Christiaan Barnard: his first transplants and their impact on concepts of death
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7327.1478 (Published 22 December 2001) Cite this as: BMJ 2001;323:1478
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Professor Sir Raymond Hoffenberg claims to have seen a dog on which
Christiaan Barnard had performed a head transplant, repeating the
experimental operation that had been performed by the Russians. Was the
dog alive? If so was the head conscious? If so how long were the warm and
cold ischaemia times?
If organ preservation techniques permit successful head
transplantation, in that the transplanted head recovers from anaesthesia
and appears to behave appropriately, these techniques might be profitably
applied to the management of head injuries.
Is Professor Sir Raymond Hoffenberg or any other transplanter able to
provide an answer?
Competing interests:
None declared
Competing interests: No competing interests
This correspondence appears to be dying out without any attempt by
those who use the UK criteria for the diagnosis and certification of death
for transplant purposes to defend their practice. This silence will be
seen as tacit acceptance of the fact that there is no logical or
scientific basis for equating the clinical syndrome known as "brain stem
death" with death itself. It is, in fact, no more than a syndrome, defined
by bedside tests, to which a generally reliable short-term prognosis of
death can be attached.
Initial claims that all brain functions had permanently ceased by the
time these criteria were satisfied were abandoned in 1995. The premise
upon which this syndrome was thereafter officially equated with death was
the suggested definition of death as the permanent loss of the capacity
for consciousness combined with the permanent loss of the capacity to
breathe [1]. This novel definition has never achieved general acceptance
by the philosophical fraternity. It affords no logical justification for
regarding the clinically "brain stem dead" as dead in any case, even on
those dubious grounds. Consciousness is not understood. It cannot be
tested directly. Still less can the capacity for its return be excluded by
any specific test. The only sound basis for a statement that it has ceased
for ever is evidence of the destruction of the whole of the brain,
including the brain stem. That is the requirement which underpins American
brain death law.
In the UK, there seems to be reliance on some unquoted theory of
consciousness which would have us believe that death of the brain stem
alone suffices to exclude its return under any circumstances.
Controversial as that idea may be, it offers no justification for
regarding those patients with brain stem areflexia and apnoea (in the face
of an hypercarbic drive stimulus) as dead on the 1995 premise. That would
require certainty that the whole of the brain stem is destroyed. The
prescribed tests lack the power to provide that assurance [2]. Indeed,
there is no means of diagnosing death of the whole of the brain stem
during life [3].
We should remember that death is not a positive state. It can be
defined only in terms of the absence of life. Where there is the
possibility of remaining life anywhere in the brain - that wonderful organ
whose function is so little understood - it behoves us to be especially
cautious about pronouncing its death.
1. RCP Working Group.Criteria for the diagnosis of brain stem death.
J Roy Coll Physns Lond 1995;29:381-382
2. Evans DW, Hill DJ. The brain stems of organ donors are not dead.
Catholic Medical Quarterly 1989;40:113-121
3. Swash M. Personal communication 2002
Competing interests: No competing interests
Sir, in addition to his valuable historical testimony [1] Hoffenberg
emphasises his confidence in the reliability and safety of current
diagnostic procedures for the diagnosis of brain stem death. However,
during the progression of intracranial hypertension, the brain blood flow
(BBF) cannot decrease to levels capable of causing irreversible neuronal
damage without crossing the range of ischaemic penumbra, when brain stem
function may be only reversibly suppressed. Hence, a global impairment of
blood supply to the whole brain or solely to the infratentorial structures
down to the critical range of ischaemic penumbra for hours/days (here
referred to as global ischaemic penumbra or "GIP") [2] may lead to
misdiagnosis of irreversible brain or brain stem damage in a subset of
deeply comatose patients with cephalic areflexia. Accordingly, direct
measurements of BBF in patients in deep coma and with cephalic areflexia
showed results consistent with GIP in 50% of cases [3-5] - a percentage
similar to that not showing diffuse brain necrosis even after 48 hours
under mechanical ventilation and clinically undetectable brain function
[6].
