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>> Kim Ricketts: Good afternoon, everyone, and welcome. My name is Kim Ricketts, and I manage, along
with Kirsten Wiley, the Microsoft Research Visiting Speakers Series. Thank you for joining us today.
Today we welcome Carl Zimmer here to Microsoft Research to discuss the biography of a microbe. Yes,
the story of how E. Coli was discovered and, more importantly, the role that this fast growing and
sophisticated bacteria has played in everything from proving Watson and Cricks theory about DNA, to
helping us understand how genes work, to the creation of human insulin.
While most of us know it from its deadly outbreaks of undercooked food, in fact, we all carry billions of E.
Coli in our intestines. And this microbe continues to lead the way in the search life saving drugs, clean fuel
and a deeper understanding of our own genetic makeup.
When I sent out the announcement for this talk internally one e-mail came back to me saying: Yuck.
[Laughter] That's what it was titled. I opened it up and it continued on by saying: But upon further
reflection this topic is actually fascinating. Ended by saying thanks for bringing speakers that broaden our
understanding of the world.
Carl Zimmer is one of those speakers. Carl is the author of five earlier books and is also a frequent
contributor to the New York Times National Geographic, Scientific American, Discover and is a frequent
guest on NPR's Fresh Air and This American Life.
Zimmer has been awarded fellowships from the Gugenheim Foundation, the Alfred Sloan Foundation. His
honors include the American Association for the Advancement of Sciences and Science Journalism Award
and many, many others.
So please join me in welcoming Carl Zimmer to Microsoft Research.
(Applause)
>> Carl Zimmer: Thanks very much. So can you hear me? Is my mic on? Okay. Well, I suppose most
writers would take "yuck" as harsh criticism. But I am a person who has written an entire book praising
parasites. So I take yuck as a badge of honor.
And I suppose people were not terribly surprised when they found out I was going to be writing about
something about like E. Coli. And, of course, as soon as I would tell them I'm writing this book about E.
Coli their minds would jump to getting very sick.
Just so happened that there was another outbreak of E. Coli when I was working on this. And I would try to
explain to them. I would say, no, actually, there's something else I'm after here.
For scientists, E. Coli means something else entirely. E. Coli is really a guide to what it means to be alive.
Scientists understand E. Coli arguably better than any other species on earth. And if you want to
understand what it means to be alive, then E. Coli is a good thing to get to know.
So let me just tell you quickly about what E. Coli is and I'll start with its name. It's full name is Estrichae
Coli. And it's named after Theodore Estrich, this gentleman here.
He was a German pediatrician. And in the 1880s he was trying to figure out why it was that all the babies
that were his patients were dying. The mortality rate in 19th century Germany was quite staggering.
You'd have to go to a place like Angola today to really find comparable levels of child mortality. And a lot of
that was due to intestinal diseases. And so Estrich subscribed to this radical notion that there were germs
that were responsible for these diseases.
So he was an early adopter of the germ theory of disease. And he thought that he could isolate the germs
that made these children sick and the way that he could do that was, first of all, to figure out all the germs
that are in healthy children and then compare them to the sick ones. Because he knew very well that we
are full of bacteria.
And he wanted to start doing an inventory. So he made a study of diapers. And I'll leave it at that. And
tried to figure out what was growing in there. And he was quite intrigued by these little rod-shaped
bacteria. He called them bacillus communus coli, just a common bacteria.
He was impressed by how fast they grew in his lab in the presence of oxygen and how well they could grow
on just about anything. And he describes feeding them milk and potatoes and blood. And they would just
grow on all of this stuff.
That's basically where things stayed for the next few decades. I mean scientists came to recognize that E.
Coli was one of these resident of our guts. You have about a billion, a few billion of them.
You were infected with E. Coli a few days after you were born. You're born sterile and then your parents or
a nurse or someone gets you infected. Not just with E. Coli but with maybe a thousand other species and
they just set up shop inside of you.
And you depend on them to help digest your food. To regulate your immune system. All sorts of things.
E. Coli itself is obviously not a big organism. You could fit about 10,000 of them across your finger. It's got
this rod shape and it's packed with molecules. Maybe 50, 60 million molecules. And those little lines that
you see are tails called the flagella, that I'll get to in a second, because they have an interesting story to tell.
