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Julia Polak

Director of the Tissue Engineering and Regenerative Medicine Centre, Imperial College London

Julia Polak has been at the cutting edge of medical research since the late 1960s and is one of the most cited scientists in the world. She was among the first to demonstrate the existence of a hormone system in the gut and was on the team that discovered how nitric oxide – a substance produced by exhaust fumes and the magic molecule in Viagra – is made in cells throughout our bodies and governs a wealth of vital biological processes. In 1995 she was doing research into a rare lung condition, when she herself collapsed with the disease and had to have a heart-lung transplant to save her life. Later she presented her own case at a medical meeting at Hammersmith Hospital, and says of her lungs, ‘They were lovely in terms of pathology … [But] it was an extreme case of pulmonary hypertension, and I couldn’t imagine how I had managed to breathe!’

Dame Julia is one of the longest survivors of a heart-lung transplant in the UK, and the experience changed her life course. She switched to the newly emerging science of tissue engineering and regenerative medicine, which aims to find new ways of repairing damaged organs using patients’ own stem cells, and will eventually replace the need for donor transplants.

Dame Julia grew up in Argentina, to where her Jewish grandparents had emigrated from Eastern Europe to escape persecution. She and her husband Daniel Catovsky, a haematologist, came to the UK in 1967 for a year’s postgraduate study and never went back. The science in Britain was exciting and back home their own families were being persecuted by the military junta.

What was your first experience of seeing a dead body?

It was more or less when I started pathology. As a student I had to clean the pieces for the museum, and there were bits in formalin that I had to take out and in. I remember I had to come in very early one morning to the post-mortem room – it was a very cold morning, and when I reached into the bucket a hand clasped my hand. [laughs]

And how did you react?

With disgust! I ran out of the room.

But you psyched yourself up and went back in?

It wasn’t really a crisis. I’m not that kind of person. I remember after my transplant, people said: ‘You’ll need psychotherapy, some support.’ But I’m not the reflective sort.

When you chose pathology, was it the disease mechanisms that most fascinated you or were you focused on the patient and the patient’s family?

The why of diseases is what interested me. I was interested more in understanding the mechanisms of disease and the science than curing patients. I mean, to such a degree that when they took my diseased lungs for research purposes at the Hammersmith, people asked, ‘How could you look at your diseased lungs?’ But you don’t think ‘That was part of me,’ you look at the science behind it.

So tell me about your operation. How did you come to realise you needed a transplant?

It’s a long story … I’d probably had the disease all my life, but nobody realised. I was becoming more and more breathless and people said, ‘It’s asthma.’ But I had a very rare disease called pulmonary hypertension – high blood pressure in the lungs – where the incidence is one in a million. It was only diagnosed when I collapsed at the Hammersmith. I was in heart failure and it was terminal. But until then, no one had considered it.

How long had you been experiencing breathlessness?

All my life. I had probably had pulmonary hypertension all the time, although it was probably a very mild form until it suddenly deteriorated. I had my three children, and I was flying everywhere, giving lectures all over the world … But it wasn’t comfortable, and at the end I couldn’t even walk.

And did you ever suspect that’s what it might be?

I didn’t suspect pulmonary hypertension. I thought it was something more than asthma, but I couldn’t tell.

But you’d been studying pulmonary hypertension, hadn’t you? Why did it not occur to you?

I suppose I thought, ‘It doesn’t happen to me.’ It could be denial; I can’t tell. I’m not a very good psychologist.

So what exactly happened?

Well, I collapsed. That was in April 1995, and my transplant was on 17 July. I was 56 years old. When they got me to hospital they were shocked, obviously, because they went out of my room to talk, and I suppose they were discussing how to break the news. I couldn’t understand why they’d gone outside. And then when they said, ‘You have pulmonary hypertension,’ I demanded: ‘But why?’ I was so angry I wanted to hit someone! They said, ‘We don’t know why. But we have to move you to the ward.’ I said, ‘No, no, I’m going home. Get my clothes.’ They said, ‘No, you’re staying.’ And then they called my husband Danny. He was shocked and didn’t understand at first. And then they told him, ‘She’s seriously ill.’ They put me on a drip and oxygen and all that. Then an expert from the Hammersmith, Celia Oakley, made a diagnosis. That was April, early May. They started treating me with something, but it didn’t do any good; I was terminal, so I was deteriorating fast.

Were you in hospital all the time?