GIP is not currently ruled out prior to apnoea test. Alarmingly, in
24 to 39% of the cases, blood pressure drops to systolic levels equal or
lower than 90 mmHg during apnoea, despite the implementation of preventive
oxygenation procedures [7-9]. Apnoea testing is therefore in contrast with
current guidelines for management of severe traumatic brain injury (TBI)
and other conditions associated with increased ICP [10]. Even transient
hypotension may cause irreversible collapse of the intracranial
circulation in cats after severe TBI [11], and data from 2 different
clinical studies suggest that similar effects may be observed in response
to apnoea testing. When apnoea test was not used, victims of severe TBI
sustained elevated ICP and decreased perfusion pressure (PP) up to
spontaneous cardiac arrest in all cases studied [12]. In contrast, all TBI
patients involved in a second study were found with normal ICP and normal
PP, but with a BBF level equal or close to zero after apnoea test [13].
This 100% of disagreement suggests that hypotension (and/or possibly a
further increase of ICP caused by hypercarbia) during the period of apnoea
may have induced irreversible intracranial circulatory arrest in the
patients of the more recent study: the efflux of blood volume from the
intracranial space would explain the normalization of ICP and PP.
Evidently, the results of any confirmatory test may be altered by a
preceding apnoeic insult. In addition, the respiratory center is not
expected to respond to hypercarbia if BBF is within the GIP range. Hence,
the apnoea test is useless as a diagnostic procedure and may cause the
state (brain death or brain stem death) that it should only diagnose.
Moreover, it is performed without anticipation of any therapeutic benefit
to the comatose patient, and usually (if not always) without the consent
of his (her) family. Apnoea should be wisely replaced by timely
hypothermia (33°C), maintained for no longer than 24 hours. That
therapeutic approach may provide nearly full recovery of patients in deep
coma (GCS of 3) and with fixed/dilated pupils following TBI [14]. In
contrast, much longer periods of cooling (up to 72 hours) may worsen the
prognosis of TBI [15], possibly due to the effect of long-lasting
impaired coagulation on the injured brain tissue.
Affirmations like current diagnostic procedures have "proved
reliable and robust in clinical practice" [1] will not become true only
for being repeated to exhaustion. One may eventually suspect that
the actual motive for that persistent attitude is the anticipation that,
if not previously tested for apnoea, organ donors may occasionally
begin breathing in the operating room when organs are being
removed. I look forward to seeing the predictable time when the
moratorium of transparent scientific discussions on reversibility of
coma will come to an end.
1. Hoffenberg R. Christiaan Barnard: his first transplants and their
impact on concepts of death. BMJ 2001; 323:1478-80.
2. Coimbra CG. Implications of ischemic penumbra for the diagnosis of
brain death. Brazilian J Med Biol Res 1999; 32:1538-45.
3. Hoyer S, Wawersik J. Untersuchungen der Hirndurchblutung und des
Hirnstoffwechsels beim Decerebrationssyndrom, Langenbecks Arch Chir 1968;
322: 602-5
4. Bes A, Arbus L, Lazorthes Y, Delpla M, Escande M. Hemodynamic and
metabolic studies of coma depassé; Research on biological criteria for
cerebral death, International CBF Symposium 1969, Mayence.
5. Shalit MN, Beller J, Feinsod M, Drapkin AJ, Cotev S. The blood flow and
oxygen consumption of the dying brain, Neurology 1970; 20: 740-8
6. Walker AE, Diamond EI, Mosely JI. The neuropathological findings in
irreversible coma. J Neuropathol Exp Neurol 1975; 34:295-323
7. Jeret JS, Benjamin J. Risk of hypotension during apnea testing. Arch
Neurol 1994; 51: 595-9.
