00:00:01.455 --> 00:00:04.370
(BIRD AND ANIMAL SOUNDS
OF THE RAINFOREST)

00:00:04.370 --> 00:00:07.990
- They're on the hunt, in
tropical rainforests and frigid

00:00:07.990 --> 00:00:08.490
caves...

00:00:10.120 --> 00:00:13.050
- Oh my goodness,
who can live in here?

00:00:13.050 --> 00:00:15.510
- ...in the mouths
of giant lizards...

00:00:15.510 --> 00:00:17.540
- Good dragon.

00:00:17.540 --> 00:00:20.540
- ...and on the fur
of forest creatures.

00:00:20.540 --> 00:00:23.410
Scientists are hunting
for new antibiotics,

00:00:23.410 --> 00:00:26.240
because the ones we have
are rapidly failing.

00:00:29.060 --> 00:00:31.880
- We are potentially
returning to the dark days,

00:00:31.880 --> 00:00:35.260
the pre-antibiotic era, where
people would die from even

00:00:35.260 --> 00:00:36.145
a simple infection.

00:00:37.210 --> 00:00:38.730
- He couldn't even
push his button

00:00:38.730 --> 00:00:40.310
to get a nurse to come in.

00:00:40.310 --> 00:00:42.510
- Already, thousands
of people are

00:00:42.510 --> 00:00:46.720
dying of diseases easily
cured a decade ago.

00:00:46.720 --> 00:00:50.110
- I thought, well, who
dies from an infection?

00:00:50.110 --> 00:00:53.920
- Even the most powerful
antibiotics are failing.

00:00:53.920 --> 00:00:54.760
- It's been tough.

00:00:54.760 --> 00:00:57.038
It's been tough on not
only me, but my family.

00:00:59.030 --> 00:01:01.830
- The search for new
antibiotics is now

00:01:01.830 --> 00:01:06.137
an urgent challenge, drawing
scientists to remote corners

00:01:06.137 --> 00:01:07.111
of the planet.

00:01:08.572 --> 00:01:10.520
(THEME MUSIC)

00:01:22.710 --> 00:01:25.550
The rainforest
canopy of Panama --

00:01:25.550 --> 00:01:29.390
inside this forest lives
a creature so placid,

00:01:29.390 --> 00:01:32.020
you could say the
forest lives on it.

00:01:37.440 --> 00:01:41.140
Below the canopy,
biologist Bryson Voirin

00:01:41.140 --> 00:01:43.615
is leading colleagues
to a giant fig tree.

00:01:45.384 --> 00:01:47.550
- Most of the life here is
in the top of the canopy,

00:01:47.550 --> 00:01:50.550
and it's really remote
and difficult to access.

00:01:50.550 --> 00:01:52.870
- Drug researcher
Roger Linington

00:01:52.870 --> 00:01:55.790
is hoping to meet a
shy forest dweller

00:01:55.790 --> 00:02:00.050
whose fur is camouflaged
green with microbial life.

00:02:00.050 --> 00:02:01.550
- The real motivation
for this study

00:02:01.550 --> 00:02:04.580
is to see whether niche
environments such as this

00:02:04.580 --> 00:02:07.070
can yield new
classes of compounds

00:02:07.070 --> 00:02:08.940
for antibiotic development.

00:02:08.940 --> 00:02:15.900
- Bryson Voirin is a canopy
expert and, conveniently,

00:02:15.900 --> 00:02:16.860
quite the climber.

00:02:35.290 --> 00:02:38.390
- Right here behind me is
a female three-toed sloth,

00:02:38.390 --> 00:02:41.010
and you can really clearly
see her three toes and three

00:02:41.010 --> 00:02:43.140
fingers on her claws.

00:02:43.140 --> 00:02:45.390
Sloths are sort of one of
the mysteries of the jungle.

00:02:45.390 --> 00:02:48.960
They're a very weird organism
that lives only in the canopy,

00:02:48.960 --> 00:02:51.340
and they have all sorts of
different animals living

00:02:51.340 --> 00:02:52.279
on their backs.

00:02:52.279 --> 00:02:54.070
They've got a moth that
lives in their fur.

00:02:54.070 --> 00:02:56.528
They have an algae that's only
found in their fur, as well.

00:02:56.528 --> 00:02:58.470
They're like a whole
little micro ecosystem

00:02:58.470 --> 00:03:00.720
up here in the canopy.

00:03:00.720 --> 00:03:04.730
- Sloths are famously difficult
to unhook from a tree branch.

00:03:13.011 --> 00:03:15.510
- And I'm going to bring her
to the ground for a few minutes

00:03:15.510 --> 00:03:17.190
so that Roger can
take a hair sample.

00:03:28.726 --> 00:03:29.226
All right.

00:03:30.810 --> 00:03:33.297
The idea for this study
actually came as sort of a joke

00:03:33.297 --> 00:03:34.380
with some friends of mine.

00:03:34.380 --> 00:03:36.290
We were talking about how
there's a whole world that

00:03:36.290 --> 00:03:37.081
lives on the sloth.

00:03:37.081 --> 00:03:39.540
There's all these insects
and algaes and things.

00:03:39.540 --> 00:03:42.140
And she was saying, "You know,
you should really look and send

00:03:42.140 --> 00:03:45.150
some samples to this lab that's
looking at wild prospecting,

00:03:45.150 --> 00:03:47.339
to try and see if
there's antibiotics."

00:03:47.339 --> 00:03:48.380
It's a little bit feisty.

00:03:48.380 --> 00:03:49.213
- Little bit feisty.

00:03:49.213 --> 00:03:51.550
- So I'll hold her
just like a baby.

00:03:51.550 --> 00:03:55.080
- Roger Linington's lab at
the University of California

00:03:55.080 --> 00:03:58.660
has already found interesting
compounds in sloth fur

00:03:58.660 --> 00:03:59.970
from an earlier expedition.

00:04:04.080 --> 00:04:06.770
- Every niche environment
is different in its own way.

00:04:06.770 --> 00:04:09.690
We would expect that the
populations of microorganisms

00:04:09.690 --> 00:04:11.359
in each sloth will
be fundamentally

00:04:11.359 --> 00:04:12.400
different to one another.

00:04:12.400 --> 00:04:14.210
Some of the fungi from
the fur of the sloth

00:04:14.210 --> 00:04:15.910
had drug-like
properties which were

00:04:15.910 --> 00:04:18.880
very different to the current
battery of antibiotics

00:04:18.880 --> 00:04:19.935
available in the clinic.

00:04:19.935 --> 00:04:21.060
So it was very encouraging.

00:04:22.620 --> 00:04:25.460
- Linington is part of a
top-notch team of North

00:04:25.460 --> 00:04:29.600
American and Panamanian
scientists searching together

00:04:29.600 --> 00:04:33.880
for potential new drugs
from the natural world.

00:04:33.880 --> 00:04:35.970
Chemists have had
little success in making

00:04:35.970 --> 00:04:39.300
synthetic antibiotics,
so it's back to nature.

00:04:45.730 --> 00:04:47.970
The day after his
sloth adventure,

00:04:47.970 --> 00:04:50.270
Linington heads
out to Coiba Island

00:04:50.270 --> 00:04:53.700
off the Pacific coast of Panama
with the head of the research

00:04:53.700 --> 00:04:55.910
team, Bill Gerwick.

00:04:55.910 --> 00:04:56.895
- Panama is amazing.

00:04:56.895 --> 00:05:02.430
It's sort of this juxtaposition
of incredible biodiversity.

00:05:02.430 --> 00:05:05.890
- Panama is special because
it's at the junction of four

00:05:05.890 --> 00:05:07.930
big pieces of the planet.

00:05:07.930 --> 00:05:12.110
Plants and animals from two
oceans and two continents

00:05:12.110 --> 00:05:13.590
meet here.

00:05:13.590 --> 00:05:15.210
- Areas that have
high biodiversity

00:05:15.210 --> 00:05:17.830
are areas where the organisms
are in great competition

00:05:17.830 --> 00:05:18.800
with one another.

00:05:18.800 --> 00:05:20.590
It's that competition
that underlie

00:05:20.590 --> 00:05:23.140
the production of the
very bioactive molecules

00:05:23.140 --> 00:05:25.310
that we've been discovering
and working with.

00:05:28.830 --> 00:05:32.980
The island of Coiba is really
quite a remarkable place.

00:05:32.980 --> 00:05:35.380
Its forest is
essentially intact.

00:05:35.380 --> 00:05:39.480
The reason for this is that it's
been a penal colony for about

00:05:39.480 --> 00:05:39.980
a century.

00:05:42.950 --> 00:05:46.630
- Now, Coiba Island is a
national park, with forests

00:05:46.630 --> 00:05:50.030
and reefs relatively untouched.

