[MUSIC PLAYING]
NARRATOR: Children with late infantile onset
metachromatic leukodystrophy lose the ability to walk, talk,
swallow, eat, and see.
Most kids with MLD won't survive beyond their fifth birthday.
In 2010, using stem cells derived from their patient's
blood, researchers pioneered a treatment
to repair the defective gene that causes MLD.
Giovanni Price was the second child in the world
to undergo this treatment.
Today, Giovanni is five years old,
and has no symptoms of MLD.
On August 24, 2015, Giovanni Price
did something no child with this disease has ever done before--
he walked to school for his first day of kindergarten.
AMY PRICE: When he was born, his genetics
were that he, by the age that he is right now,
should be close to the end of his life.
And so we see the complete opposite.
I mean, we see him going to school,
and making friends, and riding his bike in the driveway.
The doctors don't tell me he's--
they've never used the word, "cured," they've
never told me what's going to happen,
because they don't know.
I mean, we don't know.
But I hang on to those words that he's
going to continue to grow up just
like any other five-year-old.
My hope is that gene therapy combined
with newborn screening for MLD will save other families
from going through what we went through,
and what all of our friends--
our MLD friends-- go through with their kids.
He has no idea that he's a miracle.
He has no idea.
MICHAEL GELB: OK, so thank you all for coming.
I wanted to just start with a movie--
this is obviously a very powerful subject,
very emotional.
I wanted to give you some context, put you
in the mood for this talk.
We'll come back and talk about this disease,
MLD, and how the treatment works,
and about newborn screening, of course.
So what is newborn screening?
That's the first part of the talk.
And then we're going to talk about new treatments
for a family of diseases called lysosomal storage diseases,
which is getting a little bit closer to what
we're doing here at the University of Washington.
And I'm going to talk about a new and general technology
for newborn screening of many diseases-- so many
that now we have to decide which ones.
And that leaves us with the last topic,
which I think is very important--
how do we decide what to screen for?
And as you'll see, it's a very complex, emotional topic
that involves the work of a lot of people,
as I'll point out during the talk.
So what is newborn screening?
And I'm going to get a little bit scientific now.
And I know that many of you are not scientists,
but it's really not that hard.
You have to indulge me, you have to trust me,
but you do have to listen, OK?
And just bear with me for five minutes,
because at the end of this five minutes,
there's going to be this epiphany of what
newborn screening is, and you're going
to have a deep understanding of it, pretty much
as well as the rest of us-- the experts-- understand it.
I'm going to talk about a disease called galactosemia.
So you've all heard of lactose--
it's what's for dinner when you're born,
it's the major carbohydrate in milk.
And like everything in our universe,
it's made of atoms that are bonded together
into units called molecules.
Now, this part of the lactose is the famous galactose molecule
that you've heard of, another carbohydrate.
And this part is the even mode famous, glucose.
And if you look carefully at the structure-- what
do I mean by the structure?
Like the structure of a building, right?
Where everything is.
Everything is the same, except this one oxygen atom here
is up in galactose, and it's down in glucose.
That's the only difference.
And yet, biologically, these two molecules
could not be more different.
Glucose is our major energy for everything we do.
Think of it as the gasoline of the car.
And galactose is never used as energy--
it's used as a building block to make components
in our cells and tissues.
So think of it as the fender of a car.
And then you realize that you need a lot more gasoline
than fenders.
And yet, we eat one of each.
So what happens is you eat the stuff,
it goes into your intestines, it's
broken down into two separate galactose and glucose.
They go into the blood, and they go straight to the liver
where an enzyme converts all of this excess galactose
into glucose.
Now, what is an enzyme?
An enzyme is a molecular machine that simply transforms
one biochemical into another.
So here's an enzyme, it has a pocket,
the galactose fits into the pocket.
And then this enzyme literally grabs that oxygen atom
and rips it off the ring and puts it onto the other side.
Now, it's down, now you have glucose.
And then it's released from the enzyme.
So the enzyme is converting all of this excess galactose
to glucose, because you need a lot more glucose,
and you eat too much galactose.
Now, this enzyme goes around and around
every time doing this conversion.
You might ask how fast is this enzyme?
So about 100 of these things per second.
So what is 100 per second?
Well, a machine gun is about 10 bullets per second--
so 100 per second, 10 times faster than a machine gun.
That's pretty fast.
So where do enzymes come from?
Well, enzymes belong to a bigger class of molecules called
proteins, that you've heard of.
For example, this enzyme that converts galactose to glucose,
where do proteins come from?
Starts with the chromosomes-- that you all
know that you have 23 chromosomes, pairs
of chromosomes in your cells.
For example, chromosome number five, you have two copies--
one that you got from your mother, one from your father.
And if we blow up these chromosomes,
you all know that they're made of DNA.
DNA is this long, double helical molecule
that's wound up tightly into the chromosomes.
It contains all the genetic information, as you know.
You can think of a segment of this DNA,
and we call this a gene.
It's just a piece of a longer piece.