I was in hospital only for two weeks at first. They sent me home, but I collapsed there again so I went back, and then at a certain point Sir Magdi Yacoub, the famous transplant surgeon, appeared. I was carrying out research projects with him at the time, and I said, ‘Why are you here?’ He said, ‘It’s a social visit.’ [laughs]

So they were keeping you in the dark?

Actually, they were in the dark themselves; they just couldn’t believe what they were seeing.

And they thought you weren’t going to survive?

No. But when they put the possibility of a transplant to us, we didn’t want to accept it. Remember, this was 13 years ago; it’s not the same as today. They didn’t do so well in the early days, heart and lung transplants. I was in the bed, Danny was by my bedside, and one of my colleagues at the Hammersmith walked in. He had nothing to do with my case, but he knew we were resisting making a decision, and he said, in front of me, ‘Look, she’s dying. Okay, she may die during the transplant or soon after. But it’s the only chance she has.’ It was shock therapy, and at that moment we accepted. We didn’t have any choice.

And how did you feel, being given a death sentence like that? You say you’re not a reflective person, but how did you take the news?

Actually, I was too ill to react. I was too busy trying to get better and I couldn’t think very well. They said, ‘You have to wait for a suitable donor organ,’ and then nobody contacted me again. The waiting was very, very hard. I was also wasting away, because I couldn’t eat. It was horrendous. Then they told me, ‘If you fit oxygen in your house …’ (which was a job because it was a house on several floors) ‘… you can go home on a Saturday and come back Monday. You can go for a little rest.’ So I went. It was a big palaver with the oxygen machines, and they had to get me up the stairs with a wheelchair and all the oxygen … That was Saturday. Then on Monday, two o’clock in the morning, the telephone rang. Everybody was so fast asleep that no one else heard it, and I had to drag myself over to the phone. I picked it up and someone said, ‘You have to come immediately to Harefield – we have some organs.’

I had left all my things at the Hammersmith. Everything was there, because I’d been in the hospital for months – all the cards and the flowers and the books, my nightie, shoes, make-up – everything was at the Hammersmith, but I never went back. I went to Harefield.

I’d worked with Sir Magdi at Harefield every week, so I knew the way. But Danny was driving, and he didn’t have a clue. It was the middle of the night; my son Sebastian was in the car too, and they were both terrified. I was saying, ‘Turn right, turn left, go straight.’ We must have arrived at about three or four in the morning. They asked me for authorisation to donate my heart, and apparently I signed very happily. But I don’t remember any of this.

Why did they give you a new heart as well as lungs, if your heart was good enough to give to someone else?

It’s a simpler operation to take the whole lot out and put in another lot. The other way means more dissection.

But back to our arrival. Finally, a stretcher comes to collect me, and that was horrendous. I was frightened and sick; I was saying, ‘Goodbye, goodbye’ to the family, and I really thought it was goodbye forever. Danny saw another stretcher being carried in at the same time, and he saw that I had consented to give my heart. Then when I was in intensive care after my operation, he said, ‘Don’t tell anyone, but I think that might be the man who has your heart.’ Later, when we were walking in the ward after we’d both recovered, the man said, ‘You saved my life; I got your heart.’ But he passed away about two or three months later.

After your operation, did they offer to show you your own organs?

No, not at that point. Because we were working together – the Hammersmith and Harefield teams – we had a bleep system to let us know when there were organs to collect from Harefield for our research labs. One day one of my colleagues was asked to collect a specimen of pulmonary hypertension. They all knew that I was waiting for a transplant, so he asked, ‘Is that Julia Polak?’ and they said yes. So he went to collect the organs and then dissect them. Did my colleagues find it difficult working with my organs? Some did, but apparently some not.

But afterwards I did see them, yes. Very interesting: they were lovely in terms of pathology. I presented them at the Hammersmith Hospital. They have a famous thing there called the ‘staff rounds’, where they present three cases: a clinician presents the clinical picture; if it’s a surgery case the surgeon will talk about how he did it; and then a pathologist presents what they found, either in post-mortem if the patient died, or from the surgery. It’s a regular event. This was an anniversary of some sort; I was at home recovering and they said, ‘Can you suggest someone?’ I said, ‘You can present my case, if you like.’

It was a large lecture theatre, for about 1,000 people, but many people couldn’t get in and had to be outside. Some people were crying – it was emotional, you know. [laughs] They sent a note round saying that I was very susceptible to infection, because it was still very early days. I didn’t know about that note, but I thought, ‘Funny, why don’t people come and greet me?’ Now I understand: people were told not to come near. They were all going … [she mimics them all waving from their seats]

My brother came from Argentina with his wife; Daniel was there; friends were there. Everybody was crying. For most people it was the first time they’d seen me since the transplant. It doesn’t happen often, a colleague with a transplant! And, of course, I’m not very big, so I was just standing there looking small. The clinician who’d diagnosed my disease, Professor Oakley, presented; then Sir Magdi presented the operation; then I presented the pathology. My own lungs … Everyone was [she mimics everyone gasping]! The case was published in the BMJ [British Medical Journal] as ‘The pathologist as patient’.