8. Goudreau JL, Wijdicks EFM, Emery SF. Complications during apnea testing
in the determination of brain death: predisposing factors. Neurology 2000;
55:1045-8
9. Jeret JS. Correspondence. Neurology 2001; 56:1249
10. Chesnut RM. Avoidance of hypotension: conditio sine qua non of
successful severe head- injury management; J Trauma 1997; 42:S4-S9
11. Lewelt W, Jenkins L, Miller JD. Autoregulation of cerebral blood flow
after experimental fluid percussion injury of the brain. J Neurosurg
1980; 53:500-11
12. Jørgensen PB, Heilbrun MP, Boysen G, Rosenklint A & Jørgensen EO.
Cerebral perfusion pressure correlated with regional cerebral blood flow,
EEG and aortocervical arteriography in patients with severe brain
disorders progressing to brain death. Eur Neurol 1972; 8: 207-12.
13. Obrist WD, Jaggi JL, Langfitt TW & Zimmerman RA. Cessation of CBF
in brain death with normal perfusion pressure. J Cerebral Blood Flow
Metab 1981; 1(Suppl 1): S524-S525
14. Metz C, Holzschuh M, Bein T, Woertgen C, Frey A, Frey I, Taeger K,
Brawanski A. Moderate hypothermia in patients with severe head injury and
extracerebral effects. J Neurosurg 1996; 85:533-41
15. Clifton GL, Miller ER, Choi SC, Levin HS, McCauley, Smith Jr KR,
Muizelaar JP, Wagner FC, Marion DW, Luerssen TG, Chesnut RM, Schwartz M.
Lack of effect of induction of hypothermia after acute brain injury. N
Engl J Med 2001; 344:556-63
Competing interests: No competing interests
Your photograph at the bottom of page 1479 purporting to be that of
Chris is in fact that of his brother Marius,also a cardiac surgeon in Cape
Town / Groote Schuur at that time.
Competing interests: No competing interests
“The UK definition of brainstem death, introduced by the Conference
of Royal Colleges and their faculties in 1976, has proved reliable and
robust in clinical practice.” So claims Hoffenberg in his disturbing
account of the first attempts to perform heart transplant surgery in South
Africa in 1967.
The statement of 1976 published in the BMJ (1) and the Lancet (2) was
entitled “Diagnosis of Brain Death”. The criteria described therein for
the diagnosis of brain death were “accepted as being sufficient to
distinguish between those patients who retain the functional capacity to
have a chance of even partial recovery from those in whom no such
possibility exists.” In other words, the diagnosis implies that the
patient has a hopeless prognosis - they will certainly die. Nowhere in
this document is brain death equated with the death of the individual.
Perhaps in order to rectify this obvious oversight, given that the
death of the individual is an ethical and legal pre-requisite for the
removal of their organs for transplantation purposes, a further
memorandum, “Diagnosis of death”, was published in the BMJ (3) and the
Lancet (4) in 1979. No change was made to the diagnostic protocol,
although the philosophical claim that “brain death represents the stage at
which a patient becomes truly dead” was made. No explanation was given for
this quantum leap in interpretation, except that brain death is the point
at which “all functions of the brain have permanently and irreversibly
ceased.”
In 1995 it was “suggested that the more correct term ‘brain stem
death’ should henceforth replace the term ‘brain death’ used in previous
papers produced by the Conference of Colleges and the Department of
Health”(5), a suggestion which gave the lie to the above-mentioned claim
in the 1979 memorandum.
However, even the claim that the criteria unequivocally identify a
dead brain stem is untenable with evidence of persistent function in many
individuals. Perhaps it is the final recognition of this fact that has
resulted in the advice from the Department of Health that “we no longer
use the term ‘brain stem death’ preferring the more accurate ‘death
certified by brain stem testing’”(6).
Nevertheless, the Department of Health still claims that these same
diagnostic criteria are “adequate for use in cases or organ
retrieval/donation”(7), a claim which is not at the heart of the dispute.
The key question is whether the criteria are adequate for the diagnosis of
real, actual death, as claimed in publicly distributed organ donor
recruitment literature. This problem ought, in theory, to be answerable
without any reference to transplantation whatsoever.
Such a catalogue of conceptual and scientific confusion and
backtracking can hardly be described as “robust” and is certainly not
reassuring. Nevertheless, I look forward to the publication of the 3rd
edition of Pallis’ most informative “ABC of death certified by brain stem
testing” to see whether he still recommends the use of general anaesthesia
in these “dead” donors in order to “allay any fears of residual
sentience”(8).
