A Matter of Life and Death. Sue Armstrong

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