Now, the reason that E. Coli now is so important to biology is that in the 1930s and 40s, some scientists
started to ask what does it mean to be alive? And they decided to try to answer that question with E. Coli.
Now, this is obviously a very old question and I mean Aristotle had his own answer to it. He would say that
life, he thought of life in terms of a psyche that there was something that was the source of movement
inside living things and that non-living things didn't have it.
So Erwin Shortinger (phonetic) in the 20th century, 1940s, offered kind of a new approach to life.
Shortinger, another physicist, were feeling very confident they had all the physics worked out, but they
were a bit puzzled by life, because life seemed to defy physics. How was it that something could give rise
to a nearly identical version of itself? And it seemed it had to do with this strange thing known as genes,
but nobody quite knew what genes were.
So the reason that these scientists started to study E. Coli was because it was harmless. It grew fast in
oxygen. It could feed on lots of different things. It was just an easy thing to study. You could start with one
E. Coli in the afternoon, let it breed overnight, come back in the next day and your experiment is done.
And so they would raise them in petri dishes and they had particular fun getting them sick. So this is a
virus of E. Coli.
And so Max Delbrook (phonetic) and Salvador Luria (phonetic), won a Noble Prize for their work on E. Coli,
would make these poor bacteria very sick.
You would see, for example, these are viruses that are exploding out of this microbe after it's been infected.
So no one actually knew what the viruses were doing when they landed on E. Coli and then a whole bunch
of viruses would come out.
Nobody quite understood how that kind of alchemy took place. But by studying E. Coli and its viruses, they
started to get some, get an understanding of it.
So one experiment, for example, what they did was they -- there was this question maybe genes are made
of DNA. Maybe. Or maybe they're made of protein.
So what some scientists did they did one experiment where they basically tagged the protein with
radioactive tracers and on the viruses and let them infect E. Coli and then they spun the viruses and E. Coli
apart.
It turned out when they looked for the radio activity, it was outside of the microbe. And then they tagged
the DNA and they did the experiment again. And now when they spun the E. Coli and the viruses apart
after the infection, the radio activity was inside of E. Coli. So it was clear proof for those who doubted it
that DNA is the stuff of genes.
Joshua Letterburg who just died recently discovered that E. Coli had a sex. Kind of a weird sex,
immediately. But one microbe will build a tube and pump DNA into another one.
So you can throw these E. Coli having sex into a Waring blender, which is what some scientists did, and
break them apart while they're having sex and discover which genes have made it across and which
haven't.
And you can interrupt their love life after half hour or an hour at different time intervals and you can
discover that different genes have made the journey. And that lets you make a genetic map. One of the
first detailed genetic maps came from studying E. Coli this way.
Another bit of noble prize-winning research with E. Coli was the genetic code figuring out how DNA gets
translated into protein.
What's really important about all this is once people figured this out with E. Coli then they could go and test
these ideas, test these patterns on other species.
So it turned out that E. Coli had a particular genetic code and lo and behold so did we and so did frogs and
so did mushrooms and so did all life on earth.
So that things were discovered in E. Coli kept turning up in other places. Some French researchers
discovered a similar thing about how genes are switched on and off. And so Jack Manard (phonetic) said
wonderful thing: What's true for E. Coli is true for the elephant.
By 1969, these folks were feeling very proud of themselves and very confident. And so Max Delbrook, now
here looking much older, declared: This riddle of life has been solved.
Now, I think he was getting a little bit ahead of himself. It's not like biology is all screeched to a halt. In
fact, there are lots of big open questions about E. Coli about life in general, and E. Coli is still at the
forefront of dealing with these big questions.
The reason is that one of the reasons is that we know so much now about E. Coli. So it's entire genome
has been sequenced. Actually about 30 different strains of E. Coli has been sequenced and scientists
understand what a lot of those genes do.
That's much better than we know with humans. The human genome is really quite a mysterious mess. So
one of the things that you need to understand to understand how life works is how the genes direct. Genes
don't work in isolation.
So there's just one quick example I'll tell you about is how E. Coli deals with getting hot. If E. Coli gets hot,
it could die, because these proteins become unfolded and then they're in big trouble.
So what E. Coli does is it makes an RNA molecule that stays folded up and can't be translated into protein
until a certain temperature. And it unfolds and then it can -- then it can start being made into a protein and
can start switching on other genes. These genes then can take unfolded proteins and fold them back up
again or they can destroy them.
