Tinkering with genes is actually an ethical thing to do. [kondwani] i wanna know what breakthroughs are being made. Technologies like crispr are incredibly powerful. What were doing here is really the beginning of a true revolution. That will force the future too. That is incredible. Live genetic engineering. eerie staccato music dramatic electronic music prosthetic clicking water speckles robotic arm whirring electronic tone beeping my name is kondwani phiri. Im a genetic researcher. You could say, its in my blood. From an early age of about eight or nine or so, i had just a natural curiosity for the natural world. Cancer runs in my family. In fact, i lost my aunt to breast cancer. And that peaked my interests in genetics. Im fascinated by how the genes we inherit shape our biological destiny, including our health. I believe the key to treatments and cures for diseases like these, lies in explicit efforts to engineer human genes. But can we fix not only whats broken but also enhance our genetic codes and improve on Mother Nature . Some day, will humans direct their own evolution and should we . dramatic staccato music im starting my journey in washington dc to visit a family whos grappling with the difficulties caused by genetic disease. Hello. Hi, annabel. [nina] can you shake hands annabel . Hi. Oh my gosh. How are you . Oh, i think shes shy. chuckles four year old annabel frost has a heartwrenching genetic disorder. Could you tell me a little bit about annabel . When annabel was born, it was such a wonderful moment. But we were in this happy fog and didnt notice the nystagmus. The eye movement. We didnt notice the jerky musc movements we didnt notice any of that, but the doctors realized that something was wrong. [kondwani] they diagnosed annabel with alternating hemiplegia of childhood or ahc. Hi. [kondwani] this extremely rare disorder causes debilitating spells of paralysis, delayed development, and lifethreatening seizures. Shed have days of paralysis where her full one side of her body, shed drag it along behind her as she crawled. [simon] you know, once a day, she will have these choking episodes where i need to pick her up and hit her on the back to make sure that she could breathe. ominous music dramatic electronic music annabels condition is a result of a problem in her dna. The twisng double helix of dna is made up of four different baseairs or nucleotides. The unique suence of these base pairs are instructions for the body to make proteins. The base pairs are like musical notes on a score that tell a musician how to play a song. When all the different sections of the dna are played, the result is a biological symphony. upbeat orchestral music but like the musical note played out of key that compromises the entire performance, there is an error in one of annabels genes. annabel groans tense electronic music the mutation in the atp1a3 gene is disrupting her nerve cells, leading to her severe condition. Ahc is fundamentally intertwined in her genetic code. There is no restorative treatment or cure. The medicines that they have are kind of more about masking symptoms in a very unspecific untargeted way. And we wanted to try to figure out if there was a way to address the cause and not the symptoms. [kondwani] without targeted treatment, annabel could die. Any day. [family] happy birthday, dear annabel. Theres a timeline on this for us. Weve got a ticking cloak in the back of our minds, all the time. The frosts are desperate for any kind of help. From sickle cell anea to huntingtons disease, millions of people suffer from thousands of genetic disorders, much like annabel. Unless scientists can address these genetic errors, children, like annabel, will suffer agonizing pain and some will die young. I want to know, can genetic engineering help families like this in the future . Oh, good girl. Oh, thats so nice. pensive electronic music the double helix structure in dna was first revealed in 1953 by rosalind franklin, Francis Crick and james watson, and within a few decades, scientists discovered how to alter the dna of living organisms. But gene editing really took off around 2013 when scientists harnessed a molecular mechanism found in certain bacteria. This remarkable mechanism is called crisprcas9 or crispr for short. Crisprcas9 contains an enzyme that serves as the bacterias defense mechanism against viruses. When viruses infect the bacteria, the crispr machinery targets the specific section of dna. Then the enzyme responds like a pair of scissors and literally cuts the viruss genetic code apart. Scientists are now are harnessing this natural mechanism to target and precisely edit dna of numerous organisms. To find out how, im heading to a biotech lab in brooklyn, new york. Im on my way to genspace, which is the worlds First Community biology lab. Beth tuck is the director of Science Education at genspace. We are an open access science lab. Were a Community Biology lab. So youre telling me if im Computer Programmer and i want to learn more about biology, i could essentially come down here and take a class and use your facilities . Thats it. Beth is going to show me how to use crispr in the lab to edit a bacterias genes in a new and novel way. I brought this kit. Could you explain a little bit how this kit works . Yeah, sure. Got a pipette. This is our measuring device. Got a rack where well put some of our plastic tubes. Some plates. Petri dishes, and then our e. Coli. [kondwani] e. Coli is a type of bacteria that lives in t intestines of humans and animals. Though some strains can be deadly, most are harmless. Gloved up. Lets do this. All right. So weve got our e. Coli here. These are called dh5alpha, which is a type of species that isnt harmful to people with normal immune systems. [kondwani] thats good to know. So our first thing that we need to do is actually get these bacteria out of this jar, and so you just kind of scoop it in there. Yep, swirl it around. Bring a little bit up. The way that this experiment works is were gonna spend a day to prepare the bacteria. eerie dramatic music [kondwani] next, we insert arispr construct that will alter their dna. Were gonna add in the crispr machinery and then change the