England and Wales High Court (Family Division) Decisions

IN THE HIGH COURT OF JUSTICE
FAMILY DIVISION

		Royal Courts of Justice Strand, London, WC2A 2LL
		11th December 2002

Dame Elizabeth Butler-Sloss, P.:

1. Two young people, a boy of 18, born on the 1^st June 1984, whom I shall call JS, and a girl of 16, born on the 2^nd October 1986, whom I shall call JA, suffer from probable variant Creutzfeldt-Jakob disease (vCJD). In each case their parents seek declaratory relief that each lacks capacity to make a decision about future treatment proposed for them and that it is lawful as being in their best interests for them to receive it. The proposed treatment is new and so far untested on human beings. Although JS and JA come from separate and unrelated families, each has been struck down by this appalling and fatal disease and they are at a broadly similar stage in the disease and the proposed treatment would be identical. The two families have brought the proceedings jointly with the same legal team and their cases have been listed and heard together. Mr Irwin QC and Mr Glasson represent the two families. Both JS and JA are represented by Mr Jackson QC for the Official Solicitor as their guardian. The Hospital Trust which would, in the event that I granted the declarations as sought, be likely to be asked to provide the facilities for the surgery and other treatment, has been joined as a party. It appeared on the second day by Mr Kennedy. The solicitors to the Hospital Trust wrote previously to the Official Solicitor and to me expressing concerns about the treatment being carried out at the Trust Hospital. It has also indicated that a declaration by this court might not be decisive since a decision whether the operation should be performed in a hospital within the Trust would also depend on two Hospital Committees responsible for the necessary procedures to be carried out in that event. I shall return to this question at the end of my judgment.

Variant Creuzfeldt-Jakob disease

2. Variant CJD is one of a group of rare and fatal neurodegenerative disorders which also includes sporadic CJD, Kuru, inherited and iatrogenic prion disease and fatal familial insomnia in humans, and scrapie, bovine spongiform encephalopathy (BSE) and chronic wasting disease in animals. CJD has been recognised as a disease since 1920. There was some knowledge in the nineteenth century of the transmission of scrapie to humans.
3. Variant CJD is recognised as a new disease which was first identified in March 1996, and a small number of cases of vCJD were then identified from the previous year. There have been129 recorded cases in the UK and a small number in other countries. The agent that causes BSE appears to be the same agent as that which causes vCJD. The infectious agent enters the body by the oral route to the stomach and reproduces itself in peripheral parts of the body and in the spinal cord from where it reaches the brain. Over a period which may take from 4 years to 40 years, abnormal prion proteins (PrPsc) become deposited in the brain where they multiply. A point comes when the accumulation of the PrPsc becomes apparent and clinical signs of neurological damage begin to manifest. It is at this stage that the incubation period is over and the disease can be diagnosed. Post mortem examination of the brain of those who have suffered from vCJD has revealed a range of abnormalities and a loss of neurones causing increasing neurological deficits. There are gaps in the present knowledge of the mechanism of the disease and in the precise relationship between the abnormal proteins, the loss of nerve cells and neurological dysfunction.

The patients

4. The first symptoms of JS's illness appear to have developed in September 2001 when he was 17. The first symptoms of JA's illness appear to have developed in December 1999 when she was 13. In each case the children have changed from normal, energetic teenagers into helpless invalids lying in bed and with a severely limited enjoyment of life. Both JS and JA are cared for in their respective homes and the standard of their care by their families and their dedication is extraordinarily high. Both families are also very well informed about the disease and the proposed treatment and its risks and possible benefits. Both families are strong advocates in the cause of and very committed to persuading the court that it is in the best interests of JS and JA for them to be given this treatment.

The evidence of the parents

The family of JS

5. Mr S gave evidence that before his illness JS was a second year A level student intending to go on to University and a talented and dedicated sportsman. Mr S set out the manifestations of the disease and the continuing deterioration of JS' health to the present day. Although he is now helpless and confined to bed, he can recognise his family and can communicate with them in various ways such as by an occasional word, facial expression or by grasping a hand. There are fluctuations in his responses from day to day. On a good day he is very affectionate and kisses his family. His passion is music and he can make clear whether he likes or dislikes the music put on. When it is his favourite dance music he will smile in appreciation, but he will scowl if it is music he does not like. He can watch his favourite soccer team on television with a commentary from his father and will be excited when his team scores. He can certainly feel pain such as an involuntary movement of his arm hitting the hard side of his hospital bed. Mr S considered that the disturbance to JS of a move to hospital would be minimal if his family were there all the time to support him. They have had all the possible benefits and the risks explained to them. Mr S was realistic about the prospects of success. He realised it might not work and that even if it did JS would remain severely brain damaged. They would rather have him in his present condition than not at all, and believe it is a worthwhile risk to try the treatment. If the decision went against them it would not stop them. They would search the world to get treatment elsewhere, including going to have the treatment in Japan if necessary.

