The Genetic Revolution Part 1 — Transcript

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1. 0:02the genetic revolution
2. 0:05from traditional genetics
3. 0:09to synthetic biology
4. 0:14this lecture is general overview
5. 0:18with the purpose to look on the trends
6. 0:22of genetics
7. 0:26the big picture of genetics
8. 0:30here i want you to be
9. 0:34aware of the mainstream in genetics
10. 0:39but also i'm going to take you to some
11. 0:43different directions
12. 0:47we will start to discuss some basic
13. 0:50genetic stuff that
14. 0:54we know since the mendelian genetics was
15. 0:58rediscovered
16. 0:59over a century or so
17. 1:04but we will also talk about genetics
18. 1:08that we had
19. 1:09earlier pre-mendelian
20. 1:14and later i will extrapolate
21. 1:18the genetic information towards some
22. 1:21interesting maybe even speculative
23. 1:26stuff so
24. 1:30let's zoom out to see the big
25. 1:33picture whenever parker was born
26. 1:38in 1890
27. 1:41the world was very different
28. 1:46anna parker was born before mendel's
29. 1:49laws were
30. 1:52rediscovered before
31. 1:54we add the clue about the rules of
32. 1:58genetics
33. 2:00she has died in 2008
34. 2:04the year in which an artificial cell
35. 2:06technology
36. 2:08was invented and the
37. 2:12genome of the neanderthals was
38. 2:15sequenced so our course
39. 2:20will cover the genetic revolution
40. 2:24which took place during the lifetime
41. 2:28of one person
42. 2:33from mental theory up to the recent
43. 2:38breakthroughs in genetic engineering
44. 2:42and post genomics
45. 2:46we will discuss the application of the
46. 2:49genetic
47. 2:50revolution on many aspects of our life
48. 2:54including medical
49. 2:58and ethical issues
50. 3:03we live in a remarkable time
51. 3:07genetic methods which were developed
52. 3:09recently
53. 3:11are making what was considered as
54. 3:15impossible few years ago
55. 3:18to be possible
56. 3:22and just to illustrate this
57. 3:25certain portions of science fiction
58. 3:28movies
59. 3:29from 30 years ago
60. 3:34are becoming a reality just
61. 3:38in front of our eyes
62. 3:46what if we lived in the world of star
63. 3:48trek voyager
64. 3:50talk about an easy computer
65. 3:53access bolonna torres medical file
66. 3:56lieutenant taurus is 50
67. 3:57human and 50 klingon project a
68. 4:00holographic image of the baby
69. 4:02she's also a hundred percent pregnant
70. 4:06now extrapolate what the child's facial
71. 4:08features will look like
72. 4:10at 12 years old like any caring parent
73. 4:13she doesn't want her unborn child to be
74. 4:15teased for having a forehead that looks
75. 4:17like
76. 4:18well like a tired tread display the
77. 4:21fetus gina
78. 4:22but here's the twist delete the
79. 4:24following gene sequences she can do
80. 4:26something about it
81. 4:28extrapolate what the child would look
82. 4:29like with those genetic changes
83. 4:34she threw in some blonde hair too
84. 4:39and is this the limit or could we go
85. 4:41even further
86. 4:42save changes
87. 4:49so the star trek movies
88. 4:52from the 80s we're
89. 4:56trying to suggest several things that
90. 5:00at that time was totally
91. 5:03not possible
92. 5:07but today we can do several
93. 5:10things that were mentioned in this movie
94. 5:14by the genomic information that we have
95. 5:17today
96. 5:20for example we can use dna to predict
97. 5:24some cosmetic traits
98. 5:27such color of the eyes skin
99. 5:31and air here
100. 5:34you can see an article where the
101. 5:38scientists
102. 5:39took the image of the face of a person
103. 5:44they sequence the genome of that person
104. 5:49and then use the information
105. 5:52of the genome of the person
106. 5:55in order to reconstruct
107. 5:58cosmetic traits the face
108. 6:01structure of that person
109. 6:06as you can see here well it's possible
110. 6:10this is the real face of the person
111. 6:15this is the predicted face of this
112. 6:19person
113. 6:20based on genetic information
114. 6:23here you can see two other examples
115. 6:27that are doing the same thing the real
116. 6:29face
117. 6:31versus the predicted phase
118. 6:36so yes you can
119. 6:40use the genome sequence information
120. 6:44in order to predict
