|
|
| Introduction |
|
|
|
| This
chapter
describes
the
origins
and
objectives
of
the
joint
programme,
the
leadership
of
the
programme,
the
initial
research
application
and
the
sourcing
of
brains
in
the
first
three
years.
|
|
|
|
| It
was
to
this
research
programme
that
the
brain
of
Mr
Isaacs
was
taken
on
27 February
1987
after
the
Coroner's
post
mortem
examination
at
Prestwich
mortuary.
|
|
|
|
| Prior
to
the
start
of
the
joint
programme,
Dr
Slater
had
begun
research
into
Alzheimer's
disease
for
which
brain
samples
had
been
obtained
from
a
number
of
sources.
Some
of
these
samples
appear
to
have
been
listed
in
the
first
of
the
brain
books.
See
below.
|
|
|
|
| The
joint
research
programme,
organised
by
the
Departments
of
Psychiatry
and
Physiology,
started
in
1985.
|
|
|
|
| Leaders
of
the
joint
research
team
|
|
|
|
| The
research
programme
was
jointly
led
by
Dr
J
F
W
Deakin,
Senior
Lecturer,
later
Professor,
in
the
Department
of
Psychiatry,
Dr
Paul
Slater,
Reader
in
Physiology,
and
initially
also
by
Dr Alan
Cross,
Lecturer
in
Neurochemistry
in
the
Department
of
Physiology.
|
|
|
|
| Dr
J
F
W
Deakin |
|
|
|
| Dr
Deakin
was
appointed
Senior
Lecturer
in
the
Academic
Department
of
Psychiatry
of
Manchester
University
in
the
autumn
of
1983.
|
|
|
|
| Before
moving
to
Manchester
Dr
Deakin
had,
from
1978,
held
a
Joint
Clinical-Scientific
Member
of
Staff
appointment
at
the
Clinical
Research
Centre
(CRC).
The
Centre
was
a
major
MRC
research
institute
attached
to
Northwick
Park
Hospital.
Dr Deakin
had
held
an
Honorary
Senior
Registrar
appointment
at
the
hospital
while
his
research
was
almost
entirely
laboratory-based.
|
|
|
|
| For
his
clinical
responsibilities
in
Manchester,
Dr
Deakin
worked
at
the
University
Hospital
of
South
Manchester.
|
|
|
|
| Dr
Paul
Slater |
|
|
|
| Dr
Slater
was
appointed
Reader
in
Physiology
at
Manchester
University
in
1983.
|
|
|
|
| Dr
Alan
Cross |
|
|
|
| Dr
Cross
was
appointed
Lecturer
in
Neurochemistry
in
the
Department
of
Physiology
at
Manchester
University
in
1984.
Before
taking
up
this
appointment,
Dr
Cross
had
also
worked
at
the
CRC
as
a
post-doctoral
scientist
from
1979
until
1984.
Dr
Cross
left
the
team
early
in
the
joint
programme
and
before
the
first
progress
report.
|
|
|
|
| Origins
of
the
joint
research
programme
|
|
|
|
| In
1985
there
were
a
number
of
research
programmes
in
this
country
and
abroad
that
collected
brains.
Before
moving
to
Manchester
both
Dr
Deakin
and
Dr
Cross
had
been
involved
in
brain
research
at
the
CRC.
The
CRC
programme,
which
had
included
the
collection
of
brains,
was
led
by
Dr
Tim
Crow,
Head
of
the
Mental
Illness
Division,
and
Dr
Eve
Johnstone.
|
|
|
|
| After
Dr
Deakin
and
Dr
Cross
moved
to
Manchester,
they
had
a
shared
research
interest
in
neurochemical
research
on
the
brain
with
Dr
Slater.
From
that
shared
interest
the
joint
brain
research
programme
was
planned
and
developed.
|
|
|
|
| Objectives
|
|
|
|
| The
main
focus
of
the
joint
research
programme
was
the
investigation
of
neurochemistry
in
different
parts
of
the
brains
of
patients
who
had
exhibited
in
life
well
defined
psychiatric
or
neuro
degenerative
conditions.
