, and each one of
0:13:40 > 0:13:43them grew from a single cell by repeated divisions.
0:13:43 > 0:13:48Now, on this plate, we put yeast cells that have been treated with the gene.
0:13:48 > 0:13:52These were gene-edited. So, these colonies here could grow,
0:13:52 > 0:13:56whereas here, we didn't treat them with DNA, and you can see there's no
0:13:56 > 0:14:00colonies growing at all, because they couldn't grow without that new gene.
0:14:02 > 0:14:05Gene editing in yeast was a big step forward,
0:14:05 > 0:14:10but developing the same technique in much more complex human cells would
0:14:10 > 0:14:13prove extremely challenging.
0:14:13 > 0:14:17If we take the genome in a human cell, it's much, much bigger,
0:14:17 > 0:14:20it's much more tangled up,
0:14:20 > 0:14:23and you can't use those simple methods to get access,
0:14:23 > 0:14:30so you have to use other molecular tricks to expose the gene and allow
0:14:30 > 0:14:33it to be changed by the genes that you're introducing.
0:14:35 > 0:14:39These new molecular tricks would eventually be developed, and in 2015,
0:14:39 > 0:14:42gene editing hit the headlines.
0:14:45 > 0:14:49A baby girl from London has become the first person in the world to
0:14:49 > 0:14:51receive a revolutionary genetic treatment
0:14:51 > 0:14:53which doctors have described as almost a miracle.
0:14:55 > 0:14:59The little girl was diagnosed with leukaemia when she was just
0:14:59 > 0:15:03three months old. After all conventional treatments failed,
0:15:03 > 0:15:06doctors at Great Ormond Street decided the only option left was an
0:15:06 > 0:15:08experimental technique.
0:15:11 > 0:15:16The pioneering scientist behind this treatment was Professor Waseem Qasim.
0:15:17 > 0:15:19For several months,
0:15:19 > 0:15:23he had been working on a new type of leukaemia treatment in which
0:15:23 > 0:15:26white blood cells are engineered to recognise cancer cells.
0:15:29 > 0:15:32White blood cells are the body's soldiers.
0:15:32 > 0:15:35They circulate the body, cleaning up infections,
0:15:35 > 0:15:39dealing with intruders, and are essential to stay in good health.
0:15:41 > 0:15:46Waseem focused on a type of white blood cell called a T cell.
0:15:46 > 0:15:50T cells, in particular, are thought to contribute to what we call immune
0:15:50 > 0:15:53surveillance, so they circulate the body looking for abnormal cells and
0:15:53 > 0:15:57will deal with them. But in some patients, that doesn't happen and
0:15:57 > 0:15:59leukaemias and cancers can develop.
0:16:02 > 0:16:05So, Waseem and his team took a batch of T cells from a donor and
0:16:05 > 0:16:10engineered them to be able to recognise and attack cancer cells.
0:16:12 > 0:16:13But they had to make another key
0:16:13 > 0:16:17change because of a dangerous property of T cells.
0:16:19 > 0:16:24T cells can also mistake a patient's own tissue as foreign and attack it,
0:16:24 > 0:16:27so the next step was to gene-edit the T cells
0:16:27 > 0:16:29to prevent this potentially
0:16:29 > 0:16:31deadly side effect.
0:16:32 > 0:16:34So, by the end of the process,
0:16:34 > 0:16:38those cells will then only recognise leukaemia cells and won't harm any of
0:16:38 > 0:16:40the normal tissues in the body.
0:16:42 > 0:16:46The little girl only needed a small phial of these modified blood cells
0:16:46 > 0:16:49and within weeks, it was clear that it had worked.
0:16:49 > 0:16:51The cancer cells were knocked out,
0:16:51 > 0:16:53but the rest of the body was left untouched.
0:16:55 > 0:16:59Since then, another child has been treated successfully, and clinical
0:16:59 > 0:17:02trials for children and adults have just started.
0:17:04 > 0:17:07But, for Waseem, this is just the beginning.
0:17:08 > 0:17:14Gene editing is a very fast-moving field, and the latest technique, Crispr,
0:17:14 > 0:17:18is set to revolutionise what can be done because it is much faster and
0:17:18 > 0:17:20more precise than previous methods.
0:17:21 > 0:17:27We think Crispr will be able to target a much larger number of sites in the
0:17:27 > 0:17:33genome and will form the basis of the next generation of gene editing
0:17:33 > 0:17:35as we go into the next few years.
0:17:36 > 0:17:40So far, gene editing has been used for leukaemias and lung cancers,
0:17:40 > 0:17:41but in the future,
0:17:41 > 0:17:45the hope is to use it for different types of cancer and
0:17:45 > 0:17:48perhaps even to repair other damage caused by ageing.
0:17:52 > 0:17:57However, gene editing is such a precise and powerful technique that
0:17:57 > 0:18:01it leads to profound ethical and social issues.
0:18:01 > 0:18:05For many years, we've imagined using gene therapy and manipulating human
0:18:05 > 0:18:08genes, but it was rather theoretical.
0:18:08 > 0:18:13But the modern technique of Crispr, allowing very precise gene editing,
0:18:13 > 0:18:16changes that situation completely.
0:18:16 > 0:18:20We've been discussing these ethical problems on and off, but because we
0:18:20 > 0:18:23couldn't do it, it didn't have any urgency.
0:18:23 > 0:18:26Now we can do it, it has REAL urgency.
0:18:30 > 0:18:33The fears aren't so much to do with treating cancer and thereby
0:18:33 > 0:18:39extending life, it's more that gene editing could also be used in other ways,
0:18:39 > 0:18:41for example, to modify human embryos.
0:18:44 > 0:18:46And this is already happening.
0:18:46 > 0:18:53Scientists at the Francis Crick Institute will soon be the first in the UK to do this.
0:18:53 > 0:18:56So far, it's only being done for research.
0:18:56 > 0:18:59None of the embryos will be allowed to develop beyond seven days.
0:19:01 > 0:19:05But some fear this may be the beginning of a slippery slope
0:19:05 > 0:19:06towards designer babies.
0:19:10 > 0:19:12Fertilisations were all very successful.
0:19:12 > 0:19:16There are a few things we'd like to have modified, if possible.
