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>> Reed Pence: Cindy and Jason desperately
want a child. But tragically, their first-born
died just five days after birth due to complications
from a rare inherited disease. Understandably,
the couple is wary of trying to get pregnant
again. But what if doctors had the know-how
and the technology to alter the mutant gene
present in Cindy’s egg or Jason’s sperm?
Or what if they could remove the gene from
the embryo after in vitro fertilization? What
if that rare disease could be eliminated from
Cindy and Jason’s line for generations to
come?
>> Debra Mathews: We have been talking for
decades – we, the scientific ethics communities,
have been talking for decades about the possibility
of human germline genetic modification. That
is, making changes to our DNA that is heritable
to the next generation. So not just changing
my DNA as an individual patient, but changing
the DNA of the cells that would go on to make
my children and their children and their children,
etc.
>> Pence: That’s Dr. Debra Mathews, assistant
director for science programs in the Johns
Hopkins Berman Institute of Bioethics and
an associate professor of pediatrics at the
Johns Hopkins School of Medicine.
>> Mathews: So we have been discussing this
for decades and the possibility of it, but
we have never had a technology that was anywhere
close to safe and effective for these purposes.
So, we have always been able to say, we could
never do this safely in humans, so we’re
not going to do it.
>> Pence: However, now things are changing.
In the beginning of 2012, a group of researchers
introduced a much more specific and efficient
technology for genome editing.
>> Mathews: Namely CRISPR CAS 9, which you
can really just think of as a much more specific
pair of scissors with which you can cut DNA
and potentially paste in as you would in a
computer program, cutting and pasting. So,
we now have this technology that is relatively
inexpensive, relative to all the technologies
we’ve had in the past, specific, and because
it’s specific, meaning we can make the changes
we want to make and not changes we don’t
want to make, that still happens, but it’s
much, much less common with this technology,
we actually have to now have a conversation
not about can we do it, but should we do it.
>> Pence: Now, it’s important to reiterate
the difference between gene editing and germline
editing. Gene editing, or somatic editing,
refers to changing a localized gene in one
individual patient, for example a person with
leukemia. Those changes can’t be inherited
by future generations. Germline editing refers
to altering genes in an egg, sperm or embryo
of just a few cells, which would result in
heritable changes for generations to come.
>> Mathews: There have been two cases published
in very recent history of somatic gene editing.
So, gene therapy using this technology. One
was in HIV and the other was a case that was
published in the newspaper not too long ago
of a baby girl whose cancer was cured using
this technology. The idea in these cases is
you modify a gene to prevent or cure disease,
and that is the idea with this technology
for its use in humans. The idea is that you
could cure disease either through gene therapy
in the person in front of you, or potentially
in an entire family going forward by eliminating
a disease causing mutation entirely through
germline genome editing.
>> Pence: However, researchers don’t know
what will occur for generations to come when
a gene is altered or removed from the germline.
Or when the genetic scissors aren’t quite
precise enough, and take out an unintended
gene along with the intended one.
>> Mathews: Genes interact with each other.
The gene that you’re interested in makes
some product, a protein for example, that
has a role to play in your cells, but it has
to interact in a system. It’s not acting
on its own, so by changing that individual
gene, and therefore the product it makes,
you’re having an effect on the genome, not
just that particular gene.
>> Pence: Mathews says researchers usually
take great pains to avoid DNA changes in sperm
and eggs. But only certain countries have
strict oversight and regulatory processes
in place to govern the use of these gene-editing
technologies. Researchers from countries that
do have oversight met this past fall at the
International Summit on Human Gene Editing
in Washington, D.C. One of their goals was
to draft a consensus document on gene therapy
and germline modification. Unfortunately,
we've already gotten a sad lesson about the
lack of rules for other new high tech procedures.
It's created chaos.
>> Mathews: One of the big motivators is that
in the stem field over the last ten years
we have seen many, many “clinics” turn
up all over the world offering injections
of stem cell something for hundreds, thousands
of dollars to sick people. And there is no
science backing up what folks are doing, and
there’s no transparency about what it is
they are doing. But people are crowd sourcing
fundraising on line to take their very sick
children or family member overseas to be injected
with who knows what? And people in the field
are very worried that because this technology
is relatively specific and inexpensive and
very broadly available that the same kind
of situation is going to happen here.
>> Pence: That practice of traveling to a
different country to receive stem cell treatment
came to be known as stem cell tourism.
>> Alta Charo: Stem cell tourism is a phrase
used to describe the phenomenon of patients
going from country to country looking for
what they believe will be treatments even
if they are not approved as safe and effective
in their own country. We see it with Americans
going to other countries, but also Australians
going abroad, some Europeans going abroad.