In
1985
brain
neurochemistry
had
not
been
investigated
in
many
psychiatric
disorders.
|
|
|
|
| Alzheimer's
disease
and
schizophrenia
were
the
conditions
identified
in
the
first
applications
to
the
North
West
Regional
Health
Authority
(NWRHA)
and
the
Medical
Research
Council.
|
|
|
|
| There
were
a
number
of
large
hospitals,
for
patients
with
neuropsychiatric
disorders
and
mental
handicap
conditions,
in
and
near
Manchester
in
1985.
Many
were
long-stay
patients
with
Alzheimer's
disease,
schizophrenia
and
other
mental
conditions.
|
|
|
|
| The
joint
research
programme
was
planned
to
study
these
patients
in
life
and
link
in-life
findings
to
post
mortem
neurochemistry
of
the
brain.
|
|
|
|
| Methodology |
|
|
|
| Brains
were
to
be
collected
to
provide
a
bank
of
specimens
for
the
joint
programme.
The
method
of
brain
collection
was
expected
to
adopt
procedures
similar
to
those
of
the
brain
research
programme
at
the
CRC,
with
which
Dr Deakin
and
Dr
Cross
were
familiar.
|
|
|
|
| One
CRC
programme,
for
example,
had
collected
the
brains
of
patients
with
schizophrenia
who
died
in
Shenley,
a
long-stay
mental
hospital.
Similar
clinical
and
post
mortem
arrangements
were
already
in
use
in
Manchester
by
the
Cerebral
Function
Unit
as
described
in
Chapter
8.
|
|
|
|
| The
collection
method
in
Manchester
was
therefore
planned
to
follow
methods
used
in
contemporary
research
elsewhere
in
this
country.
|
|
|
|
| The
CRC
research
programme
is
discussed
in
Chapters
31
and
32
but
two
features
should
be
noted:
|
|
|
|
1) the
consent
of
the
relatives
for
brain
retention
had
been
obtained
routinely
in
the
CRC
schizophrenia
study
of
patients
at
Shenley
Hospital.
The
only
exceptions
had
been
for
deceased
patients
with
no
known
relatives.
In
accordance
with
HM(61)98
the
Hospital
Secretary
was
approached
for
his
consent;
|
|
2) the
brains
of
persons
who
had
died
of
unrelated
diseases
were
not
collected
by
the
CRC
research
team.
Instead
'controls'
were
obtained
from
the
Corsellis
collection,
Chapters
31-33.
|
|
|
|
| No
histological
report |
|
|
|
| A
significant
difference
between
the
joint
research
programme
and
the
methodology
of
the
Cerebral
Function
Unit
was
that
no
histological
examinations
were
undertaken.
Dr
Slater
has
indicated
that
some
samples
were
sent
by
Dr
Cross
to
the
Pathology
Department,
adding
'with
the
dearth
of
neuropathologists
the
delays
in
getting
answers
just
took
far
too
long
and
we
were
forced
to
abandon
attempts'.
Both
Dr Slater
and
Professor
Deakin
emphasised
that
histology
in
schizophrenia
would
not
be
informative.
Professor
Deakin
states
that
'histology
could
not
have
been
the
primary
reason
for
retention
of
the
whole
brain
in
any
post-mortem
brain
programme
researching
schizophrenia
in
the
UK'.
However,
some
other
contemporaneous
programmes
undertook
histology
as
a
matter
of
routine.
|
|
|
|
| Another
significant
difference
between
the
methodology
of
the
Cerebral
Function
Unit
and
the
joint
programme
was
that
no
reports
were
sent
to
the
doctor
who
looked
after
the
deceased
before
death.
Dr
Slater
states
that
'the
fact
is
that
we
never
intended
to
do
this
and
had
never
been
asked
by
anyone
to
do
so'.
|
|
|
|
| Dr
Slater
recollects,
however,
that
on
more
than
one
occasion
messages
were
received
from
the
relatives
via
the
Coroner's
office
to
ask
if
anything
unusual
had
been
discovered
during
examination,
as
there
had
been
doubts
about
old
diagnosis
or
possible
exposure
to
occupational
diseases.