And think of the gene as a word made up of letters--
there's four letters in this language.
There's A, G, C, and T. And like any language,
the meaning of the word depends on the order of the letters.
So it's a good analogy.
We call this order the gene sequence.
And it's the order of these four letters
that's the critical information that's stored in our DNA.
All right, so now we translate from one language to the other,
to another.
We go from DNA to proteins.
So we have a translator.
What does a translator do?
It takes a word in one language, uses a different alphabet
to make another word in another language.
So in this case, it reads the gene,
it takes, this time, 20 letters.
So this is like, I don't know, it's like Chinese--
you have a lot more letters, 20 letters instead of four.
And it reads the gene, and it assembles these 20 protein
letters, called amino acids, into a protein sequence.
Each one of these 20 building blocks has a different shape.
We call this translation.
So the machine reads the DNA and makes the protein.
The order of these amino acids is
dictated by the order of the letters in the DNA.
Now, the protein wraps around itself--
it's like a three-dimensional jigsaw
puzzle, where each puzzle piece has
to fit together based on shape.
Each of these building blocks has a different shape,
and the thing wraps around itself,
everything fits nicely like a jigsaw puzzle.
And then what's left is this cavity that binds galactose.
In fact, this is the enzyme that converts galactose to glucose.
So now you have a deep understanding
of how the function of this protein
depends on the order of the building blocks, which
depends on the order of the letters in the gene.
So this is what we mean by information
flowing from gene to protein to functional enzyme.
And this is the central dogma of biology--
nothing more to it than that.
All right, so here's our gene again.
We have an A here, for example.
Sometimes we have a typo in our gene--
should be an A, but it's a G. Where did this typo come from?
We don't know, but it happens.
We call this a mutation.
So now, this is read by the translator.
And this time, instead of putting in the rectangle,
we put in the pentagon, and the jigsaw puzzle
doesn't work anymore.
The thing doesn't fold, there's no cavity to bind galactose--
this thing is nonfunctional enzyme.
It's broken.
So this is what we mean by a mutation leading
to an enzyme that doesn't work.
Let's do the genetics-- it's very simple.
Here's the mother-- a cell from the mother.
She has two copies of this chromosome which
has the gene for this enzyme.
Happens to be on one of the chromosomes.
Turns out she has one good copy and one with a typo.
We call this a carrier.
So she makes 50% with normal amount of enzyme,
because the good copy makes good protein,
and the bad copy makes bad proteins.
So she makes 50% of the normal amount.
But she's healthy, because you don't need 100%--
50% is good enough.
100% is overkill.
She's a carrier, but she doesn't know
she's a carrier because she's healthy.
Suppose the father has the same situation, who
is also a carrier.
They come together.
They have a kid.
The math is very simple.
There's a 50% chance that the kid
will inherit the good chromosome from the mother and the father.
So there's a 25%--
it's like getting tails twice.
The kid has two good copies.
But there's a 25% chance that the kid
gets a bad copy from the mother and a bad copy from the father.
Now this kid has no functional enzyme and has a disease.
And there's a 50% chance that the kid
has one good and one bad--
one from the mother and father, or vice versa.
This is a carrier.
All right, so this is how a genetic disease of an enzyme--
a broken enzyme-- originates.
From two carriers, that they don't
know they're carriers, and boom, a kid is born with a disease.
Inborn genetic diseases in humans--
just to sort of summarize--
DNA in our chromosomes, of all of our cells,
is the genetic material that provides the blueprint
to make all of the proteins in our body.
Some of which are enzymes that carry out
certain transformations, like the conversion of galactose
to glucose.
If the newborn carries these mutations, that
leads to a dysfunctional enzyme or a protein,
you have an inborn genetic disease.
The logic of newborn screening-- here's the epiphany part--
so about one in 40,000 newborns are born with these mutations
in their DNA, leading to a defective enzyme
converting galactose to glucose.
When this happens, the newborn becomes
ill with an inborn genetic disease called galactosemia--
so now we're giving this disease a name.
This is a rare disease.
It can take several months before the diagnosis is made.
Imagine a baby who continues to cry for hours and hours
for several months.
Galactosemia is not number one on the checklist
of the pediatrician, right?
This is far down the list.
Diagnostic odyssey becomes a nightmare.
By the time the diagnosis is made,
it's too late to save the baby.
If only you had known at birth that this baby was
galactosemia, you could have simply changed
from mother's milk to a special diet low in galactose.
The only reasonable way is to screen
every newborn for this defective enzyme,
so that steps to treat the disease
can be initiated within days after birth.
This is the logic of newborn screening.
So everybody has a complete and deep understanding
of newborn screening now, right?
It's not quite that simple.
But basically, the parents don't know they're carriers,
there's no family history--
boom.
A baby is born.
If only you had known at the time of birth,
you could have given this baby a much better life.
So the guy who of conceived of this whole notion
of newborn screening is Robert Guthrie.
And I'm pleased to say that his kids are here tonight,
they live in Seattle, and you'll get to meet them later.