But these proteins also destroy this thing, the sigma molecule, the thing that started the whole process. So
there's a feedback loop built into it. And what's really been interesting is talking to engineers, people who
do control systems, for example, I wrote a piece about John Doyle at Cal Tech who used to design
software for control systems like for the space shuttle. Now he studies E. Coli because he finds that the
way that the whole system works is incredibly elegant and uses a lot of the same principles that he needs
when he's designing some system for keeping the space shuttle from flying out of control.
So if you're going to be alive you also need to kind of have at least some sense of where you are. And E.
Coli actually has exquisite senses. It has this kind of I think it kind of as a microbial tongue at its tip. And
it's made up of thousands of these receptors of each of which can grab onto certain kinds of molecules and
then it can process that information.
It's kind of like a brain. Now, for E. Coli, the one big decision is where to go. And the way it makes that
decision is that once some molecule latches onto it, there are several molecular reactions that take place
inside the bacteria, and that affects those tails I was telling you about. The flagella.
So here's a beautiful computer rendering of a flagellum, the base of it. And it has some resemblance to a
motor. What happens is proteins stream in. They use the energy to spin around hundreds of times a
second.
And the little tails, the tails all sort of -- they're spiral-shaped and they all kind of bind together if the motor is
turning counterclockwise, and that's important. Because that's how E. Coli gets around.
So when they spin counterclockwise they go on this run as you can see here. And every second or so it
goes clockwise, and they fly apart and the poor thing goes spinning around, laser pointers are good for
something, and then they start running again.
Now, you think how are you going to get anywhere with that? Well, if there's something that they -- if
there's no stimulus, they just kind of wander around don't get anywhere in particular.
But if there's something that attracts them, they just bias their runs and their tumbles. In other words, they
run longer than they tumble.
The runs go longer, I should say. And if there's something that repels them, then there's a shorter interval
between their tumbles and once they get pointed in the right direction they go away and they get away from
what's bad.
So it's this wonderfully simple elegant system for getting E. Coli to where it wants to go to and get it away
from where it doesn't go away. It can go away from food and toxins it can go to the right temperature, can
go to places where there's enough oxygen and take the signals in and integrate them together at once.
It's remarkable. Another important thing about life is you can't be sloppy about it. And people why you had
to think bacteria were sloppy, that there was just a big sack of molecules and you didn't have to care about
how it was organized.
That's just silly, because if you popped E. Coli and let the DNA stream out you would find it's a thousand
times longer than E. Coli itself. Now, if you've got 4,000 or so genes in E. Coli and they all need to be read
at lots of different times, you've got to keep it organized.
And scientists are just starting to discover the organization that E. Coli uses and it's quite beautiful. And it
involves, for example, little clips that keep little loops in place, and they open so that the gene can be read
and they close again.
So you can be reading genes to make proteins and copying them at the same time. And you never get
tangled up. Another important thing about life that scientists are increasingly appreciating is that when
you're alive you're never alone. You might think of E. Coli as just being some isolated stupid little microbe
that just sits there and feeds and divides and feeds and divides, and that's the sum total of its life.
The fact is that E. Coli talk to each other. They release molecules that are taken up by other E. Coli, and
the other E. Coli change the way they behave in response.
And they can do very complicated things. They can, for example, build bio films together. Once they figure
out that there are enough of them in a neighborhood, they start squirting out glue and other similar
compounds. Not glue, I should say, but glue-like compounds, and will form kind of these microbial cities
that lie in your gut.
They will also become altruists. So, for example, if they're running out of food and you've got two colonies
of E. Coli, a few of them in one colony may start to make a toxin called ecolosin (phonetic), and they will
essentially like fill up with this ecolosin, like thousands upon thousands of copies of this until they explode.
They kill themselves producing this toxin, which then sprays out. Now, in their own colony, the E. Coli don't
die, because they make an antidote to this toxin.
So each E. Coli carries a toxin for its toxin and antidote. But when the toxin goes to the other colony, they
die because their antidote is the wrong antidote. They make a different kind of toxin and different kind of
antidote. They get killed off. So the colony where those few made that ultimate sacrifice, now they can eat
all the food that's left.
And this brings us to another important thing about life. I mean life, the basic fundamental fact about life is
that it evolves. And so this altruism I was telling you about, all these things are the product of evolution.