The family of JA

6. The father was ill and Mrs A gave evidence from her home by telephone link. JA has one sister. Both the father and mother are health professionals. In the written evidence of the A parents is set out the progression of the disease and the deterioration in JA's health to the present day. Although she is now helpless and confined to bed she is mostly awake and aware of her immediate surroundings. She is relaxed whilst her mother is with her and anxious if her mother leaves the room. She has slight movements and can raise a finger and can make her feelings clear to her family. She is contented and happy with her family and gains pleasure from outings. She was recently in hospital and was not too distressed by it. Mrs A was realistic about the prospects of successful treatment. JA had been treated with Quinacrine in 2001 and there had been some improvement which had raised their hopes. After that treatment came to an end, she felt that they would be more realistic about the proposed treatment if given. It was the only option they had for JA and they wanted to try it. She was aware that the best that might be achieved might be some neurological improvement but they would be content if the treatment prolonged JA's life in her present condition and slowed the course of the disease. The A family had discussed the possibilities with the consultant neurosurgeon, Mr T, and he had explained to them the risks of the treatment.
7. No-one who knows them or has seen them, whether the consultants who gave evidence, the members of both families, other doctors or nurses, have suggested that either JS or JA has no quality of life, nor that they cannot respond to their parents and others, nor that they cannot feel pleasure and pain. The evidence from those who nurse the patients, or know the patients, other than the immediate families, supports the evidence of the parents. The professional nursing staff who care for JS support the view of the parents that extending survival is worthwhile despite the severe neurological impairment. I am satisfied that both JS and JA have the ability, even now at a late stage of this disease, to feel pleasure and pain and have some enjoyment from life which is worth preserving. As Mr T said whilst giving his oral evidence, none of us have the right to assume on behalf of anyone else that a life lived with a disability is unacceptable to them. Both sets of parents gave evidence that, if either JS or JA had retained capacity, they would have been likely to have chosen for themselves to try this proposed treatment.

Medical Evidence

8. I heard evidence from four medical witnesses, Mr T, Dr Knight, Professor Will and Dr Doh-ura. I am particularly grateful to Dr Doh-ura for giving evidence at very short notice and for amplifying so helpfully his research and his paper. I am very indebted to the three English consultants for the care and clarity with which they gave their evidence and simplified for me the basic medical condition of vCJD and the proposed Pentosan Polysulphate treatment (PPS). PPS is a well known drug, licensed in Germany and in the USA as a clinical medicine for treatment in interstitial cystitis, thrombophlebitis or thrombosis.
9. The experts were in agreement about the state of the disease in each patient and the inevitable outcome in the absence of any new treatment. There is no cure and there are no recognised effective drugs which have, to date, been able to prolong life or arrest the continuing neurological deterioration. Both JS and JA are bound to die. The average length of life once the symptoms appear is 14 months. It is 15 months since the onset of JS' symptoms, and 3 years since the onset of JA's symptoms. The fact that both young people are still alive is a tribute to the outstanding care they receive at home. The three English consultants agreed that neither JS nor JA is competent to make decisions about this proposed treatment.

Dr Doh-ura

10. Dr Doh-ura, a distinguished Japanese Neuropathologist, has written a paper titled "Intraventicular infusion of pentosan polysulfate as a treatment for prion diseases," in which he sets out his research in Japan on rodents and dogs, previously infected with scrapie, which were infused with the drug, PPS. He has lectured on his research in different parts of the world, in Edinburgh in September 2002 and in Paris last week (1^st to 3^rd December 2002). Professor Will has heard him lecture twice, and in Paris had the opportunity to ask him questions about his paper. Dr Knight also heard him lecture but did not have the opportunity to talk to him. The paper has not yet been published but was submitted in October 2002 to a prestigious medical journal, the Annals of Neurology, which is the official journal of the American Neurological Association. The paper is currently in the process of being peer-reviewed. The court, the legal teams and the medical witnesses have read it. In addition Dr Doh-ura gave evidence to the court by video and telephone link from Tokyo. He told the court that he graduated in 1985. He trained as a neurologist and went to the USA to study prion diseases and has been studying prion diseases over a considerable number of years. He is a scientist and clinician and continues to see patients for half a day a week. Despite some technical difficulties of communication he was able to provide us with his conclusions on the work he has carried out and to correct some misapprehensions. He was very modest in the way he gave his evidence and I found him a most impressive witness.

Dr Doh-ura's paper and research on PPS and his oral evidence

11. A major problem in the giving of drugs to treat this type of disease has been the poor accessibility of the drugs to the brain, which I understand is called the 'blood-brain barrier'. Dr Doh-ura and his team have

"developed a more sensitive drug evaluation system, irrespective of drug accessibility to the brain, by installing a persistent intraventricular drug infusion device in an intracerebrally infected animal model with prion disease."

12. They reported

" that the intraventricular administration of PPS is a promising treatment even at a late stage in intracerebrally infected individuals."

13. They worked with genetically modified mice and with rats and dogs. The PPS treatment was evaluated over a 2 month period at varying doses. In mice inoculated with scrapie, in the absence of infusion of PPS, abnormal PrPsc deposition in the brain appeared around day 35 and the mice died around day 52. A four-week persistent intraventricular infusion of PPS was given to mice at differing dosages and at differing periods, commencing on days 10, 35 and 42. The dosage varied from 110 to 460 units (a unit being 1 (g/kg body weight/day), with the medium dosage at 230 units. A 110 unit low dosage of PPS at day 10 prolonged the incubation time from 52 to 80 days. The high dosage, 460 units, when given at day 10, prolonged the incubation time significantly, from 52 days to 142. The start of the treatment at day 35 with 460 units dosage prolonged the incubation time from 52 days to 100 days.
14. Professor Will elicited from Dr Doh-ura that treatment at day 42 extended the incubation time by about 10%. Whilst that was true of other doses, Dr Doh-ura's evidence (from 3 of his figures supporting his paper and from his oral evidence) makes it is clear that by commencing treatment at day 42 with a dosage of 230 units, life expectancy was extended by about 40%,that is to say to about 72 days.
15. The clinical symptoms in scrapie-infected mice progress very rapidly, often within hours, and the mice were humanely killed, usually within 24 hours of the clinical development of symptoms. The phrase 'later stage of the disease' used in the paper must, in my view, be read in the light of Dr Doh-ura's oral evidence (see below).
16. The report contained a safety assessment of PPS by intraventricular infusion. Higher doses showed adverse effects, but only in dogs. Several dogs showed partial or generalised seizures which began 24 hours after infusion of PPS was initiated. Two dogs survived the seizures but the other five dogs with seizures died within a week after the initiation of PPS, and three of those dogs had a large haematoma in the cerebral white mass where the infusion device was fitted.
17. The side effects were serious in the higher doses with dogs. When Dr Doh-ura treated mice at a late stage, at day 42, with the moderate yet maximum effective dose of 230 units, there were no serious side effects and there was a marked prolongation of life.
18. The conclusions in the paper were that the effects of PPS were quite dependent on the timing of infusion initiation, with the earlier initiation rendering a better prognosis. The effectiveness of the intraventricular infusion of PPS in scrapie-infected mice was demonstrated by these experiments but Dr Doh-ura pointed out in his paper that

