On the topic of therapeutic innovation,
please welcome Dorothy and Milton Flier professor
of biomedical science and genetics
at Harvard Medical School, Steven McCarroll.
Hi, I'm Steve.
Several years ago, I was given a chance to start a lab here
at Harvard Medical School.
With that came a chance to contribute
to a scientific ecosystem like no other
in the world, a discovery engine that
works to transform possibilities for human health.
But this engine is powered by people, people
like you just heard in Rachel--
brilliant, passionate students, postdocs, residents,
fellows, who come and trained here
to unravel the mysteries of biology
and to alter the course of human disease.
This is an image from one story of so many
from that kind of work here.
Schizophrenia is a devastating illness,
long in need of biological insight and innovative
therapies.
The medical treatments used to treat schizophrenia today
have hardly evolved from drugs that
were used in the 1960s, drugs that
treat a single symptom, while leaving the underlying disease
untouched, because its mechanisms are unknown.
Enter Aswin Sekar, an MD PhD student
at Harvard Medical School.
Aswin invented a new way of analyzing human genome
data, a combination of molecular biology experiments he did
in the lab, statistical approaches and computer
algorithms he wrote, to make forms of genetic variation
that were previously invisible visible to analysis.
He then applied his approach to genetic data that,
from DNA that had been contributed
from tens of thousands of schizophrenia patients
from 30 countries all over the world.
Aswin's analysis taught us how the human genome
exerts its strongest influence at a population level
on risk of schizophrenia.
He showed that this effect arises
from overactive forms of a gene called complement component
four, C4 for short.
This was surprising, because C4 was
considered an immune protein.
More surprisingly, as shown here,
we found the C4 protein present at synapses, the place
where neurons contact other neurons in the nervous system.
Nearby, at HMS, Aswin found both Mike Carroll,
an expert on the biology of the complement system,
and Beth Stevens, who had discovered
that other related complement proteins have
a surprising other job in the brain, where they act
as molecular tags that elicit the pruning
or severing of connections between nerve cells.
Together, this team, including also people in all three
of our labs, showed that the C4 genes do this also
and that these overactive forms of the C4 genes
do this excessively.
This team's findings advanced our understanding
of schizophrenia in a surprising direction.
That knowledge, we hope, will make
it possible to develop new kinds of therapies that might address
the root causes of the illness.
But this is just one of many ways
that new approaches and technology platforms
can be created and used to open new channels in our ability
to listen to human biology.
You're looking here at a movie of another one,
a technology we call drops seek.
A long-standing need in science and medicine
had been to better capture the biological information that's
present, but hidden inside of tissues.
We know the information about disease processes
must be locked up in the molecular states
of the individual cells within tissues.
But accessing this information was challenging
for a very long time.
These two Harvard Medical School postdocs,
Evan Macosko and Allon Klein, conceived and led
efforts to develop technologies for analyzing tissues
at the single cell level by encapsulating
each individual cell in a tiny water droplet
to have its molecules bar coded with DNA for its own precision
molecular analysis.
You can see from this movie the speed at which individual cells
can be packaged and bar coded and processed for analysis.
This allows single cell sequencing of tens of thousands
of individual cells at once.
And they organized interdisciplinary teams
across the Harvard physics department and the Broad
Institute to actualize this vision
at the level of droplet fluid as physics and data science.
Today, this technology is helping scientists
around the world to identify all of the cell types
in the human body, to learn which genes are expressed
in each cell population, and to identify the vulnerable cell
populations in many diseases.
This is my sister, who last year benefited
from life-saving experimental medicine
in a clinical trial for lymphoma.
Many of you in the audience may know
what it's like to experience firsthand
the transformative power of experimental medicine
in a tangible way.
The experience induces profound gratitude,
and also awe at the promises and possibilities
that biomedical research gives to people and their families.
For all of us who do such research,
such an experience also enhances a sense of urgency
about getting everything done as quickly as we can.
There is no waiting for the science to get there.
We need to drive it forward and share it exuberantly,
so that advances can benefit people
we know and love here and now.
Thank you very much.