And E. Coli is actually a great thing to study to understand how evolution works.
There's this -- if you were -- E. Coli is fantastic for how fast it reproduces. I mean at its fastest it's about
every 20 minutes it can divide. Now, if that just went on for a few days, you would have a world of E. Coli.
I mean we'd be wading through E. Coli.
But obviously we're not. The reason is that the resources are limited and so that creates the conditions for
natural selection. So some individuals are going to be able to reproduce better than others.
So Darwin had this fundamental insight about evolution, but he was thinking mainly in terms of animals and
plants. He really didn't think much at all about bacteria. And yet E. Coli is becoming one of the best things
to study to understand how evolution works in real time.
And some of the best stuff is coming from Richard Lindski at Michigan State University. So what he did he
started 20 years ago with a single E. Coli and he created 12 lines genetically identical lines he kept in
flasks and he gave them a very limited diet of glucose.
Every day they'd run out of their glucose, and then the next morning he and his colleagues would take a
little bit from each flask and put it into a new flask and start it over again.
They froze some of the original ancestors in each line and then every 500 generations they froze some
more. So they have what he likes a frozen fossil record. And then you can thaw them out and see how
they're similar and different than their descendants. You can actually pit the ancestors and descendants
together like in a petri dish to see how fast they reproduce.
Now what's interesting is after 40,000 generations they're very plump. So they're about for some weird
reason no one knows why they're twice as big as their ancestors. And this is a genetic change. This is not
some environmental change.
And just as Darwin would have expected, mean fitness, in other words how fast they can reproduce, they
are about 75 percent better than they used to be. And I actually just blogged today about a new paper that
just came out where Lindski discovered that his E. Coli have actually discovered a new way to eat.
So he feeds them glucose. And he keeps them in this broth that has a mixture of other things including a
molecule called citrate. One of the defining characters of E. Coli is they can't eat citrate. Now in one of his
lines they're now eating citrate.
These trying to figure out what happened. How did this essentially, essentially sort of the origin of species
has taken place in his lab and he's trying to figure out what just happened. Why are they eating citrate.
Obviously this has an important implication beyond sort of your basic understanding of how evolution
works. Right at the time that scientists were using E. Coli to understand the basics of biology, of genes and
proteins and so on, the first antibiotics were being used.
And right at that time scientists were discovering that E. Coli and other species were becoming resistant to
those antibiotics.
It was just a classic case of evolution in action that resistant mutants were being favored. And resistance
was spreading through populations of bacteria. And this is an issue even now as we deal with a horrible
problem with antibiotic resistance.
Now you regularly have bacteria that are resistant to one, two, three, four different antibiotics. So there's
this search for new kinds of antibiotics that could trump the bacteria.
And one of the most celebrated examples came from frog skin. Frogs produce these peptides, these small
molecules that at least when they were discovered seemed incredibly effective against bacteria. Just
lethal. They were discovered because a scientist was cutting open frogs to harvest their eggs and sewing
them back up and throwing them back into this dirty tank where they were just fine.
And he was thinking wait a minute these things should be dying of infection. But they're doing fine. And he
discovered that their skin was covered with these totally different class of antibiotics. So everyone said this
is it. Because they worked in a totally different way than other antibiotics. It seemed like there was no way
that bacteria could evolve resistance to them.
So again there was a great triumphalism until someone who knew E. Coli pretty well published a study
where basically what they did they exposed E. Coli to very low levels of this antibiotic and then high levels
and higher levels and they evolved resistance to this new group of antibiotics without much trouble at all.
So the other important thing about life is that not only does it evolve, but it diverges. It diversifies into new
kinds of species. So Darwin drew this tree to show how life evolves.
And here's actually where those disease causing strains of E. Coli really come in handy. So I do talk about
the E. Coli that makes you sick in my book.
And I talk about it in the context of the fact that, as I said, we all carry E. Coli inside of us from birth to
death. And yet there are these strains of E. Coli that can make us really sick. They are E. Coli. They
share thousands of genes with the E. Coli that we carry with us. But they do weird stuff.
So this is the kind of E. Coli you would get if you ate a bad hamburger, and it's caused the cells in your
intestines to grow up into these bizarre pedestals. It's almost like they're building themselves a throne out
of your guts.