0:19:16 > 0:19:19We'd like her to be musical and, if possible,
0:19:19 > 0:19:21also, we want her to be ambitious.
0:19:21 > 0:19:23Well, we don't want to tamper with the physical side of things
0:19:23 > 0:19:24- in any way.- No,
0:19:24 > 0:19:27except that we would like her to have my father's red hair.
0:19:27 > 0:19:31Ah. Well, let's see if we can make a budding musician out of her.
0:19:33 > 0:19:38For critics, this 1980s vision of genetic engineering no longer seems
0:19:38 > 0:19:43- so far-fetched.- Once we produce genetically modified human embryos
0:19:43 > 0:19:45in labs around the world, it's
0:19:45 > 0:19:48really not that big of a jump to try to initiate a
0:19:48 > 0:19:49pregnancy with one of those.
0:19:51 > 0:19:54And it also raises the spectre of genetic discrimination.
0:19:56 > 0:20:01You could find wealthy parents buying the latest offspring upgrades
0:20:01 > 0:20:05for their children, genetic changes that either did or even that were thought
0:20:05 > 0:20:10to make their children superior in some way. And there we could start
0:20:10 > 0:20:13seeing the emergence of genetic haves and have-nots.
0:20:13 > 0:20:16Some people have called them genetic castes.
0:20:16 > 0:20:18People have thought about this,
0:20:18 > 0:20:21they've called them the Gen-Rich and the Naturals, and we could be seeing
0:20:21 > 0:20:23much greater forms of inequality
0:20:23 > 0:20:27even than the already-horrendous levels of inequality we live with.
0:20:30 > 0:20:33I'm not really impressed by slippery-slope arguments.
0:20:33 > 0:20:38If we can learn something of great value, then that is a great prize to
0:20:38 > 0:20:42be won. It doesn't mean that automatically leads to the next step and the
0:20:42 > 0:20:45step after that and the step after that.
0:20:45 > 0:20:48We still have control over those later steps.
0:20:51 > 0:20:54Now that the gene genie is out of the bottle,
0:20:54 > 0:20:55society will have to decide what
0:20:55 > 0:20:58limits should be placed on this emerging technology.
0:20:59 > 0:21:03The danger is that powerful new genetic techniques for curing diseases
0:21:03 > 0:21:07such as cancer could be ruled out because of the risk that these same
0:21:07 > 0:21:10techniques might be used for less noble causes.
0:21:12 > 0:21:15But targeting faulty genes in our cells is just one approach to dealing with
0:21:15 > 0:21:17age-related diseases.
0:21:19 > 0:21:23Conditions such as dementia that are caused by degeneration in the brain
0:21:23 > 0:21:26may benefit from another method,
0:21:26 > 0:21:30one using a type of cell called a stem cell.
0:21:30 > 0:21:35A stem cell divides and forms cells that then go on to make tissues and
0:21:35 > 0:21:37different organs in the body.
0:21:37 > 0:21:41They are really the basis of how we make ourselves.
0:21:43 > 0:21:46It's this extraordinary ability to turn into almost any type of cell
0:21:46 > 0:21:51inside the body which has led some scientists to wonder -
0:21:51 > 0:21:53could stem cells be used to create
0:21:53 > 0:21:56new brain cells and so regenerate our brains?
0:22:10 > 0:22:15As we grow older, our bodies wear out, our organs deteriorate,
0:22:15 > 0:22:17our cells stop functioning properly.
0:22:18 > 0:22:21And the signs of time are particularly visible in one organ...
0:22:23 > 0:22:28..our brain. Almost all aged brains show signs of degeneration,
0:22:28 > 0:22:31even if they don't belong to someone who suffers from dementia.
0:22:32 > 0:22:36This happens even though our bodies work hard to keep any form of
0:22:36 > 0:22:39degeneration at bay throughout our lives.
0:22:39 > 0:22:43Many people think that our body is static and that we have what we
0:22:43 > 0:22:45have, but in fact, that's not the case.
0:22:45 > 0:22:50We're constantly replacing cells, about two million or so every second.
0:22:50 > 0:22:54Some are lost through wear and tear, some just reach the end of their
0:22:54 > 0:22:57life and others deliberately self-destruct.
0:22:58 > 0:23:02The life cycle of every cell is carefully controlled, and a healthy body
0:23:02 > 0:23:06always has just the right number of each type of cell.
0:23:06 > 0:23:10You have cells in the stomach here and in the gut in particular
0:23:10 > 0:23:14where you can have very rapid turnover, because the gut particularly is a
0:23:14 > 0:23:18very harsh environment, and so there's a constant high rate of turnover of cells.
0:23:18 > 0:23:22In fact, in the gut it's about every two or three days cells have to be
0:23:22 > 0:23:26replaced. And then you've got organs like the liver...
0:23:27 > 0:23:31..where there's a sort of gradual turnover of cells every few months.
0:23:31 > 0:23:34Even structures that you think may be very static, like bones
0:23:34 > 0:23:39for the skeleton here, is turned over probably once every ten years or so,
0:23:39 > 0:23:44so if we didn't have that self-renewal, you'd completely lose your skeleton,
0:23:44 > 0:23:47which would be pretty bad!
0:23:47 > 0:23:52This natural ability of our body to replace cells begs one question.
0:23:52 > 0:23:54Could we somehow harness it to renew
0:23:54 > 0:23:57and regenerate ourselves indefinitely?
0:23:57 > 0:23:59I think it's starting!
0:24:01 > 0:24:03Well...here we go again.
0:24:11 > 0:24:16Today, the idea of regenerating our brains or any other organ is no longer
0:24:16 > 0:24:18the science fiction it once was...
0:24:19 > 0:24:21..because we now know that it's stem
0:24:21 > 0:24:25cells that fuel this constant tissue renewal.
0:24:25 > 0:24:30So, stem cells are really central to understanding development and have a
0:24:30 > 0:24:32role later in life for making all
0:24:32 > 0:24:36the different tissues and organs of our body.
0:24:38 > 0:24:41Most organs have their own supply of them.
0:24:42 > 0:24:46Even the brain contains stem cells, but only in very limited areas.