Did you yourself feel emotional at the time?

Well, no; I was trying to remain strong, because I was still quite wobbly, and I was busy trying to concentrate on what I had to present. And I felt strange that people were waving at me and they were all crying. [we laugh]

It is an amazing story.

At these staff rounds the pathologist has to conclude. Apparently I said, ‘This pair of disgusting lungs …’ It was an extreme case of pulmonary hypertension, probably the worst I have seen, and I couldn’t imagine how I had managed to breathe through those lungs.

What relationship did you have with the material when you were presenting it as a case?

It was just slides. A fascinating case, but just slides. [we both laugh]

But people offered you all kinds of counselling support after the operation?

Well, they always do after a transplant, but I didn’t take it. I did have nightmares for a while: I’d get up in the night saying I couldn’t breathe. Of course, I could breathe, and in the end obviously I worked it out for myself.

You now have the reputation for being one of the longest-surviving recipients of a heart-lung transplant. What are the big risks?

You can die during the operation, because at certain points you are not alive: they take out your heart and lungs and put you in an artificial heart and lung machine. You can die when they put the organs back if they don’t ‘take’: you need to get the organs pumping, the new heart that has just been connected up to your own blood vessels. And then you can die – which I nearly did – when they put you in this artificial heart and lung machine because all your blood clotting is altered. I was bleeding like mad, and Sir Magdi said, ‘She needs fresh blood.’ ‘Fresh blood’ means not from the blood bank, so they had to bring in the soldiers from the barracks near to Harefield. They didn’t have time to test for HIV or anything else. I was dying. They tested for matching, and that’s all. But my lungs, the tissue, didn’t match. Sir Magdi explained the situation to Danny, but at a certain point you have to decide: do we match, or do we take the chance? You might find the perfect match if you wait, but it might be too late.

What do you have to do now to stay healthy?

I have to take drugs to suppress the immune system, to prevent rejection of my new organs. They aren’t difficult to take, except that I have to take loads in the morning and loads in the evening. But the consequences of taking these drugs are not nice. You can develop malignant tumours. You can develop very serious infections because your immune system is suppressed. And some people die from what is called chronic rejection. Tomorrow is my ‘annual’ check-up actually, my MOT.

And do you get frissons of fear before your check-up?

Oh yeah, I’m completely neurotic. Every time I do the lung function test I hate it. My lung function is declining, and it’s difficult to tell if it’s age or just the lungs. But this is uncharted territory and you just hope … Nobody knows.

But how do you feel in yourself?

I feel fine. I do gym every day; I do yoga once a week, which I hate; it’s so painful! I work all the time; I never stop. But you don’t know what’s next, and nobody can tell you, because they don’t know either.

So do you feel vulnerable because your immune system is suppressed?

Oh yes, very vulnerable. It’s not a good idea to go in aeroplanes because of the germs circulating in the air. I do fly, but we go first class, which has a bit more distance between people. Washing hands is very important, too. And I make sure that when people come to see me they are not unwell.

So tell me, what impact has your experience with this disease had on your career and on your life?

It has completely changed both.

When I got back to work after the operation, I thought I had to do something related to what happened to me, and I wanted to do more study on pulmonary hypertension. But then this new field started: tissue engineering and regenerative medicine, or stem cell research, creating lungs to overcome the lack of donor organs, etc. You could say that I would have gone into that field anyway, because I always liked to be into the exciting new areas. But it looks more glamorous to say it was as a result of my transplant. It’s like the plot of a good novel …

So you left your original field?

I changed fields completely. Well, the purpose is the same – it’s all geared to saving human lives. And the technology is the same, but the projects are different.

So you were a pioneer in the tissue engineering field. How would you describe your work to someone who isn’t a medic?

Well, we all have the capacity to regenerate, otherwise you would cut yourself and you’d die by bleeding, but you do heal. If a baby has a cut it will not easily leave a scar, because a baby has great capacity to regenerate identical skin. But the older we get, the less able we are to repair damage well, and the more we get scars and marks. If we could regenerate really well we wouldn’t get ill. If you cut off the leg of a lamprey or a frog, it regenerates very well. So the question is: what have we lost? Or what have we gained as an inhibitor of that process? And what can we learn that will enable us to get humans to repair like that?

