Recorded at | March 03, 2020 |
---|---|
Event | TEDMED 2020 |
Duration (min:sec) | 20:45 |
Video Type | TED Stage Talk |
Words per minute | 145.34 very slow |
Readability (FK) | 58.27 easy |
Speaker | Leor Weinberger |
Official TED page for this talk
Synopsis
Viruses mutate and spread from person to person, a dynamic process that often leaves us playing catch-up when there's a new disease outbreak. What if vaccines worked the same way? Virologist Leor Weinberger shares a scientific breakthrough: "hijacker therapy," a type of medical treatment that could attack, modify and spread alongside a virus, potentially treating afflicted individuals and slowing the spread of infections like HIV.
1 | 00:00 | I want to tell you about a student of mine. | ||
2 | 00:03 | A few weeks ago, she was on vacation | ||
3 | 00:06 | when at 3am she got a phone call. | ||
4 | 00:10 | It was her husband telling her | ||
5 | 00:11 | that the city that she was in would be quarantined by 10am. | ||
6 | 00:17 | She was in Wuhan, China. | ||
7 | 00:19 | The epicenter of the coronavirus outbreak. | ||
8 | 00:23 | By 8am she was on the road in a friend's car | ||
9 | 00:26 | driving 500 miles to Shanghai Airport. | ||
10 | 00:30 | The entire time, she was terrified the authorities would arrest her. | ||
11 | 00:34 | She made it out on one of the last flights. | ||
12 | 00:38 | So we're all relieved that she's back home, | ||
13 | 00:41 | safe in the US. | ||
14 | 00:43 | But what if I told you she was in this room? | ||
15 | 00:48 | What if I told you she was sitting next to you? | ||
16 | 00:52 | There's no vaccine. | ||
17 | 00:54 | There won't be a vaccine for at least 12 months. | ||
18 | 00:58 | And this virus is mutating, | ||
19 | 01:01 | so there's no guarantee that the vaccine that we produce 12 months from now | ||
20 | 01:05 | will match the mutated virus. | ||
21 | 01:10 | We're always playing catch-up. | ||
22 | 01:12 | And this is the scenario we're in every time there's an outbreak. | ||
23 | 01:17 | Our quarantines are porous, | ||
24 | 01:19 | our medical responses are flat-footed. | ||
25 | 01:24 | The fundamental problem that we face in controlling these outbreaks | ||
26 | 01:28 | is that viruses and other infections do two things really well: | ||
27 | 01:33 | they mutate | ||
28 | 01:36 | and they transmit. | ||
29 | 01:40 | Our medical tools do neither of these two things. | ||
30 | 01:43 | Our medical tools don't mutate or transmit. | ||
31 | 01:46 | We have a fundamental mismatch between our tools, | ||
32 | 01:50 | which are static, | ||
33 | 01:52 | and the infections, which are dynamic. | ||
34 | 01:56 | This mismatch is why we're always flat-footed. | ||
35 | 01:59 | This mismatch is why we're playing catch-up. | ||
36 | 02:02 | And this mismatch is universal. | ||
37 | 02:06 | It's the reason that we have antibiotic-resistant infections | ||
38 | 02:09 | that killed 40,000 Americans last year, | ||
39 | 02:13 | and it's the reason that the flu vaccine couldn't prevent the flu | ||
40 | 02:17 | from killing 60,000 Americans last year. | ||
41 | 02:23 | So how do we resolve this fundamental mismatch? | ||
42 | 02:28 | I've devoted my career to studying and solving this problem. | ||
43 | 02:34 | For 100 years, | ||
44 | 02:36 | we've used chemicals as drugs to treat infections. | ||
45 | 02:40 | Chemicals will never mutate or transmit. | ||
46 | 02:44 | Similarly, our vaccines are not designed to mutate or transmit. | ||
47 | 02:51 | 20 years ago, | ||
48 | 02:53 | I had a radical idea | ||
49 | 02:55 | to use the viruses themselves as therapies -- | ||
50 | 03:00 | as building blocks for therapies. | ||
