With an extraordinary new technology called CRISPR, we can now edit DNA—including human DNA. But how far should we go? Gene editing promises to eliminate certain genetic disorders like sickle cell disease. But the applications quickly raise ethical questions. Is it wrong to engineer soldiers to feel no pain, or to resurrect an extinct species? And is there harm in allowing parents to choose their child’s features, like eye color or height? The scientists who pioneered human genome studies and CRISPR grapple with these questions. (Premiered September 9, 2020)
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Airdate: September 9, 2020
VOICEOVER: Mother Nature gave us something that is richer than our imagination.
FRANCISCO MOJICA (Microbiologist, University of Alicante): We saw a very peculiar pattern.
JILL BANFIELD (Microbiologist, University of California, Berkeley): Never seen anything like this before.
ONSCREEN: The story of the most important scientific discovery of the 21stcentury.
ANTONIO REGALADO (Reporter, MIT Technology Review): I remember him saying, “Remember this word: CRISPR.”
JENNIFER DOUDNA (Biochemist, University of California, Berkeley): We’ve never had the ability to change the fundamental chemical nature of who we are. And now we do. And what do we do with that?
ONSCREEN: The power to end disease.
DOLORES SANCHEZ (David Sanchez’s Grandmother): David’s doctor told me, “Just hold on. There’s something coming.”
RODOLPHE BARRANGOU (Former Director of Genomics, Danisco): You can actually use CRISPR in humans to change D.N.A. You can actually do it.
ONSCREEN: The power to change the course of evolution.
GEORGE DALEY (Dean, Harvard Medical School): We could engineer a single gene, that could potentially make us all more muscular, but should we make that universally available?
VLADIMIR PUTIN (President of Russia): (Translated from Russian) Man can create a man who can fight without fear or pain. This might be worse than a nuclear bomb.
ONSCREEN: How far should we go?
ALE: Should we really be manipulating the heredity of future generations, given our lack of knowledge about so many things?
PALMER WEISS (Mother of Ruthie Weiss): I don’t know where you draw the line between not having albinism and deciding your kid needs to be an extra foot taller, so they can be a good oarsman and go to Yale. Where is that line? Who’s going to draw that?
TREVORTHOMPSON (Patient advocate): Anything that will stop my child from suffering, I’m for.
ANTONIO REGALADO: You know, “draw this ethical line wherever you want, but don’t draw it in front of my disease.”
Caption: Who gets to decide our future?
PREACHER: What does that mean for this science, where we have the capacity to edit in some things that we think are important? Are we playing God?
ALTA CHARO (Bioethicist, University of Wisconsin–Madison): You don’t realize it’s disruptive, until you look backward. Often, you don’t realize that you’re in the middle of a revolution until after the revolution has occurred.
HUMAN NATURE, right now
ONSCREEN: CALIFORNIA INSTITUTE OF TECHNOLOGY - October 26, 1966
ROBERT SINSHEIMER (Biologist/Film Clip): Dr. Bonner, fellow prophets, and ladies and gentlemen, this summer, I traveled through northern Arizona and southern Utah. In this land, the rivers have carved great gorges, and on the sheer cliffs of these gorges, one can read a billion years of the history of the Earth. On that immense scale of what represents the passage of perhaps 100,000 years, all of man’s recorded history took place as an inch was deposited; all of organized science, a millimeter; all we know of genetics a few tens of microns. The dramatic advances of the past few decades have led to the discovery of D.N.A. and to the decipherment of the universal hereditary code, the age-old language of the living cell.
And with this understanding will come the control of processes that have known only the mindless discipline of natural selection for 2-billion years. And now the impact of science will strike straight home, for the biological world includes us.
We will surely come to the time when man will have power to offer, specifically and consciously, his very genes. This will be a new event in the universe. The prospect is, to me, awesome in its potential for deliverance, or equally for disaster.
NEEDLE IN A HAYSTACK
DAVID SANCHEZ (Boy with Sickle Cell Disease): There we go. Much better.
NURSE: You want to squeeze my hand? Relax your shoulders. Relax your toes.
DAVID SANCHEZ: Being in the hospital isn’t scary to me. Having a certain new problem isn’t scary to me anymore, ’cause it’s happened so many times. I don’t know. My blood just does not like me very much, I guess. Your red cells are supposed to be round and have oxygen in them. Mine are half-moon-shaped, sickle-shaped, which is why it’s called sickle cell, so I don’t get the same amount of oxygen.
NURSE: I always say, like, oil change, you know? You’re draining the dirty out and then put a clean in. Yeah, so he just needs a tune-up every four to six weeks, yeah, uh-huh. Yeah.
DAVID SANCHEZ: Okay.
NURSE: Put this on. Take deep breath and hold. Mm. Okay. You okay, David? Mm-hmm?
DOLORES SANCHEZ: He used to tell me, “Don’t cry, Nonna. Why are you crying?” I said, you know, “Love you, baby.” He goes, “Don’t worry about it.” He says, “If I lose my life,” he goes, “you’ll see me again.” And I thought, “This child has more strength and faith than I do.”
MATT PORTEUS (Sickle Cell Researcher, Stanford University): It’s often called the first molecular disease. It’s caused by a single change in the D.N.A. sequence.
ONSCREEN: HBB GENE
MATT PORTEUS: It’s the letter A changed to a letter T.
PRODUCER: That’s it?
MATT PORTEUS: That’s it.
TSHAKA CUNNINGHAM (Minority Coalition for Precision Medicine): And that mutation causes a kink in the protein that prevents it from folding properly. If your folding structure of a protein is disrupted, now that protein can’t function. It causes the red blood cell to really collapse.
MATT PORTEUS: It becomes very stiff, and it can’t squeeze through. And you’re not able to get red blood cells to the tissues, where they can deliver oxygen. And if you block the ability of oxygen to get to those tissues, those tissues won’t work well, and they’ll get damaged.
In Africa, the life expectancy for somebody with sickle cell disease is on the order of five to eight years of age. In the U.S., it’s the early to mid-40s.
PRODUCER: What do you say to a kid? That their life is going to be…
MATT PORTEUS: We avoid it. We avoid that conver… It’s not a, it’s…
MATT PORTEUS: It’s not a conversation we’re good at having.
DOLORES SANCHEZ: Makes me very nervous.
David can go from crazy teenager, joking, jumping around, to a fetal position on his knees.
DAVID SANCHEZ: (Panting) It’s like pulsing. “This hurts. You’re having a sickle cell crisis.” I can have, like, a little pain crisis where it really doesn’t count, and then I can have something really bad. But I’m not just going to not play basketball. You can’t just not play basketball.
NURSE: This is David’s old red blood cells, we’re going to save for research.
DOLORES SANCHEZ: How do you sing?
KID: (singing) Rain, rain, go away. Come again…
TSHAKA CUNNINGHAM: It’s a genetic disorder. So, in order to cure a genetic disorder, you literally have to go in and fix the gene.
MATT PORTEUS: We just didn’t have the tools to make that single letter change in a precise fashion.
PRODUCER: Even one letter?
MATT PORTEUS: Especially one letter.
NEWS ANCHOR #1: Deoxyribonucleic acid, or D.N.A. for short, is the material that’s the basis of life. Each living thing has its unique D.N.A. that determines what that living thing will be, plant or animal, man or muskrat.
PAUL BERG (Biochemist, Noble Laureate): If we understood the structure of genes, the structure of chromosomes and how genes work, then we might better be able to understand and treat genetic diseases which occur in humans.
ALTA CHARO: The work that Paul Berg did, that was probably the beginning. This dream of gene therapy was born out of those 1970s experiments. And we were still very far away from it, but you’ll see people talking about that hope right away.
NEWS ANCHOR #2: The hope is that the isolation of the gene will lead to treatment of people with muscular dystrophy.
NEWS ANCHOR #3: Scientists are working on genetic cures for diseases such as Alzheimer’s and Parkinson’s.
DOCTOR: A, T, A, G, C…
HANK GREELY (Bioethicist, Stanford University): The idea behind gene therapy is really simple: add in a copy of the gene that works, then they’ll make the protein that works, and then they won’t be sick anymore. But the devil, as is often the case, is in the details.
