These induced pluripotent stem cells, or iPSC's, have revolutionized medicine.
They've really changed what we believe we can and can't do, I mean, fundamentally.
So the question from the front is,
"Can you individualize somebody's cells?"
Right, and use it, and that's one of the wonderful things that we can do.
So the example I have here is
someone with liver disease
gets a skin biopsy and those
fibroblasts are turned into induced
pluripotent stem cells. Okay, and these
are specific to that individual.
You could imagine then, we could do lots of things.
One of the things is if we don't know
why that person has liver disease
we can turn those iPSC's into liver cells,
hepatocytes, and study them and we could even screen for drugs
If they have a feature that's abnormal
we can screen for drugs to normalize that feature
and then we can give that drug to that individual patient.
So that's individualized personalized therapy.
Also we could take the the skin cells turn them into liver cells
and give them back to that patient. Let's say instead of
getting a liver transplant
someday we're going to be able to grow a whole liver in the lab
and we can just grow that liver and give that person their liver back.
I know, it's crazy, it's crazy.
It's not that far away either.
If we can find a cause for the liver disease and the cause is genetic we can then,
nowadays, we can think about correcting that genetic cause.
Then you have what are known as repaired induced pluripotent stem cells.
They can grow that into a liver and give a healthy liver back.
Okay, so this is the example, for liver disease.
This is what we want to do for brain diseases as well.
It is, as you can imagine, many degrees of difficulty harder for brain diseases
because brains, unlike muscle and liver,
neurons are organized into circuits and,
like i said at the beginning,
the different types of cells have different functions and we have not yet figured that out.
But this idea of gene correction
for certain types of genetically inherited brain diseases
is still very much possible.
Okay, so, gene editing.
It's been in the news a lot. Sometimes it's just called gene editing.
Sometimes it's called genome editing.
Sometimes it's called CRISPR gene editing.
And I want to just do my public service announcement and say that
gene editing, which is going to be incredibly important for human health moving forward
actually came from basic science study of bacteria
Okay, these two scientists Jennifer
Doudna, who's at Berkeley, and Emmanuel
Charpentier, who's at Inserm
in France, she's French, they were collaborating and they
were literally studying how bacteria fight off pathogens
like we think of bacteria as like pathogens
but turns out there are viruses and phages that actually attack bacteria
and they were interested in that question.
And they figured out that bacteria actually have their own form of immunity
and they figured out all the pieces of it.
And it turns out that the bacteria do this thing where they
are infected once by a virus and they take some of the viruses dna and they
chop it up and they stick it in their own genome
and the next time they see that kind of virus
they produce the DNA or RNA of that virus and they use it to
basically battle that virus. So it's the exact same
idea as we use for producing vaccines, right. So we give an exposure, so like,
I don't know how many people have gotten the flu vaccine, I haven't yet but I will next week.
We give a pre-exposure, we make antibodies and so when we see
the actual pathogen then we'll be prepared to fight and
that's exactly what bacteria figured out to do many millennia ago.
The components of this bacterial immunity include this thing
called CRISPR which stands for
Clustered Regularly Interspaced Short Palindromic Repeats
it's the way they put their,
the bacteria put the viral DNA into
their own genome and, like I said, it's a way that bacteria can fight viruses that
they've been exposed to before.
It's fascinating and that idea
was then taken by
another fellow Feng Zhang, who's at the
Broad, in Boston, and is actually a friend of mine
and he's called the Midas of Methods,
he said, "Wow, that's really neat the bacteria can do that,
can we use that to modify human DNA?"
And then he went and he figured out a super simplified system.
So, the bacterial system was actually still pretty complicated, had many moving parts,
he reduced it to basically three parts
that are shown here, that aren't particularly important
but basically it was a CAS9 protein that cuts DNA and a recognition signal
fused to a recognition, a particular fold of RNA that helped guide this
up to the right part of the genome so now it's become, i mean, literally within,
probably, six, seven years we went from this being a brand new idea
to being something that everybody can do in lab within a week.
It's amazing, it's amazing.
In cells, okay, in dividing cells I guess I should say
is also really important.
So nowadays we know that you can use CRISPR CAS9 gene editing
to take a gene that you don't want and knock it out.
You can take a gene that's normal and mutate it.
You could take a gene that's mutated and repair it.
There are new technologies that have piggybacked on top of this
where you can inactivate a gene, you could make, leave it the way it is but just inactivate it.
Or you can activate it.
And the CRISPR I, CRISPR A, activation inactivation was developed to a large degree at UCSF,
by Jonathan Weissman and colleagues.
Okay so most of this work now we do this routinely in lab, in cells, right, because
they divide quickly we control we can get DNA into them.
What about in humans, right? When is this going to go prime time for humans?
Well the American Society for Human Geneticists think it is not ready for prime time
They put out a statement in 2017 that has not been modified that they
think due to scientific, ethical, and policy concerns
that genome editing is not yet ready for humans.
Nonetheless, if you've been following the news you know
that likely this has already occurred in humans.
To some degree we think of it as rogue
science, others might say something different
but back in November, 2018 the first CRISPR edited babies were sort of
revealed and then just, I mean, it's so hard to keep on top of this field
like two days ago, once again, there's a new type of genome editing
that, you know, the headlines read
new gene editing technology could correct 89 percent of genetic defects.
We're moving really fast.
I think there's a lot of ethical, very important, ethical concerns.
Nonetheless this technology could be life-saving.
Right now, because it needs to be done in dividing cells
there are some applications in, for example, childhood genetic diseases
where repair can be done, for example, on an egg, or early in gestation.
I'm not saying whether I agree or don't agree with it,
that is not the work that I do.
But it's hard to turn back time
and so I think it's important for us to
think as individuals, and as a society,
about the rules and regulations, and the governance.
So we're not in the Wild West with genome editing.
It's one of the important questions of our time