Designer Babies – The Problem With China’s CRISPR Experiment

Designer Babies – The Problem With China’s CRISPR Experiment

This episode of Real Engineering is brought
to you by Skillshare, home to over 25,000 classes that could teach you a new life skill. On Nov 25th 2018 Dr. He Jiankui announced,
via youtube, that he had decided to push humankind across a controversial threshold. This announcement was, of course, that his
work had resulted in the birth of twins who had both been subject to genetic engineering
using CRISPR. This was a threshold widely considered to
be off limits. In 2015 two of the foremost journals in research,
Science [1] and Nature [2], both made similar statements stating that modification of human
germ cells, that is sperm and egg, should be avoided. The scientific community seemed to have come
to an agreement not to experiment with this technology until we could agree how and when
to apply it to humans, but Dr. He Jiankui has unceremoniously dragged us across this
line in the sand, whether we like it or not. Now, more than ever, there is an urgent need
to stop and ask what the outcomes of this work are for the individuals who have been
subject to it and also how the rest of society may be affected. … To understand all this we’re going to need
to understand how CRISPR technology works and what the intrinsic shortcomings of this
technology are. DNA is made of nitrogen and carbon based rings
which form 4 distinct chemical codes: Adenine (A), Guanine (G), Cytosine (C) and Thymine
(T). These codes form an easily reproducible double
stranded molecule which is read in group of threes, called codons, which are contained
within structures called genes. These genes are simply the parts of the DNA
that code for the more structurally complex proteins, which in turn, form the biological
machines and structures that are required for all life on earth. Due to DNA’s ability to copy itself, until
now the code in the DNA of all humans can be traced faithfully to the first cells on
earth. Dr. He’s work changed all of this by employing
the use of the CRISPR-CAS9 technology to purposefully change the DNA code in the two twins referred
to as Lula and Nana. As its name suggests, the CRISPR/CAS9 methodology
is dependent on two key parts: CRISPR and CAS9. CRISPR is a kind of repeating DNA structure
that was first discovered accidentally in bacterial DNA by the Japanese scientist Yoshizumi
Ishino in 1987 [3] . For 17 years following this discovery, the exact function of these
DNA repeats went undiscovered until it was identified as the means by which bacteria
identify and protect themselves against invading viral DNA [4]. It turned out that these strange DNA repeats
actually came from viruses. Bacteria have the ability to cut up invading
viral DNA, store it in their own DNA, and then subsequently use it as a guide system
for the enzymes CAS9, which destroys the viral DNA sequence should it invade again in the
future. In order to do this, CAS9 uses the stored
DNA to make something called a guide RNA. This guide RNA is usually coded for by a CRISPR
repeat, and guides CRISPR to DNA it should cut. There are two conditions for CRISPR’s binding
to its target. First Cas9 must bind to the target sequence
and a specific 3 code variation in DNA which is called a PAM (protospacer adjacent motif). Most PAMs can be recognized by Cas9 as they
contain the code: *GG. These recurring patterns are targeted by a
bacteria’s Cas9 system as they identify the DNA of invading viruses. This gives the bacteria an ability to target
and destroy the viral DNA. However, in the last 5 years, we have learned
to leverage this ability to direct CAS9 with guide RNA’s of our own design to alter the
genome of other organisms [5]. The guide RNA binds to a part of CAS9 called
the alpha-helical lobe. In turn, another domain of CAS9, the nuclease
lobe, binds to any flanking part of the DNA strands that matches with the guide RNA, causing
the double helix structure of the DNA to unwind [6]. This process is facilitated by the proximity
between the DNA and the Cas9 complex and electrostatic interactions that occur between the RNA and
DNA. At this point, 2 specific domains of the nuclease
lobe cut the DNA. Although we’re not yet fully sure how this
mechanism occurs, comparative studies suggest that the most likely way is that the two seperate
parts of Cas9 are able to rip protons from water molecules, and in turns weaponize the
deprotonated water molecule to break the DNA apart [ref]. This is done at two sites in the DNA, one
which cleaves the DNA at the target site (HNH) and another which cleaves the DNA at a non-target
site (RuvC). At this point a number of things can happen
depending on which approach is needed: – Cas9 can be modified to include a deaminase
enzyme which can target specific bases for mutation, leading to brand new mutations. – a process known as homology directed repair
can be used to insert new DNA at the cutting site. -Or the targeted piece of DNA can be simply
cut out and removed if it is deemed to be undesirable. Dr. He Jankui opted for the latter option
and simply cut a section out of a gene called CCR5. The section that was cut corresponded to a
mutation known as delta32, that confers it’s owners with protection to certain strands
of HIV. Dr. He’s data seems to suggest he may have
artificially induced a mutation, similar to, but not identical to the delta 32 mutation
in these twins [7]. In order to do this, Dr. He had to first optimize
the gene editing protocol in mice, monkey and human cells. The reason for this is to make sure the protocol
has high specificity – simply put, that the gene editing technique was editing the target
DNA and not some other sequence. This claim is of course key to the validity