00:05:50.030 --> 00:05:54.040
- This expedition is all aimed
at looking at marine sediments,

00:05:54.040 --> 00:05:55.700
and specifically
the bacteria that

00:05:55.700 --> 00:05:58.057
grow within those
sediments, and then

00:05:58.057 --> 00:06:00.015
using those bacteria as
a source of inspiration

00:06:00.015 --> 00:06:01.672
for new antibiotics.

00:06:01.672 --> 00:06:02.755
- That's the buddy system.

00:06:20.450 --> 00:06:23.630
- The world's oceans
are rich in microbes.

00:06:23.630 --> 00:06:26.320
These tiniest of
lifeforms make up

00:06:26.320 --> 00:06:29.310
90% of living matter
on the planet,

00:06:29.310 --> 00:06:32.610
and they constantly battle
each other for turf.

00:06:32.610 --> 00:06:36.540
It's the weapons they use that
can serve us as antibiotics.

00:06:39.480 --> 00:06:40.960
- Every environment
that you go to

00:06:40.960 --> 00:06:43.280
has slightly different
conditions, in terms of current

00:06:43.280 --> 00:06:46.920
and nutrients and predators
and all these other factors.

00:06:46.920 --> 00:06:48.620
And so every time you
go to a new place,

00:06:48.620 --> 00:06:50.610
you can expect that
the microbial community

00:06:50.610 --> 00:06:52.160
will be different.

00:06:52.160 --> 00:06:54.930
- The team is searching
for new antibiotics

00:06:54.930 --> 00:06:58.220
because our misuse of
these miracle drugs

00:06:58.220 --> 00:07:01.300
has rendered many
almost useless.

00:07:01.300 --> 00:07:04.510
- Antibiotic resistance is
when a microorganism no longer

00:07:04.510 --> 00:07:07.760
responds to something it
previously was killed by,

00:07:07.760 --> 00:07:08.890
namely an antibiotic.

00:07:08.890 --> 00:07:12.090
When we have an infection, it's
actually billions of cells.

00:07:12.090 --> 00:07:14.590
And if even one of those
cells has a slight mutation,

00:07:14.590 --> 00:07:16.190
a slight variation
that then allows

00:07:16.190 --> 00:07:19.120
it to survive in the
presence of that antibiotic,

00:07:19.120 --> 00:07:23.760
a whole new group of cells will
develop that similarly will

00:07:23.760 --> 00:07:25.250
be resistant to the antibiotic.

00:07:25.250 --> 00:07:27.080
And this is of grave concern.

00:07:28.720 --> 00:07:31.590
- There are hundreds of
millions of prescriptions

00:07:31.590 --> 00:07:34.370
for antibiotics
written each year

00:07:34.370 --> 00:07:38.730
and there are millions of
bacteria in each infection.

00:07:38.730 --> 00:07:41.350
So there are countless
chances for the bugs

00:07:41.350 --> 00:07:45.101
to mutate and build resistance.

00:07:45.101 --> 00:07:49.105
All of this is taking us to the
brink of a global catastrophe.

00:07:53.260 --> 00:07:57.460
In 2014, the World Health
Organization warned,

00:07:57.460 --> 00:08:01.150
"A post-antibiotic era in
which common infections

00:08:01.150 --> 00:08:05.760
and minor injuries can kill
is a very real possibility

00:08:05.760 --> 00:08:07.714
for the 21st century."

00:08:09.490 --> 00:08:11.940
Alexander Fleming
discovered penicillin,

00:08:11.940 --> 00:08:15.010
the original antibiotic,
after seeing just

00:08:15.010 --> 00:08:19.190
how deadly infections could
be during World War I.

00:08:19.190 --> 00:08:21.270
- And we saw thousands
of septic wounds

00:08:21.270 --> 00:08:24.080
that we could do
very little for.

00:08:24.080 --> 00:08:26.730
- Fleming warned that
misuse of antibiotics

00:08:26.730 --> 00:08:29.980
could lead to
resistance very quickly.

00:08:29.980 --> 00:08:32.960
Sure enough, resistance
has been accelerating

00:08:32.960 --> 00:08:36.460
at an alarming rate ever since.

00:08:36.460 --> 00:08:39.929
Streptomycin was
created in 1943.

00:08:39.929 --> 00:08:43.360
Resistance showed up in 1958.

00:08:43.360 --> 00:08:46.790
Tetracycline was
created in 1947.

00:08:46.790 --> 00:08:50.080
Resistance: 1953.

00:08:50.080 --> 00:08:54.660
Methicillin appeared in 1960
-- resistance only two years

00:08:54.660 --> 00:08:56.070
later.

00:08:56.070 --> 00:08:58.880
The modus operandi
of bacteria is,

00:08:58.880 --> 00:09:01.880
"What doesn't kill us
makes us stronger."

00:09:01.880 --> 00:09:05.140
And we're making things
worse by taking antibiotics

00:09:05.140 --> 00:09:07.510
even when they do no good.

00:09:07.510 --> 00:09:10.980
We can't seem to get it straight
that antibiotics only kill

00:09:10.980 --> 00:09:13.655
bacteria, not viruses.

00:09:13.655 --> 00:09:15.620
- For what kind of
illnesses would you

00:09:15.620 --> 00:09:19.244
think your doctor would
prescribe antibiotics?

00:09:19.244 --> 00:09:20.840
- Uh...

00:09:20.840 --> 00:09:22.010
the flu, I'm guessing.

00:09:22.010 --> 00:09:23.680
(SOUND OF BUZZER)

00:09:23.680 --> 00:09:24.880
- Infections in the body?

00:09:24.880 --> 00:09:27.020
- Which kind of infections,
bacterial or viral?

00:09:27.020 --> 00:09:28.819
- Oh, I guess...

00:09:28.819 --> 00:09:29.860
I forget which one it is.

00:09:29.860 --> 00:09:30.590
It's one or the other.

00:09:30.590 --> 00:09:31.260
I guess viral?

00:09:31.260 --> 00:09:32.980
(SOUND OF BUZZER)

00:09:32.980 --> 00:09:34.190
- Bacterial or viral?

00:09:34.190 --> 00:09:35.660
(SOUND OF BUZZER)

00:09:35.660 --> 00:09:36.920
- Not viruses...

00:09:36.920 --> 00:09:39.017
bacterial infections,
I would think.

00:09:39.017 --> 00:09:40.360
(SOUND OF DINGING BELL)

00:09:40.360 --> 00:09:42.220
- A lot of the infections
from here on up --

00:09:42.220 --> 00:09:45.790
from your bronchi on up
-- are driven by viruses.

00:09:45.790 --> 00:09:49.530
All colds, most
coughs, influenza,

00:09:49.530 --> 00:09:52.270
most middle ear
infection, most sinusitis

00:09:52.270 --> 00:09:54.370
gets by fine
without antibiotics.

00:09:54.370 --> 00:09:57.820
- Dr. David Patrick heads
a public education campaign

00:09:57.820 --> 00:10:00.710
called "Do Bugs Need Drugs?"

00:10:00.710 --> 00:10:05.177
Its goal: to reduce the
misuse of antibiotics.

00:10:05.177 --> 00:10:07.510
- There are a lot of pressures
on a doctor to prescribe,

00:10:07.510 --> 00:10:08.190
sometimes.

00:10:08.190 --> 00:10:09.970
There's time pressure
in the office.

00:10:09.970 --> 00:10:11.670
It's possible that
a parent will come

00:10:11.670 --> 00:10:14.290
in with full expectation
and a lot of heavy pressure

00:10:14.290 --> 00:10:16.520
to prescribe an antibiotic.

00:10:16.520 --> 00:10:19.100
- Even when doctors
request lab tests,

00:10:19.100 --> 00:10:22.230
in the meantime they often
prescribe a wide-spectrum

00:10:22.230 --> 00:10:27.070
antibiotic that can kill
many kinds of bacteria --

00:10:27.070 --> 00:10:29.584
including the good kind.

00:10:29.584 --> 00:10:30.500
- Whoo!

00:10:30.500 --> 00:10:34.685
- Just went for a root
canal, and after I

00:10:34.685 --> 00:10:37.190
got the procedure done
my tooth was infected.

00:10:37.190 --> 00:10:40.530
And so the dentist
prescribed me clindamycin --

00:10:40.530 --> 00:10:43.800
took clindamycin for a week.

00:10:43.800 --> 00:10:46.450
And then it was a week after
I'd been off of clindamycin

00:10:46.450 --> 00:10:48.616
that I got diarrhea.

00:10:48.616 --> 00:10:49.960
- Go down the slide?

00:10:49.960 --> 00:10:52.890
- Krista Kilback found
out she had a C. difficile

00:10:52.890 --> 00:10:56.160
infection, which can
cause severe diarrhea.

