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Alejandro Sánchez Alvarado: To solve old problems, study new species

August 19, 2016

Nature is wonderfully abundant, diverse and mysterious -- but biological research today tends to focus on only seven species, including rats, chickens, fruit flies and us. We're studying an astonishingly narrow sliver of life, says biologist Alejandro Sánchez Alvarado, and hoping it'll be enough to solve the oldest, most challenging problems in science, like cancer. In this visually captivating talk, Alvarado calls on us to interrogate the unknown and shows us the remarkable discoveries that surface when we do.

Alejandro Sánchez Alvarado - Developmental and regeneration biologist
Alejandro Sánchez Alvarado wants to understand the how and why of tissue regeneration. Full bio

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Double-click the English subtitles below to play the video.
For the past few years,
00:12
I've been spending my summers
in the marine biological laboratory
00:14
in Woods Hole, Massachusetts.
00:18
And there, what I've been doing
is essentially renting a boat.
00:20
What I would like to do is ask you
00:25
to come on a boat ride with me tonight.
00:27
So, we ride off from Eel Pond
into Vineyard Sound,
00:31
right off the coast of Martha's Vineyard,
00:36
equipped with a drone
to identify potential spots
00:39
from which to peer into the Atlantic.
00:42
Earlier, I was going to say
into the depths of the Atlantic,
00:45
but we don't have to go too deep
to reach the unknown.
00:48
Here, barely two miles away
00:52
from what is arguably the greatest
marine biology lab in the world,
00:54
we lower a simple
plankton net into the water
00:59
and bring up to the surface
01:02
things that humanity rarely
pays any attention to,
01:04
and oftentimes has never seen before.
01:07
Here's one of the organisms
that we caught in our net.
01:11
This is a jellyfish.
01:14
But look closely,
01:15
and living inside of this animal
is another organism
01:17
that is very likely
entirely new to science.
01:20
A complete new species.
01:22
Or how about this other transparent beauty
01:25
with a beating heart,
01:27
asexually growing on top of its head,
01:29
progeny that will move on
to reproduce sexually.
01:32
Let me say that again:
01:36
this animal is growing asexually
on top of its head,
01:38
progeny that is going to reproduce
sexually in the next generation.
01:41
A weird jellyfish?
01:46
Not quite.
01:48
This is an ascidian.
01:50
This is a group of animals
01:51
that now we know we share
extensive genomic ancestry with,
01:53
and it is perhaps the closest
invertebrate species to our own.
01:56
Meet your cousin,
02:02
Thalia democratica.
02:03
(Laughter)
02:05
I'm pretty sure you didn't save a spot
at your last family reunion
02:07
for Thalia,
02:11
but let me tell you,
02:12
these animals are profoundly related to us
02:14
in ways that we're just
beginning to understand.
02:17
So, next time you hear anybody
derisively telling you
02:22
that this type of research
is a simple fishing expedition,
02:26
I hope that you'll remember
the trip that we just took.
02:30
Today, many of the biological
sciences only see value
02:33
in studying deeper what we already know --
02:37
in mapping already-discovered continents.
02:40
But some of us are much more
interested in the unknown.
02:43
We want to discover
completely new continents,
02:46
and gaze at magnificent
vistas of ignorance.
02:50
We crave the experience
of being completely baffled
02:54
by something we've never seen before.
02:58
And yes, I agree
03:00
there's a lot of little ego satisfaction
in being able to say,
03:02
"Hey, I was the first one
to discover that."
03:06
But this is not
a self-aggrandizing enterprise,
03:09
because in this type
of discovery research,
03:12
if you don't feel like a complete
idiot most of the time,
03:14
you're just not sciencing hard enough.
03:18
(Laughter)
03:20
So every summer I bring onto the deck
of this little boat of ours
03:24
more and more things
that we know very little about.
03:30
I would like tonight
to tell you a story about life
03:34
that rarely gets told
in an environment like this.
03:38
From the vantage point of our 21st-century
biological laboratories,
03:42
we have begun to illuminate
many mysteries of life with knowledge.
03:48
We sense that after centuries
of scientific research,
03:52
we're beginning to make
significant inroads
03:56
into understanding some of the most
fundamental principles of life.
03:58
Our collective optimism is reflected
by the growth of biotechnology
04:03
across the globe,
04:08
striving to utilize scientific knowledge
to cure human diseases.
04:10
Things like cancer, aging,
degenerative diseases;
04:15
these are but some
of the undesirables we wish to tame.
04:20
I often wonder:
04:25
Why is it that we are having
so much trouble
04:27
trying to solve the problem of cancer?
04:30
Is it that we're trying to solve
the problem of cancer,
04:33
and not trying to understand life?
04:36
Life on this planet
shares a common origin,
04:39
and I can summarize 3.5 billion years
of the history of life on this planet
04:42
in a single slide.
04:47
What you see here are representatives
of all known species in our planet.
04:49
In this immensity of life
and biodiversity,
04:53
we occupy a rather unremarkable position.
04:56
(Laughter)
04:59
Homo sapiens.
05:00
The last of our kind.
05:03
And though I don't really want
to disparage at all
05:05
the accomplishments of our species,
05:08
as much as we wish it to be so
and often pretend that it is,
05:10
we are not the measure of all things.
05:15
We are, however, the measurers
of many things.
05:19
We relentlessly quantify,
analyze and compare,
05:23
and some of this is absolutely invaluable
and indeed necessary.
05:27
But this emphasis today on forcing
biological research to specialize
05:31
and to produce practical outcomes
05:38
is actually restricting our ability
to interrogate life
05:40
to unacceptably narrow confines
and unsatisfying depths.
05:44
We are measuring an astonishingly
narrow sliver of life,
05:49
and hoping that those numbers
will save all of our lives.
05:54
How narrow do you ask?
05:58
Well, let me give you a number.
05:59
The National Oceanic and Atmospheric
Administration recently estimated
06:01
that about 95 percent of our oceans
remain unexplored.
06:06
Now let that sink in for a second.
06:10
95 percent of our oceans
remain unexplored.
06:13
I think it's very safe to say
06:17
that we don't even know
