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Recorded at	February 20, 2014
Event	TED2014
Duration (min:sec)	17:11
Video Type	TED Stage Talk
Words per minute	216.03 very fast
Readability (FK)	46.81 difficult
Speaker	Rob Knight
Country	New Zealand
Occupation	biologist, writer, scientist
Description	New Zealand computational microbiologist


1	00:13	We humans have always been very concerned about the health of our bodies,
2	00:17	but we haven't always been that good at figuring out what's important.
3	00:21	Take the ancient Egyptians, for example:
4	00:23	very concerned about the body parts they thought they'd need in the afterlife,
5	00:27	but they left some parts out.
6	00:29	This part, for example.
7	00:32	Although they very carefully preserved the stomach, the lungs,
8	00:35	the liver, and so forth,
9	00:36	they just mushed up the brain, drained it out through the nose,
10	00:39	and threw it away,
11	00:41	which makes sense, really,
12	00:42	because what does a brain do for us anyway?
13	00:45	But imagine if there were a kind of neglected organ in our bodies
14	00:48	that weighed just as much as the brain
15	00:50	and in some ways was just as important to who we are,
16	00:53	but we knew so little about and treated with such disregard.
17	00:57	And imagine if, through new scientific advances,
18	01:00	we were just beginning to understand
19	01:01	its importance to how we think of ourselves.
20	01:04	Wouldn't you want to know more about it?
21	01:07	Well, it turns out that we do have something just like that:
22	01:10	our gut,
23	01:12	or rather, its microbes.
24	01:15	But it's not just the microbes in our gut that are important.
25	01:18	Microbes all over our body
26	01:19	turn out to be really critical to a whole range of differences
27	01:22	that make different people who we are.
28	01:25	So for example, have you ever noticed
29	01:27	how some people get bitten by mosquitos way more often than others?
30	01:31	It turns out that everyone's anecdotal experience out camping is actually true.
31	01:36	For example, I seldom get bitten by mosquitos,
32	01:38	but my partner Amanda attracts them in droves,
33	01:41	and the reason why is that we have different microbes on our skin
34	01:44	that produce different chemicals that the mosquitos detect.
35	01:48	Now, microbes are also really important in the field of medicine.
36	01:51	So, for example, what microbes you have in your gut
37	01:54	determine whether particular painkillers are toxic to your liver.
38	01:58	They also determine whether or not other drugs will work for your heart condition.
39	02:02	And, if you're a fruit fly, at least,
40	02:05	your microbes determine who you want to have sex with.
41	02:08	We haven't demonstrated this in humans yet
42	02:10	but maybe it's just a matter of time before we find out. (Laughter)
43	02:15	So microbes are performing a huge range of functions.
44	02:17	They help us digest our food.
45	02:19	They help educate our immune system.
46	02:21	They help us resist disease,
47	02:23	and they may even be affecting our behavior.
48	02:26	So what would a map of all these microbial communities look like?
49	02:30	Well, it wouldn't look exactly like this,
50	02:32	but it's a helpful guide for understanding biodiversity.
51	02:35	Different parts of the world have different landscapes of organisms
52	02:39	that are immediately characteristic of one place or another
53	02:43	or another.
54	02:45	With microbiology, it's kind of the same, although I've got to be honest with you:
55	02:49	All the microbes essentially look the same under a microscope.
56	02:52	So instead of trying to identify them visually,
57	02:55	what we do is we look at their DNA sequences,
58	02:57	and in a project called the Human Microbiome Project,
59	03:00	NIH funded this $173 million project
60	03:04	where hundreds of researchers came together
61	03:06	to map out all the A's, T's, G's, and C's,
62	03:09	and all of these microbes in the human body.
63	03:11	So when we take them together, they look like this.
64	03:14	It's a bit more difficult to tell who lives where now, isn't it?
65	03:18	What my lab does is develop computational techniques that allow us
66	03:22	to take all these terabytes of sequence data
67	03:24	and turn them into something that's a bit more useful as a map,
68	03:27	and so when we do that with the human microbiome data
69	03:30	from 250 healthy volunteers,
70	03:32	it looks like this.