cells. [kondwan ah the crispr machinery targets and edits a specific gene in the e. Coli, so that they can adapt to a lethal dose of antibiotics. Normally, bacteria cant grow in the presence of this antibiotic. The drug kills the bacteria. We need to get these bacteria onto this plate, so they can grow. Youre just gonna gently drag it across the surface of the plate. Thats it . Yeah, thats it. [kondwani] over the course of several days, beth grows the gene edited bacteria in a petri dish laced with e. Coli killing antibiotic. But despite this toxic onslaught, thgenetically altered e. Coli contue to grow. I see plenty of growth. The whole point of this is to show that changing an organisms dna can change its features, and that you can do it with crispr in a really precise way. In a way that wasnt feasible before. What kind of positive outcomes can we expect from using crispr . You can use it to design new onthespot testing for infectious diseases. You can use it to cut out hiv from human cells. Theres so many more uses that we havent even imagined yet. That, to me, is why this stuff is so exciting. [kondwani] harnessing the natural ability of crispr and transforming it into a technological tool has the potential to address all sorts of problems. dramatic electronic music [narrator] in the future, advanced gene editing techniques are reworking microbes to create healthier lives. Bacteria are engineered into many pharmaceutical facties. These microorganisms generate an inexpensive abundant supply of medicines for diseases like malaria, rabies, and coronavirus. And, specially modified yeast converts organic waste into green biofuels. This Innovative Energy source is not only renewable, but it also backs more of a punch than regular fossil fuels. water gurgling dramatic electronic music formulated by charles darwin, Natural Selection is the driving force of evolution. While many individuals perish, species st adapted to their environment survive and reproduce passing along their advantageous genetic traits to their offspring. These traits like heights, eye color, strength, and even personality are contained in genes. Over generations, the process of Natural Selection perpetually fine tunes the species at the genetic level, helping the individuals to continually adapt to changes in their environment. Humans learned to direct this evolutionary process through artificial selection. Through the intentional selection of mates, humans facilitated the breeding of animal offspring with desired characteristics. Arguably, the first known example of artificial selection happened over 15,000 years ago when humans domesticated the wolf. Breeding what we now know today as the dog. In agriculture, artificial selection has improved and even created new fruits and vegetable. Through selective breeding for certain traits, th simple wild mustard plant was transformed into cauliflower, cabbage, and even broccoli. But even artificial selection takes at least a few generations to work. Capitalizing on the natural crispr process, gene editing in the lab n compress the evolution down to a matter of months. Using crispr to manually engineer dna is the next step in accelerated evolution and with this remarkable tool, scientists can even improve our food supply. This matters because over 10 of the world suffers from hunger and malnourishment. Im in raleigh, North Carolina with pioneering food scientist, dr. Rodolphe barrangou, whos using gene editing to boost Food Production and feed the plant. Were gonna be able to breed crops that are more efficient, that are more resistant to disse. The biggest impact crispr may have shortterm, maybe the next decade or so, will be to revolutionize the food supply ain. In fact, rodolphe had a hand in the discovery of the natural crispr mechanism in bacteria, and his use of crispr as a technology in milk is leading to remarkable innovations in dairy proteins. So what were looking at here is milk that is in the process of fermenting. [kondwani] okay, so this is in the earlier stage of things. Very early stage. So we add the bacteria to start the fermentation process and then used the lactose to solidify milk into cheese and yogurt. [kondwani] in most dairy facilities, regulabacteria and yeast kickstart the fermentation process. But before starting, rodolphe added a twist. He used Crispr Technology to enhance the bacteria used in the fermentation of milk. We used it to build resistance in bacteria that make cheese and yogurt, to have better fermentations d better manufacturing of dairy products. [kondwani] by vaccinating thbacteria, his dairy ltures almost aays succd which improves the process of making yogurt and cheese. Processes like these, also make them healthier. Crispr has been a life changer and then also haopened tremendous avenues to provide a healthier and more Sustainable Food supply for humanity. [kondwani] but the true revolutionary potential of Crispr Technology is just now starting to be realized. Other people caught on to using these molecular machines to actually cut dna, to do genome editing, not just in bacteria but in other organisms. By understanding what crispr is and how it works, scientists were able toevelop technologies to enable us to now change the world. [kondwani] by 2050, the World Population is expected to soar to 10 billion people. Food production will need to increase 70 to catch up. To feed our growing population with the same amount of farmland, the mass production of food must be hyperefficient. At nc states plants and microbial biology lab, rodolphes colleague, mary beth dallas, is facing this daunting prospect. I manage this lab and i also do research on cassava. [kondwani] also known as the yuca plant, cassava is the primary food staple of nearly 1 billion people. Cassava plant is very close to my heart. [kondwani] this root vegetable is kind of like a potato and is widely grown across africa and the americas. They can actually harvest the tubers and make flour, and they can make breads out of that. They can also eat the greens. Its really a nice plant. Yeah, and me being a native zambian, thats where i was born. I grew up eating cassava, as well as cassava leaf. So chuckles it has special you