0:00:02 > 0:00:06This programme contains scenes which some viewers may find upsetting
0:00:13 > 0:00:14You are really lucky, you know.
0:00:14 > 0:00:17Because this morning I fight with
0:00:17 > 0:00:20a journalist from Swedish television.
0:00:20 > 0:00:23She wanted an interview
0:00:23 > 0:00:26about the allegations.
0:00:26 > 0:00:28We decided no, not to do it.
0:00:33 > 0:00:35This is Paolo Macchiarini,
0:00:35 > 0:00:39one of the world's best-known surgeons
0:00:39 > 0:00:41in one of his most difficult moments.
0:00:43 > 0:00:47He had declined almost every interview from the world's media,
0:00:47 > 0:00:49but he agreed to talk just to me.
0:00:50 > 0:00:54Perhaps he was hoping it would be an opportunity to tell his version,
0:00:54 > 0:00:57or that I at least would tell the story with all its complexities.
0:01:00 > 0:01:02Though neither of us knew it then,
0:01:02 > 0:01:05this would eventually lead to his spectacular downfall.
0:01:07 > 0:01:10At the time, he still enjoyed his reputation
0:01:10 > 0:01:13as one of the world's most pioneering surgeons.
0:01:20 > 0:01:24Surgeons in Sweden have carried out the world's first transplant
0:01:24 > 0:01:25of a synthetic organ...
0:01:25 > 0:01:28An 11-year-old boy has had pioneering treatment to
0:01:28 > 0:01:31rebuild his windpipe using stem cell...
0:01:31 > 0:01:35Macchiarini is trying to solve one of medicine's biggest challenges -
0:01:35 > 0:01:38the lack of spare parts when something
0:01:38 > 0:01:40goes wrong inside our bodies.
0:01:41 > 0:01:44He has already made headlines round the world,
0:01:44 > 0:01:47by attempting to create the world's first windpipe out of plastic.
0:01:49 > 0:01:51In what seems like the plot from a science fiction novel,
0:01:51 > 0:01:53researchers built a new windpipe...
0:01:53 > 0:01:56We are just a few years away from all this happening,
0:01:56 > 0:01:58all the organs being built in a lab.
0:01:58 > 0:02:02So far, there are 17 people around the world who have had one of
0:02:02 > 0:02:04Macchiarini's windpipes implanted.
0:02:07 > 0:02:11But for most of them, everything still ended the same way -
0:02:11 > 0:02:13with death.
0:02:18 > 0:02:20You think this is one of the biggest medical scandals?
0:02:21 > 0:02:26If you do experimental surgery in humans and you know beforehand
0:02:26 > 0:02:27that it's a disaster.
0:02:29 > 0:02:31Macchiarini has been accused of falsifying research
0:02:31 > 0:02:35and of experimenting on humans.
0:02:35 > 0:02:36While I was filming,
0:02:36 > 0:02:39police began investigating some of his operations
0:02:39 > 0:02:41on suspicion of causing
0:02:41 > 0:02:45bodily harm and involuntary manslaughter.
0:02:45 > 0:02:48Yet, he still enjoyed the support of the scientific establishment.
0:03:00 > 0:03:02So who is Paolo Macchiarini?
0:03:03 > 0:03:04Is he a genius?
0:03:05 > 0:03:06Or is he a fraud?
0:03:09 > 0:03:13How far can you risk a human life in the name of cutting-edge science?
0:03:14 > 0:03:18And are some of the world's top medical institutions complicit in
0:03:18 > 0:03:20supporting his experimental work?
0:03:21 > 0:03:25The process of getting answers was far tougher than I'd anticipated.
0:04:32 > 0:04:35Does a human life have a price?
0:04:38 > 0:04:40I didn't do anything wrong.
0:04:54 > 0:04:56I just did my job.
0:05:19 > 0:05:22For me, it all started at the end of 2014,
0:05:22 > 0:05:26when Macchiarini was accused of falsifying research results
0:05:26 > 0:05:28and of gross misconduct.
0:05:29 > 0:05:32Could this really have happened at the Karolinska Institute,
0:05:32 > 0:05:35Sweden's prestigious medical university,
0:05:35 > 0:05:37the home of the Nobel Prize?
0:05:38 > 0:05:40These allegations were very serious, of course.
0:05:41 > 0:05:43What if they were true?
0:05:44 > 0:05:47I decided to find out what had happened.
0:05:50 > 0:05:52And soon I got to meet Paolo Macchiarini
0:05:52 > 0:05:55at his lab in the Karolinska Institute in Sweden.
0:06:00 > 0:06:04- OK.- OK.- So this...
0:06:06 > 0:06:08KEYPAD BEEPS
0:06:23 > 0:06:26My first surprise came right away.
0:06:26 > 0:06:30Macchiarini's space at the Institute looked so small and modest.
0:06:30 > 0:06:32Thank you.
0:06:32 > 0:06:34But according to Macchiarini,
0:06:34 > 0:06:37big things were happening in this ordinary setting.
0:06:37 > 0:06:41This is, however, I think, the most advanced lab
0:06:41 > 0:06:44that we do have here.
0:06:46 > 0:06:51One of the most advanced in, I can frankly say, in the world.
0:06:51 > 0:06:55We have a series of
0:06:55 > 0:06:58devices and tools to evaluate
0:06:58 > 0:07:00the organs,
0:07:00 > 0:07:02whether biological or artificial,
0:07:02 > 0:07:06and here we do everything from the brain to the heart,
0:07:06 > 0:07:09to the lungs, to the kidney, to the intestines,
0:07:09 > 0:07:14to the urethra and other investigations.