71	03:35	Each point here represents all the complex microbes
72	03:38	in an entire microbial community.
73	03:40	See, I told you they basically all look the same.
74	03:43	So what we're looking at is each point represents one microbial community
75	03:46	from one body site of one healthy volunteer.
76	03:49	And so you can see that there's different parts of the map in different colors,
77	03:53	almost like separate continents.
78	03:54	And what it turns out to be
79	03:56	is that those, as the different regions of the body,
80	03:58	have very different microbes in them.
81	04:00	So what we have is we have the oral community up there in green.
82	04:04	Over on the other side, we have the skin community in blue,
83	04:07	the vaginal community in purple,
84	04:09	and then right down at the bottom, we have the fecal community in brown.
85	04:13	And we've just over the last few years
86	04:15	found out that the microbes in different parts of the body
87	04:18	are amazingly different from one another.
88	04:20	So if I look at just one person's microbes
89	04:23	in the mouth and in the gut,
90	04:25	it turns out that the difference between those two microbial communities
91	04:28	is enormous.
92	04:30	It's bigger than the difference between the microbes in this reef
93	04:33	and the microbes in this prairie.
94	04:36	So this is incredible when you think about it.
95	04:38	What it means is that a few feet of difference in the human body
96	04:42	makes more of a difference to your microbial ecology
97	04:44	than hundreds of miles on Earth.
98	04:46	And this is not to say that two people look basically the same
99	04:49	in the same body habitat, either.
100	04:51	So you probably heard
101	04:53	that we're pretty much all the same in terms of our human DNA.
102	04:56	You're 99.99 percent identical in terms of your human DNA
103	05:00	to the person sitting next to you.
104	05:02	But that's not true of your gut microbes:
105	05:04	you might only share 10 percent similarity
106	05:07	with the person sitting next to you in terms of your gut microbes.
107	05:10	So that's as different as the bacteria on this prairie
108	05:13	and the bacteria in this forest.
109	05:16	So these different microbes
110	05:17	have all these different kinds of functions that I told you about,
111	05:21	everything from digesting food
112	05:22	to involvement in different kinds of diseases,
113	05:25	metabolizing drugs, and so forth.
114	05:27	So how do they do all this stuff?
115	05:29	Well, in part it's because
116	05:31	although there's just three pounds of those microbes in our gut,
117	05:34	they really outnumber us.
118	05:36	And so how much do they outnumber us?
119	05:38	Well, it depends on what you think of as our bodies.
120	05:41	Is it our cells?
121	05:43	Well, each of us consists of about 10 trillion human cells,
122	05:46	but we harbor as many as 100 trillion microbial cells.
123	05:49	So they outnumber us 10 to one.
124	05:52	Now, you might think, well, we're human because of our DNA,
125	05:56	but it turns out that each of us has about 20,000 human genes,
126	05:59	depending on what you count exactly,
127	06:01	but as many as two million to 20 million microbial genes.
128	06:06	So whichever way we look at it, we're vastly outnumbered
129	06:08	by our microbial symbionts.
130	06:11	And it turns out that in addition to traces of our human DNA,
131	06:15	we also leave traces of our microbial DNA
132	06:17	on everything we touch.
133	06:19	We showed in a study a few years ago
134	06:20	that you can actually match the palm of someone's hand up
135	06:23	to the computer mouse that they use routinely
136	06:25	with up to 95 percent accuracy.
137	06:28	So this came out in a scientific journal a few years ago,
138	06:31	but more importantly, it was featured on "CSI: Miami,"
139	06:33	so you really know it's true.
140	06:35	(Laughter)
141	06:36	So where do our microbes come from in the first place?
142	06:40	Well if, as I do, you have dogs or kids,
143	06:43	you probably have some dark suspicions about that,
144	06:45	all of which are true, by the way.
145	06:47	So just like we can match you to your computer equipment
146	06:50	by the microbes you share,
147	06:51	we can also match you up to your dog.