They have lots of different ways of making you sick. There are lots of different strains that make people
sick. And the ones you find in hamburger and spinach actually cause relatively few deaths. The most
deaths are caused by other forms, sometimes called shigella. They kill about a million people worldwide,
mostly children.
So we're not that far from Theodore Estrich's days. And what a lot of them do is they build a needle that
they use to inject molecules into your cells and that causes your cells to act very strangely, in part pouring
out all sorts of nutrients that E. Coli can feed on, also causing diarrhea and bleeding and in some cases
death.
But when scientists look at the relationship between the ones that make us sick and the ones that we carry
with us our whole lives, they find that the disease causing strains have evolved from harmless ones and
vice versa, too.
So you see that -- so there is this tree here reflected in what we know now about E. Coli. And it's
continuing to evolve. This is something I read about recently in Slate when there was that outbreak in 2006
of spinach on contaminated spinach and lettuce, they sequenced it and found that there was a rapidly
evolving branch that had produced this particular epidemic. It was different than the other members of its
strain, which is called a 157H7.
This is actually happening in a weird way a way that Darwin wouldn't have predicted. What's happening
remember I talked about that bacterial sex? What's happening is that bacteria are trading genes. And in
some cases viruses are infecting one cell and then picking up genes and carrying them to another cell. So
you're getting this incredible mixing of genes. It's not just a slow process where a gene might mutate every
once in a while from ancestor to descendant.
It's really kind of a genetic orgy going on out there. It's not going on just between E. Coli but E. Coli and
lots of other species. And this is continuing to happen. The viruses themselves are mutating. So we're
going to continue to have these new, we're going to continue to have new strains of E. Coli that make us,
that continue to make us sick, unfortunately.
And this is important not just medically but in a very deep profound way. As I mentioned, scientists are
sequencing lots of genomes of different strains of E. Coli that are up to 33 or actually more now and from
one gene to the another you will find hundreds upon hundreds of genes that are not found in other strains.
So now scientists are talking about how E. Coli has sort of a core, sort of an essence of E. Coli you could
call it. But it's only about 2,000 genes. And then if you look at all the genes that are found in various
strains of E. Coli, they're up to almost 10,000. And they expect they'll get up to maybe 20,000. That's as
many genes we have.
So scientists are now talking about the pan genome. This is a phrase you'll hear about a lot in the future.
So life branches like a tree sort of. You do have a tree growing through time, but then you have all of this
transfer of genes between the branches. And so this is a profound thing about how life works and E. Coli is
really important for revealing it.
Just quickly I'll tell you a little about how E. Coli became the creationists the poster child. This is how
intelligent design people like to think about E. Coli and its flagellum. They think of it as a motor. And they
say if it looks designed, maybe it is. And if you'd like you can order this on a throw pillow or an apron or a
beer stein, it's up to you, and there's where you can get it.
And creationists have been for many years likening flagellum to technology of various sorts. And they put it
on the covers of their books. But this all came to a head a couple of years ago in this famous case where a
Board of Education in Pennsylvania was trying to get intelligent design, the newest flavor of creationism
into schools.
And one lawyer joked that you should really call it the flagellum trial, because it all -- a lot of it revolved
around this flagellum and particularly of E. Coli since E. Coli is the best studied flagellum of all.
One of the arguments that creationists make is that something like the flagellum couldn't have evolved
because if you take away one part of it, it doesn't work. So you would have no earlier form of the flagellum
that could evolve to a full blown flagellum.
But this just doesn't make sense. Because let's say we've got E. Coli is flagellum. And let's take away that
long sort of tail part of it and take away the hook, take away these other parts as well. Let's just take away
a whole bunch of it, are you left with something that works, something that has a function? You are.
Actually, you can find these things in other bacteria.
This is a close relative of E. Coli called bucnera (phonetic), which only lives inside aphids, and it actually, it
only lives inside the cells of aphids and it's essential for the aphids. It generates some of the food they
need.
And it's got protein for protein, this part of the flagellum and it uses it probably to release molecules into its
host cell.
So E. Coli not only doesn't support the creationism, but it gives you an idea of how evolution works, how
complex traits evolve.
So scientists are now looking at all the parts of E. Coli's flagellum and finding homologies, related versions
in other structures and bacteria.