0:07:18 > 0:07:23Countless people die each year because their organs stop working.
0:07:23 > 0:07:28The shortage of new organs is one of medicine's biggest problems
0:07:28 > 0:07:31and it is this issue that Macchiarini is trying to solve.
0:07:34 > 0:07:37Organs from rats float in these flasks.
0:07:38 > 0:07:42Hearts and kidneys, oesophagi and tracheas.
0:07:43 > 0:07:46Organs that will bathe in stem cells
0:07:46 > 0:07:50and perhaps, one day in the future, become artificial organs.
0:07:54 > 0:07:58Macchiarini would revolutionise the medical world, if he succeeds.
0:08:00 > 0:08:05Even though the lab is small, this was Macchiarini's main base.
0:08:05 > 0:08:10He travels constantly and collaborates with researchers around the world.
0:08:10 > 0:08:12'Especially in Russia.'
0:08:12 > 0:08:15Findings here, you may apply perhaps in Russia?
0:08:15 > 0:08:21Of course, the findings here will be available to everyone because they
0:08:21 > 0:08:23will be published in the public domain.
0:08:23 > 0:08:29But clearly, by sharing the information, we can move
0:08:29 > 0:08:32at a level, at a higher speed and knowledge.
0:08:34 > 0:08:36'But it's due to his work in Stockholm
0:08:36 > 0:08:37'that he is under pressure now.'
0:08:58 > 0:09:01One needs to explain to me what is my interest in...
0:09:03 > 0:09:05..doing illegal surgeries or...
0:09:07 > 0:09:10..fabricating or manipulating data.
0:09:10 > 0:09:13Why I should be so foolish.
0:09:18 > 0:09:23Being what the media call me, a superstar, I am always,
0:09:23 > 0:09:26in German is "Black Peter", the bad boy.
0:09:27 > 0:09:29Being famous, it's very easy to attack...
0:09:31 > 0:09:35..before even the judgment has come, the final judgment.
0:09:35 > 0:09:38I think it's quite unfair
0:09:38 > 0:09:43and has destroyed my reputation and my honourability.
0:09:45 > 0:09:49And you know exactly the media don't come back...
0:09:50 > 0:09:54..they highlight the bad things, but not the good things.
0:09:59 > 0:10:00Hi.
0:10:03 > 0:10:08In 2010, Macchiarini was headhunted by the Karolinska Institute to
0:10:08 > 0:10:12start up a centre for research and transplantation of new organs.
0:10:15 > 0:10:19The whole world of academia competes over famous scientists like
0:10:19 > 0:10:23Macchiarini. Almost how sports clubs buy players.
0:10:25 > 0:10:28Top scientists can mean both revolutionary discoveries
0:10:28 > 0:10:31and bigger grants for the university.
0:10:33 > 0:10:35The very best are hunted from all over the world.
0:10:38 > 0:10:41And Macchiarini has also been signed up by Russia.
0:10:55 > 0:10:58I travelled with Paolo to Krasnodar,
0:10:58 > 0:11:00the south of the country, his second base.
0:11:05 > 0:11:07This was the start of several long journeys.
0:11:09 > 0:11:12Macchiarini's story was much bigger and stranger
0:11:12 > 0:11:15than I ever could have imagined.
0:11:16 > 0:11:18- Hello.- Hello, how are you? - Fine, how are you?
0:11:18 > 0:11:20Good.
0:11:25 > 0:11:26Not usually.
0:11:37 > 0:11:39I'm working for the university.
0:11:41 > 0:11:43We are trying to create new organs.
0:11:46 > 0:11:47Frankenstein.
0:11:53 > 0:11:55It hit me how untouched Paolo seemed
0:11:55 > 0:11:58by the allegations that had been made against him.
0:11:59 > 0:12:02It was as if it was just a minor glitch.
0:12:03 > 0:12:06Macchiarini had set himself far more ambitious goals.
0:12:08 > 0:12:11'My dream would be, as I always say,'
0:12:11 > 0:12:14to avoid the surgery.
0:12:14 > 0:12:17It's crazy, right? A surgeon who would say that.
0:12:17 > 0:12:22But, for instance, use the cells to restore the function of an organ.
0:12:22 > 0:12:23That would be perfect.
0:12:26 > 0:12:30So cell therapy, is, to my eyes, the future.
0:12:32 > 0:12:37Paolo was hoping to change the very foundations of modern medical care.
0:12:39 > 0:12:42It's been a long fight for you to do this?
0:12:43 > 0:12:44Oh, yes.
0:12:45 > 0:12:48Do you feel that you are closer to
0:12:48 > 0:12:50actually succeeding now than you have been before?
0:12:51 > 0:12:54If I would have more time to dedicate to science,
0:12:54 > 0:12:58without dealing with all this...
0:12:58 > 0:13:00other issues and complaints,
0:13:00 > 0:13:03allegations and attacks and so forth, then, yes.
0:13:07 > 0:13:10So the allegations and the complaints,
0:13:10 > 0:13:11they do hinder your work,
0:13:11 > 0:13:14they take up a lot of time?
0:13:14 > 0:13:15Right now, I'm doing almost only that,
0:13:15 > 0:13:21so clearly I cannot have a relaxed and creative mind
0:13:21 > 0:13:23right now.
0:13:23 > 0:13:25It's been going on six months.
0:13:27 > 0:13:31Interesting, something you can talk about?
0:13:31 > 0:13:35No, because the deal was, we would not talk about this, remember that?
0:13:37 > 0:13:38'Of course I remembered.
0:13:39 > 0:13:43'Macchiarini had let me into his world on one condition,
0:13:43 > 0:13:47'he wanted to bide his time before responding to the allegations.