And he invented this concept of newborn screening.
These are the dried blood spots that babies--
we take a couple of drops of blood,
put it on a piece of paper, send it to the newborn screening
lab for newborn screening.
If you've had kids, maybe you remember this.
It's a pretty small chapter in your life of raising a kid.
You might have not even remembered.
But what are the typical numbers?
So let's think about it-- one in 100 mothers
are carriers for a typical disease, for example,
like galactosemia.
Which means-- OK, I'm going to flatter myself and say
there's 500 people here tonight--
which means five out of you are carriers for galactosemia.
So yeah, sorry to say it, five people in this room
are carriers for galactosemia, but you have no idea.
That's the truth.
And one in 100 fathers--
so they come together.
What's the chance that one of these carriers
comes together with a carrier father and a mother?
Well, one in 100 squared is one in 10,000.
Remember, one fourth of the offspring of carriers
have the disease.
So we end up at one in 40,000, the frequency of galactosemia
in the population.
Five of you in this room are carriers for this disease,
male and female, but you don't know it.
Bigger picture-- 4 million babies
born each year in the United States.
We screen now for about 40 to 50 disorders,
according to the CDC, and the American
College of Medical Genetics.
Newborn screening is one of the most successful public health
programs of all time.
One in 300 newborns, or 133,000 babies per year
are saved as a result of newborn screening.
So this is a big deal.
Every state has a newborn screening lab.
And I'm pleased to say that tonight we
have all of these folks who run the newborn screening
labs in various states, like Joe from New York,
and May from Wisconsin, and Amy from Minnesota,
and Ron and our own John Thompson from Washington state,
et cetera, are here tonight.
And you can talk to these guys tonight if you want,
they're all here.
Every state has a newborn screening lab.
It's part of the state public health system.
And we have Peter from the Netherlands.
I said Denmark earlier today--
I don't know what happened.
But I got it right.
I don't know why I did that, but--
he's like my best friend, and I said he was from Denmark.
So anyways, now we're zooming in a little bit
on the stuff that's happening here
at the University of Washington, but involves
a lot of other people who are also here tonight.
But lysosomal storage disease is a family
of serious genetic diseases, many of which
can now be treated.
One example is MLD that you saw in the video.
Caused by mutations that lead to these dysfunctional enzymes.
I'd like to thank my wife for telling me
how to spell dysfunctional.
[LAUGHTER]
Without newborn screening--
I left out 30 commas in this talk, as well.
And sometimes the comma is really important.
But without newborn screening, diagnostic odyssey--
and I misspelled odyssey, of course--
is a problem, and it's often too late to start treatment.
So diagnostic odyssey.
Expansion of newborn screening to include these diseases
is a topic of current worldwide discussion.
So we screen not for all 2,000 genetic diseases,
but for the ones that we have treatment.
That's the priority.
It kind of makes sense.
Now, we need to talk about bubbles before--
it's a good introduction for how we treat lysosomal storage
diseases.
Again, you have to trust me.
So how are bubbles formed?
You know, you have this soap film, and you blow on it.
And--
[MUSIC PLAYING]
And there's bubble music, too.
Let me turn that off.
[LAUGHTER]
You know what, let me turn it back on again, I think.
You blow on the thing, and it makes a long tube.
And then eventually a bubble breaks off.
You know how bubbles are formed.
And also, two bubbles can come together
and fuse into one bubble.
[MUSIC PLAYING]
OK-- [LAUGHS] I didn't realize it came with sound,
but anyways--
[LAUGHTER]
So why am I talking about bubbles, do you think?
So you'll see the relevance in a minute.
It's a really good analogy for lysosomal storage diseases.
Here is a cell.
The cell has a membrane that separates
the inside of the cell from the outside of the cell--
sort of like the picket fence.
You have proteins inside the cell, like these green guys.
And they're broken down--
these proteins, they don't last very long, a couple of days,
maybe a week, maybe two.
They have to be recycled.
They're constantly breaking down, kind of wearing out.
And so they're broken down into their little pieces
and then reassembled-- protein recycling.
All proteins do this.
But the thing is, on the outside of the cell,
you have these proteins that are stuck to the membrane.
They have to be recycled, as well,
but they're on the outside of the cell.
So they're not exposed to this machinery.
So then the lysosome, as you'll see, is responsible.
The lysosome has its own membrane--
it's like a cell inside of the cell--
and it has its own enzymes inside.
So what happens is kind of clever.
The cell membrane invaginates.
It forms, like, a bay.
It's just like bubble formation.
You keep pushing on this thing, making
the bay deeper and deeper, eventually, a bubble buds off.
We call this a vesicle.
And if you just look, the protein
on the outside of the cell is now
on the inside of the vesicle.
So how do we get these proteins inside the lysosome?
Bubble fusion-- these two bubbles come together,
it's very simple.
And you end up with one big bubble.
And what was inside one bubble and inside the other bubble
are now inside one bubble.