00:10:56.160 --> 00:10:56.800
- Whoo!

00:10:56.800 --> 00:10:58.030
Good job!

00:10:58.030 --> 00:10:59.920
- Clostridium difficile
is an infection

00:10:59.920 --> 00:11:03.410
that happens oftentimes
when you take antibiotics.

00:11:03.410 --> 00:11:07.590
And those antibiotics don't
just necessarily attack the bugs

00:11:07.590 --> 00:11:09.590
that they're supposed
to attack, but they also

00:11:09.590 --> 00:11:12.450
have an impact on all the
bacteria that are in your gut.

00:11:14.170 --> 00:11:17.500
- Many kinds of bacteria
inside Krista's colon

00:11:17.500 --> 00:11:20.900
were killed off, but
not the C. difficile,

00:11:20.900 --> 00:11:24.830
because it's developed a
resistance to most antibiotics,

00:11:24.830 --> 00:11:27.316
including clindamycin.

00:11:27.316 --> 00:11:28.168
- How are you?

00:11:28.168 --> 00:11:28.932
- Good, thanks.

00:11:28.932 --> 00:11:30.140
- It's good to see you again.

00:11:30.140 --> 00:11:33.750
- In fact, friendly
bacteria inside Krista

00:11:33.750 --> 00:11:37.310
were probably keeping the
C. difficile in check.

00:11:37.310 --> 00:11:40.340
When the friendly bugs were
killed off by antibiotics,

00:11:40.340 --> 00:11:44.010
the C. difficile took over.

00:11:44.010 --> 00:11:46.290
This is where the
antibiotic story

00:11:46.290 --> 00:11:48.860
becomes a little more complex.

00:11:48.860 --> 00:11:52.110
New antibiotics are
desperately needed,

00:11:52.110 --> 00:11:54.480
but many researchers
are concluding

00:11:54.480 --> 00:11:58.010
that using antibiotics
to fight every infection

00:11:58.010 --> 00:12:00.360
is counterproductive.

00:12:00.360 --> 00:12:02.670
Bill Gerwick has thought
a lot about this,

00:12:02.670 --> 00:12:05.895
even while he's searching
for new antibiotic compounds.

00:12:05.895 --> 00:12:07.910
- We're coming to
realize that we

00:12:07.910 --> 00:12:12.087
have some trillion
cells in our body,

00:12:12.087 --> 00:12:13.670
and we have about
10 times that number

00:12:13.670 --> 00:12:16.050
of bacterial cells sitting here.

00:12:16.050 --> 00:12:18.420
About 15 pounds
of any human being

00:12:18.420 --> 00:12:20.460
is actually bacterial cells.

00:12:20.460 --> 00:12:22.110
So we're not just individuals.

00:12:22.110 --> 00:12:24.250
We're sort of communities
walking around.

00:12:24.250 --> 00:12:27.060
And when we disturb that
community with an antibiotic,

00:12:27.060 --> 00:12:30.390
maybe we treat an infection
but we disturb that community

00:12:30.390 --> 00:12:31.390
enormously.

00:12:31.390 --> 00:12:34.750
And it gives rise to
other kinds of diseases.

00:12:34.750 --> 00:12:37.370
- Like Krista's
crippling infection.

00:12:37.370 --> 00:12:41.030
Not even vancomycin, the
Cadillac of antibiotics,

00:12:41.030 --> 00:12:43.240
can cure her.

00:12:43.240 --> 00:12:45.650
- She got better on vancomycin
with a couple of courses.

00:12:45.650 --> 00:12:47.110
But unfortunately,
the pattern was

00:12:47.110 --> 00:12:49.177
every time she would
get vancomycin,

00:12:49.177 --> 00:12:50.510
she'd get it for a couple weeks.

00:12:50.510 --> 00:12:52.600
She'd get better, she'd
get back to normal,

00:12:52.600 --> 00:12:54.520
and then her symptoms
would come back again.

00:12:54.520 --> 00:12:58.630
- I've actually tried also
another antibiotic called

00:12:58.630 --> 00:13:01.740
Dificid, and that
was the same story.

00:13:01.740 --> 00:13:05.300
It just always comes back
after two to three weeks.

00:13:05.300 --> 00:13:07.770
- Without an
effective antibiotic,

00:13:07.770 --> 00:13:10.980
Krista's looking at
some tough options.

00:13:10.980 --> 00:13:11.480
- Whoo!

00:13:11.480 --> 00:13:11.980
Good job!

00:13:11.980 --> 00:13:13.812
- OK, worst case, you
pretty much take out

00:13:13.812 --> 00:13:15.770
your large intestine and
all you'd be left with

00:13:15.770 --> 00:13:17.600
is your small intestine.

00:13:17.600 --> 00:13:20.240
Or you essentially
just put a bag on

00:13:20.240 --> 00:13:22.876
and you have to live with the
bag for the rest of your life.

00:13:22.876 --> 00:13:25.690
- How rough is all
this being on you?

00:13:25.690 --> 00:13:27.010
- It's been tough.

00:13:27.010 --> 00:13:30.433
It's been tough on not
only me, but my family.

00:13:30.433 --> 00:13:30.933
Yeah.

00:13:35.650 --> 00:13:38.790
- People like Krista Kilback
are in desperate need

00:13:38.790 --> 00:13:42.685
of new, effective antibiotics.

00:13:42.685 --> 00:13:44.625
And so the hunt continues.

00:13:47.540 --> 00:13:51.010
After his dives, Roger
Linington dabs the sediments

00:13:51.010 --> 00:13:53.670
he's harvested
onto Petri dishes.

00:13:53.670 --> 00:13:57.340
He hopes any bacteria captured
in the samples will multiply.

00:14:02.950 --> 00:14:06.270
Meanwhile, two other
members of the team --

00:14:06.270 --> 00:14:10.810
fungus expert Betsy Arnold and
plant expert Alicia Ibanez --

00:14:10.810 --> 00:14:13.884
come ashore onto
Panama's Coiba Island.

00:14:13.884 --> 00:14:16.490
- So would there be any
kind of fungi here also?

00:14:16.490 --> 00:14:19.508
- There'll be some, yeah,
typically some freshwater fungi

00:14:19.508 --> 00:14:20.008
that...

00:14:20.008 --> 00:14:21.720
- Look at that...

00:14:21.720 --> 00:14:23.430
- A little isopod.

00:14:23.430 --> 00:14:24.400
- Isopod, yeah.

00:14:24.400 --> 00:14:26.450
- Arnold searches
the world for fungi

00:14:26.450 --> 00:14:28.930
that might make new drugs.

00:14:28.930 --> 00:14:32.290
- Penicillin really is the
poster child for antibiotics

00:14:32.290 --> 00:14:33.090
produced by fungi.

00:14:33.090 --> 00:14:34.770
You know, the number
of people saved

00:14:34.770 --> 00:14:37.774
by the existence of
penicillin as an antibiotic

00:14:37.774 --> 00:14:38.440
is astronomical.

00:14:38.440 --> 00:14:39.340
- Let's look at them.

00:14:39.340 --> 00:14:39.839
OK.

00:14:39.839 --> 00:14:40.940
- Yeah, let's look.

00:14:40.940 --> 00:14:43.430
- Arnold wonders if
another penicillin

00:14:43.430 --> 00:14:46.750
could be found in the rare plant
communities of Coiba Island.

00:14:48.850 --> 00:14:52.490
Ibanez knows Coiba's
plants better than anyone,

00:14:52.490 --> 00:14:55.990
and wants to show Arnold
one that's unique.

00:14:55.990 --> 00:14:57.644
- It's just on the
west coast of Coiba.

00:14:57.644 --> 00:14:59.060
We haven't found
it anywhere else.

00:14:59.060 --> 00:14:59.820
- Wow.

00:14:59.820 --> 00:15:02.270
Yeah, so it's pretty
habitat-specific.

00:15:02.270 --> 00:15:05.630
- Ibanez has already
supplied Arnold with fungi

00:15:05.630 --> 00:15:08.950
from this plant for
analysis in her lab.

00:15:08.950 --> 00:15:11.050
But this is the
first time Arnold

00:15:11.050 --> 00:15:14.210
has seen the plant in
its natural habitat.

00:15:14.210 --> 00:15:16.000
- It's one of the most
interesting plants

00:15:16.000 --> 00:15:17.700
that we've investigated,
with regard

00:15:17.700 --> 00:15:20.100
to the chemical
compounds produced

00:15:20.100 --> 00:15:22.970
by the fungi inside
that plant species.

00:15:22.970 --> 00:15:24.670
The genus is desmotas.

00:15:24.670 --> 00:15:26.730
It's a member of
the citrus family

00:15:26.730 --> 00:15:30.320
and it grows on these really
steep slopes above streams.