Smoker’s lung, for example, is a very common disease. The airway epithelium [lining] is destroyed because of the nicotine. Then the air sacs become enlarged, which is emphysema. Maybe we can encourage the lungs to regenerate, or we can ameliorate the condition, or stop it getting worse. There are several ways in which you could help the body to regenerate itself. You could grow a new lung in vitro [in the laboratory]. That’s not going to happen tomorrow, but there are steps in the right direction. There are clinical trials on bladders that have been produced ex vivo [outside the body] – a whole bladder. Such an organ has been transplanted into children and they’re still functioning eight years later. It’s not a perfect bladder – they didn’t do the ureters or the urethras – but still, it improved the condition of the children.

And these started with the child’s own stem cells? So it’s a match to the individual?

Correct. But one day maybe the famous (or infamous) embryonic stem cells, which are very ‘plastic’ and can become anything, could be used – if we can overcome the immunological problems caused by the fact that they don’t come from the patient, and the ethical and moral concerns, etc. Umbilical cord stem cells are also becoming quite famous – Richard Branson is starting an umbilical cord blood bank. Why? Because so far it has been proven in a very limited way that umbilical cord blood contains stem cells, like the bone marrow, which are efficacious for leukaemia, but for nothing else, so far. The cells are not like pluripotent embryonic stem cells; they are more like the bone marrow – they are multipotent. So they are more restricted in their ability to generate different cell types, but they have great potential.

Very recently it has become possible to produce pluripotent stem cells without destroying embryos. Adult cells can be taken from skin or other organs, and transfected with genes that will induce pluripotency identical to what’s seen in embryonic stem cells. These are called ‘induced pluripotent stem’ [IPS] cells, and they were discovered by Japanese and American researchers. With more research, it may turn out that IPS cells can be used and that could obviate the ethical issues associated with the use of embryonic stem cells.

So there are several kinds of stem cells that could be useful. And the idea is: either you can have an ex vivo organ; or you could grow cells and then give them to a patient – that is, start the process of growing a new organ and then hope it will continue by itself inside the patient. Or you can kick the patient in the backside and say, ‘Mobilise your stem cells,’ and those stem cells migrate to the injured site.

And how would you do that?

You need to create drugs that will mobilise your own stem cells. It’s early days, but it’s done already in haematology, and probably will be done more widely in the future. So these are the three big approaches, and people are working all over the world on different strategies.

But there are enormous challenges. First, there is the blocking of embryonic stem cell research. Then there are problems with taking cells from a patient – they are older cells and they may all carry the same genetic defects, so they are not marvellous. Umbilical cord cells, as I said, are ideal, but there are not enough of them. So if you want to cure smoker’s lung, what do you do? You need mass production, industrial-scale production, of things for clinical application. Nobody knows how to do it.

So all those challenges need to be overcome. I don’t need to tell you all this; I could say it’s all marvellous. Yes, that’s so in a glass-half-full kind of way; we are certainly taking steps in the right direction – but my God, there are hurdles!

But at the moment have you got proof of principle that you can regenerate a lung?

No. Take my transplant, for instance. This lung belonged to another person, okay? I don’t want to test it while I’m alive, but suppose I die, then my lungs can be stained and they can be checked to see whether they’re being repopulated by my own cells. We did demonstrate and publish evidence that donor lungs can be repopulated by the patient’s own cells. So there is an attempt by the body to regenerate even a foreign lung when the lung is damaged. Obviously, there is the release of something in these damaged lungs that attracts the cells to regenerate.

We are now working with experimental animals at Imperial College on a model of emphysema. We will put in umbilical cord stem cells, which are expanding, and see what happens. And if these cells do not produce any unwanted effects, and lung function improves, then we can consider going to a larger animal model and then man. So you see, the timelines of the conventional pathologist are totally different from those of research. A pathologist wants to save life now; they are aware of all the things that can be done, and they can suggest a course of action and see the result. But I might not see any of my research come to fruition in my lifetime.

Also, we must not lose sight of the fact that many important discoveries are made in this country but are commercialised everywhere else. Like monoclonal antibodies: this country didn’t make a penny from their discovery, which is typical! That could happen to us in this field too, so we have had to make sure that we protect our discoveries.

So you’ve started a company?

Yes. I have two different things – one is my charity and one is a company. The company is going reasonably well, but it’s early days.