And just finally I want to talk about another reason that E. Coli is such a great thing to study and to use and
to learn about life, because life is changing. I mean we live in an age of bio technology. An age of
synthetic biology. And E. Coli helped us get into this new age. I'm particularly interested in what E. Coli
can do to help us to understand what's natural and what's not natural. Because a lot of the debate these
days about genetically modified foods revolves around or chymeras (phonetic) and so on, people are
nervous about it because you're crossing the species boundary.
This is Marlon Brando, The Island of Dr. Mareaux. He meets a pretty awful end because he's tampering
with the species boundary. HG Well's punished him for doing that.
Well, in the early '70s scientists figured out how to put human genes, I should say first they figured out how
to put animal genes into E. Coli.
And they started out one of the earliest things they did was put some frog DNA into E. Coli. Once they had
figured that out, then they thought, well, we can put other things in like human insulin, for example.
This generated a huge controversy. Just as intense as what we're dealing with today with genetically
modified foods and so on. And it's really interesting to go back and look at how that played out.
People were really scared that E. Coli would be killing people left and right. You would have E. Coli
delivered plagues of cancer or diabetic shock. And the City of Cambridge stopped all genetic engineering
for a few months because there was such an outcry.
Today, things have changed a bit. So while genetically modified foods may be controversial, the fact that a
lot of insulin comes from E. Coli isn't, which I find interesting. Because this is just as unnatural and a
breaking of species boundaries as a mouse with human neurons in it.
We've actually gone a long way from those early days of genetic engineering. Now we're in the age of
synthetic biology, and it's E. Coli again that's playing a big part. And right now we're kind of in the -- we're
still in the kind of I think cool stunt phase of synthetic biology. So some graduate and undergraduate
students figured out how to engineer E. Coli with pigment genes with marine bacteria and some other
genes and basically turned it into a camera.
You can take your picture with E. Coli. But there are some much more ambitious projects underway.
University of California at San Francisco. Some researchers want to engineer E. Coli to basically home in
on cancer, invade tumors. And once they're inside release a bunch of toxins.
And now E. Coli is producing gasoline and jet fuel and malaria drugs, it's been used with.
What I find interesting about this is that it not only has some real applications in the sort of commercial
world, but it might help us to answer some of these deep questions that I was talking about before.
So how far you can tinker with E. Coli might tell you what the limits of life are. NASA is very interested in
this question, because if they're going to send probes to look for life on other planets, they'd like to have
kind of an idea of what they should be looking for.
I mean is it going to be Star Trek, where you go there and, oh, look, there are people on two legs, they just
happen to have green paint on their faces, or will they be different? Does life have to be made of DNA, for
example? I mean all life on earth uses about 20 amino acids to build proteins but there are dozens and
others of amino acids they could use, theoretically.
Is there something wrong with those amino acids? Do they not allow life to exist? Well, what some
scientists have done they've engineered E. Coli to use some of these unnatural amino acids to make their
proteins. They're fine. They just go on with their lives.
They've used 30 different amino acids now that as far as we know nothing on earth has ever used. At least
we don't know of anything that's used them.
So in a sense we have made aliens on earth. They just happen to be E. Coli. So the question that I have,
if and when we ever find life on other planets is to take jack man know's saying what's true for E. Coli is
true for the elephant. I want to know is what is true for E. Coli true for aliens.
Because E. Coli is already up in space. It's in the space station. It's in the astronauts and it's floating
around in the air there. I don't think that when people go to Mars they will actually find E. Coli. But I do
wonder if knowing about E. Coli will help us to understand what they do find.
So thank you so much for coming to my talk.
(Applause)
>>: Is it really going 360 over again, around to get to the (inaudible) moving, the wheel.
>> Carl Zimmer: Yeah, it goes all the way around. I forget the figure. I think it's about two, 300 times a
second. Yeah, there's been a lot of over the years like biologists have made a big deal. I know Steven J.
Gould would talk about how life has never evolved wheels. Like there are no animals with wheels. And
talking about that as some sort of constraint, example of a constraint of how life can evolve.
I'm thinking what are you talking about? The animal kingdom is all well and good. But in the bacterial
world, they're all over the place.
>>: Can't have blood vessels, going into the wheel, that would be part.
>> Carl Zimmer: Yeah, definitely wheels or wheel-like things on E. Coli. And they spin around 360
degrees going counterclockwise and then they stop and then they spin the other way 360 degrees
hundreds of times a second and back and forth and back and forth.
