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Genetically modifying plants and animals is complicated business, but some scientists think this tool could be used to save lives in a variety of ways.

Hosted by: Olivia Gordon

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Sources:
Golden Rice:
https://www.mountsinai.org/health-library/supplement/beta-carotene
https://www.aao.org/eye-health/diseases/vitamin-deficiency
https://academic.oup.com/ajcn/article/104/3/769/4668541
https://www.ncbi.nlm.nih.gov/pubmed/10634784
https://www.nature.com/articles/nbt0718-559a
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039550
https://irri.org/news-and-events/news/golden-rice-meets-food-safety-standards-three-global-leading-regulatory-0
http://www.foodstandards.gov.au/code/applications/Documents/A1138%20Approval%20report.pdf
http://www.vib.be/en/news/Documents/vib_fact_GoldenRice_EN.pdf
https://www.acsh.org/news/2017/05/18/embrace-golden-rice-globally-remains-frustratingly-slow-11297
https://futurism.com/gmo-golden-rice-allowed-us

Spicy tomatoes:
https://www.cell.com/trends/plant-science/fulltext/S1360-1385(18)30261-9
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267963/
http://blogs.discovermagazine.com/d-brief/2019/01/08/hot-spicy-tomato-capsaicin-genetic-

Allergen-free milk:
https://www.foodallergy.org/life-with-food-allergies/food-allergy-101/facts-and-statistics
https://www.nature.com/articles/s41598-018-32024-x
https://www.pnas.org/content/109/42/16811
https://www.nature.com/articles/s41598-018-25654-8

Cancer-fighting eggs:
https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer
https://www.beltina.org/interferons-alpha-beta-and-cancer-treatment/
https://www.nature.com/articles/s41598-018-28438-2
https://splice-bio.com/genetically-modified-chickens-lay-cancer-fighting-eggs/
https://www.in-pharmatechnologist.com/Article/2007/01/16/Protein-production-in-chicken-eggs-cracked
https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-018-0495-1

Vaccine-delivering bananas:
https://pdfs.semanticscholar.org/97ff/85496c35d1b280d2adf2060b39184080bfd9.pdf
http://www.genomenewsnetwork.org/articles/07_00/VACCINE_BASE2_5_8.pdf
https://www.researchgate.net/figure/Advantages-and-disadvantages-of-edible-vaccines_tbl3_228778843
https://www.scientificamerican.com/article/edible-vaccines-2006-12/
https://www.theguardian.com/science/2000/sep/08/gm.infectiousdiseases
https://www.researchgate.net/publication/27800426_Review_Article_-_Edible_vaccines_Current_status_and_future
https://www.researchgate.net/figure/Advantages-and-disadvantages-of-edible-vaccines_tbl3_228778843
https://www.cdc.gov/rotavirus/surveillance.html

Osteoporosis-fighting carrots:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234161/

Ebola-fighting tobacco:
https://www.mdpi.com/1422-0067/16/12/26122
http://sciencenordic.com/genetically-modified-tobacco-plants-medicine-ebola
https://www.scripps.edu/news-and-events/press-room/2014/20141117ebola.html
https://www.mdmag.com/medical-news/investigative-ebola-treatment-zmapp-to-undergo-testing

Image Sources:
https://commons.wikimedia.org/wiki/File:Beta-Carotene-3D-spacefill.png
https://commons.wikimedia.org/wiki/File:Golden_Rice.jpg
https://commons.wikimedia.org/wiki/File:Agrobacterium_tumefaciens_Forsythie.jpg
https://commons.wikimedia.org/wiki/File:Capsaicin-3D-vdW.png
https://en.wikipedia.org/wiki/File:Bacterial_leaf_spot_symptoms.jpg
https://commons.wikimedia.org/wiki/File:3blg.png
https://commons.wikimedia.org/wiki/File:Human-interferon-beta-pdb-1AU1.png
[♪ INTRO].

It’s been over forty years since genetically modified organisms became a thing, and they’re still a contentious subject. And that’s in part because GMOs suffer from a serious image problem.

That’s probably because most of the GMOs we hear about are designed to increase crop yield and therefore profit for farmers and big biotech corporations. So consumers are understandably left wondering, “What’s in it for me?” The answer to that is: potentially a lot, because there are all kinds of GMOs on the horizon that are designed to save human lives rather than line pockets. It’s worth remembering that genetic engineering is a tool—and it’s how you use it that counts.

And today, we’re going to talk about 5 cases where genetic modification could be used to help people directly, from vaccine-delivering fruits to cancer-fighting eggs. Beta-carotene is one of the main pigments that gives orange and yellow fruits and vegetables their brilliant colors. It’s also an important nutrient because it gets converted into vitamin A—an essential vitamin that your body can’t make on its own.

Cells all over your body need vitamin A, but it’s especially important to your eyes because it’s used to make one of the light-sensing proteins that allows you to see. And while a typical Western diet contains enough of the stuff, in some parts of the world, vitamin A deficiency is a huge problem. It affects millions of people, especially kids.