of the experiment. Unedited embryos can be thrown away after
all – but for obvious reasons, making unspecific alterations to a human’s genetic code would
be a major red flag…and Dr. He’s work raises major red flags for this exact reason. Their check for specificity of gene editing
used parental genetics as a reference point, an inadequate approach due to the fact that
a parent’s genetic material is subject to a certain degree of randomization every time
a sperm or egg is produced. It’s further complicated by the fact that
no two sperm or eggs will be the same and that their methodology did not account for
the possibility that larger sections of the genetic code could be deleted by their implementation
of the Crispr/Cas9 system. Further to this, from the data released so
far we can tell that the mutation induced in the twins does not exactly mirror the delta32
population that He is attempting to induce in the twins [8]. Although the protein produced should in theory
largely mirror the naturally occuring mutation, we cannot tell that for sure because it has
not been tested. Standard practice at this point is to test
these mutations in an animal model in order to assess unexpected effects of the experiment. This is perhaps the most troublesome part
of this experiment. Lulu and Nana are test subjects for a genetic
mutation that we have not even taken the time and care to test in animals. Nonetheless, the mutation was induced in a
total of 31 human embryos. These embryos were grown for a period of 5-8
days and the 19 that were deemed “normal” were taken forward. Out of these 19 embryos 2 were implanted in
the mother to give rise to the twins. These concerns over Lulu’s and Nana’s
well being are only one of a myriad of issues: Perhaps most critically there was no medical
need for this treatment in the first place. It has been claimed that the biological father
of the twins is HIV positive. Given that the couple used IVF, and that there
is no evidence that HIV would be passed on from father to child using this method of
conception. The procedure was medically unnecessary. Furthermore, He claims to have induced this
mutation completely into at least one of the twins. To do this, He and his group would have had
to check the DNA in every cell in the growing blastocyst, a group of cells that exist from
days 5-9 post fertilization that eventually becomes the embryo. Given that they would have to destroy the
blastocyst to test all the cells, a clear logistical problem exists in trying to qualify
that the mutation exists in all the cells. Accordingly, He and his group only checked
a number of cells from the blastocyst. This means both twins might have a condition
called mosaicism, where the deletion only occurs in a subset of their cells. This means that different cells in their body,
have different DNA. In this context, the effects of this condition
are completely unstudied. Finally, the gene that He took aim at has
also been reported to have a role in learning. A link between the activity of the CCR5 gene
product and the dampening down of the brain’s ability to form new neural connections has
been previously described in mice models. Theoretically, there is a possibility that
the induced deletion could have a positive effect on the twin’s ability to learn. Right now there are far too many unknowns
to make an accurate prediction on what if any effect this experiment will have on the
two twins and there’s an even bigger question about what effect the announcement will have
on the progress of the field. Complicating this mess is the fact that this
study did not go in front of an adequate ethics approval board and default Chinese law prohibits
any kind of follow up with the twins. Because of this, we will likely never know
what will become of Lulu and Nana. Dr. He has stated that he plans to publish
the work in a peer reviewed journal, but given that he has gone M.I.A for almost 2 months
now [9], the scientific community may never have an opportunity to properly review and
digest the impact of this work. So where do we go from here? There is no doubt that genetic engineering
is a valuable tool that can potentially safely increase human wellbeing and productivity. It’s not unlikely that plunging into these
uncharted waters unaccounted and without approval may have a chilling effect on the proper utilization
and development of this technology though. Perhaps, until a consensus on the way forward
is established this is a good thing. Thankfully, the World Health Organization
has stepped up to take a moderating role in the process and are establishing a working
group to establish clear guidelines. We need these guidelines because we’ve stepped
into a new era of medicine. One where the genetic modification of humans
is not only a possibility but an increasingly real option. Humans have long sought to improve themselves
through technology. From the printing press to the internet, these
inventions exist to expand our knowledge and inform us. Maybe one day we’ll be able to alter our
genes to make ourselves smarter, but in the meantime we’re already surrounded by tools
for this, like watching educational videos on YouTube, or watching in-depth tutorials
and classes like the ones you’ll find on Skillshare. Skillshare gives you the perfect place to
start learn, with over 25,000 classes in a huge range of topics. Ranging from creative skills like painting
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skill to gain. As usual thanks for watching and thank you
to all my Patreon supporters. If you would like to see more from me, the
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100 thoughts on “Designer Babies – The Problem With China’s CRISPR Experiment