148	06:54	But it turns out that in adults,
149	06:56	microbial communities are relatively stable,
150	06:58	so even if you live together with someone,
151	07:00	you'll maintain your separate microbial identity
152	07:02	over a period of weeks, months, even years.
153	07:05	It turns out that our first microbial communities
154	07:08	depend a lot on how we're born.
155	07:11	So babies that come out the regular way,
156	07:13	all of their microbes are basically like the vaginal community,
157	07:16	whereas babies that are delivered by C-section,
158	07:18	all of their microbes instead look like skin.
159	07:21	And this might be associated with some of the differences
160	07:24	in health associated with Cesarean birth,
161	07:27	such as more asthma, more allergies, even more obesity,
162	07:30	all of which have been linked to microbes now,
163	07:33	and when you think about it, until recently, every surviving mammal
164	07:37	had been delivered by the birth canal,
165	07:39	and so the lack of those protective microbes
166	07:41	that we've co-evolved with might be really important
167	07:44	for a lot of these different conditions that we now know involve the microbiome.
168	07:48	When my own daughter was born a couple of years ago
169	07:51	by emergency C-section,
170	07:53	we took matters into our own hands
171	07:55	and made sure she was coated with those vaginal microbes
172	07:58	that she would have gotten naturally.
173	08:00	Now, it's really difficult to tell whether this has had an effect
174	08:03	on her health specifically, right?
175	08:05	With a sample size of just one child, no matter how much we love her,
176	08:09	you don't really have enough of a sample size
177	08:11	to figure out what happens on average,
178	08:13	but at two years old, she hasn't had an ear infection yet,
179	08:16	so we're keeping our fingers crossed on that one.
180	08:18	And what's more, we're starting to do clinical trials with more children
181	08:22	to figure out whether this has a protective effect generally.
182	08:27	So how we're born has a tremendous effect on what microbes we have initially,
183	08:32	but where do we go after that?
184	08:34	What I'm showing you again here is this map
185	08:36	of the Human Microbiome Project Data,
186	08:38	so each point represents a sample from one body site
187	08:41	from one of 250 healthy adults.
188	08:43	And you've seen children develop physically.
189	08:45	You've seen them develop mentally.
190	08:47	Now, for the first time, you're going to see
191	08:50	one of my colleague's children develop microbially.
192	08:53	So what we are going to look at
193	08:54	is we're going to look at this one baby's stool,
194	08:57	the fecal community, which represents the gut,
195	09:00	sampled every week for almost two and a half years.
196	09:03	And so we're starting on day one.
197	09:04	What's going to happen is that the infant is going to start off as this yellow dot,
198	09:08	and you can see that he's starting off basically in the vaginal community,
199	09:12	as we would expect from his delivery mode.
200	09:14	And what's going to happen over these two and a half years
201	09:17	is that he's going to travel all the way down
202	09:19	to resemble the adult fecal community from healthy volunteers down at the bottom.
203	09:23	So I'm just going to start this going and we'll see how that happens.
204	09:26	What you can see, and remember each step in this is just one week,
205	09:30	what you can see is that week to week,
206	09:32	the change in the microbial community of the feces of this one child,
207	09:37	the differences week to week are much greater
208	09:40	than the differences between individual healthy adults
209	09:42	in the Human Microbiome Project cohort,
210	09:44	which are those brown dots down at the bottom.
211	09:47	And you can see he's starting to approach the adult fecal community.
212	09:50	This is up to about two years.
213	09:51	But something amazing is about to happen here.
214	09:53	So he's getting antibiotics for an ear infection.
215	09:56	What you can see is this huge change in the community,
216	09:59	followed by a relatively rapid recovery.
217	10:01	I'll just rewind that for you.
218	10:05	And what we can see is that just over these few weeks,
219	10:08	we have a much more radical change,
220	10:10	a setback of many months of normal development,
221	10:13	followed by a relatively rapid recovery,
222	10:15	and by the time he reaches day 838,
223	10:19	which is the end of this video,
224	10:21	you can see that he has essentially reached the healthy adult stool community,
225	10:25	despite that antibiotic intervention.