That's what fusion of two bubbles would do.
So now the proteins inside, which
came from the outside of the cell,
are exposed to these enzymes.
They can be recycled.
And the whole thing is reversible--
these proteins are then delivered in reverse back
to the outside of the cell.
So this is how the cell recycles these proteins
on the outside of the cell.
All right, so what are lysosomal storage diseases?
So you have about 40 of these different enzymes
that are involved in recycling inside the lysosome.
And they're required for recycling.
And if you have a dysfunction of one of these enzymes,
you have a lysosomal storage disease.
The material that's recycled builds up,
it accumulates, the cell dies, you have a disease--
lysosomal storage disease.
All right, so how do we treat these?
So if you have a broken enzyme, and biotech
is very good at making good enzymes in bacterial factories,
why don't we just inject good enzymes into your blood,
and give you the enzyme that you're missing?
The problem is, enzymes don't know how to go across the cell
membrane-- they just cannot do that spontaneously.
There is no way for them-- we don't know how to do that.
But lysosomal enzymes, we can do it.
Because if we inject them into the blood,
and they go into the tissues outside of the cell,
they're swimming around out here and they end up inside
of San Francisco Bay.
And then this thing forms a bubble.
But the enzyme which was outside is now inside the bubble.
And you know how the enzyme gets into the lysosome-- bubble
fusion.
So we can deliver an enzyme from our injection syringe
into the blood, into the lysosome of the cell.
It's like a magic trick--
the enzyme crosses one membrane, and then another membrane,
yet it never crossed a single membrane.
Right?
It's a magic trick.
Enzyme replacement therapy-- we give you good enzyme.
It's not a very sophisticated name-- enzyme replacement
therapy.
It means what it sounds like.
The biotech industry makes the enzyme.
We inject it into the blood every few weeks
for their entire life of the patient.
Enzyme in blood can pass through the porous walls of the blood
vessel, travel into the tissues where they are taken up
by cells, and spontaneously ending up
in the lysosomes where they function.
We have here tonight, four people
that developed this therapy.
I'd like to point out Emil Kakkis, who's really
the pioneer in developing enzyme replacement therapy,
going back 10 or 15 years.
Real special people here tonight.
There's a movie-- it was the first and last movie
that Harrison Ford ever made, because nobody went and saw it.
It's a true story about John Crowley who
had kids born with this disease, and he started a company.
And then he resigned from the company
so he could put his kids in the clinical trial,
and he saved his kids' life.
It's a true story, it's remarkable.
We have this enzyme replacement therapy
for about eight lysosomal storage diseases,
and more are coming.
All right, so now, what about lysosomal storage diseases
where the pathology is mainly in the brain?
And I want to come back to this story, because it
has a lot to do with MLD--
the video that I showed you at the beginning.
We hit a snag, because lysosomal enzymes injected into the blood
cannot enter the brain.
That's because the blood vessels in our brain, that
go through the brain, they don't have porous walls.
So the enzyme in the blood can't get into the brain tissue.
They can get into the liver, they just
can't get into the brain.
So how do we treat these diseases?
And I'm going to show you what I think
is one of the most remarkable developments
in modern medicine--
the treatment for MLD, which involves gene therapy
that you've heard about, it's coming big time,
and stem cell transplant.
So how does this work?
Now, it's a little bit complicated, but not too bad.
Again, indulge me, listen, you'll get it.
We drain one pint of baby's blood from the placenta
through the umbilical cord.
We do that because we cannot take a pint of blood out
of the baby.
This is called cord blood.
And remember, the blood in the placenta is the baby's blood.
We take this blood, and we isolate the stem cells
from this blood.
What are stem cells?
These are the immature blood cells
that can become all of the mature different types of blood
cells-- red cells, white cells, platelets in your blood.
Think of it like the seeds of the tree.
A seed can become any part of the tree.
A stem cell can become any blood cell.
In vitro, in a Petri dish, we infect these cells
with an HIV virus.
Oh, my god.
But it's engineered so that it cannot cause HIV/AIDS.
But it has the capacity to go inside the cell,
carry a good gene for this enzyme,
insert it into the chromosome of these cells
so that the cells permanently carry
a good gene, which makes a good enzyme,
that fixes this disease.
All right, so the spaceship landed on the moon.
Now we got to get it back to Earth, right?
So we destroy the bone marrow cells
from the newborn with chemotherapy,
just like we do with leukemia patients.
We need to make room, because the stem cells--
we're going to inject the stem cells back into the newborn,
and they're going to swim into the bone marrow
and restore the entire bone marrow of the baby,
but with the capacity to make the good enzyme.
What does this have to do with the brain?
So this bone marrow makes all of the blood cells,
but blood cells know how to burrow out of the blood vessels
and enter the brain.
The cells of your immune system do this all the time,
because they have to fight infection in your brain.
So these cells, carrying good lysosomal enzyme,
go into the brain.
What happens?