DR. WAYNE MILLER (Medical Geneticist): Right now, we have the ability to identify the gene, to isolate it. But the ability to put it where we want it is still a long ways away.
BERNARD D. DAVIS (Harvard Medical School): If you put a gene into a cell, you cannot tell exactly where that gene is going to enter the cell’s chromosome.
FYODOR URNOV (Sangamo Biosciences, 2000-2016): Conventional gene therapy is an essentially random process. So, imagine taking this century-long narrative, which is human D.N.A., which is a very, very long text, and taking one paragraph and just sticking it somewhere random. The, the change you are creating is not a controlled one.
NEWS ANCHOR #4: (Subtitles translated from French) They’ve done it! Professor Alain Fischer’s team is the first in the world to cure a human being using gene therapy. This method has been one of medicine’s best hopes for the past 15 years.
FYODOR URNOV: There was a clinical trial that was done in France. This was for really sick children. I want to be clear, this was for children who would have died otherwise.
DAILY NEWS (Web Clip Headline, 3 October 2002): ‘Miracle’ gene therapy trial halted
FYODOR URNOV: Four of these children developed cancer; one of them died. The gene went into the wrong place, because it’s a random process, and by chance, it went into the wrong place. And that random event caused cancer.
DAVID BALTIMORE (Microbiologist, Nobel Laureate): You know, you always think that what you know is going to get a little better and a little better and a little better and soon be there. And what we knew how to do wasn’t getting a whole lot better. It was getting a little bit better. The technology was just too clumsy to actually use it with human beings.
FYODOR URNOV: It became very, very clear to us that we are at the foot of a very tall mountain, and we may not even have the right mountaineering gear.
I worked at this company called Sangamo Biosciences. We decided to figure out a way to change human genes in a precise fashion. You know, this would be like word processors for your D.N.A. This will get technical, but good technical. D.N.A. breaks all the time. You go get a dental X-ray, the technician points this thing at your face and, click, the X-rays actually hit your D.N.A., and they physically create a break, so the familiar double helix of D.N.A. physically goes pop. The good news is the cell has its own machine to fix breaks. Inside our cells, there are two identical D.N.A. molecules lying side by side, literally, side by side. If one is broken, it can say to its sister—and that, in fact, is the technical term, the “sister”—”Hey, sis, I’m sorry. I’ve had a break. I’m wondering if I can copy the missing genetic information.” And the sister goes, “Yeah.”
Chromosome broken awaits sounds of strands pairing, preserving life’s thread.
There’s really, there’s really a haiku about homology-directed repair.
Why is that useful? So, it’s useful because, if you can cut a gene inside a cell, so, if you can create a break at a place of interest, then you can change that gene. You fool the cell, give it a separate piece of D.N.A. that you have made, a piece of D.N.A. which is identical to the chromosome that you are cutting, except for the change that you wish to make.
And Mother Nature will not know she’s being fooled. She will repair the break using this piece of D.N.A. you provided as a template, and so, whatever change you brought in will then go into the chromosome.
FENG ZHANG (Bioengineer, The Broad Institute): You can think of it like a cursor in Microsoft Word. In Word, if you have a document where you edit, first, you have to place the cursor there. In D.N.A., wherever you make a cut is the equivalent of a cursor in this word processor of the genome. That’s where you can type in a new word.
JENNIFER DOUDNA: So, if you wanted to use that capability to “engineer the genome,” the challenge was to introduce breaks in the D.N.A. at places where you wanted to alter the code.
FYODOR URNOV: How were we going to do that? We need something that cuts only one gene out of the, you know, 25,000 that we have.
DAVID BALTIMORE: There were just such serious blocks in the way. So, it looked like it was going to be a long road, and that’s what changed and that came, sort of, overnight.
DOLORES SANCHEZ: David’s doctor told me, “Just hold on. There’s something coming.”
ANTONIO REGALADO: When I first heard about it, I was at a conference in New York. And it was a very strange conference of futurists. It was put on by a Russian guy whose ambition is to download his brain and become an android who lives forever.
MAN AT A CONFERENCE: In this future, people will be young, beautiful. They will have multiple bodies, not only just one.
ANTONIO REGALADO: But they had a lot of good people there, including an important geneticist from Harvard, George Church. And I remember him saying, “Remember this word: CRISPR.”
ANTONIO REGALADO: C, R, I, S, P, R.
DAVID BALTIMORE: It’s like, you know, in The Graduate, “plastics,” remember the word CRISPR.
TWEET: Doctor Mel
fellow scientists… look into CRISPR… amazing
9:47 AM - 29 Jan 2013
DAVID BALTIMORE: This is going to allow human genome engineering on a unprecedented scale.
TWEET: Rudy Marsh
If you don’t like the DNA you have, just add a
8:19 AM - 4 Mar 2014
TWEET: Lawrence Andrews
The revolution has begun…#CRISPR
4:30 PM - 3 Feb 2014 from Southampton, England
PRODUCER: How old is CRISPR?
JILL BANFIELD: Oh, in terms of millions of years?
JILL BANFIELD: Oh. I mean, probably billions.
FRANCISCO MOJICA: When you are a student, you think everything is known.
Caption: BRAS DEL PORT SALT PONDS
Santa Pola, Spain
FRANCISCO MOJICA: But there are places where no one else looked.
The organism I was working with is called Haloferax mediterranei. This microorganism is very peculiar. They only live in environments where the salinity is about tenfold that of seawater. These tiny organisms are, are, how you say, even, so clever. Clever because of evolution, of course.
JILL BANFIELD: Well, I’ll tell you the story that I know. Microbial genome sequencing started sometime in the 1990s.
PRODUCER: What does that mean?
JILL BANFIELD: See, okay, so unraveling the D.N.A. code of organisms of life, it’s a relatively recent part of biology. And in the late 1990s, people started to turn their attention to the sequencing of microbial genomes.
They’re amazingly highly-evolved entities that just chose a different way of surviving in the world than the cells that became us.
FRANCISCO MOJICA: We saw a very peculiar pattern.
These very short fragments of D.N.A. They repeated many times. And they were regularly interspaced. Eventually, we realized these peculiar sequences, they were present in many different microorganisms. But they didn’t have really any name.
CRISPR came to my mind just thinking about the main features: “clustered regularly interspaced short palindromic repeats (CRISPR);” “repetitive D.N.A. sequences;” “enigmatic.”
FYODOR URNOV: There really wasn’t much precedence for anything peculiar like this in the D.N.A. of living things, and when you see something unusual, you automatically assume that it’s interesting. That’s just how science works.
JILL BANFIELD: CRISPR is actually clustered, regularly interspaced, palindromic repeats, and so it’s actually named for the repeats.
Image on screen of D.N.A. repeating pattern:
REPEAT REPEAT REPEAT
JILL BANFIELD: But what was really interesting were these sequences in between…
Image on screen of D.N.A. repeating pattern:
REPEAT REPEAT REPEAT
SPACER SPACER SPACER
…that were completely enigmatic.
Image on screen of D.N.A. patterns:
FRANCISCO MOJICA: Spacers.
JILL BANFIELD: And each spacer was different. Never seen anything like this before.
FRANCISCO MOJICA: Where the hell come these sequences from?
ANTONIO REGALADO: I have my own way of, kind of, telling the story in short form, is I show this article from 2007, right? Five years before anybody was talking about CRISPR, and it’s this headline…
(Web Clip Headline, 23-Mar-2007):
Danisco breakthrough could boost
ANTONIO REGALADO: …from a yogurt company saying, “Holy grail is discovered.” And what was this yogurt company’s holy grail? It was CRISPR. It was CRISPR.
PRODUCER: When did you get your CRISPR license plate?
RODOLPHE BARRANGOU: The first one, I got back in the days in Wisconsin. And when I first moved to North Carolina, one of the first things I did was make sure I still had my CRISPR rights with my CRISPR mobile. People were like, “Have you heard about this CRISPR thing?” And I’m like, “Dude, like, I’ve heard of this CRISPR thing for 10 years. Like, what the hell are you talking about?”
JILL BANFIELD: Danisco is a company that sells microbes to people who want to make food. A lot of foods are produced using bacteria, and…yogurt, for example. Rodolphe was trying to work out how to deal with the problem of his bacterial cultures suddenly dying because of viral infections.