So scientists have been trying to find a way to get people more vitamin A for a long time, and genetic engineering may be a part of the solution. Golden rice is a genetically-modified rice variety with lots of beta-carotene in its grains—which is what gives it that characteristic color. And because of all that beta-carotene, studies suggest just 100 to 150 grams of cooked golden rice—about a bowlful—can provide a person with roughly half of the recommended daily amount of vitamin A.

Rice was chosen because it’s a staple in many parts of the world where vitamin A deficiency is a big problem, like Africa and southeast Asia. And unmodified rice plants can already synthesise beta-carotene. The problem is, they only do this in their leaves—two key steps are switched off in the grain.

So the enzymes needed for those steps are added back in by golden rice’s transgenes—the genes that come from other organisms. Specifically, the GE plant has a phytoene synthase from maize, and a bacterial phytoene desaturase from a common soil bacteria. These are hooked up to a grain-specific promoter—a sequence of DNA that ensures they’re only expressed in the rice grains.

And they were added to the rice’s genome with the help of a bacterium called Agrobacterium tumefaciens. It’s a plant pathogen that, in nature, injects parts of its DNA into plant cells to make the plants produce tumor-like growths that the bacteria feed on. Scientists in the 1970s were able to figure out exactly what DNA it introduces and what genes were needed to make that happen.

And that allowed them to transform this pest into a DNA-delivery vector. Even now, with all kinds of genetic technologies available, it’s one of most common methods used to modify plants. And while the process seems pretty straightforward, golden rice has been in development for nearly two decades.

Part of that has been tweaking the plants to get them to produce enough beta-carotene while still yielding enough rice for farmers. And part of it has been fighting the haters—anti-GMO groups have been campaigning against its introduction from the get-go. Despite all these challenges, golden rice is pretty close to becoming a reality.

It’s been approved by multiple regulatory agencies around the world, including the US FDA. And in places like Bangladesh, commercial cultivation could happen in 2019. Salsa lovers rejoice!

The day is coming when you won’t have to add hot peppers to your favorite spicy condiment. Scientists are considering developing a tomato variety that contains the same spicy compound as a jalapeno or habanero. It’s probably not immediately obvious to you why this would be considered a “health.

GMO,” but as it turns out, the compound that makes peppers spicy — called capsaicin — also has health benefits. Scientists are especially interested in its anti-tumor and pain-relieving properties. And that’s where tomatoes come in.

Tomatoes are a distant relative of hot peppers — the two diverged around 19 million years ago — and they still possess the genes to make capsaicin. They’re just turned off. So, to get spicy tomatoes, genetic engineering would just have to coax the plants to turn them back on.

Scientists could just get capsaicin from hot peppers directly instead of tinkering with tomato genes. But, peppers are especially vulnerable to pests, and the amount of capsaicin they produce is unpredictable. Also, it takes a lot of land to grow them in bulk.

A hectare will only produce about 3 metric tons of hot peppers, while the same plot of land can yield around 110 metric tons of tomatoes. This is all still theoretical, but scientists are considering a couple of approaches to turn those bland tomatoes into capsaicin factories. In one approach, scientists could use proteins called transcriptional activator-like effector proteins, or TAL effectors.

These bind to promoter sequences in plant DNA to turn genes on. They actually originally come from Xanthomonas species, bacterial plant pathogens which cause a disease called bacterial spot in tomatoes and peppers using these expression-changing proteins. But, like the bacteria used to make golden rice, TAL effectors can be customized to activate pretty much any plant genes scientists want—including the key genes in the capsaicin synthesis pathway.

Alternatively, scientists could use gene editing techniques like CRISPR to replace the promoter regions of the inactive genes with promoters from genes that are expressed in tomato fruits. If they used this method, there wouldn’t be any transgenes involved—the plants would just have sections of their own DNA copied and pasted elsewhere in their genome. Of course, until researchers actually try these ideas out in a lab, they won’t know for sure if reactivating the genes will work the way it’s supposed to.

If it does, though, it’ll be great news for health professionals studying capsaicin—and for pranksters looking for an especially evil practical joke. One of the most common childhood allergies is milk and dairy. Kids generally outgrow it, but about two to three percent of infants can’t be given milk products, including most formulas.

And that’s a difficult problem if they are not or cannot be breastfed. But geneticists think they have a solution: a genetically modified cow whose milk doesn’t have the whey protein beta-lactoglobulin, or BLG—the main allergen behind milk allergies. The first of these hypoallergenic cows was Daisy—a dairy cow in New Zealand whose creation was detailed in a 2012 study in the journal PNAS.

Added to her genome are two small snippets of DNA that create microRNAs—tiny RNAs that interfere with protein production. To make a protein, cells first transcribe the DNA from a gene into RNA, and then that. RNA is translated into a protein sequence.

MicroRNAs bind to these RNA sequences, keeping them from getting translated. Daisy expresses two microRNAs to target the BLG protein, so she produces basically none of it in her milk. Since the 2012 study, scientists have monitored 12 of Daisy’s female offspring, and they have no detectable levels of BLG in their milk, either—which suggests the change is lasting, so a herd of hypoallergenic cows is possible.

