This is Derek quoting Chris Redmond, 13th of November 2006, Chris, I think it came from a Cambridge family.
Did your people live in Cambridge and then switch to Oxford for clinical?
That's right. I went to Cam, went up to do my B.A. at 1960 and came here in 1964.
And how much of a love I was getting into the Oxford Clinical School.
It was completely straightforward. There was no palaver whatsoever at that time.
My brother had been here before me and I just followed in his footsteps, as indeed my brother did after me.
So there were three of us in succession. You had an interview and you that I really I think I did, but it's not clear in my mind.
It wasn't a big event in my life at that time.
And that's a question that occurred to me coming along after you've been here, you know, for a little three months, six months.
How did you feel you compared with the Oxford class?
Because, well, they were six months ahead of us. So there were there were always two intakes.
And the Oxford Group came in in the spring, late spring.
And then there was a remnant coming in in September, October.
And I was part of the remnants of everybody but Oxford.
Yes. So you never had a real chance to compare your education to the media that the would be, um.
Not at all. Um, and it wouldn't have been appropriate even if there had been that chance, because my arrival into medicine was very indirect.
I came to Cambridge to study physics. All right. And I did not get on with physics.
And during my natural sciences tripa, I drifted towards the biological sciences.
And what really converted me was biochemistry. A it was much better taught than the physical subjects.
And B, I came across the medical students in biochemistry and they were just so much more
lively and interesting that I decided after taking my B.A. to transfer to the B.
M and. And your brother was already doing medicine. Yes.
And was the younger brother known to be able to do medicine? No, not at that time.
And tell me about your clinical years. How did you enjoy them?
Um, they were fun.
They were in parts interesting and in part not.
The problem for our intake, which I think constituted six or eight people, was that we were small enough to ignore when convenient.
And there were the committed teachers and there were the uncommitted teachers.
And the clinical teaching from people like John Ledingham was absolutely superb.
Alex Cooke, I remember as a wonderful teacher, um, but, uh, no, I think you see, he retired when Nottingham came.
Yes, it has. He went on teaching. No, he was he was there when I arrived right before it was my first student firm.
Right. And I couldn't have done better. Such a wise, thoughtful person.
One piece of advice that he gave me, which I've always followed until today,
is that if somebody is standing in the hospital looking lost, always stop and direct them.
And I still do that to the stage as part of the courtesy of the man which was in men's health, as well as being a very wise clinician.
Um. So were you just one student on that firm? Oh, no, no, no, no.
The group was six and I think we were divided three and three between two.
Yes. So then it was 65 and 64.
64 is. And I'm worried about surgery.
How did you get over that? It was less well thought.
Alex, what was his name. Afghan erm and Philip Allison were in the NDIS, but Alf Gunning had no interest in teaching whatsoever.
As I remember it, Philip Harrison was a rather untypical surgeon, quiet and retiring as I remember it,
always thoughtful but never very talkative senators that cries and retired with time.
But rather than retiring for the Americans.
Yes. Um, and when you're bored during the clinical years, um, to an extent, yes.
The the medical side was fun and we did pathology at the end of the second year.
And that really, really stood me up because I realised how much I didn't understand which was coming in late in the day.
And it was the insight I gained from doing the the.
The pathology exam came early,
and the insight I gained from preparing for that led to my decision to take up an offer to go to the pathology department
in Baltimore immediately after graduating and doing an internship there before coming back to do further work here.
So you would have approved of the business plan that brought pathology much earlier?
Oh, yes, it's very nice. And I, I think that it just it must be the way my mind works.
But I like to understand what's going on rather than just look at what they now call phenotypes.
But you know, the signs and symptoms. Did you get some sort of travelling scholarship to Baltimore?
No, no, no. That I applied for a service internship and was accepted.
It was an arrangement that came through for Besom.
And his friend was he was had a very close arrangement with the pathologists there and Johns Hopkins, Walter Shelton.
And, um, I went and worked with children.
Now, in this days where people have asked about qualification and registration because you would have qualified but not registered in modern times,
um, they were a little bit fast, but nothing like I mean, now everything is so rigid that I think that people are very limited in their choices.
When I went to the United States, I had to take the easy FMG.
And so for the first until I had done that, they they kept me on as a fellow.
So I didn't I didn't join this. I didn't do any service work.
But I took part and was trained how to do the work.
And then it was always in a supervised manner. And and the teaching there for the the resident staff was superb.
And it was on a completely different level from what existed in Oxford at the time.
But that's all changed now. And that was happening in pathologies.
I mean, how would you, as it were, did you have students attached to pathology or what would happen?
Um, there were medical students there, but the training, um,
I was an intern and I was trained to do autopsies and I did, I think, 84 autopsies in that year.
And it was a very thorough job.
You have to work your way through, write a report and then present it to your supervisor, who then signed it off later.
It was I discovered at the end of that time I wasn't a natural pathologist, but I learnt an awful lot.
And chemical pathology. And with your interest in biochemistry, that got your fancy.
Um, it I didn't know chemical pathology and and Johns Hopkins.
This was classical morbid anatomy, if you like. Um, I no, I didn't.
I biochemistry interested me because the people were so different rather than the subjects and it was well taught in Cambridge,
Northcote and people like that. And uh they, they just made it extremely interesting and relevant.
But when I changed to medicine, I really wanted to work with people.
Um, I had no vision. I had no vision of becoming an academic physician or researcher at all.
I wanted to go out and be a doctor. What made you come back from America?
Oh, well, it was a one year, one year.
But you would stay the course and they they would have I think they had hoped that I would continue, but I knew that pathology wasn't my métier.
I had found it extremely interesting. Um, and, uh, but I don't think I would have wanted to stay with my family, um, links and so on.
Brought us back to Oxford. So we came back. We married when we went out.
Oh yes I am. We married when, um, I started the clinical course in 1964.
And so that coincided with the onset of our married life.