FYODOR URNOV: Most people don’t wake up in the morning and think about how bacteria defend themselves against viruses. It’s just not on their, sort of, front and center in people’s agenda, but it should be.
LUCIANO MARRAFFINI (Early CRISPR Researcher): Viruses are very simple, lean machines. They have one job to do: look for a host, take the host over and multiply. That’s it. The virus will attach to the surface, and then it will inject its genetic material. It hijacks the cell and uses the cell just as a factory of new viruses. And then it’s over. It’s over for the cell.
RODOLPHE BARRANGOU: This is when people call companies like Danisco and say, “You sold us a culture that’s not working. We want our money back.” But there’s a small subset of the population that survives the viral attack. We don’t know why they make it, but they make it. They become resistant. At that time, we still don’t know what CRISPR is or what it does, so there’s no assumption that CRISPR is involved. Then what we do is we take the survivor that made it, and then we check its D.N.A. The D.N.A. sequence had changed.
Image on screen of D.N.A. pattern:
REPEAT SPACER REPEAT SPACER REPEAT SPACER REPEAT SPACER REPEAT
FRANCISCO MOJICA: There are new spacers that were not present before, to sequences from the viruses that infected the bacteria.
JILL BANFIELD: And now it’s immune.
FYODOR URNOV: So, now, scientists have a clue. And you know, at this point, of course, you’ve sort of put your Sherlock Holmes hat on. You take in your virtual pipe, and you go, “What are these clues telling us?” We do the experiment five different times…
Image on screen of D.N.A. repeating pattern:
FYODOR URNOV: …and consistently, the bacteria acquired a spacer that contains a sequence from the virus and became resistant. So, what if I take it away? You lose the resistance.
JILL BANFIELD: Without that little piece of D.N.A., the microbial cell, the bacterial cell will die, and if it had it, it would survive.
RODOLPHE BARRANGOU: Oh, that was like, that was like, “We got it.”
Image of book highlight:
adaptive “immune” response
RODOLPHE BARRANGOU: CRISPR is an immune system.
JILL BANFIELD: What an idea! A piece of the genome of your predator now stuck in your genome, so you can recognize it in the future.
FRANCISCO MOJICA: Bacteria have memory. They are able to remember invaders, recognize them, and kill them. That was really fantastic.
RODOLPHE BARRANGOU: At the time, you know, it’s useful in manufacturing cultures that are resistant to viruses. And it’s extremely valuable to Danisco, you know? But, but we don’t know what the future holds. We have no idea how useful another’s technology is going to be or pan out in the end.
Caption: UNIVERSITY OF CALIFORNIA, BERKELEY
JENNIFER DOUDNA: I think I first heard about it when I had coffee with Jill Banfield, my colleague here at Berkeley, at the Free Speech Movement Café, classic Berkeley cafe.
JILL BANFIELD: One thing they’ll write on my tombstone is, “Told Jennifer Doudna about CRISPR case.” Like, that will be the sum of my life.
JENNIFER DOUDNA: I love things that not a lot of people are paying attention to, which certainly CRISPR was in its early days. Not anymore, but, but, you know, in the early days, it was like that. But then you always ask yourself, “Huh, is everybody else just a lot smarter than me, and they’ve figured out that this is a,you know, a dead path and…?”
RESEARCHER: So, we’ve got the antibody tethered to Cas9. It’s finding the T cells of a specific antigen.
JENNIFER DOUDNA: We’re biochemists in the lab. We study the way molecules work. We try to isolate them from all of the other pieces and parts of the cell. We love to ask, “Well, what are the essential parts of this little machine?” In nature, what CRISPR systems are doing is they’re giving bacteria immunity to viruses, so they’re protecting them from viruses.
FYODOR URNOV: When an invader shows up, the bacterium has a way to store a small bit of the invader’s D.N.A. in its own D.N.A.
Image on screen of D.N.A. pattern:
FYODOR URNOV: When the invader comes back, the bacterium makes a copy, like a little “Most Wanted” poster of that spacer, and gives it to the marvelous machine at the heart of CRISPR, this extraordinary protein that we call Cas9.
FYODOR URNOV: Cas9 is truly wondrous. When Cas9 polices the intercellular neighborhood for invasions, it literally carries a copy of that “Most Wanted” poster with it, asking everyone that comes in, “Excuse me, do you contain an exact match to this little ‘Most Wanted’ poster that I’m carrying? Yes? Then I’ll cut you.”
JENNIFER DOUDNA: The thing about Cas9 that struck me at the time was that, you know, fundamentally, this thing was a programmable protein that finds and cuts D.N.A. As a tool, right, you could immediately see a lot of uses for something like that.
FYODOR URNOV: I will never forget reading the last paragraph of Jennifer Doudna’s and Emmanuelle Charpentier’s deservedly—”immortal” is a strong word, so I’m going to use it carefully—immortal science paper in which they describe that Cas9 can be directed.
Image from paper
considerable potential for gene-targeting and genome-editing applications.
FYODOR URNOV: Cas9 cuts D.N.A. based on an instruction that it carries. And that instruction is a molecule of R.N.A. that matches perfectly the D.N.A. of the invader.
JENNIFER DOUDNA: R.N.A., I think about it as D.N.A.’s chemical cousin. Like D.N.A., it has four letters, and they can form pairs with matching letters in D.N.A. The letters in the R.N.A. allow Cas9 to find a unique D.N.A. sequence.
Bacteria were programming this thing, all the time, with different viral sequences and then using it to find and cut and destroy those viruses. But because it’s using these little R.N.A. molecules, those can easily be exchanged. R.N.A. molecules are trivial to make in a molecular biology lab or order from a company. And I can cut any D.N.A. I want just by changing this, this little piece of R.N.A. It was clearly a useful tool, and I, initially I was thinking about it that way, right? ‘Cause, I mean, again, I’m a biochemist, right? I was thinking about it as a tool. I was thinking about all the cool experiments you could now do with this tool, right? I was thinking about that.
I wasn’t thinking about, “Oh, my gosh, I mean, this is a tool that, you know, it fundamentally allows us to change our relationship with nature.” It actually allows us to change human evolution if we want to, right? It’s that, it’s that profound.
THE GENE MACHINE
RESEARCHER: In my left hand, here, I have purified Cas9 nuclease, and in my right hand, here, I have a guide R.N.A., and so CRISPR essentially is the combination of these two ingredients. It’s actually millions of Cas9 molecules, and this is millions of RNA molecules.
GEORGE DALEY: I have to say, it didn’t immediately hit me, until I started seeing the data, that this could be an extraordinary transformation. You know, it was real.
RODOLPHE BARRANGOU: You can actually use CRISPR in humans to change D.N.A. You can actually do it.
Image on screen
FYODOR URNOV: Here’s a copy of a human gene. You give it to Cas9 and put it inside human cells. It runs away, finds that D.N.A. and cuts it.
MATT PORTEUS: Before CRISPR, we were getting one percent to two percent correction. We’re now up to 50 percent to 80 percent of the cells. This could really work. This could really cure a patient.
DAVID SANCHEZ: I think it’s going to help a lot of people, not just people with sickle cell, ’cause I know they’re working on it for other things. And I know so many other people that have, that have things like this. Like, like my friend, he uh, had leukemia. He actually, he didn’t make it out of the hospital. If he had it just a little bit later, of course, he probably could have been cured of that, ’cause that’s what they’re working on.
(Web Clip Headline, 12 October 2016):
CRISPR deployed to combat sickle-cell anemia
(Web Clip, February 27, 2017): Rewriting Life: Startup Aims to Treat Muscular
Dystrophy with CRISPR Patients groups are backing gene-editing as potential “home run” against disease.
by Antonio Regalado February 27, 2017
(Web Headline, February 27, 2017):
…American CRISPR Trial
…ns Will Target Cancer
EMMANUELLE CHARPENTIER (Biochemist Max Planck Institute): CRISPR has, really, the ability to recognize and to target any piece of D.N.A. in any type of cell and organism. It’s really a universal tool. It’s often described as a kind of Swiss Army Knife.