More recent studies have used other gene editing approaches to simply turn off the BLG gene. A 2018 paper in the journal Scientific Reports used zinc-finger nucleases, a kind of molecular scissors, to snip BLG’s promoter region, creating a mutation that makes it inactive. Both of these are still proof of concept studies, though.

And they’ve run into the same problem. A cow’s body seems to compensate for the lack of BLG by increasing expression of other milk proteins, including casein, which can separately trigger allergies. So more research is needed before GMO cows can actually start providing the world with allergen-free milk.

Cancers are a major medical problem, and it doesn’t help that the drugs we use to treat them can be expensive and difficult to produce. Take interferon-beta, a tumor-suppressor that doctors can prescribe to help tackle several kinds of cancer. The protein is produced naturally by the human body to help regulate the immune response.

But since we can’t really extract large amounts of it from people, for pharmaceutical use, it’s manufactured in what’s called a mechanical bioreactor. The process involves growing tons cells that have been genetically modified to produce the drug, then extracting the drug afterwards. Then one day, some scientists in Japan apparently thought, “You know what’s less expensive than a mechanical bioreactor?

A chicken.” As they explain in a 2018 paper in Scientific Reports, the team used CRISPR to insert human interferon-beta DNA into the chicken’s primordial germ cells—the ones that become sperm. They stuck the gene next to the one for ovalbumin—the main protein in egg whites—to ensure the drug would be heavily expressed in eggs. The modified cells were then injected into two and a half day-old embryonic roosters, which grew up into healthy adults with the new gene in their genome.

That’s only step 2. These males were then bred with hens so that they’d end up with offspring that carried the protein-producing gene. The hens from that generation were the ones that went on to lay eggs with interferon-beta in their whites, from which the drug could be extracted.

This seems like an awful lot of trouble, but chicken-produced interferon-beta could be up to 90 percent more cost-effective than the stuff made with the usual production method. In fact, these chickens are so efficient at producing the protein that some estimates say a small flock of a few hundred birds could satisfy worldwide demand for the drug. And there are other benefits to using chickens, as opposed to plants or other animals.

It turns out chicken proteins and human proteins have similar patterns of sugar groups added to them. So human immune systems are less likely to attack proteins produced by chickens than those made by traditional methods. And these Japanese drug-making chickens aren’t the only ones out there.

Scientists in the UK have also successfully created GMO chickens that produce cancer-fighting proteins in their eggs. But so far, these engineered chickens only show it’s possible. We’re years away from such research changing the way many drugs are manufactured.

People in places like the US might take for granted the fact that there are no logistical barriers keeping them from getting vaccinations to prevent some of the world’s worst diseases. But vaccines generally have to stay refrigerated and be administered by a doctor, and that means they’re a lot harder to get in some parts of the world. That’s why scientists are trying to make edible vaccines — plants that are genetically engineered to provide immunity to the people who consume them.

The idea is that they’d work a lot like a regular vaccine—they’d deliver some benign target that looks like a key part of the dangerous pathogen, so your immune system can learn to recognize that and mount an effective defense if you’re ever exposed to the real deal. Researchers have already made a banana that contains a chunk of DNA from the bacteria that causes cholera, for example. The transgene in the fruit—which encodes for a harmless part of the cholera toxin—was added using Agrobacterium, in a process much like the one that created golden rice.

And in the end, the bananas contain enough of the protein that one dried banana chip could be an effective vaccine dose. Banana-based vaccines are also being developed against hepatitis B, but they’re likely to work best against gastrointestinal diseases like rotavirus—a highly contagious childhood stomach ailment that kills more than 200,000 children a year. That’s because the bananas come into direct contact with the mucosal lining of the stomach, stimulating the immune defenses there.

You could theoretically choose any edible plant for such vaccines, but bananas are a pretty great choice because they don’t need to be refrigerated and are already a common staple in areas where these vaccines are most needed. And, they’re often eaten raw. And that’s an important piece of the puzzle, because cooking could destroy the vaccine part.

Banana-vaccines could also be really cost-efficient. According to one estimate, about 81 hectares of land could be enough to produce hepatitis. B vaccines for every baby in the world.

But, these edible vaccines aren’t quite ready to hit the world stage—there are some kinks to work out, like getting them to make reliable amounts of the inserted protein in each fruit. Perhaps the biggest hurdle, though, is simply the long path to clinical approval. Like any other vaccine, GM bananas will have to run the regulatory gauntlet to show they’re both safe and effective before they’re approved for use, and that could take decades.

There are a lot of other awesome GMOs in the works, too—like carrots with more calcium to fight osteoporosis. Or, tobacco plants that produce antibodies which inactivate the ebola virus. Our ability to manipulate genomes has all sorts of potential medical uses.

Because genetic engineering isn’t an inherently bad thing. And when it’s used well, it can do a lot of good. Thanks for watching this episode of SciShow!

And extra thanks to all of our supporters, including our channel members and our Patreon patrons. If you like what you just saw, stick around! If you subscribe to the channel and you’ll get notified every time we upload a new episode.

And if you want to learn more about genetic engineering specifically, you might like our episode on CRISPR. [♪ OUTRO].