0:13:48 > 0:13:51'His Swedish employer, the Karolinska Institute,
0:13:51 > 0:13:53'was still investigating his case.
0:13:53 > 0:13:57'The process must be allowed to run its course.'
0:13:57 > 0:13:58Perfect.
0:14:10 > 0:14:11Like it.
0:14:11 > 0:14:12Changes.
0:14:15 > 0:14:17OK, see you later or tomorrow morning.
0:14:17 > 0:14:19Later, or tomorrow morning? About six.
0:14:21 > 0:14:24OK. See you, cheers, Paolo, it was really nice.
0:14:24 > 0:14:25Good.
0:14:49 > 0:14:53Here, in southern Russia, near Crimea and the Black Sea,
0:14:53 > 0:14:58Paolo is creating a centre for transplantation and research.
0:14:58 > 0:14:59It aims to be world leading.
0:15:04 > 0:15:08The base of the project is Paolo's lab at the University of Krasnodar.
0:15:25 > 0:15:27Wait...
0:15:28 > 0:15:30- Sorry.- You should come now...
0:15:30 > 0:15:32Who? Now.
0:15:32 > 0:15:33OK...
0:15:33 > 0:15:38Elena Gubareva is Paolo's research director here.
0:15:38 > 0:15:40She has created an artificial diaphragm,
0:15:40 > 0:15:43one of the muscles we use to breathe.
0:15:43 > 0:15:44She has done,
0:15:44 > 0:15:46I mean, the leader on this,
0:15:46 > 0:15:50transplanting the entire diaphragm on the left side...
0:15:50 > 0:15:52- Incredible.- ..which is incredible.
0:15:52 > 0:15:56Just incredible. Nobody has done that with that success rate.
0:15:56 > 0:16:00But...nobody believes it.
0:16:00 > 0:16:05Whether it is because it is coming from Russia,
0:16:05 > 0:16:09whether it is because I am under investigation
0:16:09 > 0:16:11from all these allegations,
0:16:11 > 0:16:14whether it is because it is too incredible.
0:16:14 > 0:16:18So we are having difficulties in...
0:16:18 > 0:16:23publishing it, but you will see it, how it works.
0:16:23 > 0:16:25So that's...
0:16:27 > 0:16:34..part of the challenge of this new field, this high technology,
0:16:34 > 0:16:37this new advanced field.
0:16:37 > 0:16:41Everything that is new scares and people do not trust,
0:16:41 > 0:16:43it's like Mahatma Gandhi,
0:16:43 > 0:16:45first they don't believe,
0:16:45 > 0:16:48then they criticise you and then they start to...
0:16:48 > 0:16:52When you were dying, when you die, maybe you were right.
0:16:52 > 0:16:53Maybe.
0:16:54 > 0:16:55But I'm not Mahatma Gandhi.
0:16:58 > 0:17:01OK, I think you should wear your coat
0:17:01 > 0:17:04because we should go...
0:17:04 > 0:17:05OK.
0:17:05 > 0:17:08'Elena shows me the rest of the lab.
0:17:08 > 0:17:11'This is a controversial part of medical research.
0:17:11 > 0:17:13'Most people are never allowed in.'
0:17:13 > 0:17:15You should go to animal.
0:17:22 > 0:17:25This is cages for animals, this is for big animals,
0:17:25 > 0:17:29for pigs, which will bring us in future.
0:17:29 > 0:17:33These cages are for rabbits and rats.
0:17:33 > 0:17:37They live here. This is for different types of investigation.
0:17:44 > 0:17:46Right, are you ready?
0:17:48 > 0:17:51- Just a minute, please. - Just a minute, OK.
0:17:51 > 0:17:56We will go in the surgical room to do all the steps of the operation.
0:18:08 > 0:18:13You can see. And now we will bring it to a surgical room.
0:18:32 > 0:18:37Experiments on cells alone are often not enough to prove if a treatment
0:18:37 > 0:18:39will work on the human body.
0:18:40 > 0:18:44But if the experiments aren't performed on a human guinea pig,
0:18:44 > 0:18:46you may need something else.
0:18:49 > 0:18:51It might seem cruel,
0:18:51 > 0:18:53and at times it is.
0:18:58 > 0:19:03First, you remove the diaphragm from the donor rat.
0:19:06 > 0:19:08The muscle is then washed in strong chemicals
0:19:08 > 0:19:11so that all the donor cells are gone.
0:19:13 > 0:19:16You are then left with a dead scaffold of a diaphragm.
0:19:20 > 0:19:25This scaffold is then submerged in a solution of stem cells from the rat
0:19:25 > 0:19:27that will receive the new muscle.
0:19:30 > 0:19:33Then the rat that will get the new muscle, the receiver rat,
0:19:33 > 0:19:36is opened up and the old diaphragm is removed.
0:19:38 > 0:19:43The new muscle scaffold is taken out of its bath and implanted into the
0:19:43 > 0:19:44receiver rat.
0:19:47 > 0:19:50The idea is that the stem cells will morph into different
0:19:50 > 0:19:53cell types to create a new organ.
0:19:57 > 0:20:02This is animals after treatment and these two rats are rats after
0:20:02 > 0:20:06transplantation of diaphragm after six months.
0:20:06 > 0:20:08They are absolutely healthy
0:20:08 > 0:20:11and there are no problems with health.
0:20:11 > 0:20:14They have a good health status.
0:20:14 > 0:20:16These two guys are basically world unique, right?
0:20:16 > 0:20:18Yep, yep.
0:20:18 > 0:20:20- The first?- The first.