The
circumstances
of
these
enquiries
are
not
mentioned
in
the
brain
books.
|
|
|
|
| Research
proposals |
|
|
|
| The
first
of
three
research
applications
submitted
to
the
Locally
Organised
Clinical
Research
Scheme
of
the
North
West
Regional
Health
Authority
in
May
1985
describes
the
initial
proposals
of
the
joint
programme.
|
|
|
|
| This
application,
entitled
'An
Investigation
of
Amino
Acid
Neurotransmitters
in
the
Temporal
Lobe
of
Brain
in
Alzheimer's
Disease
and
Schizophrenia'
was
submitted
by
Dr
Deakin,
Dr
Cross
and
Dr
Slater.
A
grant
for
three
years,
to
start
in
October
1985,
was
requested.
|
|
A
preambular
paragraph
states
'At
present
there
is
no
funding
for
collaborative
projects
between
Psychiatry
and
Physiology'.
|
|
| Features
of
the
application
that
are
common
to
later
applications
to
the
NWRHA
|
|
|
|
| Normal
and
diseased
brains
would
be
studied:
|
|
|
|
| 'It
is
proposed
to
apply
these
techniques
to
study
amino
acid
neurotransmission
in
the
human
temporal
lobe
of
post-mortem
brains
of
those
without
brain
disease
and
those
with
Alzheimer's
disease
and
schizophrenia'.
|
|
|
|
| Brains
would
be
obtained
from
a
number
of
hospitals
in
or
near
Manchester:
|
|
|
|
| '…
studies
of
normal
brain
will
be
an
essential
part
of
the
investigation.
Brains
from
subjects
with
no
history
of
neuropsychiatric
disorders
will
be
obtained
from
Manchester
Royal
Infirmary
(MRI).
We
have
secured
a
formal
arrangement
with
the
Department
of
Pathology
which
allows
us
access
to
brains
removed
at
post-mortem
examination
and
within
a
few
hours
of
death.
We
have,
in
storage,
brains
from
patients
with
pathologically-confirmed
Alzheimer-type
dementia
that
are
obtained
via
the
Pathology
Department.
These
will
be
supplemented
for
this
project
by
brains
from
subjects
with
Alzheimer's
disease
from
the
Pre-Senile
Dementia
Unit
at
Prestwich
Hospital.
Arrangements
have
been
made
with
Dr D Neary
(MRI),
the
administrator
of
the
Unit
and
Dr
I
Stout,
the
Consultant
in
charge
for
the
supply
of
brains
whenever
pre-mortem
consent
has
been
obtained.
A
similar
arrangement
exists
with
Dr
S
D
Soni,
Consultant
Psychiatrist
at
Prestwich
Hospital,
for
brains
from
subjects
with
clinically-confirmed
schizophrenia
…
Post-mort em
brains
may
also
be
obtained
from
Withington
Hospital.'
|
|
This
extract
is
taken
verbatim
from
the
application
submitted
to
NWRHA.
However,
it
is
contested
by
Professor
Neary
and
Dr
Stout.
|
|
|
|
| Professor
Neary
states
in
a
letter
to
me
dated
3
January
2003
'that
the
CFU
and
the
schizophrenia
groups
were
and
are
seen
in
practice
to
be
independent
is
attested
by
the
decision
of
clinicians
such
as
Dr
Ian
Stout,
who
has
supported
my
work
in
dementia
for
over
20
years,
not
to
take
part
in
the
schizophrenia
project.
|
|
|
|
| I
do
not
consider
myself
as
having
taken
part
in
a
collaboration
and
I
remain
uninformed
about
the
workings
of
the
schizophrenia
group.
The
latter
has,
I
understand,
sought
some
pathological
assistance
from
David
Mann,
which
was
minimal
and
non-reciprocal'.
|
|
Dr
Stout
in
a
letter
dated
10
January
2003
states
'At
no
time
that
I
can
remember
was
I
ever
approached
to
participate
in
a
formal
research
study'.
|
|
|
|
| On
the
matter
of
consent
by
the
relatives,
Dr
Stout
emphasises
'the
only
such
examinations
that
I
was
aware
of
were
on
those
patients
whose
families
had
already
provided
me
with
written
consent
that
they
would
be
investigated
thereafter
by
Professor
Neary
and
Professor
Mann
and
colleagues,
but
no
other'.