RNA Synthesis Factory
MICHAEL DABROWSKI (Co-founder Synthego): We have thousands of customers who are working with CRISPR in a wide variety of organisms: pretty much any organism you can think of, from butterflies to dogs to horses to wheat to corn.
WEB CLIP: Build Better Experiments with Guaranteed CRISPR Edits.
With access to world-class genome engineering products you can focus on your research instead of optimizing CRISPR
MICHAEL DABROWSKI: We have a design tool online. Specify a gene that you’re looking to knock out.
You can specify the types of edit that you’re looking to do. You swipe your credit card, and a few days later, a couple tubes of all the materials that you need show up at your door.
PAUL DABROWSKI (Co-founder Synthego): Obviously, we like to validate the researchers’ authenticity and credibility with regard to their institution.
PRODUCER: Meaning you’re not just shipping it off?
PAUL DABROWSKI: Correct. We don’t ship to just anyone.
MICHAEL DABROWSKI: That’s correct.
HANK GREELY: The analogy I like is automobiles. There were cars before there were Model Ts, but they were expensive and they broke down all the time. Ford comes out with the Model T, and suddenly, it’s cheap, and it’s reliable. Pretty soon, everybody’s got a car.
CRISPR gives us the chance to make precise, targeted changes in the D.N.A. of any living organism. It’s a power to change the biosphere. That’s what makes CRISPR revolutionary.
WEB CLIP #1: Scientists Can Now Repaint Butterfly Wings
WEB CLIP #2: ‘Gene drive’ mosquitoes engineered to fight malaria
Mutant mozzies could rapidly spread through wild populations.
Caption: CAMBRIDGE BIOLABS
PRODUCER: Can you just sort of describe where we are right now?
LUHAN YANG (Co-founder, eGenesis): Oh, here?
PRODUCER: Yeah, yeah, yeah.
LUHAN YANG: Oh. So, here is the eGenesis garage. This is our lab space. It’s literally the basement. I feel it’s a humble start for us, where we embark on a very exciting journey.
WEB CLIP #3: BUSINESS INSIDER
A startup cofounded by a 30-year old just got $38 million to revolutionize the way we transplant organs
JORGE PIEDRAHITA (Translational Medicine, North Carolina State University): The field is called xenotransplantation: transplantation of an organ from one species to the next.
These things have actually been tried a lot, and some of them are pretty weird, like, people were, were, you know, in the early 1800s, that kind of stuff, they were trying to transplant monkey testes into men to make them more virile. So it’s a, you know, conceptually, people have been trying this for a long time. But scientifically, this field is probably about 20 years old.
Whether we like to believe or not, we are very similar to the pig.
NEWS REPORTER: This pig, this pig, this pig—all the organs in these pigs have been modified very, very slightly.
GEORGE CHURCH: They tried it 20 years ago. Novartis, that had a billion-dollar investment in it, sort of, gracefully retreated. They did…, they just didn’t have the technology.
JORGE PIEDRAHITA: Without the CRISPRs, can’t do it.
GEORGE CHURCH: Luhan Yang and her team, they started as a ragtag team of scientists in my academic lab, and then they went to a ragtag team in the basement of a startup incubator.
YINAN: Nice to meet you. Hey, happy Halloween. You know, I dressed up today. How are you?
LUHAN YANG: Can you see anything?
YINAN: Kind of. Some things, not everything.
LUHAN YANG: So this is Yinan. Yinan is quite creative, probably more creative than me.
YINAN: When I first heard the story, I thought, it is sci-fi. You know? “We’re going to make a pig that doesn’t speak human language, but that can donate organs for the patient and save the world from organ shortage.”
I mean, it really takes a lot.
LUHAN YANG: As you can imagine, if you put the organ from the pig into the human, there’s a rejection. We can really exercise the power of CRISPR to engineer immunocompatibility by knocking out genes and knocking in genes.
YINAN: If you compare the pig genome to an encyclopedia…this thick. So, what CRISPR does is it can find a specific word in the encyclopedia and delete that word.
But instead of deleting a few words, we have to change paragraphs after paragraphs.
LUHAN YANG: Right now, the conventional practice is doing one or two genes, and the record, before us, is five. We did 62 genes in a single step.
GEORGE CHURCH: We have a revolution going on. We’ve never had a revolution like this. Closest we’ve come is maybe the Internet and computer revolution, and that took us kind of unaware.
LUHAN YANG: We do a lot of iteration of the pig production.
PRODUCER: How are the pigs coming along?
LUHAN YANG: They are coming. So, we are expecting some pigs in a few weeks. We’re so excited, we even named the pig. The first one is Laika. It’s the name of the Soviet dog which orbited the Earth first. We want to symbolize it as an animal which can lead us to a new era of science.
BRAVE NEW WORLD
SPEAKER: (WORLD FESTIVAL OF YOUTH, Sochi, Russia, October 21, 2017): (Translated from Russian) I would like to give the floor to the distinguished president of the Russian Federation, Vladimir Vladimirovich Putin.
VLADIMIR PUTIN (Film Clip): (Translated from Russian) Genetic engineering will open up incredible opportunities in pharmacology: new medicine, altering the human genome if a person suffers from genetic diseases.
All right, that is good. But there is another part to this process. It means—we can already imagine it—to create a person with a desired features. This may be a mathematical genius. This may be an outstanding musician. But this can also be a soldier, an individual who can fight without fear or pain.
You are aware that humankind will probably enter a very complicated period of its existence and development. And what I have just said may be more terrifying than a nuclear bomb.
NEWS CLIP: This is Aldous Huxley, a man haunted by a vision of hell on earth. Mr. Huxley, 27 years ago, wrote Brave New World. Today, Mr. Huxley says that his fictional world of horror is probably just around the corner for all of us.
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BRAVE NEW WORLD
And then we are much better than the Gammas and Deltas. Gammas are stupid. They all wear green, and Delta children wear khaki.
GEORGE DALEY: I first read Brave New Worldin a literature class in high school, and, yeah, it was startling, and, yeah, it was provocative, but I reread it recently, and I was startled by how a book written in 1932,…
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‘These,” he waved his hand, “are the incubators.
GEORGE DALEY: …could have the foresight to predict in vitro fertilization.
Video on screen
Caption: Oldham General Hospital
25 July 1978
FIRST BIRTH BY IN VITRO FERTILIZATION
GEORGE DALEY: Now, of course, it went beyond it. It told a story where human beings were literally manufactured to play specific roles in society. It was so sobering to me, because CRISPR makes that original worry about engineering human heredity actually feasible.
ALDOUS HUXLEY: We mustn’t be caught by surprise by our own advancing technology. This has happened again and again in history, where technology has advanced, and this changes social conditions, and suddenly, people have found themselves in a situation which they didn’t foresee and doing all sorts of things they didn’t really want to do.
FYODOR URNOV: There is no question in my mind that as this field advances, people will be able to order a change in their genetic makeup to create an outcome of interest to them: in their metabolism, in their appearance, in principal, potentially, in who they are as people; personality changes. And again, we have to be delicate to not cross into science fiction territory.
GEORGE DALEY: We know that we could engineer a single gene, myostatin, in a way that could potentially make us all more muscular. But should we make that universally available?
FYODOR URNOV: They discovered that there are people who can go by on four hours of sleep. What would I give for that mutation?
FYODOR URNOV: One gene, one change, four hours of sleep, no problem. So, should this be, I don’t know, a job requirement for air traffic controllers? Do I want the world to go there?
There are people who feel no pain. This was discovered by studying a 14-year-old boy in Pakistan who felt no pain, and guess what he did? He performed street theater.
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Absence of pain phenotype
He placed knives through his arms
FYODOR URNOV: He died before his 14th birthday. He jumped, for money, off a house roof. He knew it would be painless. The study of his D.N.A. revealed he has a mutation in one gene.
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FYODOR URNOV: It makes a protein that transmits the pain signal from the periphery, your finger or your skin, through the spine to your brain.
FYODOR URNOV: You get rid of that gene, you cannot transmit the signal. You feel no pain. Why? Well, I’ll give you a legitimate reason. Pain due to cancer is terrible, especially if it’s terminal cancer and we know a person has months to live. Why not get rid of that gene? And I’m sure this will be. I am sure this will be. We will have gene editing of that gene to treat cancer pain.