51 | 03:02 | To build therapies that could mutate and transmit. | ||
52 | 03:08 | Let me share with you how we've had a major breakthrough, | ||
53 | 03:11 | and we're already testing these new therapies. | ||
54 | 03:16 | HIV is the most devastating pandemic of our era. | ||
55 | 03:22 | 75 million infected; | ||
56 | 03:24 | 33 million dead. | ||
57 | 03:27 | Most of us think that HIV is a solved problem. | ||
58 | 03:31 | We have truly amazing antiviral drugs: | ||
59 | 03:33 | they're safe and effective, | ||
60 | 03:35 | and we've spent 15 years | ||
61 | 03:36 | and billions of dollars deploying these drugs | ||
62 | 03:39 | around the world. | ||
63 | 03:41 | So let's look at the numbers. | ||
64 | 03:44 | In 2019, | ||
65 | 03:46 | 1.7 million people acquired HIV. | ||
66 | 03:51 | This number only hit home for me last year | ||
67 | 03:53 | when I visited this rural village outside of Durban, South Africa. | ||
68 | 03:59 | I was driving along this dirt road | ||
69 | 04:02 | with my 10-year-old daughter in the back seat, | ||
70 | 04:04 | and walking next to us on the side of the road were girls, | ||
71 | 04:09 | the same age as my daughter, | ||
72 | 04:11 | barefoot. | ||
73 | 04:12 | My daughter asked about why these girls are barefoot | ||
74 | 04:15 | and I had to explain disparity to her, | ||
75 | 04:18 | which was hard. | ||
76 | 04:21 | But what really shocked me was when my colleagues, | ||
77 | 04:25 | the local African scientists explained to me | ||
78 | 04:29 | that these young girls the same age as my daughter -- | ||
79 | 04:32 | (Breathes) | ||
80 | 04:33 | sorry -- | ||
81 | 04:34 | had an 80 percent chance of acquiring HIV in their lifetime. | ||
82 | 04:40 | It blew me away. | ||
83 | 04:42 | How can these girls have an 80 percent risk | ||
84 | 04:44 | if we have safe and effective drugs? | ||
85 | 04:49 | The reason is the fundamental mismatch. | ||
86 | 04:52 | It creates barriers to controlling infectious disease, | ||
87 | 04:55 | particularly in resource-limited settings. | ||
88 | 05:00 | The first barrier is mutation: | ||
89 | 05:02 | viruses mutate, our drugs don't. | ||
90 | 05:05 | The second barrier: adherence. | ||
91 | 05:08 | It's really hard to get these drugs to those who need the most. | ||
92 | 05:13 | I can't even adhere to a week-long antibiotic regimen in this country. | ||
93 | 05:20 | We're asking those in resource-limited settings | ||
94 | 05:23 | who face enormous adversity | ||
95 | 05:24 | to adhere to lifelong regimens. | ||
96 | 05:27 | And the third barrier is deployment, | ||
97 | 05:31 | or access. | ||
98 | 05:32 | It's super hard to get these drugs to those who need them most. | ||
99 | 05:38 | Not these girls but those who engage in high-risk activities, | ||
100 | 05:42 | such as commercial sex work and injection drug use. | ||
101 | 05:48 | In the epidemiological parlance, | ||
102 | 05:49 | these groups are called "super-spreaders." | ||
103 | 05:52 | And in the 1900s, | ||
104 | 05:54 | a small subset of super-spreaders | ||
105 | 05:57 | drove HIV along the Trans-Africa Highway | ||
106 | 06:00 | and spread the virus through the continent like this. | ||
107 | 06:04 | These groups are exceptionally hard to identify, | ||
108 | 06:07 | they're small, | ||
109 | 06:08 | they face enormous social stigma so they don't self-identify | ||
110 | 06:12 | and they're the ones we need to get to the most. | ||
111 | 06:15 | All of these barriers combined created the situation we have today, | ||
112 | 06:21 | where greater than 15 percent of people in Southern Africa live with HIV. | ||
113 | 06:29 | Now, conventional wisdom is: | ||