Bubbles-- the enzyme comes out of the cell
and is transferred from one cell to the other--
like I showed you, without crossing membranes--
and all of the cells in the brain
are fed by these cells that came from the bone marrow.
And we have a tremendous impact on this disease.
And notice, also, that the stem cells are the baby's own stem
cells.
So this is not a foreign donor.
So the baby does not reject any of these cells.
So it's his own or her own blood cells
that have been repaired by gene therapy.
And more and more of this is coming for hemophilia,
for bubble baby disease--
SCID, for example.
All of these things.
This is the team in Italy.
They're not here tonight.
I visited them a couple of weeks ago in Ospedale San
Rafaelle in Milan.
It's an amazing treatment that these guys developed.
But we do have Maria Escolar and David Wenger tonight--
these are some of the best gene therapy
experts in the United States working on these rare diseases.
I'd like to thank them for coming.
All right, newborn screening for lysosomal storage diseases--
now that we have treatment, we have new technology
developed at the University of Washington
over the past 10 years.
So I'm coming closer to the work that was done here,
but it will be very short.
All right, so we want to measure the activity of these enzymes.
What does that mean, the activity of the enzymes?
Well, remember, enzymes convert one biochemical into another.
And they do so 100 per second.
So the activity of the enzyme is simply
how many of these conversions occur per unit time.
And we want to be able to assay, or we
want to be able to measure this activity for several enzymes
at the same time, because we want
to cover a lot of territory, a lot of diseases cheaply,
efficiently.
So you can imagine one enzyme that
converts purple into orange molecules,
enzyme two, enzyme three--
how do we do this?
Let's see, how do we do this?
So we have to measure how many of these biochemicals
are converted from one to the other over time.
So somehow, we have to count the glucose that
was made from the galactose.
We have to count them.
Like counting red jelly beans in a jar of jelly beans.
The reason I say jelly beans, because blood
is very, very complicated.
How do we count only the red jelly beans?
All right, let me show you.
So we take a 3 millimeter punch of this dried blood spot.
We give it water, because all life happens in the water,
we put it in water.
And we give it the molecules that the enzyme acts on.
We let it incubate, so these molecules are
converted over a few hours--
if the enzyme works--
and we count the number of new molecules
made by these enzymes.
Remember, enzymes convert one molecule to another.
The number of these enzyme-produced molecules
made in few hours tells us how functional these enzymes are.
All right, so how do we count these molecules?
In a very complicated mixture of thousands of different kinds
of molecules known as blood.
We use this amazing molecular counter
called a mass spectrometer.
It separates molecules according to how much they weigh.
So all of the different molecules in blood
have different weights, some are lighter than others.
And we can separate them.
This is the same machine that you
use to count illegal drugs in urine,
or explosives in your carry-on luggage at the airport,
or toxins in your drinking water.
All of the major problems that we have in our world today.
Let me show you a little movie about how this machine works.
These molecules spiral through these electric fields--
I won't get into the physics.
And certain molecules that have the right weight,
they make it all the way through the tube.
Other ones crash into the wall.
And the green guys make it through.
So we have this filter that depends on how much you weigh.
It's like a guy throwing balls, and he's
throwing with the same force.
And the heavy balls don't go as far as the lighter balls.
We can separate things according to weight.
It's very easy to do.
And that's what we do.
Here are some of the pioneers in newborn screening using
this technology that are here tonight,
from around the United States.
You'll meet them later.
All right, so here's the deal-- so with this mass spectrometer,
we can count hundreds of different kinds of molecules
with this 3 millimeter punch of dried blood spot.
We can test for hundreds of inborn genetic diseases
for a few dollars in a few minutes.
We can screen all 250,000 newborns
in New York for 50 diseases, 100 diseases,
200 diseases-- we have the technology.
So how do we decide what to screen for?
And this is one of the hardest problems in this field.
This movie you're going to see, it's a little bit--
I'll warn you, it's a little bit intense.
But it was on the CBS Evening News at 6
o'clock five years ago.
So if the whole country can handle it,
you'll probably do OK.
[VIDEO PLAYBACK]
- Now to an issue that is beginning
to face new parents all across the country.
CNN's Dr. Sanjay Gupta, a CBS News contributor,
tells us why some parents say they have
the right and the need to know.
- After years of struggling to have a family,
Steve and Nicole Aldrian were overjoyed
to have healthy twin boys, Tyler and Trevor.
- Everything was normal, everything was great.
You know, my dad made special trips to hold the boys.
- Trevor blossomed first.
- Can you look into the camera?
I'll forget, when he was three months, I looked at him
and I said, can you say O?
O?
- O.
- But by four months, Trevor was vomiting, fussy, stiff.
And by six months, was diagnosed with a rare genetic disease
called Krabbe.
Krabbe babies lack an enzyme needed to protect their nerves.
[CRYING]
It is so painful, Trevor cried 15 hours a day.
[CRYING]
- My child is dying, and I'm angry every day.
- Angry because Nicole believes Trevor could have been treated,
and received a test that cost less than $1.