And then you came back. What has jobe's that you do then.
Um, I first with John letting him and Brian Prout.
Yeah. Um um what a what a great introduction to, to put my ground.
He was on that and he was. Yes. Um what can I say about Gurantee.
You always knew he was there. He was always sharp and acidic and he always had um a contribution to make.
But, um, it was it was like living with a knight in the room where it was going to fall,
whereas John Ledingham is was then, as he is now, a very affable, uh, thoughtful, um.
Teaching sort of person, he's a natural teacher. And you did that, he has tried to do the surgery job on obstetrics?
Um, no, no, I applied to do surgery,
but I didn't get a position in Oxford probably reflecting my lack of interest in the speciality when I was a student.
So I then went to the Jessopp hospital in Sheffield and did a six months in paediatric surgery.
And then I did another six months in neonatal and paediatrics at the end of which I decided I wanted to be a paediatrician.
And then I was. I forget how it worked out, but I got I think I was still doing the paediatric surgery and it was after I'd gone into the neonates,
I got a call from Laurie Bailen on behalf of Richard Doll saying they had a junior lectureship
and would I be interested in and applying for it or coming down and talking about it.
A lectureship in what? In general medicine? Yes and no.
I'm sure it was a moving target.
The surgeon knew I could have shounen shift. And the the name of the man you worked for in Sheffield.
And I know Sheldon was the pathologist and Johns Hopkins.
Yes. And then it was, um, Hinderer that they there were two surgeons and their speciality was spinal surgery.
And there was one who was I think his name became with Z, but I just can't remember.
And they that it was so most of the time I was involved with the care of of the babies and the children,
the survivors of spinal and hydrocephalus, who, of course, hardly exists now because then then then terminated.
Well, I remember it well, it's not show, so then you turn to paediatrics, but got the message from Richard, though, what made you accept it?
Um. I knew that to do, um, to to get progressive paediatrics,
I had to get my MCP and there was no no paediatric channel that had to do some adult medicine.
And I thought it was interesting to, um, to get that opportunity, which was part of the job.
But also they were talking with Margaret and said, I don't know if you do it.
So do who had approached Doll because she wanted to do what nowadays, um, would be called a cohort study.
But in those days, she just wanted to study the children of women with hypertension, the offspring.
And Laurie Bailamos was the hypertension man so rich you don't pass the issue to Laurie Balen,
who being who he was, just didn't want to do an observational study.
He wanted something more interesting. So he proposed a trial of the treatment of women with chronic hypertension, a randomised controlled trial.
And he said, well, this is the nearest you're going to get to paediatrics.
So the unborn child. So that's what we can do.
We can offer you. So it sounded interesting and it seemed that I could kill two birds with one stone, get the MCP,
which I did quite quickly, and, um, complete this study and get a name and an M.D. with the equivalent.
And that's what that's what I did. So you got there must be a yeah.
Six months after the intercourse with two years of growth and during that time you'd have been doing routine takes.
And so I was as a registrar, therefore, yes, I could hear just fine.
And then how did you enjoy that? Um, well, uh, I certainly, uh, I found it challenging.
I found that, um, you know, I learnt a lot.
I found that the people I was working with were amazingly supportive and helpful.
That was Glynn Williams by then with, um, John Ledingham.
People like him, you know, who you couldn't want better, really.
So, I mean, you start with Larry Bird. And was there another consultant with Laurie?
Um, there must have been better. Uh, you know, I don't see how you switch to Germany and if you see what I mean.
Well, I did a text for everybody. Yeah. Oh, right. It must have been some sort of invitation, you know.
Um, but so I wasn't just doing the the of IBM.
Yes. As I remember it, I did take as of when they wanted people to take it because I wasn't part of the firm.
I was on the academic side. Yes. No, I understand.
And how long did your thesis take? Uh, my thesis was an interesting experience.
It, uh, it was a trial. Uh, it was the world's worst trial as best I can, uh, document.
Uh, there was no, um, on Richard Dolz advice, he said, uh, you can't do it double blind.
You can't you don't need ethics. There was no need for a protocols of calculating the power of what was needed.
They just said, you want to get lots and lots and lots of recruits and you will be working with
this person in the obstetrics department who was a man called Peter Bailey.
And you won't ever remember him. He was a South African research fellow employed by John Stallworth.
He was the then professor of obstetrics.
And he was very, very, very highly rated as being the finest star that had ever worked in obstetrics and Oxford.
Um, and he talked the talk.
And I couldn't understand a word that he was saying, um, and I thought he must be brilliant because it's way beyond me.
It was only after he left that I realised I couldn't understand it because it was incomprehensible.
He was talking gobbledegook. He was a.
And during this time, I was trying to recruit these patients and they'd all assured me that there'd be no problem, I could recruit anybody I liked.
Edward Cope, adding the proviso, providing they got the treatment he wouldn't accept.
And they, um. So you didn't recruit his people?
Oh, no, I did. Should I learn to ignore them because they weren't helpful.
Um, and and also it was quite clear that getting the target amount, which was of the order of six or seven hundred, simply wasn't going to work.
So Richard Peto, whom I was sharing an office with at the time, I shared an office with him for five years, who I know Richard very well said.
Well, you've got to make it multicenter. But there was no funding for this study.
There was absolutely no it was me and me and how could I go out to North Hampton, Redding and so on and and manage it out there and collect the data.
The deal with Peter Bailey was that I would collect the strictly the trial information.
He would collect the ancillary obstetric data at the started.
The first patient was recruited in April 1970.
And at the end of 1970, on December the 24th, I had a wrap up session with Peter Bailey in preparation for 1971.
We agreed that recruitment was slow. We need to find methods of improving it and that it wasn't quite running as it should.
It was not running at all as it should. And in his pocket, unbeknown to me, he had his return ticket to South Africa.
And on Boxing Day, he met Margaret Anstead on the platform of Oxford Station,
saying that he was going back to South Africa and he left and never came back.