  1. Big thanks to my brother Dr. Seán McManus, who wrote this episode. He has a PhD in genetics, and I could not have made this episode without him.

  2. Next thing you know, China is gonna force all Uyghur and Tibetan couples to use designer babies to produce obedient Chinese citizens.

  3. CRISPR Cas-9 is a double-edged sword. One one hand, if used properly, it can be used to better the lives of humans and improve our standards of living. It can also be used to improve ourselves to complete with robots for jobs in abilities, improve our environment, and improve humans in general (Before anybody goes apeshit about eugenics and me being a nazi here, I'm mostly talking about curing genetic diseases, curing impediments to human living like HIV, you know, things that humans would be way better off without). However, it can also be used for dark purposes, like the aforementioned eugenics or by a state like North Korea to permanently cement its control over its populace.

    In my opinion, this event has both good and bad ramifications. On the good side, it has forced the world to finally confront the issue of CRISPR, in order to improve upon it, and to fix it. On the bad side, can you imagine what a nation like China would do with this technology? Let's be real here, China does not have a good track record for human rights. Everybody who has a rational mind should know this, no matter how reliant on Chinese products you are. They oppress Tibetans, imprisoned millions of Uyghurs in Soviet-style gulags, suppress all forms of wrongthink, for the lack of better terms, and permit child labor. Child labor and sweatshops are the things used to make most of our "made in China" products, it is something that we must live with. Now knowing all of this, do you seriously think you can trust China with CRISPR? Can you seriously imagine what the heck they would do with this? Let your imagination run wild.

  4. Never should have made it public, should have kept the gene engineering a secret and see how they lived throughout their lives and then publish the work to the public, but only if it was positive.

  5. It’s incredible how naïve these scientists are. Pushing for things like this are not only dangerous but completely unnecessary when you take a step back at all the stigma there already is around naturally occurring differences in humans, much less towards lab-modified lives.

    Do you really think the world will be better off with any number of people born with scientific mods that are done without their consent? We can’t even get the Chinese government to leave Africa alone, I doubt they’d see this going on in their country and not try anything malicious.

  6. Why not? We don't want our children to be sick,get cancer or any diseases. I think it's a good idea to have healthy babies & people

  7. I look forward for Germany and Japan to start improving their race.
    If Hitler had not spoiled the image of the idea of improving humanity, we would have got rid of most diseases 50 years ago and would have become much better. Eugenics, pharmacology, genetic engineering, it all exists for so long but does not develop (For real benefit to people). After 100 years, people will think that we are idios who wanted to get stuck in the Stone Age.

  8. China failed to realize they have a man who can make new generation of china kids , who are taller and dont have lazy eyes.

  9. Wait so this guy had the balls to dive deep into what is considered "taboo" also saying he would publish his work.

    So the medical community lashed out, and now you haven't heard from him in months?

    What's he doing now? How are the subjects? You don't know. It's almost as if we forced him underground by clinging to some "wah think of the children".

    Think of the fucking human race. We aren't evolving anymore, this is the next step to improve. People might get hurt in the process, just like in every single new technology. Nuclear, aviation, etc. Get over it.

