pnadel/npi_all_transcripts · Datasets at Hugging Face

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45,400	315	QUESTION: And were any steps taken by the school to try to mitigate the risk of any future outbreaks? ANSWER: When you say by the school, do you mean by my part of the school?
45,401	315	QUESTION: Yes. 68 ANSWER: Well, no. It was not our -- there was nothing -- I wouldn't have seen that as being something that I had really anything to do with.
45,402	315	QUESTION: So your expectation would be if there were further steps to be taken it would be the haemophilia doctors ? ANSWER: No, tha t had to be the haemophilia doctors, yes . Yes.
45,403	315	QUESTION: And do you know whether -- ANSWER: We didn't have a haemophilia -- at that time we didn't have a Haemophilia Centre in the school, of course.
45,404	315	QUESTION: And do you know whether there was any report of the outbreak made by the school or the doctors to an external body ? ANSWER: No, I've no idea. Why , are you supposed to report these things?
45,405	315	QUESTION: It's just an open question , Mr Macpherson . The questions I asked about research were about research in relation to the boys with haemophilia. Was research undertaken , as far as you know , in relation to any of the other pupils at the school, so the non-haemophiliac pupils? ANSWER: When you say " research " , it depends what you mean by research. I mean , people sort of investigating numbers of this and numbers of that, and parents and so on. I remember our -- a deputy head who investigated or researched into the situation with 24 June 2021 9 parents at our -- of children at our school , and found that only 40 per cent of the children at the school were from what you would call a " normal " family, two-parent family home. Which is a bit of a surprise. Well, it was a surprise to me that it was -- that 60 per cent were from not a completely normal -- and quite a number had no parents at all, or their parents had rejected them. And she found that quite a lot were single - parent families, and that the child was actually the cause of the break-up of the marriage. And the child usually knew that, which was another psychological factor. But I wouldn't -- I couldn't tell you how many of these were haemophiliacs. So that sort of research went on . Is that what you're talking about?
45,406	315	QUESTION: Do you recall whether there was any medical or clinical research in relation to any of the other cohorts of pupils, the non-haemophiliac pupils? ANSWER: I know that Pat Tomlinson talked about it a bit but I don't think she actually did anything particularly. Not at the school. I mean , there were -- certainly a lot of our pupils went to Great Ormond Street, and I know Great Ormond Street were doing research into a number of things which quite a number of our pupils 70 were absolutely definitely involved in there. There's no question about it. I remember hearing about them , things like bone marrow transfers that would cure this and cure that, and they never did , and operations that were meant to make pupils walk again . And I remember a boy coming in to me and saying, "Next time you see me, I'll be walking because I'm going to have this such-and-such an operation ", and he actually was walking at that time on crutches . And you know what? He came back in a wheelchair for the rest of his life . And we used to look at these and we used to say , " Well , oh dear , is this in the best interests? " But these weren't haemophiliacs. So I'm going off the subject now. So yes , there was quite a lot of research going on to do with our pupils. I don't think there was a lot -- I mean , there wasn't really very much at our school . There wasn't time. They were busy. There were lessons that were being taught. There were ... so no, I don't think there was really very much -- not that we were involved in anyway . Does that answer your question? I'm not absolutely sure what your question was .
45,407	315	QUESTION: If I can then just go back to the question of Dr Rainsford. 71 ANSWER: Right.
45,408	315	QUESTION: When you joined the school in 1974 , and in the following years during the course of the 1970s, what was your understanding of what Dr Rainsford's role was , in connection with the college in the pupils there? ANSWER: Do you mean detailed? Are you asking for a detailed answer to that --
45,409	315	QUESTION: No , I'm asking -- ANSWER: I mean, my understanding was that he was doing some research of some -- and I thought worthwhile -- I was given the impression it was worthwhile -- to do with giving transfusions of Factor VIII , and prophylactic transfusions , and all that sort of thing. But, I mean, that's about as far as it went with me.
45,410	315	QUESTION: And was it your understanding that -- or what was your understanding of his involvement with the actual treatment of the boys? Was that part of his job as far as you understood it, or not? ANSWER: I think he was -- I think he was involved with the treatment. Yes . Yes . As far as I know, he was. I couldn't guarantee that . I mean , I really had no involvement with the medical side except where I heard about it or talked about it, or whatever.
45,411	315	QUESTION: I'd asked you before the break about counselling. Was 72 there anything further about counselling that you can assist us with? ANSWER: Yeah , well, I think, yes -- yes , I did want to add a bit about that. You were saying that Mr Scott was saying that he thought we could have done more. And my answer to that would be: you can always do more. You can always improve on things. But we had -- the housemasters did meet with this -- our psychiatrist. He visited about once a week and I think most of these times the housemasters did have a meeting with him, for -- to discuss whatever they wanted and I'm sure that this would be one of the topics that they would discuss with him. I went -- I occasionally went to these meetings , but very occasionally, because -- only if there was something particularly coming up that I wanted to hear about. But I can't guarantee it but I'm pretty sure they discussed with him the counselling of boys with haemophilia. But I would say that all the boys, I think the boys -- I'm pretty sure that they all had someone that they could talk to, and who was willing to listen to them and I would just point out that they weren't mentally ill. They didn't need psychiatric help. They weren't -- they were perfectly sane. What 24 June 2021 3 they had was a rage inside them, a frustration that here they were, that they had suddenly been made ill and they were probably going to die in the not too distant future. And, " Why me? Why me?" And it was -- you could see it when you -- because they -- you know, they broke out quite often and they would be very rude to staff and go into town and get drunk and this sort of thing. Smoking, the younger ones . I mean , the older ones were allowed to smoke but the younger ones smoking . You know, they were rebelling. Well, young boys rebel , but this was much -- this was way over the top rebelling , because they just -- you know, " Why me? " They had this rage in side them and you could see it when you talked to them . You could see it. And this was the result of being given these -- this disease. It had a dreadful effect on them. If you're trying to say that we should have done more in terms of counselling them, I would say I don't think we could have done any more. I think the staff probably did everything they could and did as much as they could. There was actually nothing you could do about it. They were infected and they were going to die and that was it. And you just had to help them get on with life and live life to the full, and make 74 the best of life that they could. And what we did was , we tried to stop them thinking about their lives, their -- this horrible thing that was happening to them, as much as we could. We tried to -- and our way of doing it was to try to keep them busy. So after school, the staff ran all sorts of clubs and took outings and organised table tennis and billiards and -- swimming was a great one. The doctors did approve of swimming. So I think everyone on the staff, and including me, were on a rota to supervise free swims at -- you know, when they were free , and at weekends. So they were able to go and have a -- we'd very good swimming pools at both schools. And it was a question of trying to keep them busy and keep them from thinking about the horrible future that they had. That was ... And I think that the staff did their best in that respect. I don't know. I don't know. Well, you can ask some of these people over there whether they feel that they -- we could have done more for them . But we didn't think we could. I don't know. I think the staff did everything they could. They weren't mentally ill, you know. They were just in a rage for what had happened to them.