121. 6:47how people are going to look like
122. 6:54and there is something else that was
123. 6:57mentioned
124. 6:58in this movie well the mother
125. 7:03is able to make changes
126. 7:06to the genome of the fetus
127. 7:10is it possible to do so the answer is
128. 7:14yes
129. 7:16now you can actually customize your baby
130. 7:20in many ways
131. 7:22originally the technology was developed
132. 7:27for
133. 7:27health related reasons to prevent
134. 7:30genetic diseases
135. 7:33but soon after it became
136. 7:37a major tool for non-medical
137. 7:40trait for example
138. 7:43customizing gender to keep the embryos
139. 7:48which are male
140. 7:49or females according to the preference
141. 7:52of
142. 7:52the parents and not the other gender
143. 7:56that the parents don't want
144. 8:00technologically we are well positioned
145. 8:03to customize babies for any non-medical
146. 8:06trait you have in mind
147. 8:08as long you know what is the basic
148. 8:11genetics behind the trait
149. 8:15so how you can edit the genome
150. 8:19of an individual
151. 8:22today we have a system called crispr
152. 8:26cas9 which can add
153. 8:29the dna now the question is what type of
154. 8:34cells you are using
155. 8:37if you are using skin cells and changing
156. 8:41the genetic makeup that's one thing
157. 8:46it's not going to influence the
158. 8:48following generations
159. 8:51but today we are looking also
160. 8:56in some options to do
161. 8:59germline gene editing
162. 9:03well in general it's considered
163. 9:06unethical when it comes to human being
164. 9:10we can do it on animals but not on human
165. 9:13being
166. 9:15but you can say that scientists
167. 9:18are trying to get around this to some
168. 9:20level
169. 9:22here for example the scientists
170. 9:26are manipulating a zygote which is a
171. 9:30very
172. 9:30early embryonic development
173. 9:34after the union between the sperm
174. 9:37and the egg but here
175. 9:40they were using defective zygote
176. 9:44so it's not going to stay
177. 9:47after the experiment and it's not going
178. 9:51to result
179. 9:52in a human which happened
180. 9:56to have some gene editing
181. 9:59in all the cells including sperm
182. 10:02and eggs which means that the mutation
183. 10:05is going to
184. 10:06be around for the following generations
185. 10:10as well so
186. 10:13gene editing of germline
187. 10:17is considered to be unethical
188. 10:21however the ethical rules can be
189. 10:24different
190. 10:25in one place versus another
191. 10:29and a few years ago in china
192. 10:33a scientist was able to
193. 10:36manipulate the genome
194. 10:40in all cells including germ cells
195. 10:43of two babies
196. 10:47well it was considered an unethical
197. 10:50in china and the scientists have lost
198. 10:54his job
199. 10:55but yes it is possible to do gene
200. 10:58editing
201. 11:00on zygotes mean germline mutations
202. 11:04and technically it can be done
203. 11:08in people from a
204. 11:11perspective of a fan of star trek movies
205. 11:16the science fiction episode presented
206. 11:19earlier
207. 11:20from the 80s is today's
208. 11:23reality the future
209. 11:28is now or
210. 11:32maybe we should put a question mark why
211. 11:35because we know that we still do not
212. 11:38know a lot of things
213. 11:40we are very far from the end
214. 11:43for example we know that we do not know
215. 11:46anything about
216. 11:47over 90 percent of the organisms on our
217. 11:51planet
218. 11:53here you can see a bunch of organisms
219. 11:56that were found in the bottom of the
220. 11:58ocean
221. 12:00surprisingly they have a very rich life
222. 12:03over there and you can find
223. 12:07different type of animals and a lot of
224. 12:10microorganisms there
225. 12:13so yes there are a lot of
226. 12:17life that we don't know about on our
227. 12:21planet
228. 12:23we are expecting in some cases
229. 12:27that the finding of new organisms
230. 12:29especially in extreme conditions
231. 12:33will expand to some level the existing
232. 12:36principles
233. 12:37of genetics
234. 12:40however so far all the organisms that we
235. 12:45found
236. 12:46are using dna as their genetic material
237. 12:50which is expressed to rna which is
