e
p
o
s
a
ú
d
e
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ú
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l
i
c
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www.else ie .p / psp
O iginal
a icle
E hical
and
legal
challenges
o
pe sonalized
medicine:
Pa adigma ic
examples
o
esea ch,
p e en ion,
diagnosis
and
ea men 夽
João
V.
Co dei o
Escola
Nacional
de
Saúde
Pública,
Uni e sidade
No a
de
Lisboa
and
Cen o
de
Es udos
Sociais
da
Uni e sidade
No a
de
Lisboa;
CESNOVA,
Cen o
de
Es udos
de
Sociologia
da
Uni e sidade
No a
de
Lisboa,
Lisbon,
Po ugal
a
i
c
l
e
i
n
o
A icle
his o y:
Recei ed
28
July
2014
Accep ed
9
Oc obe
2014
A ailable
online
18
No embe
2014
Keywo ds:
Pe sonalized
medicine
Biobanks
Gene ics
Genomics
Gene ic
es s
Gene
he apy
Public
heal h
law
and
e hics
a
b
s
a
c
This
a icle
o e iews
he
impo an
e hical
and
legal
challenges
o
di e en
s eps
o
he
pe sonalized
medicine
jou ney
such
as
esea ch,
p e en ion,
diagnosis
and
ea men
by
discussing
pa adigma ic
examples
including
biobanks,
gene ic
es s
and
gene
he apy.
Sci-
en ific
p og ess
in
he
a ea
o
gene ics,
he
comple ion
o
he
Human
Genome
P ojec
and
he
abili y
o
sequence
genomes
o
compe i i e
p ices
ha e
o e ed
he
p omise
o
e olu ion-
izing
heal hca e
and
aised
impo an
challenges
o
classical
pa adigms
in
he
biomedical
law
and
e hics
fields.
Issues
such
as
in o med
consen ,
p i acy
and
confiden iali y,
and
disc imina ion
equi e
pa icula
analysis
in
his
con ex .
In
he
las
yea s
he
concep
o
pe sonalized
medicine
has
been
a
sou ce
o
conside able
hype
and
hope.
Law
and
e hics
should
be
impo an
allies
o
limi
he
o me
and
po en ia e
he
la e .
©
2014
Escola
Nacional
de
Saúde
Pública.
Published
by
Else ie
España,
S.L.U.
All
igh s
ese ed.
Desafios
é icos
e
legais
da
medicina
pe sonalizada:
exemplos
pa adigmá icos
de
in es igac¸ão,
p e enc¸ão,
diagnós ico
e
a amen o
Pala as-cha e:
Medicina
pe sonalizada
Biobancos
Gené ica
Genómica
Tes es
gené icos
Te apia
génica
Di ei o
e
é ica
em
saúde
pública
e
s
u
m
o
Es e
a igo
suma iza
alguns
dos
desafios
é ico-legais
mais
impo an es
das
di e en es
e apas
da
medicina
pe sonalizada,
pa indo
da
in es igac¸ão,
passando
pela
p e enc¸ão
e
pelo
diagnós ico,
e
e minando
no
a amen o.
Es a
análise
é
ealizada
a a és
da
dis-
cussão
de
exemplos
pa adigmá icos
de
cada
e apa,
como
os
biobancos,
os
es es
gené icos
e
a
e apia
génica.
O
p og esso
cien ífico
na
á ea
da
genómica,
a
finalizac¸ão
do
P o-
je o
do
Genoma
Humano
e
a
capacidade
de
sequencia
genomas
in ei os
a
p ec¸os
cada
ez
mais
compe i i os
o igina am
a
p omessa
de
e oluciona
a
á ea
da
saúde
e
colo-
ca am
desafios
impo an es
a
alguns
concei os
adicionais
nas
á eas
da
é ica
e
do
di ei o
biomédico.
Consequen emen e,
emas
como
o
consen imen o
in o mado,
a
p i acidade
e
夽Sec ions
2
and
3
o
his
a icle
a e
based
on
and
con inue
he
wo k
s a ed
in
Fa ia,
PL
and
Co dei o,
JV
“Public
Hea h:
e hical
and
legal
challenges
in
a
nu shell”.
In:
Yann
Joly
&
Ba ha
Ma ia
Knoppe s,
eds.,
Rou ledge
Handbook
o
Medical
Law
and
E hics,
Rou ledge,
2014.
E-mail
add ess:
joao.co dei [email protected]
h p://dx.doi.o g/10.1016/j. psp.2014.10.002
0870-9025/©
2014
Escola
Nacional
de
Saúde
Pública.
Published
by
Else ie
España,
S.L.U.
All
igh s
ese ed.
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
165
a
confidencialidade
e
a
disc iminac¸ão
exigem
uma
análise
a en a
e
pa icula
nes e
con-
ex o.
Nos
úl imos
anos,
o
concei o
de
medicina
pe sonalizada
em
sido,
simul aneamen e,
uma
on e
de
expe a i as
exage adas
e
de
g ande
espe anc¸a.
O
di ei o
e
a
é ica
de em
se
aliados
undamen ais
pa a
limi a
as
p imei as
e
po encia
a
úl ima.
©
2014
Escola
Nacional
de
Saúde
Pública.
Publicado
po
Else ie
España,
S.L.U.
Todos
os
di ei os
ese ados.
In oduc ion
Pe sonalized
medicine
is
a
e m
ha
e e s
o
medicine
ha
is
specifically
designed
o
a
gi en
indi idual
based
on
i s
genomic
in o ma ion.1In
he
las
yea s,
pa icula ly
since
sequencing
genomes
le
he
ealm
o
science
fic ion
and
became
a
ac
o
li e,
he
concep
o
indi idualized
heal hca e
has
become
a
sou ce
o
g ea
hope.
In
pa allel,
he
capaci y
o
use
gene ic
da a
o
de elop
specific
ailo -made
he apies
in
he
immedia e
u u e
has
been
g ea ly
exagge a ed
by
some,
gene a ing
un ounded
hype.
In
o de
o
sepa a e
hype
om
hope
in
his
con ex
we
mus
s i e
o
ully
unde s and
and
no
unde es ima e
bo h
he
po en ial
and
he
limi a ions
o
cu en
knowledge
abou
he
gene ic
basis
o
disease.
Wi h
ha
in
mind,
he e
is
li le
doub
ha
he
ad ances
in
gene ics
and
genomics
in
ecen
decades
ha e
been
ou s anding.
O
hese,
he
Human
Genome
P ojec
(HGP),
due
o
i s
massi e
dimension
and
he
unp eceden ed
a en ion
i
ecei ed
om
ou side
he
scien ific
communi y
has
pola ized
mos
discussions.2,3 Howe e ,
i espec i e
o
how
en husias ic
o
skep ical
we
a e
abou
he
p og ess
ha
he
HGP
has
al eady
o ged,
we
mus
no
isola e
his
p ojec
om
o he
wo k
–
pas ,
p esen
and
u u e.4
A
global
analysis
o
he
ad ances
in
he
a ea
o
gene ics
and
genomics
highligh s
one
end
ha
is
common
o
mos
sci-
en ific
and
echnological
p og ess
–
exponen ial
p og ession.
This
end
can
be
illus a ed
by
a
popula
anecdo e
abou
he
o igin
o
he
boa d
game
o
chess.
The
s o y
goes
ha
some-
ime
du ing
he
6 h
cen u y
a
izie
made
an
ex ao dina y
o e
o
an
Indian
ule :
a
beau i ul
chessboa d.
The
king
was
so
imp essed
by
i
ha
he
ga e
he
izie
he
possibili y
o
choose
any
p esen
o
his
liking.
Used
o
be
me
wi h
ex a -
agan
eques s,
he
king
was
su p ised
when
he
izie
asked
o
a
g ain
o
whea
o
he
fi s
squa e
o
he
chessboa d,
wo
g ains
o
he
second,
ou
o
he
hi d,
and
so
on,
doubling
he
amoun
o
whea
o
each
new
squa e.
Unawa e
o
he
con-
sequences,
he
king
o de ed
his
men
o
calcula e
he
amoun
o
whea
necessa y
o
sa is y
he
izie ’s
eques
and
gi e
i
o
him
as
p omised.
As
he
calcula ion
was
comple ed,
he
king
ealized
i
was
no
possible
o
find
enough
whea
in
he
en i e
wo ld
o
sa is y
he
eques .5
Like
he
king
in
his
s o y,
mos
o
us
do
no
easily
g asp
he
ull
implica ions
o
he
exponen ial
unc ion
a
fi s .
I
is
mo e
in ui i e
o
hink
in
linea
e ms.
The e o e,
as
ad ances
in
sci-
ence
a e
some imes
w ongly
placed
in
a
linea
scale
ins ead
o
in
an
exponen ial
one,
u u e
con ex
is
no
p ope ly
e al-
ua ed
and
es ima ions
o
u u e
amifica ions
miss
he
poin .