45,412	315	QUESTION: And you were head master until 1990 , when you retired. 75 So for another five years or so after it became known within the school as a whole that the pupils had been infected with HIV. During those years, did the school -- the school, the college -- try to learn lessons from what had happened to try to prevent anything like that happening again? ANSWER: Well, are you talking about infecting pupils with -- in some way?
45,413	315	QUESTION: Well , was there any aspect in which the college looked at what had happened and said, "We should do things differently " -- or , " could do things differently from now onwards"? In any respect at all? Treatment, support, parental involvement? ANSWER: Well, I'm sure we learnt a lot about how to help pupils who were -- who were ill in a way that they were going to die . I mean, we had lots of other pupils in the school who were going to die. We had about 20-odd boys -- boys again -- suffering from Duchenne Muscular Dystrophy, and they actually died a lot earlier than the haemophiliacs. Most of them died before they left the -- before they left us . Whereas most of the haemophiliacs had left the school before they died. So , I mean, it was -- these were things that 76 were happening in the school anyway. I'm sure we -- I'm sure that a lot of things were learned but I'm not sure what you're getting at here .
45,414	315	QUESTION: It was an open question, Mr Macpherson, I'm not getting at anything -- ANSWER: I think one -- you spend your life as a schoolmaster and as a headmaster and as a housemaster , or whatever it is you're doing, looking at what's going on and seeing if you can improve on it next time. And yes , I'm sure we did try to learn from everything we did, not just to do with the haemophiliacs , and make a better job of the way we ran the place. You're always trying to improve, aren't you? Well , I think we were. But I'm not sure what you're getting at, actually .
45,415	315	QUESTION: I'm really not getting at anything, Mr Macpherson, I'm just asking questions. ANSWER: Mm.
45,416	315	QUESTION: With the benefit of hindsight, do you think that the school , college, should have had greater oversight into the activities of the Haemophilia Centre? ANSWER: Well, I don't -- I don't -- you're -- I think we've probably got to wait to hear the result of this Inquiry before I can answer that, because , I mean, to my knowledge -- I mean, I always thought they were 24 June 2021 7 doing the best they could, and that they were honest . And if they didn't immediately take action when they knew that infected blood was being used, I'm very surprised, and I think that -- I think that was remiss and that was a mistake which I would say was culpable . And I think that's what you've been implying, to a certain extent here. Maybe you haven't .
45,417	315	QUESTION: -- (overspeaking) -- Mr Macpherson -- ANSWER: Maybe you haven't, maybe I picked that incorrectly, but if that was true, then that's disgraceful. But as to -- I don't think any of us in the school had really had enough -- we didn't know about it, and we didn't have any authority or reason to interfere in any way. No reason whatsoever. I mean , you can't -- doctors are -- doctors are god, let's face it, aren't they?
45,418	315	QUESTION: Because the housemaster or mistress would be perhaps the person in a position to provide pastoral care and support ? ANSWER: Yeah , I think the -- I think even -- yes , and I think parents would have -- should have been much more involved, by the sound of it, as well . I have to say, if what you say is true -- I really don't know. I find it hard to believe that's how they did it. It sounds pretty -- a pretty horrific way to do it. I can't believe that's true, actually. But these chaps, they'll be able to tell you whether it's true or not. But that's -- I just -- that would not have been -- that wouldn't have been the way we would have done it, if it had been left to the school staff to do it , I'm pretty sure. That wasn't -- that was not -- that was not good.
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45,423	320	QUESTION: Yes. I will jump, if I may, to paragraph 1.10, which records that: "The Licensing Authority [wrote] to the company on 27 November 1980 stating their proposal to vary the product licence ..." The wording is given, which I won't go through now, because it will come up again. On 30 July 1980, the company had written to the 39 Committee giving notice that they intended to avail themselves of the opportunity to appear before the Committee to ensure that their position was fully understood. So this the working through of the Medicines Act 1968. The Licensing Authority is proposing to vary, the company has an opportunity to put its cas e and this report from Dr Fowler is part of the proce ss that then follows. Paragraph 2, or section 2, "Additional information": "The Company had submitted a paper giving the background to their case and why the variation to t he licence should not be imposed. "On the day of the hearing, the Company handed in a copy of the a notarised statement from Parlier Medical Supply Company which certified that bulk unlabelled antihaemophilic factor (human) shipped t o Speywood was: "(i) manufactured and sold by Cutter Laboratories, "(ii) approved and released for general sale in the USA by the FDA (Bureau of Biologics division) "(iii) derived from human plasma collected in plasmapheresis centres licensed by and conforming t o 40 the regulations of the US Bureau of Biologics. "Preliminary discussion "The following points emerged from the preliminary discussion: "(i) that 4% of the batches supplied for testing in 1980 came from Speywood "(ii) that of 50% of the batches from US sources, there had been need to refer back to the manufacturers." We understand that to mean that in 50 per cent of the cases where batches of factor concentrates a re tested, there's a need to go back to the manufactur er to ask of them some questions, which shows the importance of having that chain going all the way back. "(iii) that Speywood were merely being asked to give information which was routinely supplied by al l manufacturers of anti-haemophilic globulin sold in the UK." Section 4, the "Hearing": "The representatives of the Company were as follows ..." Mr Williams, the spokesman and Dr Jones, from Newcastle. "The Company's representatives were welcomed by 1 the Chairman, who introduced the Committee, the secretariat, and the DHSS officials present. The representatives had no objection to the presence of any officials. "Mr Williams referred to the affidavit from Parlier Medical Supply Company which had been furnished and with the aid of slides explained that the Cutter material was subject to Cutter in-house quality control, before submission to the FDA/BOB f or clearance. The material was purchased after cleara nce and thus its integrity was in his view guaranteed. Following delivery to Parlier Medical Supply Compan y, all packaging was removed and the product shipped intact to the UK. On arrival in the UK, the (unlabelled) material was subject to quality contro l, carried out in the laboratories of Toxicol and the Oxford Haemophilia Centre. Samples were then submitted to NIBSC together with protocols and following approval, the material was repackaged as Humanate. "He considered that all Factor VIII products carried a risk of Non-A, Non-B hepatitis, but that the risk was minimised by the monitoring of donors by t he FDANSWER: "Mr Williams felt that any additional data could 42 be obtained from the FDA possibly by NIBSC, under t he US Freedom of Information Act. "He explained that his objective in appearing before the Committee was to seek an extension of th e present arrangements to enable the company to make other arrangements if possible for the purchase of Factor VIII and eventually to remove the Company's financial dependence on this imported Factor VIII. "Dr Jones then explained that he had come to the hearing as an independent consultant (unpaid) to advise the Committee that in his capacity as direct or of a Haemophilia Centre, he had satisfactorily trea ted patients with Humanate. "In reply to questions Mr Williams stated that he thought that, if necessary, donors of blood migh t be traced from Cutter's records by means of the Freedom of Information Act. "He had accepted that the batches he imported (unlabelled) were consistent with Cutter batches, because of the assurances given by Parlier Medical Supply. "Mr Williams said that he did not know of any other manufacturer who was asked to provide the information required. "Findings 43 "The Committee found that there was insufficient evidence of any firm arrangement which would enable Speywood to obtain the data specified in [paragraph] 1.9."