Until there is evidence of more openness, honesty and clear
scientific and philosophical thinking in this debate, I remain…
Yours, most sincerely, OFF the organ donor register,
Gavin Jarvis
(1) Conference of the Medical Royal Colleges (1976) Diagnosis of
brain death. BMJ ii 1187-1188
(2) Conference of the Medical Royal Colleges (1976) Diagnosis of brain
death. Lancet ii 1069-1070
(3) Conference of the Medical Royal Colleges (1979) Diagnosis of death.
BMJ i 332
(4) Conference of the Medical Royal Colleges (1979) Diagnosis of death.
Lancet i 261-262
(5) Working Group of Royal College of Physicians (1995) Criteria for the
diagnosis of brain stem death. J. Royal Coll. Phys. Lon. 29 381-382
(6) Department of Health, (22nd May 2001) Private correspondence
(7) Department of Health, (17th Jan 1995) Private correspondence
(8) Pallis & Harley (1996) ABC of brainstem death, p46. BMJ Publishing
Group, London
Competing interests: No competing interests
Sir;
as we see from the rapid responses to Bill Hoffenberg's delightful
reminiscences, Britain has not been spared misunderstandings and
controversy over death and brain function. Skegg has chronicled the
confusion that followed the Conference of Medical Royal Colleges report in
1976, when the Conference was not asked, nor apparently was it able to
agree, whether the patient with brain death was dead, and so avoided
saying so until 1979; yet even the editor of the British Medical Journal
failed to notice the point in 1976, and declared that the Report 'sets out
clear guidelines for the diagnosis of death...'(1).
The only reason we
need to label patients without brain stem function dead is to make beating
-heart organ harvesting from them legal, and attempts to extend the label
dead to patients with what we now call persistent vegetative state were
not generally accepted (1). The major premise on which the Colleges have
argued the propriety of accepting brain death as death of the person has
always been the claimed inevitability that when brain stem function ceases
'the heart will stop beating shortly thereafter'(2). There is no
physiological reason why this should happen, and review of the published
evidence shows that it is not true (3).
A major danger of persisting with
this false premise is that more perceptive observers and critics of
medical practice have already noticed the discrepancy and have concluded
(inappropriately) that misdiagnoses are being made(4). I suggest that it
is time to revise the law, perhaps by a new Human Organ Transplant Act, to
allow family to give informed consent to beating-heart organ donation
under anaesthesia for patients certified to have irreversible loss of
brain stem function. The unanswerable semantic question of whether the
donor is dead would then disappear.
1/ Skegg PDG. Law, ethics and medicine. Oxford, Clarendon Press 1984.
2/ A Working Party of the Academy of Medical Royal Colleges. A Code of
Practice for the Diagnosis of Brain Stem Death. Department of Health,
1998.
3/ Shewmon DA. Chronic ‘brain death’: meta-analysis and conceptual
consequences. Neurology 1998;51:1538-45.
4/ Mason JK and McCall Smith RA. Law and Medical Ethics. London,
Butterworths 1999
Competing interests: No competing interests
Sir,
Might organ donation have contibuted to a complacany with the status quo
and a therapeutic nihilism in the management of head injuries? It is
acknowleged that the management of strokes in the NHS leaves much to be
desired. What of the management of head injuries?
How many patients who began to receive optimal care more than an
hour after their injuries might have survived had optimal care been
delivered sooner? How many more might have survived had the adequaxy of
their cerebral and systemic tissue oxygemation been monitored and
maintained in accordance with current concepts of the pathophysiology of
tissue oxygenation and the pathogeneis of multiple organ dysfunction and
failure? Might much earlier and more aggressive decompression in those
whose inadequacy of cerebral tissue oxygenation was due in part to the
development of an intracranial compartment syndrome have saved many
patients?
I suspect that many a donor has been the product of suboptimal care.