0:24:49 > 0:24:53As a result, when nerve cells are lost in people with dementia,
0:24:53 > 0:24:56the brain doesn't have the capacity to repair the damage.
0:24:58 > 0:25:02But what if healthy stem cells could be injected directly into the brain
0:25:02 > 0:25:04to help repair it?
0:25:04 > 0:25:08The first steps towards this goal were taken in the early 1980s by
0:25:08 > 0:25:12Anders Bjorklund at Lund University in Sweden.
0:25:12 > 0:25:15He was interested in Parkinson's,
0:25:15 > 0:25:19a degenerative brain disease that often leads to dementia.
0:25:19 > 0:25:21If this is the brain...
0:25:22 > 0:25:26..the area we are interested in is an area up in the forebrain called
0:25:26 > 0:25:30the striatum, which regulates movement.
0:25:30 > 0:25:35Normally, dopamine neurons send nerve fibres up to the striatum,
0:25:35 > 0:25:37which produce dopamine in the striatum.
0:25:38 > 0:25:40In the Parkinson's patient,
0:25:40 > 0:25:44dopamine is missing in this area, and that is,
0:25:44 > 0:25:47in all likelihood, the major cause of their symptoms.
0:25:48 > 0:25:52Anders realised that crucial dopamine-producing brain cells were missing
0:25:52 > 0:25:53in Parkinson's disease...
0:25:54 > 0:25:59..so he decided to take dopamine cells from a rat foetus and inject them
0:25:59 > 0:26:03into the brain of an adult rat unable to produce dopamine in one part of
0:26:03 > 0:26:06its brain.
0:26:06 > 0:26:07The hope was that this would
0:26:07 > 0:26:10replenish the dopamine and restore its motor function.
0:26:12 > 0:26:14The results were remarkable.
0:26:15 > 0:26:20This rat lacks dopamine in one half of its brain and is moving around in
0:26:20 > 0:26:23circles because of this imbalance.
0:26:23 > 0:26:27But when a rat in a similar condition has had foetal dopamine cells
0:26:27 > 0:26:31transplanted, it behaves normally and no longer moves in circles.
0:26:33 > 0:26:38The success of experiments like these led scientists to consider
0:26:38 > 0:26:41transplanting foetal brain cells into humans.
0:26:41 > 0:26:45But they immediately faced strong opposition.
0:26:45 > 0:26:48The way in which you collect the foetal tissue is from...
0:26:49 > 0:26:52..women who've decided to have a termination of pregnancy,
0:26:52 > 0:26:56an abortion. This has always been a highly controversial area.
0:26:58 > 0:27:01For some, abortion itself is anathema.
0:27:02 > 0:27:05For others, the ethical issues have more to do with the point at which
0:27:05 > 0:27:09it becomes unacceptable to take material from a developing foetus.
0:27:11 > 0:27:12Most people - not all people,
0:27:12 > 0:27:17but most people - are comfortable with work on the first week or two of a
0:27:17 > 0:27:23human embryo, when it's a ball of cells, and most people would be extremely
0:27:23 > 0:27:28uncomfortable doing similar things with a much more advanced foetus,
0:27:28 > 0:27:30at 20, 22 weeks, for example.
0:27:30 > 0:27:34And somewhere between these limits,
0:27:34 > 0:27:37there's a place where it becomes unacceptable,
0:27:37 > 0:27:42but how can we define that place? And that's a really difficult debate to
0:27:42 > 0:27:46have, because there are clearly benefits to be gained,
0:27:46 > 0:27:51but there are also great concerns about the sanctity of human life.
0:27:52 > 0:27:57In the 1980s, the White House put a ban on all federal funding for this
0:27:57 > 0:28:00kind of research in the United States.
0:28:00 > 0:28:04But back in Sweden, human trials eventually got the go-ahead.
0:28:05 > 0:28:08And so, after 30 full rehearsals for the surgery,
0:28:08 > 0:28:12the Swedish team was ready and two patients with advanced Parkinson's
0:28:12 > 0:28:16disease underwent a transplant of foetal dopamine cells.
0:28:17 > 0:28:22But one year after the surgery, the patients were only slightly better.
0:28:23 > 0:28:27These initial results didn't tell the whole story, though.
0:28:27 > 0:28:29Over time, when they waited,
0:28:29 > 0:28:33they started to see some fairly dramatic results, and in the best-case
0:28:33 > 0:28:37scenario, patients, five or ten years after having the transplant,
0:28:37 > 0:28:38had, on scanning of the brain,
0:28:38 > 0:28:42normal dopamine levels produced by the dopamine cells they'd grafted.
0:28:42 > 0:28:45The patients clinically looked normal,
0:28:45 > 0:28:48they looked as though they hadn't got Parkinson's disease, and they'd
0:28:48 > 0:28:51managed to stop all of their medication.
0:28:51 > 0:28:55These extraordinary results caught the world's attention, and several
0:28:55 > 0:28:57groups tried to replicate the Swedish study.
0:28:59 > 0:29:01But they didn't succeed,
0:29:01 > 0:29:05so the area of foetal cell transplants was effectively killed off...
0:29:06 > 0:29:10..that is, until Roger Barker and Anders Bjorklund took a closer look at the
0:29:10 > 0:29:14data and realised that there were significant differences in the way these
0:29:14 > 0:29:16latest studies had been conducted.
0:29:18 > 0:29:21The main difference, I would say, between the Swedish studies and many
0:29:21 > 0:29:24of the studies that followed on was that the Swedish study used quite a lot
0:29:24 > 0:29:27of tissue, so you were never going to see a big effect if you didn't put
0:29:27 > 0:29:29in enough of the cells you wanted.
0:29:29 > 0:29:32And the other thing that became clear was that younger patients,
0:29:32 > 0:29:35slightly earlier in the disease course, probably benefit most from this.
0:29:36 > 0:29:40So, Roger and Anders decided there was enough encouraging evidence to
0:29:40 > 0:29:43justify a new study on Parkinson's patients.
0:29:45 > 0:29:48Their latest study is already under way.
0:29:48 > 0:29:52So far, nine patients have been treated with foetal dopamine cells and
0:29:52 > 0:29:55another five are to follow in 2017.