Almos
eigh
millennia
wen
by
be ween
he
ag icul u al
and
he
indus ial
e olu ions.
Ye ,
only
one
hund ed
and
wen y
yea s
passed
be ween
he
indus ial
e olu ion
and
he
c e-
a ion
o
he
ligh
bulb.6Human
communica ion
in
oday’s
wo ld
is
la gely
web-based
bu
he
in e ne
was
only
launched
wo ldwide
less
han
25
yea s
ago.7
The
same
p inciple
applies
o
p og ess
in
he
a ea
o
gene -
ics
and
genomics.
Following
on
cen u ies
o
ques ioning
ha
led
o
Mendel’s
laws
o
gene ics
in
he
second
hal
o
he
nine-
een h
cen u y,
i al
b eak h oughs
eme ged
in
he
las
fi y
o
six y
yea s.
These
include
he
disco e y
o
he
s uc u e
o
DNA,
which
was
epo ed
in
1953
and
he
gene ic
code
in
1966,
which
led
o
he
es ablishmen
o
he
so-called
“cen-
al
dogma”
o
molecula
biology
(DNA
makes
RNA
makes
P o ein).4,8,9 A
decade
o
so
la e ,
Sange
and
o he s
de eloped
DNA
sequencing
me hods.10 In
1991
he
HGP
was
launched
and
in
2003
i
was
finished.2,11 In
he
las
decade,
he
genomes
o
di e en
species
ha e
been
sequenced
–
including
he
fi s
human
pe sonal
genome
in
2008
–
and
he
fi s
syn he ic
genome
was
p oduced
and
used
o
s a
up
a
bac e ial
cell.4,12
Also,
di e en
p ojec s
ha e
sp ou ed
om
hese
ad ances,
such
as
he
sequencing
o
disease
genomes,
including
can-
ce ,
he
de elopmen
o
biobanks
o
he
o e ing
o
gene ic
es s
di ec ly
o
consume s.4Hence,
in
science
in
gene al
and
in
gene ics
and
genomics
in
pa icula ,
p og ess
is
happening
as
and
i s
amifica ions
a e
mul iple
and
di ficul
o
es ima e
and
p edic .
This
a icle
aims
o
analyze
and
discuss
ele an
challenges
posed
o
law
and
e hics
by
some
o
he
ad ances
in
gene -
ics
and
genomics
and
he
possibili y
o
achie ing
meaning ul
pe sonalized
medicine
in
he
u u e.
Much
has
been
w i -
en
abou
he
ad en
o
genomics
and,
pa icula ly,
abou
i s
e hical
and
legal
implica ions.3The
conclusions
in e wine
wi h
de elopmen s
in
o he
scien ific
a eas
and
wi h
b oade
socioeconomic
ans o ma ions,
which
in ol e
complex
issues
such
as
p i acy,
libe y,
disc imina ion
and
ma ke
eco-
nomics.
The e o e,
his
a icle
can
only
aim
o
o e
a
gene al
analysis
on
his
opic.
I
aims
o
discuss
di e en
s eps
o
he
pe sonalized
medicine
jou ney
h ough
a
law
and
e hics
lens,
including
esea ch,
p e en ion
and
diagnosis,
and,
finally,
ea men .
The
examples
ha
will
be
discussed
o
each
s ep
a e
biobanks,
gene ic
es s
and
gene
he apy,
espec i ely.
Resea ch:
biobanks
Biobanks,
which
in
gene al
e ms
can
be
desc ibed
as
o ga-
nized
collec ions
o
biological
ma e ial
and/o
associa ed
in o ma ion,
can
a y
significan ly
in
e ms
o
na u e,
size,
aim,
du a ion,
owne ship
o
go e nance
model.13 This
a i-
a ion
con ibu es
o
he
di ficul y
in
selec ing
clea
and
p ecise
legal
defini ions,
which
a e
impo an
o
es ablishing
166
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
adequa e
egula o y
egimens.
In
he
las
yea s,
biomedical
esea ch
biobanks
ha e
gained
imp essi e
momen um,
pa -
icula ly
because:
(i)
hey
acili a e
he
es ing
o
basic
science
obse a ions
in
samples
wi h
clinical
ele ance;
(ii)
expand
access
o
a
la ge
numbe
o
samples
con e ing
g ea e
signi -
icance
o
esea ch
s udies;
(iii)
gua an ee
uni o miza ion
o
sample
p epa a ion
and
imp o e
ep oducibili y
o
esea ch
esul s;
(i )
po en ia e
esea ch
collabo a ions
be ween
scien-
is s,
clinicians,
e hicis s
and
o he
p o essionals.14,15
In
e ms
o
e hical
and
legal
challenges,
he
deba e
has
in ensified
since
he
his o ic
case
o
he
na ional
DNA
da abase
in
Iceland,
which
ecei ed
legal
suppo
by
he
1998
Ac
on
Heal h
Sec o
Da abase
(HSD)
o
he
na ional
Pa lia-
men .
Such
Ac
allowed
he
cons i u ion
o
a
na ion-wide
biobankaand
i s
licensing
o
a
p i a e
company,
deCODE
Gene ics.
These
ac s
aised
significan
conce ns,
namely
ela ed
o
p i acy
o
indi iduals
included
in
he
da abank,
he
selec ed
in o med
consen
p ocesses
and
he
possible
col-
lision
be ween
public
in e es
and
p ofi -o ien ed
company
in e es s.16,17,bSince
he
Icelandic
HSD
case
g ea
discus-
sion
su ounding
he
e hical,
legal
and
social
issues
and
implica ions
o
esea ch
biobanks
has
ensued.
In
summa y,
hese
issues
a e
a ied
and
can
use ully
be
di ided
in
main
clus e s
as
Solbakk
and
o he s
ha e
sugges ed18:
(i)
issues
conce ning
how
biological
ma e ials
a e
en e ed
in o
he
bank;
(ii)
issues
conce ning
esea ch
biobanks
as
ins i u ions;
(iii)
issues
conce ning
unde
wha
condi ions
esea che s
can
access
ma e ials
in
he
bank;
p oblems
conce ning
owne ship
o
biological
ma e ials
and
o
in ellec ual
p ope y
a ising
om
such
ma e ials;
(i )
issues
ela ed
o
he
in o ma ion
collec ed
and
s o ed,
e.g.
access- igh s,
disclosu e,
confiden iali y,
da a
secu i y,
and
da a
p o ec ion.
As
hese
au ho s
poin
ou
he e
is
conside able
o e lap
be ween
clus e s
and
ce ainly
all
a e
e y
ele an .
This
a i-
cle
will
ocus
on
he
challenges
o
in o med
consen
and
o
p i acy
and
confiden iali y.
In o med
consen
is
he
co ne s one
o
biomedical
e hics19
and,
in
mos
coun ies,
pa icipa ion
in
a
biobank
o
esea ch
pu poses
equi es
in o med
consen
p ocedu es,
as
does
pa icipa ion
in
mos
esea ch
p ojec s
ha
equi e
he
use
o
biological
ma e ial.20,21 This
equi emen
cons i u es
one
o
he
mos
undamen al
no ms
o
esea ch
egula ion,
which
is
condensed
in
he
fi s
sen ence
o
he
Nu embe g
Code:
“The
olun a y
consen
o
he
human
subjec
is
absolu ely
essen ial”.22 Acco dingly,
he
main
in e na ional
law
and
e hics
no ma i e
ins umen s
ela ed
o
esea ch
on
gene ic
da a
ei he
di ec ly
o
indi ec ly
e e
o
he
p imacy
o
he
human
being
and
consequen ly
o
he
p imo dial
impo ance
o
in o med
consen .23,cSuch
p inciples
a e
also
insc ibed
aI
was
in
ac
a
ipa i e
biobank
–
one
biobank
con aining
DNA
samples
om
a
significan
p opo ion
o
he
Icelandic
popula ion,
and
wo
sepa a e
da abases
consis ing
o
genealogical
in o ma ion
and
heal h
eco ds.
bMo e
ecen ly,
some
o
hese
issues
ha e
e-eme ged,
ollowing
wo
significan
financial
mo es
in ol ing
he
company,
one
in
2009
(deCODE
sold
he
da abase
o
a oid
bank up cy)
and
a
mo e
ecen
one
in
2012
(deCODE
was
bough
by
ano he
company).
cSee
as
examples
he
Con en ion
on
Human
Righ s
and
Biomedicine
(Council
o
Eu ope
1997,
a icle
2);
he
Decla a ion
o
Helsinki
(WMA
in
he
na ional
legal
amewo ks
o
di e en
coun ies,24,d
bo h
a
a
Cons i u ional
and
in a-Cons i u ional
le el.
Hence,
mos
egula ions
equi e
ha
biological
ma e ial
and
associa ed
in o ma ion
a e
only
used
o
esea ch
pu poses
wi h
he
knowledge
and
consen
o
he
pe son
om
which
hese
we e
de i ed.