00:15:30.320 --> 00:15:32.070
We had to be careful
not to fall in --

00:15:32.070 --> 00:15:34.100
some crocodile
possibilities down there.

00:15:35.640 --> 00:15:37.270
Any of the leaves
that we're looking at

00:15:37.270 --> 00:15:40.780
will have 20 or 30 different
fungal species living inside.

00:15:40.780 --> 00:15:44.680
And they need to eat the
products of the plant.

00:15:44.680 --> 00:15:47.834
And so when you've got two fungi
going after the same material,

00:15:47.834 --> 00:15:49.500
then they will fight
against each other.

00:15:49.500 --> 00:15:50.958
And in fighting
against each other,

00:15:50.958 --> 00:15:53.640
they'll produce compounds that
will limit the growth of one

00:15:53.640 --> 00:15:54.530
or the other species.

00:15:54.530 --> 00:15:57.890
And it's those compounds that
then have antibiotic potential.

00:15:57.890 --> 00:16:01.210
So you can sort of see
where the lichens begin.

00:16:01.210 --> 00:16:02.460
This is a pressing need.

00:16:02.460 --> 00:16:06.020
We need to go out to places that
we've never looked into before

00:16:06.020 --> 00:16:09.130
and capture those organisms,
look at their antibiotics

00:16:09.130 --> 00:16:11.250
and retain the organisms
in collections,

00:16:11.250 --> 00:16:14.430
so that when our technologies
improve decades down the line

00:16:14.430 --> 00:16:16.090
we might be able
to tap antibiotics

00:16:16.090 --> 00:16:18.450
that now we can't even
imagine discovering

00:16:18.450 --> 00:16:19.450
from that same material.

00:16:22.990 --> 00:16:26.990
- From a remote beach in Panama
to a cave beneath a British

00:16:26.990 --> 00:16:30.220
Columbia valley,
the hunt is on --

00:16:30.220 --> 00:16:34.340
taking some scientists
beyond their comfort zone.

00:16:34.340 --> 00:16:36.400
- Actually, I have fear.

00:16:36.400 --> 00:16:38.360
I'm a microbiologist.

00:16:38.360 --> 00:16:39.410
I'm not a caver.

00:16:45.580 --> 00:16:47.750
- That was probably
what, two years ago?

00:16:47.750 --> 00:16:49.684
- Yeah, it's got to be.

00:16:49.684 --> 00:16:50.725
That's a good one of him.

00:16:50.725 --> 00:16:52.175
- Yeah, nice smile.

00:16:52.175 --> 00:16:55.060
- Jen Quarrell lost her dad.

00:16:55.060 --> 00:16:57.560
Darlene Quarrrell
lost a brother --

00:16:57.560 --> 00:17:02.320
to an infection that
antibiotics could not cure.

00:17:02.320 --> 00:17:06.359
John Quarrell initially went
to Regina General Hospital

00:17:06.359 --> 00:17:09.640
because of complications
from his diabetes.

00:17:09.640 --> 00:17:12.279
- Mr. Quarrell came in
with a severe problem

00:17:12.279 --> 00:17:13.839
with his right leg.

00:17:13.839 --> 00:17:16.300
And the leg couldn't be
saved, so he ended up

00:17:16.300 --> 00:17:18.412
with an amputation.

00:17:18.412 --> 00:17:21.260
- But soon, Quarrell
was back in the hospital

00:17:21.260 --> 00:17:24.490
with more circulation problems.

00:17:24.490 --> 00:17:26.650
- He would be good
for a little while

00:17:26.650 --> 00:17:28.710
and then he'd go downhill.

00:17:28.710 --> 00:17:29.770
It was up and down.

00:17:29.770 --> 00:17:31.850
- Towards the end of
that hospitalization,

00:17:31.850 --> 00:17:35.830
he suddenly and quite
unexpectedly became unwell

00:17:35.830 --> 00:17:36.645
with a fever.

00:17:40.100 --> 00:17:43.470
- Quarrell had contracted the
drug-resistant superbug, MRSA.

00:17:46.140 --> 00:17:49.560
He was prescribed various
antibiotics and finally

00:17:49.560 --> 00:17:53.480
vancomycin -- but even it
couldn't stop the infection.

00:17:55.560 --> 00:17:58.650
- One of the heart
valves had evidence

00:17:58.650 --> 00:18:01.495
of a bacterial infection
on the heart valve.

00:18:01.495 --> 00:18:03.370
- So many times, my
auntie Darlene and I went

00:18:03.370 --> 00:18:05.980
to the hospital and he was
just laying in his bed -- like,

00:18:05.980 --> 00:18:07.940
dangling off the bed.

00:18:07.940 --> 00:18:10.860
He couldn't even push his button
to get a nurse to come in.

00:18:13.640 --> 00:18:16.900
- It's the people who are
already weak and frail who

00:18:16.900 --> 00:18:20.160
tend to pick it up
in the first place.

00:18:20.160 --> 00:18:22.910
- Dr. Kopriva phoned
me and said he

00:18:22.910 --> 00:18:26.480
has no hope that my dad
would survive the infection.

00:18:26.480 --> 00:18:28.810
But I never believed
that, you know,

00:18:28.810 --> 00:18:31.724
you could die from an
infection like that.

00:18:33.700 --> 00:18:37.285
- Six weeks after the phone
call, Jen's father died.

00:18:40.790 --> 00:18:43.090
With his compromised
immune system,

00:18:43.090 --> 00:18:46.455
John Quarrell was typical
of most of MRSA's victims.

00:18:48.800 --> 00:18:54.420
As many as 12,000 people die of
antibiotic-resistant infections

00:18:54.420 --> 00:18:56.820
every year in Canada.

00:18:56.820 --> 00:19:00.450
Like hospitals everywhere,
Regina General constantly

00:19:00.450 --> 00:19:02.730
battles these superbugs.

00:19:02.730 --> 00:19:05.590
- We've had outbreaks of
antibiotic-resistant organisms

00:19:05.590 --> 00:19:09.470
in the hospital, and
those require huge amounts

00:19:09.470 --> 00:19:10.025
of resources.

00:19:11.630 --> 00:19:14.560
- A large section of the
hospital's ground floor

00:19:14.560 --> 00:19:16.610
is dedicated to
infection control.

00:19:19.100 --> 00:19:21.700
- The surveillance component
is becoming ever more

00:19:21.700 --> 00:19:24.550
important: the
thousands of screens

00:19:24.550 --> 00:19:27.550
that patients in the
hospital have to go through,

00:19:27.550 --> 00:19:32.380
throwing out lots of supplies,
the intensive cleaning

00:19:32.380 --> 00:19:35.720
efforts from our
housekeeping department.

00:19:35.720 --> 00:19:38.580
- But inevitably,
resistant bacteria

00:19:38.580 --> 00:19:41.160
will occasionally get through.

00:19:41.160 --> 00:19:44.040
Hospitals desperately
need whole new families

00:19:44.040 --> 00:19:47.680
of antibiotics, drugs
the superbugs have never

00:19:47.680 --> 00:19:48.575
encountered before.

00:19:51.940 --> 00:19:54.390
Perhaps they will come
from beneath the Earth.

00:19:56.545 --> 00:19:59.080
- It's almost like the
first time in every cave

00:19:59.080 --> 00:20:00.200
that I go in.

00:20:00.200 --> 00:20:01.310
Each cave is so unique.

00:20:03.810 --> 00:20:06.360
- Microbiologist
Naowarat Cheeptham

00:20:06.360 --> 00:20:09.960
is one of a very small
handful of people worldwide

00:20:09.960 --> 00:20:12.830
who hunt for potential
drugs from the bacteria

00:20:12.830 --> 00:20:16.770
and fungi of caves.

00:20:16.770 --> 00:20:20.450
- What we have seen
so far in our lab

00:20:20.450 --> 00:20:24.386
is the fact that there
is a great promise.

00:20:24.386 --> 00:20:26.180
- OK, guys, this is it.

00:20:26.180 --> 00:20:28.080
- Cheeptham and
her team have come

00:20:28.080 --> 00:20:30.730
to the Chilliwack Valley
in British Columbia

00:20:30.730 --> 00:20:33.400
to investigate a new site.

00:20:33.400 --> 00:20:38.800
Caver Rob Wall discovered the
Iron Curtain Cave in 1993,

00:20:38.800 --> 00:20:41.150
and he's invited
Cheeptham to explore it.

00:20:41.150 --> 00:20:43.070
- There's a handle
here to grab onto.

00:20:43.070 --> 00:20:45.320
You have to lower yourself
onto the ladder down below.

00:20:56.410 --> 00:21:00.200
- It's dangerous work crawling
around this slippery cave,

00:21:00.200 --> 00:21:02.960
with only the erratic
light of the headlamps.