0:29:56 > 0:29:59It's too early to say whether the transplants have worked or not,
0:29:59 > 0:30:02but the results so far are encouraging.
0:30:03 > 0:30:06I'm just going to pull you backwards and I just want you to keep your
0:30:06 > 0:30:08balance. So, one, two, three.
0:30:09 > 0:30:10Very good.
0:30:10 > 0:30:15But for Roger, foetal transplants are just a stepping stone.
0:30:15 > 0:30:19Even if this trial works and the foetal dopamine cells do end up curing
0:30:19 > 0:30:23Parkinson's disease, there's a practical problem with this approach.
0:30:24 > 0:30:28We simply can't get hold of enough foetal tissue to treat the number of
0:30:28 > 0:30:31patients we need to treat.
0:30:31 > 0:30:34So, the next step for Roger is to create the same kind of dopamine cells in
0:30:34 > 0:30:36the lab.
0:30:39 > 0:30:44To do this, he needs to start off with a particular type of stem cell,
0:30:44 > 0:30:46an embryonic stem cell.
0:30:46 > 0:30:49When the egg gets fertilised and we get the cells developing in the very
0:30:49 > 0:30:52early embryo, these are called embryonic stem cells.
0:30:53 > 0:30:57Embryonic stem cells are cells which can turn into any cell in the body,
0:30:57 > 0:31:01and every single one of us began life as an embryonic stem cell.
0:31:01 > 0:31:06Embryonic stem cells are the most versatile of all stem cells, and Roger
0:31:06 > 0:31:09and his team have already been able to coax them into dopamine cells in
0:31:09 > 0:31:11the lab.
0:31:13 > 0:31:16But embryonic stem cells come with their own ethical problems.
0:31:17 > 0:31:23Embryonic stem cells are produced from leftover embryos from IVF
0:31:23 > 0:31:27procedures, so they would be discarded normally,
0:31:27 > 0:31:31but, in this instance, they're being used to make embryonic stem cells, and
0:31:31 > 0:31:34some find this an ethical issue.
0:31:34 > 0:31:37They feel that the sanctity of human life would mean that they shouldn't
0:31:37 > 0:31:39be used for this purpose.
0:31:39 > 0:31:44My own personal view is that we SHOULD use early embryos to make embryonic
0:31:44 > 0:31:47stem cells. I think that's a good thing.
0:31:47 > 0:31:52It's making use of this life that's never going to be developed to help
0:31:52 > 0:31:54other people's lives.
0:31:55 > 0:31:58Because of the ethics surrounding embryonic stem cells,
0:31:58 > 0:32:01scientists have long been looking for an alternative source for
0:32:01 > 0:32:04regenerative cells.
0:32:04 > 0:32:08And on their hunt for a new type of stem cell, one obscure experiment with
0:32:08 > 0:32:11frogs conducted in the 1960s would prove crucial.
0:32:13 > 0:32:17- ARCHIVE:- Dr John Gurdon at Oxford University wanted to test the idea that each
0:32:17 > 0:32:21of the millions of specialised cells in our bodies contains the complete
0:32:21 > 0:32:24genetic blueprint for a whole new individual.
0:32:24 > 0:32:27He chose frogs for his experiments because they are cheap,
0:32:27 > 0:32:28easy to look after
0:32:28 > 0:32:32and they lay large numbers of eggs which can put up with rough treatment.
0:32:35 > 0:32:39Eggs from a green female are set out on a microscope slide with the part
0:32:39 > 0:32:42containing the nucleus facing upwards.
0:32:42 > 0:32:46The nucleus contains the female chromosomes, which Dr Gurdon destroys
0:32:46 > 0:32:49by exposing the eggs to ultraviolet light.
0:32:50 > 0:32:55Next, albino tadpoles are dissected to provide cells for transplantation.
0:32:55 > 0:32:59Gurdon uses cells from the tissues lining the tadpole's intestine.
0:33:01 > 0:33:03With the micromanipulating gear,
0:33:03 > 0:33:07Dr Gurdon inserts one albino cell nucleus into each egg.
0:33:12 > 0:33:17Each batch of eggs is put into a dish of solution, and within a few hours
0:33:17 > 0:33:19some of the transplanted nuclei will
0:33:19 > 0:33:23begin dividing and subdividing normally.
0:33:23 > 0:33:25And this is the point of Dr Gurdon's experiment.
0:33:25 > 0:33:30It proves that each intestine cell nucleus can be switched on to multiply
0:33:30 > 0:33:32into dozens, hundreds,
0:33:32 > 0:33:35thousands and millions of cells which make up a living creature.
0:33:37 > 0:33:42As the cells multiply, they also specialise to form skin, muscle, eyes,
0:33:42 > 0:33:44brain tissue and so on.
0:33:45 > 0:33:50John Gurdon effectively managed to reprogram a tadpole cell and switch its
0:33:50 > 0:33:54genes from the duties of a gut cell to those needed to develop into an
0:33:54 > 0:33:56entire frog.
0:33:57 > 0:34:02John Gurdon's work changed the way that we think about how cells become
0:34:02 > 0:34:07specialised. What it showed was that even in specialised cells, all the
0:34:07 > 0:34:10genes were there that can make other cells,
0:34:10 > 0:34:12but what matters is which genes are
0:34:12 > 0:34:15turned on and which genes are turned off.
0:34:17 > 0:34:20John Gurdon's discovery turned on its head the view that becoming a
0:34:20 > 0:34:23specialised cell is a one-way system.
0:34:23 > 0:34:27This bold experiment suggested that even when cells perform one
0:34:27 > 0:34:31specialised role they still retain all the instructions needed to turn
0:34:31 > 0:34:33into any other type of cell.
0:34:33 > 0:34:37This raised the possibility that perhaps we could create stem cells from
0:34:37 > 0:34:40something like skin or fat cells.
0:34:40 > 0:34:43It took 50 years, but in 2006,
0:34:43 > 0:34:48a young Japanese researcher called Shinya Yamanaka finally made a
0:34:48 > 0:34:54- breakthrough.- What he showed is that he could take an adult cell and treat
0:34:54 > 0:34:59it in a particular way to turn it into a cell that had more stem cell
0:34:59 > 0:35:03properties, that could turn into other sorts of cells.