These
ules
apply
also
o
la ge-scale
esea ch
p ojec s
such
as
biobanks.
On
he
con a y,
he e
is
conside able
deba e
abou
whe he
he
adi ional
in o med
consen
pa adigm
is
app op ia e
o
hese
p ojec s.
E en
assuming
he
e minology
“in o med
consen ”
is
app o-
p ia e,
which
is
no
s aigh o wa d,
he
adequa e
ype
o
ha
in o med
consen
is
deba able.25,26 Di e en
au ho s
p esen
di e en
a gumen s
o
sus ain
ha
he
classical
models
o
in o med
consen
a e
no
adequa e
o
gene ic
biobanks
and
should
be
adap ed
o
subs i u ed
by
di e en
pa adigms.21,27–31 These
a gumen s
a e
a ied
and
include:
(i)
he
scope
o
he
o iginal
consen
ega ding
seconda y
uses
o
samples
and
he
imp ac icali y
o
he
cons an
need
o
e-consen ;
(ii)
he
complex
issue
o
au ho iza ion
o
eques
o
sample
des uc ion;
(iii)
he
na u e
o
he
in o ma ion
o
p o ide
o
dono s;
(i )
he
di ficul ies
in
ully
gua an eeing
gene ic
sample
anonymi y;
and
( )
he
lack
o
clea
and
uni o m
ules
o
delimi
he
ex en
o
p ope y
igh s
o e
samples
and
esea ch
esul s.32–34 Mo eo e ,
as
biobanks
a e
o en
inse ed
in
la ge
na ional
and
in e na ional
ne wo ks,
in o med
consen
models
(o
al e na i e
ag eemen s)
mus
ei he
be
uni e sal
o
easily
adap able
o
pe mi
in o ma ion
and
sample
sha ing
while
s ill
accommoda ing
e hical,
legal,
social
and
cul u al
di e ences.35–38 Taken
all
his
oge he
and
ac o ing
in
public
pe cep ions,
o he
au ho s
p opose
ha
in o med
consen
models
–
o
any
ype
–
should
be
a e ed.
Al e na i ely,
i
should
be
assumed
ha
pa icipan s
a e
willing
o
delega e
decisions
on
p oxies,
which
mos
o
he
imes
a e
esea ch
e hics
commi ees,
ha
a e
be e
placed
o
e alua e
and
manage
he
si ua ion.39,40 On
he
o he
hand,
o he s
sugges
adop ing
unde e mined
models
such
as
b oad
o
open
consen ,25,28,41 o
al e na i es
such
as
condi ional
au ho iza ions
o
sample
dona ion
and
gi
ag eemen s.25,30
In
conclusion,
clea
ules
a e
bo h
lacking
and
essen ial
in
his
field.
E o s
o
selec
he
mos
adequa e
ag eemen s
o
biobank
pa icipa ion
mus
be
mind ul
ha
indi idual
and
undamen al
alues
such
as
libe y
and
au onomy
mus
be
balanced
and
made
compa ible
wi h
he
common
good
and
he
human
igh
o
enjoy
he
benefi s
o
science
and
i s
applica ions.33,e
2013,
a icles
24–29);
he
Uni e sal
Decla a ion
on
he
Human
Genome
and
Human
Righ s
(UNESCO
1997,
a icle
5(b),
a icle
5(e));
and
he
In e na ional
Decla a ion
on
Human
Gene ic
Da a
(UNESCO
2003,
a i-
cle
2(iii),
a icle
6(d),
a icle
8,
a icle
9).
dIncluding
Iceland.
Iceland´
s
o iginal
Ac
on
Heal h
Sec o
Da abase
om
1998
did
no
speci y
he
equi emen
o
in o med
consen
bu
se
up
an
op -ou
scheme
ins ead
(a icle
8).
Subse-
quen ly,
he
Iceland
Sup eme
Cou
decla ed
he
Ac
on
Heal h
Sec o
Da abase
uncons i u ional,
which
p omp ed
he
inclusion
o
an
in o med
consen
equi emen
in
he
Ac .
eSee:
Uni e sal
Decla a ion
o
Human
Righ s
(Uni ed
Na ions
1948,
a icles
27
and
29/2);
In e na ional
Co enan
on
Economic,
Social
and
Cul u al
Righ s
(Uni ed
Na ions,
1966,
a icle
15).
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
167
One
addi ional
ye
ela ed
and
undamen al
issue
ha
dese es
e hical
and
legal
analysis
in
he
con ex
o
biobanks
is
ha
o
p i acy
and
confiden iali y.25,42–46, This
issue
is
pa icula ly
impo an
because
gene ic
in o ma ion
has
he
inhe en
po en ial
o
link
biological
ma e ial
o
he
indi idual
om
which
i
o igina ed
and,
mo eo e ,
because
he
in o -
ma ion
included
in
biobanks
o
esea ch
pu poses
is
usually
linked
o
o he
heal h
da a.47 Fu he mo e,
espec
o
p i-
a e
li e,
in
he
case
o
gene ic
in o ma ion
dese es
ca e ul
analysis
as
his
in o ma ion
ela es
no
only
o
he
indi id-
ual
bu
also
o
his/he
amily.48,gIn
he
case
o
p i acy
igh s
and
gene ic
in o ma ion
included
in
biobanks,
we
can
once
again
u n
o
Iceland’s
Ac
on
Heal h
Sec o
Da abase
o
his o i-
cal
con ex .
In
a
e y
in e es ing
case
om
he
las
decade,
he
Iceland
Sup eme
Cou
held
ha
in
he
case
o
gene ic
in o -
ma ion,
p i acy
igh s
a e
b oadened
beyond
an
indi idual
sphe e
o
encompass
close
amily
membe s
(in
his
pa ic-
ula
case
a
daugh e ).49,50 Hence,
in
he
con ex
o
gene ics,
indi idual
igh s
can
blend
in o
amily
igh s.
The e o e,
his
should
be
explained
in
he
clea es
e ms
o
biobank
dono s,
which
is
a
e y
di ficul
ask.
Fu he mo e,
confiden iali y
igh s
(and
hei
possible
limi a ions),
which
lie
downs eam
o
p i acy
igh s,
should
also
be
explained,
unde s ood
and
espec ed.
Weigh ing
and
balancing
o
he
alues
a
s ake
a e
s ill
impo an
despi e
he
ac
ha
mos
pa ien s
choose
o
sha e
in o ma ion
o
gene ic
isk
wi h
amily
membe s.51
The e o e,
i
is
essen ial
o
implemen
sa egua ds
o
p o-
ec
confiden iali y
ag eemen s
in
he
con ex
o
biobanks
and
o
p e en
o
minimize
confiden iali y
b eaches
ha
could
conside ably
damage
public
us .
Such
us
is
essen-
ial
o
po en ia e
hese
undamen al
esea ch
in as uc u es
which
o e
g ea
hope
o
u u e
diagnosis
and
ea men
o
disease.
P e en ion
and
diagnosis:
gene ic
es s
Since
he
beginning
o
he
HGP,
pa icula ly
om
he
second
hal
o
he
las
decade
onwa ds,
he
cos s
o
gene ic
sequenc-
ing
ha e
dec eased
d ama ically.52,hIn
pa allel,
gene ic
es ing
is
now
widely
a ailable
and
can
assume
mul iple
o ms,
which
complica es
he
adop ion
o
uni o m
defini ions
o
egula o y
pu poses.53,54 Fo
example,
gene ic
es s
can
be
pe o med
a
di e en
s ages
–
p econcep ion,
p eimplan a-
ion
(on
human
emb yos),
p ena al
(on
a
e us),
on
newbo ns,
du ing
childhood
and
adul hood;
use
di e en
echniques
–
ch omosome
analysis,
flu escence
in
si u
hyb idiza ion
(FISH),
DNA
mic oa ays,
whole
exome
sequencing
(WES)
o
whole
genome
sequencing
(WGS),
and
se e
di e en
pu -
poses
–
diagnos ic,
p edic i e
o
disease
o
esponse
o
d ugs,
This
subjec
is
also
cen al
o
deba es
in
public
heal h.
See,
o
example,
he
D a
NIH
Genomic
Da a
Sha ing
Pol-
icy
Reques
o
Public
Commen s
o
la e
2013,
a ailable
he e:
h p://www.gpo.go / dsys/pkg/FR-2013-09-20/pd /2013-22941.pd .
gSee
also:
In e na ional
Decla a ion
on
Human
Gene ic
Da a
(UNESCO
2003,
a icle
4
a(ii)).
hSee
also
DNA
Sequencing
Cos s,
Da a
om
he
NHGRI
Genome
Sequencing
P og am
(GSP)
a ailable
he e:
h p://www.genome.go /sequencingcos s/.
o ensic
o
esea ch.