45,424	320	QUESTION: Ms Middleton, you provided the Inquiry with a statement dated 14 April 2021. I'd just like to ask you one or two things about your qualifications and 102 your early career. If we could have on screen, please, WITN5666001, please, Soumik. We can see from the statement that you did a BSc in biochemistry at the University of Saint Andrews between 1966 and 1969; is that right? ANSWER: Yes.
45,425	320	QUESTION: Then if we go over to the second page, please, Soum ik. The outline of your career, I'll come back to fill in some more detail on this in due course, but from 19 69 to 1976 you were at the Protein Fractionation Centr e in Edinburgh as a biochemist; is that right? ANSWER: Yes.
45,426	320	QUESTION: So was that your first job after university? ANSWER: That was my first job, yes.
45,427	320	QUESTION: 1976 to 1979, you were at the Department of Medicin e University of Glasgow, again as a biochemist? ANSWER: Yes.
45,428	320	QUESTION: Then 1979 to 1987 it says here, "Speywood Laborator ies Ltd: Chief Scientist"? ANSWER: Yes.
45,429	320	QUESTION: Is the 1987 date correct? ANSWER: I think that includes consultancy work that I did subsequently.
45,430	320	QUESTION: I understand. 1987 to 1996, another firm, Delta Biotechnology Limited? 103 ANSWER: Yes.
45,431	320	QUESTION: Working on recombinant human albumin in yeast? ANSWER: Yes.
45,432	320	QUESTION: 1986 to 2001, "Andaris Ltd: Director of Targeted Therapeutics"? ANSWER: Yes.
45,433	320	QUESTION: Then 2001 to 2016, you founded Haemostatix Ltd, as CEO and CTO; is that right? ANSWER: Yes.
45,434	320	QUESTION: You haven't, as I understand it, given evidence previously to any Inquiry about the infected blood? ANSWER: No.
45,435	320	QUESTION: But you were interviewed with respect to a US class action. Without giving away any confidences that y ou can't give away, what were the circumstances of tha t interview? ANSWER: I have very little recollection, actually. I was called to London, and interviewed by American attorneys, and I thought that is a class action on behalf of haemophiliacs in the United States. And I was interviewed twice, but nothing ever came of i t, and there were no written papers or anything.
45,436	320	QUESTION: Do you know on whose behalf the attorneys were acti ng? ANSWER: I suspect they were acting on behalf of the haemophiliacs. 104
45,437	320	QUESTION: Plaintiffs in the action? ANSWER: Yes, the plaintiffs.
45,438	320	QUESTION: Thank you. I'd like to begin, if I may, by asking you a few questions about the protein fractionation cen tre in Edinburgh, and your time there. ANSWER: Yes.
45,439	320	QUESTION: As we have seen, you joined in 1969, directly after university? ANSWER: Yes.
45,440	320	QUESTION: Who was your line manager, if such a thing -- ANSWER: Jim Smith. Dr Smith.
45,441	320	QUESTION: Which department were you in? ANSWER: Well, we were one big department, or one little department, in the bowels of the Royal Infirmary in Edinburgh, and we were just -- there were a group o f us, about 15 of us, I guess, fractionating, learnin g to fractionate blood.
45,442	320	QUESTION: Under the guidance of Dr Smith? ANSWER: Yes. Well, Dr Smith was my immediate boss. The organisation was run by Mr John Watt, who was a vet .
45,443	320	QUESTION: How -- ANSWER: And then he was, I suppose, reporting to -- it wasn 't John Cash, it was the predecessor. I'm sorry, I ca n't remember his name.
45,444	320	QUESTION: I understand. 05 ANSWER: Head of Blood Transfusion Service.
45,445	320	QUESTION: You say there were about 15 of you? ANSWER: Approximately.
45,446	320	QUESTION: What kind of gradations were there in terms of the different work that was being done, in terms of the seniority of -- ANSWER: Well, I was first employed as a technician, and was promoted to biochemist, but mostly we were technicians. They were technicians.
45,447	320	QUESTION: When you say you were promoted to biochemist from a technician, can you recall when that happened? ANSWER: After about a year, I think, about a year.
45,448	320	QUESTION: Should I understand from what you said there that y ou weren't in any policy formulating at that time? ANSWER: No, no. I was doing what I was told.
45,449	320	QUESTION: By Dr Smith? ANSWER: By Dr Smith.
45,450	320	QUESTION: Thank you. So we are clear, that's the same Dr Jim Smith -- ANSWER: Yes.
45,451	320	QUESTION: -- who later moves to BPL and with whom you -- ANSWER: Yes.
45,452	320	QUESTION: -- worked at BPL? ANSWER: Yes.
45,453	320	QUESTION: And if we could have page 1 of your witness stateme nt 106 back onscreen, please -- sorry, page 2 of your witn ess statement back onscreen. The description that you give of the different processes involved, if I could just ask you to expa nd a little and explain, in layperson's terms, insofar as is able, the different elements of your work there, the first being: "Purification of Factor IX, for human plasma ..." ANSWER: Yes.
45,454	320	QUESTION: "... using ion exchange resin." ANSWER: Yes.
45,455	320	QUESTION: Could you explain what you were doing, when you wer e doing it and what the product was? ANSWER: The purification took the supernatant from cryoprecipitate, which was cryosupernatant, and was then diluted and passed over an exchange resin in order to prepare a concentrate of factor II, IX and X. There was no Factor VII, which was in some concentrates. The issue for Factor IX is that it can be thrombogenic, in other words it can actually promot e clotting outside of the action of Factor IX, so you want it to be controlled and not produce clots when you're not expecting it. And this Factor IX was ve ry 107 clean, and didn't appear to activate clotting facto rs, as some concentrates did. So it was a very -- regarded as very safe.
45,456	320	QUESTION: Is this a forerunner of the products that became Defix? ANSWER: No, that is Defix.
45,457	320	QUESTION: It is Defix? ANSWER: Yes.
45,458	320	QUESTION: So the first bullet point there we should understan d to be working on the production of -- ANSWER: Defix, yes.
45,459	320	QUESTION: And was that the first time that it was being produced? ANSWER: Yes.
45,460	320	QUESTION: 1969 time? ANSWER: Yes, it was.
45,461	320	QUESTION: Could we have onscreen, please, Soumik, PRSE0003648 , please. This is a document that we provided you with. We have provided two sets of documents, it's in the second set. ANSWER: Yes.
45,462	320	QUESTION: And it is an article from Vox Sang, volume 24, pages 441 to 456, from 1973, entitled "A Therapeuti c Concentrate of Coagulation Factors II, IX and X fro m 108 Citrated Factor VIII-Depleted Plasma"? ANSWER: Yes.
45,463	320	QUESTION: And you're listed as the lead author there. ANSWER: Yes.
45,464	320	QUESTION: With Ida Bennett and JK Smith, presumably Dr Smith? ANSWER: Yes.
45,465	320	QUESTION: If we could look at the abstract, please, Soumik: "Abstract. A simple procedure is described for large-scale absorption on to DEAE-cellulose of coagulation factors II, IX and X from citrated, factor VIII-depleted plasma. The coagulation facto rs are eluted frontally from the exchanger in a high yield and in a form suitable for therapeutic use, without further fractionation. The lyophilised concentrate is very stable without the addition of heparin and, when redissolved to iso-osmolar soluti on ..." Forgive my repeated butchering of pronunciations as we go through! "... contains approximately 30 U/ml factors II, IX and X, 250-300 times purified from the starting plasma. The effectiveness of the concentrate in th e treatment of haemophilia B is discussed." ANSWER: Yes.
45,466	320	QUESTION: So that's the abstract of the article. Should I ta ke 09 it that this article is describing the process that you have just described to us? ANSWER: Yes.
45,467	320	QUESTION: This is the formulation of Def -- ANSWER: Yes.
45,468	320	QUESTION: To the best of your knowledge, was this article fro m 1973 the first publication of the Defix product? ANSWER: Yes.
45,469	320	QUESTION: If we just look at the introduction section, there are a couple of points to pick out from it: "Until 1967, only fresh-frozen plasma could be offered in Scotland for correcting deficiencies of coagulation factors II, VII, IX and X. Such treatm ent was frequently inadequate to maintain haemostatic levels of factor IX in patients with severe haemophilia B during major bleeding episodes or surgery." ANSWER: Yes.
45,470	320	QUESTION: "Since 1967 the Protein Fractionation Centre has ma de approximately 1,100 doses of 'PPSB' from blood collected in EDTA, by the method published by Soulier ..." What was PPSB? ANSWER: That was a full factor concentrate which contained Factor VII in addition to factor II, IX and X. 110 Now, I can't actually remember how PPSB was made, but obviously it started off in blood collect ed in EDTA, which is rather different because none of the other fractions can be collected from that blood.
