A Matter of Life and Death. Sue Armstrong

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СКАЧАТЬ 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. СКАЧАТЬ