Fu he mo e,
as
es ing
human
genes
and
genomes
can
now
cons i u e
a
p ofi able
ma ke able
ac i i y,
gene
es s
a e
cu en ly
o e ed
no
only
by
public
labo a o-
ies
bu
also
by
p i a e
companies.55 The
expansion
o
gene ic
es ing
is
such
ha
unde
he
p omise
o
indi idualized
solu-
ions,
public
labo a o ies
and
p i a e
companies
now
o e
o
diagnose
gene ic
disease
o
es
ou
p edisposi ion
o
de elop
di e en
condi ions
in
he
u u e,
all
his
a
compe i i e
p ices.
The e
a e
cu en ly
gene ic
es s
ha
co e
diseases
such
as
ce ain
ypes
o
cance ,
diabe es,
ca dio ascula
and
men al
diseases,
condi ions
such
as
obesi y,
and
a ibu es
such
as
muscle
pe o mance,
and
baldness,
among
o he s.
Mo e,
ou
indi idual
esponses
o
pa icula
d ugs
and
chemicals,
ou
ances y
de ails
and
e en
gene ic
ma chmaking
a e
all
es able
o
p omised
as
such
so
long
as
we
ag ee
o
p o ide
a
sample
o
ou
DNA
o
analysis,
which
in
mos
cases
is
as
simple
and
isk- ee
as
p o iding
a
blood
o
sali a
sample.
In
his
complex
con ex ,
i
is
essen il
o
sepa a e
hype
om
hope.
Indispu ably,
his
gene ics- o -all
eali y
(maybe
no
eally
o
all
as
discussed
in
he
final
sec ion)
yields
g ea
po en ial
bu
is
also
accompanied
by
significan
challenges,
some
o
which
a e
e hical
and
legal.56
Many
o
hese
challenges
a e
posed
by
he
expanding
eal-
i y
o
di ec - o-consume
(DTC)
gene ic
es s,
which
as
he
name
indica es
a e
o e ed
by
companies
and
labo a o ies
di ec ly
o
consume s
ia
he
in e ne ,
ele ision
o
o he
media,
wi hou
he
in ol emen
o
an
heal hca e
p o ide
o
p ac i ione .
In
some
cases,
hese
es s
a e
o e ed
using
in ica e
ma ke ing
and
esul s
communica ion
p ac ices
in ol ing
pa ies
om
di e en
ju isdic ions,
which
com-
plica es
an
e hical
and
legal
analysis.56 None heless,
some
challenges
can
be
clea ly
iden ified.
Fi s ly,
wi hou
he
in e -
media ion
o
a
heal hca e
p ac ione
o
he
di ec
access
o
a
gene ic
counselo
consume s
a e
unp o ec ed
om
he
pe -
nicious
e ec s
ha
may
a ise
om
misleading
o
unhelp ul
in o ma ion.
In
his
con ex ,
i
is
impo an
o
pay
a en ion
o
he
gene ic
es ’s
analy ical
alidi y,
clinical
alidi y
and,
clin-
ical
u ili y.55,56 The
analy ical
alidi y,
a
measu e
o
a
es ’s
de ec ion
accu acy,
mus
be
well
es ablished
and
ce ified.
This
necessi y
has
p omp ed
e o s
on
di e en
coun ies
o
license
labo a o ies
ha
pe o m
gene ic
es ing
by
equi ing
specific
p o essional
aining,
clea
eco d
keeping
s anda ds
and
pe iodical
assessmen
o
me hodologies.56 Fu he mo e,
egula o y
lacunae
should
be
filled
by
ca e ul
adap a ion
o
quali y
con ol
no ms
al eady
in
place
o
o he
clinical
labo a o y
es s
o
p egnancy
es s,
o
example.
Secondly,
ansla ing
a
posi i e
esul
in o
clinical
significance,
which
de e mines
he
clinical
alidi y
o
he
es ,
is
no
s aigh -
o wa d
and
in ol es
mas e ing
accu a e
scien ific
no ions
o
p obabili y,
isk,
and
a iance.
These
concep s
a e
di ficul
o
es ima e,
o
explain
and
o
be
ully
unde s ood.
None heless,
he
es ’s
esul s
and
limi a ions
should
be
explained
(and
unde s ood)
as
clea ly
as
possible.
Thi dly,
we
need
o
conside
he
es s’
clinical
u ili y,
o
he
use ulness
o
he
es ’s
esul s
in
e ms
o
p e en ion,
diagnosis
o
ea men .
Undoub edly,
he
u ili y
o
a
posi i e
o
nega i e
esul
is
di ficul
o
es i-
ma e,
pa icula ly
when
no
he apy
o
p ophylac ic
measu es
a e
a aillable.
Hence,
he
decision
o
ake
a
gene ic
es
should
be
p eceeded
by
a
comp ehensi e
in o med
consen
p ocess
ha
includes
discussion
abou
wha
he
es
can
and
canno
168
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
p edic
and
he
exis ence
o
inexis ence
o
a ge ed
he a-
peu ical
o
p e en i e
s a egies.57 Misleading
in o ma ion
po en ially
esul ing
in
delayed
isi s
o
he
doc o ,
aised
anx-
ie y
and
s ess
o
ba e ies
o
unnecessa y
addi ional
es s,
mus
be
a oided
o
mi iga ed.
In
pa allel,
he
p i acy
o
gene ic
in o ma ion
should
also
be
p o ec ed42 and
i
is
essen ial
o
gua an ee
ha
he
es s’
esul s
a e
confiden ial
and
no
acces-
sible
o
hi d
pa ies
wi hou
consen .
O e all,
clea
bounda ies
o
DTC
gene ic
es ing
should
be
es ablished,
including
condi ional
in ol emen
o
heal hca e
p o ide s
and
p o essional
couseling;
s anda ds
o
p ema ke
e iews;
limi s
o
ad e ising
and
ma ke ing;
specific
o e sigh
o
esul s
epo s;
delimi a ion
o
p o isions
om
public
budg-
e s
and
heal h
insu ance
co e ages.58 To
en o ce
hese
ules,
public
powe s
may
need
o
in e ene.
In
a
ecen
example
om
he
USA,
conce n
su ounding
some
o
hese
issues,
pa ic-
ula ly
he
lack
o
analy ical
and
clinical
es
alida ion,
es
ad e isemen
wi hou
p ema ke
app o al,
and
he
use
o
in o ma ion
om
consume s,
led
he
FDA
o
issue
a
wa ning
o
he
DTC
gene ic
es s
company
23andMe,
asking
i
o
s op
e u ning
esul s
o
consume s
un il
comple ion
o
a
e iew
p ocess.iIn
esponse,
he
company
suspended
i s
heal h-
ela ed
gene ic
es s
o
comply
wi h
he
di ec i e
and
la e
p esen ed
he
app op ia e
co ec i e
measu es.59,jThis
p o-
cess,
al hough
pe cei ed
by
some
as
an
unjus ified
inge ence
in
a
ma e
o
pe sonal
libe y
and
indi idual
au onomy,60
demons a es
ha
public
heal h
au ho i ies
play
a
key
ole
in
demanding
he
necessa y
sa e y
and
quali y
s anda ds
o
gene ic
es s
in
o de
o
p o ec
consume s.59
On
a
di e en
no e,
as
labo a o ies
expand
analysis
and
look
beyond
single
genes,
he
issue
o
inciden al
findings
gains
impo ance.
Should
pa ien s
be
in o med
abou
findings
in
genome
egions
ha
di e
om
he
ocus
o
he
o iginal
sea ch?
And
wha
i
ha
sea ch
is
conduc ed
wi hou
seek-
ing
he
pa ien ’s
consen ?
These
ques ions
ha e
gene a ed
a
ai
amou
o
discussion
in
Eu ope
and
he
USA
ecen ly61,62,k
and
some
o
he
answe s,
which
a e
cu en ly
s aigh o wa d
o
s anda d
medical
es s,
migh
equi e
addi ional
ponde -
ing
in
he
case
o
gene ic
es s.63–65 None heless,
acco ding
o
ele an
legal
no ms,
he
in o med
consen
pa adigm
and
he
p inciple
o
pa ien
au onomy,
pa ien s
ha e
a
igh
o
decide
wha
o
be
and
no
o
be
es ed
o .
Fu he mo e,
hey
also
ha e
a
igh
o
know
and
a
igh
no
o
know.62,66 Being
mind ull
o
hese
pa ien ’s
igh s
wi hou
neglec ing
specific
challenges
posed
by
gene ics
is
he
bes
(and
pe haps
only)
way
o
ex ac
he
ull
po en ial
o
gene ic
es s
o
medicine.
Impo an ly,
pa icula
and
added
a en ion
mus
be
ded-
ica ed
o
p e en
un es ic ed
es ing
o
he
mos
ulne able.
