Robert Winston: pioneering IVF

And the risk of epigenetic complications...
26 September 2023


IVF technology


The second part of Chris' sit down with Robert Winston explores the early days of IVF treatment through to today, where 7 million people have been conceived this way...

Chris - I met Louise Brown when she was 40. She came back to Bourn Hall, which was the clinic that Patrick Steptoe and Bob Edwards founded and set up. They operated from there, didn't they, in Cambridge? And it's still a pioneering IVF clinic. She said there's always a lot of demand for her time when there's a zero or a five in her age, but she came back because she was 40 that year. One of the things she memorably said to me was, there are now millions of us - meaning millions of babies born by IVF. Has it surprised you how far or fast this has gone? Or did you expect that sort of trajectory because of the reason you outlined, which is women had had a raw deal in medicine?

Robert - I never thought it was going to be very valuable. I didn't see IVF as being a big area in public medicine.

Chris - Why not?

Robert - I thought it was going to be too complicated and I was quite a Luddite. I was doing it early, but I thought it was going to always be quite specialised. You would have to have a good laboratory, you had a whole lot of stuff that you weren't going to get through the NHS. But actually I had it much easier than he did up in Oldham. I had a hospital that was a research hospital that actually was prepared to take risks and didn't care what it really cost, providing we could help get some help and so on. And we found it very easy to pave our way. But I didn't really think it was going to be that. So when in fact we got to about 7 million babies, I was very surprised.

Chris - Were you concerned when IVF first came along about what the consequences might be long term? I think it was Jim Watson behind that Daily Mail headline. Were you worried about what the genetic consequences could be of doing this sort of playing God in a dish?

Robert - Jim Watson was always prepared to say things. He still does.

Chris - He still does very much so.

Robert - You can't take him very seriously. I think we were concerned. I think I'm much more concerned now than I was then because I think now we have a lot of evidence to suggest there might be epigenetic effects.

Chris - Of IVF?

Robert - Yes, what you have in the culture media is still a bit of a black box. That five days in culture media is still the biggest failure rate. And so there needs to be much more research. And actually that's what I'm doing at the moment. So I've got a small team at Imperial where we're looking at culture media, we're doing very detailed analysis of what we're seeing and we're finding some very interesting molecules which are being produced by the embryo which are not in the original solution. So it's a rather exciting area.

Chris - So did we go down this road of waving through IVF because we saw there was a need, we saw there was a big demand, many people probably were motivated financially to do this, but because we were blithely ignorant of the role of this epigenetic component where there was an additional layer of control over how genes work, that we just didn't have any idea of at the time, is that why we were just prepared to let it go and we may be we may be cruising for a biological bruising later.

Robert - I think it's much more to that. I think one of the problems has been that actually, once you start to set up a clinic and do IVF, it's very easy to do. You don't need to think about what you're doing. It's regulated, there are certain things you can do and you can't do and so on. And it's a process which you go through.

Chris - But it's not so much the practitioners, I'm getting at the science and the concern about the biology.

Robert - Basically, for people who go to an IVF clinic, infertility is seen as a diagnosis. Like having pain in the chest and asking for, let's say, some form of heart surgery. It's complete nonsense. Of course we should be making a diagnosis, and what we're doing is treating people with the least successful treatment in the whole fertility spectrum. So nowadays the NHS is doing a pretty poor job at treating people with anovulatory infertility, with male infertility, with tubal infertility. The main causes of infertility are not being properly treated. People are just diverted into IVF which, internationally, and you can see what the world results are, run at about 21-23% per cycle at a huge expense with a failure of investment in proper medicine. A key to bad medicine is not to make a prognosis, but just to treat the symptoms. And that's actually what we're doing. We're treating the symptoms of infertility rather than trying to understand it.

Chris - But once you've created a life - you use the figure 7 million IVF people have been conceived - is there a risk that, because we didn't know at the time that there are additional genetic factors at play, these people may have skeletons in their genetic closet that we haven't discovered yet?

Robert - We can't say that for sure, but what we can say is that we know increasingly that when an embryo is in an environment which is not particularly favourable or too favourable, you end up with certain changes which result in their not being able to accommodate a different environment when they are adults. So, for example, that classic work that was done years ago in Sweden, where they looked at a birth cohort from the 1800s and 1790s showing that if you were subjected to a good harvest at the age of nine as a boy, your male grandchildren were more likely to have heart disease and so on almost certainly because of epigenetic effects. And we know increasingly that epigenetic effects are almost certainly transferrable. And that's now increasingly obvious with very recent research and probably not just through one generation. So I think we have to be aware that a lot of the diseases that we're most worried about, some of which will be psychological and psychogenic diseases, are possibly related to epigenetics. And that's a fascinating area. But of course it may be much more than that as well; maybe vascular disease and a whole range of other diseases. I don't think we're going to get lots of people with cancer. But you might want to ask yourself what is the effect of changing metabolic issues in culture? What will be the risk to sugar metabolism, for example, and so on. I think there are some real questions to ask and I think at the very least we should be documenting what we're culturing embryos in much more carefully and actually doing proper research to see how we can optimise what we're doing because we're not doing that properly. So talking to you now, I would say, look, if you're listening to this as a young person thinking about research, think about what opportunities there really are in human reproduction at the moment. It's wide open for somebody to really just have another look at. There's some ethical difficulties about doing some of that research, but much of it doesn't require huge difficulty and some of it can be mimicked in some animal work as well, which we always, regretfully, rather ignore.


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