0:35:03 > 0:35:08And this actually removes the need to always work with embryonic stem cells,
0:35:08 > 0:35:11and so that removed that ethical problem.
0:35:11 > 0:35:13It was also a great bit of science.
0:35:17 > 0:35:22These new stem cells are already proving an invaluable tool in the lab,
0:35:22 > 0:35:24where they are helping scientists study dementia.
0:35:25 > 0:35:29The hope is that one day these cells can be used to regenerate many
0:35:29 > 0:35:33different parts of the brain and ultimately allow us to live longer.
0:35:38 > 0:35:42But stem cells are not only showing great promise because of their ability
0:35:42 > 0:35:45to regenerate tissues inside the body.
0:35:46 > 0:35:48Some scientists have started using
0:35:48 > 0:35:51them to create whole new organs in the lab.
0:36:07 > 0:36:12Our heart beats, without ever stopping, about 100,000 times every day...
0:36:15 > 0:36:19..and yet it is one of the few organs where cell renewal doesn't take place,
0:36:19 > 0:36:23or if it does, it does so at an almost imperceptible pace.
0:36:25 > 0:36:29This makes the heart extremely vulnerable, and any damage you accumulate
0:36:29 > 0:36:34during your lifetime simply remains there.
0:36:34 > 0:36:38A few years ago, I was privileged to go to Antarctica to visit Scott Base,
0:36:38 > 0:36:44and they made me have a full medical because there's no hospitals near
0:36:44 > 0:36:45Scott Base, of course.
0:36:45 > 0:36:52And that revealed that I had major coronary disease.
0:36:52 > 0:36:57Five of my arteries feeding the heart had partial blockages.
0:36:57 > 0:37:00That meant, within weeks, I was in hospital and I had a quadruple heart
0:37:00 > 0:37:06bypass, but I'm very lucky because I was a disaster waiting to happen.
0:37:10 > 0:37:13But not everyone is as lucky as Paul.
0:37:13 > 0:37:18Ageing can also lead to much more severe heart failure, and in some cases,
0:37:18 > 0:37:23the damage will be so big that the only hope of survival
0:37:23 > 0:37:25is a transplant.
0:37:25 > 0:37:30Surgeons had long dreamt of doing something as extreme as a transplant,
0:37:30 > 0:37:32but this remained firmly in the realm of fantasy...
0:37:34 > 0:37:38..until one man made headlines around the world in 1967.
0:37:38 > 0:37:42The world's first heart transplant has been performed.
0:37:42 > 0:37:45Medical history has been made in South Africa.
0:37:45 > 0:37:48Newspapers everywhere carry banner headlines and for medical men as far
0:37:48 > 0:37:52away as the Soviet Union, there is a claim for the dramatic breakthrough.
0:37:54 > 0:37:56The surgeon was Dr Christiaan Barnard,
0:37:56 > 0:38:00an outsider who had taken the world completely by surprise.
0:38:00 > 0:38:02That was a new experience,
0:38:02 > 0:38:06because I've never seen a human being that was
0:38:06 > 0:38:09actually alive without a heart inside his chest.
0:38:09 > 0:38:13And I realised at that stage that I was doing something different.
0:38:13 > 0:38:15I'd never done this before,
0:38:15 > 0:38:18and I realised that I have to put a heart back there.
0:38:20 > 0:38:22The patient was Louis Washkansky.
0:38:22 > 0:38:27For the first time, a transplanted heart beat inside the chest of another
0:38:27 > 0:38:28human being.
0:38:30 > 0:38:34It was amazing to see how he lost all evidence of heart failure.
0:38:34 > 0:38:38The swelling in his legs disappeared and he was well, mentally well,
0:38:38 > 0:38:42and I really did not believe that it will not be successful.
0:38:44 > 0:38:49Sadly, Louis Washkansky died two weeks after transplantation,
0:38:49 > 0:38:53but despite the death of his patient, Barnard's life was transformed.
0:38:56 > 0:38:58I'm a celebrity, everybody wants to talk to me,
0:38:58 > 0:39:00everyone wants to meet me.
0:39:00 > 0:39:03I get invitations left, right and centre. It was exciting.
0:39:03 > 0:39:07Naturally, other doctors wanted to share his popularity.
0:39:07 > 0:39:10In 1968, transplant fever gripped the world.
0:39:11 > 0:39:15102 people were given new hearts in 18 different countries.
0:39:17 > 0:39:19But as the '60s drew to a close,
0:39:19 > 0:39:23the heart transplant dream was beginning to fade.
0:39:23 > 0:39:27The problem was that patients required huge amounts of drugs to stop the
0:39:27 > 0:39:29rejection of their newly transplanted heart.
0:39:30 > 0:39:34And even with the drugs, the survival rates made grim reading.
0:39:35 > 0:39:41Cardiac surgeons who knew absolutely nothing about transplantation,
0:39:41 > 0:39:46transplant immunity, the immune transaction of rejection,
0:39:46 > 0:39:51wanted to show that they also could transplant the heart, with a 100%
0:39:51 > 0:39:54mortality, and that was a disaster.
0:39:57 > 0:40:00The man who started it all, Christiaan Barnard,
0:40:00 > 0:40:02may have become a celebrity,
0:40:02 > 0:40:06but many other medics were getting anxious, and when the BBC invited him to
0:40:06 > 0:40:09face his peers, he got a kicking.
0:40:11 > 0:40:15The nauseating publicity, I think, has done harm to the profession,
0:40:15 > 0:40:17it's done harm to yourself.
0:40:17 > 0:40:21We're going to get so many failures that the public reaction against it
0:40:21 > 0:40:27will effectively postpone the day when we can all say that this can be
0:40:27 > 0:40:29safely done.
0:40:31 > 0:40:35It wasn't until the discovery of the drug ciclosporin years later that
0:40:35 > 0:40:38organ rejection could be properly controlled.
0:40:40 > 0:40:45When you are on the edge of modern advances, it can be quite a risky
0:40:45 > 0:40:49venture. In hindsight, Christiaan Barnard got it right,
0:40:49 > 0:40:54but it probably would have only required a few more failures and we'd
0:40:54 > 0:40:57judge him, perhaps, quite differently.