114 | 06:31 | what we need to do is get more drugs to more people more effectively. | ||
115 | 06:37 | I'd argue we need to solve the fundamental mismatch; | ||
116 | 06:40 | we need to eliminate these barriers. | ||
117 | 06:44 | If we can build therapies that mutate and transmit, | ||
118 | 06:48 | we can overcome drug resistance, | ||
119 | 06:50 | overcome adherence barriers, | ||
120 | 06:54 | and if we do it properly, | ||
121 | 06:56 | we will convert the super-spreaders from the greatest barrier | ||
122 | 07:00 | to the most powerful deployment strategy that we can imagine. | ||
123 | 07:06 | This is a radical concept. | ||
124 | 07:09 | It has huge potential payoff, | ||
125 | 07:12 | but there's a catch. | ||
126 | 07:15 | And it's serious. | ||
127 | 07:19 | Before we deploy a therapy that may transmit, | ||
128 | 07:24 | even if it's only in a limited population of already infected individuals, | ||
129 | 07:28 | before we do this, | ||
130 | 07:30 | we need to be exceptionally careful, | ||
131 | 07:32 | and we need to test safety in the most rigorous ways possible. | ||
132 | 07:37 | The reason I'm here today is because for the first time 20 years, | ||
133 | 07:41 | we got it to work, | ||
134 | 07:43 | and this is the first time I'm sharing it publicly. | ||
135 | 07:47 | (Applause and cheers) | ||
136 | 07:56 | Last two times I did this I cried, so -- | ||
137 | 07:58 | (Laughter) | ||
138 | 08:01 | So in order to help you understand this breakthrough, | ||
139 | 08:05 | let me take you back 20 years to 1999. | ||
140 | 08:10 | I was a graduate student in Berkeley, California, | ||
141 | 08:13 | studying the biophysics of HIV. | ||
142 | 08:15 | For such a complex epidemic, | ||
143 | 08:17 | the simplicity of this virus fascinated me. | ||
144 | 08:22 | HIV, like all viruses, is just an instruction set -- | ||
145 | 08:26 | malware. | ||
146 | 08:27 | It hijacks a cell and converts that cell into a factory to do one thing: | ||
147 | 08:32 | single-mindedly churn out more virus. | ||
148 | 08:35 | All the normal functions of the cell get wiped away. | ||
149 | 08:38 | HIV infects the white blood cell that keeps us healthy. | ||
150 | 08:41 | This cell has already been hijacked and converted into a factory. | ||
151 | 08:46 | And if we magnify, | ||
152 | 08:48 | we can see the anatomy of the virus. | ||
153 | 08:50 | Those squiggly red lines in the middle? | ||
154 | 08:53 | That's HIV's instruction set. | ||
155 | 08:55 | Its genetic material. | ||
156 | 08:58 | This genetic material directs the hijacking process, | ||
157 | 09:02 | converting that cell into a factory first | ||
158 | 09:05 | to make more copies of the instruction set, | ||
159 | 09:09 | and then all the other components of the virus | ||
160 | 09:11 | and assemble them into a particle. | ||
161 | 09:15 | This is how the virus replicates. | ||
162 | 09:19 | Each of these particles can go in and hijack a new cell. | ||
163 | 09:24 | This is how the virus transmits. | ||
164 | 09:26 | And every time a cell is hijacked, | ||
165 | 09:29 | little mistakes are made in copying the genetic material. | ||
166 | 09:33 | That's how the virus mutates. | ||
167 | 09:36 | This ability to replicate, transmit and mutate | ||
168 | 09:39 | is something that our current drugs cannot do. | ||
169 | 09:43 | So, being young and naïve and a little bit ignorant, | ||
170 | 09:47 | I thought: | ||
171 | 09:49 | why can't we create therapies that mutate and transmit and replicate? | ||
172 | 09:57 | Here was the idea. | ||
173 | 09:59 | If we can take the virus | ||
174 | 10:02 | and engineer it to amputate the genetic material in blue here, | ||