how much about life we do not know.
06:19
So, it's not surprising
that every week in my field
06:25
we begin to see the addition
of more and more new species
06:28
to this amazing tree of life.
06:31
This one for example --
06:34
discovered earlier this summer,
06:35
new to science,
06:37
and now occupying its lonely branch
in our family tree.
06:38
What is even more tragic
06:42
is that we know about a bunch
of other species of animals out there,
06:44
but their biology remains
sorely under-studied.
06:47
I'm sure some of you
have heard about the fact
06:51
that a starfish can actually
regenerate its arm after it's lost.
06:53
But some of you might not know
06:57
that the arm itself can actually
regenerate a complete starfish.
06:59
And there are animals out there
that do truly astounding things.
07:04
I'm almost willing to bet
07:09
that many of you have never heard
of the flatworm, Schmidtea mediterranea.
07:11
This little guy right here
07:16
does things that essentially
just blow my mind.
07:18
You can grab one of these animals
and cut it into 18 different fragments,
07:22
and each and every one of those fragments
will go on to regenerate
07:26
a complete animal
07:29
in under two weeks.
07:31
18 heads, 18 bodies, 18 mysteries.
07:33
For the past decade and a half or so,
07:38
I've been trying to figure out
how these little dudes do what they do,
07:40
and how they pull this magic trick off.
07:44
But like all good magicians,
07:46
they're not really releasing
their secrets readily to me.
07:48
(Laughter)
07:51
So here we are,
07:52
after 20 years of essentially
studying these animals,
07:53
genome mapping, chin scratching,
07:58
and thousands of amputations
and thousands of regenerations,
08:00
we still don't fully understand
how these animals do what they do.
08:03
Each planarian an ocean unto itself,
08:08
full of unknowns.
08:11
One of the common characteristics
08:14
of all of these animals
I've been talking to you about
08:16
is that they did not appear
to have received the memo
08:18
that they need to behave
according to the rules
08:21
that we have derived from a handful
of randomly selected animals
08:24
that currently populate the vast majority
08:28
of biomedical laboratories
across the world.
08:31
Meet our Nobel Prize winners.
08:34
Seven species, essentially,
08:36
that have produced for us the brunt
of our understanding
08:38
of biological behavior today.
08:42
This little guy right here --
08:45
three Nobel Prizes in 12 years.
08:46
And yet, after all the attention
they have garnered,
08:50
and all the knowledge they have generated,
08:52
as well as the lion's share
of the funding,
08:55
here we are standing [before] the same
litany of intractable problems
08:57
and many new challenges.
09:01
And that's because, unfortunately,
09:03
these seven animals essentially correspond
09:05
to 0.0009 percent of all of the species
that inhabit the planet.
09:07
So I'm beginning to suspect
09:15
that our specialization is beginning
to impede our progress at best,
09:18
and at worst, is leading us astray.
09:23
That's because life
on this planet and its history
09:26
is the history of rule breakers.
09:29
Life started on the face of this planet
as single-cell organisms,
09:31
swimming for millions
of years in the ocean,
09:34
until one of those creatures decided,
09:37
"I'm going to do things differently today;
09:39
today I would like to invent
something called multicellularity,
09:41
and I'm going to do this."
09:44
And I'm sure it wasn't a popular
decision at the time --
09:45
(Laughter)
09:48
but somehow, it managed to do it.
09:49
And then, multicellular
organisms began to populate
09:51
all these ancestral oceans,
09:53
and they thrived.
09:55
And we have them here today.
09:56
Land masses began to emerge
from the surface of the oceans,
09:58
and another creature thought,
10:01
"Hey, that looks like a really nice
piece of real estate.
10:03
I'd like to move there."
10:06
"Are you crazy?
10:07
You're going to desiccate out there.
Nothing can live out of water."
10:08
But life found a way,
10:11
and there are organisms
now that live on land.
10:13
Once on land, they may have
looked up into the sky
10:15
and said, "It would be nice
to go to the clouds,
10:17
I'm going to fly."
10:20
"You can't break the law of gravity,
there's no way you can fly."
10:21
And yet, nature has invented --
10:24
multiple and independent times --
10:26
ways to fly.
10:28
I love to study these animals
that break the rules,
10:30
because every time they break a rule,
they invent something new
10:32
that made it possible for us
to be able to here today.
10:36
These animals did not get the memo.
10:40
They break the rules.
10:42
So if we're going to study animals
that break the rules,
10:44
shouldn't how we study them
also break the rules?
10:47
I think we need to renew
our spirit of exploration.
10:51
Rather than bring nature
into our laboratories
10:55
and interrogate it there,
10:57
we need to bring our science
10:59
into the majestic laboratory
that is nature,
11:01
and there, with our modern
technological armamentarium,
11:03
interrogate every new form
of life we find,
11:07
and any new biological attribute
that we may find.
11:10
We actually need to bring
all of our intelligence
11:14
to becoming stupid again --
11:18
clueless [before] the immensity
of the unknown.
11:20
Because after all,
11:25
science is not really about knowledge.
11:26
Science is about ignorance.
11:28
That's what we do.
11:31
Once, Antoine de Saint-Exupéry wrote,
11:32
"If you want to build a ship,
11:35
don't drum up people to collect wood
11:37
and don't assign them tasks and work,
11:39
but rather teach them to long
for the endless immensity of the sea ..."
11:42
As a scientist and a teacher,
11:46
I like to paraphrase this to read
11:48
that we scientists need
to teach our students
11:50
to long for the endless
immensity of the sea
11:53
that is our ignorance.
11:56
We Homo sapiens are the only
species we know of
11:58
that is driven to scientific inquiry.
12:02
We, like all other species on this planet,
12:05
are inextricably woven
into the history of life on this planet.
12:07
And I think I'm a little wrong
when I say that life is a mystery,
12:12
because I think that life
is actually an open secret
12:16
that has been beckoning our species
for millennia to understand it.
12:18
So I ask you:
12:23
Aren't we the best chance
that life has to know itself?
12:24
And if so,
12:29
what the heck are we waiting for?
12:30
Thank you.
12:32
(Applause)
12:33