00:21:02.960 --> 00:21:05.660
And Cheeptham is
still an amateur.

00:21:05.660 --> 00:21:07.900
- Actually, I have fear.

00:21:07.900 --> 00:21:09.251
I'm a microbiologist.

00:21:09.251 --> 00:21:11.685
I'm not a caver by training.

00:21:15.770 --> 00:21:18.970
Studying this type
of extreme habitat

00:21:18.970 --> 00:21:23.180
gives us tremendous
information about life

00:21:23.180 --> 00:21:25.890
that has been exposed
to extreme conditions.

00:21:29.920 --> 00:21:33.000
These bacteria have been in
here for millions of years.

00:21:33.000 --> 00:21:36.270
They have evolved and
adapted to these kind

00:21:36.270 --> 00:21:38.400
of low-nutrient conditions.

00:21:42.150 --> 00:21:47.200
- Cheeptham normally
explores dry lava tube caves.

00:21:47.200 --> 00:21:50.390
- This one is totally
different in many ways.

00:21:50.390 --> 00:21:52.100
First of all, it's wet.

00:21:52.100 --> 00:21:53.565
I've never been this wet caving.

00:21:55.710 --> 00:21:59.490
- Cheeptham's team takes samples
from the cave's textured walls.

00:22:02.640 --> 00:22:05.950
Cavers have whimsically
used soda shop lingo

00:22:05.950 --> 00:22:08.680
to name the cave's decorations.

00:22:08.680 --> 00:22:13.830
There's popcorn, soda
straws, and moon milk --

00:22:13.830 --> 00:22:16.490
all of which can harbor life.

00:22:16.490 --> 00:22:18.960
- This is interesting,
because there are not

00:22:18.960 --> 00:22:21.460
many organic
matters around here.

00:22:21.460 --> 00:22:23.240
So when you think
as a microbiologist,

00:22:23.240 --> 00:22:25.630
you look at this and
you see, oh my goodness,

00:22:25.630 --> 00:22:27.070
who can live in here?

00:22:27.070 --> 00:22:30.350
But really, when you
look closer and look

00:22:30.350 --> 00:22:35.206
in a more microscopic level,
it's just full of life.

00:22:35.206 --> 00:22:35.955
Full of potential.

00:22:38.790 --> 00:22:43.040
- Some bacterial samples will
be left behind for a few months

00:22:43.040 --> 00:22:46.490
to see if they grow differently
than the samples coming back

00:22:46.490 --> 00:22:47.070
to the lab.

00:22:51.970 --> 00:22:55.710
- We don't fully understand
the relationships

00:22:55.710 --> 00:22:59.600
of microorganisms and minerals
in different types of caves.

00:23:03.920 --> 00:23:06.880
- In her lab at Thompson
River University,

00:23:06.880 --> 00:23:09.510
Cheeptham uses an
electron microscope

00:23:09.510 --> 00:23:12.640
to search amidst the
limestone for anything

00:23:12.640 --> 00:23:14.540
that looks organic.

00:23:14.540 --> 00:23:15.690
- So let me see.

00:23:15.690 --> 00:23:17.690
That is 20 microns.

00:23:17.690 --> 00:23:23.280
We would like to see whether we
can detect bacterial activity

00:23:23.280 --> 00:23:24.410
in real time.

00:23:24.410 --> 00:23:26.180
What are they doing in there?

00:23:26.180 --> 00:23:28.420
Are they actually
using those minerals

00:23:28.420 --> 00:23:30.280
as the source of their energy?

00:23:30.280 --> 00:23:32.065
Oh!

00:23:32.065 --> 00:23:33.010
- They're pretty, eh?

00:23:33.010 --> 00:23:33.510
- Yes.

00:23:33.510 --> 00:23:35.383
And look at all those.

00:23:35.383 --> 00:23:36.270
What was that?

00:23:36.270 --> 00:23:38.603
Like all that, look at that,
look at that, look at that!

00:23:38.603 --> 00:23:40.137
- I don't know yet!

00:23:40.137 --> 00:23:41.470
Boy, that would be lucky to see.

00:23:41.470 --> 00:23:43.386
- Ann just gets so excited
when she's on this.

00:23:43.386 --> 00:23:44.960
It's fun.

00:23:44.960 --> 00:23:48.400
- Learning how these
bacteria survive in the cave

00:23:48.400 --> 00:23:51.915
could tell her what
antibacterial weapons they use.

00:23:55.940 --> 00:23:58.940
Students work long
hours separating out

00:23:58.940 --> 00:24:02.760
the components of samples
brought back from the cave.

00:24:02.760 --> 00:24:04.460
- Bacteria are like us.

00:24:04.460 --> 00:24:07.350
They're actually so unique.

00:24:07.350 --> 00:24:09.610
Each of them like to
eat different things,

00:24:09.610 --> 00:24:13.020
like to grow on
different things.

00:24:13.020 --> 00:24:15.010
They like to live
in a community.

00:24:15.010 --> 00:24:19.800
We can't study a community, so
we try to isolate each of them

00:24:19.800 --> 00:24:20.840
out.

00:24:20.840 --> 00:24:23.610
As you can see, from
that many plates

00:24:23.610 --> 00:24:26.416
it could turn out to be
1,000 different isolates.

00:24:29.150 --> 00:24:32.580
- Once they've isolated a
promising cave bacterium,

00:24:32.580 --> 00:24:35.240
they'll place that on
a plate with bacteria

00:24:35.240 --> 00:24:37.320
dangerous to humans.

00:24:37.320 --> 00:24:39.260
Then, they'll watch
for the formation

00:24:39.260 --> 00:24:44.090
of an "inhibition zone" or
"dead zone" around the sample.

00:24:44.090 --> 00:24:46.880
This indicates that
that bacterium can

00:24:46.880 --> 00:24:50.110
kill the pathogen.
But this is just

00:24:50.110 --> 00:24:52.550
an early step in the
development of an antibiotic.

00:24:54.790 --> 00:24:58.020
Cheeptham often sends her
samples for further study

00:24:58.020 --> 00:25:01.400
to Julian Davies'
microbiology lab.

00:25:01.400 --> 00:25:06.280
- There's no doubt that
she has a gold mine

00:25:06.280 --> 00:25:09.650
of interesting
bacteria and bacteria

00:25:09.650 --> 00:25:11.590
that have never been
looked at before.

00:25:11.590 --> 00:25:15.191
Some are quite active
as antibiotics.

00:25:15.191 --> 00:25:18.640
- But once interesting
bacteria are found,

00:25:18.640 --> 00:25:21.710
you still have to be able
to grow and mass-produce

00:25:21.710 --> 00:25:23.310
the active molecule.

00:25:23.310 --> 00:25:25.250
That's not always easy.

00:25:25.250 --> 00:25:29.120
And after the right molecule
is built into a potential drug

00:25:29.120 --> 00:25:33.400
by a pharmaceutical firm, it
has to be tested on animals,

00:25:33.400 --> 00:25:36.490
and finally on people.

00:25:36.490 --> 00:25:40.270
Davies despairs of any of
these promising compounds

00:25:40.270 --> 00:25:42.480
ever becoming drugs.

00:25:42.480 --> 00:25:45.450
- The major reason why
pharmaceutical companies

00:25:45.450 --> 00:25:49.970
are not involving themselves
in antibiotic discovery

00:25:49.970 --> 00:25:52.280
is that they don't make
any money out of it.

00:25:52.280 --> 00:25:55.100
- For drug companies,
the big profits

00:25:55.100 --> 00:25:57.760
are made by treating
chronic conditions.

00:25:57.760 --> 00:26:00.760
- The pharmaceutical companies,
they make their money out

00:26:00.760 --> 00:26:03.380
of diseases of old people
more than anything else.

00:26:03.380 --> 00:26:04.690
I mean, I'm not...

00:26:04.690 --> 00:26:07.090
I'm not criticizing
them for this.

00:26:07.090 --> 00:26:07.590
They have...

00:26:07.590 --> 00:26:09.650
they're commercial
organizations.

00:26:09.650 --> 00:26:13.660
- And the irony of antibiotics
is the less they're used,

00:26:13.660 --> 00:26:15.600
the more useful they are.

00:26:15.600 --> 00:26:18.710
And that gets in the
way of corporate profit.

00:26:18.710 --> 00:26:22.460
Julian Davies believes
governments should step up.

00:26:22.460 --> 00:26:25.180
- And I think there
has to be more money

00:26:25.180 --> 00:26:26.700
funding small companies.

00:26:26.700 --> 00:26:31.010
Small companies can
make money on drugs that

00:26:31.010 --> 00:26:33.690
have a relatively small market.

00:26:33.690 --> 00:26:38.290
- Cubist Pharmaceuticals is one
of those small drug companies.