Mos
in e na ional
e hical
and
legal
no ms
a e
clea
in
es ab-
lishing
ha
in o med
consen
o
p ocedu es
in ol ing
hose
iFDA
Wa ning
Le e
a ailable
he e:
h p://www. da.go /iceci/
en o cemen ac ions/wa ningle e s/2013/ucm376296.h m.
jFDA
Close
Ou
Le e
a ailable
he e:
h p://www. da.go /ICECI/
En o cemen Ac ions/Wa ningLe e s/ucm391016.h m.
kSee
also
he
ollowing
upda e
om
he
Ame ican
College
o
Medical
Gene ics
and
Genomics:
h ps://www.acmg.ne /docs/
Release
ACMGUpda esRecommenda ions
final.pd .
who
a e
incapable
o
consen ing
is
undamen al.lSuch
con-
sen
should
be
gi en
by
legal
ep esen a i es
only
a e
being
p o ided
wi h
su ficien
in o ma ion
“ ega ding
he
pu pose
and
he
na u e
o
he
es ,
as
well
as
he
implica ions
o
i s
esul s”.m
Fu he mo e,
whene e
possible,
he
will
o
he
pe son
being
es ed
should
be
conside ed
in
p opo ion
o
his/he
deg ee
o
ma u i y
and
capaci y
o
unde s and,nwhich
unde lines
he
impo ance
(and
di ficul y)
o
ansmi ing
and
unde s anding
no ions
such
as
p obabili y
and
isk.
In
e ms
o
es ing
he
mos
ulne able,
he
subjec
o
gene ic
es ing
in
child en67 and
specifically
o
New-
bo n
Gene ic
Sc eening
P og ams
[NGSP]
is
pa icula ly
impo an .68,69 Fi s ly,
in
e ms
o
in o med
consen ,
he
ole
o
pa en s
and
legal
ep esen a i es
is
no
always
clea .70
One
one
hand,
pa en al
consen
seems
necessa y,
as
pa -
en s
a e
in
a
p i ileged
posi ion
o
de end
he
child en’s
own
in e es ,
mos
es ed
diseases
a e
a e
and
a
possible
alse
posi i e
esul
will
cause
unnecessa y
s ess.
On
he
o he
hand,
he
o e all
benefi s
o
es ing
a
ou -weigh
indi id-
ual
ha ms
and
bu eauc a ic
p ocedu es
place
conside able
bu dens
on
heal h
sys ems.
This
dillema
is
ongoing
and
o
example
o
di e en
NGSP,
olun a y,
op -in,
op -ou ,
con-
di ional,
implied
and
manda o y
consen
models
ha e
been
p oposed
and
selec ed.68,70 Ul ima ely,
decisions
on
a
egu-
la o y
le el
should
espec
human
igh s,
conside
p ac ical
aspec s
and
all
a aillable
op ions,
ake
in o
accoun
he
al-
ues
o
each
socie y
and
be
e iewed
pe iodically
in
o de
o
be
adjus ed
i
necessa y.
In
conclusion,
di e en
gene ic
es s
pose
di e en
eg-
ula o y
challenges
and
equi e
dedica ed
a en ion.71 The
di ficul ies
in
es ablishing
gene al
isk–benefi
analyses
in
his
con ex
jus ifies
he
need
o
unc ional,
nuanced
and
adap -
able
legal
and
e hical
esponses
ha
simul aneously
p o ec
indi idual
igh s
and
pe mi
he
ad ancemen
o
medicine
and
science.
T ea men :
gene
he apy
Disco e ing
he
gene ic
basis
o
disease,
making
isk
p edic-
ions
based
on
gene ic
in o ma ion
and
imp o ing
diagnos ics
a e
he
fi s
s eps
owa d
a
cu e.
Ad ances
in
esea ch,
p e en ion
and
diagnos ics
should
be
accompanied
by
he
de elopmen
o
alid
he apies.
The e
a e,
pa icula ly
in
he
field
o
pha macogenomics,
impo an
and
al eady
e y
sig-
nifican
examples
o
how
gene ic
da a
can
imp o e
ea men
op ions.72–75 Concu en ly,
when
we
hink
abou
pe sonalized
medicine
mos
o
us
hink
o
adminis e ing
he
igh
d ug
o
lSee,
o
example,
he
Decla a ion
o
Helsinki
(WMA
2013,
a icles
19–20
and
29);
he
Addi ional
P o ocol
o
he
Con en ion
on
Human
Righ s
and
Biomedicine,
conce ning
Gene ic
Tes ing
o
Heal h
Pu poses
(Council
o
Eu ope
2008,
a icles
9–12);
he
Con en ion
on
Human
Righ s
and
Biomedicine
(Council
o
Eu ope
1997,
a icles
5–6);
and
he
Uni e sal
Decla a ion
on
he
Human
Genome
and
Human
Righ s
(UNESCO
1997,
a icle
5).
mAddi ional
P o ocol
o
he
Con en ion
on
Human
Righ s
and
Biomedicine,
conce ning
Gene ic
Tes ing
o
Heal h
Pu poses
(Council
o
Eu ope
2008,
a icle
11).
nCon en ion
on
Human
Righ s
and
Biomedicine
(Council
o
Eu ope
1997,
a icle
6).

e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
169
he
igh
pa ien
a
he
igh
ime.
In
pa allel
o
he
ad ances
in
pha macogenomics,
o he
gene ics-based
ea men s
ha e
been
de eloped,
including
gene
he apy.
Di e en
gene
he -
apy
defini ions
exis
and
wo
o
hem
a e
pa icula ly
ele an
om
an
e hical
and
legal
pe spec i e
because
hey
o igina e
om
he
compe en
egula o y
agencies
in
bo h
he
USA
and
Eu ope.
Acco ding
o
he
Eu opean
Medicines
Agency
(EMA),
gene
he apy
medicinal
p oduc s
mus
ha e
wo
cha ac e is-
ics:
(a)
“con ain
an
ac i e
subs ance
which
con ains
o
consis s
o
a
ecombinan
nucleic
acid
used
in
o
adminis e ed
o
human
beings
wi h
a
iew
o
egula ing,
epai ing,
eplacing,
adding
o
dele ing
a
gene ic
sequence;
(b)
i s
he apeu ic,
p ophylac ic
o
diagnos ic
e ec
ela es
di ec ly
o
he
ecombinan
nucleic
acid
sequence
i
con ains,
o
o
he
p oduc
o
gene ic
exp ession
o
his
sequence”.76
As
o
he
FDA,
gene
he apy
p oduc s
a e
defined
as
“p od-
uc s
ha
media e
hei
e ec s
by
ansc ip ion
and/o
ansla ion
o
ans e ed
gene ic
ma e ial
and/o
by
in eg a ing
in o
he
hos
genome
and
ha
a e
adminis e ed
as
nucleic
acids,
i uses,
o
gene -
ically
enginee ed
mic oo ganisms.
The
p oduc s
may
be
used
o
modi y
cells
in
i o
o
ans e ed
o
cells
ex
i o
p io
o
admin-
is a ion
o
he
ecipien ”.77
As
he
complexi y
o
bo h
defini ions
illus a es,
gene
he -
apy
can
be
pe o med
in
e y
di e en
ways
and
o igina e
di e en
ypes
o
gene ic
al e a ions.
An
essen ial
fi s
dis-
inc ion
in
e ms
o
gene
he apy
egula ion
is
be ween
ge m
line
and
soma ic
gene ic
changes.
The
o me
in ol es
gene ic
al e a ions
ha
can
hen
be
passed
on
o
he
o sp ing
and
he
la e
consis s
in
gene ic
changes
ha
a e
es ic ed
o
he
indi idual
and
no
passed
on
o
u u e
gene a ions.78
Ge m
line
gene
he apy
(o
he
b oade
e m
“inhe i able
gene ic
modifica ion”79,80)
is
p ohibi ed
o
sa e y
and
e h-
ical
easons
in
mos
coun ies
and,
di ec ly
o
indi ec ly,
dese es
he
a en ion
o
in e na ional
biolaw
and
bioe hics
documen s.81–84,oOn
he
con a y,
he
limi s
o
soma ic
gene
he apy
ha e
been
he
subjec
o
in ense
deba e
in
he
las
decades
and
a e
a
mo e
con o e sial,
pa icula
o
sa e y
easons.78,85,86 E e
since
he
fi s
FDA-app o ed
gene
he apy
ial
in
Sep embe
1990
in
he
USA,
which
aimed
a
ea -
ing
he
monogene ic
disease
adenosine
deaminase
deficiency
(ADA-SCID),
se e al
o he
ials
we e
app o ed
in
he
USA
and
elsewhe e,
including
Eu ope.78 None heless,
he
issue
o
pa ien
sa e y
became
a
se ious
conce n
ollowing
he
dea h
o
18-yea
old
Jesse
Gelsinge
du ing
a
gene
he apy
ial
a
he
Uni e si y
in
Pennsyl ania,
in
1999.87,88 This
agic
e en
p omp ed
he
scien ific
and
legal
communi ies
o
pause
and
eassess
he
me hodologies
applied
o
gene
he apy
in
bo h
fields.