0:20:20 > 0:20:22'According to Gubareva and Macchiarini,
0:20:22 > 0:20:25'these two rats are the first animals in the world
0:20:25 > 0:20:28'to breathe with the help of an artificial muscle.'
0:20:28 > 0:20:34100 years ago, everybody said that heart transplantation is impossible,
0:20:34 > 0:20:38but now we can see that heart transplantation is not routine,
0:20:38 > 0:20:42but everybody knows it is possible to do.
0:20:42 > 0:20:44It's very important, never stop.
0:20:44 > 0:20:47Try to do everything what you can.
0:20:48 > 0:20:49- Bye.- Bye-bye.
0:20:50 > 0:20:54'I got to see more and more of the lab and I couldn't help but be
0:20:54 > 0:20:59'impressed. What they were trying to achieve was simply great.
0:20:59 > 0:21:03'To Gubareva and Macchiarini it didn't seem to be questioned IF
0:21:03 > 0:21:07'the new method with transplanted organs would ever become reality,
0:21:07 > 0:21:10'but rather WHEN the big breakthrough would happen.'
0:21:10 > 0:21:13We started with the trachea and now we are at
0:21:13 > 0:21:15a higher level of complexity
0:21:15 > 0:21:19because the oesophagus needs to contract,
0:21:19 > 0:21:24the muscle diaphragm needs to contract, so all this capacities,
0:21:24 > 0:21:26function capacities, needs to be preserved.
0:21:28 > 0:21:31We do hope that
0:21:31 > 0:21:36possibly in the middle of next year we could think to,
0:21:36 > 0:21:39after having all the ethical commissions clearance,
0:21:39 > 0:21:42to have the green light to do it in humans.
0:21:49 > 0:21:54Paolo told me he intends to go from rat to human in just one year,
0:21:54 > 0:21:56which is fast.
0:21:59 > 0:22:00And during this time,
0:22:00 > 0:22:04he will also need to test his new artificial muscles on more animals.
0:22:11 > 0:22:13Here in Sochi, near the Black Sea,
0:22:13 > 0:22:16there is one of the world's largest facilities
0:22:16 > 0:22:17for experiments on monkeys.
0:22:19 > 0:22:23Under communism, well guarded secret departments of the Soviet military
0:22:23 > 0:22:24were located here.
0:22:26 > 0:22:28Civilian scientists are now able to experiment
0:22:28 > 0:22:31on the thousands of monkeys that live here.
0:22:34 > 0:22:37But the preparations for Paolo's trials here in Sochi
0:22:37 > 0:22:38have been delayed.
0:22:45 > 0:22:47- Hello. - Hello, nice to meet you.
0:22:47 > 0:22:48How are you?
0:22:55 > 0:22:57'We are about four months...'
0:22:59 > 0:23:01We have a four-month delay
0:23:01 > 0:23:07on the timescale because we haven't done that much progress since we
0:23:07 > 0:23:09started, and this...
0:23:11 > 0:23:15Research grants are so strict that if we don't provide results,
0:23:15 > 0:23:18then we will not be able to continue the grant.
0:23:26 > 0:23:28She wanted to know which,
0:23:28 > 0:23:31- what timing for grant, this research.- Yesterday.
0:23:31 > 0:23:35- Yesterday.- My problem is that nothing happens, and I hate that.
0:23:35 > 0:23:40I mean, it makes no sense, and then we talk and we talk and we talk,
0:23:40 > 0:23:41and nothing happens.
0:23:41 > 0:23:45The last time we met in December and now we are
0:23:45 > 0:23:51almost in April and nothing has been done, and clearly we cannot
0:23:51 > 0:23:54continue in this way because otherwise when we need to do
0:23:54 > 0:23:56the technical report of the project...
0:23:56 > 0:24:00Nyet, nyet, nyet.
0:24:00 > 0:24:02Then it's very bad.
0:24:07 > 0:24:10Unfortunately, things need to be done, so...
0:24:13 > 0:24:14Ladies!
0:24:23 > 0:24:27Normally, scientists would start with test tubes,
0:24:27 > 0:24:29then experiment on rats,
0:24:29 > 0:24:33move on to bigger animals and after that, humans.
0:24:35 > 0:24:40That is usually how medical research works to avoid the risks escalating.
0:24:42 > 0:24:44If Paolo had always worked in this way,
0:24:44 > 0:24:46this film may never have happened.
0:24:48 > 0:24:49But he hasn't.
0:24:55 > 0:24:59Though Paolo aimed to test on animals here in Krasnodar,
0:24:59 > 0:25:02he'd already tested a similar method on humans.
0:25:04 > 0:25:07It was in 2008 that he took that controversial step.
0:25:11 > 0:25:12This is Claudia Castillo.
0:25:14 > 0:25:16She sought Macchiarini's help
0:25:16 > 0:25:18after one of her bronchi had closed up.
0:25:20 > 0:25:22A defect which medicine back then couldn't cure.
0:25:37 > 0:25:41This was something completely new - tracheas and stem cells.
0:25:41 > 0:25:43This is how it was explained to the world...
0:25:46 > 0:25:49Paolo cut out a piece of the windpipe from a dead donor.
0:25:53 > 0:25:55The piece was then washed clean of donor cells.
0:25:59 > 0:26:02Then Claudia's stem cells were taken from her bone marrow.
0:26:06 > 0:26:11The cleansed windpipe was bathed in Claudia's stem cell solution and
0:26:11 > 0:26:14a little piece of it was inserted into Claudia.
0:26:34 > 0:26:36Even if Macchiarini had taken big risks,
0:26:36 > 0:26:39it all seemed to have worked out.