Now, do I want a scenario where there are parts of the world where Special Forces soldiers are made immune to torture?
ANTONIO REGALADO: I don’t think my job is that different than what scientists do. There’s a lot of, kind of, hunting around, hunting and pecking, you know, looking under things, turning over stones. And then, eventually, you know, you kind of get on the scent of something, and then that’s when the fun starts. Before science gets published, it circulates among scientists. The papers go out for review. Someone passes it to somebody else. Like, they have a certain circulation.
Web Clip, Apr 22, 2015): Rewriting Life:
Chinese Team Reports Gene-Editing Human Embryos
A research team finds that gene editing isn’t yet reliable enough to engineer the human species.
ANTONIO REGALADO: And so I’d gotten onto the trail of these papers coming out of China.
(Web Clip, Apr 24, 2015):
Printed from THE TIMES OF INDIA
Chinese edit human embryos, spark fury
ANTONIO REGALADO: This was the first case where someone had said about, you know, “I’m going to use CRISPR, and I’m going to modify a human embryo.”
(Web Clip, April 11, 2016):
Second Chinese Team Reports Gene Editing in Human Embryos Study used CRISPR technology to introduce HIV-resistance mutation into embryos
ANTONIO REGALADO: They had knocked out CCR5.
ANTONIO REGALADO: This is a receptor that if you don’t have it, you can’t get infected with H.I.V. But think about what they were proposing. They said, “We’re going to make someone who’s immune to H.I.V.”
(Web Clip, March 5, 2015): Rewriting Life:
Engineering the Perfect Baby
Scientists are developing ways to edit the D.N.A. of tomorrow’s children. Should they stop before it’s too late?
ANTONIO REGALADO: Once I started digging into it…
The Washington Post(Web Clip):
This fertility doctor is pushing the boundaries of human reproduction, with little regulation
ANTONIO REGALADO: I found more examples of people that were thinking along these lines. John Zhang runs the third or fourth biggest fertility clinic in the country, and then he started a company called Darwin Life.
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“Everything we do is step toward designer babies,” Zhang says of Darwin Life. “With nuclear transfer and gene editing together, you can really do anything you want.”
ANTONIO REGALADO: He said that he was enthusiastic about the whole idea of designer babies. He basically said that, “Of course. That’s the whole point.”
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A WOMAN’S BIOLOGY
ANTONIO REGALADO: There was a company called OvaScience, that I discovered a tape recording that they had put on their own website of an investor meeting.
PERSON IN A LAB: We will be able to correct mutations before we generate your child. It may not be 50 years, actually. It may only be 10, the way things are going.
JENNIFER DOUDNA: I ended up having several dreams that were very intense for me at the time, where I walked into a room, and a colleague said, “I want to introduce you to someone, and I want you to tell them…they want to…they want to know about CRISPR.” And I walked into this room, and it was…there was a silhouette of a chair with someone sitting with their back to me. And as they turned around, I realized, with horror, that it was Adolf Hitler, you know? And he leaned over, and he said, “So, tell me all about how Cas9 works.”
I remember waking up from that dream, and I was shaking. And I thought, “Oh, my gosh. I mean, what have I done?”
MATT PORTEUS: Five-and-a-half years ago, it was recognized that we could take the CRISPR system out of bacteria and move it, first into a test tube and then into mammalian cells, and use it as a tool for genome editing. The Cas9 protein is going to make the cut in the D.N.A. We are correcting the sickle mutation in blood cells.
So, if it’s a woman, their eggs are not corrected. If it’s a man, the sperm is not corrected. That change will not get passed along to future generations, so they will be cured, but their children might get the disease, as well. Now we need to give the cell another piece of D.N.A., except instead of having the T, it has an A. So, why not just do it so that the disease gene never gets passed along to future generations? And there’s some people out there who think that’s what we should do. But we may be creating things that we can’t put back into the bottle.
GEORGE DALEY: When we engineer gene changes into my blood or into my skin, those gene changes die with me, but the germ cells, sperm and eggs, embryos, those cells are very different. They’re part of what we call, “the germ line.” If we engineer gene changes into my sperm, they’re passed to my son. They’re passed to his son and forever.
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…unpredictable effects on future generations.
FYODOR URNOV: My colleagues and I wrote a fairly strongly worded piece, in Nature, with the fairly unequivocal title, Do Not Edit the Human Germ Line, end of quote. We proposed that there be an unconditional moratorium: don’t edit human embryos, don’t use edited sperm and eggs to make human embryos, just, nothing. We must understand that when we authorize research on human embryo editing, we are enabling, ultimately, human embryo editing for human enhancement. That’s what we’re doing. We’re putting the recipe out into the world.
ANTONIO REGALADO: The debate that’s being had is whether society should go in this direction. Should you be allowed to make a genetic change into the next generation that’ll then go on to other generations? The gene pool, like nature itself, is kind of a common good. I used to have a T-shirt, and it had a little, a guy that was kind of a D.N.A. spiral, right? But he was the lifeguard and he’s blowing a whistle and he says, “Hey, you, get out of the gene pool!” I loved that shirt.
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Projected Data At Maturity
VIDEO NARRATOR: Baby shopping. Imagine being able to program the IQ of a baby.
GERALDO RIVERA: Will we be sitting at computer terminals, like this one, punching up the traits we would like in our children, like the shape of their faces or the color of their eyes?
ALTA CHARO: Well, you know, the fear that everybody focuses on most is just this, sort of, “designer baby” business.
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Photograph of baby
JENNIFER DOUDNA: We’re turning reproduction into production. We’re turning children into consumer products.
ALTA CHARO: Every time there’s a new technology, we hear the same concerns.
TED KOPPEL (NIGHTLINE/APRIL 4, 1997/FILM CLIP): If there is a market for cloning, there is no force on Earth that will keep buyer and seller apart.
FILM CLIP: Perhaps Saddam Hussein would like to give birth to himself.
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MIT Technology Review
WE CAN NOW ENGINEER THE HUMAN RACE
ALTA CHARO: With CRISPR, even reputable magazines could not resist the temptation.
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The prospect of genetic enhancement
ALTA CHARO: The little thing that says “high IQ,”—as if we know what intelligence is, let alone how to measure it, let alone how to design it. Why do we keep ignoring the fact that we’ve seen the same argument every decade for the last five decades? And these nightmares, they haven’t come to pass.
We are capable of really evil things, but we don’t need technology to commit evil acts. If the goal is genocide, if the goal is eugenics, if the goal is discrimination, there will be another way to do it and it will be found. I kind of divide the world into the bio-optimists and the bio-pessimists.
NARRATOR OF STAR TREK: Space: the final frontier.
ALTA CHARO: I grew up with the original Star Trekand have been a devoted follower of all of the Star Trekssince then. I’ve read pretty much every Star Treknovel. Don’t get me started.
It is a vision of progress and the potential of science to make life better. There are other people who have read the cautionary tales.
NARRATOR OF BLADE RUNNER, 1982 Film Clip: A blade runner’s job is to hunt down replicants, manufactured humans you can’t tell from the real thing.
ALTA CHARO: But I don’t think the technologies are inherently good or evil. The technologies are tools. They are power. What you do with the power determines if the result is something that we applaud or something that we deplore. But it’s not the tool that determines the end point. It’s the user.
FILM NARRATION: Now here are 23 representing mother’s chromosomes, 23 for father’s. Now we put them together.
DAVID BALTIMORE: Our way of determining the inheritance of the next generation is a lottery. And it’s a perfectly good argument to say, “I would rather determine it than take a lottery.”
STEPHEN HSU (Co-founder, Genomic Prediction):Well, I think the right way to say it is that sex is for recreation, and science is for procreation.
Fifty years from now, people may say, like, “I can’t believe those barbaric people in the early 21st century. They were having kids this crazy, old-fashioned way. They were just, like, rolling the dice with their kids’ lives.
We’ve gone through in vitro fertilization. We’ve harvested the eggs. It’s not uncommon to produce multiple viable embryos. Which one do you choose? One possibility is, “Yeah, just, we’ll just roll the dice. We’ll just, I’ll just point at one.” Another option would be I run some fancy genetic tests.
