UTSKRIFT 🔗
1
00:00:01,200 --> 00:00:05,010
Kristelle Shulman: My name is
Kristelle Shulman. I am a nurse
2
00:00:05,010 --> 00:00:09,540
practitioner for about almost 20
years,
3
00:00:09,720 --> 00:00:13,290
Evan Shulman: and I'm Evan
Shulman, and I've been a PA, or
4
00:00:13,350 --> 00:00:15,270
physician assistant, for 20
years.
5
00:00:15,270 --> 00:00:18,720
Kristelle Shulman: That's
actually how we met. In the
6
00:00:18,810 --> 00:00:19,260
hospital.
7
00:00:19,380 --> 00:00:25,065
Evan Shulman: Yep, that was it.
She said hello to me in the
8
00:00:25,065 --> 00:00:28,575
elevator, and we had both looked
at each other, I guess, for a
9
00:00:28,575 --> 00:00:32,145
while, but at the time Kristelle
was working in the recovery
10
00:00:32,145 --> 00:00:37,035
area, and I never had an excuse
to talk to her, and the elevator
11
00:00:37,035 --> 00:00:41,175
was, was it one day.
12
00:00:41,175 --> 00:00:44,055
Lauren Arora Hutchinson: In many
ways, Evan and Kristelle are an
13
00:00:44,055 --> 00:00:50,370
ordinary couple, two working
people with busy lives. They're
14
00:00:50,370 --> 00:00:54,240
now married. They live in New
York City. They love to
15
00:00:54,240 --> 00:00:59,190
exercise. And shortly after
getting married in 2015, they
16
00:00:59,190 --> 00:01:04,710
did what many couples do. They
decided to start a family.
17
00:01:04,709 --> 00:01:07,109
Kristelle Shulman: We had a
normal pregnancy, as well as
18
00:01:07,109 --> 00:01:14,504
delivery. Noah was born on
December 29th, 2016 It was the
19
00:01:14,504 --> 00:01:21,674
best feeling in the world.
Inexplicable, I would say.
20
00:01:21,675 --> 00:01:26,325
Evan Shulman: He was born
relatively healthy, initially
21
00:01:26,325 --> 00:01:31,335
had some low glucose levels. He
was checked multiple times by
22
00:01:31,335 --> 00:01:34,710
the pediatric team, by the NICU.
They assured us everything was
23
00:01:34,710 --> 00:01:39,510
fine, and he was right from the
beginning pretty difficult to
24
00:01:39,510 --> 00:01:41,040
feed.
25
00:01:41,040 --> 00:01:43,530
Lauren Arora Hutchinson: Noah
struggled to breastfeed. While
26
00:01:43,530 --> 00:01:47,040
this was troubling to Evan and
Kristelle, the hospital staff
27
00:01:47,040 --> 00:01:50,490
reassured them there was nothing
to worry about.
28
00:01:50,490 --> 00:01:53,550
Evan Shulman: In the hospital,
we were assured that he's, you
29
00:01:53,550 --> 00:01:57,705
know, newborn, and he'll get it.
He just needs time to get it. By
30
00:01:57,705 --> 00:02:01,365
the time we were discharged
home, Kristelle had actually met
31
00:02:01,365 --> 00:02:06,555
with a lactation consultant, in
addition to the pediatric team,
32
00:02:06,555 --> 00:02:10,335
the NICU team. Everybody met
with us and reassured that
33
00:02:10,335 --> 00:02:12,315
everything's normal, so we went
home…
34
00:02:13,425 --> 00:02:17,265
Lauren Arora Hutchinson: Unfortunately,
the feeding troubles continued.
35
00:02:17,265 --> 00:02:19,860
Evan Shulman: And this went on.