0:26:40 > 0:26:44'The scientists believe their technique can immediately help up to
0:26:44 > 0:26:46'3,000 people like Claudia across Europe
0:26:46 > 0:26:48'and eventually tens of thousands
0:26:48 > 0:26:51'more with diseases like cancer of the larynx.'
0:26:51 > 0:26:54Macchiarini's method became world news.
0:26:55 > 0:27:00The prestigious medical journal the Lancet ranked his research article
0:27:00 > 0:27:02amongst the year's ten most important.
0:27:04 > 0:27:07So, in this case, it's not just a promise,
0:27:07 > 0:27:08we've achieved what we set out to do.
0:27:08 > 0:27:11It's a major achievement in the history of medicine.
0:27:15 > 0:27:17In a short space of time,
0:27:17 > 0:27:20Macchiarini went on to transplant several new tracheas.
0:27:25 > 0:27:28In London, he participated in an operation
0:27:28 > 0:27:30on a ten-year-old Irish boy,
0:27:30 > 0:27:32who was born with a trachea too small.
0:27:32 > 0:27:37'It saved his life and has been described as a kind of miracle.'
0:27:37 > 0:27:41In Moscow, on a woman from Kazakhstan,
0:27:41 > 0:27:45and in Florence, on a young British woman with cancer.
0:27:50 > 0:27:54Macchiarini's status as a star was now at its peak.
0:28:11 > 0:28:14He was desirable prey for universities and hospitals
0:28:14 > 0:28:17around the globe,
0:28:17 > 0:28:21but in the end, it was Russia and Sweden who hired him.
0:28:23 > 0:28:26Macchiarini took the Karolinska Institute by storm,
0:28:26 > 0:28:29not least among the surgeons, who thought he was fantastic.
0:28:31 > 0:28:34Here was a colleague who was not only extremely competent in his
0:28:34 > 0:28:39handiwork, but he also seemed to be revolutionising an entire science.
0:29:09 > 0:29:13Karl-Henrik Grinnemo is a surgeon and researcher.
0:29:13 > 0:29:16Together with his colleague, Matthias Corbascio,
0:29:16 > 0:29:19he was asked to help Macchiarini set up the unit.
0:29:40 > 0:29:44Macchiarini was now commissioned to start up an international centre for
0:29:44 > 0:29:47transplantation and surgery at the Karolinska Institute.
0:29:48 > 0:29:51He was meant to do research at the Institute
0:29:51 > 0:29:54and also perform experimental surgery at its hospital.
0:30:17 > 0:30:22Paolo had also been asked to do research on other vital organs.
0:31:12 > 0:31:14But the pressure was intense.
0:31:16 > 0:31:18Paolo was expected to have started
0:31:18 > 0:31:21ground-breaking operations within three months.
0:31:24 > 0:31:28But months went by without Paolo performing a single transplant.
0:31:31 > 0:31:34And he was also facing other problems.
0:31:36 > 0:31:38Paolo had carried out transplants
0:31:38 > 0:31:40on nearly ten patients using his new method,
0:31:40 > 0:31:44but several tracheas had started to collapse.
0:31:45 > 0:31:47How was he going to solve this?
0:31:48 > 0:31:50Paolo had a new idea.
0:31:50 > 0:31:53This time, something really untested.
0:31:54 > 0:31:58He would stop the transplants using donated wind pipes,
0:31:58 > 0:32:02and instead manufacture artificial ones out of plastic.
0:32:04 > 0:32:06But who would be the guinea pig?
0:32:12 > 0:32:15By chance, he came across a patient in Iceland.
0:32:16 > 0:32:20A student from Eritrea by the name of Andemariam Beyene.
0:32:21 > 0:32:24Andemariam was studying geothermal energy.
0:32:27 > 0:32:29He was finding it hard to breathe.
0:32:31 > 0:32:35For a while he thought it was asthma, but the drugs didn't help.
0:32:35 > 0:32:40Then his Icelandic doctor discovered he had cancer of the trachea.
0:32:56 > 0:33:01In 2011, Andemariam's ability to breathe worsened again.
0:33:01 > 0:33:05His Icelandic doctor began to look abroad for specialist help.
0:33:05 > 0:33:09The Karolinska Hospital suggested Macchiarini.
0:33:09 > 0:33:14One patient was referred from Iceland that was given,
0:33:14 > 0:33:16in Harvard in Boston,
0:33:16 > 0:33:20a life expectancy of six months because he was already operated on.
0:33:20 > 0:33:22He had a shortness of breath
0:33:22 > 0:33:27and the case was discussed here, multidisciplinary and...
0:33:29 > 0:33:31..we decided that he was at risk of suffocation.
0:33:33 > 0:33:37We were in need of something now and not tomorrow.
0:33:37 > 0:33:41Paolo now decided to try his new idea with plastic tracheas on Andemariam.
0:33:43 > 0:33:48Compared to the old procedure that we did so far since 2008,
0:33:48 > 0:33:51a completely new approach where
0:33:51 > 0:33:56we don't use natural wind pipes,
0:33:56 > 0:34:04but synthetic polymers to build a custom-made individual windpipe.
0:34:07 > 0:34:09The operation was performed
0:34:09 > 0:34:12at Karolinska University Hospital in June 2011.
0:34:18 > 0:34:21Karl-Henrik Grinnemo was one of several surgeons
0:34:21 > 0:34:23who assisted during the operation.
0:35:09 > 0:35:11The surgery was very difficult.
0:35:11 > 0:35:15You had three experienced surgeons at the operating table,
0:35:15 > 0:35:19but believe me, it was one of the most difficult surgeries we did
0:35:19 > 0:35:22and it was the first time we used this material.