45,471	320	QUESTION: Could you just explain EDTA to us? ANSWER: Ethylenediaminetetraacetic acid.
45,472	320	QUESTION: I won't try and repeat that! Going back to the article: "This product represented an important advance in the treatment of haemophilia B, and its use has been extended to a number of other deficiencies of the prothrombin complex of coagulation factors. The demand for PPSB for use, eg, in liver disease and t he reverse of anticoagulant therapy, at times threaten ed to exhaust the stocks required for emergency treatm ent of haemophilia B, and prompted us to look for new methods of recovering factor IX or prothrombin comp lex from normal citrated plasma. A large increase in t he production of PPSB was considered uneconomical of limited fresh blood resources, because cellular components and factor VIII are not readily recovere d from blood collected in EDTANSWER: It was hoped that an alternative method could be devised to improve the yield of factor IX (only about 30% in large scale production of PPSB) and end our dependence on 111 procuring batches of tricalcium phosphate with the appropriate absorbtive properties." If I just pause there for a moment, am I right in understanding that to mean that your work in try ing to create Defix was a response to the need for more product and concerns about running short of the existing product?
45,473	320	QUESTION: Going back to the article: "This report describes the absorption of factors II, IX and X from large batches of citrated Cohn supernatant ... on DEAE-cellulose, and their select ive elution in a form suitable for freeze-drying and administration to patients without further purification or stabilisation." ANSWER: Yes.
45,474	320	QUESTION: Sorry, my printed version is not -- ANSWER: It's actually cryosupernatant.
45,475	320	QUESTION: I'm not going to go through the technical detail of the article but, if we could please go to electroni c page 11, which is internal page 451, the section dealing with "Transmission of serum hepatitis". Wh at 112 is written is this: "More than 20 batches, each made from 200 to 600 donations of plasma, have been used since May 1970. In Scotland the screening of all donations of blood for Australia antigen by immunodiffusion or immunoelectroosmopheresis became routine during 197 1. Using such methods, which detect probably less than 50% of Australia antigen carriers, the incidence of antigenaemia among blood donors in Scotland has fou nd to be about 0.07%. All batches of the factor II, I X and X concentrate have been tested for Australia antigen by the methods used for donor plasma, usual ly in five-fold concentration. Australia antigen has not been found in any batch, nor has any recipient developed hepatitis or Australian antigenaemia following treatment with the concentrate alone. "Since the methods used to detect the agent causing serum hepatitis were very insensitive and since no systematic attempt has been made to assess the incidence of sub-clinical hepatitis among the recipients, it would be prudent to assume that the concentrate could be infective if made from infecti ve plasma, but it seems likely that the concentration of the infective agent is substantially reduced by the preparative procedure." 13 A couple of things to pick up from there. First of all, the batch size that is cited there, which i s 200 to 600 donations of plasma, am I right to understand that that was -- those were the batch si zes that were used in the work that you were doing at t hat time? ANSWER: Yes.
45,476	320	QUESTION: Do you know why there was such a variation between 200 and 600 donations? ANSWER: Well, I suspect that, at the time, we were -- well, I'm fairly sure we were -- we were making it and scaling up as we went along.
45,477	320	QUESTION: Scaling up to use -- ANSWER: Scaling up to use more plasma and bigger columns.
45,478	320	QUESTION: Do you know how the batch size developed in terms o f the Factor IX product produced at PFC, during the remainder of your time there -- to 1976? ANSWER: Err ... I'm actually not sure what size it went up to.
45,479	320	QUESTION: Do you recall what discussions were taking place within PFC about batch size around this time? ANSWER: No.
45,480	320	QUESTION: The article here clearly demonstrates an awareness of the risk of what is described as Australia antigen -- ANSWER: Yeah.
45,481	320	QUESTION: -- serum hepatitis, at the time. 114 ANSWER: Yeah.
45,482	320	QUESTION: Do you know whether there was discussion, recogniti on, of whether or not that risk increased with a larger batch size? ANSWER: No, I don't know whether there was. But it's likel y, isn't it, that it would have been?
45,483	320	QUESTION: Do you think you would have been involved in those discussions? ANSWER: I was only a lowly technician at the time. I wasn' t involved in those discussions.
45,484	320	QUESTION: Those would have been matters for whom? ANSWER: Er ... probably Jim Smith, um ... and/or the direct or of the Blood Transfusion Service, whoever that was. I don't think it was John Cash. It was --
45,485	320	QUESTION: The predecessor -- ANSWER: The predecessor.
45,486	320	QUESTION: Do you remember what information you were given, wh at training you were given, about the risk of hepatiti s from such products at this time? ANSWER: We were -- yes. We were aware of hepatitis as a potential problem but, I have to say, I don't thi nk we took a great deal of precautions for it, at the time. We weren't that aware of it. I suspect Scottish plasma was thought to be a fairly clean plasma, so I can't really answer that question, but we 115 did actually have a technician in the Blood Transfusion Service who did have an accident with a positively -- a positive hepatitis B donation, an d she subsequently died. So there was definitely an awareness.
45,487	320	QUESTION: Are you able to say approximately when that occurre d? ANSWER: Well, it was probably in the first couple of years, I think, that I was there. Maybe a bit longer.
45,488	320	QUESTION: Early 1970s? ANSWER: Yeah, early '70s.
45,489	320	QUESTION: Are you able to -- this is a very difficult questio n thinking back all these years -- are you able to recall what kind of journals and learning that you would have been keeping up to date with at that tim e? ANSWER: Well, obviously Vox Sanguinis was one of them, Bloo d, Thrombosis and Haemostasis, those are the ones I so rt of remember. Vox Sanguinis was very much the one t o do with fractionation. Obviously Blood. No virolo gy journal specifically, but hepatitis would have been discussed in some of those -- in those other ones t hat I've mentioned.
45,490	320	QUESTION: Were they made available to you at the PFC or did y ou have to find them off your own back? ANSWER: No, they were available.
45,491	320	QUESTION: I'd like to just again pick up a couple of more thi ngs 116 from that section. There's a reference to the test ing that became routine during 1971. Should we underst and that, before that, there was no routine testing for hepatitis? ANSWER: Possibly not. The assays, as they say, were rather insensitive at the time.
45,492	320	QUESTION: That's what I was going to ask next. ANSWER: Yeah.
45,493	320	QUESTION: There's a figure of probably less than 50 per cent given. ANSWER: Yes.
45,494	320	QUESTION: An awareness, then, that testing wasn't going to ca tch everybody? ANSWER: Yes.
45,495	320	QUESTION: Apologies. If we could highlight the middle paragraph, "Transmission of Serum Hepatitis". Than k you. ANSWER: Yes.
45,496	320	QUESTION: Sir, we can see that figure there given of 0.07 per cent -- ANSWER: Yeah. 17
45,497	320	QUESTION: -- for instance, among blood donors in Scotland. H ow much faith should we put in that figure, given the limited sensitivity of testing at the time? ANSWER: I can't answer that question. I won't answer that question. Something just in, sort of, qualification of all of this. There was insufficient Factor IX availabl e, and very much the emphasis with everything I did at PFC, and subsequently, really, was with the aim of getting a product out there to treat haemophilia because there were problems, obviously, for haemophiliacs who didn't get treatment. So bleedin g was regarded as the first problem.
45,498	320	QUESTION: The question of the risk and benefit of those products, was that a question for you to consider a s biochemist and previously a technician, or is that for others? ANSWER: That was more for others, I think. But it was definitely very important.
45,499	320	QUESTION: The conclusion of that sentence says: "... it would be prudent to assume that the concentrate could be infective if made from infecti ve plasma, but it seems likely that the concentration of the infective agent is substantially reduced by the preparative procedure." 118 ANSWER: Yes.