This went on for almost 10-11
36
00:02:19,860 --> 00:02:24,540
days, and every night was
difficult, because we'd wake up
37
00:02:24,540 --> 00:02:29,970
to feed him. Feeds were taking
half hour, 45 minutes, an hour,
38
00:02:29,970 --> 00:02:32,910
sometimes. Sometimes an hour and
a half, just to get him to take
39
00:02:32,910 --> 00:02:40,410
down 15 or 20 mls of milk. So he
was, he was expending so much
40
00:02:40,410 --> 00:02:45,225
energy to feed that he was
falling asleep during the feed,
41
00:02:45,225 --> 00:02:49,815
and we said something is clearly
wrong. Like this is… this cannot
42
00:02:49,815 --> 00:02:53,175
be normal. We addressed these
concerns with our pediatrician
43
00:02:53,175 --> 00:02:56,745
in the office. At one point, he
kind of played it off as, oh,
44
00:02:56,745 --> 00:02:58,725
you're both medical
professionals and probably a
45
00:02:58,725 --> 00:03:02,265
little hyper sensitive, and
don't worry, just go home, he's
46
00:03:02,265 --> 00:03:05,310
going to feed. So, anyway, we
said something is definitely not
47
00:03:05,310 --> 00:03:09,660
right, and we called the
pediatrician's office, and the
48
00:03:09,660 --> 00:03:13,290
pediatrician, who we usually see
was not in, and we saw a much
49
00:03:13,290 --> 00:03:18,480
more junior pediatrician in the
office who spent, I would say, a
50
00:03:18,480 --> 00:03:22,680
good 30 minutes with Noah, held
him, tried to feed him, didn't
51
00:03:22,680 --> 00:03:25,860
just listen to our story and
send us out. He devoted a
52
00:03:25,860 --> 00:03:30,315
significant amount of time, and
then told us he was concerned,
53
00:03:30,315 --> 00:03:34,095
said he wasn't quite sure what
he's concerned about, and he
54
00:03:34,095 --> 00:03:38,355
said, “Go home if he's not
feeding in the next hour or two,
55
00:03:38,355 --> 00:03:43,275
then you need to take him to the
pediatric ER.” We went home, got
56
00:03:43,275 --> 00:03:47,145
a bag, and then went straight to
the ER, and that was really when
57
00:03:47,145 --> 00:03:52,455
everything started to unfold.
Um, sorry.
58
00:03:59,145 --> 00:04:00,960
Lauren Arora Hutchinson: What
happened next would change their
59
00:04:00,960 --> 00:04:04,950
lives and turn them into
accidental pioneers of genetic
60
00:04:04,950 --> 00:04:09,810
medicine. Over the next two
episodes, we're bringing you the
61
00:04:09,810 --> 00:04:13,845
story of Evan and Kristelle.
We'll retrace the steps of their
62
00:04:13,845 --> 00:04:18,585
heartbreaking journey, and hear
how they navigated a series of
63
00:04:18,585 --> 00:04:22,755
scientific and ethical
quandaries with no obvious
64
00:04:22,755 --> 00:04:28,185
answers. Along the way, their
story takes unexpected turns and
65
00:04:28,185 --> 00:04:31,815
ventures into new scientific
territory, more than we could
66
00:04:31,815 --> 00:04:36,750
cover in a single episode.
Perhaps unsurprisingly, their
67
Load full transcript
00:04:36,750 --> 00:04:42,660
story deals with some difficult
themes and challenging moments.
68
00:04:42,660 --> 00:04:47,460
Please take care while
listening. I'm Lauren Arora
69
00:04:47,460 --> 00:04:52,440
Hutchinson, director of the
iDeas Lab at the Johns Hopkins
70
00:04:52,440 --> 00:04:58,800
Berman Institute of Bioethics,
and this is playing god?
71
00:04:58,800 --> 00:05:07,275
Evan Shulman: So, when we got
there, he was pretty lethargic,
72
00:05:07,665 --> 00:05:12,165
and immediately they said that
they were concerned and started
73
00:05:12,165 --> 00:05:16,725
doing a full panel of labs on
him. We waited out through the
74
00:05:16,725 --> 00:05:20,685
night, we just stayed by his
side, and then I think the next
75
00:05:20,685 --> 00:05:27,180
day was when the metabolic team
came and saw him and they
76
00:05:27,180 --> 00:05:29,670
started to mention, for the
first time, concern for
77
00:05:29,670 --> 00:05:31,830
mitochondrial disease.