He didn't notify stoneware that he didn't notify me.
The first we heard of it was via Margaret said on Boxing Day he did make an appointment to meet her.
It was an accident that they met. But, well, when they met.
And by chance. By chance. By chance.
And so he just disappeared, leaving me.
My project was in tatters, and I then had to make a decision as to whether to give it up and go away and be a GP,
which in those days was a very low grade aspiration, or leave Oxford and go and find something else,
um, or get in a head and shoulders and just do it all myself.
So I did I did that. I started managing the whole thing myself and I did one other very important thing in my life.
I went to see John Boehner right now, the first assistant to stalwartly and John Boehner said, oh, no, I'm too busy, I can't help you there.
But I said, well, do what you can. But he came on full on and he reorganised the whole department and he had a strong
enough presence that people like Arthur Williams and Edward Koch did what he told them.
And so and we and he and he he reorganised the the data collection on the obstetric side to introduce a flow sheet,
which is, um, in its derivative form, has been in use ever since and on the clinical side and things began to go.
So that was a relief. But then I found that, um, I was because I was a hypertensive expert, which I wasn't,
I kept being referred people with pre-eclampsia, intractable pre-eclampsia.
They weren't ideal for the study, which was about the long term management of hypertension.
But they certainly were the most interesting.
And they certainly I thought that, you know, out there, there were people who knew how to deal with and knew what the problem was.
And it was my realisation during 1971, 72, 73,
that these were the hard core of the hypertensive problems of pregnancy, not the women with hypertension.
Most of them had very benign pregnancies.
It's only a statistical thing that they have trouble more often, but it's like doubling to five percent to five percent.
But these are severe pre-eclampsia were awful.
And the belief in those days, believe it or not, was that because their problem was hypertension, the use of antihypertensive medication,
which I was the bringer of, I was the first person to use them under Lawrie's direction in the department would solve the problem.
So they would say, come and treat this woman expecting her blood pressure to normalise and then for her to go home and come back at it was that naive.
And of course, it didn't happen. And and then I it just went from, you know,
there's a whole vacancy area of torment and trouble and unhappiness and disease and destruction and death affecting this small group of women.
And that obstetric department just walked around them. They were a delivery issue.
And then when it became to any medical problems, they were a physician issue.
Their job was simply to make sure she didn't get preeclampsia and survived the experience.
Uh, and during this time, I developed a technique of managing these women,
which in its it was probably one of the first to apply hypertensives aggressively because they had
no idea how to administer 125 milligrams method over twice a day and expect something to happen.
And I quickly learnt that you had to go, you know, quickly up to two or three grams a day.
I taught myself basically, were you injecting something as well as a.
Yes, something which was a standard treatment then. And and then I added an oral hydrazine into the mix with the method and worked extremely well.
This is pre the calcium channel blockers.
And so I could stabilise the women so they didn't have to be delivered or and they there they weren't at risk.
But then the babies kept dying. They just kept dying. And there was no way of knowing how the babies were.
They weren't all the gadgets that people have now, no ultrasound, no monitoring.
And at that time, um, a, uh, an electronic foetal heart rate monitoring device was introduced into delivery suite from the United States.
And this was the first time that it was used in labour.
And it wasn't a very insightful thing for me to think, well, if this is useful and Labour can tell you when babies can die,
since all my babies are dying, these are at twenty eight, thirty, thirty two things.
Think I'll have a look with that. And it worked.
And over the next five years I cut down the stillbirths about six or seven fold for the first half was bad news.
Oh, there are specific patterns. It's not just a false start, it's the variation.
It's decelerator active. It's quite complex. So by 1975, um, uh, I was well into that as a sub interested, I'll come back to that.
You asked about my thesis in nineteen seventy four or thereabouts by the trial,
reached a sort of a conclusion and Dole was getting impatient to move me on.
And so he said, you stop it, you can write it up now.
And I wrote my abstract for my M.D. in Cambridge and I had a phone call from the then Regius Professor of Medicine, a man called Mills.
I don't remember him. And it was you won't believe this.
It was quite bizarre. He said, we've just reviewed your submission and we can't accept it, I'm afraid.
And I said, well, why can't you accept this, because essentially the outcome was negative, you didn't show a benefit.
So, um, you can't mean that if you do an experiment, you have to accept those conclusions.
Oh, no, no, no, no, no. I did not mean that. So I then tried to pin him down and we went out to the sample and then we got back ten minutes later.
Well, he said it's because the result was negative. Um, and I couldn't deal with this.
I really could not deal with this. Everything was happening in my life.
They were we just we had four children, um, and and, uh, it's a domestic life was hard.
And I submitted my first report on the trial to the BMJ and I got a personal letter back from the editor of the BMJ, which I should have preserved.
But I've lost saying, dear Dr. Redmond, thank you for referring, uh, with, uh, for sending us your manuscript, which we cannot accept.
I would just like you to know that this was the worst paid written paper that I have ever had to review.
Yeah. Yeah. Um, and I thought what a way of boosting.
Uh, well, I didn't think anything. I was just shattered. Yeah. And so I had a paper that was the worst written paper.
I had a thesis that was turned down because it had a negative result.
And I thought, well, I've just got to get my papers out and blow the thesis.
Um. Um, and so I, I thought I had no advice from anybody on this.
I have the most almost contempt for people who want to be babysat all the way throughout their careers as they do now.
Then I went away and then dissected why it was badly written and I found it was the English language that he objected to,
not the scientific structure, the content. Have they sent you a line by line of criticism or not?
No, no. You had to do it. I got out Fowler's English language usage.
I taught myself how to write properly and I could see what he was objecting to once I had studied this and I rewrote it for The Lancet,
and that was when my research career started.
And that was just about the time that, um, dog got this this job for me on the NHS, um, through Rosemary Rew.
Right. Which led eventually to my consultant. Um, well, to begin with, you were a sort of senior registrar.
