Welcome back. Now, let's consider the insects. An early and economically important use of transgenic technology was the genetic engineering of plants that produce their own insecticide. Chemical insecticides kill a lot of things besides the insects they're meant to control. And insecticides accumulate in our bodies and are linked with cancer, particularly in the United States amongst migrant workers who apply the things. And insects are also becoming resistant to conventional insecticides. So instead of spraying the insects themselves, we need to equip the plants with new chemical weapons to defend themselves. And again we go to our little friends the bacteria for help.

Bacillus thuringiensis usually referred to as Bt, produces a crystalline protein shown here in this figure, that produces paralysis of an insect's digestive tract causing it to stop feeding within hours and die within a few days. So the Bt bacteria itself was first used as an insecticide in 1920. And spray formulations containing Bt bacteria or Bt proteins used for more than 40 years for crop protection including organic farming operations. But beginning in the 1980s, the genes responsible for making Bt proteins were isolated and transferred into corn plants. Dr. Braun has already described how this was done.

And other Bt proteins have been used to genetically modify potatoes and cotton and many other crops. The Bt toxin is particularly attractive as an insecticide because there are about a hundred different kinds specific to different insects. And they break down quickly in the environment and they're not toxic to humans and other animals. So what you're looking at now is an adult corn root worm.

The larvae of this beetle are one of the most damaging pests in the United States. The economic impact of the insects in terms of crop damage and the cost of pesticides used to be around $1 billion a year before transgenic corn varieties. You can see how dramatic the effects of the Bt are in this figure with Wade French is comparing the tatty threadbare roots of a corn plum versus corn plum which is actually making the Bt toxin yet there's an equally dramatic in other plants. Have a look at these peanuts. Caterpillars extensively the leaves of the unprotected peanut plant.

After only a few bites of this genetically engineered plant, which is containing Bt genes the caterpillar crawled off the leaf and it died. Well this sounds great but there two mottos to bear in mind with pest control. Firstly, it's always hard to keep a bad pest down. And two, evolution will find a way. A major worry about planting thuringiensis Bt crops on a very large scale. What if it could potentially lead to the evolution of resistant insects. But so far the pictures goes here than anyone predicted. A review published in June 2013 found that Bt crops are largely holding their own after about 15 years of global use. Cases of resistance are rare, cropping up only where farmers fail to cultivate properly. Additionally, increasingly researchers of producing transgenic plants are having more than one toxin gene which makes it much more difficult for insect resistance to revise. Well microbes like the like the Bt bacteria that can be used to kill insects are called biocontrol agents or microbial insecticides. Microbiologists has been working on another biocontrol agent, a fungus called Metarhizium. And in one of our projects we've been using it to target mosquitoes and the malaria they carry. Blood infects some 300 million new people every year and kills 2 million a year, mostly children.

That natural fungus can kill mosquitoes but too slowly to prevent people getting bitten and catching malaria. So we engineered the fungus to express a gene from a scorpion that encodes a powerful toxin completely specific to insects. On the left here is a killed by mosquito, killed by the normal water fungus. And on the right is one killed by the transgenic Metarhizium. Then he took a few spores of the transgenic to kill the mosquito, and they killed much faster. You can see the wings of the insect killed by the transgenic fungus are all spread out, that's due to spasms caused by the toxin.

We were concerned that deploying such a potent pathogen could induce the systems to revolve in the mosquitoes, just in mosquitoes had become resistant to all sorts of insecticides. They'd find some way of evolving resistance to the fungus.

So we also developed another strategy and engineered the fungus to express an antimalarial toxin or human antibody. So what you're looking at is some mosquito blood containing the malaria parasite in red and the wall type natural fungus in green, throw in the mosquito blood. When we get the fungus to express the antimalarial antibody or toxin in the mosquito's blood, the malaria is very rapidly killed off.

So the mosquito bites are itchy but otherwise harmless.

Well the other goal in generating transgenics is to modify the quality of the produce. For instance, increasing the nutritional value or providing more industrially useful qualities or quantities of the produce. The Amflora potato for example, which uses a more industrially useful blend of starches. They taste terrible but they're not intended to be eaten. But due to lack of acceptance of transgenic crops in Europe in 2012, the German company that developed Amflora relocated its corporate headquarters to the United States.