78
00:05:31,830 --> 00:05:33,900
Lauren Arora Hutchinson:
Mitochondria are like many
79
00:05:33,900 --> 00:05:38,550
little power plants in each of
our cells. Throughout our body,
80
00:05:38,550 --> 00:05:42,570
they take nutrients and convert
them into energy that cells use
81
00:05:42,570 --> 00:05:46,455
to multiply, divide, and
regulate. The doctors worried
82
00:05:46,455 --> 00:05:50,085
that something might be wrong
with these tiny power plants,
83
00:05:50,085 --> 00:05:54,015
that Noah could have been born
with a small error in the DNA of
84
00:05:54,015 --> 00:05:58,125
his mitochondria, that this
mutation could be the cause of
85
00:05:58,125 --> 00:06:02,505
Noah's problems, and that if it
was, the prognosis could be
86
00:06:02,505 --> 00:06:08,355
dire. Receiving this news, they
decided to transfer Noah to
87
00:06:08,400 --> 00:06:12,720
Mount Sinai in Manhattan, a
hospital better equipped to help
88
00:06:12,720 --> 00:06:13,800
him.
89
00:06:13,800 --> 00:06:15,900
Evan Shulman: We got there
probably around midnight. I
90
00:06:15,900 --> 00:06:20,490
mean, it was like… we had the
biggest greeting by this huge
91
00:06:20,490 --> 00:06:25,590
team, like Noah was really
swarmed by people, and we stayed
92
00:06:25,590 --> 00:06:30,810
with him there through the
night, and they said it looks
93
00:06:30,810 --> 00:06:33,495
like for sure this is going to
be a mitochondrial disease, and
94
00:06:33,495 --> 00:06:36,555
we need to wait for genetic
testing.
95
00:06:36,555 --> 00:06:38,475
Lauren Arora Hutchinson: You
might remember from biology
96
00:06:38,475 --> 00:06:42,285
class that most of your DNA is
held in the nucleus of each
97
00:06:42,285 --> 00:06:46,755
cell. That's the genetic code
that shapes our bodies and many
98
00:06:46,755 --> 00:06:51,315
of our traits, but all of your
mitochondria also carry their
99
00:06:51,315 --> 00:06:56,370
own separate bits of DNA. That
mitochondrial DNA isn’t the same
100
00:06:56,370 --> 00:07:00,600
as the rest of our DNA. It
doesn’t determine or shape most
101
00:07:00,600 --> 00:07:03,840
of who we are, but it is
essential for how our cells
102
00:07:03,840 --> 00:07:08,010
produce energy. And so when
there’s a mutation in
103
00:07:08,010 --> 00:07:13,710
mitochondrial DNA, it can cause
mitochondrial disease. That's
104
00:07:13,710 --> 00:07:18,885
what the doctors at Mount Sinai
were testing. Noah stayed in the
105
00:07:18,885 --> 00:07:23,895
hospital for days, then weeks,
as his parents waited for the
106
00:07:23,895 --> 00:07:26,295
results.
107
00:07:26,295 --> 00:07:30,375
Evan Shulman: He had a lot of
difficulties. He had seizures.
108
00:07:30,375 --> 00:07:35,235
He ended up getting intubated.
He had respiratory distress.
109
00:07:35,235 --> 00:07:38,685
Kristelle Shulman: Evan and I
would sit right by his room,
110
00:07:38,685 --> 00:07:43,350
just alone, and like, how did we
get here? What happened? You
111
00:07:43,350 --> 00:07:46,620
know, we'd come back to his room
and just make sure that we, you
112
00:07:46,620 --> 00:07:50,010
know, wipe our tears and make
sure that we, that he hears us,
113
00:07:50,010 --> 00:07:56,580
and he and I, and when we know
that he knows we're there, it's
114
00:07:56,580 --> 00:08:01,020
just like that room was
surrounded by his like essence,
115
00:08:01,020 --> 00:08:01,530
you know.
116
00:08:04,590 --> 00:08:07,935
Evan Shulman: It took about 30
days from the date of admission
117
00:08:07,935 --> 00:08:13,095
to get back the mitochondrial
panel, and the team sat down
118
00:08:13,095 --> 00:08:18,915
with us and told us that Noah
has mitochondrial disease
119
00:08:18,915 --> 00:08:25,005
confirmed, and that he has 100%
mutation load, which also known
120
00:08:25,005 --> 00:08:31,320
as homoplasmy, meaning all his
cells are affected by it.