    Now China has the research and isn't sharing. Good on you. 👍

    Can you spell S U P E R S O L D I E R S?

  10. I see no issue with smh man you know how far back we’re keeping our selfs as a species from not testing these gene modifications. And who cares if it’ll be born with it fuck it I’d don’t all my but for then to experiment with it fuck them kids!

  11. WAIT THERE ISNT GOING TO BE A FOLLOWUP? so there are going to maybe be descendants of these twins with unnatural DNA? oh boy.

  12. 0:50 because it seems like he is the only guy who understands that it's impossible. Humans would never come to an agreement that important, we can't even agree to stop dumping plastic everywhere.

  13. There’s a chance in the future people will look back at dr. J (the name I’m calling the Chinese doctor whom made the crisper babies because I don’t wanna butcher his name or the Chinese language) and see him as the person whom took the first step into a bigger furores of Genetic editing and genetic engendering

  14. Ahh I see so China marches on in the development of easily controllable, expendable, super soldiers/workers in their quest for domination.

  15. Do it I think is fine as long as it's all for study only till we figure the long term and unseen affects before it goes commercial. People that volunteer should be explained the risk in great detail and they must agree to be a lab rat. To know all side effects this would take 50-100+ years. If we get all this worked out it can help all humans but not before we put in the work first to understand short and long term effects and risks.

  16. Change the genes of other organisms… but not our own? Freedom of will is limited and as I see it this modern assumption deserves inversion. Parent's choice is the key to legitimizing this technology. We should not be doing this to other species however. Not even corn.

  17. all I can think about as I watch this is when thor is like: WHAT DID YOU DO?! WHAT DID YOU DO?! after thanos snaps and then thanos just dips.
    On a more serious note though, this shit scares me, and that chinese genetic scientist is a dumbass and an asshole. I really hope this can be dealt with before it becomes a crisis

  18. It is said that the doctor is recruited by the Chinese government to make the next generation of super soldiers

  19. It’s pretty obvious making the twins immune to AIDS is a false front. This is all about getting a leg up on their ability to learn.

    Edit: just noticed this argument was already made. lol, it’s pretty obvious.

    When have humans been responsible and safe with new and dangerous science? Never… So now, as science/tech advances exponentially, we're going to have tech so advanced as to be so dangerous it will END US so fast… Yet we have not changed at all in our sociological…collective maturity? I don't know what to call it but we are like retarded children or teenagers with unbalanced brains who were brought up by BAD parents… still fighting each other… wrecking the planet…
    More and more advanced tech… Just wait till that 1st nano-bot programmed to self replicated itself (by eating matter) gets chomping! 😉

  21. Such technologies MUST be EXTENSIVELY researched BEFORE implementing. Whenever we play God(?), we fail miserably.

  22. I'm sure its fine. No difference than getting cucked by nature and being born with physical defects. At least if it goes wrong here you have someone who will apologise to you. I've yet to get an apology from nature.

    As long as the surrogate mothers have their well-being protected, are aware of the experiment and consent to it in full knowledge and without coersion, I don't see a problem. There are people suffering right now because this technology isn't ready yet. We need this if we are going to fight devolution due to medical and societal advancement. Idk, I see a lot of unethical practice in the world but this doesn't seem like one, not on the surface.

    I mean, what are we going to do to prevent google and others from birthing an authoritarian dystopian future?

  23. It’s just religious fuckers throwing spanner in the works to prevent progress. Fucking moral and ethics stick it up your religious asses and go fuck yourself.

  24. I would only use this technology to help save babies survive possible diseases and deformities from possible abuse of miscare from the parents.
    Or to prevent hindering problems later in their lives.

    But we all know some mofo will want to weaponize something…like hamsters or bird shit.

  25. The same happened with Invitrio Fertilization. Someone went out side the world science club and did it anyway. Now it is of common use. What happens next is up to the science community and China's regulatory agencies. Stay Tuned. The road may get rocky.

  26. Mario says "genetically altering embryos for science is unethical"

    Luigi says "a r y a n s u p r e m a c y h e r e w e c o m e"

    Note: I do not approve of the angry moustache man's ideas, and am not a nazi.