Gelsinge ’s
dea h
was
di ec ly
ela ed
o
he
adeno i us
ec o
used
o
deli e
he
gene
(in
his
case
he
o ni hine
an-
sca bamylase
gene),
which
elici ed
a
a al
immune
eac ion.
oSee
also:
Con en ion
on
Human
Righ s
and
Biomedicine
(Coun-
cil
o
Eu ope
1997),
Uni e sal
Decla a ion
on
Bioe hics
and
Human
Righ s
(UNESCO
2005),
Uni e sal
Decla a ion
on
he
Human
Genome
and
Human
Righ s.
(UNESCO
1997),
Decla a ion
o
Helsinki
(WMA
1964).
In
o he
ci cums ances,
ano he
ec o
ype
used
in
gene
he -
apy
–
e o i us
–
has
caused
oncogene
ac i a ion
and
cance .
The
mos
p ominen
cases
we e
hose
o
he
F ench
child en
who
de eloped
leukemia
as
a
esul
o
hei
pa icipa ion
in
gene
he apy
ials
o
X-linked
se e e
combined
immunode-
ficiency
(SCID-X1),
du ing
he
fi s
hal
o
he
las
decade.89–92
In
e ms
o
pa ien
sa e y,
he
challenge
lies
on
how
o
eason-
ably
es ima e
isks
and
benefi s,
be
i
o
ial
pa icipan s
in
expe imen al
he apies
o
o
pa ien s
in
he
case
o
app o ed
he apies.86 The e o e,
a
igo ous
in o med
consen
p ocess
is
pa icula ly
impo an
in
o de
o
gua an ee
ha
he
isks
and
po en ial
benefi s
a e
p ope ly
explained
(and
no
exag-
ge a ed)
and
unde s ood.
Au onomous
in o med
decisions
a e
only
made
when
he
subjec
is
compe en ,
awa e
o
po en ial
isks,
has
access
o
a
easonable
es ima ion
o
benefi s
and
is
ee
om
coe cion.19 Hence,
like
in
o he
he apies,
spe-
cial
a en ion
mus
be
paid
o
he
mos
ulne able,
such
as
he
e minally
ill,
in
o de
o
gua an ee
ha
he
di e ences
be ween
clinical
ca e
and
clinical
esea ch
a e
p ope ly
cla i-
fied
and
unde s ood.93–95 Fu he mo e,
in o med
decisions
a e
only
possible
once
ele an
conflic s
o
in e es
a ec ing
in es-
iga o s
and/o
clinicians
a e
ully
disclosed
and
app op ia e
measu es
a e
in
place
o
gua an ee
ha
hose
conflic s
do
no
damage
he
in eg i y
o
he
p ocess.86
Since
Jesse
Gelsinge ,
gene
he apy
has
come
a
long
way
in
dealing
wi h
e hical
issues,
echnical
obs acles
and
sa e y
conce ns.
Concu en ly,
he
numbe
o
app o ed
and
con-
duc ed
ials
wo ldwide
has
g own
significan ly
in
he
las
yea s.96 The e o e,
i
is
expec ed
ha
an
expanding
numbe
o
gene
he apy
p oduc s
will
be
app o ed
o
clinical
use
in
he
nea
u u e.
The
fi s
e e
app o al
occu ed
a
decade
ago
in
China,
bu
again
no
wi hou
e hical
con o e sy.
In
2003
and
2005,
he
Chinese
S a e
Food
and
D ug
Adminis a-
ion
(SFDA),
app o ed
he
p oduc s
Gendicine
and
Onco ine
o
clinical
use
( ecombinan
adeno i uses
con aining
he
umo
supp esso -gene
P53
o
ea men
o
head-and-neck
squamous
cell
ca cinoma
and
nasopha yngeal
ca cinoma,
espec i ely).
No ably,
his
app o al
was
gi en
wi hou
p io
conduc ion
o
phase
III
clinical
ials.97–99 Conduc ion
o
phase
III
clinical
ials
o
gene
he apy
is
some imes
excep ionally
challenging,
especially
in
he
case
o
monogenic
diso de s,
which
ha e
low
p e alence
wi hin
a
popula ion
making
pa ien
ec ui men
pa icula ly
di ficul .
Howe e ,
ha
was
no
he
case
in
he
swi
app o al
o
Gendicine
and
Onco ine
in
China,
which
seem
o
ha e
esul ed
mo e
om
an
o e all
pe missi e
egula o y
amewo k
han
om
he
impossibili y
o
mee
p ac ical
con ingencies.
Impo an ly,
disc epan
eg-
ula o y
landscapes
o
inno a i e
he apies
in
di e en
pa s
o
he
wo ld
can
ha e
significan
amifica ions
ha
dese e
e hical
and
legal
a en ion
such
as
he
expanding
eali y
o
medical
ou ism
ha
has
been
ex ensi ely
deba ed
in
he
con-
ex
o
s em
cell-based
he apies
bu
o
which
gene
he apy
is
no
excep ion.100–102
The
educed
ec ui men
pool
o
la ge
clinical
ials
and
he
lack
o
in e es
om
in es o s
in
de eloping
he apies
o
a
small
ma ke
ha e
long
been
iden ified
as
obs acles
in
he
case
o
mos
o phan
diseases
and
he e o e
apply
also
o
di e en
gene
he apies.
These
obs acles
ha e
been
ackled
by
dedi-
ca ed
legisla ion
in
some
coun ies,
including
he
USA,
Japan,
170
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
Aus alia
and
also
in
he
Eu opean
Union.pMo e
ecen ly,
as
gene
he apy
clinical
ial
sponso s
became
mo e
awa e
o
eg-
ula o y
cons ain s,
inc easing
numbe s
o
gene
he apies
a e
being
de eloped
as
o phan
d ugs
in
o de
o
make
he
mos
o
he
flexibili y
ha
hese
legal
egimes
allow.103 Rema k-
ably,
in
July
2012,
gene
he apy
o
an
ul a-o phan
disease,
lipop o ein
lipase
deficiency,
was
his o ically
app o ed
by
he
EMA.104,qHence,
he
fi s
–
and
so
a
only
–
gene
he apy
p od-
uc
app o ed
o
clinical
use
ou side
China
(alipogene
ipa -
o ec,
also
known
as
Glybe a,
an
adeno-associa ed
i al
ec o
ca ying
he
LPL
gene)
benefi ed
om
egula ion
ha
ook
in o
accoun
he
di ficul y
in
ob aining
da a
in
a e
diseases
and
conside ed
e idence
de i ed
om
a
e y
small
numbe
o
pa ien s.105 In
spi e
o
his,
he
app o al
p ocess
o
Glybe a
was
no
s aigh o wa d
and
exposed
he
di ficul ies
o
p od-
uc
e alua ion
and
au ho iza ion
ha
companies
de eloping
gene
he apy
p oduc s
ace
oday.103,106 Some
o
hese
di ficul-
ies,
p ominen ly
ime
and
financial
p essu es
and
he
lack
o
p edic abili y
and
p ecise
c i e ia
o
u u e
app o al
can
jeop-
a dize
ongoing
esea ch
and
de elopmen
e o s96 and
he e-
o e
equi e
dedica ed
a en ion
om
egula o y
bodies.105
As
gene
he apy
becomes
clinically
a ailable
an
addi ional
issue
ha
begs
u he
e hical
analysis
is
ha
o
i s
accep able
aims.
In
which
medical
con ex s
is
i
accep able
o
conside
gene ic
al e a ions
–
in
all
condi ions
o
only
in
se e e
ones?
And
i
we
choose
he
la e
wha
should
be
conside ed
as
“se e e”
and
how
o en
should
such
assessmen
be
e ised?
In
ac ,
deciding
on
whe he
o
no
a
gi en
medical
condi ion
is
wo hy
o
gene ic
in e en ion
is
a
complex
decision
ha
in i es
ca e ul
conside a ion.
In
o de
o
do
so,
specific
disease
mechanisms,
indi idual
ci cums ances
o
pa ien s,
po en ial
benefi s
and
expec ed
ha ms
mus
be
aken
in o
accoun .
Fu -
he mo e,
gene
he apy
is
expensi e
he apy.
The e o e,
he
ques ions
o
access,
equali y
and,
om
a
p o ide ’s
pe spec-
i e,
esou ce
alloca ion,
a e
c i ical
issues
o
be
deal
wi h
also
by
e hics
and
he
law.
The
human
igh
o
enjoy
he
benefi s
o
science
and
i s
applica ions
should
be
balanced
by
app op ia e
public
and
p i a e
unding
schemes
ha
comba
he
po en-
ial
o
deepening
inequali y
and
he
onse
o
new
sou ces
o
disc imina ion.