121
00:08:31,320 --> 00:08:33,210
Lauren Arora Hutchinson: Not
everyone with mitochondrial
122
00:08:33,210 --> 00:08:38,220
disease is affected in the same
way. The human body is made up
123
00:08:38,220 --> 00:08:42,210
of trillions of cells, and every
cell contains hundreds,
124
00:08:42,210 --> 00:08:46,410
sometimes thousands of
mitochondria, each with its own
125
00:08:46,410 --> 00:08:51,525
genetic code. Some people have a
mix of healthy and mutated
126
00:08:51,525 --> 00:08:56,955
mitochondrial DNA. That's called
heteroplasmy, but Noah's test
127
00:08:56,955 --> 00:09:02,295
showed homoplasmy. 100% of his
mitochondria carried the
128
00:09:02,295 --> 00:09:09,195
mutation. Doctors refer to this
percentage as mutation load, and
129
00:09:09,195 --> 00:09:11,805
Noah's was the highest it could
possibly be.
130
00:09:11,805 --> 00:09:17,580
Kristelle Shulman: You know,
sitting in that family room, and
131
00:09:17,580 --> 00:09:20,580
just, you know, we were
surrounded by fellows and
132
00:09:20,580 --> 00:09:25,260
doctors and attendings, just the
two of us sitting like this, and
133
00:09:25,320 --> 00:09:26,940
you know, holding each other's
hands.
134
00:09:26,940 --> 00:09:33,120
Lauren Arora Hutchinson: People
meet devastating news in
135
00:09:33,120 --> 00:09:41,625
different ways. Some turn
inward. Some lean on family.
136
00:09:41,625 --> 00:09:46,785
Some focus on simply getting
through each hour. For Kristelle
137
00:09:46,785 --> 00:09:51,465
and Evan, even in the midst of
their shock, there was a sense
138
00:09:51,465 --> 00:09:56,925
of purpose, an instinct to do
everything they could for Noah.
139
00:09:56,925 --> 00:10:01,470
Evan Shulman: So, while Noah was
sick in the hospital, Kristelle
140
00:10:01,470 --> 00:10:06,120
and I sort of took on different
roles. She was obviously Noah's
141
00:10:06,120 --> 00:10:11,550
mom and was there for, you know,
the best compassion that she
142
00:10:11,550 --> 00:10:17,100
could ever give her son, and my
role was figuring out how are we
143
00:10:17,100 --> 00:10:20,250
gonna make sure that Noah's
getting the best care possible
144
00:10:20,250 --> 00:10:25,575
at the same time. So, I did a
PubMed search, which searches
145
00:10:25,575 --> 00:10:29,385
all medical journals, and I
searched for the specific
146
00:10:29,385 --> 00:10:35,025
mutation that Noah has, and I
emailed every author on every
147
00:10:35,025 --> 00:10:40,155
paper that I could get a hold
of… had a tremendous response,
148
00:10:40,155 --> 00:10:43,035
almost everybody wrote back to
me whether they had any
149
00:10:43,035 --> 00:10:50,010
information to provide or not.
And in particular, Newcastle
150
00:10:50,010 --> 00:10:54,510
University in England wrote
back, and it turns out Newcastle
151
00:10:54,510 --> 00:10:58,200
had a family with the exact same
mutation that they've been
152
00:10:58,200 --> 00:11:03,540
following. They, they asked us
what they were doing for Noah.
153
00:11:03,540 --> 00:11:07,680
We told them, and sadly the only
treatment was supportive care,
154
00:11:08,415 --> 00:11:13,455
and they assured us that, you
know, what was being done is the
155
00:11:13,455 --> 00:11:17,115
best that can be done.
156
00:11:17,115 --> 00:11:19,155
Lauren Arora Hutchinson: For
Evan and Kristelle, it was
157
00:11:19,155 --> 00:11:23,385
confirmation that Noah's life
couldn't be saved, only made
158
00:11:23,385 --> 00:11:24,915
more comfortable.
159
00:11:24,915 --> 00:11:30,375
Kristelle Shulman: Having our
son just, you know, laying in
160
00:11:30,375 --> 00:11:37,770
that incubator, sorry, like
really just holding on to his
161
00:11:37,770 --> 00:11:45,540
dear life, you know, and I
wasn't ready to let him go. You
162
00:11:45,540 --> 00:11:52,260
know, we weren't ready to let
him go.
163
00:11:52,260 --> 00:11:56,415
Evan Shulman: Noah spent more
than two months in the NICU,
164
00:11:56,415 --> 00:12:01,605
like that became his home, and
we were very fortunate. The team
165
00:12:01,605 --> 00:12:05,115
taking care of him, and the
nurses, they were
his family,
166
00:12:05,115 --> 00:12:07,845
the things that they saw him go
through, and we saw him go
167
00:12:07,845 --> 00:12:12,825
through. I mean, how do you, how
do you, why would this happen to
168
00:12:12,825 --> 00:12:20,385
a baby? There's really no
explanation.