Yes. Yes. Through all of this, while I was a lecturer, I moved up and after I was a CPA senior registrar.
But then that was a major stroke through Rosemary Room and it was NHS funded.
It was her academic, um, Dole and the thought that the NHS should have fun, some of the academia.
And so I was funded in the Department of Obstetrics on the university, um, as a as a university lecturer.
But the funding didn't come through. It wasn't funded there. That was it was an outside funding.
So Islamic Turnbull and of those when I arrived in 1972.
And what difference compared to still where they stood still?
Well, he was always supportive, but he was primarily a clinician and he didn't really know what I was trying to do.
But he was hugely supportive then. Uh, and Turnbull was also.
Did Boehner leave? No, no, not yet. As I went over to Cardiff to before he had arrived from Cardiff, Alec,
and to tell him about what I was doing, I had a most charming hour with him in which I didn't say anything.
He just talked about all the things that he was doing and then got out, said Chris.
It's so nice to hear what you're having. Um, but he came and he was totally supportive.
And he, uh, he was a remarkable man, as you know, and he really, truly liked everybody.
Everybody was worth knowing. And so he transformed the department immediately into a really friendly department.
And I was still working with John Boehner, who was looking for pastures new,
and he eventually left for Dublin about nineteen seventy five, seventy six, I think at the end of seventy six.
He was gone just after I took up my new position. And after that, did you work with any particular obstetrician to begin with?
I try to work with Gordon Stewart, who replaced John Farmer, and he was very nice and he was very supportive.
And, uh, but he didn't have, um, John Boehner's ruthless streak.
He was too nice. Um, and he eventually moved on to become the head of department about nineteen eighty one, I think.
But he was a very nice guy. But by this time several things had happened first.
I had had realised that I needed to have my own pairs of hands in the department, and so I was now working with research midwives.
In fact, it was a research midwife who was appointed in 1973 or something who just transformed the way I work
because she she was wonderful and she would go around and find suitable people to recruit for this trial.
And if she when she was stumping the clinic, Edward Clinical could be seen running away into his room to hide from her because she was tough.
But she was the daughter of a naval officer and she brooked no, no, no consternation.
And so I had these and there was a constant succession after those that.
And so I became more independent of any one clinician.
And, you know, Arthur Williams and Edward Cope sort of tolerated me without liking what I was doing.
Douglas Ellis was very practical. We set the borders between what we did and what we didn't do.
And until he left, we could work together.
And John Boehner and muscle memory in those days were highly supportive.
But then Gordon Stewart and Austin and so on and so forth.
So I think and this was the time when I began to realise that there was a future in obstetric medicine.
And, um, this position that I got in 1976 was the first full time academic position in obstetric medicine in the world.
Indeed. Uh, Michael, the suite had preceded me. You know, I had been in Oxford together in 1971, 72.
Then he went off to work at Charlottes as a physician. But that was always part time.
You knew he had a full time commitment, I think, at UCL. And, um, it was and as an NHS appointment to mine was an academic appointment.
And there was no question and there still is no question that in that terrain between complicated medicine and complicated obstetrics,
there are these women in the middle who have both the complicated problems that they have, medication that is rarely tested in pregnancy.
They have issues that are life threatening. And they and those days and to some extent, even nowadays,
neither the obstetricians or the the general or specialist decisions were comfortable with the issue of pregnancy.
It's changed a bit as they have become more super specialised.
Someone like all of whole world now is perfectly comfortable with managing women in pregnancy.
And so but it does raise the question and I fill that gap.
So how a patient referred to if their blood pressure was above a certain limit was the indication?
Well, um, while I was running the trial, they weren't referred and we went out.
Yes, but you found what, people above a certain number?
Yes. And it was all very tightly controlled. And and then we randomised them and then we stopped.
And after that, people would, by word of mouth, they would say with this woman, we want your advice.
And then the others came in, the people with renal disease, with autoimmune disease, diabetes.
I steered clear of because my Gilma Yes.
Arrived and he took those over and he, he was very good and he was very good.
And um and then there are always the oddities people with, with conditions that you rarely rarely see,
but because they become pregnant I couldn't describe them, I wasn't.
But I could describe something quite incredible cases which even to this day I don't think it was clear what was wrong with them.
Then they and they died. There were this is the terrain where maternal deaths happened and there were maternal deaths.
And it wasn't because of neglect so much.
And but some of them were avoidable because there was no proper joint between complicated obstetrics and complicated medicine.
So what did they do? What was the eclampsia or hypertension itself?
But the other ones were dying of renal failure.
Uh, there was one woman who just kept getting kidney infections and then she would recover and then she got another kidney infection.
She recovered and then she came into some sort of terminal state and went off to the
medical world world wards and couldn't feed herself and had a nasogastric tube.
And then she vomited and inhaled and, um. Yeah.
And she died of lung disease. And that's I mean, it was one ofthe things there wasn't any trend.
There was a one maternal death from eclampsia in 1971.
And then the next one was about 25 years later in the 1990s.
Uh. And so in I think in the whole of of my association with department, there were four deaths.
Were they maternal deaths being reviewed then? Oh, yes, I thought so.
I mean, just announced with the national system. And how did that impinge on you?
Do have to give evidence to somebody who can you the notes had to be made available, um, in a in a anonymise form.
The first death I happened to be on annual leave at the time, so I wasn't involved at all.
The next one, I certainly had to make a written comment, but that was in 2000 and something was that did you feel an educational process?
So I and I think first of all, yes, of course.
Um, and if this process goes on and it is within the hospital every year,
event is subjected to quite close scrutiny and people spend their souls and try to learn from it.
I think it was the confidential enquiries were one of the most wonderful audit, um, activities ever.
I mean, it always amazes me. Demonstrations, you know, great.
And they were reliable figures on what was going on over a 30 year period.
And you could learn such a lot just by looking at them.
And they continue to work on it and not quite so thorough as they were,
but they've been eating away at the edges and and the situation is always better.
