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TEDGlobal 2005

Craig Venter: Sampling the ocean's DNA

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Genomics pioneer Craig Venter takes a break from his epic round-the-world expedition to talk about the millions of genes his team has discovered so far in its quest to map the ocean's biodiversity.

- Biologist, genetics pioneer
In 2001, Craig Venter made headlines for sequencing the human genome. In 2003, he started mapping the ocean's biodiversity. And now he's created the first synthetic lifeforms -- microorganisms that can produce alternative fuels. Full bio

At the break, I was asked by several people
00:25
about my comments about the aging debate.
00:27
And this will be my only comment on it.
00:30
And that is, I understand
00:32
that optimists greatly outlive pessimists.
00:34
(Laughter)
00:36
What I'm going to tell you about in my 18 minutes is
00:41
how we're about to switch from reading the genetic code
00:44
to the first stages of beginning
00:48
to write the code ourselves.
00:50
It's only 10 years ago this month
00:53
when we published the first sequence
00:55
of a free-living organism,
00:57
that of haemophilus influenzae.
00:59
That took a genome project
01:01
from 13 years down to four months.
01:03
We can now do that same genome project
01:07
in the order of
01:09
two to eight hours.
01:11
So in the last decade, a large number of genomes have been added:
01:13
most human pathogens,
01:16
a couple of plants,
01:19
several insects and several mammals,
01:21
including the human genome.
01:24
Genomics at this stage of the thinking
01:27
from a little over 10 years ago
01:30
was, by the end of this year, we might have
01:32
between three and five genomes sequenced;
01:34
it's on the order of several hundred.
01:37
We just got a grant from the Gordon and Betty Moore Foundation
01:40
to sequence 130 genomes this year,
01:43
as a side project from environmental organisms.
01:46
So the rate of reading the genetic code has changed.
01:50
But as we look, what's out there,
01:54
we've barely scratched the surface
01:56
on what is available on this planet.
01:58
Most people don't realize it, because they're invisible,
02:02
but microbes make up about a half of the Earth's biomass,
02:05
whereas all animals only make up about
02:09
one one-thousandth of all the biomass.
02:12
And maybe it's something that people in Oxford don't do very often,
02:14
but if you ever make it to the sea,
02:17
and you swallow a mouthful of seawater,
02:19
keep in mind that each milliliter
02:22
has about a million bacteria
02:24
and on the order of 10 million viruses.
02:26
Less than 5,000 microbial species
02:29
have been characterized as of two years ago,
02:32
and so we decided to do something about it.
02:34
And we started the Sorcerer II Expedition,
02:36
where we were, as with great oceanographic expeditions,
02:39
trying to sample the ocean every 200 miles.
02:42
We started in Bermuda for our test project,
02:47
then moved up to Halifax,
02:49
working down the U.S. East Coast,
02:51
the Caribbean Sea, the Panama Canal,
02:53
through to the Galapagos, then across the Pacific,
02:58
and we're in the process now of working our way
03:00
across the Indian Ocean.
03:02
It's very tough duty; we're doing this on a sailing vessel,
03:04
in part to help excite young people
03:07
about going into science.
03:09
The experiments are incredibly simple.
03:12
We just take seawater and we filter it,
03:14
and we collect different size organisms on different filters,
03:17
and then take their DNA back to our lab in Rockville,
03:21
where we can sequence a hundred million letters
03:24
of the genetic code every 24 hours.
03:27
And with doing this,
03:29
we've made some amazing discoveries.
03:31
For example, it was thought that the visual pigments
03:33
that are in our eyes -- there was only one or two organisms
03:35
in the environment that had these same pigments.
03:38
It turns out, almost every species
03:42
in the upper parts of the ocean
03:44
in warm parts of the world
03:46
have these same photoreceptors,
03:48
and use sunlight as the source of their energy
03:50
and communication.
03:53
From one site, from one barrel of seawater,
03:55
we discovered 1.3 million new genes
03:58
and as many as 50,000 new species.
04:01
We've extended this to the air
04:05
now with a grant from the Sloan Foundation.
04:07
We're measuring how many viruses and bacteria
04:10
all of us are breathing in and out every day,
04:12
particularly on airplanes
04:15
or closed auditoriums.
04:17
(Laughter)
04:19
We filter through some simple apparatuses;
04:22
we collect on the order of a billion microbes from just a day
04:24
filtering on top of a building in New York City.
04:27
And we're in the process of sequencing all that
04:31
at the present time.
04:33
Just on the data collection side,
04:35
just where we are through the Galapagos,
04:37
we're finding that almost every 200 miles,
04:40
we see tremendous diversity
04:42
in the samples in the ocean.
04:44
Some of these make logical sense,
04:47
in terms of different temperature gradients.
04:49
So this is a satellite photograph
04:52
based on temperatures -- red being warm,
04:54
blue being cold --
04:56
and we found there's a tremendous difference between
04:59
the warm water samples and the cold water samples,
05:02
in terms of abundant species.
05:04
The other thing that surprised us quite a bit
05:07
is these photoreceptors detect different wavelengths of light,
05:09
and we can predict that based on their amino acid sequence.
05:13
And these vary tremendously from region to region.
05:17
Maybe not surprisingly,
05:20
in the deep ocean, where it's mostly blue,
05:22
the photoreceptors tend to see blue light.