|
|
|
|
| Dr
Stout
adds
'I
have
absolutely
no
idea
whatsoever
as
to
what
was
meant
by
the
statement
'arrangements
have
been
made
with
Dr
D
Neary
(MRI),
the
administrator
of
the
Unit,
and
Dr
I
Stout'
'.
|
|
|
|
| Dr
Stout
does
not
recall
any
subsequent
request
in
the
late
1980s
from
the
joint
research
team
to
provide
clinical
material
or
extract
information
from
case
notes.
|
|
|
|
| For
further
details
of
the
CFU
programme,
see
Chapter
8.
|
|
|
|
| The
brain
collection
and
investigations
would
be
in
the
neurochemical
laboratories
in
the
Department
of
Physiology
|
|
|
|
| The
brains
would
be
held
in
the
neurochemical
laboratories
of
the
Department
of
Physiology
in
the
Medical
School.
|
|
|
|
| Clinicians
would
be
contacted
and
case
records
would
be
accessed |
|
|
|
| 'The
post-doctoral
worker
will
be
expected
to
liase
with
the
clinicians
and
mortuary
staff
who
are
providing
the
clinical
material
for
the
project,
and
to
extract
the
information
relevant
to
the
diagnoses
from
the
case
notes'.
|
|
|
|
| In
practice,
for
patients
who
died
in
hospital
the
case
notes
were
later
obtained
by
the
research
team.
When
brains
were
obtained
from
cases
of
sudden
death
reported
to
the
Coroner,
the
deceased's
general
practitioner
would
usually
be
identified
through
the
information
available
to
the
pathologist
at
the
time
of
the
post
mortem.
The
mortician
would
include
the
name
of
the
GP
in
the
form
that
accompanied
the
brain
to
Manchester
University.
|
|
|
|
| Where
the
general
practitioner
was
not
known
at
the
time
of
the
post
mortem,
the
research
team
would
write
to
the
relevant
Family
Practitioner
Committee
in
order
to
identify
the
general
practitioner
who
would
then
receive
a
copy
of
the
letter
requesting
details
of
the
deceased's
mental
health
and
medication.
|
|
|
|
| Two
relevant
matters
were
not
included
in
the
first
application
|
|
|
|
| Ethics
Committee
Referral |
|
|
|
| Ethics
Committee
referral
was
not
mentioned
in
the
first
application
to
the
NWRHA
but
was
included
in
a
later
application
to
the
authority
for
an
extension
of
the
original
grant.
Ethics
Committee
applications
are
described
in
Chapters
12-15.
|
|
|
|
| Coroners'
Cases |
|
|
|
| The
inclusion
of
brains
obtained
from
post
mortems
ordered
by
the
Coroner
is
not
mentioned
in
this
or
subsequent
applications
to
the
NWRHA.
The
retention
of
brains
from
Coroners'
cases
from
the
North
Manchester
coronial
district
is
described
in
Chapter
10.
|
|
|
|
| Award
of
the
NWRHA
grant
|
|
|
|
| The
research
application
was
approved
after
scientific
referees
had
been
consulted
and
the
project
began
in
October
1985.
|
|
|
|
| Progress
October
1985
-
February
1988
|
|
|
|
| Brains
collected |
|
|
|
| The
first
brain
collected
for
the
joint
programme
and
coded
in
the
brain
book
as
85/01(1),
was
obtained
from
Prestwich
mortuary
on
1
November
1985.
The
number
of
brains
obtained
in
the
first
three
years
of
the
programme
by
mortuary
were:
|
|
|
|
| This
illustrates
the
heavy
predominance
of
Coroners'
cases
in
the
first
three
years
of
the
programme,
which
continued
in
the
following
eight
years.
The
inclusion
of
Coroners'
cases
was
not
mentioned
in
the
applications
to
the
NWRHA
and
the
MRC
in
1988
and
1989.
However,
the
involvement
of
the
'Rochdale
Coroner'
was
referred
to
in
the
1989
application
to
the
Mental
Health
Foundation.
|
|
|
|
| Research
reports
and
subsequent
applications
to
the
NWRHA
|
|
|
|
| June
1987 |
|
|
|
| A
progress
report
on
the
research
grant
awarded
following
the
application
made
in
May
1985,
was
submitted
to
the
NWRHA
by
Dr
Deakin
and
Dr Slater.