0:35:22 > 0:35:27Not optimum material, because it was done in a hurry and to afford.
0:36:48 > 0:36:52A ground-breaking surgery gave a man back his trachea and his life.
0:36:52 > 0:36:54He is the first person...
0:36:54 > 0:36:57There were great headlines, and just as they had hoped,
0:36:57 > 0:36:59Macchiarini and the Karolinska Institute
0:36:59 > 0:37:00caught the world's attention.
0:37:00 > 0:37:02It's his tissue, it's his cells,
0:37:02 > 0:37:04but those cells have differentiated
0:37:04 > 0:37:07from bone marrow cells to become all the different cell types.
0:37:07 > 0:37:10So it really is a living, breathing organ at this point.
0:37:10 > 0:37:12Over a month later, Beyene is not only breathing,
0:37:12 > 0:37:15but on the road to recovery.
0:37:15 > 0:37:19He is soon to be discharged from the hospital and heading home to his family.
0:37:19 > 0:37:21But things didn't look quite as good
0:37:21 > 0:37:25for one of Macchiarini's earlier patients, Keziah Shorten...
0:37:27 > 0:37:30..the young British woman who Macchiarini had
0:37:30 > 0:37:33transplanted a donated trachea into in Florence.
0:37:35 > 0:37:38After some time at home in England,
0:37:38 > 0:37:40her doctors observed that
0:37:40 > 0:37:44the transplant had failed and that her windpipe was hanging loose.
0:37:46 > 0:37:48For a long time, her British doctors
0:37:48 > 0:37:51had been collaborating with Macchiarini,
0:37:51 > 0:37:55but now they had to manage a disastrous situation on their own.
0:37:56 > 0:38:02We were faced with a very difficult clinical problem here at UCL,
0:38:02 > 0:38:06of a girl, aged 20, who had had a terrible carcinoma,
0:38:06 > 0:38:08cancer of her windpipe,
0:38:08 > 0:38:11and had had this operated on elsewhere.
0:38:12 > 0:38:14She'd had the windpipe essentially removed,
0:38:14 > 0:38:18reconstructed in a different way, and that had all broken down.
0:38:20 > 0:38:23However, having seen what had happened in Sweden,
0:38:23 > 0:38:26we felt this offered her some chance.
0:38:28 > 0:38:31The plastic trachea Macchiarini had used on Andemariam had been
0:38:31 > 0:38:35manufactured in London by one of Birchall's colleagues.
0:38:37 > 0:38:40Birchall now ordered one more for Keziah.
0:38:43 > 0:38:45We did put a synthetic.
0:38:45 > 0:38:48I was the one who stitched in the top end, and my thoracic colleagues
0:38:48 > 0:38:51stitched from the bottom end of this synthetic implant.
0:38:51 > 0:38:55Even when working with it, you could tell it was too rigid, it wasn't...
0:38:55 > 0:38:58You couldn't see any evidence of any cells there.
0:38:58 > 0:39:01Microscopically, there may have been some cells.
0:39:01 > 0:39:03There was certainly no respiratory lining.
0:39:03 > 0:39:05Um, I...
0:39:05 > 0:39:07You know, it was a bit of plastic.
0:39:07 > 0:39:09An expensive bit of plastic.
0:39:10 > 0:39:13I couldn't see it working, and sure enough, it didn't work.
0:39:15 > 0:39:19Keziah's trachea was made from the same plastic as Andemariam's.
0:39:21 > 0:39:24It was a special plastic called POSS-PCU.
0:39:26 > 0:39:29The POSS-PCU had not performed as well as we'd hoped.
0:39:29 > 0:39:32It hadn't integrated into its surroundings very well
0:39:32 > 0:39:34and had become infected,
0:39:34 > 0:39:36principally with fungus, but also with some bacteria as well.
0:39:39 > 0:39:42The two ends of the trachea, really, were very loose,
0:39:42 > 0:39:44they had not integrated at all.
0:39:44 > 0:39:47There were sutures that were holding it in place, but very loosely.
0:39:48 > 0:39:51She remained on the intensive care unit at UCL
0:39:51 > 0:39:52for another six weeks or so,
0:39:52 > 0:39:55but then was able to be discharged back to Brighton,
0:39:55 > 0:39:58on the south coast of England, to be with her family for a few months.
0:40:02 > 0:40:04Keziah's condition worsened.
0:40:05 > 0:40:08Shortly afterwards, she passed away.
0:40:11 > 0:40:13The material doesn't really work, basically.
0:40:13 > 0:40:17In its present form, that particular material
0:40:17 > 0:40:22is not the solution to tracheal transplantation right now.
0:40:39 > 0:40:41But the British surgeons weren't the only ones
0:40:41 > 0:40:43doubting Paolo's plastic tracheas.
0:40:45 > 0:40:49A colleague of theirs, Pierre Delaere, was working in Belgium.
0:40:50 > 0:40:54He was astounded to hear about Paolo's operation on Andemariam.
0:41:42 > 0:41:45Delaere warned the Vice Chancellor at Karolinska.
0:41:46 > 0:41:49He claimed that Macchiarini's research studies
0:41:49 > 0:41:51were misleading the general public and the medical world,
0:41:51 > 0:41:55making people believe that plastic tracheas actually worked,
0:41:55 > 0:41:58despite it being physically impossible.
0:42:37 > 0:42:40Karolinska ignored the warning.
0:42:41 > 0:42:45And the hospital went ahead with the next plastic operation
0:42:45 > 0:42:48on an American suffering from cancer,
0:42:48 > 0:42:50who had found Macchiarini on the internet.