05:24
When there's a lot of chlorophyll around,
05:28
they see a lot of green light.
05:30
But they vary even more,
05:32
possibly moving towards infrared and ultraviolet
05:34
in the extremes.
05:37
Just to try and get an assessment
05:40
of what our gene repertoire was,
05:42
we assembled all the data --
05:44
including all of ours thus far from the expedition,
05:46
which represents more than half of all the gene data on the planet --
05:49
and it totaled around 29 million genes.
05:52
And we tried to put these into gene families
05:56
to see what these discoveries are:
05:58
Are we just discovering new members of known families,
06:00
or are we discovering new families?
06:03
And it turns out we have about 50,000
06:05
major gene families,
06:07
but every new sample we take in the environment
06:10
adds in a linear fashion to these new families.
06:13
So we're at the earliest stages of discovery
06:16
about basic genes,
06:18
components and life on this planet.
06:21
When we look at the so-called evolutionary tree,
06:25
we're up on the upper right-hand corner with the animals.
06:28
Of those roughly 29 million genes,
06:32
we only have around 24,000
06:36
in our genome.
06:38
And if you take all animals together,
06:40
we probably share less than 30,000
06:42
and probably maybe a dozen
06:45
or more thousand different gene families.
06:48
I view that these genes are now
06:52
not only the design components of evolution.
06:54
And we think in a gene-centric view --
06:57
maybe going back to Richard Dawkins' ideas --
06:59
than in a genome-centric view,
07:02
which are different constructs of these gene components.
07:04
Synthetic DNA, the ability to synthesize DNA,
07:09
has changed at sort of the same pace
07:12
that DNA sequencing has
07:14
over the last decade or two,
07:16
and is getting very rapid and very cheap.
07:18
Our first thought about synthetic genomics came
07:21
when we sequenced the second genome back in 1995,
07:23
and that from mycoplasma genitalium.
07:27
And we have really nice T-shirts that say,
07:29
you know, "I heart my genitalium."
07:32
This is actually just a microorganism.
07:34
But it has roughly 500 genes.
07:38
Haemophilus had 1,800 genes.
07:42
And we simply asked the question,
07:44
if one species needs 800, another 500,
07:46
is there a smaller set of genes
07:48
that might comprise a minimal operating system?
07:50
So we started doing transposon mutagenesis.
07:54
Transposons are just small pieces of DNA
07:57
that randomly insert in the genetic code.
08:00
And if they insert in the middle of the gene, they disrupt its function.
08:02
So we made a map of all the genes
08:06
that could take transposon insertions
08:08
and we called those "non-essential genes."
08:10
But it turns out the environment is very critical for this,
08:13
and you can only
08:16
define an essential or non-essential gene
08:18
based on exactly what's in the environment.
08:21
We also tried to take a more directly intellectual approach
08:25
with the genomes of 13 related organisms,
08:27
and we tried to compare all of those, to see what they had in common.
08:32
And we got these overlapping circles. And we found only 173 genes
08:36
common to all 13 organisms.
08:40
The pool expanded a little bit if we ignored
08:43
one intracellular parasite;
08:45
it expanded even more
08:47
when we looked at core sets of genes
08:49
of around 310 or so.
08:51
So we think that we can expand
08:53
or contract genomes, depending on your point of view here,
08:55
to maybe 300 to 400 genes
08:58
from the minimal of 500.
09:01
The only way to prove these ideas
09:03
was to construct an artificial chromosome with those genes in them,
09:06
and we had to do this in a cassette-based fashion.
09:09
We found that synthesizing accurate DNA
09:12
in large pieces was extremely difficult.
09:14
Ham Smith and Clyde Hutchison, my colleagues on this,
09:17
developed an exciting new method
09:20
that allowed us to synthesize a 5,000-base pair virus
09:22
in only a two-week period
09:25
that was 100 percent accurate,
09:27
in terms of its sequence and its biology.
09:30
It was a quite exciting experiment -- when we just took the synthetic piece of DNA,
09:33
injected it in the bacteria and all of a sudden,
09:37
that DNA started driving the production of the virus particles
09:39
that turned around and then killed the bacteria.
09:44
This was not the first synthetic virus --
09:47
a polio virus had been made a year before --
09:49
but it was only one ten-thousandth as active
09:53
and it took three years to do.
09:55
This is a cartoon of the structure of phi X 174.
09:58
This is a case where the software now builds its own hardware,
10:02
and that's the notions that we have with biology.
10:06
People immediately jump to concerns about biological warfare,
10:10
and I had recent testimony before a Senate committee,
10:14
and a special committee the U.S. government has set up
10:18
to review this area.
10:20
And I think it's important to keep reality in mind,
10:22
versus what happens with people's imaginations.
10:25
Basically, any virus that's been sequenced today --
10:29
that genome can be made.
10:32
And people immediately freak out about things about Ebola or smallpox,
10:34
but the DNA from this organism is not infective.
10:38
So even if somebody made the smallpox genome,
10:42
that DNA itself would not cause infections.
10:45
The real concern that security departments have
10:49
is designer viruses.
10:52
And there's only two countries, the U.S. and the former Soviet Union,
10:54
that had major efforts
10:58
on trying to create biological warfare agents.
11:00
If that research is truly discontinued,
11:03
there should be very little activity
11:06