169
00:12:20,385 --> 00:12:23,820
Kristelle Shulman: He had like
these two episodes of like
170
00:12:23,820 --> 00:12:31,950
cardiac arrest, and like the
first one I like yelled out from
171
00:12:31,950 --> 00:12:37,080
outside, and I said, I'm not
ready to let you go yet. Don't
172
00:12:37,080 --> 00:12:45,375
go, and he didn't go, and then I
think that the last time, the
173
00:12:45,375 --> 00:12:50,865
last one, we were actually able
to say goodbye, like I felt like
174
00:12:50,865 --> 00:12:56,505
I was able to say I need you to
rest now. I don't want you to
175
00:12:56,505 --> 00:13:04,065
suffer anymore. No one, babies,
any humans, any one should ever
176
00:13:04,515 --> 00:13:05,520
go through this.
177
00:13:10,560 --> 00:13:15,030
Evan Shulman: Noah passed away
at just shy of three months old.
178
00:13:15,030 --> 00:13:24,510
Lauren Arora Hutchinson: It was
a terrible end to a
179
00:13:24,510 --> 00:13:29,235
heartbreaking three month
ordeal, but it was also the
180
00:13:29,235 --> 00:13:34,485
start of a much longer odyssey,
because when Noah was tested and
181
00:13:34,485 --> 00:13:39,375
diagnosed with mitochondrial
disease, the doctors also tested
182
00:13:39,375 --> 00:13:47,115
Kristelle, and the results there
weren't good news either.
183
00:13:47,115 --> 00:13:53,010
Kristelle Shulman: I had about
75% of the dysfunction, the
184
00:13:53,010 --> 00:13:57,630
mitochondrial dysfunction, and
so I had to also worry about my
185
00:13:57,630 --> 00:14:00,540
health as well.
186
00:14:00,540 --> 00:14:02,970
Evan Shulman: And, sort of in
the same breath, they said you
187
00:14:02,970 --> 00:14:11,040
guys cannot have healthy
biologic children.
188
00:14:11,040 --> 00:14:13,995
Lauren Arora Hutchinson: You
see, while the nuclear DNA that
189
00:14:13,995 --> 00:14:19,455
shapes who we are is inherited
from both parents...
190
00:14:19,455 --> 00:14:21,465
Marni Falk: All of our
mitochondria comes through our
191
00:14:21,465 --> 00:14:24,345
mother through the egg.
192
00:14:24,345 --> 00:14:26,895
Lauren Arora Hutchinson: This is
Dr. Marni Falk, a clinical
193
00:14:26,895 --> 00:14:32,085
geneticist and pediatrician. She
runs the mitochondrial medicine
194
00:14:32,085 --> 00:14:35,295
frontier program at the
Children's Hospital of
195
00:14:35,295 --> 00:14:36,105
Philadelphia.
196
00:14:36,105 --> 00:14:40,260
Marni Falk: When somebody's a
carrier of a mitochondrial DNA
197
00:14:40,260 --> 00:14:45,120
mutation, the question becomes:
do all of her eggs have this?
198
00:14:45,120 --> 00:14:50,610
Will every child get this? If
you had jelly beans in a jar,
199
00:14:50,610 --> 00:14:54,330
like some were red and some were
green, and you put your hand in,
200
00:14:54,330 --> 00:14:57,930
how many red would you pull out?
Well, it's very hard to predict,
201
00:14:57,975 --> 00:15:01,065
right? And you'd probably pull
out a different percentage each
202
00:15:01,065 --> 00:15:04,005
time, and that's what happens
with these mutations.
203
00:15:05,385 --> 00:15:08,235
Evan Shulman: And...
204
00:15:08,210 --> 00:15:10,700
Kristelle Shulman: Yeah, that
was um... sorry.
205
00:15:10,700 --> 00:15:11,090
Evan Shulman: Kristelle -
206
00:15:11,420 --> 00:15:15,410
Kristelle Shulman: Do you mind?