Triennium on triennium. Were you involved in doing it to me and Roseanne Anderson coming in the department, which is separate from you?
She came in with Alec Turnbow from Cardiff and she ran his research lab.
He had to NRC programmes whilst he was up there.
And, uh, when the second one needed to be renewing her, he failed to get the third.
And this coincided with Anderson's illness. She got breast cancer and then died at a very young age and early 1980s.
She was absolutely lovely. And she ran a she ran gynae clinics and er and she got me involved with menopause clinic, um,
because in those days little was known about the menopause, except that it was uncharted territory.
And I went and did consultations with her.
And I must say I could see this was a trait unique to rate and I couldn't understand any part of it.
But anyway, um, she she did that and then she got ill and wasted away, and then after that,
Alec had his first brain tumour and he that was successfully treated and but he hadn't he'd lost his research funding, his major research assistant.
So he was he focussed on keeping that happy department happy, which he did so beautifully.
He was just such an artful, nice person.
And having seen different heads of department store and the store where they and he and then latterly David Barlow,
who succeeded Turnbull and now Steven Kennedy and John Bell.
And so you can see how different heads of department have different impacts.
And what about your original trial? What was happening to them?
Well, it was published in The Lancet. There was a marginal improvement in in second trimester, uh, deaths, which I didn't believe in.
But so I played it down. It established that the treatment with method data was safe and it still remains the best documented and,
uh, most, uh, best known for that reason, the safest.
And it Margaret Downstair then did her bit and she followed these children up at the age of two and
seven and published the follow up story that makes it almost unique in a drug treatment trial.
And she showed that it was safe for the babies because they were and the children were just fine.
They had not suffered as a result of exposure to methadone, but the two groups were the same.
The children in the group. Yes.
And, uh, and so in the world, um, it's always had a very, very high status, even though, uh, by current trial management protocols,
it would be considered to be primitive, but in those days that it was the best that could be done.
And, you know, people still refer to it quite highly cited.
No. Great. Um, did you ever meet Chris Ansted? Harris Oh, yes.
Oh, yes. Yes, yes. I mean, did you work with him? No, I did.
I guess. I met them quite a lot and they were fine.
Oh, they're still two sorts of pre-eclampsia. So what were you inhabiting your first pregnancy?
And they have always had babies. Uh, that was to an extent, both say it's moved on enormously.
Um, it's, um. And now the heterogeneity is seen in terms of early and late onset disease early in pregnancy,
the sort that was worrying me right back in the 1970s and women at 30 weeks
with intractable problems and then the late onset disease which comes on it.
And the it's all both of these conditions are thought to be secondary to placental mal
perfusion from the mother so that the placenta is relatively or absolutely toxic.
Oxidative stress often infarct it. And the origins of the perfusion are different in, um, early onset disease,
its failure to to form the placental circulation properly for presentation.
And this was a subject where John Boehner did a lot of work. And so there was a natural link up there.
We did some very nice stuff together. But Plantation is finished by 18 weeks, 20 weeks.
And is the preeclampsia, which starts happening in the third trimester,
is the sequel to that with the what is essentially and structurally abnormal uterine placental circulation just isn't coping with late pregnancy.
But then there is the late onset disease, which is when,
not because the European central circulation is okay, but because the placenta is growing to its limits.
The uterus can provide so much and when the placenta begins to outgrow the uterus,
it becomes more diffuse and then you get pre-eclampsia from the same placental insult but of a different origin.
And it's very interesting. Um, and then did you get some medical help?
I mean, you got your research midwife, but did you get a registrar or whatever, you know?
Um, no, not for ten years. Well, actually, from 1976 to about nineteen eighty eight, I was essentially single handed.
Yeah, I remember that. And it was a burden too much.
And then Sue Sellers was appointed as a new consultant specifically to the high risk clinic.
Should she and I were together and I thought God help at last.
And the first thing she did as they always do and she arrived, she says, I have something to tell you.
She's going to have a baby. And so the help I was to make it arrived again.
Yes. And she was great because and then then it began to improve and the and the whole thing became formalised within the obstetrics service.
And they developed the speciality of foetal maternal medicine, which was long overdue.
So for the first time, there were men and women who weren't gynaecologists just doing obstetrics because they had to they were not doing gynaecology.
They were focussing on the obstetric problems and they were much better trained.
So when did that start? And you said nineteen ninety. Yes.
How old were you when you became a consultant level. Uh, in nineteen seventy six.
I was uh forty, thirty five years. Yeah.
That's good. Um and you asked what, what stage as it were, did you begin to be called on your back shows around the country.
In the world I suppose, um, around about the 1930s, early 1980s.
And um, I began to be known and, um, this was facilitated by a man called Marshall Lindheim,
of whom you will never have heard, who was a renal nephrologist in Chicago who, uh, focussed on pregnancy related problems.
And he got to have a meeting organised in nineteen seventy five of.
The sort of workshop meeting in Chicago where people were invited from around the world to contribute
and John Boehner was asked and he suggested that I was also invited that put me on the map.
And, uh, from then on, it increased.
And I was asked to be to attend meetings and, um, both clinical and research.
We were asked to give a lecture. And Oxford, uh, really than meant the Oxford Medical Society asked me to give one.
Um, and, uh. I presented to the grand rounds from time to time, but I don't think they found it and there was the medical.
Yes, it's not good. Um, and what as it were, do you feel you've done since that's a two thousand.
What did you tend to work on after that then? Oh, it's become more and more and more interesting.
I have about 30 years of research left in me and about three years to do it.
And so it's a hopeless situation. But, um, in 1991, I published a paper which just reiterated what had been known for many,
many years, that, um, preeclampsia derived from the placenta.
It's a it's a placental condition and the hypertension is secondary. And that has become quite a well cited paper.
And it brought in a previous paper, which was published in 1989 by Jim Roberts, who's now in Pittsburgh,
um, who pointed out that the maternal problem was essentially endothelial dysfunction.