on the know-how to make designer viruses in the future.
11:08
I think single-cell organisms are possible within two years.
11:12
And possibly eukaryotic cells,
11:16
those that we have,
11:19
are possible within a decade.
11:21
So we're now making several dozen different constructs,
11:24
because we can vary the cassettes and the genes
11:28
that go into this artificial chromosome.
11:31
The key is, how do you put all of the others?
11:33
We start with these fragments,
11:35
and then we have a homologous recombination system
11:37
that reassembles those into a chromosome.
11:40
This is derived from an organism, deinococcus radiodurans,
11:44
that can take three million rads of radiation and not be killed.
11:47
It reassembles its genome after this radiation burst
11:53
in about 12 to 24 hours,
11:57
after its chromosomes are literally blown apart.
11:59
This organism is ubiquitous on the planet,
12:02
and exists perhaps now
12:04
in outer space due to all our travel there.
12:06
This is a glass beaker after
12:10
about half a million rads of radiation.
12:12
The glass started to burn and crack,
12:14
while the microbes sitting in the bottom
12:16
just got happier and happier.
12:18
Here's an actual picture of what happens:
12:20
the top of this shows the genome
12:22
after 1.7 million rads of radiation.
12:24
The chromosome is literally blown apart.
12:27
And here's that same DNA automatically reassembled
12:29
24 hours later.
12:33
It's truly stunning that these organisms can do that,
12:35
and we probably have thousands,
12:38
if not tens of thousands, of different species
12:40
on this planet that are capable of doing that.
12:42
After these genomes are synthesized,
12:45
the first step is just transplanting them
12:47
into a cell without a genome.
12:49
So we think synthetic cells are going to have tremendous potential,
12:53
not only for understanding the basis of biology
12:57
but for hopefully environmental and society issues.
13:00
For example, from the third organism we sequenced,
13:03
Methanococcus jannaschii -- it lives in boiling water temperatures;
13:06
its energy source is hydrogen
13:10
and all its carbon comes from CO2 it captures back from the environment.
13:12
So we know lots of different pathways,
13:17
thousands of different organisms now
13:19
that live off of CO2,
13:22
and can capture that back.
13:24
So instead of using carbon from oil
13:26
for synthetic processes,
13:29
we have the chance of using carbon
13:31
and capturing it back from the atmosphere,
13:34
converting that into biopolymers
13:37
or other products.
13:39
We have one organism that lives off of carbon monoxide,
13:41
and we use as a reducing power
13:44
to split water to produce hydrogen and oxygen.
13:46
Also, there's numerous pathways
13:50
that can be engineered metabolizing methane.
13:52
And DuPont has a major program with Statoil in Norway
13:56
to capture and convert the methane
14:00
from the gas fields there into useful products.
14:02
Within a short while, I think there's going to be a new field
14:06
called "Combinatorial Genomics,"
14:08
because with these new synthesis capabilities,
14:10
these vast gene array repertoires
14:13
and the homologous recombination,
14:16
we think we can design a robot to make
14:18
maybe a million different chromosomes a day.
14:20
And therefore, as with all biology,
14:24
you get selection through screening,
14:26
whether you're screening for hydrogen production,
14:29
or chemical production, or just viability.
14:31
To understand the role of these genes
14:34
is going to be well within reach.
14:36
We're trying to modify photosynthesis
14:38
to produce hydrogen directly from sunlight.
14:41
Photosynthesis is modulated by oxygen,
14:44
and we have an oxygen-insensitive hydrogenase
14:47
that we think will totally change this process.
14:50
We're also combining cellulases,
14:55
the enzymes that break down complex sugars into simple sugars
14:57
and fermentation in the same cell
15:00
for producing ethanol.
15:03
Pharmaceutical production is already under way
15:06
in major laboratories
15:08
using microbes.
15:10
The chemistry from compounds in the environment
15:12
is orders of magnitude more complex
15:15
than our best chemists can produce.
15:17
I think future engineered species
15:20
could be the source of food,
15:22
hopefully a source of energy,
15:24
environmental remediation
15:26
and perhaps
15:29
replacing the petrochemical industry.
15:31
Let me just close with ethical and policy studies.
15:33
We delayed the start of our experiments in 1999
15:37
until we completed a year-and-a-half bioethical review
15:41
as to whether we should try and make an artificial species.
15:44
Every major religion participated in this.
15:48
It was actually a very strange study,
15:51
because the various religious leaders were using their scriptures as law books,
15:53
and they couldn't find anything in them prohibiting making life,
15:58
so it must be OK. The only ultimate concerns
16:01
were biological warfare aspects of this,
16:04
but gave us the go ahead to start these experiments
16:08
for the reasons we were doing them.
16:11
Right now the Sloan Foundation has just funded
16:13
a multi-institutional study on this,
16:15
to work out what the risk and benefits to society are,
16:18
and the rules that scientific teams such as my own
16:21
should be using in this area,
16:24
and we're trying to set good examples as we go forward.
16:26
These are complex issues.
16:30
Except for the threat of bio-terrorism,
16:32
they're very simple issues in terms of,
16:34
can we design things to produce clean energy,
16:36
perhaps revolutionizing
16:40
what developing countries can do
16:42
and provide through various simple processes.
16:45
Thank you very much.
16:48