238. 12:52translated to proteins
239. 12:55so we do not have a surprise
240. 13:00so far in the new organisms
241. 13:03that were found in the last 20 years
242. 13:06also
243. 13:08but from time to time we can see some
244. 13:12surprises for example when we discovered
245. 13:16retroviruses
246. 13:17during the 70s we found that there is a
247. 13:21virus
248. 13:22that is not working according to the
249. 13:24central dogma
250. 13:27the genetic material rna
251. 13:31is transcribed back
252. 13:34to dna that was very different from the
253. 13:38central dogma
254. 13:40that suggested that dna
255. 13:43can be made into rna but
256. 13:46not the other way around
257. 13:50and the other surprises that we had
258. 13:53in 2012 a group of scientists
259. 13:56reported that they found the bacteria
260. 14:01that can replace to some extent
261. 14:04the phosphate in its dna and other
262. 14:07molecules
263. 14:08with alcenate so
264. 14:13even the exact structure of the dna
265. 14:16can still be challenged later on
266. 14:20i will show you that in the lab you can
267. 14:22make the dna
268. 14:24which is quite different from the
269. 14:27dna that we have in nature and it's
270. 14:30still going to work
271. 14:32at least in the lab so
272. 14:35can we say that the future of genetics
273. 14:39is
274. 14:40now well i would say
275. 14:43that the future of genetics is
276. 14:46still down the road
277. 14:50we do not have a crystal ball to make
278. 14:54an educated predictions about the future
279. 14:57trends of genetics
280. 14:59for example we cannot predict evolution
281. 15:05but every time we reach into a major
282. 15:07milestone
283. 15:09in genetics we think
284. 15:12we cannot get much farther
285. 15:15so time magazine suggested in
286. 15:191994 that the future of genetics
287. 15:22is now in some ways that they were
288. 15:26correct
289. 15:27because at that time we had
290. 15:30a lot of progress in genetic engineering
291. 15:35however in many other ways they were
292. 15:39too early today
293. 15:42the star trek movie
294. 15:45is our reality in many ways
295. 15:50and there is still a long way
296. 15:54we can go
297. 15:57but before going further let's go back
298. 16:01to the big picture
299. 16:04and here i want to
300. 16:08let you in a virtual time machine
301. 16:13and to zoom in to the genetics
302. 16:17before mendel
303. 16:22mendel deserve huge credit
304. 16:26for the mathematical statistical model
305. 16:31of genetics however
306. 16:35since the beginning of human history
307. 16:39people have wondered how traitor
308. 16:42inherited
309. 16:43from one generation to the next
310. 16:48children look like their parents and
311. 16:52siblings
312. 16:54domestic plants and animals
313. 16:59are bred for useful traits by controlled
314. 17:02matings
315. 17:06we are doing control meetings
316. 17:10probably since we became an agricultural
317. 17:14society like 10 000
318. 17:17years ago mandel outlined the rules
319. 17:21and published them but it is very likely
320. 17:27it was not the first one to use what we
321. 17:30call
322. 17:30today mendelian genetics
323. 17:34actually it seems like that
324. 17:38the first documented genetic experiment
325. 17:42can be found in the bible
326. 17:46in genesis
327. 17:50like 4 000 years ago
328. 17:57the holy bible is a religious
329. 18:01book respected by major
330. 18:04religions but
331. 18:07we can find there a lot of
332. 18:10interesting stories and information
333. 18:16you can retrieve from the bible
334. 18:20information about your history
335. 18:25you can have from the bible information
336. 18:29related to archaeology
337. 18:32which can confirm the bible
338. 18:36in some cases
339. 18:39the bible is actually a psychology
340. 18:43textbook
341. 18:45relationship between people
342. 18:49but you can also retrieve from the bible
343. 18:54some genetic information
344. 18:59first by looking
345. 19:03at an amazing 4 000
346. 19:06years old family tree
347. 19:10of people that directly or indirectly
348. 19:14are related to all of us
349. 19:18and second you can find in genesis
350. 19:23chapter 30 a
351. 19:26genetic experiment which took place
352. 19:30four thousand years ago
353. 19:34interestingly the name of the first book