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QUESTION: And were any steps taken by the school to try to mitigate the risk of any future outbreaks? ANSWER: When you say by the school, do you mean by my part of the school?

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QUESTION: Yes. 68 ANSWER: Well, no. It was not our -- there was nothing -- I wouldn't have seen that as being something that I had really anything to do with.

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QUESTION: So your expectation would be if there were further steps to be taken it would be the haemophilia doctors ? ANSWER: No, tha t had to be the haemophilia doctors, yes . Yes.

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QUESTION: And do you know whether -- ANSWER: We didn't have a haemophilia -- at that time we didn't have a Haemophilia Centre in the school, of course.

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QUESTION: And do you know whether there was any report of the outbreak made by the school or the doctors to an external body ? ANSWER: No, I've no idea. Why , are you supposed to report these things?

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QUESTION: It's just an open question , Mr Macpherson . The questions I asked about research were about research in relation to the boys with haemophilia. Was research undertaken , as far as you know , in relation to any of the other pupils at the school, so the non-haemophiliac pupils? ANSWER: When you say " research " , it depends what you mean by research. I mean , people sort of investigating numbers of this and numbers of that, and parents and so on. I remember our -- a deputy head who investigated or researched into the situation with 24 June 2021 9 parents at our -- of children at our school , and found that only 40 per cent of the children at the school were from what you would call a " normal " family, two-parent family home. Which is a bit of a surprise. Well, it was a surprise to me that it was -- that 60 per cent were from not a completely normal -- and quite a number had no parents at all, or their parents had rejected them. And she found that quite a lot were single - parent families, and that the child was actually the cause of the break-up of the marriage. And the child usually knew that, which was another psychological factor. But I wouldn't -- I couldn't tell you how many of these were haemophiliacs. So that sort of research went on . Is that what you're talking about?

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QUESTION: Do you recall whether there was any medical or clinical research in relation to any of the other cohorts of pupils, the non-haemophiliac pupils? ANSWER: I know that Pat Tomlinson talked about it a bit but I don't think she actually did anything particularly. Not at the school. I mean , there were -- certainly a lot of our pupils went to Great Ormond Street, and I know Great Ormond Street were doing research into a number of things which quite a number of our pupils 70 were absolutely definitely involved in there. There's no question about it. I remember hearing about them , things like bone marrow transfers that would cure this and cure that, and they never did , and operations that were meant to make pupils walk again . And I remember a boy coming in to me and saying, "Next time you see me, I'll be walking because I'm going to have this such-and-such an operation ", and he actually was walking at that time on crutches . And you know what? He came back in a wheelchair for the rest of his life . And we used to look at these and we used to say , " Well , oh dear , is this in the best interests? " But these weren't haemophiliacs. So I'm going off the subject now. So yes , there was quite a lot of research going on to do with our pupils. I don't think there was a lot -- I mean , there wasn't really very much at our school . There wasn't time. They were busy. There were lessons that were being taught. There were ... so no, I don't think there was really very much -- not that we were involved in anyway . Does that answer your question? I'm not absolutely sure what your question was .

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QUESTION: If I can then just go back to the question of Dr Rainsford. 71 ANSWER: Right.

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QUESTION: When you joined the school in 1974 , and in the following years during the course of the 1970s, what was your understanding of what Dr Rainsford's role was , in connection with the college in the pupils there? ANSWER: Do you mean detailed? Are you asking for a detailed answer to that --

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QUESTION: No , I'm asking -- ANSWER: I mean, my understanding was that he was doing some research of some -- and I thought worthwhile -- I was given the impression it was worthwhile -- to do with giving transfusions of Factor VIII , and prophylactic transfusions , and all that sort of thing. But, I mean, that's about as far as it went with me.

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QUESTION: And was it your understanding that -- or what was your understanding of his involvement with the actual treatment of the boys? Was that part of his job as far as you understood it, or not? ANSWER: I think he was -- I think he was involved with the treatment. Yes . Yes . As far as I know, he was. I couldn't guarantee that . I mean , I really had no involvement with the medical side except where I heard about it or talked about it, or whatever.

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QUESTION: I'd asked you before the break about counselling. Was 72 there anything further about counselling that you can assist us with? ANSWER: Yeah , well, I think, yes -- yes , I did want to add a bit about that. You were saying that Mr Scott was saying that he thought we could have done more. And my answer to that would be: you can always do more. You can always improve on things. But we had -- the housemasters did meet with this -- our psychiatrist. He visited about once a week and I think most of these times the housemasters did have a meeting with him, for -- to discuss whatever they wanted and I'm sure that this would be one of the topics that they would discuss with him. I went -- I occasionally went to these meetings , but very occasionally, because -- only if there was something particularly coming up that I wanted to hear about. But I can't guarantee it but I'm pretty sure they discussed with him the counselling of boys with haemophilia. But I would say that all the boys, I think the boys -- I'm pretty sure that they all had someone that they could talk to, and who was willing to listen to them and I would just point out that they weren't mentally ill. They didn't need psychiatric help. They weren't -- they were perfectly sane. What 24 June 2021 3 they had was a rage inside them, a frustration that here they were, that they had suddenly been made ill and they were probably going to die in the not too distant future. And, " Why me? Why me?" And it was -- you could see it when you -- because they -- you know, they broke out quite often and they would be very rude to staff and go into town and get drunk and this sort of thing. Smoking, the younger ones . I mean , the older ones were allowed to smoke but the younger ones smoking . You know, they were rebelling. Well, young boys rebel , but this was much -- this was way over the top rebelling , because they just -- you know, " Why me? " They had this rage in side them and you could see it when you talked to them . You could see it. And this was the result of being given these -- this disease. It had a dreadful effect on them. If you're trying to say that we should have done more in terms of counselling them, I would say I don't think we could have done any more. I think the staff probably did everything they could and did as much as they could. There was actually nothing you could do about it. They were infected and they were going to die and that was it. And you just had to help them get on with life and live life to the full, and make 74 the best of life that they could. And what we did was , we tried to stop them thinking about their lives, their -- this horrible thing that was happening to them, as much as we could. We tried to -- and our way of doing it was to try to keep them busy. So after school, the staff ran all sorts of clubs and took outings and organised table tennis and billiards and -- swimming was a great one. The doctors did approve of swimming. So I think everyone on the staff, and including me, were on a rota to supervise free swims at -- you know, when they were free , and at weekends. So they were able to go and have a -- we'd very good swimming pools at both schools. And it was a question of trying to keep them busy and keep them from thinking about the horrible future that they had. That was ... And I think that the staff did their best in that respect. I don't know. I don't know. Well, you can ask some of these people over there whether they feel that they -- we could have done more for them . But we didn't think we could. I don't know. I think the staff did everything they could. They weren't mentally ill, you know. They were just in a rage for what had happened to them.