Gene ics
and
genomics:
di e si y
and
disc imina ion
In
o de
o
ake
ull
ad an age
o
he
po en ial
o
pe sonalized
medicine
we
mus
dis inguish
hype
om
hope.
Sequencing
pSee,
amongs
o he s:
USA
–
O phan
D ug
Ac
(1983),
Japan
–
O phan
D ug
Regula ion
(1993),
Aus alia
–
O phan
D ug
Policy
(1998),
EU
–
Regula ion
(CE)
N◦141/2000
(2000).
Mo e
in o
a :
h p://www.o pha.ne /conso /cgi-bin/Educa ion
Abou O phan
D ugs.php?lng=PT&s apage=ST
EDUCATION
EDUCATION
ABOUT
ORPHANDRUGS
COMPARISON.
qMo e
in o ma ion
he e:
h p://www.ema.eu opa.eu/ema/index.
jsp?cu l=pages/news
and
e en s/news/2012/07/news
de ail
001574.jsp&mid=WC0b01ac058004d5c1,
he e:
h p://www.ema.
eu opa.eu/ema/index.jsp?cu l=pages/medicines/human/
medicines/002145/human
med
001480.jsp&mid=
WC0b01ac058001d124
and
he e:
h p://ec.eu opa.eu/heal h/
documen s/communi y- egis e /h ml/o194.h m.
ou
genomes
has
become
inc easingly
cheape
and
we
a e
now
able
o
access
an
amoun
o
da a
ha
was
unimaginable
a
ew
yea s
ago.
Howe e ,
ou
capaci y
o
manage
and
in e p e
such
big
da a
is
s ill
insu ficien
o
ully
unde s and,
p e en ,
diagnose
and
ea
disease.
Fu he mo e,
as
we
us
scien-
ific
p og ess
o
help
us
achie e
a
be e
heal h,
we
mus
also
con on
ou sel es
wi h
he
downsides
o
he
pe sonalized
medicine
endea o ,
in
o de
o
p ope ly
add ess
hem.
One
o
he
mos
impo an
isks
ha
should
be
men ioned
is
ha
o
gene ic
disc imina ion.
In
his
espec ,
I
selec
one
sen ence
om
Sou h
A ica’s
an i-apa heid
ac i is
and
Nobel
Peace
P ize
lau ea e
A chbishop
Desmond
Tu u
ha
p ope ly
illus a es
he
basis
o
his
discussion.
W i ing
o
he
jou nal
Science
abou
he
commemo a ion
o
he
10 h
anni e sa y
o
he
HGP,
he
said:
“My
d eam
is
ha
by
including
all
peoples
in
unde s anding
and
eading
he
gene ic
code
we
will
ealize
ha
all
o
us
belong
in
one
global
amily
–
ha
we
a e
all
b o he s
and
sis e s.
Wow!”107
In
2010,
Tu u
had
dona ed
his
own
cells
o
he
s udy
o
gene ic
di e si y.
Resul s
om
ha
s udy
showed
ha
he
sha ed
ances y
wi h
a
Kalaha i
Bushman
om
Namibia.108
These
and
o he
findings
dese ed
he
ollowing
commen s
om
Webb
Mille ,
a
p o esso
o
biology
a
Penn
S a e
Uni e -
si y
and
co-au ho
o
he
s udy:
“On
a e age
he e
a e
mo e
gene ic
di e ences
be ween
any
wo
bushmen
in
ou
s udy
han
be ween
a
Eu opean
and
an
Asian”,
and:
“To
know
how
genes
a ec
heal h,
we
need
o
see
he
ull
ange
o
human
gene ic
a ia ion,
(.
.
.)”.
Fundamen ally,
he
beau y
o
gene ic
di e si y
should
be
s udied
and
unde s ood
in
pa allel
wi h
he
uni e sali y
o
ou
human
he i age.
Simul aneously,
we
should
all
be
p o ec ed
om
in e p e a ions
ha
may
lead
o
gene ic
disc imina-
ion.
Hence,
biobanks
ha
selec i ely
a ge
a
subse
o
he
popula ion
based
on
social
no ions
o
ace
o
he
ac ions
o
employe s,
insu e s
o
go e nmen s
ha
use
gene ic
in o ma-
ion
esul ing
om
gene ic
es s
o
a o
a
gi en
gene ic
ai ,
a e
all
o ms
o
gene ic
disc imina ion
ha
may
cons i u e
a
iola ion
o
human
igh s.
Fu he mo e,
gene ic
in e en-
ions
in
he
con ex
o
gene
he apy
could
also
in ol e
a
isk
o
disc imina ion
ha
should
no
be
unde es ima ed.
Fi s ly,
s ic ly
speaking
o
soma ic
in e en ions,
hese
he apies
a e
ex emely
expensi e
and
a e
expec ed
o
emain
so
in
he
nea
u u e.
This
ac
should
highligh
he
impo ance
o
ai ness
and
equali y
in
access
o
heal h
–
which
a e
elemen s
o
he
human
igh
o
heal hs–
and
emembe
he
human
igh
o
enjoy
he
benefi s
o
science
and
i s
applica ions.
Secondly,
one
mus
bea
in
mind
he
unknown
challenges
o
ge mline
al e a ions
and
he
po en ial
o
disc imina ion
ha
jus i y
he
See
The
Gua dian
news
a icle
he e:
h p://www. hegua dian.
com/science/2010/ eb/17/desmond- u u-genome-gene ic-
di e si y.
sSee
WHO
Fac
shee
n◦323
a ailable
he e:
h p://www.who.in /
mediacen e/ ac shee s/ s323/en/.
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
171
gene al
p ohibi ion
ha
is
in
place
oday
and
ha
is
likely
o
be
main ained
and
pe haps
e en
s eng hened
in
in e -
na ional
law
in
he
u u e.50,109,110 Impo an ly,
his
issue
is
linked
wi h
he
b oade
issue
o
human
enhancemen
ha
has
been
he
subjec
o
in ense
deba e
since
he
HGP
and
will
ce ainly
con inue
o
be
o
yea s
o
come.
In
pa allel,
he
po en ial
o
gene ic
disc imina ion
in
he
con ex
o
he
pe sonalized
medicine
endea o
is
ne e
comple e
wi hou
add essing
he
issue
o
da a
p i acy.
This
ma e
is
e y
complex
and
canno
be
looked
a
in
isola-
ion
om
b oade
social
phenomena
ha
poin
owa d
an
e osion
o
p i acy
in
ou
daily
li es.
Fu he mo e,
he
issue
o
p i acy
is
ecu en
whe he
we
discuss
esea ch,
diag-
nosis
o
he apy.111 A
good
example
is
ha
o
companies
o e ing
DTC
gene ic
es s,
which
aim
o
o
do
al eady
un
biobanks
o
esea ch
pu poses.
The
possibili y
ha
indi id-
ual
in o ma ion,
including
gene ic
in o ma ion,
p esen
in
biobank
da abases
is
coupled
wi h
p i a e
heal h
da a
and
held
by
p ofi -o ien ed
en i ies
aises
impo an
e hical
and
legal
ques ions
in
e ms
o
anspa ency
and
da a
p o-
ec ion
egula ion.
Addi ionally,
aw
gene ic
in o ma ion,
held
by
ins i u ions
should
no
only
be
p o ec ed
om
access
by
hi d
pa ies
wi hou
consen
bu
also
be
accessible
by
he
indi iduals
om
which
ha
in o ma ion
was
de i ed.66,112,113
This
discussion
is
undamen al
whe he
one
de ends
he
pa -
icula
na u e
o
gene ic
in o ma ion
o
whe he
one
sees
gene ic
da a
as
simila
o
any
o he
heal h
da a.21,45,114,115
The e o e,
he
issue
o
gene ic
p i acy
is
cen al
o
he
pe son-
alized
medicine
deba e
and
i s
pa icula
challenges
should
be
add essed
in
o de
o
ga he
public
us
and
app oxima e
he
ad ancemen
o
science
and
echnology
o
socie al
conce ns,
p inciples
and
alues.
Finally,
hese
undamen al
p emises,
he
na u e
o
DNA
and
gene ic
in o ma ion
and
he
app oxi-
ma ion
o
science
and
socie y,
a e
also
cen al
o
a
deba e
ha
canno
be
de eloped
he e
bu
which
is
o
e hical
and
legal
ele ance
as
well
–
he
issue
o
pa en ing
o
human
genes.
This
deba e
has
significan
amifica ions
and
ecen
de elop-
men s
on
he
subjec
dese e
a
dedica ed
analysis,
which
can
be
ound
elsewhe e.116,117
Conclusion
Scien ific
p og ess
is
exponen ial
and
so
a e
i s
highes
p omises
and
sub e si e
po en ial
when
i
is
used
abusi ely.