You could explain every single clinical feature of preeclampsia in the mother by her endothelium being dysfunctional for the baby.
You couldn't it was a different issue. And my contribution was to to point out that there were two steps to the process.
First of all, there was the placental dysfunction. And then as a consequence of that,
there was the theory of dysfunction and then the middle there were factors which were yet to be discovered connecting the two.
And then, um, and it's just gone on from there.
And so in the early 2000s, some of the factors were discovered to be the the antiangiogenic factors which are, uh, inhibit the action of Jeff.
And these were discovered because VEGF inhibitors given to cancer sufferers give some of those sufferers preeclampsia,
that they get hypertension and proteinuria.
And due to the renal biopsy and they've got glomerular endothelium, which is the better mnemonic lesion, preeclampsia.
And so they found that the placenta is a rich source of antiangiogenic factors,
particularly the patch for one receptor, which is released and acts as a decoy,
sucking the life out of the system when the mother is deprived and she gets that's the cause of part of the cause of her endothelial dysfunction.
But I published another paper showing that a more profound problem for all pregnant women is activation of the innate immune system in pregnancy.
I published that at nineteen ninety nine. We were the pioneer of that.
Were you the pioneer? These are all ideas that I know. No, great.
Because that's a terrific idea. I mean, which is been born out of the area.
And I was absolutely pilloried for people because this isn't sensible.
It just doesn't make sense. Um, but since then, not a single piece of evidence has been found to disprove it.
And I've been developing that theory. And so the the latest one where I've linked it to a placental dysfunction is to
point out that the vital part of the placenta in pre-eclampsia is the in situ.
And this is a remarkable cellular structure. It's an epithelium in the blood system.
So it's you know, the mother temporally has 12 square metres of epithelium contacting her blood.
And it has a it is always damaged in pre-eclampsia.
And it's the damage, the danger alert signals the damage, the various molecules falling off,
dead and damaged in situ that can account for everything about preeclampsia that are published in 2015.
I mean, there I can see that the fact is coming out damaged epithelium at large.
Yes. And do you think of the hypertension because of that?
Yeah, it's the and it's endothelium dependent, but it's one of the few sort of hypertension we're circulating.
Endothelium is increasing. But in general, medical hypertension, you don't see high chrysanthemum and smoking affected.
Oh, yes. Oh, yes. This is just so interesting.
Smoking is one of the only activities that pregnant women can take to reduce their incidence of pre-eclampsia.
And that may well be because the carbon monoxide, which comes with smoking, stimulates the enzyme.
Homogenise, which is very is an important activator of endothelium health.
But then smoking brings all sorts of other penalties, the tyres and the poisons and so on.
So the baby suffers. Motherson is relatively protected and as Peter Redcliffs system coming doing this, yes, um, yeah,
he he discovered the Heferen Alpha kind of thing and that's very active in that since the overclass.
Um, but it's quite interesting and this is where my theory is kind of builds on what he produced,
because if one alpha is not just a hypoxia sensor, it's a danger sensor.
And so if you get other cellular stresses like, um,
which there are here on Alpha is no normal actually activated because it's part of the stress response system.
So the the evolution of the idea that I'm promoting that, um,
it was innate immune cells and the inflammatory system, which is the part of the problem.
Preeclampsia is now generalised to the fact that it's all part of the stress response system activated by the placenta.
And you can then, you know, it's like the theory of everything in relativity.
It's I mean, totally preposterous that this is on a very small thing.
But, you know, having journeyed the journey and started seeing these cases with preeclampsia that nobody could make any sensible comment on,
to get to the point where you can identify systems which you think can explain everything that you see, I mean, the proof is there.
Yeah, it's it's really quite exciting. The prolongation of pregnancy with steroids.
Right. Is that because of the effect on the autoimmune? Uh, no.
Um, it's, um, the steroids are given to to activate maturation of the foetal lungs and they temporarily damp down the inflammation.
So if you've got low platelets, they will temporarily rise.
But they're they can't put back the damage that the nooner since nothing can people still can't learn.
Once the system is damaged, it's damaged. It's like and and, you know, you're you're stuck with it.
So how many papers are emerging as the sort of vulgar question? How many papers published?
Depends what you mean by papers. Yes. I mean, everything that's cited in PubMed, it's about 300 deaths.
And if you talk about papers that matter with me as the first or the last of which are cited, say, more than 50 times, they're probably 20 or 30.
That's great. Widespread. And my my largest citation is about seventeen hundred.
And that's a review I did for science about 2000 and are used to working with the same clinician.
Was she moved on? Oh, no. Sue moved to Bristol with her husband, Andres Lopez by now, um, round about 2000 and she's since retired.
You see, I'm 74. I want to ask how old you are, but you're probably about seventy six.
It is what it is. You're eighty seven of you are doing well.
That's an excellent. And um. So yes.
And so a lot of the people I've worked with have now retired and uh and the clinical
activity has been taken over by people that no one should be who you probably don't know.
No. Um and the kind of and I have a successor who's someone called, um, Lucy McKillip,
who trained as an obstetric physician with Katherine Nelson Piercey and the Thomases.
And so she she is doing what I used to do clinically, but she has no academic appointment.
And those and I, I left clinical activity in 2008 when I was found to have a and just a non functional pituitary adenoma,
which was causing these symptoms.
And, um, you can imagine, James, what's his name, the medical director, absolutely did not want me doing clinical work with a lump in my head.
So he said, get Ms. Morris. Joan James Morris. Yes. He told me to go.
Um, so I went to have my operation and I was within a year of retirement,
my recuperation took about three months at the end of which I had the returned to work programme.
And I realised by then, having stopped clerical work, that not only did I not miss it, but life became enjoyable.
And so I had only one year to go. And Lucy McKillop was already my temporary locum.
I just said, look, I'm not coming back to do both jobs. I will do other.