00:26:38.290 --> 00:26:40.200
They've been
developing antibiotics

00:26:40.200 --> 00:26:44.520
for almost 25 years in
Lexington, Massachusetts.

00:26:44.520 --> 00:26:45.700
- Hey Steve, how are you?

00:26:45.700 --> 00:26:46.200
- Good.

00:26:46.200 --> 00:26:49.610
- Steve Gilman is head of
research and development.

00:26:49.610 --> 00:26:52.490
- We have a staff that's very
experienced in developing

00:26:52.490 --> 00:26:54.680
antibacterials, and
being able to pick

00:26:54.680 --> 00:26:57.440
the winners from all the
possible opportunities

00:26:57.440 --> 00:26:58.300
out there.

00:26:58.300 --> 00:27:02.530
- So why is Cubist able to stay
in business making antibiotics

00:27:02.530 --> 00:27:06.580
when larger companies
aren't up for the challenge?

00:27:06.580 --> 00:27:10.250
- We spend nearly
25% of our revenue

00:27:10.250 --> 00:27:11.630
on research and development.

00:27:11.630 --> 00:27:13.950
And at the same time,
compared to other companies,

00:27:13.950 --> 00:27:16.210
we spend much less on
sales and marketing

00:27:16.210 --> 00:27:18.400
and administrative expenses.

00:27:18.400 --> 00:27:21.870
- To make any profit at
all, their drugs can be very

00:27:21.870 --> 00:27:26.640
expensive, like fidaxomicin
-- brand name Dificid.

00:27:26.640 --> 00:27:30.470
Designed specifically
to treat C. difficile,

00:27:30.470 --> 00:27:35.670
it was developed from a soil
bacterium discovered in 1967

00:27:35.670 --> 00:27:39.000
and it took 30 years
to bring it to market.

00:27:39.000 --> 00:27:41.350
The cost for one full treatment?

00:27:41.350 --> 00:27:42.162
About $3,000.

00:27:46.050 --> 00:27:48.360
It's a slow, costly process.

00:27:48.360 --> 00:27:51.870
So now, governments are
stepping in with incentives.

00:27:53.710 --> 00:27:57.070
The US has announced
a five-year plan

00:27:57.070 --> 00:28:00.050
to combat antibiotic resistance.

00:28:00.050 --> 00:28:03.940
Canada and the European Union
have invested $30 million

00:28:03.940 --> 00:28:06.590
into the problem.

00:28:06.590 --> 00:28:08.780
And in Britain, the
public was asked

00:28:08.780 --> 00:28:13.240
to vote for a worthy cause
to receive a research prize.

00:28:13.240 --> 00:28:16.410
- The 10-million-pound
science prize is Antibiotics.

00:28:16.410 --> 00:28:18.050
(GAME SHOW MUSIC)

00:28:18.050 --> 00:28:21.530
- 10 million pounds to the
researcher who can develop

00:28:21.530 --> 00:28:25.530
a cheap, quick test to see
if a patient has a bacterial

00:28:25.530 --> 00:28:30.260
or viral infection -- but
are these incentives enough

00:28:30.260 --> 00:28:33.450
to rebuild our antibiotic
storehouse in time?

00:28:38.260 --> 00:28:41.660
Microbiologist Cheeptham
is returning to the cave

00:28:41.660 --> 00:28:43.923
to collect her
remaining Petri dishes.

00:28:46.090 --> 00:28:49.070
- This field of drug discovery
actually takes a lot of time --

00:28:49.070 --> 00:28:52.460
and also, it costs a lot.

00:28:52.460 --> 00:28:55.890
- She knows she's one small
player in a drug system

00:28:55.890 --> 00:28:58.910
that seems to her to
be unable to deliver.

00:29:01.310 --> 00:29:05.660
- As a scientist, I
feel very frustrated.

00:29:05.660 --> 00:29:08.740
It's just beyond
my understanding.

00:29:08.740 --> 00:29:10.560
At the end of the day,
it has to be profit.

00:29:10.560 --> 00:29:13.670
Everything has to be
able to make the money.

00:29:13.670 --> 00:29:18.470
But that is my opinion
in terms of a scientist.

00:29:18.470 --> 00:29:22.140
However, as a mom of
a 6 and 1/2 year old,

00:29:22.140 --> 00:29:25.680
I truly feel devastated
if I have, you know....

00:29:25.680 --> 00:29:27.890
if you have all this
information and know

00:29:27.890 --> 00:29:36.650
that no one wants to pay
for drug discovery research.

00:29:36.650 --> 00:29:38.470
So what are we as
a human species?

00:29:41.320 --> 00:29:45.500
- While Cheeptham keeps
searching for new antibiotics,

00:29:45.500 --> 00:29:49.590
up on the surface we continue
to misuse the ones we have.

00:29:51.430 --> 00:29:53.880
A big part of that
misuse happens

00:29:53.880 --> 00:29:56.400
in industrial agriculture.

00:29:56.400 --> 00:29:59.750
Incredibly, up to
80% of antibiotics

00:29:59.750 --> 00:30:03.710
are used not on people,
but on farm animals,

00:30:03.710 --> 00:30:07.160
with the intent of fattening
them faster and keeping them

00:30:07.160 --> 00:30:09.570
healthy in crowded conditions.

00:30:09.570 --> 00:30:12.410
This widespread
use of antibiotics

00:30:12.410 --> 00:30:15.652
is contributing to
antibiotic resistance.

00:30:15.652 --> 00:30:17.830
- It's becoming a
serious problem.

00:30:17.830 --> 00:30:21.070
It's just getting bigger
and bigger and bigger.

00:30:21.070 --> 00:30:24.670
- Amee Manges studies the
connection between the farm use

00:30:24.670 --> 00:30:28.030
of antibiotics and
drug-resistant bacteria

00:30:28.030 --> 00:30:28.640
in our food.

00:30:30.340 --> 00:30:32.680
- When you apply low
doses of antibiotics,

00:30:32.680 --> 00:30:35.790
you eliminate the susceptible
bugs in the environment

00:30:35.790 --> 00:30:38.390
and you're allowing the
resistant ones to develop

00:30:38.390 --> 00:30:40.960
and be amplified,
you know, grow...

00:30:40.960 --> 00:30:44.180
overgrow in that environment
and be disseminated.

00:30:44.180 --> 00:30:47.020
So that's really the issue, is
you're not treating one animal

00:30:47.020 --> 00:30:50.120
and helping that sick
animal, basically using it

00:30:50.120 --> 00:30:51.365
in that entire environment.

00:30:54.870 --> 00:30:57.690
- There's always been some
chance of bringing E. coli

00:30:57.690 --> 00:30:59.860
home from the grocery store.

00:30:59.860 --> 00:31:02.160
But now, the bugs
you eat are also

00:31:02.160 --> 00:31:04.970
more likely to be
drug-resistant.

00:31:04.970 --> 00:31:07.310
- The highest burden
of contamination

00:31:07.310 --> 00:31:10.590
is in poultry and chicken
and turkey, especially.

00:31:10.590 --> 00:31:12.940
Depending on how the
meat is processed,

00:31:12.940 --> 00:31:15.600
the final retail meat that
you take off the shelves

00:31:15.600 --> 00:31:17.830
may have more or
less bacteria on it.

00:31:17.830 --> 00:31:19.920
And the more intensively
the antibiotics

00:31:19.920 --> 00:31:23.030
are used on the farm, the
more likely the bacteria

00:31:23.030 --> 00:31:26.620
that remain on the retail
meat will be drug-resistant.

00:31:26.620 --> 00:31:30.200
- The precautionary use of
antibiotics on farm animals

00:31:30.200 --> 00:31:34.900
was banned outright in the
European Union in 2006,

00:31:34.900 --> 00:31:37.050
but the practice
is still allowed

00:31:37.050 --> 00:31:38.850
on American and Canadian farms.

00:31:41.640 --> 00:31:44.975
Of course, there are many
different kinds of farms.

00:31:44.975 --> 00:31:48.030
On this farm, the
animals manufacture

00:31:48.030 --> 00:31:49.070
their own antibiotics.

00:31:49.070 --> 00:31:51.252
(ALLIGATOR GROWLING)

00:31:56.990 --> 00:32:01.530
The next great antibiotic could
be hiding in a weird and exotic

00:32:01.530 --> 00:32:04.940
place -- far beneath
the Earth's surface,

00:32:04.940 --> 00:32:07.920
on the fur of a
three-toed sloth,

00:32:07.920 --> 00:32:10.530
or how about an alligator farm?

00:32:13.280 --> 00:32:15.970
- We thought maybe we could
find a very evolutionarily

00:32:15.970 --> 00:32:19.330
ancient animal that maybe
would have a very strong innate

00:32:19.330 --> 00:32:21.755
immune system, having survived
for millions of years.