354. 19:37of the bible
355. 19:39genesis is quite similar
356. 19:42to the words genes and
357. 19:45genetics
358. 19:49so let me take you to
359. 19:54the life of jacob
360. 19:59jacob was a
361. 20:02young shepherd he was
362. 20:06working for his father-in-law
363. 20:10and then he got into a trouble
364. 20:15that made him to come with a very
365. 20:18interesting
366. 20:20genetic experiment
367. 20:25well i mean think about jacob young
368. 20:28person
369. 20:30he was a shepherd have a lot of time
370. 20:34in his hand well no cell phone at that
371. 20:37time no internet
372. 20:39all he had is just himself and
373. 20:42the ghosts he probably asked themselves
374. 20:48where the color of the gold is coming
375. 20:51from
376. 20:54so we started to learn the pedigree
377. 20:58of the goats and came with an
378. 21:01interesting conclusion
379. 21:03which he applied later on
380. 21:10so let me take you to my translation
381. 21:15of part of chapter 13
382. 21:18in genesis and my interpretation
383. 21:22here in green based on the scientific
384. 21:27knowledge that we have today
385. 21:31now after the birth of joseph
386. 21:35jacob said to lavon his father-in-law
387. 21:38let me go away to my place in my country
388. 21:43levanan said do not go away
389. 21:46say what you want as a payment
390. 21:50and i will give it to you
391. 21:53gekko basketlavan let me go
392. 21:57through all your flock today
393. 22:00taking out among them
394. 22:03all the shapes and gold with
395. 22:06pattern speckled
396. 22:10and spotted those will be
397. 22:13my salary the white and black without
398. 22:17pattern are the majority of the goats
399. 22:21in a regular health today we know
400. 22:26that white or black without pattern
401. 22:30are dominant to white or black
402. 22:34with pattern
403. 22:38so jacob asked for the recessive
404. 22:41phenotype
405. 22:43shapes and gold with pattern
406. 22:48well today we know quite a lot about the
407. 22:52genetics of goat
408. 22:55white is dominant to white with pattern
409. 22:58black is dominant to black with pattern
410. 23:02that's what we know from quite a lot of
411. 23:05studies
412. 23:06that were published for quite a few
413. 23:09years
414. 23:12so the genetics of color in goat
415. 23:17well i mean it is quite complicated
416. 23:20because it consists of several alleles
417. 23:23for
418. 23:24coloring goats i mean initially when i
419. 23:27looked on the
420. 23:29real genetics i told myself it's going
421. 23:32to be quite complicated to come with any
422. 23:34clear conclusion over here
423. 23:37but check of agreement made the genetic
424. 23:40analysis
425. 23:41to be quite simple
426. 23:45jacob grouped the recessive
427. 23:49together has requested
428. 23:52all the gold with pattern for himself
429. 23:57and the other group the dominant without
430. 24:00the pattern
431. 24:01is going to be kept by levan
432. 24:05so is agreement separated
433. 24:08between the dominant and the recessive
434. 24:12so here the experiment is easy
435. 24:17there is a recessive group and there is
436. 24:20a dominant group
437. 24:23and now let's say what was the
438. 24:27complication
439. 24:28that led jacob
440. 24:32to do a real genetic experiment
441. 24:36well lavana grit let's it be as you say
442. 24:41you're going to have the recessive
443. 24:43traits i'm going to keep the dominant
444. 24:45traits
445. 24:47and if that was the case if levan was
446. 24:50honest we had no genetic experiment
447. 24:54there
448. 24:54at all but levano was quite tricky
449. 24:59immediately afterwards he took all the
450. 25:02goats and ships
451. 25:03with the pattern all the recessive
452. 25:06gave them into the care of his sons
453. 25:11and they took the recessive goat
454. 25:14three days journey away so
455. 25:18yeah lavan was quite a tricky guy
456. 25:24and jacob was left with the rest of
457. 25:27lavan flock
458. 25:30fin julia there is the dominant color
459. 25:33phenotype
460. 25:34means that you have the goat
461. 25:37with no pattern
462. 25:41so jacob had
463. 25:44the dominant trait
464. 25:48he tried to induce the goat
465. 25:52to become sexually active
466. 25:55when jacob took the young branches of
467. 25:58trees