And yet, only New York screens all babies for it.
- He would have had a chance at life.
And he doesn't now.
- If Krabbe is detected before symptoms appear,
an experimental transplant, using stem cells
from umbilical cord blood, can slow or stop
the disease in some cases.
- Families really want this.
They should have the right to know
that the child has Krabbe disease when we can still
do something about it.
- Ann Rugari wanted her newborn, Gena,
to have the test immediately.
Krabbe had killed her first child, Nick.
Gena also tested positive.
But just days later, had the stem cell transplant.
- How are you?
- Gena is 11 now, and attends regular fifth grade.
She can't walk, and she uses a computer to talk.
- I like to watch American Idol.
- Good!
- She swims, is a Girl Scout.
- The parents out there that don't get the opportunity
to test their babies at birth, they
don't get the opportunity to save their children's lives.
- You both going to sleep now?
- As for the Aldrians--
- Good job, Tyler.
- Tyler doesn't yet understand, his twin, Trevor,
will be gone soon.
- I would take Trevor in a wheelchair any day of the week,
knowing that my child is still alive.
- You want to take a picture?
- Yeah.
- Take a picture of Trevor and I?
- Cheese!
- Cheese!
- We embrace Trevor to save the next child.
That will give us a little bit of peace in our heart, that we
can do something now.
[END PLAYBACK]
MICHAEL GELB: So you get the idea some states screen
for this disease, and some don't.
It's controversial, it's contentious.
So what's the problem?
Seems like a no-brainer.
These parents are mad.
Their kid didn't have a chance.
Well, it's not so simple, I'm sorry to say, unfortunately.
So how do we expand newborn screening?
There's two ways-- we have parent advocacy, state
by state legislation.
And we have federal-level scientific advisory committee,
and the Recommended Uniform Screening
Panel called the RUSP, and I'll come back to that.
Some of you remember Jim Kelly--
he went to the Super Bowl with the Buffalo Bills four times,
I think, maybe 20 years ago.
He had a kid, Hunter, who died of this disease,
Krabbe disease, that you saw in the movie.
When the treatment became developed by Maria Escolar--
who I mentioned earlier in the talk, who's
here tonight, and also Joanne Kurtzberg of Duke University--
the Hunter's Hope Foundation, which is the foundation
that Jim and his wife and kids started in New York,
lobbied and got the governor to expand newborn screening
for every child in New York for Krabbe disease.
Because once the treatment is available--
and you have to start the treatment early before
the neurological damage--
you need screening.
So what's the problem?
We also have Elisa Seeger tonight, whose son, Aiden,
died of another disease called x-linked adrenoleukodystrophy
in New York, and she got grass-roots efforts newborn
screening for XLAD in New York.
And Brad Zakes, here in Washington state,
is here tonight.
This is the parent advocacy route.
The federal advisory committee, and the Recommended Uniform
Screening Panel, called RUSP--
I'm pleased to say that Rodney Howell, who
is a significant figure in creating this panel that's
here tonight.
This is a panel of eight or so newborn screening experts,
maybe 10, that are nominated by people in the field.
They look at evidence-based review of these-- anybody
in the public can nominate a new condition for consideration.
They go to evidence-based review over maybe a year,
and then they vote.
And then the Secretary of Health and Human Services,
if they accept the vote-- let's say it's a yes vote,
and they vote yes--
it is added to the RUSP, the Recommended Uniform Screening
Panel.
It is non-binding for the states--
it's a federal recommendation that all states and territories
of the United States start screening for this disease.
But it is not binding.
Remember, every state has their own state newborn screening
program.
These things are sorted out by parents and state health
boards in each state, and they don't always go with the RUSP.
A few years ago, in part from work done here
at University of Washington, and elsewhere around the world,
many people involved, two of these lysosomal storage
disease, called Pompe and MPS-1 were added to the RUSP.
About six states are now live for newborn screening-- that
means they're doing it in real time,
on real babies that are born going forward.
And several states are gearing up to do this.
Here in Washington state, Pompe and MPS-1
was recently approved at the state level.
And John Thompson, the director of the newborn screen lab,
is working hard to add these to his team.
It's a team-- the newborn screening lab is up the road
in Shoreline, and they're working
to add these in the next six months, or so.
So why is this such a laborious and contentious process?
Why does New York, and now Missouri, Kentucky,
Ohio, Illinois, and Minnesota screen for Krabbe,
but other states do not?
Why isn't Krabbe disease on the RUSP?
There are many challenges and unresolved issues--
now this is the hard part of the talk I want you to think about.
So screening for these diseases will
lead to identification of newborns
who have an infantile disease.
These infants will usually be confirmed
by a diagnostic center to have the disease,
and will receive immediate and lifesaving treatments.
And here's the big but-- screening
for these diseases will also lead to identification
of newborns who lack disease symptoms at birth,
but who are at risk to develop the symptoms later in life.
Maybe one year, two years, 10 years later.
This leads to family anxiety, obviously, and challenges
for medical follow-up of these patients,
in order to know if treatments should be initiated
and when to start.