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QUESTION: And you were head master until 1990 , when you retired. 75 So for another five years or so after it became known within the school as a whole that the pupils had been infected with HIV. During those years, did the school -- the school, the college -- try to learn lessons from what had happened to try to prevent anything like that happening again? ANSWER: Well, are you talking about infecting pupils with -- in some way?

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QUESTION: Well , was there any aspect in which the college looked at what had happened and said, "We should do things differently " -- or , " could do things differently from now onwards"? In any respect at all? Treatment, support, parental involvement? ANSWER: Well, I'm sure we learnt a lot about how to help pupils who were -- who were ill in a way that they were going to die . I mean, we had lots of other pupils in the school who were going to die. We had about 20-odd boys -- boys again -- suffering from Duchenne Muscular Dystrophy, and they actually died a lot earlier than the haemophiliacs. Most of them died before they left the -- before they left us . Whereas most of the haemophiliacs had left the school before they died. So , I mean, it was -- these were things that 76 were happening in the school anyway. I'm sure we -- I'm sure that a lot of things were learned but I'm not sure what you're getting at here .

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QUESTION: It was an open question, Mr Macpherson, I'm not getting at anything -- ANSWER: I think one -- you spend your life as a schoolmaster and as a headmaster and as a housemaster , or whatever it is you're doing, looking at what's going on and seeing if you can improve on it next time. And yes , I'm sure we did try to learn from everything we did, not just to do with the haemophiliacs , and make a better job of the way we ran the place. You're always trying to improve, aren't you? Well , I think we were. But I'm not sure what you're getting at, actually .

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QUESTION: I'm really not getting at anything, Mr Macpherson, I'm just asking questions. ANSWER: Mm.

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QUESTION: With the benefit of hindsight, do you think that the school , college, should have had greater oversight into the activities of the Haemophilia Centre? ANSWER: Well, I don't -- I don't -- you're -- I think we've probably got to wait to hear the result of this Inquiry before I can answer that, because , I mean, to my knowledge -- I mean, I always thought they were 24 June 2021 7 doing the best they could, and that they were honest . And if they didn't immediately take action when they knew that infected blood was being used, I'm very surprised, and I think that -- I think that was remiss and that was a mistake which I would say was culpable . And I think that's what you've been implying, to a certain extent here. Maybe you haven't .

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QUESTION: -- (overspeaking) -- Mr Macpherson -- ANSWER: Maybe you haven't, maybe I picked that incorrectly, but if that was true, then that's disgraceful. But as to -- I don't think any of us in the school had really had enough -- we didn't know about it, and we didn't have any authority or reason to interfere in any way. No reason whatsoever. I mean , you can't -- doctors are -- doctors are god, let's face it, aren't they?

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QUESTION: Because the housemaster or mistress would be perhaps the person in a position to provide pastoral care and support ? ANSWER: Yeah , I think the -- I think even -- yes , and I think parents would have -- should have been much more involved, by the sound of it, as well . I have to say, if what you say is true -- I really don't know. I find it hard to believe that's how they did it. It sounds pretty -- a pretty horrific way to do it. I can't believe that's true, actually. But these chaps, they'll be able to tell you whether it's true or not. But that's -- I just -- that would not have been -- that wouldn't have been the way we would have done it, if it had been left to the school staff to do it , I'm pretty sure. That wasn't -- that was not -- that was not good.

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QUESTION: Yes. I will jump, if I may, to paragraph 1.10, which records that: "The Licensing Authority [wrote] to the company on 27 November 1980 stating their proposal to vary the product licence ..." The wording is given, which I won't go through now, because it will come up again. On 30 July 1980, the company had written to the 39 Committee giving notice that they intended to avail themselves of the opportunity to appear before the Committee to ensure that their position was fully understood. So this the working through of the Medicines Act 1968. The Licensing Authority is proposing to vary, the company has an opportunity to put its cas e and this report from Dr Fowler is part of the proce ss that then follows. Paragraph 2, or section 2, "Additional information": "The Company had submitted a paper giving the background to their case and why the variation to t he licence should not be imposed. "On the day of the hearing, the Company handed in a copy of the a notarised statement from Parlier Medical Supply Company which certified that bulk unlabelled antihaemophilic factor (human) shipped t o Speywood was: "(i) manufactured and sold by Cutter Laboratories, "(ii) approved and released for general sale in the USA by the FDA (Bureau of Biologics division) "(iii) derived from human plasma collected in plasmapheresis centres licensed by and conforming t o 40 the regulations of the US Bureau of Biologics. "Preliminary discussion "The following points emerged from the preliminary discussion: "(i) that 4% of the batches supplied for testing in 1980 came from Speywood "(ii) that of 50% of the batches from US sources, there had been need to refer back to the manufacturers." We understand that to mean that in 50 per cent of the cases where batches of factor concentrates a re tested, there's a need to go back to the manufactur er to ask of them some questions, which shows the importance of having that chain going all the way back. "(iii) that Speywood were merely being asked to give information which was routinely supplied by al l manufacturers of anti-haemophilic globulin sold in the UK." Section 4, the "Hearing": "The representatives of the Company were as follows ..." Mr Williams, the spokesman and Dr Jones, from Newcastle. "The Company's representatives were welcomed by 1 the Chairman, who introduced the Committee, the secretariat, and the DHSS officials present. The representatives had no objection to the presence of any officials. "Mr Williams referred to the affidavit from Parlier Medical Supply Company which had been furnished and with the aid of slides explained that the Cutter material was subject to Cutter in-house quality control, before submission to the FDA/BOB f or clearance. The material was purchased after cleara nce and thus its integrity was in his view guaranteed. Following delivery to Parlier Medical Supply Compan y, all packaging was removed and the product shipped intact to the UK. On arrival in the UK, the (unlabelled) material was subject to quality contro l, carried out in the laboratories of Toxicol and the Oxford Haemophilia Centre. Samples were then submitted to NIBSC together with protocols and following approval, the material was repackaged as Humanate. "He considered that all Factor VIII products carried a risk of Non-A, Non-B hepatitis, but that the risk was minimised by the monitoring of donors by t he FDANSWER: "Mr Williams felt that any additional data could 42 be obtained from the FDA possibly by NIBSC, under t he US Freedom of Information Act. "He explained that his objective in appearing before the Committee was to seek an extension of th e present arrangements to enable the company to make other arrangements if possible for the purchase of Factor VIII and eventually to remove the Company's financial dependence on this imported Factor VIII. "Dr Jones then explained that he had come to the hearing as an independent consultant (unpaid) to advise the Committee that in his capacity as direct or of a Haemophilia Centre, he had satisfactorily trea ted patients with Humanate. "In reply to questions Mr Williams stated that he thought that, if necessary, donors of blood migh t be traced from Cutter's records by means of the Freedom of Information Act. "He had accepted that the batches he imported (unlabelled) were consistent with Cutter batches, because of the assurances given by Parlier Medical Supply. "Mr Williams said that he did not know of any other manufacturer who was asked to provide the information required. "Findings 43 "The Committee found that there was insufficient evidence of any firm arrangement which would enable Speywood to obtain the data specified in [paragraph] 1.9."

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QUESTION: Ms Middleton, you provided the Inquiry with a statement dated 14 April 2021. I'd just like to ask you one or two things about your qualifications and 102 your early career. If we could have on screen, please, WITN5666001, please, Soumik. We can see from the statement that you did a BSc in biochemistry at the University of Saint Andrews between 1966 and 1969; is that right? ANSWER: Yes.

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QUESTION: Then if we go over to the second page, please, Soum ik. The outline of your career, I'll come back to fill in some more detail on this in due course, but from 19 69 to 1976 you were at the Protein Fractionation Centr e in Edinburgh as a biochemist; is that right? ANSWER: Yes.