It's, you know, it was
207
00:15:15,410 --> 00:15:20,180
heartbreaking because we had a
vision, you know, like of our
208
00:15:20,180 --> 00:15:27,050
family and of a big family. And
so, you know, when we heard
209
00:15:27,050 --> 00:15:35,015
that, we thought that was like a
death sentence. We were told
210
00:15:35,015 --> 00:15:39,515
that that was it, you know, we
could either do adoption or egg
211
00:15:39,515 --> 00:15:44,765
donation, but… so that was a
really tough thing to swallow.
212
00:15:45,095 --> 00:15:46,265
It was hard.
213
00:15:48,495 --> 00:15:50,445
Lauren Arora Hutchinson: But
they weren't ready to give up on
214
00:15:50,445 --> 00:15:54,285
their dream of having
biologically related children,
215
00:15:54,285 --> 00:15:59,025
and so the Shulmans wrote back
to the people in Newcastle.
216
00:15:59,025 --> 00:16:01,485
Evan Shulman: I emailed them
back, and I said, what are...
217
00:16:01,485 --> 00:16:06,135
what other options would we have
in the future for other children
218
00:16:06,135 --> 00:16:11,220
when we first heard about
mitochondrial replacement
219
00:16:11,220 --> 00:16:15,840
therapy, or MRT.
220
00:16:15,840 --> 00:16:18,750
Lauren Arora Hutchinson: MRT is
a fascinating science fiction
221
00:16:18,750 --> 00:16:21,510
sounding technology.
222
00:16:21,510 --> 00:16:23,940
Marni Falk: Colloquially, people
refer to it as a three parent
223
00:16:23,940 --> 00:16:27,510
baby, but the proper term is
mitochondrial replacement
224
00:16:27,510 --> 00:16:29,160
technology.
225
00:16:29,160 --> 00:16:31,980
Jeffrey Kahn: You're combining
genetic material from two women
226
00:16:32,430 --> 00:16:36,705
to make one egg, which is then
fertilized by one sperm.
227
00:16:36,705 --> 00:16:39,525
Lauren Arora Hutchinson: Jeffrey
Kahn, our resident bioethicist
228
00:16:39,525 --> 00:16:42,795
and director of the Johns
Hopkins Berman Institute of
229
00:16:42,795 --> 00:16:47,115
Bioethics. And he says a
technology like this could work
230
00:16:47,115 --> 00:16:50,745
well in cases like the Shulmans,
because of how our cells are
231
00:16:50,745 --> 00:16:55,440
structured and how mitochondrial
DNA is passed from mothers to
232
00:16:55,440 --> 00:16:57,030
their children.
233
00:16:57,030 --> 00:17:00,000
Jeffrey Kahn: Mitochondria are
in the cytoplasm of a cell, so
234
00:17:00,000 --> 00:17:03,360
think
of that as the white part
of a chicken egg. If you don't
235
00:17:03,360 --> 00:17:06,720
want that white part to be
passed on, you need to figure
236
00:17:06,720 --> 00:17:09,840
out how to get the yolk part,
where the nucleus is, where the
237
00:17:09,840 --> 00:17:15,060
DNA that makes us who we are
resides out of the egg of a
238
00:17:15,060 --> 00:17:18,870
woman who we know carries
mitochondrial DNA disease. So,
239
00:17:18,870 --> 00:17:22,455
think of it as plucking out the
yellow and putting it into the
240
00:17:22,455 --> 00:17:27,555
white part of a chicken egg that
has had its yellow part removed.
241
00:17:27,555 --> 00:17:32,055
Marni Falk: And you basically do
a swap. You take out the nucleus
242
00:17:32,055 --> 00:17:35,085
from the intended parents, and
you put it into the cell that
243
00:17:35,085 --> 00:17:39,165
has healthy mitochondria from
the donor.
244
00:17:39,165 --> 00:17:44,250
Jeffrey Kahn: MRT seems to offer
a way to eliminate the risk of
245
00:17:44,250 --> 00:17:48,330
mitochondrial DNA disease, and
it certainly holds out the
246
00:17:48,330 --> 00:17:51,870
prospect of that in a way that
other options at that time
247
00:17:51,870 --> 00:17:56,010
certainly did not.