175 | 10:06 | this amputated instruction set can no longer hijack a cell. | ||
176 | 10:11 | But this amputated instruction set can do something very special. | ||
177 | 10:16 | In an already infected cell, | ||
178 | 10:18 | this amputated instruction set can hijack the hijacker. | ||
179 | 10:23 | It can commandeer HIV's machinery to make more copies of itself, | ||
180 | 10:29 | the amputated instruction set, | ||
181 | 10:31 | and then each of these copies can steal all of HIV's other components | ||
182 | 10:36 | so that the cell gets converted from a factory that produces virus | ||
183 | 10:41 | to a factory that produces therapy. | ||
184 | 10:44 | Hijackers. | ||
185 | 10:46 | These carry no disease. | ||
186 | 10:48 | This dramatically lowers HIV levels | ||
187 | 10:51 | and keeps the cell healthier. | ||
188 | 10:55 | This idea consumed me for months. | ||
189 | 10:58 | It was the most intense intellectual experience of my life. | ||
190 | 11:03 | On every bike ride to lab, | ||
191 | 11:06 | on every walk to the coffee shop, | ||
192 | 11:09 | on every run in the hills above campus, | ||
193 | 11:11 | the ideas, the arguments, | ||
194 | 11:13 | the counterarguments, | ||
195 | 11:15 | they all came so rapidly in my head, in my inner monologue, | ||
196 | 11:18 | that I was physically out of breath. | ||
197 | 11:20 | I thought if we can create a therapy that replicates, | ||
198 | 11:24 | it would only need to be taken once. | ||
199 | 11:27 | It could mutate along with the virus | ||
200 | 11:30 | and possibly it could transmit between infected individuals | ||
201 | 11:34 | to treat them. | ||
202 | 11:36 | It was a therapy that could do all of the things that the virus could do. | ||
203 | 11:41 | It solved the fundamental mismatch. | ||
204 | 11:46 | The most radical part of this concept | ||
205 | 11:49 | was that the super-spreaders would also be converted | ||
206 | 11:52 | from transmitting the virus to now transmitting the therapy. | ||
207 | 11:58 | It was a therapy that would go viral along with the virus. | ||
208 | 12:04 | This scared some people. | ||
209 | 12:06 | But there's already a precedent: | ||
210 | 12:09 | we already inadvertently use therapies that transmit. | ||
211 | 12:14 | The vaccine that eradicated polio in the US, | ||
212 | 12:17 | the oral polio vaccine, | ||
213 | 12:20 | transmits between people. | ||
214 | 12:23 | It's not well-known, | ||
215 | 12:24 | but the fact that this vaccine transmits | ||
216 | 12:27 | is part of the reason that it was chosen for the worldwide eradication effort | ||
217 | 12:32 | despite its safety issues. | ||
218 | 12:36 | So the bigger problem was that these hijacker therapies didn't exist. | ||
219 | 12:42 | My Berkeley advisors said to me, | ||
220 | 12:45 | "Lovely idea, so sad it will never work," | ||
221 | 12:49 | or, "Regulators will never allow it, | ||
222 | 12:51 | drop it." | ||
223 | 12:54 | But the idea wouldn't drop me. | ||
224 | 12:59 | If it ever worked, | ||
225 | 13:01 | it would solve the fundamental mismatch. | ||
226 | 13:04 | So we tried for years to build it. | ||
227 | 13:07 | We tried every trick in the book | ||
228 | 13:10 | and failed over and over again. | ||
229 | 13:13 | We -- | ||
230 | 13:15 | every time we thought we had a good idea, | ||
231 | 13:17 | we'd spend months, sometimes years working on it | ||
232 | 13:21 | only to come up empty. | ||
233 | 13:24 | We once spent five years | ||
234 | 13:28 | building 150,000 versions of a hijacker therapy. | ||
235 | 13:33 | Every single one failed. | ||
236 | 13:37 | I once asked a really bright student what he hoped to learn from me | ||
237 | 13:40 | during his PhD -- | ||