"it remains to be established that this treatment has universal validity for the prion diseases, especially human illness."

19. In his oral evidence, Dr Doh-ura made clear an aspect of his research that had been misunderstood by all those who had read his paper for the purpose of these two cases before me. The clinical signs of neurological impairment in the mice were obvious and severe at 50 to 52 days. They could not move or eat and were in the terminal stage of the illness and were 2 or 3 days from death. It was difficult to say precisely when the symptoms started in the mice, but abnormalities in performance began to show quite early after the introduction of the infection. From the data obtained, such abnormalities appeared earlier at about 35 days. There were some signs of the mice becoming clinically ill much earlier than 35 days but observation of abnormalities is difficult since mice cannot speak about their symptoms. There was detailed evidence that the mice were clinically affected much earlier than in the final days, or 'terminal stage'.
20. Dr Doh-ura considered that the mechanism of the drug to the abnormal (diseased) protein was that the PPS was inhibiting the abnormal prion protein. PPS was a direct inhibitor of the formation of abnormal prion protein. He was asked whether the research showed the possibility of a good effect on humans with an advanced stage of this disease. He said it was a difficult question to answer. His data showed the effectiveness of PPS to be quite dependent on the time when the infusion was introduced. He could not say at what clinical stage PPS was effective. It would be very difficult to have better outcomes from terminal stage patients.
21. He was asked whether in his opinion it was medically correct to use PPS in humans at this stage of scientific knowledge. He expressed hesitation about what would be the position in England. He pointed out that there were no cases of vCJD in Japan but many cases of iatrogenic CJD. There is no difficulty in giving the PPS treatment in Japan. They are planning to use PPS on patients with iatrogenic CJD and are prepared to start treatment immediately, either in January or, if they can get the co-operation of the surgeons, possibly this month. They intend to treat patients already showing clinical signs of the disease, and not only those who are at high risk without yet manifesting symptoms. They will probably treat patients who are already showing advanced neurological signs and patients with different types of prion diseases.

Evidence of Mr T

22. Mr T is a consultant neurosurgeon attached to the Hospital Trust. Both patients were referred to him by their general practitioners. He had read the Doh-ura paper. He recognised that the benefits and risks of the treatment as recorded in the Doh-ura research were species-specific and that the infection introduced into the animals was scrapie and not CJD. He agreed that the treatment may not work in humans, or may not work against CJD, and that the available data is limited. But he said he is prepared to try it as he believes that it may have an effect on the accumulation of abnormal proteins in the brain, thereby limiting the deterioration of the patient's condition. Further, he said, the animal testing models will only take us so far; ultimately, the only proper place for the study of CJD is in CJD patients. Whilst it would be a very considerable leap to a new disease and a new species if the PPS treatment were carried out on humans, such a leap had to be made at some time.
23. The Doh-ura research did demonstrate a considerable prolongation of the life of the mice even at a late stage of introduction of the PPS treatment. He set out at some length in his second report, dated the 29^th November 2002, his views on the prospects of success from the PPS treatment and his conclusion that it would be in the best interests of both patients to carry it out. He was prepared to carry out the two operations necessary to make it possible to provide for the infusion of the PPS.
24. He wrote a trial protocol and set out for the court the model he proposed to adopt. The two operations were simple and routine ones, but they would each require a general anaesthetic. According to the report of Professor Will

"The surgical procedure would involve the insertion of an Ommaya reservoir, connected to a ventricular catheter, which would be inserted into the brain through a right frontal burrhole. A second operation would be undertaken if the presumed therapeutic dose were administered safely during a trial period. The second operation would require the insertion of a subcutaneous pump under the skin of the abdomen via a catheter connected to the existing ventricular catheter."