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Alejandro Sánchez Alvarado - Developmental and regeneration biologist
Alejandro Sánchez Alvarado wants to understand the how and why of tissue regeneration.

Why you should listen

Alejandro Sánchez Alvarado is fascinated by the fact that the natural ability to restore missing body parts after injury is broadly yet unevenly distributed across the animal kingdom. Why, for instance, can snails grow new heads after decapitation, or salamanders sprout new limbs, tails, even hearts after amputation, while we humans are so impoverished when it comes to these regenerative abilities? To attack this problem Alvarado, his team and his trainees have collectively developed methods and approaches to dissect this problem at unprecedented levels of molecular, genetic and cellular resolution.

Alvarado runs a Howard Hughes Medical Institute laboratory at the Stowers Institute for Medical Research in Kansas City, Missouri, where he is an Investigator. Alejandro and his team of researchers are vigorously dissecting the problem of regeneration using state-of-the-art nucleic acid sequencing, genomic, proteomic, bioinformatics, light and electron microscopy, flow cytometric and histological methods. Their efforts are centered around the flatworm Schmidtea mediterranea, an organism with astonishing regenerative capacities. Small fragments of tissue removed from these animals, for instance, can regenerate complete animals in under two weeks. The basic, discovery research efforts of Alvarado and his team have begun to shed much mechanistic light into the long-standing biological problem of regeneration, and they are poised to inform poorly understood aspects of our own biology. 

Alvarado, a member of the American Academy of Arts and Sciences, has grown concerned with the current approach of biomedical research of focusing the brunt of its efforts on a handful of randomly selected species. He believes this approach is preventing us from uncovering huge amounts of unknown and relevant biology to understand our own. As Quanta Magazine wrote "Some scientists … argue that by focusing on roughly seven animals out of the estimated 9 million species on Earth, we are missing a huge chunk of interesting biology. 'We are due for a renaissance,' said Alejandro Sánchez Alvarado. 'We have narrowed our focus to a handful of organisms that statistically are highly unlikely to encompass the gamut of biological activity on the planet.'"


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