The company is fully integrated with all the discoveries at Imperial, and I am the chairman of the scientific advisory board. We have a management group who are financiers, and they understand business. And then I run the science. And that’s fascinating, because the science moves from the test tube to something that could become reality. Doing research and writing papers about your discoveries is beautiful, and you become famous. But it’s real life that’s important. In real life, you want to save lives … And to protect your discoveries, and make money to bring it back to the research.

Tell me about your trust, your charity.

When I was in hospital, and quite sick after my transplant, I was trying to collect money for the Harefield, and Sir Magdi said, ‘No, set up your own charity, for your own research.’ We started collecting and we supported a lot of research students, and now Imperial College wants to establish a prize for young women, called the Dame Julia Prize. We’re collecting that money to help give the young women a chance.

Have you experienced barriers as a woman doing science?

I am very thick skinned, so I didn’t. But lots of people say there are barriers. I do strongly believe we need to nurture women, because they lack confidence. We need to discriminate in favour of them. So giving this prize will help.

You say you are too thick skinned to have noticed any kind of sexual discrimination. Are you an ambitious person?

Yes, I’m driven. I am all the time organising and getting into new things. I mean, I will never be fully retired because I will always find other things I want to do.

You obviously have an extraordinarily busy life and yet you’ve brought up three kids … How did you manage it?

I have a good husband. And we had an amazing nanny. Danny and I had a rule that we never went away at the same time; one of us would always be here. And when the children were young, we were back home at 6 p.m. So it was a very structured life.

Golda Meir, when she was the Israeli prime minister, once told an interviewer that as a woman with a high-flying career as well as children you just have to come to terms with the fact that you will always feel guilty about something. Do you agree?

Oh yes, completely horrible! My son reminded us … Now he denies this story, but he was such a difficult person when he was a teenager. [said with an indulgent smile] He said, ‘I’m writing a play to say goodbye to school; will you come?’ We were so proud: the great genius writing a play, acting in it and staging it … Somebody said, ‘I don’t think you should come.’ And we said, ‘What d’you mean? Of course we’ll come – all the family! Nanny and all her family too.’ We were in the front row, and the story was about a disturbed child, who is disturbed because his parents are academics and flying all over the place, and he commits suicide in the middle of the stage because his parents forgot his birthday. We never forgot his birthday! We said, ‘We’re going to get out every single photo album with pictures of him blowing out candles at his birthday.’ And then we couldn’t find the damn albums. [we both laugh]

It’s hard dealing with teenagers. I could have killed them all. [laughs] They’re lovely now, absolutely wonderful.

And what about your Argentinian family? You say your grandparents came from Eastern Europe – under what circumstances?

You know, a lot of people emigrated at the turn of the century from Russia and Poland and places. I think it was just chance where they ended up. We grew up thinking of ourselves as completely Argentinian. But now we have been here much longer than we were in Argentina and the children are more English than Argentinian.

My family were lovely middle-class types. A very friendly, Jewish family. My mother was very intellectual; my father was a lawyer and then a judge. They were never practising Jews, so I don’t know when our Jewish faith stopped meaning anything. We know it as our roots, that’s all. My husband comes from a very similar background, but not wealthy at all. His father had a great intellect.

And how did your families fare during the dictatorships?

It was very hard. Daniel’s brother, my brother-in-law, is one of the ‘disappeared’. It was the mid-1970s. He was taken away in front of his father. They said, ‘If he has done nothing he will come back.’ He had done nothing, but he never came back. They most probably threw him in the Atlantic, and they never recovered the body. I think when he was taken away it virtually killed his father – he died some years later, but I think he died of a broken heart.

Culturally, as Latin Americans, how did you find working with people here?

Everything is so civilised here, and the culture… I mean we’re spoilt here; it’s amazing.

Finally, Dame Julia, what specifically are you working on at the moment?

Right, the biggest challenge at the moment … There is lots of research being done all over the place on cultured cells two-dimensionally in a Petri dish. But we are three-dimensional beings, so therefore we need to learn how we can culture in three dimensions – because the cells talk to each other, and talk to the surrounding tissue.

This is another area where we have strong collaboration with engineers, because we need to grow the cells in what is called a ‘bioreactor’. The best example of a bioreactor is the womb. The development of the baby in the womb is controlled by all these natural signals in the three-dimensional environment. We need to grow the cells in this kind of way, and people can’t do that at the moment, so that’s what the challenge is. Not mine alone, but for everyone working in this field.

As far as you’re concerned, is this the future?

I think regenerative medicine – in my unbiased opinion – will rewrite the books of medicine. Of course! I mean, that’s where we should be going.