We
mus
bea
in
mind
ha
he
same
p og ess
ha
has
led
o
eno mous
gains
in
e ms
o
bo h
quan i y
and
quali y
o
li e
h oughou
he
yea s,
has
also
pe mi ed
ha
a
g ea
deal
o
des uc i e
beha io
hinde ed
science’s
mos
al uis ic
e o s.
Es ima ing
he
po en ial
o
p og ess
and
dis up ion
in ol es
no
only
analyzing
cu en
de elopmen s
by
di e en
social,
cul u al
and
his o ical
pe spec i es
bu
also
emba king
on
p ognosis
exe cises
o
en isage
u u e
endencies.
Bo h
hese
exe cises
a e
e y
complex
and
p one
o
e o
and
bias
and
he e o e
mus
be
app oached
wi h
cau ion.
Howe e ,
com-
plexi y
should
no
se e
as
an
excuse
o
inac ion.
His o y
is
ull
o
examples
whe e
abusi e
uses
echnology
and
science
o
he
mis ep esen a ion
o
i s
aims
led
o
g ea
p oblems
and
in
some
cases
su e ing.
Also
in
he
case
o
gene ics
and
pe son-
alized
medicine
we
mus
make
su e
ha
we
ha e
collec i ely
lea ned
om
hose
episodes.
We
can
s a
by
dis inguishing
hope
om
hype
and
finding
in
law
and
e hics
essen ial
allies
o
limi
he
la e
and
po en ia e
he
o me .
Final
no e
In
Po ugal,
some
o
he
mos
ele an
e hical
and
legal
challenges
discussed
abo e
ha e
been
subjec
o
dedica ed
legisla ion
and
he
opinion
o
impo an
na ional
e hics
bod-
ies.
The
gene al
solu ions
o
he
Po uguese
e hical
and
legal
amewo k
in
his
con ex ,
some
o
which
a e
e y
unique,118
oge he
wi h
he
co esponding
main
no ma i e
ins umen s
o
each
example
discussed
in
his
a icle,
a e
p esen ed
in
Table
1.
Conflic s
o
in e es
The
au ho s
ha e
no
conflic s
o
in e es
o
decla e.
172
e
p
o
s
a
ú
d
e
p
ú
b
l
i
c
a
.
2
0
1
4;3
2(2):164–180
Table
1
–
Summa y
o
he
Po uguese
e hical
and
legal
amewo k
on
some
o
he
mos
ele an
e hical
and
legal
challenges
o
pe sonalized
medicine.
Examples
o
esea ch
(biobanks),
p e en ion
and
diagnosis
(gene ic
es s),
and
ea men
(gene
he apy)
a e
p esen ed,
as
well
as
o he
ele an
gene al
no ms.
The
co esponding
main
no ma i e
ins umen s
o
each
example
a e
also
indica ed.
Rele an
na ional
no ma i e
ins umen s
In o med
consen
P i acy
and
confiden iali y
O he
Gene al
Legal
and
egula o y
documen s
-
Cons i u ion
o
he
Po uguese
Republic
(CRP);
-
Po uguese
Penal
Code;
-
Po uguese
Ci il
Code;
-
Heal h
Basis
Law
(Law
48/90
o
24
Augus );
-
Law
12/2005
o
26
Janua y
on
pe sonal
gene ic
in o ma ion
and
heal h
in o ma ion;
-
Law
67/98
o
26
Oc obe
on
he
p o ec ion
o
pe sonal
da a;
-
Law
21/2014
o
16
Ap il
on
clinical
esea ch
-
No m
015/2013
o
he
Di ec o a e-Gene al
o
Heal h
on
in o med
consen
o
ea men ,
diagnosis
and
pa icipa ion
in
esea ch
s udies
-
No m
16/DSMIA
(2001)
o
he
Di ec o a e-Gene al
o
Heal h
on
in o med
consen
in
p e-na al
diagnosis
Opinions
o
he
Na ional
Council
o
E hics
o
he
Li e
Sciences
-
43/CNECV/2004
on
pe sonal
gene ic
in o ma ion
and
heal h
in o ma ion;
-
Gene al
p inciple
–
he
mo al
and
physical
in eg i y
o
e e y
indi idual
is
in iolable.
The
law
p o ec s
indi iduals
agains
any
illici
o ense
o
h ea
o
hei
physical
and
mo al
pe sonali y.
(CRP,
a .
25/1;
Ci il
Code,
a .
70);
-
In o med
consen
excludes
he
unlaw ulness
o
he
ac
when
i
e e s
o
eely
disposable
legal
in e es s
and
he
ac
does
no
o end
social
mo es.
P esumed
consen
equals
exp ess
consen
when
i
can
be
easonably
assumed
ha
he
agen
would
ha e
consen ed
unde
hose
specific
ci cums ances.
Minimum
age
o
alid
consen
is
16
yea s
old.
(Penal
Code,
a s.
38,
39;
Ci il
Code,
a .
340);
-
E e y
pa ien
has
he
igh
o
consen
o
e use
heal h
ca e
and
o
be
in o med
abou
his/he
si ua ion,
al e na i e
ea men
and
p ognosis
(Heal h
Basis
Law
-Law
48/90,
Base
XIV/1/a,
b):
-
In o med
consen
ules
in
he
case
o
medical-su gical
ea men s
and
he
du y
o
in o m
and
cla i y
(Penal
Code,
a s.
149,
150,
156,
157).
-
E e yone
shall
possess
he
igh
o
p o ec
he
p i acy
o
hei
pe sonal
and
amily
li e
(CRP,
a .
26/1);
-
Gene al
p inciple
-
he
p ocessing
o
heal h
and
gene ic
da a
is
p ohibi ed.
Excep ions:
o he
legal
p o isions;
exp ess
consen
om
he
da a
subjec ;
i al
in e es s
o
he
da a
subjec
in
he
case
o
incapaci y;
Na ional
Da a
P o ec ion
Au ho i y
(CNPD)
au ho iza ion
on
he
g ounds
o
public
heal h
in e es
p o ided
ha
non-disc imina ion
and
secu i y
measu es
a e
implemen ed;
necessi y
o
he
pu poses
o
p e en i e
medicine,
medical
diagnosis,
ea men
o
he
managemen
o
heal h-ca e
se ices
p o ided
ha
in o ma ion
is
p ocessed
by
an
indi idual
bound
by
p o essional
sec ecy
and
CNPD
is
no ified
(Law
67/98,
a s.
7,
15,
27);
-
P ocessing
o
heal h
and
gene ic
in o ma ion
mus
espec
all
adequa e
measu es
o
p o ec
confiden iali y
(includes
secu i y
o
he
p emises,
equipmen
and
in o ma ion)
and
o
en o ce
he
p o essional
du y
o
confiden iali y
(Law12/2005,
a .
4/1);
-
Heal h
in o ma ion
can
only
be
used
wi h
w i en
au ho iza ion
om
he
pe son
o
whom
i
pe ains
(o
legal
ep esen a i e)
(Law12/2005,
a .
4/3);
-
Gene ic
in o ma ion
mus
be
subjec
o
legisla i e
and
adminis a i e
measu es
o
ein o ced
p o ec ion
in
e ms
o
access,
secu i y
and
confiden iali y
(Law12/2005,
a .6/6);
-
Fundamen al
p inciple
–
digni y
o
he
human
pe son
(CRP,
a .
1);
-
E e yone
shall
possess
he
igh
o
legal
p o ec ion
agains
any
o m
o
disc imina ion
(CRP,
a .
26/1);
-
The
law
shall
gua an ee
he
pe sonal
digni y
and
gene ic
iden i y
o
he
human
pe son,
pa icula ly
in
he
c ea ion,
de elopmen
and
use
o
echnologies
and
in
scien ific
expe imen a ion
(CRP,
26/3);
-
Heal h
in o ma ion,
including
gene ic
da a
is
p ope y
o
he
pe son
o
whom
i
pe ains
and
i
canno
be
used
o
any
o he
pu poses
han
heal h
ca e
and
heal h
ela ed
esea ch,
o
o he
pu poses
defined
by
law
(Law
12/2005,
a .
3/1);
-
S o ed
biological
ma e ial
emains
p ope y
o
he
pe son
om
whom
i
was
collec ed
and,
in
case
o
dea h
o
incapaci y,
o
his/he
ela i es
(Law
12/2005,
a s.
18/2,
19/13);
-
In
special
ci cums ances,
when
in o ma ion
is
impo an
o
he
ea men
o
he
p e en ion
o
a
gene ic
disease
in
he
amily,
in o ma ion
can
be
used
in
he
con ex
o
gene ic
counseling
–
e en
i
i
is
no
longe
possible
o
ob ain
he
in o med
consen
om
he
pe son
o
whom
i
belongs
(Law
12/2005,
a .
18/6);
-
Rela i es
in
di ec
line
o
ascen
o
descen ,
as
well
as
second
deg ee
ela i es,
can
access
a
s o ed
sample
o
gene ic
ma e ial,
in
case
i
is
necessa y
o
ob ain
a
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