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QUESTION: So was that your first job after university? ANSWER: That was my first job, yes.

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QUESTION: 1976 to 1979, you were at the Department of Medicin e University of Glasgow, again as a biochemist? ANSWER: Yes.

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QUESTION: Then 1979 to 1987 it says here, "Speywood Laborator ies Ltd: Chief Scientist"? ANSWER: Yes.

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QUESTION: Is the 1987 date correct? ANSWER: I think that includes consultancy work that I did subsequently.

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QUESTION: I understand. 1987 to 1996, another firm, Delta Biotechnology Limited? 103 ANSWER: Yes.

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QUESTION: Working on recombinant human albumin in yeast? ANSWER: Yes.

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QUESTION: 1986 to 2001, "Andaris Ltd: Director of Targeted Therapeutics"? ANSWER: Yes.

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QUESTION: Then 2001 to 2016, you founded Haemostatix Ltd, as CEO and CTO; is that right? ANSWER: Yes.

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QUESTION: You haven't, as I understand it, given evidence previously to any Inquiry about the infected blood? ANSWER: No.

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QUESTION: But you were interviewed with respect to a US class action. Without giving away any confidences that y ou can't give away, what were the circumstances of tha t interview? ANSWER: I have very little recollection, actually. I was called to London, and interviewed by American attorneys, and I thought that is a class action on behalf of haemophiliacs in the United States. And I was interviewed twice, but nothing ever came of i t, and there were no written papers or anything.

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QUESTION: Do you know on whose behalf the attorneys were acti ng? ANSWER: I suspect they were acting on behalf of the haemophiliacs. 104

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QUESTION: Plaintiffs in the action? ANSWER: Yes, the plaintiffs.

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QUESTION: Thank you. I'd like to begin, if I may, by asking you a few questions about the protein fractionation cen tre in Edinburgh, and your time there. ANSWER: Yes.

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QUESTION: As we have seen, you joined in 1969, directly after university? ANSWER: Yes.

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QUESTION: Who was your line manager, if such a thing -- ANSWER: Jim Smith. Dr Smith.

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QUESTION: Which department were you in? ANSWER: Well, we were one big department, or one little department, in the bowels of the Royal Infirmary in Edinburgh, and we were just -- there were a group o f us, about 15 of us, I guess, fractionating, learnin g to fractionate blood.

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QUESTION: Under the guidance of Dr Smith? ANSWER: Yes. Well, Dr Smith was my immediate boss. The organisation was run by Mr John Watt, who was a vet .

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QUESTION: How -- ANSWER: And then he was, I suppose, reporting to -- it wasn 't John Cash, it was the predecessor. I'm sorry, I ca n't remember his name.

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QUESTION: I understand. 05 ANSWER: Head of Blood Transfusion Service.

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QUESTION: You say there were about 15 of you? ANSWER: Approximately.

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QUESTION: What kind of gradations were there in terms of the different work that was being done, in terms of the seniority of -- ANSWER: Well, I was first employed as a technician, and was promoted to biochemist, but mostly we were technicians. They were technicians.

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QUESTION: When you say you were promoted to biochemist from a technician, can you recall when that happened? ANSWER: After about a year, I think, about a year.

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QUESTION: Should I understand from what you said there that y ou weren't in any policy formulating at that time? ANSWER: No, no. I was doing what I was told.

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QUESTION: By Dr Smith? ANSWER: By Dr Smith.

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QUESTION: Thank you. So we are clear, that's the same Dr Jim Smith -- ANSWER: Yes.

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QUESTION: -- who later moves to BPL and with whom you -- ANSWER: Yes.

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QUESTION: -- worked at BPL? ANSWER: Yes.

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QUESTION: And if we could have page 1 of your witness stateme nt 106 back onscreen, please -- sorry, page 2 of your witn ess statement back onscreen. The description that you give of the different processes involved, if I could just ask you to expa nd a little and explain, in layperson's terms, insofar as is able, the different elements of your work there, the first being: "Purification of Factor IX, for human plasma ..." ANSWER: Yes.

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QUESTION: "... using ion exchange resin." ANSWER: Yes.

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QUESTION: Could you explain what you were doing, when you wer e doing it and what the product was? ANSWER: The purification took the supernatant from cryoprecipitate, which was cryosupernatant, and was then diluted and passed over an exchange resin in order to prepare a concentrate of factor II, IX and X. There was no Factor VII, which was in some concentrates. The issue for Factor IX is that it can be thrombogenic, in other words it can actually promot e clotting outside of the action of Factor IX, so you want it to be controlled and not produce clots when you're not expecting it. And this Factor IX was ve ry 107 clean, and didn't appear to activate clotting facto rs, as some concentrates did. So it was a very -- regarded as very safe.

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QUESTION: Is this a forerunner of the products that became Defix? ANSWER: No, that is Defix.

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QUESTION: It is Defix? ANSWER: Yes.

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QUESTION: So the first bullet point there we should understan d to be working on the production of -- ANSWER: Defix, yes.

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QUESTION: And was that the first time that it was being produced? ANSWER: Yes.

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QUESTION: 1969 time? ANSWER: Yes, it was.

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QUESTION: Could we have onscreen, please, Soumik, PRSE0003648 , please. This is a document that we provided you with. We have provided two sets of documents, it's in the second set. ANSWER: Yes.

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QUESTION: And it is an article from Vox Sang, volume 24, pages 441 to 456, from 1973, entitled "A Therapeuti c Concentrate of Coagulation Factors II, IX and X fro m 108 Citrated Factor VIII-Depleted Plasma"? ANSWER: Yes.

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QUESTION: And you're listed as the lead author there. ANSWER: Yes.

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QUESTION: With Ida Bennett and JK Smith, presumably Dr Smith? ANSWER: Yes.

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QUESTION: If we could look at the abstract, please, Soumik: "Abstract. A simple procedure is described for large-scale absorption on to DEAE-cellulose of coagulation factors II, IX and X from citrated, factor VIII-depleted plasma. The coagulation facto rs are eluted frontally from the exchanger in a high yield and in a form suitable for therapeutic use, without further fractionation. The lyophilised concentrate is very stable without the addition of heparin and, when redissolved to iso-osmolar soluti on ..." Forgive my repeated butchering of pronunciations as we go through! "... contains approximately 30 U/ml factors II, IX and X, 250-300 times purified from the starting plasma. The effectiveness of the concentrate in th e treatment of haemophilia B is discussed." ANSWER: Yes.

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QUESTION: So that's the abstract of the article. Should I ta ke 09 it that this article is describing the process that you have just described to us? ANSWER: Yes.

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QUESTION: This is the formulation of Def -- ANSWER: Yes.

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QUESTION: To the best of your knowledge, was this article fro m 1973 the first publication of the Defix product? ANSWER: Yes.

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QUESTION: If we just look at the introduction section, there are a couple of points to pick out from it: "Until 1967, only fresh-frozen plasma could be offered in Scotland for correcting deficiencies of coagulation factors II, VII, IX and X. Such treatm ent was frequently inadequate to maintain haemostatic levels of factor IX in patients with severe haemophilia B during major bleeding episodes or surgery." ANSWER: Yes.

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QUESTION: "Since 1967 the Protein Fractionation Centre has ma de approximately 1,100 doses of 'PPSB' from blood collected in EDTA, by the method published by Soulier ..." What was PPSB? ANSWER: That was a full factor concentrate which contained Factor VII in addition to factor II, IX and X. 110 Now, I can't actually remember how PPSB was made, but obviously it started off in blood collect ed in EDTA, which is rather different because none of the other fractions can be collected from that blood.