00:32:23.780 --> 00:32:26.576
- Monique van Hoek
searches for antibiotics

00:32:26.576 --> 00:32:27.700
in the blood of alligators.

00:32:30.420 --> 00:32:33.470
- We can't tell age by
looking at these animals.

00:32:33.470 --> 00:32:36.470
Bigger doesn't
always mean older.

00:32:36.470 --> 00:32:37.650
- This place is amazing.

00:32:37.650 --> 00:32:40.310
There's 40 or so
alligators in this pit.

00:32:40.310 --> 00:32:42.290
There are many other
wonderful displays.

00:32:45.150 --> 00:32:47.960
- This is van Hoek's first
visit to the source of the blood

00:32:47.960 --> 00:32:49.800
she's been studying.

00:32:49.800 --> 00:32:52.410
Florida's St. Augustine
Alligator Farm

00:32:52.410 --> 00:32:57.580
houses hundreds of alligators
and other kinds of crocodiles.

00:32:57.580 --> 00:33:00.500
It's also home to a
couple of Komodo dragons.

00:33:02.950 --> 00:33:05.020
- I'm very interested
in the Komodo dragons.

00:33:05.020 --> 00:33:07.560
They are also
evolutionarily ancient.

00:33:07.560 --> 00:33:10.590
These animals are very large,
they're six to nine feet long.

00:33:10.590 --> 00:33:12.340
They're the largest
lizards on the planet.

00:33:13.980 --> 00:33:17.860
- van Hoek is hoping to get
not just more alligator blood,

00:33:17.860 --> 00:33:20.320
but also some Komodo
dragon saliva.

00:33:23.080 --> 00:33:26.100
- They will eat carrion, which
is dead and rotting flesh.

00:33:26.100 --> 00:33:28.680
And the other interesting thing
about Komodo dragons is that

00:33:28.680 --> 00:33:31.100
they are known... if they
sample the saliva of the Komodo

00:33:31.100 --> 00:33:33.900
dragon, it has more than
50 species of bacteria

00:33:33.900 --> 00:33:35.400
in their saliva.

00:33:35.400 --> 00:33:38.040
And many of these are
pathogens, dangerous bacteria

00:33:38.040 --> 00:33:39.950
that can affect
mammals, for example.

00:33:39.950 --> 00:33:41.770
So we think that the
Komodo dragon also has

00:33:41.770 --> 00:33:44.530
very robust, innate immunity.

00:33:44.530 --> 00:33:48.140
- van Hoek isn't looking
for bacteria or fungi.

00:33:48.140 --> 00:33:51.610
She's searching for a
special defensive molecule

00:33:51.610 --> 00:33:54.260
built into the immune
system of ancient animals.

00:33:56.780 --> 00:34:00.100
- An antimicrobial peptide
is a very small protein,

00:34:00.100 --> 00:34:02.550
and these are made by the
bodies of most animals

00:34:02.550 --> 00:34:05.110
as part of what we call
our "innate immune system."

00:34:05.110 --> 00:34:07.170
Antimicrobial
peptides kill bacteria

00:34:07.170 --> 00:34:09.090
by attacking their membranes.

00:34:09.090 --> 00:34:11.419
They kind of glom onto
the bacterial membrane

00:34:11.419 --> 00:34:13.460
and they punch holes into
the bacterial membrane,

00:34:13.460 --> 00:34:17.860
and this causes the bacteria
to blow up and thus die.

00:34:17.860 --> 00:34:20.699
- Kent Vliet, the
zoo's science adviser,

00:34:20.699 --> 00:34:24.659
will help van Hoek get her
vial of alligator blood.

00:34:24.659 --> 00:34:28.423
Curator Kevin Torregrossa
will do the wrestling.

00:34:28.423 --> 00:34:30.355
- Let's go get a gator.

00:34:30.355 --> 00:34:34.710
(DRAMATIC MUSIC)

00:34:34.710 --> 00:34:38.199
- Lots to choose from -- might
as well go for the small ones.

00:35:07.140 --> 00:35:09.450
- We want to use these
peptides as a scaffold

00:35:09.450 --> 00:35:13.335
to maybe build or create a
next generation of antibiotics.

00:35:15.320 --> 00:35:17.947
- And there's the blood.

00:35:17.947 --> 00:35:20.530
- So we got a tube and a half
of wonderful, precious alligator

00:35:20.530 --> 00:35:22.690
blood for our experiments.

00:35:22.690 --> 00:35:24.300
- Kudja!

00:35:24.300 --> 00:35:25.830
That's a good lizard.

00:35:25.830 --> 00:35:29.610
- Now, the bigger challenge
-- the Komodo dragon for some

00:35:29.610 --> 00:35:31.010
saliva.

00:35:31.010 --> 00:35:32.970
They'll try the male first.

00:35:32.970 --> 00:35:34.102
He's more docile.

00:35:34.102 --> 00:35:35.060
(KOMODO DRAGON HISSING)

00:35:35.060 --> 00:35:37.370
By the way, the mouse
is already dead.

00:35:39.720 --> 00:35:42.263
- Oh, I had to get
something there, right?

00:35:42.263 --> 00:35:44.040
- There you go.

00:35:44.040 --> 00:35:47.070
- Nice, dirty lizard mouth.

00:35:50.770 --> 00:35:54.580
- At her George Mason
University lab in Virginia,

00:35:54.580 --> 00:35:57.230
van Hoek has been able
to isolate peptides

00:35:57.230 --> 00:35:58.190
from the gator blood.

00:36:00.430 --> 00:36:02.970
Next, a test on worms.

00:36:02.970 --> 00:36:05.855
They infect the worms and then
inject them with the peptide.

00:36:08.300 --> 00:36:11.260
van Hoek can judge the
effectiveness of the peptides

00:36:11.260 --> 00:36:13.850
by the number of
surviving worms.

00:36:13.850 --> 00:36:16.930
There are some
dramatic findings.

00:36:16.930 --> 00:36:19.470
- We test against six
different bacteria

00:36:19.470 --> 00:36:21.510
and we found at
least five peptides

00:36:21.510 --> 00:36:23.290
that are very, very
good at killing

00:36:23.290 --> 00:36:26.450
all of the different bacteria
that we've tested them against.

00:36:26.450 --> 00:36:29.530
So we're really excited
about our results.

00:36:29.530 --> 00:36:32.310
- van Hoek is
tantalizingly guarded

00:36:32.310 --> 00:36:34.890
about the Komodo dragon saliva.

00:36:34.890 --> 00:36:37.150
We have found some
Komodo peptides,

00:36:37.150 --> 00:36:40.800
but I'm not really ready
to share that with you yet.

00:36:40.800 --> 00:36:42.182
We're very excited.

00:36:42.182 --> 00:36:43.140
(KOMODO DRAGON HISSING)

00:36:43.140 --> 00:36:46.370
- But it's a long way
from a promising peptide

00:36:46.370 --> 00:36:47.390
to a new antibiotic.

00:36:51.140 --> 00:36:54.580
So some teams of scientists
are looking for shortcuts

00:36:54.580 --> 00:36:57.300
by breathing new
life into old drugs.

00:36:59.940 --> 00:37:04.190
At Boston University, they're
borrowing from ancient medicine

00:37:04.190 --> 00:37:08.710
by using silver to make our
existing arsenal of antibiotics

00:37:08.710 --> 00:37:10.312
stronger.

00:37:10.312 --> 00:37:11.770
- Too much silver
can be a problem.

00:37:11.770 --> 00:37:14.220
Your body doesn't
well process silver,

00:37:14.220 --> 00:37:17.130
and so it can lead to
very nasty reactions

00:37:17.130 --> 00:37:20.484
and can itself cause
somebody to be ill.

00:37:20.484 --> 00:37:22.150
One of the advantages
that we discovered

00:37:22.150 --> 00:37:23.691
is that you could
actually use silver

00:37:23.691 --> 00:37:26.805
in very low amounts,
non-toxic levels,

00:37:26.805 --> 00:37:28.430
as a way to boost
existing antibiotics.

00:37:30.290 --> 00:37:34.490
- Even the best antibiotics
we have, like vancomycin,

00:37:34.490 --> 00:37:37.910
have a tough time combating
a class of bacteria called

00:37:37.910 --> 00:37:41.900
"gram-negative", because those
bugs have an extra protective

00:37:41.900 --> 00:37:43.190
shell.

00:37:43.190 --> 00:37:45.710
Silver can come to the rescue.

00:37:45.710 --> 00:37:47.530
- We have challenges
finding molecules

00:37:47.530 --> 00:37:49.550
that can get inside those.

