Healthcare

GLOBAL INVESTOR 2.12 — 25
“The tools that we have for sequencing
genomes now allow us to look at the
genome of any cancer and actually see
what derangements it contains.”
Which enables you to do what?
Eric Green: Everybody has known for
some time that cancer is not one disease.
People with the same apparent type of
cancer can have very different outcomes.
If you look at those cancers under a microscope,
they look identical. But when you
look at their genomes, they can look completely
different. That information makes
it possible, say, to predict a good outcome
versus a bad one.
So we cannot yet say we have
better therapies?
Eric Green: In most cases, no, but at
least we have better ways of predicting
outcomes. Worldwide, there are dozens of
different cancer sequencing projects where
many tumors of a particular type of cancer
are being collected, sequenced and catalogued.
We think that in the next few years,
these efforts will change the face of
cancer diagnostics for some cancers, and
(fingers crossed!) maybe also provide better
insights for how to treat cancer.
It’s not just disease outcomes that are
different. People respond differently
to drugs too.
Eric Green: How people respond to
medication is also largely genetic. It has to
do with how we metabolize drugs and with
other things about how the drugs are acting.
And we’re learning how to predict that in
advance. There is the whole field of “pharmacogenomics”
that basically uses information
about an individual’s genome to determine
which medication they should get.
Pharmacogenomics is already standard care
for certain medications involved in the
treatment of AIDS, asthma and some types
of cardiovascular disease.
The cost of genome sequencing
has fallen dramatically. Why?
Eric Green: When the Human Genome
Project ended in April of 2003, our institute
published a paper describing a vision for
the future of genomics and calling for the
development of revolutionary new technologies
for sequencing DNA. In fact, we asked,
wouldn’t it be incredible if we could come
up with a technology that would allow us to
sequence a human genome for a thousand
dollars?
You had just sequenced the first
human genome for a billion dollars!
Eric Green: Which is why setting a goal
of sequencing a human genome for a
thousand dollars was, frankly, nothing short
of audacious. But we knew the cost had
to come down. We gave out millions of dollars
to all sorts of scientists, hoping that they’d
take risks and come up with some crazy new
ideas. The private sector saw this as a huge
opportunity as well, and poured in lots of
money. Good ideas emerged, they worked,
and what cost a billion dollars only ten years
ago is now down to just a few thousand.
What was the most surprising
finding about the human genome?
Eric Green: How few genes we have!
For a long time, we figured that, because
we are so complex and smart, the human
genome would have many more genes than
simpler organisms like fruit flies and worms.
But in fact, we have around 20,000 genes
(a few thousand more than a fruit fly
and roughly the same number as a mouse).
The other thing that’s been surprising is
that the majority of the functional parts of
our genome are not genes at all and do
not directly code for protein.
What do they do?
Eric Green: We are still learning about
those other functional parts. We know that
many of them act like dimmer switchers,
determining when and where and how
much a given gene gets turned on, how
much protein gets made and so forth. And
that’s where we probably get most of our
biological complexity.
Earlier you mentioned that, aside from
being able to predict response to this or that
drug or treatment, one day, hopefully,
we might even be able to make better drugs
based on genomic information. What
do we have to know to get to that point?
Eric Green: I think it’s unrealistic to think
about designing drugs just for us based
on our own unique genomic makeup. That’s
just not going to happen.
What will happen?
Eric Green: Genes act in complicated
networks of pathways where A affects B and
B affects C and C leads to D and so forth.
And through genomics – the name we give
to the discipline that studies the genome –
we are learning about what pathways are
altered in a given disease. And that immediately
gives insight about what existing
drugs or what newly developed drugs might
be useful for compensating for that alteration
in that pathway. So knowing which pathway
is altered can actually be more important
for developing therapies than just knowing
what individual gene is broken.
What has been the greatest
disappointment of the genome?
Eric Green: If there is a “disappointment,”
it is that we are recognizing just
how complicated the human genome is. It
has been a bit of a reality check. Because
it is not simply understanding the genes:
my grandchildren, and probably my
great-grandchildren, will still be interpreting
and reinterpreting the human genome
sequence. But it also means that the field
of genomics is going to be a hot one for