HANK GREELY: Pre-implantation genetic diagnosis is the process of doing genetic tests on an embryo. When I talk to most people about it, they think it’s science fiction, but it was first used clinically in 1990. With today’s technology, you’ve been limited to looking at only a handful of traits. But soon, genome sequencing will become cheap enough, easy enough, and accurate enough that you’ll be able to learn everything genetics can tell you.
Breast Cancer Risk
STEPHEN HSU: In the future, let’s imagine that CRISPR gets really, really good.
STEPHEN HSU: Maybe you don’t need to produce lots of embryos. Maybe you just produce one, but you can make whatever edits you want to it.
KELSEY MCCLELLAND (Genetic Counselor): So, the carrier screening that I was talking about earlier tends to focus on disorders that show up early. Everyone wants to have a healthy, perfect baby. I think that’s a universal truth. You know, “How can I make sure that my child will be healthy? How can I make sure that, you know, they’re going to have some of these positive traits, that they’re going to do well, they’re going to learn well?”
Looking at this family history, certainly I…
The opinion is that information is good, and almost everyone that talks to me wants more information and even wants more like, we’ll give them a whole bunch of information, and they even want more.
I actually first heard about genetic counseling from my mother. Hemophilia A is the condition that runs in my family. It’s a genetic bleeding disorder. There is a gene on the X chromosome. It encodes for a protein called “factor VIII.”
Caption: HEMOPHILIA A
KELSEY MCCLELLAND: When factor VIII isn’t working, you can have a bleed that will lead to death. If I decide to have children naturally, without reproductive technology, I’m putting that child at 25 percent risk to have a really severe disorder. That responsibility feels like it’s on me. It takes it from the universe’s decision to my decision.
Today, I’m unusual, because I know that I’m a carrier of a genetic condition. But soon, everyone will know genetic information about themselves.
PRODUCER: What about the cost of it?
STEPHEN HSU: In the short term, there’s a disturbing possibility that people with means will be availing themselves of this technology, and people who don’t have those means will not. So, I kind of hope for a future where government makes it free for everybody. You would have a generally healthier population, maybe longer lived population on average, maybe slightly smarter population on average. So, if you have a smaller fraction of your population with Down syndrome, the average intelligence is a little bit higher, and, you know, society might run a little bit more efficiently if people are a little bit smarter.
JULIAN HUXLEY (Evolutionary Biologist, England, 1937/Film Clip): What is the bearing of the laws of heredity upon human affairs? Eugenics provides the answer, so far as this is known. Eugenics seeks to apply the known laws of heredity so as to prevent the degeneration of the race and improve its inborn qualities.
STEPHEN HSU: Well, the concept of eugenics, if you, if you go way back, it really just means good genes. The idea is that the human race could improve itself.
Caption: NAZI PROPAGANDA FILM
DOCTOR IN FILM: (Translated from German) Children are not brought into the world just for their own sake - rather they should be healthy, worthwhile people. And that’s why it’s important that we make sure that our bodies are physically and genetically healthy. And that we investigate whether the genetics of our ancestors are fit to pass on.
STEPHEN HSU: It was, of course, hijacked. And when people today talk about eugenics, they think specifically of the Nazis, of Nazi Germany, of compulsory sterilization, where, by force, people were compelled to be sterilized or killed because the state didn’t like their genes.
Caption: United States, 1980
NEWS ANCHOR: There was shock last month over the revelation that the state of Virginia sterilized thousands of persons between 1922 and ’72 in a program aimed at ridding the state of so-called “misfits.”
STEPHEN HSU: What we’re talking about here, where we’re being paid to do these genetic tests by loving parents who want to have a healthy child, to equate that with Nazism is, I think, just, not just stupid but actually insane.
GATTACA, Film Clip, Geneticist: I’ve taken the liberty of eradicating any potentially prejudicial conditions: alcoholism and addictive susceptibility, propensity for violence, obesity, et cetera.
GATTACA, Film Clip, Woman #1: We didn’t want…I, I mean, diseases, yes, but, uh…
GATTACA, Film Clip, Woman #2: Right, we were just wondering if, if it’s good to just leave a few things to chance.
GATTACA, Film Clip, Geneticist: You want to give your child the best possible start. Now, keep in mind, this child is still you, simply the best of you.
PALMER WEISS: My greatest fear in life, honestly, I, my two greatest fears, going back to me wanting to be a mom, at the age of five, my first greatest fear is that I wouldn’t be able to have a child, and my second greatest fear is that something would be wrong with my child.
ETHAN WEISS (Father of Ruthie Weiss): Oh, careful, sweetie.
PALMER WEISS: With Ruthie, I started seeing that she, kind of, wasn’t tracking. When I would feed her, her eyes would slide back and forth.
And then one day I went to my friend’s house, and her baby looked me right in the eyes, and I came home to Ethan, and I said, “There’s something wrong.”
ETHAN WEISS: We did genetic testing. She inherited one mutated copy of this OCA2 gene from me and one from Palmer.
ETHAN WEISS: I don’t think I even really understood that people with albinism had such impairment of their vision.
PALMER WEISS: It’s kind of like wrapping Saran Wrap over your eyes with Vaseline, very, very hard for her to see.
Now I just, like, wanted to protect her. Like, “this isn’t true. This isn’t happening.” It was horrible, it was bad.
One, two, three, four. Okay, Ruthie, Ruthie. Whoa.
ETHAN WEISS: She was really easy and happy. And early on, I think we wondered if she was sort of, I don’t know, protected by the fact that she couldn’t see a lot.
RUTHIE WEISS (Child with Albinism): Look, I have a flashlight!
ETHAN WEISS: The world wasn’t as noisy to her.
RUTHIE WEISS: Blue.
RUTHIE’S SISTER: Light it. Light it.
ETHAN WEISS: She was smart and talkative.
Come here, Yoda.
RUTHIE WEISS: Oops…(laughs)
PALMER WEISS: You don’t know what you don’t know. You don’t know that even though it’s going to be different than what you thought, you don’t know, you know, maybe how much better that’s going to be.
RUTHIE WEISS: I want to be a professional basketball player, but I don’t think that’s going to happen.
Can I hold him?
(Reading from large print screen) “Mission is simply one…”
ETHAN WEISS: Well, I mean, I’ve known about CRISPR, from the perspective of being a doctor, probably since the first publications in whatever it was, 2012.
RUTHIE WEISS: Oh, they come to teach the natives.
ETHAN WEISS: It really didn’t intersect with our own world with Ruthie, until probably about a year and a half ago, when I read something on Twitter.
TWEET: Daniel McArthur
Prediction: my grandchildren will be embryo-screened, germline-edited. Won’t “change what it means to be human”. It’ll be like vaccination.
ETHAN WEISS: A scientist, who I respect a lot, said he thought that in one or two generations, that all children would be born with all of these genetic abnormalities edited out.
PALMER WEISS: I know people who have children who have really debilitating diseases that make their children suffer, make their family suffer a lot, so I totally understand that desire to change that, but the rest of it scares me to death.
I don’t know where you draw the line between not having albinism and deciding your kid needs to be an extra foot taller, so they can be a good oarsman and go to Yale. You know, where, where is that line? Who’s going to draw that?
KELSEY MCCLELLAND: We’re maybe a society who is afraid of things that are different, or afraid of people who are different, afraid of people who have needs. I worry that when we’re manipulating future generations, those opinions are going to be passed on.
GEORGE DALEY: You know, we as a society may think that doing better on the S.A.T.s is better than doing worse. Being taller, being handsomer, being more creative, being more courageous, those are traits that we would want to potentially select for.
Should we go there? Is there an inevitability to going there?
STEPHEN HSU: You know, sometimes, I’m invited to give a talk on, like, kind of futuristic science things. And I’ve had tall, blonde trophy wives come up to me after the talk and say, “Wow, that was incredible. That was an incredibly interesting talk, but don’t you think there’s a problem with all this? Won’t every parent just select their kids to be tall and blonde?” The geeks all come up to me and say, “Isn’t this dangerous, ’cause all the parents are going to select for the smartest kid they can possibly get,” ’cause that’s what the geeks think is cool. You know, probably if you were talking to some N.F.L. coaches, they’d say, “Oh, what, everyone’s going to, everyone’s going to select their kid to be 6’5” and run a 4.2 40,” you know? So, there will be a wide range of what people think is the right thing to select for or engineer for, and, actually, there’s nothing wrong with that, right? Let a million flowers bloom.