My university research and teaching job, I do the NHS job, each demands 50 percent more of what I'm contracted to give.
I'll do one or the other.
And, um, Steven Kennedy, who was then head of development, negotiated for me to come back, only doing my academic job, which was wonderful.
And I so I lost, um, did any clinical work in March 2008.
And then once I had retired, I just registered myself with the GMC.
So there was just no way of getting to get, um.
And, you know, sometimes I dream about it and sometimes I think, you know,
someone asked me the question in the corridor and I can see the old interests coming back.
But I think the modern NHS, the way it works, the way it's fragmented with Rotor's and so the way it's all about tick boxes and not about brains,
it's a trap of saying, you know, I mean, they're trying to degrade the profession.
I mean, deliberately or accidentally, I don't know. But they do regret it to this checkboxes.
I mean, you stop thinking you stop it. Is it is it is really so inappropriate.
Is I. I talk to people and they they give the tick box responses.
It makes me so angry and I have to not be angry.
So your job, is it now funded by grants from, uh.
Well, I'm actually tired, so I have no idea where you're working.
I'm working. But that's because they give me an office and and I don't draw a salary.
But I have had various consultancies and I'm involved with international collaboration.
So there is one based in Pittsburgh, which is called CoLab, funded by the Gates Foundation.
That's one based in Norway, which is funded by Norwegian money.
And then, um, when I retired, um, I was working with the sergeant who is was a bench scientist who he had started working in 79.
And we continued through and he was we were on our fourth programme by then and that's still running an MLC programme.
He was one of the very, very, very few people to get a new programme here.
He was the P.I. and, uh, this is.
It's the tail end of this is just so this is why I say I want another 30 years.
They're just discovering the things that we needed to know about them.
They said the bench, the chequebook. So the bench isn't an orchestra? No.
Yes. No, here he I got him as a welcome base post stopped in 1979.
He was appointed to a permanent lectureship in the university in 1983 and the new blood initiative that Maggie Thatcher had.
And he remained in the post until last year when.
His work in as one I mean, the maternity ward, he was he was he stopped now.
Yeah. You know, I was there as well where he was best he had.
And he and he and I did a lot of pioneering things together. We were the first department in the world to have our own flow cytometer.
In 1985, we were the first department in the world to discover the first unit anywhere
to discover the blast circulating through the blast deprived motor vehicles,
which we discovered in 1990. How did you discover them then?
I mean, how does one do that? Um, in nineteen eighty eight, the Americans,
they got this endothelium little damage theory and they said we can find a factor
circulating in the plasma and when we put the plasma on the endothelium we see damage.
So we try to replicate that and we just couldn't, we just had so I thought blow this factor is important.
It must come from the placenta. What factor? How can we test something coming from the placenta?
Now, there was a long standing method of preparing, um, purified and such a dreadful blast,
microcephaly, um, called the Smith Prussian Lockette preparation.
So at the end of it all, you had these micro physicals which had exfoliated off the syncytial in situ epithelium that sort of reformed the membranes,
reform them, and they were in the right orientation inside, in and outside out so you could use them for transfer studies or whatever.
So you got those from Presente from the result.
So we had a research fellow from Iceland called Alex Marrison, and I said, well, why don't you just make a preparation,
a Smith brush in preparation and apply it to cultured into Psyllium from the Bellocchio,
uh, veins, which is a standard source of cultured and the theme Kubek psychology, human umbilical, venous epithelial cells.
So he did that and he got a normal placenta, did a free market preparation,
pure since the glass membrane popped it on the cultured membranes and he came in.
It was one of those major, major moments. He was so excited.
Just the morphology of the that was just ripped apart.
They were so toxic. This is just the normal, um, the normal surface of the abnormal placenta.
And so that kick started a process.
And he and sergeant then, um, said, well, we've got to find them circulating in the in the in the blood if they're real.
This was an artificial preparation. And so he set up another postdoc to to look into that.
And they developed a preparation for finding them, measuring them.
And, yes, they were there. And by then people were well acquainted with platelet micro vessels and red blood cell microbicides.
This was the third time that was discovered, Trevor Glassmaker, and they were there in greater numbers,
in pre-eclampsia, lesser numbers in normal pregnancy and everything fitted.
And that's what we're working on now. And so but now what we've got our perfused placental globules, um, so much more, uh, physiological preparation.
We perfuse the lobby and in the perfuse eight off the surface of the lobby, all these vessels are secreted.
Then we can, um, purify them and they they form into three groups.
There are what they call apoptotic micro recycles, which are dying.
Then there are extrude expertise, micro vehicles which have a different origin.
And then there are exosomes which are nano vesicles. And we've got preparation's of normal and pre-eclampsia, placenta after perfusion.
And we've separated them into the different categories of micro vehicles and sent them off to the ER.
Makes people, whether it's are they are people who do nonbiased assays of every single molecule in the whole thing.
It's the modern fad where the name and they're in every university element is a huge this is what John Bowlsby developed right over in the church.
There are people who do nothing else.
And this has spawned, uh, something called bioinformatics, which is very sophisticated statistics to make sense of it all.
And what you get there, about a million data points and then you start making you start digesting them through your computer.
And we've got a shortlist of six or eight. Actors, which are some of them have been known before to report some of them.
Nobody has ever heard them. And the most important, which is really is different between the pre-eclampsia and the normal,
is a factor which has never been mentioned in relation to the strength of the Australian centre before.
But previously, when we say talking about endothelium, were you doing that?
By really mean I say or I mean, how did one do end up being an entertainer is a regular Venessa?
Yes. No, no, it's Analisa now because they don't do radio.
No, no. It's been abolished with no time marches on.
How much teaching medical students did you do in Oxford? I do.
Um, I think they come through every eight weeks or every 12 weeks.
Gone are the days of the though were three months, no attachment,
and they used to get to lectures on hypertension because it took me to lectures, then they didn't have time for that.