0:42:50 > 0:42:52My name is Christopher Lyles.
0:42:54 > 0:42:58Born and raised in Maryland, graduated Morgan State University.
0:42:58 > 0:43:01I have a four-year-old.
0:43:01 > 0:43:02I want to see her grow.
0:43:05 > 0:43:06I'm not going anywhere.
0:43:10 > 0:43:13Lyles was operated on in November 2011.
0:43:14 > 0:43:17Just four months later he was dead.
0:43:19 > 0:43:21Two out of the world's three patients
0:43:21 > 0:43:24with plastic tracheas were now dead.
0:43:26 > 0:43:29But Delaere's warnings never took hold in the media.
0:43:29 > 0:43:32From the outside it all looked good.
0:43:35 > 0:43:37During the spring of 2012,
0:43:37 > 0:43:41a German TV crew began to follow Macchiarini very closely.
0:43:41 > 0:43:45The scan would be, eventually, of some help as well.
0:43:45 > 0:43:47So...
0:43:47 > 0:43:50Here are some shots from the German team's unedited footage.
0:43:51 > 0:43:55When I see this, it feels like stepping into a time machine,
0:43:55 > 0:43:58as everything was caught on tape,
0:43:58 > 0:44:01not least the difficulties with Macchiarini's project.
0:44:02 > 0:44:05But, please, try to answer this question,
0:44:05 > 0:44:07because he's making me crazy. I hate that.
0:44:07 > 0:44:12In this material, I would make several serious discoveries.
0:44:12 > 0:44:14May Lin.
0:44:15 > 0:44:16You do not forget me.
0:44:18 > 0:44:19OK, bye.
0:44:20 > 0:44:21Bye.
0:44:22 > 0:44:24Wow.
0:45:04 > 0:45:09Behind the scenes, Paolo was obviously well aware of the death.
0:45:09 > 0:45:11But it didn't seem to stop him.
0:45:33 > 0:45:37Even though Paolo couldn't be sure why his patient had died,
0:45:37 > 0:45:39he still made plans for new operations.
0:45:41 > 0:45:46In the US, he collaborated with the biotech company Harvard Bioscience.
0:45:46 > 0:45:51Here's how the president of the company, David Green, presented the method.
0:45:51 > 0:45:53The bioreact we build is actually no bigger than this.
0:45:53 > 0:45:55It's about the size of a shoebox,
0:45:55 > 0:45:57and inside there's a rotating part...
0:45:57 > 0:46:01Green manufactured Macchiarini's bioreactor,
0:46:01 > 0:46:04the plastic box with the tracheas bathed in stem cells.
0:46:04 > 0:46:07For the viewers, David Green described
0:46:07 > 0:46:10the method as if it was magic.
0:46:10 > 0:46:12The plastic would come to life in no time.
0:46:12 > 0:46:14What's it made out of?
0:46:14 > 0:46:16It's actually made out of a plastic polymer material
0:46:16 > 0:46:20that's a bit porous and so the cells can settle into those pours
0:46:20 > 0:46:23inside the matrix and start to grow. It feels like home to them.
0:46:23 > 0:46:28After a few days, the patient's own blood vessels actually grow into the
0:46:28 > 0:46:30scaffold and make it really part of him.
0:46:30 > 0:46:33And what's going on? Are they actually growing and multiplying?
0:46:33 > 0:46:34Yes, that's exactly right.
0:46:34 > 0:46:38But on the beach in 2012, everything sounded a little different.
0:46:43 > 0:46:47What I was about to hear would come as a shock to me.
0:47:12 > 0:47:15Paolo was explaining there was something wrong
0:47:15 > 0:47:17with Andemariam's plastic trachea.
0:47:17 > 0:47:21And not only with that one, but also with the new plastic tracheas.
0:47:22 > 0:47:25And despite the problems being unsolved,
0:47:25 > 0:47:30he intended to go ahead with new operations in just a few weeks.
0:47:30 > 0:47:33I am quite unhappy about this,
0:47:33 > 0:47:36because either we know exactly what's going on,
0:47:36 > 0:47:37because otherwise... I mean...
0:47:37 > 0:47:41Seven people in my lab have worked 24 hours a day for
0:47:41 > 0:47:44the last three weeks doing biocompatibility,
0:47:44 > 0:47:45and then this is shit now.
0:47:45 > 0:47:48So I think that we need to redo everything again.
0:47:48 > 0:47:50We lost two weeks
0:47:50 > 0:47:52by doing this.
0:48:15 > 0:48:18Macchiarini's team in Stockholm was desperately trying
0:48:18 > 0:48:20to solve the problems.
0:48:20 > 0:48:23And his haste to develop these techniques
0:48:23 > 0:48:26seem to have become ingrained in his working practices.
0:48:29 > 0:48:33If you have a patient that dies because of the new technology
0:48:33 > 0:48:35then you always ask you...
0:48:37 > 0:48:41Did I do something wrong? Do I have the right to continue?
0:48:41 > 0:48:42Should I continue?
0:48:43 > 0:48:44Um...
0:48:46 > 0:48:47What should we do better?
0:48:47 > 0:48:51So even with 25, these yellow...
0:48:52 > 0:48:54..things are appearing.
0:48:56 > 0:48:57It's very draining.
0:48:58 > 0:49:03It's not a pleasant sensation at all.
0:49:05 > 0:49:08Good. Thank you again for outstanding work.
0:49:11 > 0:49:14But still, you learn only by doing.
0:49:15 > 0:49:18It's going to be quite difficult to distinguish
0:49:18 > 0:49:21the two measurements that we get.