NEWS REPORTER #1: On this estate, 30 miles north of San Diego, is housed a sperm bank said to be made up exclusively of donations by Nobel-Prize-winning scientists. The bank’s founder will consider for fertilization only women of high intelligence.
ALTA CHARO: You don’t know about the Nobel sperm bank?
NEWS REPORTER #2: Businessman inventor Robert Graham adds liquid nitrogen once a week to a lead-shielded sperm repository in an underground concrete bunker in his backyard.
ROBERT GRAHAM: The more good genes in the human gene pool, the more good individuals will come out of it. We aren’t even thinking in terms of the super race.
ALTA CHARO: The so-called “genius sperm bank,” a sperm bank to provide women, for free, with donor semen from men that they viewed as geniuses.
ROBERT GRAHAM: We utilize sources such as this: Who’s Who of Emerging Leaders.
ALTA CHARO: Very few women actually went ahead and took advantage of this offer to be given superior sperm for free. I did a tour of sperm banks for the U.S. Congress. I think I’m the only person who’s ever gone on a congressionally-financed tour of California sperm banks.
Despite the fact that the donors are described taller skinnier, you know, better-looking, or not, people tended to pick somebody who looked like their partner, no matter how imperfect, because the emotional importance of the connection outweighed any notion of improvability or perfectibility.
If I were trying to have a child and my partner was light-skinned, short, with eczema, I would have had a child with a guy who was light-skinned, short, and prone to eczema.
PRODUCER: But what if you could take that guy’s sperm and edit those specific things out?
ALTA CHARO: Could I change his sperm so it’s still him but a better him?
PRODUCER: Exactly, yeah.
ALTA CHARO: Right? Maybe, but every change does come with risks that you’ll make changes you didn’t intend. So, I think it’d be a long, long time before you would take that risk for anything other than something that was pretty significant. But I might want to take advantage of editing something out that would give my kid a very strong chance of developing a severe cancer, even if it’s 40 years in the future. Yeah. So maybe that will happen.
Caption: NATIONAL ACADEMY OF SCIENCES
ALTA CHARO: (Film Clip) This committee’s going to be looking at both somatic and germ line applications of gene editing.
The committee that I co-chaired for the National Academy of Sciences, we were asked to look deeply at whether or not there was something intrinsically unethical about manipulating genes in a way that makes them heritable.
GEORGE DALEY: Significant degree of uncertainty.
HILLE HAKER, LOYOLA UNIVERSITY OF CHICAGO/FILM CLIP: This should be the goal of society, to promote a better life for all and to ensure that everybody can live a life in dignity and freedom. Can this be achieved by germ line gene editing? My view is no.
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AMA Policy Finder
Code of Medical Ethics
7.3.6 Research in Gene Therapy & Genetic Engineering
ANTONIO REGALADO: The American Medical Association, bunch of European countries,…
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COUNCIL OF EUROPE
COUNSEIL DE L’EUROPE
Statement on genome editing technologies
ANTONIO REGALADO: …you know, any number of organizations all had positions, like meddling in the germ line would be wrong. It would be unethical. But they all said those things at a time when it couldn’t be done, so it was easy to say. It was a “gimme,” right? And then as soon as it comes that you can do it, then the positions change.
PATIENT ADVOCATE: Huntington’s lurks in our D.N.A. like a time bomb. It would really eliminate a scourge in the world, so I would say, “go for it.”
ANTONIO REGALADO: At the big National Academy meeting, there was not a good representation of patients, but the few who did speak were definitely in favor.
ABBY: I say, yes, it is worth pursuing in a safe and rational manner. Definitely. Let’s go.
TREVOR THOMPSON: Anything that will stop my child from suffering, I’m for.
ANTONIO REGALADO: You know, draw this ethical line wherever you want, but don’t draw it in front of my disease.
PATIENT ADVOCATE: He was six days old.
ANTONIO REGALADO: I remember one woman told a story about a child that she had and died of an inheritable disease.
WOMAN: He had seizures every day. We donated his body for research. If we have the skills and the knowledge to fix these diseases, then freaking do it.
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U.S. panel gives yellow light to human embryo editing
ALTA CHARO: The statement of task demanded that we try to follow the evidence and follow the logic, not that we follow the politics.
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A Report of the National Academies of Science – Engineering – Medicine
Human Genome Editing
SCIENCES, ETHICS, AND GOVERNANCE
ALTA CHARO: We said, “We conclude it is not intrinsically evil.” It is, what we called “ethically defensible,” but we understood that this was now a break from the past in the thinking on this topic, yes.
PREACHER: In Genesis 1, we discovered the concept of the Imago Dei, being in the image and likeness of God. What does that mean for this science where we have the capacity to edit in some things, perhaps, that we think are important? Are we playing God?
RACHEL CARSON (Author, Silent Spring, Film Clip): The balance of nature is built of a series of interrelationships between living things and between living things and their environment.
Now, to these people, apparently, the balance of nature was something that was repealed as soon as man came on the scene.
LUHAN YANG: This is Laika, this is Nova and this is Joy.
Our pig is the most advanced genome-modified animal running on the Earth.
YINAN: Wow. So cute.
GEORGE CHURCH: The babies that came out of that are now adults. And the adults are having their own babies, so it seems like making that many edits is completely compatible with a happy, healthy pig.
I tell people they’ll be visually underwhelmed by my lab. It’s just a bunch of small rooms with usually very few people in them. But in terms of what I see, it’s very exciting.
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Playing God With Our Genes
GEORGE CHURCH: I’ve never really felt that “mad scientist” was realistic for anybody that I knew, including myself. My lab has been accused of taking science fiction and turning it into science fact. I consider that very high praise. But turning science fiction into science fact is not mad. It actually can be quite useful.
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George Church: The maverick geneticist now wants to reverse ageing
GEORGE CHURCH: Aging reversal is the term that I prefer. You know, I’m 63 years old. I feel like I just barely got trained to do my job last year, and so now you’re going to pull the plug and recycle me? That doesn’t make sense.
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Any age you want… the body and mind of a 22-year-old but the experience of a 130-year-old
GEORGE CHURCH: We need to be cautious in that, you know, there’s a, there’s this whole population problem. So, we could do that, if we have a place to put all those people.
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Engineering the Perfect Astronaut
GEORGE CHURCH: Almost everything we do, people just think, “This is goofy, this is not feasible, it’s science fiction.” But I think, originally, people thought that sequencing human genomes inexpensively was a pipe dream.
PRODUCER: I can’t not ask you about mammoths, because there’s a bunch of them behind you.
GEORGE CHURCH: Yeah, that should be up at the top of the list of things that seem quixotic or misguided.
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Can we grow woolly mammoths in the lab? George Church hopes so
GEORGE CHURCH: So, in the Mammoth Project, we read the ancient D.N.A., decide which genes we’re going to resurrect, put those into the Asian elephant’s cells. And then we’re developing technology that is not yet working to make, take those embryos all the way to term. Then we scale that up to make a herd of these things, maybe 80,000 of them, to repopulate the tundra.
Caption: JURASSIC PARK
JEFF GOLDBLUM (as Malcolm, in Jurassic Park/Film Clip): Don’t you see the danger, John, inherent in what you’re doing here? Genetic power is the most awesome force the planet’s ever seen, but you wield it like a kid that’s found his dad’s gun.
LORD RICHARD ATTENBOROUGH (as HAMMOND IN Jurassic Park/Film Clip): I don’t think you’re giving us our due credit. Our scientists have done things which nobody’s ever done before.
JEFF GOLDBLUM: Yeah, yeah, but your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.
RYAN PHELAN (Co-Founder, Revive & Restore): Well, I often try to avoid talking about Jurassic Park, but I’ll, I’ll give you this. You know, Jurassic Parkwas about hubris.
SAM NEILL (as GRANT, in Jurassic Park/Film Clip): What species is this?