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About the speaker:

Craig Venter - Biologist, genetics pioneer
In 2001, Craig Venter made headlines for sequencing the human genome. In 2003, he started mapping the ocean's biodiversity. And now he's created the first synthetic lifeforms -- microorganisms that can produce alternative fuels.

Why you should listen

Craig Venter, the man who led the private effort to sequence the human genome, is hard at work now on even more potentially world-changing projects.

First, there's his mission aboard the Sorcerer II, a 92-foot yacht, which, in 2006, finished its voyage around the globe to sample, catalouge and decode the genes of the ocean's unknown microorganisms. Quite a task, when you consider that there are tens of millions of microbes in a single drop of sea water. Then there's the J. Craig Venter Institute, a nonprofit dedicated to researching genomics and exploring its societal implications.

In 2005, Venter founded Synthetic Genomics, a private company with a provocative mission: to engineer new life forms. Its goal is to design, synthesize and assemble synthetic microorganisms that will produce alternative fuels, such as ethanol or hydrogen. He was on Time magzine's 2007 list of the 100 Most Influential People in the World.

In early 2008, scientists at the J. Craig Venter Institute announced that they had manufactured the entire genome of a bacterium by painstakingly stitching together its chemical components. By sequencing a genome, scientists can begin to custom-design bootable organisms, creating biological robots that can produce from scratch chemicals humans can use, such as biofuel. And in 2010, they announced, they had created "synthetic life" -- DNA created digitally, inserted into a living bacterium, and remaining alive.

More profile about the speaker
Craig Venter | Speaker | TED.com