25. In the absence of complications, each patient would spend about 12 days in hospital. After the first operation there would be careful monitoring for post-operative haematomas.
26. The protocol proposed a cautiously low dosage, being the equivalent of just 3% of the higher dose used in the Doh-ura research. The dosage would be increased daily with careful monitoring until day 11. He would continue the infusion indefinitely subject to regular review.
27. Mr T explained that he would follow the existing CJD hospital protocols in order to eliminate the risk of transmission, including destroying all surgical equipment used in the procedures. This aspect would have no effect on the patient's clinical interests.
28. Mr T said he had carefully considered the potential risks and side-effects of the proposed treatment. The general and anaesthetic risks of complications in the implantation of a subcutaneous pump are about 2%. The ordinary risk of haemorrhage associated with ventricular cannulation is 0.5%. However this risk may be increased in association with PPS, a potential anti-coagulant, which at high doses might cause intra-cranial haemorrhage. It was the risk of haemorrhage which was judged to be the major potential complication and appeared to be directly related to the treatment dosage. The consequences of a haemorrhage could range from minor to extreme. Minor effects could include slight bleeding which would resolve itself after 2 to 3 days, possibly causing headaches for a short period. Alternatively, there could be serious adverse consequences after surgery such as an immediate massive seizure or stroke, resulting in the possibility that JS or JA could die. The third possibility was of a seizure, or series of seizures, which did not kill but caused neurological or other damage to JS or to JA which would not have otherwise arisen from the disease and which did not necessarily reduce life, but significantly impaired the present ability of the patient to enjoy life. Taking into account the increased risk of infusing an anti-coagulant, but recognising that the risks are minimised by diluted infusion into the ventricular CSF and that dilution further occurs through diffusion, Mr T assessed the risk of post-operative haemorrhage to be, at its highest, a maximum of 5%.
29. Mr T also explained the other possible risks and disbenefits of the treatment. He agreed that there would be some inevitable disruption to each patient in being admitted to hospital and undergoing the procedure, but said this disruption would be minimised by the provision of a private room and replication of the home environment, with family members present at all times. The post-operative pain might last between 24 and 72 hours, with morphine required for perhaps the first 24 hours. In the longer term, there would be no negative effect on daily life save for the cosmetic effect.
30. Mr T thought it also possible that the operations and treatment would have no adverse but equally no beneficial effect. He had discussed the prospects of any benefit and the risks with the families of each patient.

Evidence of Dr Knight

31. Dr Knight is a consultant clinical neurologist and was asked by the families to give evidence in these two cases. He did not examine either patient but had a telephone discussion with JS's father. He did some research on CJD in the 1980s. He works part time as a clinician, and occasionally sees CJD patients in the course of his work as a consultant clinical neurologist to the National CJD Surveillance Unit in Edinburgh. He has worked from time to time with Professor Will. He had read the Doh-ura paper. He was impressed by the research and considered there was a rational basis for coming to the conclusion that the proposed treatment did provide the possibility of a positive effect on the progress of the disease and a prolongation of life for each patient. His view was based upon his occupation and experience. It was not possible at this stage to have any scientific proof of the efficacy of the proposed treatment, as there was no way of directly extrapolating from data on mice to humans given the differences in their respective incubation and symptomatic processes. He thought it was highly probable that the progression from normal to abnormal proteins in the brain is a central feature of the progression of the CJD disease in humans, and of prion diseases in animals, but he could not say for certain what the disease mechanism is, or whether PPS would have any effect on it.
32. His concerns were about the risks involved. He was asked whether, if JS and JA were his patients, he would advise that the treatment should be given. He said that given the strong views of both families, he could not on balance see grounds for denying JS and JA the treatment. He would be worried if the families unreasonably expected there would be a good chance of benefit, but he did believe there was some chance of benefit. If the families wanted it he would be prepared to give the treatment on the understanding that there was a very theoretical chance. If a family really understands the uncertainties he would give a great deal of weight to their views. He was also concerned about the effect of withholding the treatment from the families. If treatment were denied to them there would be an impact on the families and on the patient during the patient's life and after the death of the patient.
33. Dr Knight was very aware of his duty not to cause undue suffering to a patient. He agreed that the risks of haemorrhage or seizure and the toxic nature of the PPS treatment needed to be carefully weighed against the uncertainty of success, but he said that unless there was no prospect whatsoever of success, the balance was affected by the progressive and fatal nature of the CJD disease. Whilst there was no firm scientific basis and no evidence of efficacy and safety, he would nevertheless administer it.

Evidence of Professor Will

34. Professor Will gave evidence at the request of the Official Solicitor. He is Professor of Clinical Neurology based at Edinburgh. He did research on the epidemiology of CJD and in 1990 he established the National CJD Surveillance Unit in Edinburgh which studies all suspected cases of CJD throughout the United Kingdom. His Unit was responsible for identifying vCJD in 1996. He has been Co-Ordinator of the European CJD Surveillance System and is clearly a leading expert in this field. He saw both patients. He has read the Doh-ura paper and heard Dr Doh-ura lecture. His second report to the court reflects discussions he had with Dr Doh-ura on the paper at the beginning of December.
35. Professor Will's first report set out his understanding of the Doh-ura research and its results. Since I had the enormous advantage of hearing Dr Doh-ura himself give evidence, it is not necessary to set out Professor Will's evidence on this research.
36. Professor Will said in his first report that the use of life expectancy as an outcome measure might be very difficult to assess in view of the marked variation in the figures of survival of other vCJD patients. In his opinion, even if the treatment were effective, it would be unlikely that there would be evidence of neurological improvement. In his conclusion he said

"PPS …. represents to my knowledge the only current treatment that could possibly influence survival in variant CJD, if given by this route. Treatment of cases of vCJD with intraventricular PPS will inevitably involve discomfort, possible distress and even if it is effective, may only prolong survival and in my view is unlikely to result in clinical improvement. The parents of [JS and JA] have very carefully considered the issues involved and are firmly of the opinion that this treatment is the only hope for their children and, in the full knowledge of the uncertainties and potential risks, are firmly of the opinion that this treatment should be given. From a scientific perspective, in my opinion, the likely benefits of the treatment are speculative and there are clearly significant risks. However, this has to be balanced against the firmly held and informed views of two families, whose dedication and commitment to their affected children is remarkable."

37. His second report was written and his oral evidence was given shortly after he heard Dr Doh-ura's lecture in Paris and discussed his paper with him. His conclusion in his second report was that

" The question is whether the potential benefits of the treatment outweigh the potential risks. Although the treatment…. might extend survival and could possibly result in some clinical improvement there is great uncertainty about whether there would be any benefit on the basis of available scientific evidence……..