BD WONG (as Wu, in Jurassic Park/Film Clip): It’s a velociraptor.
RYAN PHELAN: It’s just the opposite of what scientists like George Church and others that we work with are thinking about.
When people say, “Aren’t you playing God?” My real reaction is, nobody is playing in this field. Nobody is toying with it just to see if it can happen. You know, in order to even fathom bringing back an extinct species, there’s no end of engineering that has to happen. And it is all novel, important, new science that can be used to protect any species, endangered as well as extinct.
Once you realize the magnitude of humans’ impact on the environment, you know, it’s hard for me to say that we can’t try to correct it.
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TIME Magazine: Article excerpt
How Gene Editing Could Save Coral Reefs
RYAN PHELAN: We can’t have our head in the sand. We have a responsibility to use our human ingenuity and our human skills and our wherewithal. Sometimes it’s leaving nature alone, and sometimes it might be intervening.
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CRISPR: can gene-editing help nature cope with climate change?
Research Triangle, NC
RESEARCHER: So, the gene we’ve edited controls how the pores on the underside of the leaves open and close. In the non-edited plant, these stomata or pores will stay open during the hot, dry conditions. Water is lost, and then these leaves lose water. They wilt, and they roll. In the edited plant, those stomata pores close sooner under dry conditions, and the water is retained inside the plant.
HANK GREELY: We have been messing with nature ever since we came out of the trees. Most of the life forms we eat are things we’ve made. Corn used to be a grass. Tomatoes used to be tiny little berries that were bitter. Geneticists changed that. Now, we didn’t call them geneticists, we called them farmers.
Caption: ÇATALHÖYÜK, TURKEY
Early Human Settlement, 7000 BC
PRODUCER: Do you think among these people there was anyone that would be fair to call a scientist?
IAN HODDER (Archaeologist, Stanford University): Well, that’s a really interesting question. I think there’s lots of different types of scientists that were involved.
The first people who invented pottery were really chemists, in a way. And certainly the people who were inventing agriculture and controlling plants and animals, they were biologists, you know, botanists and biologists, in our sense. You know, you can see people trying things out. What is the best way to grind grain? And how do you make bread? You know, that was invented here. To work that out is really not straightforward. In this period of time, something more modern-like in terms of our relationship with nature was beginning to emerge.
As far as we understand it, hunter-gatherers had a relationship of equality with nature and had to look after nature. And if you hunted an animal, you would have to give a gift to nature to thank it for the animal that you’d been given. And then, as people started domesticating plants and animals, they started having a new relationship where they were dominating and controlling the natural world. That made it something that you could transform.
We definitely see great advantages in genetic engineering, as agriculture, you know, was a great advance. Certainly it’s the building block of civilization as we understand it. But it definitely comes with its negatives. You could say that the long term consequences were pollution and environment degradation and so on and so forth, but you would have had to be very farseeing, you know, 9,000 years ago, to realize that that was what was going to happen.
ALTA CHARO: These things creep in slowly. It’s not like everybody was hunting and gathering and then next year, somebody said, “Oh, let’s farm,” right? It happened slowly. And so it is disruptive, but it creeps up on people. You don’t realize it’s disruptive until you look backward. Often, you don’t realize that you’re in the middle of a revolution until after the revolution has occurred. All right, so I don’t know where we are right now. It’ll be interesting to see. I hope I live long enough to see it.
PRODUCER: Do you think you want to have kids?
DAVID SANCHEZ: I have too many siblings for that. The answer’s probably going to change, but for now, probably not, no. I’m not crazy.
PRODUCER: They’re saying maybe one day, with CRISPR, they could go in and change the gene in the embryo, so that the kid, when it’s born, doesn’t have sickle cell.
DAVID SANCHEZ: Hmm. I guess that’s kind of cool, that they’re thinking that it can do that in the future, but I think that would be up to the kid later.
PRODUCER: What do you mean?
DAVID SANCHEZ: There’s a lot of things that I learned having sickle cell, just because I had it. I learned patience with everyone. I learned just to be positive.
PRODUCER: So, you don’t wish that you never had it?
DAVID SANCHEZ: I don’t wish that I never had it, no. I don’t think I’d be me, if I didn’t have sickle cell.
HANK GREELY: Sickle cell’s a really interesting, unusual genetic disease. If you’ve got two copies of the sickle gene, you’re really sick, and without modern medicine, you die young. If you’ve got two copies of the normal gene, you don’t get sickle cell at all. It turns out, though, that if you’ve got one sickle gene and one non-sickle gene, you make cells that are somewhat sickle? You’re not sick, but the organism that causes malaria doesn’t like those red blood cells.
MATT PORTEUS: Having a sickle gene is protective against getting severe malaria. So, in the environment where there’s lots of malaria, it’s better to be sickle cell trait than not to be sickle cell trait.
HANK GREELY: And that’s why you see sickle cell anemia in sub-Saharan Africa, but you also see it in the Mediterranean, in Greece and in Sardinia. It’s because they had mosquitoes and malaria.
MATT PORTEUS: The relationship between our genes and our environment is incredibly complex,…
WOMAN READING TO BABY: “Thanks, little brothers…”
MATT PORTEUS: …and we don’t understand that.
FENG ZHANG: I think we have to have humility. Nature is one of the greatest inventors of all time. What we can do is a very, very insignificant fraction of what nature has already done. Nature invented CRISPR.
RESEARCHER: So now we’re mixing the cells with the CRISPR.
DAVID SANCHEZ: That’s beautiful.
RESEARCHER: Once it’s into the cell, that starts the editing process. We can’t see that, we just know it happens.
DAVID SANCHEZ: I don’t know how, out of all the genes that you have, that it targets the one that’s doing sickle cell and not the thing that’s making you grow hair. Oh. But it does, apparently. Like, that’s cool.
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JENNIFER DOUDNA: You have to appreciate that this is a technology that’s only about five years old, but it’s been deployed incredibly rapidly. We’ve never had the ability to change the fundamental chemical nature of who we are in this way, right? And now we do. And what do we do with that? It does make us really think deeply about what it means to be human. What do we value about human society? And I know from…
FYODOR URNOV: The things that make us most human are some of the most genetically complex, which is kind of a relief: creativity,emotionality, love. Now, I want to be clear. They all have a biological basis. They are all written in our D.N.A. But we are a very, very, very long way away from being able to edit the person.
PRODUCER: You think that day will come?
FYODOR URNOV: I do, but I’m hopeful that we will mature as a species before we get this incredible technology to play with, for our own detriment. I am hopeful for that, yes. Is that hope based in fact? We’ll see.
ROBERT SINSHEIMER (Film Clip): How might we like to change our genes? Perhaps we would like to alter the uneasy balance of our emotions. Could we be less warlike, more self-confident, more serene? Perhaps.
Ours is, whether we like it or not, an age of transition. After 2-billion years, this is, in a sense, the end of the beginning.
TEXT ON SCREEN
IN NOVEMBER 2018, REPORTS SURFACED THAT CRISPR WAS USED TO ALTER THE DNA OF TWIN GIRLS BORN IN CHINA. IT MARKED THE FIRST TIME IN HISTORY THAT HUMANS EDITED THE GENETIC CODE OF A FUTURE GENERATION.
THIS CONTROVERSIAL EXPERIMENT HAS INTENSIFIED THE GLOBAL DEBATE ABOUT WHERE WE, AS A SPECIES, SHOULD DRAW THE LINE.
Adam Bolt & Regina Sobel
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- David Baltimore, Jill Banfield, Rodolphe Barrangou, Paul Berg, Rachel Carson, Alta Charo, Emmanuelle Charpentier, George Church, Tshaka Cunningham, Michael Dabrowski, Paul Dabrowski, George Daley, Bernard Davis, Jennifer Doudna, Robert Graham, Hank Greely, Ian Hodder, Stephen Hsu, Julian Huxley, Luciano Marraffini, Kelsey McClelland, Wayne Miller, Francisco Mojica, Ryan Phelan, Jorge Piedrahita, Matt Porteus, Antonio Regalado, David Sanchez, Dolores Sanchez, Robert Sinsheimer, Fyodor Urnov, Ethan Weiss, Palmer Weiss, Luhan Yang, Feng Zhang