248
00:17:56,010 --> 00:17:58,620
Lauren Arora Hutchinson: The
science behind MRT first began
249
00:17:58,620 --> 00:18:04,140
to take shape in the early
2000s. Over the next decade,
250
00:18:04,170 --> 00:18:07,365
researchers showed that these
techniques could work, first in
251
00:18:07,365 --> 00:18:12,105
animals and then in human
embryos, raising the possibility
252
00:18:12,105 --> 00:18:17,445
of preventing mitochondrial
disease. But MRT would also
253
00:18:17,445 --> 00:18:21,615
raise profound ethical questions
about altering the genetics of
254
00:18:21,615 --> 00:18:24,045
children who might be born this
way.
255
00:18:27,585 --> 00:18:29,430
Jeffrey Kahn: You're changing
the genetic makeup of the
256
00:18:29,430 --> 00:18:39,210
mitochondria in that individual.
It's a heritable genetic change.
257
00:18:39,210 --> 00:18:42,270
Lauren Arora Hutchinson:
Heritable, meaning the genetic
258
00:18:42,270 --> 00:18:46,320
changes created through MRT can
be passed down to future
259
00:18:46,320 --> 00:18:53,655
generations. This creates an
ethical conundrum. How should we
260
00:18:53,655 --> 00:18:58,005
think about the risks and
consequences, not only for the
261
00:18:58,005 --> 00:19:02,835
baby born through this process,
but that baby's future children,
262
00:19:03,915 --> 00:19:13,770
or their children's children?
Around the world, policymakers
263
00:19:13,770 --> 00:19:19,380
began grappling with MRT. In the
United Kingdom, the government
264
00:19:19,380 --> 00:19:23,640
launched a formal process,
including public consultation,
265
00:19:23,640 --> 00:19:27,840
to consider whether, and how, to
allow the procedure on a case by
266
00:19:27,840 --> 00:19:35,280
case basis. In the United
States, federal agencies were
267
00:19:35,325 --> 00:19:39,195
also beginning to weigh the
scientific and ethical questions
268
00:19:39,195 --> 00:19:48,075
raised by MRT. The U.S. Food and
Drug Administration, or FDA,
269
00:19:48,075 --> 00:19:52,485
asked the U.S. National Academy
of Medicine to convene an expert
270
00:19:52,485 --> 00:19:57,555
committee in 2015, chaired by
our very own, Jeffrey Kahn.
271
00:19:57,555 --> 00:20:01,320
Jeffrey Kahn: And so the first
question we wrestled with is, is
272
00:20:01,320 --> 00:20:04,500
it ethically acceptable to
create that kind of heritable
273
00:20:04,500 --> 00:20:07,770
genetic change which would be
passed on to future generations?
274
00:20:11,010 --> 00:20:13,080
Lauren Arora Hutchinson: The
expert committee spent a year
275
00:20:13,080 --> 00:20:17,220
reviewing the latest science and
debating the ethics of such a
276
00:20:17,220 --> 00:20:23,325
novel reproductive technology.
They heard testimony from
277
00:20:23,325 --> 00:20:27,705
scientists, physicians, and,
importantly, affected families.
278
00:20:30,195 --> 00:20:35,025
In the end, they issued a report
with recommendations to the FDA
279
00:20:35,055 --> 00:20:39,165
about how to move forward.
280
00:20:39,210 --> 00:20:42,090
Jeffrey Kahn: In the case of
mitochondria, that passage only
281
00:20:42,090 --> 00:20:46,560
happens through the maternal
line from mothers to their
282
00:20:46,560 --> 00:20:52,050
offspring, and so if a daughter
were created this way, then she
283
00:20:52,050 --> 00:20:56,730
would pass on that mitochondrial
DNA change to her offspring, but
284
00:20:56,730 --> 00:21:04,095
if a male, a boy was born, he
would not. So, if you don't
285
00:21:04,095 --> 00:21:07,425
implant female embryos, there's
no way of passing on the
286
00:21:07,425 --> 00:21:10,965
heritable genetic change to
future offspring. So, that was
287
00:21:10,965 --> 00:21:15,495
one way for us to avoid the
concerns about heritable genetic
288
00:21:15,495 --> 00:21:19,965
change through generations has
its own ethics concerns when
289
00:21:19,965 --> 00:21:23,235
you're talking about sex
selection, but we thought that
290
00:21:23,235 --> 00:21:26,610
was a reasonable trade off,
certainly for the purpose of FDA
291
00:21:26,790 --> 00:21:28,260
review in a clinical trial.
292
00:21:39,310 --> 00:21:42,430
Lauren Arora Hutchinson: But in
the end, the agency’s hands were
293
00:21:42,430 --> 00:21:47,410
tied. The U.S. government took a
different position.