238 | 13:42 | (Laughter) | ||
239 | 13:44 | And he replied, | ||
240 | 13:46 | "How to keep going, | ||
241 | 13:48 | how to continue moving forward | ||
242 | 13:50 | despite zero evidence that there's anything there." | ||
243 | 13:53 | (Laughter) | ||
244 | 13:56 | I wonder if he was trying to tell me something. | ||
245 | 13:58 | (Laughter) | ||
246 | 14:01 | By 2018, things looked bad. | ||
247 | 14:06 | There was no evidence | ||
248 | 14:08 | that a hijacker therapy could be engineered. | ||
249 | 14:10 | In fact, we had evidence that it might be impossible. | ||
250 | 14:15 | It was time to face the hard truth. | ||
251 | 14:18 | This solution that I'd wanted so badly, | ||
252 | 14:20 | this hijacker therapy just didn't exist. | ||
253 | 14:26 | For 20 years, | ||
254 | 14:27 | I had been chasing a ghost. | ||
255 | 14:32 | Then one day, | ||
256 | 14:35 | Elizabeth, a postdoc in my lab, | ||
257 | 14:37 | came to me with this picture. | ||
258 | 14:40 | It doesn't look like much. | ||
259 | 14:42 | My wife thinks it looks like a pregnancy test. | ||
260 | 14:45 | (Laughter) | ||
261 | 14:47 | But this little band down here -- | ||
262 | 14:51 | that was the amputated genetic material | ||
263 | 14:54 | that we had been looking for for 20 years. | ||
264 | 14:56 | The entire time that we had been trying to build it and failing, | ||
265 | 15:01 | it had evolved by itself in a flask in the back of the lab. | ||
266 | 15:04 | (Audience) What? | ||
267 | 15:05 | (Laughter) | ||
268 | 15:07 | We finally had a foothold. | ||
269 | 15:08 | And we used this to build the first hijacker. | ||
270 | 15:13 | But we had no evidence that what we built was a therapy. | ||
271 | 15:18 | The first hurdle that any therapy has to clear is testing in a mouse. | ||
272 | 15:22 | It can be risky. | ||
273 | 15:24 | In our case, if our mice died, | ||
274 | 15:27 | so did our funding, | ||
275 | 15:29 | and with it, any hopes of this becoming a therapy, | ||
276 | 15:32 | let alone a transformative one. | ||
277 | 15:36 | After so many failures, | ||
278 | 15:37 | we were all pretty skeptical but we didn't really have an alternative. | ||
279 | 15:42 | We had to give it a shot; we had to try. | ||
280 | 15:46 | Amazingly, the hijacker therapy worked in a mouse, | ||
281 | 15:52 | and it worked exactly as we'd predicted 20 years before. | ||
282 | 15:56 | It protected the cells in a mouse from HIV. | ||
283 | 15:59 | Here are the cells under a microscope. | ||
284 | 16:01 | First, HIV in red infects those cells, | ||
285 | 16:05 | and then the hijacker, in blue, can be activated, | ||
286 | 16:09 | protects those cells and transmits to other cells. | ||
287 | 16:14 | We'd finally built the hijacker after 20 years. | ||
288 | 16:18 | Everyone in the lab was elated. | ||
289 | 16:21 | For me, this was proof of concept. | ||
290 | 16:25 | If we could do it for one virus we could do it for others. | ||
291 | 16:30 | To understand how this hijacker might impact HIV levels worldwide, | ||
292 | 16:35 | we ran computer simulations. | ||
293 | 16:37 | Epidemiological models. | ||
294 | 16:39 | And the results were pretty amazing. | ||
295 | 16:43 | If we do nothing in the hardest-hit parts of Africa, | ||
296 | 16:46 | HIV prevalence will stay between 25 and 30 percent. | ||
297 | 16:52 | If we manage to introduce drugs to three-quarters of the population | ||
298 | 16:56 | or if we ever get the long-sought-after vaccine, | ||
299 | 17:00 | we would reduce those numbers down to 20 percent. | ||
300 | 17:04 | But those are best-case scenarios. | ||
301 | 17:07 | If HIV evolves resistance | ||