On balance I do not believe that treatment with intraventricular PPS is in the best interests of [JS] and [JA]……..

Although it could be argued that there is little to lose in this tragic situation, my personal view is that there is a significant risk of causing pain or distress if the treatment is given and very little prospect of any benefit."

38. In his oral evidence he pointed that he had had no access to the figures in the research paper which might be very relevant (as indeed they turned out to be). He felt intuitively that there was a possibility that the treatment might work in the early part of the clinical stage of the disease before there was significant damage to the brain. He could not say that there would be no potential benefit.
39. Professor Will gave his opinion as to the risks of the proposed treatment and agreed that the major risk was from intracerebral haemorrhage. He pointed out that it was impossible to predict whether or not, and at which dosage, there would be adverse effects in humans treated with intraventricular PPS. He agreed with Mr T that the direct surgical risks appeared to be low. The possibility of unexpected adverse events could not be excluded, and in particular he was concerned about the increased risks of haemorrhage associated with the infusion of an anti-coagulant. He was also concerned about the potential distress to each patient, although he accepted that these disbenefits would be transient.
40. Professor Will discussed the risks and disbenefits with the two families, and had great respect for the position of the families. He was asked how he would advise the family if he were the treating clinician. He thought that would be a very difficult situation. This was experimental therapy. There would be a different set of pressures upon him if he were treating the patients himself, which would affect his decision. It would be a much simpler decision if PPS could be given in tablet form. I gained the clear impression that Professor Will would consider giving the PPS treatment if it did not involve the risks of surgery and that if he had been the clinician he might well have supported the treatment even when surgery was required. He agreed that by giving the treatment one would learn about the effect of PPS in humans, although one would be more likely to learn of what goes wrong than what goes right unless, contrary to expectation, there was an improvement in neurological function. He also said that by giving the treatment, one would avoid denying the family the benefit of trying it.
41. One difficulty I have had in assessing the overall evidence of Professor Will, is that he gave evidence before the parties were able to track down Dr Doh-ura in Japan and gave evidence without the advantage of the latter's explanations of his research. In the light of Dr Doh-ura's evidence, I do not consider that Professor Will would have come to his more pessimistic conclusion in his second report from which he retreated to some extent in his oral evidence. In my judgment the conclusions in his second report were based on the understandable but in fact erroneous belief that the experiments on the infected mice were all at a time prior to any manifestations of the disease in the mice. In his opinion there was no indication that intraventricular PPS would be an effective treatment in already established clinical disease. His conclusion however was that the earlier the treatment is given the greater the chance of prolongation of the life of the mice.

The legal basis for the applications

42. In a situation where there is no application to the court, and the patient does not have capacity to make a decision about medical or surgical treatment, the doctor has, in my judgment, two duties. First he must act at all times in accordance with a responsible and competent body of relevant professional opinion, generally described as the 'Bolam test' (see Bolam v Friern Hospital Management Committee [1957] 1 WLR 582). That is the professional standard set for those who make such decisions. There is a second duty. As I said in re A (Male Sterilisation) [2000] 1 FLR 549 at page 555

"The doctor, acting to that required standard, has, in my view, a second duty, that is to say, he must act in the best interests of a mentally incapacitated patient." (see also re S (Adult Patient:Sterilisation) [2001] Fam 12)

43. This concept of best interests is relevant to those who are unable to decide for themselves including JA who although a child would have the right to consent to medical treatment if she were competent as she is now 16.
44. Lord Goff in his speech in re F (Mental patient: Sterilisation) [1990] 2 AC 1 said at page 77

"I find myself to be respectfully in agreement with Lord Donaldson of Lymington MR, when he said at page 18

'" I see nothing incongruous in doctors and others who have a caring responsibility being required, when acting in relation to an adult who is incompetent, to exercise a right of choice in exactly the same way as would the court or reasonable parents in relation to a child, making due allowance, of course, for the fact that the patient is not a child, and I am satisfied that is what the law does in fact require."'

45. In re F (above), unlike the present applications, there was no need to investigate the meaning or the extent of the phrase of 'best interests'. They are not limited to best medical interests (see re MB (Medical Treatment) [1997] 2 FLR 426 at page 439). I said in re A (above) at page 555

"In my judgment best interests encompasses medical, emotional and all other welfare issues."

46. In a case where an application is made to the court, as it was entirely properly made in these two cases, it is the judge, not the doctor, who makes the decision that it is in the best interests of the patient that the operation be performed or the treatment be given. The medical issues are not therefore the only matters to which I should have regard in considering the outcome of these two cases.

The questions

1. The first question in this very unusual case is whether either JS or JA has the mental capacity to make decisions about his or her medical treatment.

2. The second question is whether the proposed treatment does come within the 'Bolam test'.

3. The third question is whether it is in the best interests of the patients, or either of them to have the PPS treatment.

4. The fourth question is whether, in the event that I say yes to questions 2 and 3, the treatment proposal is capable of being carried out within the National Health Service.

Mental capacity

47. There can be no doubt from the unanimous evidence of the three English medical witnesses that both JS and JA lack the mental capacity to make any decisions and clearly cannot decide whether to undergo this proposed PPS treatment.