294
00:21:48,340 --> 00:21:50,770
Archive: If there is no further
debate, the member from Alabama,
295
00:21:50,770 --> 00:21:52,555
Lauren Arora Hutchinson: while
Jeffrey Kahn and the other
296
00:21:52,555 --> 00:21:55,465
committee members were in the
meeting room to deliver their
297
00:21:55,465 --> 00:21:57,805
recommendations to the FDA.
298
00:21:57,840 --> 00:22:00,630
Archive: Thank you, Madam Chair.
The bottom line is the science
299
00:22:00,630 --> 00:22:04,230
and the bioethics need to catch
up with potential disasters that
300
00:22:04,230 --> 00:22:06,120
could occur.
301
00:22:07,170 --> 00:22:11,580
Jeffrey Kahn: We were told that
the budget bill, the last budget
302
00:22:11,580 --> 00:22:15,570
bill in the Obama administration
included a rider restricting the
303
00:22:15,570 --> 00:22:20,325
FDA from receiving any
applications for licensure of a
304
00:22:20,325 --> 00:22:25,935
technology that modified a human
embryo genetically or led to any
305
00:22:25,935 --> 00:22:28,215
heritable genetic change.
306
00:22:28,215 --> 00:22:30,705
Archive: Question is on the
amendment offered by the member
307
00:22:30,705 --> 00:22:35,535
from Alabama, all those in favor
say aye. Aye. Those opposed, say
308
00:22:35,535 --> 00:22:39,135
no. No. In the opinion of the
chair, the ayes have it, and the
309
00:22:39,135 --> 00:22:40,365
amendment is adopted.
310
00:22:43,140 --> 00:22:46,380
Jeffrey Kahn: And therefore, it
would mean they would be
311
00:22:46,380 --> 00:23:03,630
prohibited from receiving
license applications to do MRT.
312
00:23:26,055 --> 00:23:28,125
Lauren Arora Hutchinson: Next
time on playing god?
313
00:23:29,370 --> 00:23:31,770
Evan Shulman: We have to figure
out a way to do MRT.
314
00:23:31,770 --> 00:23:34,110
Kristelle Shulman: I wanted to
keep going. I wasn't going to
315
00:23:34,110 --> 00:23:42,120
stop. I knew once I held him, I
knew once I had him, like it's
316
00:23:42,120 --> 00:23:48,990
just something that I don't want
to miss out on.
317
00:23:48,990 --> 00:23:50,820
Lauren Arora Hutchinson: Many
thanks to our guests in this
318
00:23:50,820 --> 00:23:55,815
episode. To Kristelle and Evan
Shulman for sharing their story
319
00:23:55,815 --> 00:24:01,785
with us, and to Jeffrey Kahn and
Marni Falk.
playing god? is a
320
00:24:01,785 --> 00:24:04,935
production of the
Dracopoulos-Bloomberg iDeas Lab
321
00:24:04,935 --> 00:24:09,465
at the Johns Hopkins Berman
Institute of Bioethics, made in
322
00:24:09,465 --> 00:24:13,845
association with Sea Salt and
Mango Productions.
This
323
00:24:13,845 --> 00:24:17,730
episode was produced by Redzi
Bernard, with help from Brian
324
00:24:17,730 --> 00:24:22,800
Ricker and Lyric Bowditch.
Our Executive Editor is Tony
325
00:24:22,800 --> 00:24:28,290
Phillips.
Music and sound
design by Alexander Overington.
326
00:24:28,290 --> 00:24:33,120
iDeas Lab Producer, Lyric
Bowditch.
Researcher, Brian
327
00:24:33,120 --> 00:24:38,475
Ricker.
Story Editor, Simon
Adler.
Show art by Barry
328
00:24:38,475 --> 00:24:43,515
Pousman and Shawn Carney.
Our
Production Coordinators are Leah
329
00:24:43,515 --> 00:24:48,345
Lord and Susan Snead.
Our
Executive Producers are Jeffrey
330
00:24:48,345 --> 00:24:52,845
Kahn and Anna Mastroianni.
I’m Lauren Arora Hutchinson,
331
00:24:53,805 --> 00:24:59,055
host and Managing Editor.
Come back next week for more
332
00:24:59,055 --> 00:25:01,155
playing god?