302 | 17:10 | or if people change their behaviors, | ||
303 | 17:12 | these numbers could go right back up to 30 percent | ||
304 | 17:15 | or even beyond. | ||
305 | 17:17 | The blue is the hijacker therapy. | ||
306 | 17:22 | And we've not found a way, | ||
307 | 17:24 | either theoretically or experimentally, | ||
308 | 17:27 | that HIV can evolve resistance to the hijacker. | ||
309 | 17:32 | The reason this hijacker works so well is the super-spreaders. | ||
310 | 17:37 | If the hijacker is introduced in one place over here, | ||
311 | 17:42 | the super-spreaders can pick it up and transmit it through the population. | ||
312 | 17:51 | Imagine if 10 years from now, HIV is no longer a pandemic. | ||
313 | 17:57 | To get there, | ||
314 | 17:58 | we have to start large-scale clinical trials in five years, | ||
315 | 18:02 | which means initial human tests next year. | ||
316 | 18:06 | The FDA has cleared us to start testing in HIV-positive patients | ||
317 | 18:11 | who have a terminal cancer | ||
318 | 18:14 | and have less than a year left to live. | ||
319 | 18:20 | Volunteering for this trial | ||
320 | 18:21 | is their last incredibly generous gift to the world. | ||
321 | 18:25 | They're called the "Last Gift cohort." | ||
322 | 18:27 | And to test in these altruistic patients next year, | ||
323 | 18:32 | we have to finish our preclinical tests this year ... | ||
324 | 18:36 | and I think we will. | ||
325 | 18:38 | I still meet colleagues who push back | ||
326 | 18:40 | and are stridently opposed to letting us move forward with testing. | ||
327 | 18:44 | They say, "What if something goes wrong? | ||
328 | 18:47 | You can't unrelease it." | ||
329 | 18:50 | They say, "There are ethical issues; | ||
330 | 18:52 | people can't consent." | ||
331 | 18:55 | Well, oral polio vaccine faced similar ethical and safety concerns. | ||
332 | 18:59 | In fact, oral polio vaccine faced such an effective misinformation campaign | ||
333 | 19:04 | that most people still don't know that it transmits, | ||
334 | 19:07 | that it successfully eradicated polio in many countries | ||
335 | 19:10 | or that this vaccine is the basis for new vaccines. | ||
336 | 19:15 | When we presented this hijacker therapy idea in Africa last year, | ||
337 | 19:20 | the African scientists had a different response. | ||
338 | 19:25 | They said, "How can you not test this?" | ||
339 | 19:28 | They said it's unethical to not test it. | ||
340 | 19:32 | So even though we might fail, | ||
341 | 19:35 | I think the stakes are too high not to try. | ||
342 | 19:38 | If we do nothing, | ||
343 | 19:40 | those girls outside of Durban will acquire HIV, | ||
344 | 19:43 | and the next time that there's a new virus that emerges, | ||
345 | 19:48 | we'll be in the same vulnerable position that we are today | ||
346 | 19:53 | with quarantines that are porous | ||
347 | 19:57 | and vaccines that we need to wait months for that may not match. | ||
348 | 20:04 | I think it's time for a new approach | ||
349 | 20:06 | that's different than the static approaches of the last century. | ||
350 | 20:11 | It's time for a new technology that is less reactive | ||
351 | 20:14 | and more proactive. | ||
352 | 20:16 | I think it's time for treatments | ||
353 | 20:18 | that don't just benefit the most affluent among us | ||
354 | 20:22 | but also those who face the greatest adversity. | ||
355 | 20:30 | I think it's time for a new type of weapon | ||
356 | 20:33 | that matches, | ||
357 | 20:35 | or that solves the fundamental mismatch. | ||
358 | 20:38 | I think it's time for therapies that can go viral. | ||
359 | 20:40 | Thank you very much. | ||
360 | 20:42 | (Applause) |