The onus is opon those dictating healthcare policy and the allocation of
resouces to ensure that patients with head injuries receive optimal care
on New Year's eve and other nights and holidays in addition to normal
working hours if they are to be considered potential organ donors.
Competing interests: No competing interests
Dear Sir,
There is something of the confessional in Hoffenberg's account [1] of
the first heart transplants. The enormous pressures put upon him by the
transplant team led by a man "egocentric, hardworking, clever, ambitious,
brash and somewhat arrogant", and by the political situation in South
Africa, swayed his judgement, allowing the removal of the beating heart
from the second "donor" (his use of inverted commas) although initially he
"could not agree to the removal of the heart of someone who still showed
signs of life". He questions the motives and ethics involved in both
procedures and the dubious benefits to the recipients.
He writes that "the process of removal, by which life was terminated,
began to worry the more thoughtful critics". A number remain worried.
Sadly, Hoffenberg still gives misinformation to support his cause. The UK
criteria of 1979 are on the basis that all functions of the brain have
permanently and irreversibly ceased; there is ample evidence, to which he
alludes, that some function often (if not always) remains. The series of
over 1,000 patients who did not survive on supportive measures were
diagnosed as brain dead on a variety of criteria - not on the present Code
of Practice protocol - and a significant number of pregnant mothers,
diagnosed as brain dead, have continued with support to the successful
delivery of their live child. It is an idiosyncratic opinion without
substance that "without function of the brain stem, life does not exist".
In addition, Coimbra has shown [2] that normothermia and the apnoea
test may administer the coup de grace to a recoverable patient. There is
divergence of opinion and practice by anaesthetists whether to give full
anaesthesia to supposedly dead organ donors [3]. For neither of these
procedures is consent required nor sought.
Perhaps Hoffenberg's revelations will at last serve to concentrate
minds on the paradoxes and deceptions with which prospective donors and
their families are faced in order to obtain their consent.
Yours faithfully,
David J. Hill
1 Hoffenberg R Christiaan Barnard: his first transplants and their
impact on concepts of death. BMJ 2001;323:1478-80
2 Coimbra Implications of ischaemic penumbra for diagnosis of brain
death. Braz Med Biol Res 1999;32:1479-87
3 Young PJ Matta BF Anaesthesia for organ donation - why bother?
(Editorial) Anaesthesia 2000;55:105-6
Competing interests: No competing interests
EDITOR - Hoffenberg's disclosures [1] are to be welcomed as a first-hand account capable of putting the record straight after too many years of misrepresentation of these surgical misadventures. However, his portrayal of his own role in the saga as "very minor" and "rather tenuous" is surely disingenuous. His involvement was, in fact, crucial to the success of the enterprise. His willingness, under whatever pressures, to pronounce (and presumably to certify) his patient "dead" while his heart was still beating - there being no agreed basis for so doing in any country at that time - provided the surgeons with a heart of sufficient viability to go on beating in the recipient for a further 18 months. That survival, miserable as it now appears to have been from the point of view of the recipient and his relatives, "led to a euphoric, uncontrolled epidemic of heart transplantation around the world" [2].
Many attempts have been made subsequently to re-define death, for transplant purposes, in terms of loss of brain function but, as several recent publications attest, the debate about their validity and practical application continues as vigorously as ever. There is certainly no international consensus. Views range from total non-acceptance in China, through legal recognition that "brain death" is distinct from death as traditionally understood and diagnosed in Japan [3] and the USA legal requirement that the whole of the brain shall be dead, to the idiosyncratic UK version. The highly controversial UK protocol, which used to be held to diagnose death of the brain stem, relies solely upon simple bedside tests including a dangerous apnoea test. It has never been accepted in the USA [4], nor in many European countries. And yet our Department of Health refuses to inform the public from whom it seeks prospective donors that there is this controversy, preferring to allow them to think that they will be really dead before their organs are removed.
Hoffenberg claims that the UK "definition has proved robust" and that it "has not evoked similar criticism" to that seen elsewhere in the world. That there has not been such open debate in this country as in some others cannot be denied. But, as will be seen from study of Potts's anthology [5], some of us have tried quite hard during the past twenty years to make the underpinning false assumptions and bad science more widely known.