know all about it. I know all about it. So it has a special place in my heart, its supposed to. But theres a problem. A malady called cassava mosaic disease is ravaging this critical food source. In africa alone, its destroyed cassava crops, leading to numerous famines. You can see here, the devastation of the plants. It gets really thin leaves and a mosaic pattern occurs. When the leaves get destroyed like this, they cannot photosynthesize properly and the tubers that are under the ground cannot get th to nutrition. The right nutrients and they get all shriveled, and then you cant use the tubers for the food. We want to combat and try to find a way to stop the devastation of these crops. [kondwani] to wage this war, marys lab must take an experimental approach. upbeat music using whats called a gene gun, crispr altered dna is injected into the cassava plant. And we bombarded the stems with the crispr construct, and what happens is the leaves grow up. Ah. In principle, as the leaves and tubers grow from the stem, the nds will become more resistant to the crippling mosaic disease. When can we see a possible usage in african countries that are afflicted . Were still trying to hone in that technique. So hopefully, well get it soon. Hopefully soon. both chuckling dramatic staccato music [kondwani] imagine, gene editing could help end world hunger. This is also applicable beyond crops to things like trees. Forests may be the biggest farms that we have. [kondwani] but as the human population grows, so do our agricultural needs. This leads to deforestation which is one of the primary causes of Climate Change contributing to the record high temperatures we see today. To reverse this scary trend, one solution is to plant more trees to absorb Greenhouse Gases like Carbon Dioxide. Rodolphe is collaborating with tree biologist, dr. Jack wang, to grow more trees and fast. What do we have here . [jack] so these are transgenic trees. [kondwani] jacks lab has created over 10,000 types of genetically modified trees. The goal is to optimize traits for different industries, like timber or paper, to reduce their environmental footprint. We deliver crispr into these cells. [kondwani] once crispr has altered the tree dna, the embryos then grown enhanced roots and shoots. So this has been engineered precisely for a specific genetic trait using crispr. [kondwani] this helps jack to select for specific tits more quickly and efficiently than traditional plant breeding. [jack] so theres a little bit of seedling. This now is a tiny little crispr edited forestry species. This is, at this stage, just before it goes into the greenhouse. [jack] this splice is now ready to be grown for five to six months. [kondwani] fantastic, its so cool. Jacks next step is taking these seedlings over to the greenhouse where theyre fully grown and studied. Compared to 15, 20 years it take to breed a tree in the natural population. In the greenhouse setting, we can analyze and produce new genetically improved trees in as little as five to six months. [kondwani] that is incredible. 6 months. Here theyre quickly growing poplar trees, which is the most effective species at absorbing Carbon Dioxide from the air. They can capture a very large amount of carbon from the atmosphere and we have to start solving the problem right here, right now. We cannot afford to wait for another 20 or 30 years. This technique for breeding trees is giving reforestation efforts a major lifeline. Our environmental clock is ticking if we want to create a better, healthier environment for future generations. Its something that has to be done now. What were doing here is really the beginning of a true revolution. The next green revolution. Coming to a forest near you. [kondwani] yes. I think its gonna revolutionize our world and solve the grand challenges that we have on the planet. [kondwani] a new crispr fueled green revolution will forge a path to a more bountiful world. dramatic electronic music [narrator] in the future, gene edited plants are addressing world hunger and Climate Change. Enhaed food crops grow in harsh conditions. Even in waterparched deserts. Thanks to these disease resistant plants, famines across the world are a thing of the past. New, fastgrowing forests collectively take in the excess Carbon Dioxide from the atmosphere, cooling the climate, and restoring balance to the worlds ecosystem. dramatic electronic music as i see it, gene editing is both a faster and more precise method for artificial selection. While it works in microbes and plants, how feasible is gene editing in our biologically complex organisms, like animals . Im in davis, california to meet geneticist, alison van eenennaam. Shes a pioneer in this eld. Now im getting acquainted with her work. cattle snorts oh, no scientists tend to be problem solvers and wanna try and address problems using the best method they can, and my lab is trying to breed better cattle. [kondwani] there are about 1 billion cattle on earth. Thats a lot of animals to manage, but allison is making cattle farms safer by eliminating one particular trait. I see some horns up here. Okay. [alison] dairy cows have been bred to be very optimal for dairy production. And as it happens, dairy cows grow horns. [kondwani] and these horns are a problem because they injure other cattle and ranchers. You could imagine if this was a particularly aggressive bull, he could hurt his pen mates. [kondwani] instead of manually sawing off these horns, allison is breeding dairy cow that doesnt grow them in the first place. Woing withhe type of cattle that has no horns, she had their hornless gene inserted into horned dairy bu cells. These cells we cloned make theornless imal. These hornless cows are descendants of a gene edited hornless bull. Laser proof of concept animals. They are kind of a prototype of how you could use genome editing. [kondwani] this genetic technique produces offspring, with a desired trait, much more quickly than the decades of breeding normally required in traditional animal husbandry. Thats really what editing does for us, is it enables us to bring in one useful characteristic that we want. In this case, not growing horns, and not alter the rest of th