So why do we have these late onset diseases?
Remember, these are enzyme dysfunctional diseases.
If you have very low enzyme, you have an infantile disease.
But what if your enzyme is partly broken?
You know, the more enzyme you have, the later the disease
onset.
It's a gray scale-- it's not black and white.
Genetic diseases come from severe, to adult onset,
all over the place.
It's not black and white.
We have parents here tonight-- your newborn is identified
by your state's newborn screening program
to be at risk to develop a lysosomal storage disease,
yet your newborn is healthy.
You follow the recommendation of your medical support team
by bringing your newborn to regularly
scheduled follow-up visits, perhaps every few months.
On a bad day, you live with the anxiety
of your family situation.
On good days, you are reminded by parents
with symptomatic kids that treatment for this disease
is available, and treatment works best
if started at the first signs of symptoms.
Without this knowledge, your baby
is going to go undiagnosed for many months.
And it's going to be often too late to treat.
Yet you have to live with anxiety for a late onset
disease.
It's a very serious, complicated situation.
We don't have the answers.
And scientists don't know any better
than anybody else on topics like this.
But numbers are useful.
Over the past 10 years, New York has screened 3 million newborn
for Krabbe.
Five were identified with infantile Krabbe disease,
and most families elected treatment.
29 families out of 3 million over 10 years
were informed that they have a high-risk infant.
So these are asymptomatic infants
that might develop Krabbe disease, but we don't know if,
and we don't know when.
Most received follow-up by the medical system,
some are lost to follow-up.
So far, these kids are asymptomatic out to 10 years,
but most experts feel that some will develop disease.
In recent years, we've improved the post-screening prognosis
process, suggesting that about half of these 29
are very unlikely to develop Krabbe disease
and no longer require follow-up.
So that leaves about 15 families out of 3 million
that have to live with this anxiety.
OK, so numbers are useful.
So let's do a survey in your mind,
and you're going to be thinking about this
for the next few days.
Would you want your newborn tested at birth
for a rare genetic disease, where early diagnosis is
critical to treatment outcome?
So I think most parents say yes to this, when we do surveys.
You can think about it.
You're not going to decide in five minutes.
You're not going to decide in two days.
Maybe you'll decide in a month.
I don't know.
Would you want this newborn screening when there's a 1
in 20,000 chance, let's say, that your newborn may
be labeled at risk for development of a late onset
disease, knowing that treatment works best
if started at the first signs of symptoms?
Can you live with this anxiety in the asymptomatic period?
For years?
Surveys would say most people say yes to this.
I was surprised.
Would you want screening where there
is no good treatment for the disease,
so you can avoid diagnostic odyssey.
Most people would say no to this.
We don't want to know about all 1,000 genetic diseases
that we have no treatments for.
Better not to know.
But you have to go through the diagnostic odyssey
if your kid becomes ill, but most people-- so you
can think about this.
It's not simple anymore, right?
So over the years, I've met many parents with affected kids.
They are part of disease foundations.
I'd like to say a few things about these amazing people.
Sue and Paul Rosenow and their daughter Stacey--
Stacey had a kid who died of Krabbe disease.
These guys won the Minnesota State Lottery-- $180 million,
and have given most of the money back to research
for this disease.
I don't know-- maybe the government
should be paying for it.
Well, the government-- I don't know.
Anyways--
[LAUGHTER]
I don't want to get too political.
But it's just an amazing story, right?
I mean, these are great people.
Elisa Seeger's child, Aiden, died of ALD.
She, like Jim Kelly, pushed very hard
for newborn screening in New York.
They went live about three or four years ago.
The Recommended Uniform Screening Panel now
includes this disease, and most states
are gearing up to do this.
Scientists were kind of behind on this one.
I think Elisa led the charge.
And once we had it on the uniform screening panel,
it's not automatic that Washington state will do it.
Brad Zakes has been pushing hard,
in memory of his son, Ethan, who died from this disease.
And now we have newborn screening
for ALD in Washington state.
You met Steve, in the CBS movie, The Peace Love Trevor
Foundation.
Terry Klein is here tonight.
All these people here-- well, they got stuck in Minnesota,
but they were listening today.
Terry Klein is head of the National NPF society,
as a family of lysosomal storage diseases.
Dean and Teryn Suhr are in charge of the MLD foundation--
remember the video you saw.
And Jessica Smart, a daughter recently
diagnosed with potentially late onset Pompe disease,
and you can talk to her tonight about how she feels about that.
And on good days, she says, good thing I know,
I can start treatment.
On bad days, you know--
Summary in inborn genetic disease
occurs when a newborn inherits mutations
from parents who are almost always unaware that they are
carriers for these diseases.
These people are not aware--
the only way to do it is screen everybody.
It's a public health program.
Nobody should be left out.
We don't know who to leave out, even if we wanted to.
A subset of these diseases are now treatable.
We focus on the treatable ones.