David W. Evans (Cambridge, UK)
1 Hoffenberg R. Christiaan Barnard : his first transplants and their impact on concepts of death. BMJ 2001;323:1478-80
2 Smith T. Clinical freedom. BMJ 1987;295:1583
3 Morioka M. Reconsidering brain death : a lesson from Japan's fifteen years of experience.
Hastings Center Report 2001;31:41-46
4 Youngner SJ,Arnold RM. Philosophical debates about the definition of death : who cares?
Journal of Medicine and Philosophy (Issue title : Revisiting brain death)2001;26:530
5 Beyond Brain Death : the case against brain based criteria for human death. Eds. Potts M,Byrne PA,Nilges RG Kluwer Academic Publishers,2000,Dordrecht/Boston/London
Competing interests: No competing interests
The Vatican interests in head transplantation
I am curious to know why the Pope wanted to meet Barnard after he had
performed his first heart transplants and am even more curious to know why
in 1994 Dr Robert J White was made a member of The Pontifical Academy of
Sciences, an advisory body appointed by the Vatican, and apparently a
frequent visitor. Might Presidents Reagan, Bush, Clinton and Bush have had
knowlege of these matters given the very close collaboration between
Reagan and the Vatican in bringing about the demise of communism,
described in the offical biography of the Pope "His Holiness".
DR ROBERT J White, who was 75 three years ago, has spent his
profesional life devoted to the brain, both as a physician and in the
course of research backed by the city's Case Western Reserve University
where he is or was until vry recently Professor of Neurological Surgery.
His PhD at Harvard examined the effects of hemispherectomy, an operation
that has since been adapted for the treatment of epilepsy. He is evidently
known for his work on the appliction of cooling to the of brain function.
I obtained this information from the internet in my efforts to obtain
more information about the head transplant Professor Sir Raymond said he
had first hand evidence of being performed by Barnard. It transpires that
Dr White performed the first effective mammalian head transplant on March
14, 1970 at the Metrohealth Medical Centre in Cleveland, Ohio. The
experiment is said to have been successful in that the head woke up,
looked around by moving it's eyes, and took a bite off the end of one
researcher's fingers. It is also said that by cooling the brain to 50
degrees Dr White was able to keep the brain viable for at last an hour.
The many reports of complete recovery of brain function after submersion
in cold water for much longer periods suggests that viability might be
preserved for very much longer than an hour.
Dr White is said to have presented details of his experiements at the
Hammersmith. Furthermore Harold Hillman, former director of the Unity
Laboratory of Applied Neural Biology at the University of Surrey, is said
to have been a keen observer of White's work. A consultant at Bart's is
also said to have been privy to the information. There exists, therefore,
amongst reputable professionals in both the US and the UK and indeed
elsewhere knowlege of the degree to which the application of organ
preservation techniques might be profitably applied to the managment of
head injuries, cardiac arrests and other acute intracranial pathology.
Indeed hypothermia is one of the exclusion criteria in establishing the
clinical and legal diagnosis of brain death before harvesting organs for
transplantation.
Why have these data not been considered in the development of
clinical and legal criteria for establishing brain death? If they have why
have the data not been made available to all those managing head injuries
and other acute intracranial pathology? Might it be that religious bodies
or the fear of offending the religious have lead to the suppression of
this information just as Gallileo's works were suppresed for several
centuries until very late in the 20th century. Might it alternatively be
that anecdotes do not provide a good enough evidence-base for doing so or
that the topic has been deemed politically incorrect? Might it be that the
US and the Vatican and even South Africa have been collaborating in the
investigation of the covert use and abuse of advances in cognitive
neuroscience?
If anyone knows the answers to those questions as they might apply to
clinicans it should be Professor Sir Raymond Hoffenberg given his
extended access to priviledged mdical information. He must have been
aware of the results of head transplantation for almost 40 years.
Competing interests:
None declared
Competing interests: No competing interests