The 'Bolam test'

48. To the question: 'Is there a responsible body of medical opinion which would support the PPS treatment within the United Kingdom?' the answer in one sense is unclear. This is untried treatment and there is so far no validation of the experimental work done in Japan. The 'Bolam test' ought not to be allowed to inhibit medical progress. And it is clear that if one waited for the 'Bolam test' to be complied with to its fullest extent, no innovative work such as the use of penicillin or performing heart transplant surgery would ever be attempted (see Lord Diplock in Sidaway v Bethlem Royal Hospital Governors [1985] AC 871 at page 893). I do however have evidence from responsible medical opinion which does not reject the research. Mr T is a very experienced and clearly very responsible neurosurgeon. He has carefully thought through at considerable length in his two reports, the research, its implications, the uncertainties, the risks and the doubts about the benefits to these two patients. He has come to the conclusion that

"…..it is in the best interests of [JS and JA] to be treated and I would personally be prepared to carry out that treatment."

49. His conclusion, in my view, ought to carry significant weight with the court. His view is supported cautiously by Dr Knight who has great experience as a neurologist in the field of CJD. He has said that on balance he did not see grounds for denying the PPS treatment to these two patients. For the reasons which I have set out above, the somewhat more pessimistic approach of Professor Will, based on the confusion over the Doh-ura paper, has to be reconsidered in the light of the oral evidence and explanations of Dr Doh-ura. Even without those explanations from Dr Doh-ura, in his oral evidence Professor Will was more concerned about the risks of the operations than the giving of the treatment. He would not, as I understand his evidence, have opposed the treatment itself if it could be given in tablet form. The conclusion to which I have come, based on the evidence of the three English medical witnesses together with that of Dr Doh-ura, is that it would not in itself be irresponsible or unethical to give the treatment to these patients, although the requirement for surgery raises issues as to the assessment of the risks of that surgery.
50. Dr Doh-ura was impressive in his approach to his research. He did not display any over-confidence in his work but he had results of experiments showing benefit at a point when the clinical stage of the disease had been reached. The 40% extension of life at the medium dose at day 42 showed a benefit at quite a late stage of the experiments. I was also impressed by the fact that he and his colleagues were on the point of giving the PPS treatment to CJD patients who, by definition as he pointed out, were already at the clinical stage of their illness.
51. I am satisfied, consistent with the philosophy that underpins the 'Bolam test', that there is a responsible body of relevant professional opinion which supports this innovative treatment. That is, in my view, subject to the seriousness of the risks involved and the degree of benefit that might be achieved.

The medical risks associated with the treatment

52. The risks posed by the infusion of PPS are dose dependent. In high doses PPS is toxic and there has to be a balance achieved between effectiveness and potential toxicity. At the cautious dosage suggested in the trial protocol, that risk does not appear great. The effect upon a human is of course unknown.
53. There are risks involved in general anaesthesia. The risks of infection associated with the installation of the subcutaneous pump are about 2%. The usual risk of a cerebral haemorrhage arising from the operation to insert the Ommaya reservoir connected to a ventricular catheter was assessed at 0.5% and local infection of ventriculitis at about 2%. Allowing for an increase in risk due to the potential anti-coagulant effect of PPS, these risks are assessed by Mr T at their highest to be about 5%. There was no dispute as to these levels of risk.
54. I understood from the evidence of Mr T that the anti-coagulant effect of the infusion of PPS would be significantly reduced by its dilution within the fluid surrounding the brain. There would however remain a risk of bleeding beyond the time of surgery and Mr T provided in his trial protocol for monitoring during the period of the treatment.
55. The two operations are routine. They would have to be carried out on patients with vCJD but there was no evidence to suggest that JS or JA would be more prone to the risks of the surgery or of the necessary general anaesthesia which would be required than other patients without vCJD. Three of the dogs in the Doh-ura experiments, who had received higher than medium doses, were found to have had a large haematoma in the cerebral matter where the cannula was fitted.
56. The 5% risk of a haemorrhage encompasses a range of possible outcomes, from a minimal and transient effect, to a maximum effect from a seizure causing death, or an intermediate effect of significant impairment of the present ability of the patient to enjoy life. A 5% risk would not seem to me to fall outside the bounds of responsible surgical and medical treatment so as to be an unacceptable risk. The reasonableness of taking that risk with these two patients is a matter that more appropriately comes within the considerations of best interests. There are other risks, for instance of pain from the surgery and distress caused to the patient by the whole process, raised in particular by Professor Will, which I shall also address below.

Benefits from treatment

57. The benefits that might be gained from the PPS infusion are less tangible and more difficult to assess. There may not be any obvious benefit or any benefit at all. None of the medical witnesses entirely ruled out the possibility of some benefit. Even though the patients will not recover, it seems to me that the concept of 'benefit' to a patient suffering from vCJD does encompass an improvement from the present state of illness, or a continuation of the existing state of illness without deterioration for a longer period than might otherwise have occurred, or the prolongation of life for a longer period than might otherwise have occurred. The medical evidence that I heard provided for the possibility of one of those three benefits occurring. Dr Doh-ura said that PPS acts as a direct inhibitor of the abnormal protein, which would seem to suggest the possibility of improvement to nerve cells or at least the prevention of deterioration of the neurological damage. At best there might be some improvement. The fact that both JS and JA have good days and bad days allows for the possibility that some nerve cells might respond to the infusion of PPS. Such a possibility could not be entirely ruled out. The second benefit allows for the possibility of arresting the otherwise inevitable deterioration of the nerve cells. The third possibility would be the prolongation of the life of the patient in his or her present state. The Doh-ura research clearly demonstrates that the earlier the treatment can be given, the greater opportunity there is for improvement or at least prolongation of life. Even at day 42 in the Doh-ura experiments, there was real evidence of prolongation of life. Where there is no alternative treatment available and the disease is progressive and fatal, it seems to me to be reasonable to consider experimental treatment with unknown benefits and risks, but without significant risks of increased suffering to the patient, in cases where there is some chance of benefit to the patient. A patient who is not able to consent to pioneering treatment ought not to be deprived of the chance in circumstances where he would have been likely to consent if he had been competent.
58. Whether or not those are reasons to approve the treatment in the best interests of these patients I shall consider below. It does not seem to me however that it can be said that in principle this is treatment which is clearly futile or that it would not, in suitable cases, be proper to give the PPS treatment to those suffering from prion diseases, and I am therefore satisfied that the proposed PPS treatment complies with the 'Bolam test'.
59. Although PPS is not, I understand, licensed in the United Kingdom, according to the skeleton argument of Mr Jackson, on behalf of the Official Solicitor, the Medicines Control Agency would be unlikely to raise objections to its use on individual patients upon the taking by the treating doctor of direct personal responsibility.