So now I get one lecture on hypertension, pre-eclampsia, and I've been giving that and non-stop since about 1975.
He started quite early. That's good. And then had to teach English and John Bell.
Do you have anything to do with him or are you just facing towards obstetrics all the time?
Very little. He doesn't think anything that, uh, matches up with what I'm doing.
And John was a very focussed man, and it's not relevant to him.
He's away doing something else. So who would be the informatic chap at the church of the to do?
Um, he's he's a man called Adam Thrip. Um, he's, uh, relatively young.
I mean, he's about 40 and he's quite hooked.
I mean, he sees all these things happening and we can produce very, very clear discrimination between health and disease by looking at the placenta.
Right. Because, um, it's the cost of tissue and you get it.
You don't have to do a biopsy. It arrives at delivery. Yes.
And there are 24 placentas delivered every day in the John Radcliffe.
You can't complain about a shortage of biological material. I mean, is each of them examined nowadays and examined the pathology?
You see, because it's a sensitive problem and because in situ or submicroscopic,
the classical pathologists don't find it very interesting unless you've got an infarct.
It's not not looking at that. They're using the wrong techniques to look for a lesion which is invisible to them.
How early in pregnancy can you pick up your factors in the blood?
Depends. Depends who you're working with.
Um, if the woman's got very severe impairment of placental formation, um, it becomes apparent around 16 to 20 weeks.
But that that's for pre-eclampsia. That's going to come on at 24 to 28 weeks.
And you then treat the patient, you know, what do you do?
The factors are raised before the blood pressure.
And there's no way that anybody knows that the information is not clinically useful except to say watch out.
Yes. So you would keep an arm here. You would watch, look for trouble.
And that's what happens. That's been going on for 15 years. But you can't administer something and say that's the end of the problem.
It doesn't work like that. It's like type two diabetes.
It's a complex disease and all sorts of environmental and genetic inputs.
And by the time people are aware of what's going on, it's too late.
You never go around to diabetes. And then, um, I'm not in a clinical sense, research wise.
It's very good, sir. I mean, you work on that, too. Oh, yes.
As if obesity and type in our national obesity and glycaemic stress is very close to hypoxic stress.
And and so the two are joining together. What sort of level is it?
Glycaemic stress? Oh, well, it would be at the sort of levels that you would want to treat anyway in terms of what's going on in the lab and in vitro.
Um, the arguments as to when you start worrying clinically about the blood sugar has gone out of control and
they they are setting thresholds so low that the clinics can't cope with that is their maths slightly.
And I think, you know, I came across that through there and it seems it's even more absurd.
Right. And and so they have huge clinics. They can't manage that.
I don't think they know whether or not they're doing any good. And I suspect they're not.
Yeah, it's it's just it's hopeless. Um, they what happened last year that I should have.
What do you want to tell me? Um,
all I can say is that I came into medicine completely uninterested in research and I've ended up completely obsessed with the fruits of the research.
I'm an absolute convert and I love it.
And that's why I want another 30 years to get that. And how many times a year would you go abroad at all?
Um, roughly about six or eight years. Now I'm still in demand for meetings.
I'm sure I'm going to Sweden twice at the end of this month for two different events.
I'm going to, uh, uh, Reproductive Immunology Conference in the Reunion Island in December.
I'm going to, um, Norway in January.
South Africa and being in Brazil, which just being in business, um, as you travel around, uh, probably impossible to get a real feel.
But do you get a feeling of how the NHS compares with other countries now?
Uh. Yes and no in America, they are absolutely bemused why the conservative government is privatising the services as quickly as they can.
They said we've been fighting for years to get out of privatisation. It's very counterproductive, wastes money and and so on.
The very intelligent positions over there who are not into profiteering know perfectly what it's all about.
And they just wish they had more of an NHS.
Um, I in in places like Norway, they still got enough money to run good systems, um, because they're very, very rich, much richer than ours.
But they are, um,
they've got all the problems of Rotor's and then nine to five Nixon and so even worse than in England and that's where it falls apart.
I in the old days we did what needed to be done and stopped when it was done.
Nowadays they say, Oh, I've done my best. I'll tell you about what the problem is.
And, uh, and they could but anybody who's been in hospital and I have more than my,
uh, what I'd like to be knows that you you get no continuity of care whatsoever.
And when I was in after I had a quadruple bypass in 2012, um,
and I was really well looked after until I came out of ICU, after that, I had to direct my own care and I was a doctor.
So I was lucky what other people did. I wasn't getting my medication. I was getting the wrong medication.
I was being asked to do things were inappropriate. And I had completely and they the nurses are not what they used to be.
They they're very self regarding they they regard their activity as steps on a career ladder.
They don't see any commitment, you know, very few of them to other enough midwives then.
Mm hmm. But they're committed to this.
Uh, they have change because they don't do any, um, general medical training now.
So they don't do the nursing training, their direct entry into midwifery didn't.
And so they are so ignorant. Oh, uh, and they are so small minded.
They're only interested in getting a woman delivered this year. That's what they want to do.
And if she happens to have hypertension or is dying of this or that, uh, that just spoils the fun.
So they don't really want to have much to do with. And I'm exaggerating. Oh, sure.
Sure. Gosh, anything else. So we finished, um, anything else.
You've obviously enjoyed it over is uh. I've been all right with tough periods.
I mean, you're I probably didn't enjoy the, uh, decade beginning 2000 until I got out of it by illness in 2008.
Then I began to enjoy it again.
Um, and, uh, I always thought that progress was incremental, that you got things better than people held wasn't better and got them even better.
And what I hadn't realised is that you get to a point where people have lost,
forgotten all the lessons of the past and just throw it away and say there's
this element of going around in circles and getting back to square one again.
And that's very much happens in medicine. Yeah, they, uh.
Well, these people just have to learn the lessons and they go.
Thank you very much for that interview. A really interesting book.
OK, well, thanks for coming.