<s>
A	O
biological	B-Algorithm
pacemaker	I-Algorithm
is	O
one	O
or	O
more	O
types	O
of	O
cellular	O
components	O
that	O
,	O
when	O
"	O
implanted	O
or	O
injected	O
into	O
certain	O
regions	O
of	O
the	O
heart	O
,	O
"	O
produce	O
specific	O
electrical	O
stimuli	O
that	O
mimic	O
that	O
of	O
the	O
body	O
's	O
natural	B-Algorithm
pacemaker	I-Algorithm
cells	O
.	O
</s>
<s>
Biological	B-Algorithm
pacemakers	I-Algorithm
are	O
indicated	O
for	O
issues	O
such	O
as	O
heart	B-Algorithm
block	I-Algorithm
,	O
slow	B-Algorithm
heart	I-Algorithm
rate	I-Algorithm
,	O
and	O
asynchronous	B-Algorithm
heart	I-Algorithm
ventricle	I-Algorithm
contractions	I-Algorithm
.	O
</s>
<s>
The	O
biological	B-Algorithm
pacemaker	I-Algorithm
is	O
intended	O
as	O
an	O
alternative	O
to	O
the	O
artificial	B-Device
cardiac	I-Device
pacemaker	I-Device
that	O
has	O
been	O
in	O
human	O
use	O
since	O
the	O
late	O
1950s	O
.	O
</s>
<s>
Despite	O
their	O
success	O
,	O
several	O
limitations	O
and	O
problems	O
with	O
artificial	B-Device
pacemakers	I-Device
have	O
emerged	O
during	O
the	O
past	O
decades	O
such	O
as	O
electrode	O
fracture	O
or	O
damage	O
to	O
insulation	O
,	O
infection	O
,	O
re-operations	O
for	O
battery	O
exchange	O
,	O
and	O
venous	O
thrombosis	O
.	O
</s>
<s>
The	O
need	O
for	O
an	O
alternative	O
is	O
most	O
obvious	O
in	O
children	O
,	O
including	O
premature	O
newborn	O
babies	O
,	O
where	O
size	O
mismatch	O
and	O
the	O
fact	O
that	O
pacemaker	B-Device
leads	O
do	O
not	O
grow	O
with	O
children	O
are	O
a	O
problem	O
.	O
</s>
<s>
However	O
,	O
the	O
implanted	O
biological	B-Algorithm
pacemaker	I-Algorithm
cells	O
still	O
typically	O
need	O
to	O
be	O
supplemented	O
with	O
an	O
artificial	B-Device
pacemaker	I-Device
while	O
the	O
cells	O
form	O
the	O
necessary	O
electrical	O
connections	O
with	O
cardiac	O
tissue	O
.	O
</s>
<s>
The	O
first	O
successful	O
experiment	O
with	O
biological	B-Algorithm
pacemakers	I-Algorithm
was	O
carried	O
out	O
by	O
Arjang	O
Ruhparwar	O
'	O
s	O
group	O
at	O
Hannover	O
Medical	O
School	O
in	O
Germany	O
using	O
transplanted	O
fetal	O
heart	O
muscle	O
cells	O
.	O
</s>
<s>
The	O
investigators	O
postulated	O
latent	O
pacemaker	B-Device
capability	O
in	O
normal	O
heart	O
muscle	O
cells	O
.	O
</s>
<s>
This	O
potential	O
ability	O
is	O
suppressed	O
by	O
the	O
inward-rectifier	O
potassium	O
current	O
Ik1	O
encoded	O
by	O
the	O
gene	O
Kir2	O
which	O
is	O
not	O
expressed	O
in	O
pacemaker	B-Algorithm
cells	I-Algorithm
.	O
</s>
<s>
By	O
specific	O
inhibition	O
of	O
Ik1	O
below	O
a	O
certain	O
level	O
,	O
spontaneous	O
activity	O
of	O
cardiomyocytes	O
was	O
observed	O
with	O
resemblance	O
to	O
the	O
action	O
potential	O
pattern	O
of	O
genuine	O
pacemaker	B-Algorithm
cells	I-Algorithm
.	O
</s>
<s>
Meanwhile	O
,	O
other	O
genes	O
and	O
cells	O
have	O
been	O
discovered	O
,	O
including	O
heart	O
muscle	O
cells	O
derived	O
from	O
embryonic	O
stem	O
cells	O
,	O
"	O
HCN	O
"	O
genes	O
which	O
encode	O
the	O
wild	O
type	O
pacemaker	B-Device
current	O
I(f )	O
.	O
</s>
<s>
In	O
2010	O
,	O
Ruhparwar	O
's	O
group	O
again	O
demonstrated	O
a	O
type	O
of	O
biological	B-Algorithm
pacemaker	I-Algorithm
,	O
this	O
time	O
showing	O
that	O
by	O
injection	O
of	O
the	O
"	O
Adenylate	O
Cyclase	O
"	O
gene	O
into	O
the	O
heart	O
muscle	O
a	O
biological	O
cardiac	B-Algorithm
pacemaker	I-Algorithm
can	O
be	O
created	O
.	O
</s>
<s>
In	O
2014	O
,	O
a	O
gene	O
called	O
TBX18	B-Algorithm
has	O
been	O
non-invasively	O
applied	O
to	O
speed	O
up	O
heart	O
rates	O
caused	O
by	O
heart	B-Algorithm
block	I-Algorithm
.	O
</s>