This
included
a
request
for
additional
funds
to
take
account
of
new
developments
and
stated
'We
have
made
considerable
progress
towards
the
aims
set
out
in
the
original
application'.
'Recently,
we
have
secured
a
large
number
of
samples
from
the
Cambridge
Brain
Bank
and
work
on
schizophrenia
will
therefore
be
expanded'.
|
|
| February
1988 |
|
|
|
| A
further
progress
report
stated
'We
have
obtained
brain
samples
from
control
subjects
and
from
subjects
with
clinically
diagnosed
schizophrenia
from
the
Cambridge
Brain
Bank
laboratory'.
The
report
recorded
'very
exciting
findings
and
we
have
been
fortunate
in
securing
from
the
Clinical
Research
Centre,
Northwick
Park
Hospital,
brain
samples
from
a
particularly
well-defined
group
of
schizophrenic
subjects'.
It
is
not
clear
in
this
report
whether
the
control
samples
were
obtained
from
the
Cambridge
brain
bank
or
collected
locally.
|
|
|
|
| The
award
of
a
Wellcome
Trust
Fellowship
was
also
reported.
|
|
|
|
|
March
1988
|
|
|
|
| A
second
grant
application
was
submitted
to
the
NWRHA.
|
|
|
|
| Plans
to
expand
the
programme
|
|
|
|
| Between
November
1985
and
March
1988,
the
promising
results
reported
in
the
two
progress
reports
to
the
NWRHA
encouraged
the
team
to
expand
the
work.
This
expansion
required:
|
|
|
|
|
i.
additional
research
funding,
Chapter
11;
|
|
|
ii.
an
increase
in
the
number
of
brains
obtained
for
the
programme.
Action
taken
to
increase
the
number
of
brains
collected
is
described
in
Chapters
14
and
15.
|
|
|
|
| Summary |
|
|
|
| The
joint
research
team
began
working
on
the
programme
in
1985.
The
team
leaders
were
Dr
Deakin
in
the
Department
of
Psychiatry,
Dr
Cross
and
Dr
Slater
in
the
Department
of
Physiology.
|
|
|
|
| The
system
for
brain
collection
was
planned
to
adopt
the
procedures
that
had
been
in
place
at
the
Clinical
Research
Centre,
Northwick
Park,
where
Dr
Deakin
and
Dr
Cross
had
previously
worked.
|
|
|
|
| The
programme
would
involve
the
collection
of
brains
of
patients
with
Alzheimer's
disease
and
schizophrenia
who
died
in
mental
hospitals
in
the
Manchester
area.
|
|
|
|
| Pre-mortem
consent
from
relatives
was
planned.
|
|
|
|
| Brains
from
'normal'
persons
without
any
evidence
of
mental
or
neurological
disease
were
to
be
collected
as
'controls'.
|
|
|
|
| Where
the
deceased's
general
practitioner
was
not
identified
at
the
time
of
post
mortem,
the
Family
Practitioner
Committee
would
be
asked
for
this
information.
|
|
|
|
| Initial
funding
was
obtained
from
the
NWRHA.
A
brain
bank
was
established
in
the
Department
of
Physiology.
|
|
|
|
| Good
scientific
progress
followed.
Novel
and
'very
exciting
findings'
encouraged
the
team
to
develop
their
work
and
apply
for
further
NWRHA
grants.
|
|
|
|
| Some
brain
specimens
were
obtained
from
the
Cambridge
and
Northwick
Park
brain
banks.
|
|
|
|
| Referral
to
Ethics
Committees
was
not
mentioned
in
the
1985
application
or
the
1987
and
1988
reports
to
the
NWRHA.
|
|
|
|
| The
collection
of
brains
from
Coroners'
cases
was
not
mentioned
in
any
of
the
applications
or
reports
to
the
NWRHA
between
1985
and
1988.
|
|
|
|
| The
collection
of
brains
from
Coroners'
cases,
set
out
in
Chapter
10,
was
a
major
feature
of
the
programme
and,
in
view
of
the
large
proportion
of
brains
collected
from
Coroners'
cases,
should
have
been
mentioned
in
the
reports
to
the
NWRHA.
|
|
|
|
| Reference |
|
|
|
| 1 Entry
in
the
brain
books. |
|