>>: E. Coli to have the extra proteins that we don't normally have, have those been kind of dangerous, are
they so divorced from our biology that they wouldn't infect us?
>> Carl Zimmer: Are you talking about the ones using unnatural amino acids? I don't think anybody
knows. But people are thinking about medical applications for those proteins. Because they might interact
with our bodies in interesting ways.
Hopefully in good ways. But there is medical research going on about how to use these unnatural proteins.
Sort of a variation on that is so when our cells make proteins, once the basic chain of amino acids is made
then they are further processed and in some cases different compounds are added onto some of the amino
acids. Normally bacteria can't do that. They don't have that equipment.
So what some scientists have been doing is saying, well, maybe you can engineer E. Coli to take amino
acids that already have some of those extra molecules added to them and put them together. So that you
can still get E. Coli to make these proteins that have these little additions on them.
So it's a different way to get E. Coli to make human proteins by just changing its genetic code.
>>: They're talking about trying to create bacterial from scratch. How much more complicated is E. Coli
than what he's ->> Carl Zimmer: So Craig Ventor (phonetic) is working on a species called mycoplasm genetalium, which
has one of the smallest genomes known. I think it's maybe five or 600 genes. What he and his colleagues
have been working on is figuring out of those genes what are the bare minimum that it would need to
survive. And I think they're down to maybe 350 or something like that.
Now what they do is they knock out one Gene at a time and see if the thing still lives. Now to really know
whether that's the minimal set of genes, they'd have to recreate it with just those 350 genes from scratch
and see if it boots up.
And nobody knows if it would or not. But he's taken so many steps now towards that goal that a lot of
people -- I mean within months, maybe, he might have something like that.
Some other people have suggested using E. Coli instead only because it's so well studied. I mean there
are a bunch of genes in mycoplasma that people don't know what they do. They're essential but we don't
know what they do, which is surprising.
With E. Coli scientists know a lot more about all those genes. And so George Church at Harvard and some
other researchers have said here are the -- I think it's just about 200 genes, that he thinks from E. Coli you
could use to make something live, the minimal set of genes.
Once you've figured that out, then maybe you could just build up on that chassis and create things that are
very different from any bacteria known today.
That's the thinking. I mean other people say why bother, because there's so many bacteria out in the world
that are so well adapted to doing so many different things, what we need to do is we need to be searching
for those natural experiments rather than trying to start one from scratch on our own.
>>: Do you think this could help solve the problem of the biological degraded plastic. We have so many
plastic things in there because no bacterias can digest them. Do you think E. Coli could be evolved into
this?
>> Carl Zimmer: We may not need to engineer E. Coli. There was actually a story that just came out a few
days ago. Some kid I believe in Canada for a science fair project thought maybe I could find some bacteria
that would break down plastic bags. So he just went and looked in some soil and found a species
belonging to a group called pseudomonas that loves eating plastic bags.
And this is actually like a big discovery. I mean it blew a lot of microbiologists away. This thing will just
feast on plastic bags. I mean this could be a very rich kid some day. Seriously.
And once scientists could identify what it is this bacteria is doing, some might transfer some of those genes
to E. Coli, combine them with other genes to optimize what it's doing. That could happen.
So, yeah, breaking down plastic is one of the applications generating energy in less harmful ways than we
do today. That's another possibility. Craig Ventor likes to talk about taming our habit of spewing carbon
dioxide into the atmosphere, drawing them down with carbon dioxide guzzling bacteria.
You know, that naturally raises a question like, okay, what happens if some of those bacteria get out of
Ventor's grasp and just start sucking down carbon dioxide uncontrollably? Would we suddenly find
ourselves in an ice house instead of a greenhouse. I'm being a little flippant but the point is there are a lot
of issues that have to be dealt with synthetic biology.
The bacteria have a habit of slipping away. You can't -- it's not exactly a lock and key that you can use. So
scientists are trying to find out ways to basically make it possible for them to live outside of certain very
constrained conditions.
So they don't get some particular kind of food they can't survive; they'll just die. But then the question
becomes, well, what if they had enough time to pass on some of their genes in the way I was telling you to
other bacteria in the environment, what would happen then. Who knows.
>> Kim Ricketts: If you have any further questions you can ask Carl as he stays here a little longer. Thank
you very much.
>> Carl Zimmer: Thank you very much.