00:37:49.550 --> 00:37:52.220
When we discovered
that silver will change

00:37:52.220 --> 00:37:56.420
the permeability of the membrane
in gram-negatives like E. coli,

00:37:56.420 --> 00:37:59.180
we had the hypothesis
that maybe you

00:37:59.180 --> 00:38:00.930
could use this to
enable vancomycin

00:38:00.930 --> 00:38:02.350
to get into those
cells and kill.

00:38:02.350 --> 00:38:05.630
And we in fact found,
not only in the dish

00:38:05.630 --> 00:38:08.007
could silver in small
amounts make vanco effective,

00:38:08.007 --> 00:38:09.340
but it also worked well in mice.

00:38:13.360 --> 00:38:17.320
- Any new, improved vancomycin
wouldn't be ready in time

00:38:17.320 --> 00:38:19.360
to help Krista Kilback.

00:38:19.360 --> 00:38:21.810
On her doctor's
advice, she's going

00:38:21.810 --> 00:38:25.230
to try a very
different solution.

00:38:25.230 --> 00:38:26.650
- It was actually
very easy to do,

00:38:26.650 --> 00:38:29.025
that I actually didn't believe
that it was going to work.

00:38:36.280 --> 00:38:40.480
- Krista Kilback has struggled
for months with a C. difficile

00:38:40.480 --> 00:38:43.290
intestinal infection.

00:38:43.290 --> 00:38:48.250
Her doctor, Alex Wong, has tried
all the antibiotics available.

00:38:48.250 --> 00:38:50.090
Nothing has worked.

00:38:50.090 --> 00:38:53.060
But there's one
unusual option left.

00:38:53.060 --> 00:38:55.330
- Now, she's basically
on vancomycin

00:38:55.330 --> 00:38:57.890
as we wait for a
fecal transplant.

00:38:57.890 --> 00:39:02.040
- A fecal transplant is
just what it sounds like.

00:39:02.040 --> 00:39:04.540
- It's literally taking
someone else's poop --

00:39:04.540 --> 00:39:07.980
which theoretically has a
much more healthy composition

00:39:07.980 --> 00:39:11.170
of sort of good bacteria
-- and literally instilling

00:39:11.170 --> 00:39:16.010
or infusing that, either via
an enema or via some sort

00:39:16.010 --> 00:39:21.180
of endoscopy-type procedure,
into Krista's colon so that we

00:39:21.180 --> 00:39:25.510
essentially repopulate her
colon with good bacteria.

00:39:25.510 --> 00:39:27.970
- Krista was willing
to give it a try,

00:39:27.970 --> 00:39:32.000
but unfortunately the
transplant had to be postponed.

00:39:32.000 --> 00:39:35.840
Health Canada defined the
microbiota in the feces

00:39:35.840 --> 00:39:39.960
as a drug, and declared that
fecal transplants could only

00:39:39.960 --> 00:39:43.880
be done as part of
a clinical trial.

00:39:43.880 --> 00:39:48.420
So Krista decided to perform
the fecal transplant at home.

00:39:48.420 --> 00:39:49.800
The good news?

00:39:49.800 --> 00:39:54.354
It completely cleared up
her C. difficile infection.

00:39:54.354 --> 00:39:55.770
- I had the best
possible outcome.

00:39:55.770 --> 00:39:57.330
I'm able to eat anything I want.

00:39:57.330 --> 00:39:59.490
I don't have any
stomach issues anymore.

00:39:59.490 --> 00:40:02.140
I'm pretty much, I
would say, back to what

00:40:02.140 --> 00:40:03.830
I was prior to this happening.

00:40:03.830 --> 00:40:05.660
So I feel really fortunate.

00:40:05.660 --> 00:40:08.300
- Although it wasn't
available for Krista,

00:40:08.300 --> 00:40:11.020
there is another
unorthodox treatment that

00:40:11.020 --> 00:40:13.940
might well have helped her.

00:40:13.940 --> 00:40:16.040
It's called phage therapy.

00:40:19.120 --> 00:40:22.350
Each strain of these
bizarre-looking viruses,

00:40:22.350 --> 00:40:26.970
called bacteriophages,
kills specific bacteria.

00:40:26.970 --> 00:40:29.570
This treatment has been
used in Russia and Georgia

00:40:29.570 --> 00:40:35.020
for 90 years, but it's never
been fully accepted elsewhere.

00:40:35.020 --> 00:40:38.590
- The advantage of phage
in today's world is that

00:40:38.590 --> 00:40:40.620
they're highly specific,
species-specific,

00:40:40.620 --> 00:40:42.036
and in some cases
strain-specific.

00:40:43.580 --> 00:40:45.840
- Because they are
very fussy about what

00:40:45.840 --> 00:40:49.750
bacteria they inhabit
and kill, bacteriophages

00:40:49.750 --> 00:40:52.240
won't kill off
the friendly bugs.

00:40:52.240 --> 00:40:54.650
And Jim Collins
has shown that they

00:40:54.650 --> 00:40:57.656
can work against stubborn
bacteria called biofilms.

00:41:00.140 --> 00:41:02.636
- So the plaque on your
teeth is a biofilm.

00:41:02.636 --> 00:41:04.510
The stuff on the side
of a ship is a biofilm.

00:41:04.510 --> 00:41:07.850
The stuff in your sink, in
your drain, is a biofilm.

00:41:07.850 --> 00:41:10.720
The bugs in biofilms are
1,000 times more resistant

00:41:10.720 --> 00:41:13.160
to antibiotics than
free-swimming bugs, one.

00:41:13.160 --> 00:41:16.250
Two, bugs like to form
biofilms on anything

00:41:16.250 --> 00:41:18.030
we put in somebody's body.

00:41:18.030 --> 00:41:20.310
So if it's a catheter, if
it's an artificial knee,

00:41:20.310 --> 00:41:22.932
an artificial hip,
pacemaker for your heart,

00:41:22.932 --> 00:41:24.640
the number-one risk
is not the procedure.

00:41:24.640 --> 00:41:26.431
The number-one one risk
now is you're going

00:41:26.431 --> 00:41:27.650
to get a biofilm infection.

00:41:27.650 --> 00:41:31.710
What we did was engineer
bacteriophage to break up

00:41:31.710 --> 00:41:33.610
biofilms.

00:41:33.610 --> 00:41:36.420
- Like silver, these
viruses might also

00:41:36.420 --> 00:41:41.280
be used to boost the strength
of existing antibiotics.

00:41:41.280 --> 00:41:43.790
- And we showed that when you
delivered those phage with

00:41:43.790 --> 00:41:46.350
existing antibiotics, you could
boost their killing efficacy

00:41:46.350 --> 00:41:48.925
of the antibiotics
100-fold to 10,000-fold.

00:41:51.170 --> 00:41:54.030
- If those preliminary
findings hold up,

00:41:54.030 --> 00:41:57.080
it will be an incredibly
useful discovery,

00:41:57.080 --> 00:42:00.320
whether it's used on today's
antibiotics or tomorrow's.

00:42:03.030 --> 00:42:05.520
- As scientists, we
really feel an obligation

00:42:05.520 --> 00:42:08.105
to develop new antibiotics
as best as we can,

00:42:08.105 --> 00:42:11.210
and to contribute to the
resource of antibiotics

00:42:11.210 --> 00:42:12.555
that have helped humanity.

00:42:15.270 --> 00:42:17.700
- I think the situation
is getting more and more

00:42:17.700 --> 00:42:20.260
grim, really with each year.

00:42:20.260 --> 00:42:22.260
We are increasingly
seeing infections

00:42:22.260 --> 00:42:24.670
that are not treatable.

00:42:24.670 --> 00:42:27.150
And so if those start
spreading, we could be...

00:42:27.150 --> 00:42:28.924
we could be in dire straits.

00:42:28.924 --> 00:42:33.900
- I firmly believe that we will
not solve the problem unless we

00:42:33.900 --> 00:42:36.290
do find new antibiotics.

00:42:36.290 --> 00:42:41.010
We cannot control resistance,
but we can control the use

00:42:41.010 --> 00:42:41.590
of new...

00:42:41.590 --> 00:42:42.550
brand-new antibiotics.

00:42:45.538 --> 00:42:48.830
- And so the antibiotic
hunters continue

00:42:48.830 --> 00:42:54.320
to comb the wild world for
promising new compounds.

00:42:54.320 --> 00:42:56.090
- Are those the colors
you're looking for?

00:42:56.090 --> 00:42:57.700
- Oh, yeah.

00:42:57.700 --> 00:43:01.310
Hunting for new antibiotics
is an incredible adventure,

00:43:01.310 --> 00:43:03.440
and it's also
incredibly productive.

00:43:03.440 --> 00:43:06.389
As long as we have wild
environments with biodiversity,

00:43:06.389 --> 00:43:07.680
we have a chance for discovery.

00:43:12.480 --> 00:43:15.830
(THEME MUSIC)