Best interests

60. The duty of the court is to consider the best interests of a patient who does not have the capacity to make decisions, as I have found is the position of JS and JA. In my judgment, I have to assess the best interests in the widest possible way to include the medical and non-medical benefits and disadvantages, the broader welfare issues of the two patients, their abilities, their future with or without treatment, the views of the families, and the impact of refusal of the applications. All of these matters have to be weighed up and balanced in order for the court to come to a decision in the exercise of its discretion.
61. I am satisfied from all the evidence that both JS and JA have a life that is worth preserving and that any treatment that might be beneficial would be of value to them. It has to be recognised that the treatment proposed for these two patients would not lead to recovery. Nonetheless, on the totality of the medical evidence I find that that there are possible benefits both to JS and JA from this pioneering treatment. The chance of improvement is slight but not non-existent. The families ought to regard that possibility as unlikely but not impossible, since no-one knows the outcome. There is, from the medical evidence, a possibility of arresting the disease temporarily, and the possibility of prolonging the life of these two patients to some extent, although whether that be in weeks, months or years is impossible to tell. Each patient is entitled under Article 2 of the European Convention to the right to life. Article 8 gives to each patient the right to respect for his family life. Is a prolongation of life as it is led worthwhile for JS and JA? The parents of each say emphatically yes. There is undoubtedly evidence that there is some value to their lives. A reduced enjoyment of life even at quite a low level is to be respected and protected. Each patient is at present within a devoted and wonderfully caring family and is being provided with the best life possible in these tragic circumstances. I consider that even the prospect of a slightly longer life is a benefit worth having for each of these two patients. There is sufficient possibility of unquantifiable benefit for me to find that it would be in their best interests to have the operations and the treatment subject to an assessment of the risks. There is no alternative treatment available.
62. The risks of the surgery and anaesthesia as such are slight. The risk of the insertion of the device to enable the PPS infusion to be given is the only medical risk that requires careful consideration. Is an up to 5% risk of bleeding with the possible outcomes a risk worth taking on behalf of JS and JA? Again the two families would say unhesitatingly yes. If the risk materialised and there were to be a serious outcome, neither family would wish to see their child suffer. I am assured and accept that neither family would prolong the life of their child in those circumstances. I think it is reasonable, at this stage of my judgment, to put into the balance that, if there is a possibility of continuation of a life which has value to the patient and the patient is bound to die sooner rather than later without the treatment, these two young people have very little to lose in the treatment going ahead. I am satisfied it is a reasonable risk to take on their behalf. These patients have a real interest in the manner of their remaining lives and their death. Hoffman LJ in Airedale NHS Trust v Bland (CA) [1993] AC 789 said at page 829

"It is demeaning to the human spirit to say that, being unconscious, he can have no interest in his personal privacy and dignity, in how he lives or dies."

63. The parents do not consider that the dislocation to their children's lives, the move to hospital and the undergoing of the two operations would cause much distress to JS or JA. Despite the general view that vCJD patients need routine and do not like to be moved, the parents consider that both JS and JA would be able to manage the changes so long as they had their families with them to support and reassure them. Although Professor Will was anxious about this aspect of the case, having heard all the evidence, I am satisfied that the pain of the surgery and the distress caused by the admission to hospital would be short-lived and manageable.
64. The unanimous medical evidence was that the views of the families carried great weight. I agree. In my judgment the views of both families should carry considerable weight in the circumstances of these two young people. I have no doubt that the A family have their feet firmly on the ground and understand very well the limitations on the prospects of benefits and the risks attached. They would not wish to prolong her life if she were suffering as a result of the treatment but they feel very strongly that this treatment should be carried out. In the 3 years course of the disease the As' have had to put up with great disappointments and the agony of watching their daughter's deterioration in her health. The S family has had the same agony over 15 months. They also would not wish to see to see their son suffer. Both families are deeply and sincerely committed to this treatment. As I understand it, all three doctors would probably agree to this treatment if either JS or JA were their patient. If the treatment were not to be given, both families would be deeply distressed. They would, of course, continue to care for their children with the same dedication. Mr S would clearly continue fighting. The As might well carry on fighting. Dr Knight expressed concern about the effect on the patient and on the families of the loss of this opportunity not only during the life of JS and JA but after the death of each of them. The impact of refusal by this court of granting the declarations on each set of parents and, in one case, 5 siblings, and in the other case, one sibling, would in my view be enormous and palpable. In a finely balanced case I should give the views of the parents and the effect upon them of refusal great weight in the wider considerations of the best interests test which the court has to apply to each patient.
65. Furthermore, the Official Solicitor, having heard the evidence and acting on behalf of JS and JA, supported the proposals for treatment.

Conclusion

66. Lord Donaldson MR said in re J (Wardship: Medical Treatment) [1993] Fam 33 at page 46 that there is

"a very strong presumption in favour of a course of action which will prolong life".