226	10:27	So this is really interesting because it raises fundamental questions
227	10:30	about what happens when we intervene at different ages in a child's life.
228	10:35	So does what we do early on, where the microbiome is changing so rapidly,
229	10:38	actually matter,
230	10:39	or is it like throwing a stone into a stormy sea,
231	10:42	where the ripples will just be lost?
232	10:45	Well, fascinatingly, it turns out that if you give children antibiotics
233	10:49	in the first six months of life,
234	10:50	they're more likely to become obese later on
235	10:53	than if they don't get antibiotics then or only get them later,
236	10:56	and so what we do early on may have profound impacts
237	10:59	on the gut microbial community and on later health
238	11:03	that we're only beginning to understand.
239	11:05	So this is fascinating, because one day, in addition to the effects
240	11:09	that antibiotics have on antibiotic-resistant bacteria,
241	11:12	which are very important,
242	11:14	they may also be degrading our gut microbial ecosystems,
243	11:17	and so one day we may come to regard antibiotics with the same horror
244	11:20	that we currently reserve for those metal tools
245	11:22	that the Egyptians used to use to mush up the brains
246	11:25	before they drained them out for embalming.
247	11:27	So I mentioned that microbes have all these important functions,
248	11:30	and they've also now, just over the past few years,
249	11:32	been connected to a whole range of different diseases,
250	11:35	including inflammatory bowel disease,
251	11:37	heart disease, colon cancer,
252	11:39	and even obesity.
253	11:41	Obesity has a really large effect, as it turns out,
254	11:44	and today, we can tell whether you're lean or obese
255	11:46	with 90 percent accuracy
256	11:48	by looking at the microbes in your gut.
257	11:50	Now, although that might sound impressive,
258	11:52	in some ways it's a little bit problematic as a medical test,
259	11:56	because you can probably tell which of these people is obese
260	11:59	without knowing anything about their gut microbes,
261	12:01	but it turns out that even if we sequence their complete genomes
262	12:04	and had all their human DNA,
263	12:06	we could only predict which one was obese with about 60 percent accuracy.
264	12:10	So that's amazing, right?
265	12:12	What it means that the three pounds of microbes that you carry around with you
266	12:16	may be more important for some health conditions
267	12:18	than every single gene in your genome.
268	12:23	And then in mice, we can do a lot more.
269	12:25	So in mice, microbes have been linked to all kinds of additional conditions,
270	12:29	including things like multiple sclerosis,
271	12:32	depression, autism, and again, obesity.
272	12:35	But how can we tell whether these microbial differences
273	12:38	that correlate with disease are cause or effect?
274	12:41	Well, one thing we can do is we can raise some mice
275	12:44	without any microbes of their own in a germ-free bubble.
276	12:46	Then we can add in some microbes that we think are important,
277	12:49	and see what happens.
278	12:51	When we take the microbes from an obese mouse
279	12:54	and transplant them into a genetically normal mouse
280	12:56	that's been raised in a bubble with no microbes of its own,
281	12:59	it becomes fatter than if it got them from a regular mouse.
282	13:04	Why this happens is absolutely amazing, though.
283	13:06	Sometimes what's going on is that the microbes
284	13:08	are helping them digest food more efficiently from the same diet,
285	13:11	so they're taking more energy from their food,
286	13:13	but other times, the microbes are actually affecting their behavior.
287	13:17	What they're doing is they're eating more than the normal mouse,
288	13:20	so they only get fat if we let them eat as much as they want.
289	13:24	So this is really remarkable, right?
290	13:27	The implication is that microbes can affect mammalian behavior.
291	13:33	So you might be wondering whether we can also do this sort of thing across species,
292	13:37	and it turns out that if you take microbes from an obese person
293	13:40	and transplant them into mice you've raised germ-free,
294	13:43	those mice will also become fatter
295	13:45	than if they received the microbes from a lean person,
296	13:48	but we can design a microbial community that we inoculate them with
297	13:52	that prevents them from gaining this weight.