  27. 1:18 – 2:10
    Your over exaggeration, makes it sound, as the Dr. made the woman birth actual aliens;
    also, that they use another molecule, to store genetic information, instead of DNA… 🤦‍♂️
    It's not as if they stopped being humans, which means, there shouldn't be any problems,
    doing the retrace with those kids, compared to with anyone else;
    there will probably be a few weird tell-tale signs, that something's off, but they're still human.

  28. Codons are mRNA nucleotide triplets, the ones in DNA are called, well, triplets and the ones on tRNA are called anticodons

  29. The way he did it was wrong, the concept itself is 100% positive for humanity. It's just needs to be done minimally, non-augmental, and regulated.

  30. Kudos to Chinese doctor. Otherwise the other scientists would have sat on their lazy butts for another 1000 years

  31. Kids for sale….Asian brain.. African body and Caucasian face.. germ resistant.. $100,000. limited supply

  32. Great man, nothing came from sticking to ethics, it's a drag slows down progress, he was wrong yes but doing so he did what many did who came before him he took risks.

  33. I literally see no issue with this, as bad as it may sound you can't make a omelette without braking some eggs.

  34. i can so easily imagine Chinese "doctors" making changes in genes that massively impact our species within a couple of hundred years, because they didn't want to wait before doing tests, if they had common sense all of these people would be marked and they wouldn't allow bloodline mixing i mean that is cruel.. what if one of the twins wants to leave china marry somebody in japan.. but it'd be safer if these children never leave china.
    It may already be too late if they cause changes they dont understand and those changes spread.

    sigh.. humanity is too arrogant for its own good.

  35. There will be a day like our phones when a virus update will come out for us….and well just update like our phones…cause like they can just keep checking for foreign dna in our system and edit it out lol

  36. Does anyone remember the movie gattaca.

    The technology should only be used to correct serious genetic flaws.

    Like deformities, Down syndrome and other genetic debilitating conditions

  37. Great cover on this article since it has been black listed story even getting information on cas 9 genetic studies involving treatment for virus and HIV isnt published much. At no point am i saying we should play god but just cause we have medication to fight these virus there will be mutations so option to render them inert is still a important topic to study.

  38. Wait, he deleted the CCR5-D32? But why? That mutation prevents HIV access to cell (aka HIV immunity) so, why even delete that?

    Edit: maybe not complete immunity (few cases of homozygous carriers reporting to have HIV) but it does show HIV resistance nonetheless

  39. I'm fully in favor of making people healthier, smarter, fitter, and with better hairlines. I don't see a downside.

  40. flatworm cut it 30 times it will self replicate itself 30 times tardigrade there are tardigrades that can live in the vacuum of space by hints sleeping hibernation there are some that can survive extreme cold there are some that can survive extreme heat and hibernate for very long periods of time there is the immortal jellyfish that can go from juvenile to sexual maturity and reverse back to juvenile we are cutting these out and putting in the human genome

  41. Master blank self-replicating stem cell it is the only stem cell that can be used on any other stem cell and you can regrow the master blank self-replicating stem cell

  42. Time for the people of planet Earth to know the truth people no more holding back cut the ethics out cut the religion out and cut the powers-that-be out we are here to give the people the choice to take the gift of life

  43. The NSA and the FBI question me they thought that I was involved with some retarded group they have no clue who I'm involved with we are not bad people we are here to give the people at Planet Earth what they deserve what is rightfully theirs the real tree of life perfect genetics that they wanted in a machine that can replicate any wavelength think about that people a machine that can replicate any wavelength anybody in physics will tell you that's something like that can do anything Higgs boson field okay let's see here some things get caught in the field and they stay wavelengths and the ones that go through what do they do they become matter they become Mass so now you just replicate before during and after those waves going through and turning into mass now Yuri controlling what turns into Mass I have it on paper exactly how to build it you have to build it from the base wave up just like building a computer program from the binary code up

  44. To see how long it takes the feds in the NSA to come get me I hope they do because then I'm releasing the files we got from the main one

  45. I think china is in the right trying to learn genetic engineering. So many genetic diseases like downs, sickle cell anemia and many more would become a thing of the past.

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