0:49:21 > 0:49:23Difficult but not impossible, right?
0:49:25 > 0:49:28So he should do it, he must do it.
0:49:28 > 0:49:31There is no changes or no choices.
0:49:31 > 0:49:37I am seeing that we are still improving and we need to improve all the time.
0:49:37 > 0:49:39And only by doing, we improve.
0:49:52 > 0:49:54All these studies are ongoing.
0:49:54 > 0:49:56This could be the future.
0:49:56 > 0:49:58Thank you so much.
0:49:58 > 0:50:00APPLAUSE
0:50:16 > 0:50:18That's the kind of surgeon I want on my team.
0:50:18 > 0:50:20If I'm on the wrong side of the knife,
0:50:20 > 0:50:22I want a guy like Paolo Macchiarini trying to get me through this.
0:50:25 > 0:50:27He's very experienced in transplantation,
0:50:27 > 0:50:29experienced tracheal surgery,
0:50:29 > 0:50:31so you don't say anything.
0:50:36 > 0:50:38We need people like Paolo to force the issue,
0:50:38 > 0:50:40to get a decision, to say,
0:50:40 > 0:50:44"Let's just do this, even though we don't have all the answers."
0:50:44 > 0:50:45The idea of this
0:50:45 > 0:50:49trachea transplantation is something magic, really.
0:50:58 > 0:51:00- He's the only one.- Yes.
0:51:06 > 0:51:10But the result so far makes you hopeful?
0:51:10 > 0:51:14Oh, yes. Of course, otherwise I would already have stopped.
0:51:22 > 0:51:27Paolo had the support of some of the leading lights in his field.
0:51:27 > 0:51:31And you can view the setbacks in more than one way.
0:51:31 > 0:51:36Sure, two out of the three patients with plastic tracheas were dead,
0:51:36 > 0:51:40but you might also point out that one of the three was alive,
0:51:40 > 0:51:43and you could count that as a success to build on.
0:51:45 > 0:51:48So how do you feel, physically?
0:51:48 > 0:51:49I'm OK.
0:51:49 > 0:51:53Always, we speak of relatively,
0:51:53 > 0:51:59so from time to time it was going to be positive, going OK.
0:51:59 > 0:52:03So I'm very optimistic in the future.
0:52:03 > 0:52:06So, how is this day for you?
0:52:06 > 0:52:10One year exactly after the operation of Andemariam.
0:52:12 > 0:52:15I'm very pleased to see him doing so well and it is
0:52:15 > 0:52:19a gratification for all the efforts that we have done
0:52:19 > 0:52:21in the past and we continue to do.
0:52:21 > 0:52:23So it is a major achievement
0:52:23 > 0:52:29for every other patient that would need this type of transplantation.
0:52:31 > 0:52:35What if the plastic method was fundamentally correct,
0:52:35 > 0:52:38but that the patients had been too ill?
0:52:55 > 0:52:59So far, Paolo had been allowed to use the plastic tracheas
0:52:59 > 0:53:01in order to save lives.
0:53:03 > 0:53:07Now he wanted to test this method on healthier and stronger patients
0:53:07 > 0:53:10who were not in any immediate danger of dying.
0:53:25 > 0:53:29Paolo had succeeded with something almost impossible.
0:53:29 > 0:53:31Without extensive animal testing,
0:53:31 > 0:53:34he got the go-ahead for using humans as guinea pigs.
0:53:41 > 0:53:45He was to test the plastic tracheas in Russia,
0:53:45 > 0:53:48on subjects who suffered from old injuries
0:53:48 > 0:53:51but were not acutely ill or dying.
0:53:53 > 0:53:55In order to choose the right subjects,
0:53:55 > 0:53:57they trawled many candidates.
0:53:59 > 0:54:02The German TV crew was there to record the operation.
0:54:05 > 0:54:10This is Julia Tuulik, a teacher and former dancer from St Petersburg.
0:54:13 > 0:54:17She won the chance to be the first experimental subject.
0:54:19 > 0:54:23She was asked to record a video explaining why they should pick her.
0:56:15 > 0:56:17Thank you for everybody that you came.
0:56:17 > 0:56:21This is the final brainstorming before the transplantation and,
0:56:21 > 0:56:23as a matter of fact, the patient, Julia,
0:56:23 > 0:56:26tomorrow will be the first patient
0:56:26 > 0:56:29entering a clinical trial.
0:56:29 > 0:56:31So tomorrow we plan to do the
0:56:31 > 0:56:34first in human ever done tracheal transplant
0:56:34 > 0:56:36using bio-artificial scaffolds.
0:57:06 > 0:57:10Julia was about to receive the world's fourth plastic trachea.
0:57:15 > 0:57:18Her only living predecessor was in Iceland, Andemariam.
0:57:21 > 0:57:24And at the Karolinska Hospital in Stockholm
0:57:24 > 0:57:26there waited yet another patient.
0:57:27 > 0:57:31By testing it on a patient as healthy as Julia,
0:57:31 > 0:57:35would Macchiarini now be able to prove that his method was ingenious?
0:57:37 > 0:57:39Would it be a success?
0:57:41 > 0:57:42Nice to meet you.
0:57:43 > 0:57:45Do they know the problem?
0:57:46 > 0:57:47No, what is your problem?
0:58:05 > 0:58:06Being at the cutting edge...
0:58:08 > 0:58:10..you are always wrong,
0:58:10 > 0:58:16until sooner, more likely later, you demonstrate the opposite.
0:58:18 > 0:58:21Why should I give up?
0:58:21 > 0:58:22I'm not the type to give up.