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QUESTION: Could you just explain EDTA to us? ANSWER: Ethylenediaminetetraacetic acid.

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QUESTION: I won't try and repeat that! Going back to the article: "This product represented an important advance in the treatment of haemophilia B, and its use has been extended to a number of other deficiencies of the prothrombin complex of coagulation factors. The demand for PPSB for use, eg, in liver disease and t he reverse of anticoagulant therapy, at times threaten ed to exhaust the stocks required for emergency treatm ent of haemophilia B, and prompted us to look for new methods of recovering factor IX or prothrombin comp lex from normal citrated plasma. A large increase in t he production of PPSB was considered uneconomical of limited fresh blood resources, because cellular components and factor VIII are not readily recovere d from blood collected in EDTANSWER: It was hoped that an alternative method could be devised to improve the yield of factor IX (only about 30% in large scale production of PPSB) and end our dependence on 111 procuring batches of tricalcium phosphate with the appropriate absorbtive properties." If I just pause there for a moment, am I right in understanding that to mean that your work in try ing to create Defix was a response to the need for more product and concerns about running short of the existing product?

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QUESTION: Going back to the article: "This report describes the absorption of factors II, IX and X from large batches of citrated Cohn supernatant ... on DEAE-cellulose, and their select ive elution in a form suitable for freeze-drying and administration to patients without further purification or stabilisation." ANSWER: Yes.

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QUESTION: Sorry, my printed version is not -- ANSWER: It's actually cryosupernatant.

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QUESTION: I'm not going to go through the technical detail of the article but, if we could please go to electroni c page 11, which is internal page 451, the section dealing with "Transmission of serum hepatitis". Wh at 112 is written is this: "More than 20 batches, each made from 200 to 600 donations of plasma, have been used since May 1970. In Scotland the screening of all donations of blood for Australia antigen by immunodiffusion or immunoelectroosmopheresis became routine during 197 1. Using such methods, which detect probably less than 50% of Australia antigen carriers, the incidence of antigenaemia among blood donors in Scotland has fou nd to be about 0.07%. All batches of the factor II, I X and X concentrate have been tested for Australia antigen by the methods used for donor plasma, usual ly in five-fold concentration. Australia antigen has not been found in any batch, nor has any recipient developed hepatitis or Australian antigenaemia following treatment with the concentrate alone. "Since the methods used to detect the agent causing serum hepatitis were very insensitive and since no systematic attempt has been made to assess the incidence of sub-clinical hepatitis among the recipients, it would be prudent to assume that the concentrate could be infective if made from infecti ve plasma, but it seems likely that the concentration of the infective agent is substantially reduced by the preparative procedure." 13 A couple of things to pick up from there. First of all, the batch size that is cited there, which i s 200 to 600 donations of plasma, am I right to understand that that was -- those were the batch si zes that were used in the work that you were doing at t hat time? ANSWER: Yes.

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QUESTION: Do you know why there was such a variation between 200 and 600 donations? ANSWER: Well, I suspect that, at the time, we were -- well, I'm fairly sure we were -- we were making it and scaling up as we went along.

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QUESTION: Scaling up to use -- ANSWER: Scaling up to use more plasma and bigger columns.

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QUESTION: Do you know how the batch size developed in terms o f the Factor IX product produced at PFC, during the remainder of your time there -- to 1976? ANSWER: Err ... I'm actually not sure what size it went up to.

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QUESTION: Do you recall what discussions were taking place within PFC about batch size around this time? ANSWER: No.

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QUESTION: The article here clearly demonstrates an awareness of the risk of what is described as Australia antigen -- ANSWER: Yeah.

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QUESTION: -- serum hepatitis, at the time. 114 ANSWER: Yeah.

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QUESTION: Do you know whether there was discussion, recogniti on, of whether or not that risk increased with a larger batch size? ANSWER: No, I don't know whether there was. But it's likel y, isn't it, that it would have been?

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QUESTION: Do you think you would have been involved in those discussions? ANSWER: I was only a lowly technician at the time. I wasn' t involved in those discussions.

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QUESTION: Those would have been matters for whom? ANSWER: Er ... probably Jim Smith, um ... and/or the direct or of the Blood Transfusion Service, whoever that was. I don't think it was John Cash. It was --

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QUESTION: The predecessor -- ANSWER: The predecessor.

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QUESTION: Do you remember what information you were given, wh at training you were given, about the risk of hepatiti s from such products at this time? ANSWER: We were -- yes. We were aware of hepatitis as a potential problem but, I have to say, I don't thi nk we took a great deal of precautions for it, at the time. We weren't that aware of it. I suspect Scottish plasma was thought to be a fairly clean plasma, so I can't really answer that question, but we 115 did actually have a technician in the Blood Transfusion Service who did have an accident with a positively -- a positive hepatitis B donation, an d she subsequently died. So there was definitely an awareness.

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QUESTION: Are you able to say approximately when that occurre d? ANSWER: Well, it was probably in the first couple of years, I think, that I was there. Maybe a bit longer.

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QUESTION: Early 1970s? ANSWER: Yeah, early '70s.

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QUESTION: Are you able to -- this is a very difficult questio n thinking back all these years -- are you able to recall what kind of journals and learning that you would have been keeping up to date with at that tim e? ANSWER: Well, obviously Vox Sanguinis was one of them, Bloo d, Thrombosis and Haemostasis, those are the ones I so rt of remember. Vox Sanguinis was very much the one t o do with fractionation. Obviously Blood. No virolo gy journal specifically, but hepatitis would have been discussed in some of those -- in those other ones t hat I've mentioned.

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QUESTION: Were they made available to you at the PFC or did y ou have to find them off your own back? ANSWER: No, they were available.

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QUESTION: I'd like to just again pick up a couple of more thi ngs 116 from that section. There's a reference to the test ing that became routine during 1971. Should we underst and that, before that, there was no routine testing for hepatitis? ANSWER: Possibly not. The assays, as they say, were rather insensitive at the time.

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QUESTION: That's what I was going to ask next. ANSWER: Yeah.

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QUESTION: There's a figure of probably less than 50 per cent given. ANSWER: Yes.

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QUESTION: An awareness, then, that testing wasn't going to ca tch everybody? ANSWER: Yes.

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QUESTION: Apologies. If we could highlight the middle paragraph, "Transmission of Serum Hepatitis". Than k you. ANSWER: Yes.

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QUESTION: Sir, we can see that figure there given of 0.07 per cent -- ANSWER: Yeah. 17

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QUESTION: -- for instance, among blood donors in Scotland. H ow much faith should we put in that figure, given the limited sensitivity of testing at the time? ANSWER: I can't answer that question. I won't answer that question. Something just in, sort of, qualification of all of this. There was insufficient Factor IX availabl e, and very much the emphasis with everything I did at PFC, and subsequently, really, was with the aim of getting a product out there to treat haemophilia because there were problems, obviously, for haemophiliacs who didn't get treatment. So bleedin g was regarded as the first problem.

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QUESTION: The question of the risk and benefit of those products, was that a question for you to consider a s biochemist and previously a technician, or is that for others? ANSWER: That was more for others, I think. But it was definitely very important.

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QUESTION: The conclusion of that sentence says: "... it would be prudent to assume that the concentrate could be infective if made from infecti ve plasma, but it seems likely that the concentration of the infective agent is substantially reduced by the preparative procedure." 118 ANSWER: Yes.