468. 25:59cutting off their skin so
469. 26:02that the white wood was seen
470. 26:06in a in bands
471. 26:09he put the banded sticks
472. 26:12in the drinking water of the flock
473. 26:16the goat and shapes were drinking from
474. 26:19the water
475. 26:21and became sexually active
476. 26:25now here jacob did
477. 26:28two things the first things
478. 26:32he made they go to become
479. 26:35sexually active so they're going to have
480. 26:38more kids
481. 26:39and well according to his understanding
482. 26:43is going to get recessive traits as well
483. 26:47they go tweet pattern certain level
484. 26:53how you can make the goal to become
485. 26:55sexually active
486. 26:57if you're making an extract of certain
487. 26:59plants
488. 27:01you can have some chemicals that
489. 27:04can induce sexual activity in those
490. 27:07animals
491. 27:09we have something that called
492. 27:12horny goat weed
493. 27:16means that if you're giving the goat to
494. 27:18eat a certain weed
495. 27:20they're going to become sexually active
496. 27:24and actually we even know from other
497. 27:26scientific paper
498. 27:28that you can induce sexual activity in
499. 27:31goats
500. 27:32by melatonin which is
501. 27:35made in plants as well
502. 27:40so they goat and ships
503. 27:45were drinking from the water they became
504. 27:48sexually active
505. 27:49and as a result of this later on
506. 27:53the floor gave birth to many goats with
507. 27:56pattern
508. 27:59the recessive trait is back
509. 28:03in just one generation that's really
510. 28:06interesting that's actually
511. 28:09a result of
512. 28:12clear understanding in
513. 28:15genetics mendelian genetics the
514. 28:18recessive trait
515. 28:20is back in just one generation
516. 28:26that's actually not something which is
517. 28:29happening
518. 28:30very easily jacob
519. 28:33must have some genetic information
520. 28:37in order to reach to this level
521. 28:40of transition from dominant
522. 28:44trait to recessive trait now one way
523. 28:49to do this is
524. 28:52by making between heterozygotes
525. 28:56heterozygotes have the dominant traits
526. 28:59but when you have mating between
527. 29:02heterozygotes
528. 29:04you're likely to have some recessive
529. 29:07traits as well
530. 29:10now jacob did another thing which is
531. 29:13quite important
532. 29:15it's separated between the
533. 29:18ships and gold which add the
534. 29:22pattern the recessive shape and gold
535. 29:25trades from the white elements
536. 29:29so that's something that if you are
537. 29:32a geneticist you know if you want to
538. 29:35keep the recessive trait
539. 29:37don't keep the excessive traits together
540. 29:40with the dominant
541. 29:42because the recessive trait is going to
542. 29:44disappear
543. 29:45in the following generation so
544. 29:48what he tried to do it's not to
545. 29:50contaminate the recessive
546. 29:52with dominant alleles again
547. 29:55classical genetics experiment
548. 30:00so jacob wealth was greatly increased
549. 30:04much larger than the one that lavan had
550. 30:10as the biblical story jacob was able to
551. 30:14switch
552. 30:14a dominant phenotype into
553. 30:18a recessive phenotype
554. 30:22that's really the conclusion
555. 30:25that we can get from all the different
556. 30:28things that happen there
557. 30:31the only way to do it is by control
558. 30:35meetings
559. 30:35between heterozygotes a big question
560. 30:39is how jacob was able
561. 30:42to recognize the heterozygotes
562. 30:46well the heterozygotes are dominant
563. 30:50they look dominant for the trait that
564. 30:53they are heterozygotes
565. 30:56in other words when you have a
566. 30:59heterozygote sometimes
567. 31:02you're going to have a unique traits
568. 31:05which are linked to the heterozygotes
569. 31:07and you don't find them
570. 31:09in any of the homozygotes
571. 31:12you can find it in many traits sickle
572. 31:15cell disease is a recessive trait
573. 31:18if both genes are mutated you are very
574. 31:22sick
575. 31:24but if your retro zygote for the mutated
576. 31:28gene
577. 31:29you're immune against malawian infection
578. 31:32and
579. 31:33you're going to be in a better fitness
580. 31:37as compared to the homozygote normal