67. Balancing all the relevant considerations, in my judgment it is in the best interests of JS and of JA that this treatment should be carried out and that surgery should be performed by Mr T in order to make possible the intraventricular infusion of PPS.

The carrying out of the treatment

68. The Hospital Trust made it clear prior to the hearing that it was not intending to take part in the hearing but raised the concerns to which I referred earlier in my judgment. In a letter to me the solicitors to the Trust explained that, under the new Clinical Procedures Policy, it was necessary for an application to be made to the Clinical Governance Committee. In addition an application would have to be made to the Drugs and Therapeutic Committee. The Official Solicitor wrote to the solicitors to the Hospital Trust pointing out that the court would be assisted by the Trust being represented at court. In the final paragraph of his letter of the 3^rd December 2002, he said

"It would also be a matter for some criticism if the court were to make a declaration and if the Trust subsequently through its committee procedures would not give effect to it."

69. Mr Kennedy attended court on behalf of the Hospital Trust on the second day but preferred not to address the court on the issues raised by the proposed treatment. Mr Kennedy said that he would wait for a decision by the court on the applications before it but wished to be heard on the question where the treatment would be carried out if I granted the declarations applied for. He helpfully indicated however that the Trust had brought forward the meeting of its Clinical Governance Committee to Wednesday 11^th December. I therefore arranged to give my judgment in private before the Committee met.
70. I am however somewhat concerned at the way in which this matter has come before the court. It is not unusual for the High Court to be asked by an NHS Hospital Trust to decide whether medical or surgical treatment would be lawful. In the present case, I understand that Mr T was about to make the relevant applications to the Committees and was dissuaded from doing so. I am somewhat concerned to find that I have been asked to declare whether the proposed treatment is lawful and then find that the hospital, to which the consultant surgeon is attached with patients properly referred to him (albeit outside the Trust area) may not choose to accept the patients for the treatment. Interesting though this case and particularly the medical evidence has been, it would be an unacceptable academic exercise for a High Court judge, exercising the inherent jurisdiction of the High Court, to hear a case and hold that the treatment is lawful, if after the judicial decision is made the NHS Hospital Trust is not then prepared to carry it out. In the case of the families of those suffering from as tragic illness as JS and JA are, it would be an unbelievably cruel blow to have the High Court say yes to the treatment and the two Committees of the Hospital Trust to say no. The Committees, of course, must exercise their own discretion in the applications made to them. I would hope, however, in the broader interest, that such a situation would not be allowed to happen again and that in future a Hospital Trust would have an opportunity to form its own conclusions before the court makes its decision. I appreciate, of course, that the parents of JS and JA are the Claimants and that the Hospital Trust was joined as the Second Defendant at the outset.
71. The position of JA is different in that she is a child and there are different and more direct considerations. I have a direct responsibility for children who come before the courts whose welfare by section 1 of the Children Act 1989 is paramount. I have directed that this operation on JA should be carried out by Mr T and I make that order, although I cannot of course bind the Trust. Should it reject the applications made by Mr T we may be faced with an impasse.
72. If the Committees reject the applications now made by Mr T, on behalf of his two patients, I would invite the Department of Health, in this unique case, to consider how best to help these families. There is the special position of JA since she is a child. I would hope however that such a distinction would not actually be drawn between JS and JA in considering whether to provide a venue for the PPS treatment. I would hope it would be possible to find an NHS Hospital Trust prepared to carry out the necessary surgery and to provide the PPS treatment. Since the surgery is routine it ought not to be a very expensive procedure. Although this cannot be a research project, there would be an opportunity to learn, for the first time, the possible effect of PPS on patients with vCJD and to have the opportunity to compare it with the treatment about to be given to patients in Japan.
73. My order is as follows:

IT IS ORDERED AND DECLARED THAT:

1 It would be lawful and in the best interests of the Defendants JS and JA for them to receive medical treatment for the condition Variant Creutzfeldt Jakob Disease by intracerebral infusion of Pentosan Polysulphate and to undergo surgical and other ancillary treatment to enable this to happen.

2 In the case of JA, a minor, the treatment shall be carried out by Mr T, Consultant Neurosurgeon, the Court consenting thereto.

3 In the event that the Defendant NHS Trust does not agree to the treatment being carried out under its auspices, there be liberty to the other parties to restore the matter before the President for further directions at short notice. On such an occasion the Department of Health is invited to be represented by counsel.

____________________

Appendix (17^th December 2002)

74. Since the above judgment was delivered in private on 11^th December, there have been further developments:

a) I have been made aware that the Department of Health has received recent advice from its CJD Therapy Advisory Group and from the Committee on Safety of Medicines to the effect that neither committee currently recommends the use of PPS for established vCJD in humans. I have also been informed that this advice is due to be reconsidered in the light of the most recent information.

b) On 11^th December, following my judgment, the Trust's Clinical Governace and Quality Committee met and decided that it did not feel able to approve this treatment taking place at its hospital. The Chairman of the Drugs and Therapeutic Panel is also recorded as having indicated that the Panel could not contemplate approving the administration of the drug in question for the therapy intended.

c) However, in the special circumstances of these cases the Department of Health is taking urgent steps to investigate other possible facilities for the provision of the treatment.

75. On 26^th November 2002, to protect JS, JA, their families and carers and those treating them, I made an order restricting publication of identifying information. I have today made a fresh order in the light of the current situation. The terms of that order, which replaces the previous order, are annexed to this judgment. References in my judgment to JS are to a young man named Jonathan Simms. The Claimant is his father, Donald Simms. I conclude by reminding anyone reading this judgment of the importance of complying with that order.