It is not restricted to the U.S. Typically
they go from a highly regulated country to
a less regulated country in order to seek
out these so-called treatments.
>> Pence: That’s Alta Charo, Warren P. Knowles
professor of law and bioethics at the University
of Wisconsin Law School and Medical School.
>> Charo: Typically, you’ll have on the
web clinics that are advertising something
that they call stem cell treatment. It’s
often very unclear. It’s hard to be specific
because the clinics vary in what they do and
they are under no reporting requirements.
So getting precise information is virtually
impossible.
>> Pence: The lack of regulation also makes
it nearly impossible to document problems,
but Charo says people have been injured from
such treatments. At least one death due to
such treatments has been documented in Germany.
Charo and others fear that something like
gene editing tourism may occur as well.
>> Charo: The thing that really may happen
first is that while patients in regulated
environments like the U.S., the European Union,
Japan, Australia, and such, while they’re
waiting for their local regulatory authorities
to confirm the safety and effectiveness of
some of these techniques, they may go to less
regulated environments. In the past we’ve
seen that happen in Mexico, in the Ukraine,
in Russia, for example. So, germline may not
be the first thing you need to be thinking
about. It could be claims that we can treat
your cancer tumor, which will certainly touch
on a much broader range of people, and does
have, in theory, the same possibility for
tourism that we’re now seeing with stem
cells, and which we’ve seen in the past
with other kinds of highly hyped technologies.
Back in the ‘70s it was about apricot seeds
to cure cancer that sent Americans across
the boarder into Mexico.
>> Pence: You may be surprised to learn that
anyone can go online and order CRISPR CAS
9 technology for under a thousand dollars.
There are no buying restrictions and no screening
applications. So, what’s to stop unscrupulous
clinicians in an unregulated country from
marketing gene-editing therapy that they claim
will cure your cancer? Or perhaps germline
editing that will eliminate sickle cell anemia,
M.S., Parkinson’s or countless other inheritable
diseases from a family line? Or perhaps, even
more troubling, germline editing to create
promising designer babies? Order your tall,
intelligent, blue-eyed genius today.
>> Mathews: That is certainly what people
are worried about, because it is not absolutely
– underscored, bold, exclamation point – not
ready to be used in humans. I’m very concerned
about the safety of the individuals who use
this or have this done before it’s ready.
I am worried that we just don’t know enough
about the human genome to necessarily start
making long-term changes in it. We just don’t
know. We have just started sequencing lots
and lots of genomes and what we’re primarily
learning is that there’s a ton we don’t
know and that’s about individual genes and
the effects of individual genes. But then
figuring out how this gene interacts with
that gene, which interacts with that network
– we have no clue.
>> Pence: However, despite those scary scenarios,
both Mathews and Charo are less concerned
with unregulated germline editing than they
are with gene editing. The difference is in
the numbers.
>> Mathews: From my perspective, more about
the safety of the individuals and not as much
about affecting the gene pool, because the
human population is enormous, and expanding.
And even if this becomes widespread, it’s
not going to be widespread enough that it
actually affects the human genome writ large.
But I’m very worried about the safety of
individuals who would go through this when
we are just not anywhere approaching ready
to do it.
>> Charo: If one looks at the potential population
of the patients who might be interested in
gene editing, it’s going to be much larger
when we talk about somatic cell applications
because it applies to a much wider range of
diseases, many of which are fatal, and in
the area of reproductive options, we do have
options now that allow people to screen for
diseases either before they conceive, after
they conceive, even after they are pregnant,
so that we don’t have as large a population
of people who lack other options.
>> Pence: However, Mathews and many other
researchers are worried that if a clinic in
an unregulated country were to use this technology
reproductively in humans, then oversight regulators
may shut down all legitimate research, even
somatic uses of the technology that appear
to be promising.
>> Mathews: I do know that the decisions that
we make now about how this technology should
or shouldn’t move forward will have long-term
effects both positive and negative, right?
There are opportunity costs to not going down
particular roads, but there are also absolutely
areas that we shouldn’t touch. We need to
make decisions about which category or some
intermediate category this falls into, because
science can tell you, we now have a relatively
safe, effective technology. We can tell you
that we can do it; we can tell you that it’s
relatively safe. The scientific community
cannot tell you whether we should or should
not use it. That’s a societal decision.
>> Pence: The National Academy of Sciences
and Medicine has formed a committee headed
by Charo to solicit broad input from researchers,
clinicians, policymakers, and the public.
The committee's meetings are public and any
presentations will appear on its website.
If you want to be heard, or merely stay abreast
of developments concerning human gene editing,
you can find a link on our website at radiohealthjournal.net.
Our writer/producer this week is Polly Hansen.
I’m Reed Pence.
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