And it's often best to start treatment
before the irreversible damage, right?
That makes sense.
The only way to find these guys is
to do comprehensive, population-based, statewide,
government-run, public newborn screening.
In certain parts of the world, we
have targeted screening for disorders
that are common to certain regions of isolated
populations, like in Taiwan, like in Israel.
But in the United States, we don't have
this isolated population thing.
We're a melting pot.
Inborn genetic diseases come in early and late onset forms,
and newborn screening detects all of them,
leading to patients who need immediate treatment,
and those who need follow-up perhaps for decades--
a high-anxiety situation.
So you see it's very complicated, unfortunately.
Lysosomal storage diseases are a subset
of these inborn genetic diseases,
for which good treatment options have emerged in recent years,
leading to an expansion of newborn screening programs
to include these disorders.
Mass spectrometry technology has been
developed for newborn screening of several of these diseases,
and others.
The technology, I think we can do many diseases.
That's not the problem.
Deciding which diseases is the problem to add to these panels.
As a result of parent advocacy, and an expert based federal
panel that provides non-binding recommendations to states,
each state decides how to proceed,
resulting in non-uniformity and the conditions that are tested
for--
as we have now for lysosomal storage diseases.
And you saw the video about the Krabbe situation in New York.
We screen, other places, we don't.
So I'd like to end with a few slides.
So I'd like to thank the university for this award.
I've been here my whole career for 33 years,
I will end my career here.
I love this place.
I think there's something to be said about remaining
in one place for your whole career,
and some degree of loyalty.
There's no more loyalty it seems anymore.
We move around.
I'm proud of the fact that I've been here my whole career.
I really love it here.
The medical community, chemistry department, et cetera, et
cetera-- it's a wonderful place.
So this thing that we developed here at University
of Washington is a team effort.
It started-- my wife had amniocentesis,
and I asked the nurse, what do you test for?
And the nurse said, Down syndrome.
And I said-- I'm an enzymologist-- and I said, why
don't we test for everything?
And I said, I know how to test for everything
in mass spectrometry.
And then I had lunch with Ron Scott, who brought me back
to planet Earth, and told me there are certain rules, Mike.
We don't test for everything.
There has to be a treatment.
There are issues.
So Ron and I have been working together for about 15 years.
Ron is Professor of Pediatrics.
He's in charge of a lot of these diseases in the Pacific
Northwest.
He works closely with people at Seattle Children's Hospital.
Then I said, we need a mass spectrometerist--
so that would be Frank Turecek in the chemistry department.
So the three of us, as a team, for 15 years.
So the people in my group that contributed to this,
I can't leave them out.
They did a wonderful jobs.
So we have Farideh, and Martin, and Ga, and Arun.
Ryan's in charge of the tech transfer.
John's helped us do all of these pilot studies
in the newborn screening lab.
Sophia, Fan, and Xinying, Naveen, Susan, and my friend
Bruce for 30 years.
[INAUDIBLE] chairman, this is Alvin.
He hired me.
This is Paul, who took care of me.
And this is Mike that's trying to figure out
what to do with me.
[LAUGHTER]
And this is Diana Knight, who organized
an event we had today.
Let me tell you about this event.
This is my family, sorry.
Yeah, you know, I had a picture of me with a fire hose,
pouring water on one side of the wall,
and my wife plugging the hole on the other.
So, I don't know, pretty much the story of my life.
And this is the meeting we had today.
So all the people you heard about in the talk
are the world's experts in newborn screening
and treatment, pioneers, the parents.
They're all here today, you can meet them.
They're going to be in groups at the reception.
You can talk to the parents, the doctors, the newborn screening.
We had this little meeting today, here they are.
So this is the part of the talk where
I haven't figured out what I want to say yet,
so I think sometimes shooting from the hip
is the best way to end the story.
I don't know, this is my friend, Steve.
Let me tell you about Steve.
And I'd like to dedicate this talk tonight to Steve,
and all the parents that have dealt with this.
What they endure is amazing.
So Steve has a kid with Krabbe disease.
And his kid, Trevor, is the longest living kid
with infantile Krabbe disease.
He was born, and there was no screening,
and they lost the opportunity for treatment.
You've seen some of the controversies about that.
So Steve has, I don't know, he spends his life
taking care of Trevor.
He's lost his job.
And despite all of that--
you know, he's out of money--
and despite all of that, and what these parents go through,
he's told me something that I can never get out of my mind.
And he said, I cannot imagine another day in my life without
Trevor.
You know?
I don't know.
And the other thing I'll say is, these parents
they go around the world and they thank all the scientists
for what we do.
And, I don't know, my life is--
my kids are healthy, I get paid well.
I love what I do.
And I guess these parents, they endure so much,
and they fight so hard for treatments,
and newborn screening.
And so I would like to reflect their thanks to me
100 times back to them.
And to say to them, thank you so much for what
you've done for me.
So thank you very much for coming tonight,
and we'll see you at the reception.
[APPLAUSE]
[MUSIC PLAYING]
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