Soybeans and Canola have been genetically modified to produce more healthy oils. Pigs are popular with genetic engineers and likewise have been transformed with a worm gene encoding a fatty acid, desaturase, that converts heart unhealthy omega-6 fatty acids into heart healthy omega-3s.

Cows have been engineered to produce more protein in their milk to help cheese production or do resist disease. This pretty lady is Anna or 2000. She's a clone of a purebred Jersey calf whose cells were modified with genes for producing lysostaphin, which is a protein that kills the Staphylococcus bacteria that causes mastitis disease. She's the first transgenic cow clone engineered to resist mastitis which costs the United States dairy industry $1.7 billion, annually.

Transgenics have also been used as biological factories for producing valuable or rare materials. One example is farming which uses crops of animals as bio reactors to produce vaccines or drugs.

In the poorest countries, many people lack the resources to buy vaccines that could save their lives or the means to store them. They have to be kept frozen and in many places, freezers and electricity are in short supply. While scientists all over the world are making vaccines much more accessible by engineering edible plants to make them. Plants as a banana or rice are chosen which are easy to cultivate locally and will keep producing the vaccine so it's always fresh. So you'd eat a banana expressing some combination of pathogen proteins that would immunize you against tuberculosis, measles, cholera, hepatitis, pneumonia or STDs. Scientists are placing particularly high priority on combating the diarrhea agents responsible for about 3 million infant deaths a year for Indian developing countries.

The first vaccines produced from plants are just starting to become available. Another twist on plant technology involves using tobacco plants to treat cancer. That's a tobacco plant genetically reprogrammed with a virus to produce a patient specific vaccine against lymphoma.

The strategy is to identify a gene sequence in specific for the tumor of a patient and incorporate it into a virus that infects the tobacco. The tobacco produces the protein encoded by the viral genome very rapidly and in extremely high levels. The protein can then be used as a vaccine to trigger the patient's body to attack the cancer. The non-Hodgkins lymphoma cancer vaccine from plants is soon entering phase three clinical trials.

Animals have also been used to produce medicinal products. Several animal proteins have been produced in the milk of cows and sheeps or goats in order to treat cystic fibrosis, emphysema, and hemophilia.

Human protein expressed in milk are much more likely to function properly than when they're made in bacteria that's because mammals do some extra chemical modifications of protein and start folding them up. Well getting the proteins made in milk means not having to kill the animals to get the protein. You don't want to kill the goose that laid the golden egg to reap the protein harvest. To get the protein produced in milk, the promoter for a milk specific gene, such as casein, is linked to the coding sequence for the human gene. The DNA is then injected into a fertilized egg and the egg implanted into the uterus of a surrogate mother. But transgenic animals are often cloned so that the entire herds of animals can produce useful proteins in this way. Transgenic animals are not confined to producing pharmaceutical proteins, they can produce other kinds of protein as well. I've already mentioned the most way out example, which addresses the questions what do you get when you cross a spider with a goat? Well, if you're a bacteriologist you get goats with spider silk in their milk. Look at these goats. These goats look perfectly normal. They have bright eyes, healthy white coats. They play around as exactly as you'd expect young goats to do. To the casual observer and to their keepers they show no signs that they're not perfectly normal farmyard goats. There a long way from normal. These are very special goats. They contain a single gene for the golden orb web spider. It's the gene responsible for making drag line, it's the silk that spiders catch themselves with when they fall. It's one of the strongest natural fibers known to man. But it's also light and flexible. It has some amazing properties for any kind of a fiber. So it's not surprising there are many possible medical uses, from artificial ligaments to sutures in surgery. The question was, how do you get a lot of spider silk? You can't farm spiders, they'd eat each other. That's why they put the gene in goats to produce what they call spider goats. To be precise, they're only about 170,000 spider. They have no hint of spider except for the highly prized spider protein in their milk. They find out of the milk, the silk protein produces a syrupy liquid. The real challenge is getting a super-tough fiber. Now, the spider does it by spinning the liquid protein through her spinerettes. Tiny holes in the stainless steel plate become man made spinnerets. The salt protein is pushed through the holes and can form filaments several miles long, this is the weakest part of the technology.

Artificial spinnerets have so far only been able to replicate a strand one tenth of the strength of a spider's drag line.

It's the eight legs, web spinners have the advantage for now.

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Spider Goats

Genes and the Human Condition (From Behavior to Biotechnology)

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