0:40:59 > 0:41:01But thanks to ciclosporin,
0:41:01 > 0:41:06heart transplants eventually succeeded and survival rates began to soar.
0:41:06 > 0:41:10But this also meant the demand for organs rocketed.
0:41:12 > 0:41:16And it soon became clear that, when it came to heart transplants, demand would
0:41:16 > 0:41:19always outstrip supply,
0:41:19 > 0:41:21so the race began to find an alternative.
0:41:22 > 0:41:27One of the most obvious questions was could we build an artificial heart.
0:41:30 > 0:41:32But for many people, artificial
0:41:32 > 0:41:34organs raised fears of Frankenstein science.
0:41:34 > 0:41:38And look, here's the final touch.
0:41:40 > 0:41:44- The brain you stole, Fritz. - Yes!- Think of it,
0:41:44 > 0:41:49the brain of a dead man waiting to live again in a body I made with my
0:41:49 > 0:41:52own hands. With my own hands!
0:41:55 > 0:41:58Let's have one final test. Throw the switches.
0:42:04 > 0:42:07For the scientists working in this field, however,
0:42:07 > 0:42:11"Frankenstein science" simply means that their research is pushing the
0:42:11 > 0:42:15boundaries of the possible. Doris Taylor is one of them.
0:42:16 > 0:42:20In her quest to help us conquer the degeneration caused by ageing,
0:42:20 > 0:42:23she uses real hearts as a starting material.
0:42:24 > 0:42:27The heart is made from billions of muscle cells,
0:42:27 > 0:42:31but what Doris is most interested in is the support structure they're
0:42:31 > 0:42:36built on, so she drains the heart cells to expose this scaffold and then
0:42:36 > 0:42:40uses stem cells to build up the required heart cells on top of it.
0:42:41 > 0:42:43You need a scaffold,
0:42:43 > 0:42:46you need a place to put those cells so they know that they're a heart.
0:42:49 > 0:42:53She started by taking a rat heart and removing all its cells.
0:42:56 > 0:43:00Then she successfully introduced stem cells to the rat heart scaffold and
0:43:00 > 0:43:02made it beat again.
0:43:03 > 0:43:05Now she's gone one step further.
0:43:05 > 0:43:09She's trying the same method on human hearts.
0:43:09 > 0:43:12It's a process which, for now, begins with a donor heart.
0:43:14 > 0:43:18First, Doris needs to hang it in the best position possible to strip it of
0:43:18 > 0:43:20its own cells.
0:43:22 > 0:43:27It takes three days for the scaffold to emerge - a fine mesh of collagen,
0:43:27 > 0:43:31originally secreted from the heart cells that are no longer there.
0:43:31 > 0:43:35And that we call our "ghost heart". It's beautiful.
0:43:36 > 0:43:40It's when stem cells are placed on the ghost heart that their amazing
0:43:40 > 0:43:43potential for regeneration can be realised.
0:43:44 > 0:43:47But how do they really know how to be a heart?
0:43:47 > 0:43:49We think it's architecture.
0:43:49 > 0:43:52If you think about it, cells in a dish beat,
0:43:52 > 0:43:54but that doesn't make a heart.
0:43:54 > 0:43:59When we put them back in this scaffold, they find themselves in the right
0:43:59 > 0:44:02place. They're surrounded by the right things.
0:44:02 > 0:44:07They know they're in a thin region or a thick region, and we really think
0:44:07 > 0:44:12that to build an organ is not just a combination of cells,
0:44:12 > 0:44:15it's cells and architecture and physiology.
0:44:17 > 0:44:22Doris's ultimate goal is to create the scaffold from pigs' hearts.
0:44:22 > 0:44:26The thought would be that we would take a heart, probably from a pig...
0:44:27 > 0:44:30..do this process, wash all the cells out...
0:44:31 > 0:44:33..and then take your cells...
0:44:34 > 0:44:39..and grow enough of them to repopulate this with your cells,
0:44:39 > 0:44:42build a heart that matches your body.
0:44:42 > 0:44:46If this works, it will be revolutionary.
0:44:46 > 0:44:51But using pigs to grow human body parts is not uncontroversial.
0:44:52 > 0:44:55In thinking about this, I don't think it's really an ethical problem,
0:44:55 > 0:44:58it's more of, if I can be colloquial,
0:44:58 > 0:45:00more of a sort of "yuck factor" problem.
0:45:00 > 0:45:03It just doesn't seem quite right.
0:45:03 > 0:45:09And that still needs to be discussed, because yuck factors can influence
0:45:09 > 0:45:11whether something is accepted or not.
0:45:13 > 0:45:17But even if Doris's approach works and society accepts using animal parts
0:45:17 > 0:45:21for human transplant, could science provide a better solution?
0:45:23 > 0:45:26What if we could create an entirely artificial organ from scratch?
0:45:28 > 0:45:31One of the scientists pursuing this radical idea is
0:45:31 > 0:45:36Professor Paolo Macchiarini of the Karolinska Institute in Sweden.
0:45:36 > 0:45:40His approach is to create a scaffold from plastic and then,
0:45:40 > 0:45:44in the same way as Doris, seed it with stem cells.
0:45:45 > 0:45:49The heart is an exceptionally complex structure,
0:45:49 > 0:45:52so Paolo decided to start with something much simpler,
0:45:52 > 0:45:54the windpipe, or trachea.
0:45:56 > 0:46:00And, in 2011, he achieved the seemingly impossible.
0:46:03 > 0:46:07Surgeons in Sweden have carried out the world's first transplant using a
0:46:07 > 0:46:08synthetic organ.
0:46:08 > 0:46:11The recipient, a 36-year-old man, is said to be recovering well.
0:46:14 > 0:46:16After this initial success,
0:46:16 > 0:46:20two more synthetic tracheas were implanted into patients who suffered from
0:46:20 > 0:46:23cancerous growths on their windpipe.
0:46:23 > 0:46:25But soon things started to go wrong.
0:46:25 > 0:46:29Both these patients died shortly after their surgery.
0:46:35 > 0:46:38If you have a patient that dies because of the new technology,
0:46:38 > 0:46:44then you always ask yourself, "Did I do something wrong?