298	13:55	We can also do this for malnutrition.
299	13:57	So in a project funded by the Gates Foundation,
300	14:00	what we're looking at is children in Malawi
301	14:02	who have kwashiorkor, a profound form of malnutrition,
302	14:05	and mice that get the kwashiorkor community transplanted into them
303	14:08	lose 30 percent of their body mass
304	14:11	in just three weeks,
305	14:12	but we can restore their health by using the same peanut butter-based supplement
306	14:16	that is used for the children in the clinic,
307	14:18	and the mice that receive the community
308	14:19	from the healthy identical twins of the kwashiorkor children do fine.
309	14:24	This is truly amazing because it suggests that we can pilot therapies
310	14:27	by trying them out in a whole bunch of different mice
311	14:30	with individual people's gut communities
312	14:32	and perhaps tailor those therapies all the way down to the individual level.
313	14:38	So I think it's really important that everyone has a chance
314	14:41	to participate in this discovery.
315	14:43	So, a couple of years ago,
316	14:45	we started this project called American Gut,
317	14:47	which allows you to claim a place for yourself on this microbial map.
318	14:51	This is now the largest crowd-funded science project that we know of --
319	14:54	over 8,000 people have signed up at this point.
320	14:57	What happens is, they send in their samples,
321	15:00	we sequence the DNA of their microbes and then release the results back to them.
322	15:04	We also release them, de-identified, to scientists, to educators,
323	15:07	to interested members of the general public, and so forth,
324	15:10	so anyone can have access to the data.
325	15:13	On the other hand,
326	15:15	when we do tours of our lab at the BioFrontiers Institute,
327	15:18	and we explain that we use robots and lasers to look at poop,
328	15:21	it turns out that not everyone wants to know.
329	15:25	(Laughter)
330	15:26	But I'm guessing that many of you do,
331	15:28	and so I brought some kits here if you're interested
332	15:30	in trying this out for yourself.
333	15:35	So why might we want to do this?
334	15:36	Well, it turns out that microbes are not just important
335	15:39	for finding out where we are in terms of our health,
336	15:42	but they can actually cure disease.
337	15:44	This is one of the newest things we've been able to visualize
338	15:47	with colleagues at the University of Minnesota.
339	15:50	So here's that map of the human microbiome again.
340	15:53	What we're looking at now --
341	15:54	I'm going to add in the community of some people with C. diff.
342	15:57	So, this is a terrible form of diarrhea
343	16:00	where you have to go up to 20 times a day,
344	16:02	and these people have failed antibiotic therapy for two years
345	16:05	before they're eligible for this trial.
346	16:08	So what would happen if we transplanted some of the stool from a healthy donor,
347	16:12	that star down at the bottom,
348	16:14	into these patients.
349	16:15	Would the good microbes do battle with the bad microbes
350	16:18	and help to restore their health?
351	16:20	So let's watch exactly what happens there.
352	16:22	Four of those patients are about to get a transplant
353	16:25	from that healthy donor at the bottom,
354	16:27	and what you can see is that immediately,
355	16:29	you have this radical change in the gut community.
356	16:31	So one day after you do that transplant,
357	16:33	all those symptoms clear up,
358	16:35	the diarrhea vanishes,
359	16:36	and they're essentially healthy again, coming to resemble the donor's community,
360	16:40	and they stay there.
361	16:42	(Applause)
362	16:49	So we're just at the beginning of this discovery.
363	16:51	We're just finding out that microbes have implications
364	16:54	for all these different kinds of diseases,
365	16:56	ranging from inflammatory bowel disease to obesity,
366	16:58	and perhaps even autism and depression.
367	17:01	What we need to do, though,
368	17:03	is we need to develop a kind of microbial GPS,
369	17:05	where we don't just know where we are currently
370	17:07	but also where we want to go and what we need to do
371	17:11	in order to get there,
372	17:12	and we need to be able to make this simple enough
373	17:15	that even a child can use it. (Laughter)
374	17:17	Thank you.
375	17:20	(Applause)

Rob Knight: How our microbes make us who we are