581. 31:41when it comes to malawia infection
582. 31:44that's a major fitness factor
583. 31:47if you live in such an environment with
584. 31:51the spouses
585. 31:54so you can see several things
586. 31:59related to heterozygotes
587. 32:02heterozygote in some situation
588. 32:06can have certain phenotype
589. 32:10that can identify them as heterozygote
590. 32:14gecko was a shepherd of this ad
591. 32:18for 14 years by that time
592. 32:21he had the time to do his own
593. 32:24observations
594. 32:26maybe found a unique phenotype
595. 32:29of detrozygots and this unique phenotype
596. 32:34of this heterozygote
597. 32:35can be that those heterozygotes
598. 32:39can be more reducible to have sexual
599. 32:43activity
600. 32:44means that the heterozygote goats have
601. 32:48a higher sexual drive and
602. 32:51if you are giving them those in your
603. 32:53cells
604. 32:54from certain plants maybe they're the
605. 32:57first one
606. 32:59to have sexual activity
607. 33:02so we may speculate the first group to
608. 33:06have sexual activity of heterozygous
609. 33:09and here you're going to find quite a
610. 33:12lot of
611. 33:13recessive trait which is coming
612. 33:17from heterozygote matings
613. 33:21so it is possible that that's
614. 33:25actually the case that heterozygote
615. 33:28have higher sexual drive and if you're
616. 33:32inducing
617. 33:33the animals with those type of
618. 33:36extract from plant you are going
619. 33:40to have first the heterozygotes
620. 33:43to have sexual activity
621. 33:47and when heterozygote have sexual
622. 33:49activity
623. 33:50you are going to come with homozygous
624. 33:54recessive
625. 33:55where the homozygous recessive alleles
626. 33:58are going to come from mother and
627. 34:02father so they
628. 34:06respond to the goat and ships to
629. 34:08chemicals
630. 34:09made by certain trees which jacob put in
631. 34:13the drinking water
632. 34:14which mainly use early mating in
633. 34:17heterozygote in the flock
634. 34:20it's possible we don't know we don't
635. 34:23know
636. 34:24because jacob didn't publish his
637. 34:27experiment
638. 34:28in science or nature he
639. 34:32published is experiments
640. 34:35in the bible after like 2000 years that
641. 34:39the story was moving
642. 34:41from one generation to another
643. 34:46as a story as an interesting story
644. 34:50taking out all the question mark that
645. 34:53you have here
646. 34:55you can say that gecko probably did
647. 34:59a mendelian genetic experiment
648. 35:02mendel was able to show us
649. 35:07that it can bring back the recessive
650. 35:10trait from
651. 35:14a dominant trait heterozygote
652. 35:20and that's something that jacob knew as
653. 35:23well
654. 35:24at least from practical point of view
655. 35:28think about young jacob during the first
656. 35:31year
657. 35:32of being shepherd he
658. 35:36realized that there is some occurs focus
659. 35:39in nature
660. 35:40some sort of invisible hybrids
661. 35:43with the dominant white color
662. 35:47and mating between those hybrid
663. 35:51can bring back the recessive pattern
664. 35:55eventually overall jacob was able to
665. 35:58select the recessive threat well
666. 36:02about the naturally expected ratio
667. 36:06in the original head his recessive trait
668. 36:10had
669. 36:11was louder than lavon's dominant head
670. 36:14he got a lot of trouble because of this
671. 36:19he can do it only
672. 36:22by applying somehow
673. 36:25classical mendelian
674. 36:28genetics so
675. 36:32why i told you this long story about
676. 36:35jacob
677. 36:37because it's very likely that jacob was
678. 36:40not the only person
679. 36:43that was able to figure out mendelian
680. 36:46genetics
681. 36:47where before mendel people
682. 36:51in those old days thousand years ago
683. 36:56were able to develop different type of
684. 36:59strands of
685. 37:00animals for their needs that's probably
686. 37:03[Music]
687. 37:05what we had quite a lot
688. 37:08during the pre-medallion time
689. 37:12mender explained this in scientific way
690. 37:17mendel gave us the mathematical model
691. 37:21to explain genetics
692. 37:25but practical mendelian genetics
693. 37:28was used well before
694. 37:33mendel