0:46:44 > 0:46:48"Do I have the right to continue? Should I continue?"
0:46:51 > 0:46:54But still, you learn only by doing.
0:46:55 > 0:47:00It's going to be quite difficult to distinguish the two...
0:47:00 > 0:47:03- measurements that we get.- Difficult but not impossible, right?
0:47:04 > 0:47:06'So, this is an interesting case.'
0:47:06 > 0:47:10Here we have a surgeon wanting to do experiments right on the edge of our
0:47:10 > 0:47:16understanding. We probably have leadership at the Karolinska who perhaps
0:47:16 > 0:47:21didn't pick up the warning signs that something was not working well, and
0:47:21 > 0:47:26there is a sort of atmosphere that develops that allows, perhaps, risks to
0:47:26 > 0:47:27take place.
0:47:31 > 0:47:33Despite these setbacks,
0:47:33 > 0:47:37Paolo carried on with his highly experimental work on patients...
0:47:38 > 0:47:43..and so over the next three years he implanted six more synthetic tracheas.
0:47:46 > 0:47:49Dmitri Onogda was his ninth patient.
0:47:50 > 0:47:55In 2007, Dmitri was involved in a serious road accident.
0:47:55 > 0:48:00His windpipe was so badly damaged that he is unable to speak and can only
0:48:00 > 0:48:02breathe through a hole made in his throat.
0:48:02 > 0:48:06Dmitri's only hope of being able to breathe and speak normally again is to
0:48:06 > 0:48:11have a new windpipe, so he's agreed to undergo this operation.
0:48:13 > 0:48:15The patient had a car accident,
0:48:15 > 0:48:17had multiple surgeries and then
0:48:17 > 0:48:22complication over complication after these surgeries.
0:48:22 > 0:48:25Here is the point where you have your vocal cords.
0:48:29 > 0:48:33Paolo's team has extracted some of Dmitri's bone marrow and then isolate
0:48:33 > 0:48:35stem cells from it.
0:48:35 > 0:48:38The hope is that by adding them to the scaffold they will grow into the
0:48:38 > 0:48:40same cells that make up the windpipe.
0:48:41 > 0:48:45The aim is not to build a completely finished windpipe in the lab.
0:48:47 > 0:48:51Paolo believes that once the scaffold is inside the body,
0:48:51 > 0:48:55the stem cells on the surface will give out a signal that will attract
0:48:55 > 0:48:59more cells to it and it will eventually develop into a fully functioning
0:48:59 > 0:49:02windpipe after transplantation.
0:49:03 > 0:49:05Can we have a smaller suction?
0:49:05 > 0:49:07When do you need it?
0:49:07 > 0:49:10- As soon as possible. - OK.
0:49:10 > 0:49:15He is above 90. So, that's not a problem. As long as it is not 40,
0:49:15 > 0:49:18that's OK.
0:49:18 > 0:49:21Don't do what you want. Go up in this here.
0:49:21 > 0:49:24I want to see the scaffold, if it is OK or not.
0:49:24 > 0:49:26Yes.
0:49:27 > 0:49:31- So, looks perfect. - So I start the next one.
0:49:32 > 0:49:34After six hours,
0:49:34 > 0:49:38Paolo is satisfied that the stem- cell-coated scaffold is in place.
0:49:40 > 0:49:42Everything OK.
0:49:42 > 0:49:45Yeah. Sure, yes, you are alive!
0:49:50 > 0:49:54Sadly, Dmitri's plastic trachea never functioned.
0:49:54 > 0:49:57It had to be removed and replaced by one from a donor,
0:49:57 > 0:50:00but Dmitri survived.
0:50:00 > 0:50:04However, he is one of only two plastic-trachea patients still alive today.
0:50:07 > 0:50:10It's not clear whether the deaths were related to the windpipe surgery...
0:50:11 > 0:50:17..but by the end of 2014, allegations emerged against Paolo.
0:50:17 > 0:50:20It was questioned whether he had exaggerated the success of his implants
0:50:20 > 0:50:23in scientific papers and conducted
0:50:23 > 0:50:26enough basic research before the human trials.
0:50:29 > 0:50:34If you have a clinical situation where you are...
0:50:34 > 0:50:35forced to take a risk,
0:50:35 > 0:50:39then you take it if you see any chance to help the patient.
0:50:46 > 0:50:49It appears Paolo was hoping that ultimately history would vindicate
0:50:49 > 0:50:51the risks he took.
0:50:51 > 0:50:53Being at the cutting edge...
0:50:55 > 0:50:57..you are always wrong...
0:50:57 > 0:51:02until sooner, more likely later, you demonstrate the opposite.
0:51:05 > 0:51:09Why should I give up? I'm not the type to give up.
0:51:11 > 0:51:17But in March 2016, Paolo was fired from the Karolinska Institute.
0:51:19 > 0:51:24We really do have to pay attention to this, because we have to maintain
0:51:24 > 0:51:30standards but we also have to have the possibility of doing experimental
0:51:30 > 0:51:33interventions like this but doing them properly.
0:51:33 > 0:51:38The real issue here, for me, was that the basic research of understanding
0:51:38 > 0:51:42what was going on here had not been carried out adequately
0:51:42 > 0:51:46so that you could more safely do the interventions in human beings.
0:51:50 > 0:51:53For Paul, these failed experiments
0:51:53 > 0:51:57are a reminder of how complex our cells are.
0:51:58 > 0:52:04As for heart transplants, the immediate future is still human donors.
0:52:06 > 0:52:10But perhaps there is an altogether simpler way of overcoming the diseases
0:52:10 > 0:52:12of old age.
0:52:12 > 0:52:15What if we could just stop getting old?
0:52:25 > 0:52:30For me, ageing is things just breaking down.
0:52:30 > 0:52:34Everything breaks down - our human bodies, also our cars.
0:52:34 > 0:52:38It's the wear and tear of working over many years that things just stop
0:52:38 > 0:52:40working properly.
0:52:43 > 0:52:46But not everyone agrees with the wear-and-tear theory of ageing.
