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Duration:06:05
Uploaded:2017-08-11
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MLA Full: "What the CRISPR Embryo Editing Study Really Taught Us." YouTube, uploaded by SciShow, 11 August 2017, www.youtube.com/watch?v=BCO-U1glK14.
MLA Inline: (SciShow, 2017)
APA Full: SciShow. (2017, August 11). What the CRISPR Embryo Editing Study Really Taught Us [Video]. YouTube. https://youtube.com/watch?v=BCO-U1glK14
APA Inline: (SciShow, 2017)
Chicago Full: SciShow, "What the CRISPR Embryo Editing Study Really Taught Us.", August 11, 2017, YouTube, 06:05,
https://youtube.com/watch?v=BCO-U1glK14.
What did the recent study using the CRISPR gene editing technique actually entail, and what did we learn from it?

Hosted by: Hank Green
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Sources:

https://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature23305.pdf
https://www.nature.com/nature/journal/vaop/ncurrent/full/nature23533.html
http://www.nature.com/news/crispr-fixes-disease-gene-in-viable-human-embryos-1.22382
https://www.clinicaltrials.gov/ct2/show/NCT02793856?term=NCT02793856&rank=1
https://www.wired.com/story/first-us-crispr-edited-embryos-suggest-superbabies-wont-come-easy/
http://www.mayoclinic.org/diseases-conditions/hypertrophic-cardiomyopathy/home/ovc-20122102
http://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137
https://www.newscientist.com/article/2133095-boom-in-human-gene-editing-as-20-crispr-trials-gear-up/
http://www.heart.org/HEARTORG/Conditions/More/Cardiomyopathy/Hypertrophic-Cardiomyopathy_UCM_444317_Article.jsp#.WYj4rojyuM8

Images:

https://en.wikipedia.org/wiki/File:Crispr.png
(SciShow Intro)

Hank: There's been a lot of hype in the last couple of weeks about a study that used the gene editing technique CRISPR to modify human embryos. The study was published on August 2nd in the journal Nature by American and Korean researchers, and since then you might have heard concerns about designer babies and human genetic engineering run amok, but the study's real findings were a little more modest. A possible way to decrease the impact of one disease, and a surprising discovery about how the human genome could protect itself from being changed. 

CRISPR, more formally known as CRISPR-Cas9, is a relatively new genetic engineering technique. It gives scientists more power and flexibility to edit DNA in living cells than they've ever had, so lots of experiments are underway, from cancer treatments in adults to modifying disease-transmitting mosquitoes. The system uses an enzyme called Cas9, which makes cuts in DNA. A piece of RNA, which cells normally use as a chemical messenger, guides the Cas9 to a DNA sequence that matches up with the RNA sequence. Then, Cas9 makes a cut through both DNA strands. It's called a double stranded break. 

After that, a couple of things could happen. The cell might jam those loose DNA ends together as quickly as it can, even if it introduces mistakes, but sometimes, cells will fix the break by copying a DNA template instead. This can happen, for example, if a cell is getting ready to divide and it's made a couple of copies of its DNA. The cell can copy the copy to fix the original and everything's good.  

With CRIPSR, researchers can provide a specific DNA sequence for the cells to use as a template during these repairs. That way, they can introduce any changes they want, like adding a different version of the gene. In this study, the researchers were specifically looking at a gene called MYBPC3. It's involved in hypertrophic cardiomyopathy, a disease that makes the heart muscle thicker, and it can lead to sudden heart failure and death in young, otherwise health athletes when they push their hearts too hard while exercising. The disease can be managed with a variety of treatments, but there's no real cure, and if just one of a person's two copies of the gene has a mutation, they're affected by the disease and can pass it on to their children.  

These researchers wanted to use CRISPR-Cas9 to fix the gene in embryos to see if they can prevent it from being passed on from parent to child. For their experiment, they got sperm from a man with a mutant MYBPC3 gene and eggs from several healthy women with no mutant genes. They injected the sperm and the Cas9 protein with its guide RNA directly into the eggs, along with a single-stranded DNA template for a healthy version of the gene. Their goal was to get Cas9 to slice out any copies of the mutant gene and repair it with a healthy gene instead, and the fertilized eggs went on to produce embryos with two healthy MYBPC3 genes in 42 out of 58 trials, over 70% of the time. In the control experiment, without any CRISPR, it was around 50/50. That's what you'd expect because the man had one mutant copy and one normal copy, so half of his sperm were carrying the mutant gene.

So the treatment worked a little more efficiently than no treatment. Plus, the researchers were trying to avoid getting a mix of CRISPR-treated and -untreated cells in a single embryo. They seemed to succeed in all but one fertilized egg because they injected the sperm at the same time as CRISPR, but when the researchers took a closer look at the DNA sequences, they found something that they didn't expect  

See, the scientists had marked their template in ways that wouldn't change the final gene product but would show up in sequencing, but their markers weren't in almost all of the embryo cells with two healthy genes. So they realized that when the fertilized egg cells fixed the double-stranded breaks made by Cas9, almost all the cells totally ignored the template that the researchers provided. Instead, the cells used the healthy gene from the egg cell as a template to fix its diseased counterpart from the sperm. That's a mechanism for DNA repair that the researchers didn't see coming and it means a couple of big things.  

First, it suggests that there might be a way for our sperm and egg cells to resist changes in their DNA in a way that our cells don't. The researchers think that this kind of makes sense, since DNA in those cells is what lets us reproduce, so it's really important to keep it intact. Second, this newly-discovered repair system could mean that embryos will reject new DNA we try to give them, so we could possibly use CRISPR to fix a problem like MYBPC3 where one parent's gene is bad and the other is fine, but if genes from both parents are broken, this mechanism might resist any attempts to introduce new DNA that's supposed to fix them.  

Other than this surprising finding, the scope of this research is more modest than you might think from all the clickbait. Sometimes a parent might know that they carry a dangerous gene like MYBPC3 or the mutant BRCA gene that often leads to breast cancer, so they might use in vitro fertilization with pre-implantation genetic diagnosis, basically, that's when a doctor helps people create fertilized eggs, grows them into embryos, and then screens them for diseased genes and then implants only the healthy egg into someone's uterus. The technique in this new study could help doctors grow healthy embryos more often and improve the efficiency of IVF. Having to create fewer embryos is easier on parents.  

The patchwork of laws in different countries will make it difficult for this new technique to get off the ground, though. The study using human embryos, for instance, was only legal in the US because it was privately funded. Genetically engineering embryos to grow up into human beings is still way, way off. These were only grown in a culture for three days and were still just a tiny ball of 4-8 cells, and a great deal of research is needed to refine the techniques developed in this study and make sure they're absolutely safe for any theoretical human use. 

So whatever the headlines are saying, we are really looking at a narrow but surprising study. It showed us, once again, that there's still a lot we don't understand about how our bodies work and it's an incremental piece of research, which is usually the case with science, and if anything, its results make designer babies less likely, not more.

Thanks for watching this episode of SciShow News. The other big science news right now is the solar eclipse that's happening next Monday. We are very excited about it here at SciShow, so if you wanna learn more, you can check out our video on SciShow Space, and if you want more of this, you can go to youtube.com/scishow and subscribe.

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