0:52:46 > 0:52:51I think a lot of the evidence that we're finding now is that ageing isn't
0:52:51 > 0:52:57just a consequence of things falling apart in response to direct insults
0:52:57 > 0:52:59of daily living,
0:52:59 > 0:53:05some of it is the body's own activities causing the ageing process.
0:53:05 > 0:53:07It's actually the real biology of
0:53:07 > 0:53:09the cells themselves that's going wrong.
0:53:10 > 0:53:14Professor Dame Linda Partridge studies the genetics of ageing with the
0:53:14 > 0:53:17hope that one day she can slow it down.
0:53:17 > 0:53:21Her experimental subjects - fruit flies.
0:53:21 > 0:53:24In particular, she has been investigating the effects of a gene
0:53:24 > 0:53:29- called chico.- It turns out that if you knock out this gene,
0:53:29 > 0:53:33the fly lives about 30% longer than usual.
0:53:33 > 0:53:37But what's more, without the chico gene the flies also become healthier.
0:53:38 > 0:53:42They learn better when they're old, they've got better immunity,
0:53:42 > 0:53:43they move around more.
0:53:43 > 0:53:46They don't only outlive the control flies
0:53:46 > 0:53:50but they remain active long after the controls are dead.
0:53:50 > 0:53:54Linda then went on to show that there is a similar gene in mice.
0:53:54 > 0:53:56It isn't called chico in the mouse,
0:53:56 > 0:53:58it's called insulin receptor substrate 1,
0:53:58 > 0:54:01which doesn't sound quite so interesting, but if you knock it out,
0:54:01 > 0:54:07again you see this nice increase in lifespan, and also as it gets older,
0:54:07 > 0:54:12the mouse shows a broad-spectrum improvement in health and resistance to
0:54:12 > 0:54:15disease, so it's a very similar story,
0:54:15 > 0:54:20just a single gene but a very broad-spectrum effect of removing it.
0:54:22 > 0:54:26When single genes are changed, animals that should be old stay
0:54:26 > 0:54:30young and are able to resist age-related diseases.
0:54:30 > 0:54:35So does this mean we can begin to think of ageing itself as a disease?
0:54:35 > 0:54:40I would regard ageing as the king of all diseases.
0:54:40 > 0:54:43It's regarded as normal because ageing is something that happens to
0:54:43 > 0:54:47everybody. If they live that long, we tend to take it for granted.
0:54:50 > 0:54:54And if ageing is a disease, perhaps it can one day be cured
0:54:54 > 0:54:57or at least postponed.
0:54:57 > 0:55:01The next step now is to look for similar genes in humans, and early results
0:55:01 > 0:55:04suggest that they do indeed exist.
0:55:05 > 0:55:10But as tempting as it may be to knock out these genes, there is a problem.
0:55:10 > 0:55:14They turn out to be important early in life.
0:55:14 > 0:55:18We think that these genes and their activity are very valuable in young
0:55:18 > 0:55:20organisms, so we're definitely not
0:55:20 > 0:55:24talking about genetic manipulation of people.
0:55:24 > 0:55:27For Linda, rather than knocking out these ageing genes,
0:55:27 > 0:55:32the way forward will be using drugs to alter their activity later in life.
0:55:32 > 0:55:37What we'd love to be able to do is to take humans in middle age
0:55:37 > 0:55:43and start to use drugs to control the activity of these processes that
0:55:43 > 0:55:49turn out to be damaging as they get old and in that way prevent
0:55:49 > 0:55:51ageing-related diseases.
0:55:55 > 0:55:58Whether or not you think that ageing in humans will one day be a curable
0:55:58 > 0:56:03disease, one thing recent developments in biomedicine show us is that most
0:56:03 > 0:56:08of our age-related illnesses begin with the cell and the genes within it.
0:56:10 > 0:56:13Today, we're at the start of an exciting new era.
0:56:13 > 0:56:18Science is making huge leaps in tackling the killer diseases that cut us
0:56:18 > 0:56:20down in old age.
0:56:20 > 0:56:26Advances in science are really leading to a potential revolution in
0:56:26 > 0:56:31the way that we can treat disease, ways that involve gene editing,
0:56:31 > 0:56:34ways that involve stem cell therapies.
0:56:34 > 0:56:37So, there's a real promise for the future.
0:56:39 > 0:56:41But for Paul, none of this must
0:56:41 > 0:56:44happen without exploring the ethical implications.
0:56:46 > 0:56:52We have to have a society comfortable with the applications of
0:56:52 > 0:56:56science to medicine. And that means having proper debate with society,
0:56:56 > 0:56:58so that they
0:56:58 > 0:57:02are engaged and feel comfortable with what scientists are trying to do,
0:57:02 > 0:57:04because if we don't,
0:57:04 > 0:57:08then scientists will lose their licence to operate and the whole of
0:57:08 > 0:57:10society will lose out.
0:57:12 > 0:57:17But ultimately, we also need to ask ourselves how far we want to push
0:57:17 > 0:57:20the boundaries in our quest to prolong life.
0:57:20 > 0:57:22I've never seen anything like it.
0:57:22 > 0:57:25It means Linden found a way to stop ageing, maybe permanently.
0:57:25 > 0:57:29I hope you are wrong. It will be a disaster.
0:57:29 > 0:57:34Overpopulation, starvation... It will be the end of this planet.
0:57:34 > 0:57:36Or the beginning of a new civilisation.
0:57:36 > 0:57:37Come on, Dr Land.
0:57:37 > 0:57:41Sooner or later, we all have to surrender our places to others, and the more
0:57:41 > 0:57:43gracefully we do it, the better.
0:57:45 > 0:57:50For Paul, the science that aims to conquer the diseases of old age
0:57:50 > 0:57:54may deliver a bigger prize than extending life.
0:57:54 > 0:57:57I think all of us would like to live longer, as long as it's healthy,
0:57:57 > 0:58:01but do we really want immortality?
0:58:01 > 0:58:05Is there perhaps not a curse in living forever?
0:58:05 > 0:58:10All the trials and tribulations of life that we have, would never end.
0:58:12 > 0:58:16But what we should aim at is maybe living the longest normal span that
0:58:16 > 0:58:21we can imagine with a very healthy body and mind, and that's what
0:58:21 > 0:58:23I would aim at.