Good Things About Genetic Engineering

Here I want to talk about one of the good things about genetic engineering: using it to clean up the environment. I’ve already written about the benefits of genetic engineering in medicine and agriculture; let’s turn to the good things about genetic engineering regarding the environment. We can use bacteria as nature’s recyclers. Bacteria thrive on all sorts of nutrients, including things that we refer to as waste. There are species of bacteria that have the genetic capacity to produce enzymes that humans don’t. Composting uses bacteria to break down the carbon rich stores such as cellulose, which are the indigestible parts of wood chips, paper or straw. Also, they break down nitrogen rich sources, such as protein wastes and coffee grounds. When the bacteria work on these things, they produce four things: carbon dioxide, water, heat and humus.

Waste water treatment uses bacteria to act on human waste, paper products and household chemicals. The liquids and solids are treated differently. There is one group of bacteria that digest harmful substances in the solids of our wastes. Some of these bacteria, by the way, make a gas called methane as a byproduct, which is used for energy. Liquid wastes are digested by other bacteria. There is a whole series of bacteria that will digest different substances that are in things we call waste.

We’re still discovering more efficient and better ways to use bacteria for our purposes. This is called bioremediation.

Bacteria and plants have or can be given genes that remove pollutants. In addition to being nature’s recyclers, bacteria break down many human-made pollutants. How do we know this? We take soil with water, and we take that pollutant, oil for example. Then we look and see whether any of it gets broken down. We grow up the bacteria that thrive on the pollutant and use it.

In 1989, the oil tanker Exxon Valdez ran aground near the Alaskan shore, releasing 11 million gallons of crude oil over a thousand miles of shoreline. This was an environmental disaster of major proportions. Cleanup by physical methods was used first and the result was a dispersion of two thirds of the oil. Genetically engineered bacteria did the rest by bioremediation. Genetic strains of bacteria that can eat up oil were used. This process is ongoing.

The government of Kuwait is using bioremediation to try to clean up 150 million gallons of oil that was spilled probably deliberately by exploding oil wells during the Gulf War of 1991. This is probably the largest single remediation project in the world, and it is going on as I write. This is maybe one of the most useful of the good things about genetic engineering.

Good Things About Genetic Engineering? Environmental Cleanup

There is a type of bacteria called extremophiles. They have many genes that are useful in bioremediation. Extremophiles are bacteria that love the extremes of nature. They are kind of the ultimate athletes of the biological world. They can live in very hot places or icy places like Antarctica, or deep in the ocean, or very salty environments like the Dead Sea. These organisms form a separate group from bacteria called the archaea. They are called archaea because they resemble the organisms that are believed were the first living cells.

The archaea genomes have been sequenced and half of the genes of the archaea do not resemble anything in any types of bacteria or eukaryotes. Some of them have genes that use carbon dioxide, just like plants do, not to make sugars but to make methane gas. Archaea are by far the major producers of this gas.

The granddaddy of all archaea is called Deinococcus radiodurans. This organism lives in probably the most dangerous environment on Earth: ones with extremely high levels of radiation. Normally, radiation kills cells by damaging DNA. When DNA in any cell is damaged by radiation, we can repair it thanks to a system that we have. Large amounts of radiation, however, overwhelm that, and you get permanent mutations and cancers as a result.

Deinococcus radiodurans gets around this by having the most efficient and sensitive radiation repair system in nature. It is a phenomenally good system. This wonderful organism is responsible by one of the good things about genetic engineering. Genes from other extremophiles are being engineered into Deinococcus radiodurans. People call this new organism Conan the Bacterium. It is used to clean up the most toxic sites we know of. For example, in America there are sites extremely contaminated with extremely bad stuff. These Deinococcus radiodurans are being used there.

Plants can be genetically engineered for environmental cleanup. For instance, bacterial genes that allow environmental cleanup can be put into transgenic plants to break down oil. There are plants that would convert solid mercury into harmless substances. They might ask why use plants when microbes are available. The issue is that you want to get the microbe out of the soil when you don’t need it anymore. You don’t want extra microbes. Getting bacteria out of the soil is quite difficult. Plants are easy to take out. You plant it, it does its thing, and you take it out. This might be a better way of doing bioremediation in some cases.

Genetic Engineering in Agriculture, Part 2

Genetic engineering in agriculture overcomes some of the limitations of traditional agriculture. Until now, we’ve spent enormous efforts to adapt the environment to the plant. That’s what a farm is, an adapted environment with the purpose of maximizing the growth of a plant. Now, we have the possibility of being able to adapt the plant to fit the environment. Here I will list the limitations of traditional methods that genetic engineering in agriculture overcomes. Also, I’ll list some of the genetically modified plants in widespread use over the world today.

1. Limitation number one: in traditional agriculture they select specific traits (genes) for crosses, but at the same time other hidden genes that are not desirable may also be transferred. Using genetic engineering in agriculture, single genes are transferred.
   
2. Limitation number two: there are many genes in nature that can’t be crosses into crop plants because they are in different species. Using genetic engineering in agriculture, genes from any organism can be transferred.
   
   
3. Limitation number three: traditional agriculture is slow. Genetic engineering is rapid. You can see results in weeks.
   
   
4. Limitation number four: the ecological thrust of agriculture has remained to use genetics and technology to adapt the environment to the plant. With genetic engineering, the plant can be adapted to the environment.
   

Genetically modified plants are in widespread use. I’ll give you three examples.

Plants That Make Their Own Insecticide

Insecticides are chemicals that kill insect pests. The problem with insecticides, however, is that many of them are not specific. They target many insects, not just the pest. In addition, some insecticides are toxic to the environment in other ways. Insect larvae (the immature stage of insects) eat, among other things, bacteria.

There is a bacterium called Bacillus thuringiensis that has a gene that defends itself against insect larvae. This gene codes for a protein that binds to the insect larvae’s intestine, and makes it loose all of its fluids. The insect gets chronic diarrhea and dies.

The gene coding for this toxin protein has now been introduced to corn, cotton, soybeans and tomato cells. These cells were cloned to make plants that express the toxin in the leaf. As a result, the insect caterpillars land on the leaf, begin to eat and die very quickly. The population of this pest goes way down.

This technology has reduced insecticide use by 90%. This is an environment-friendly use of genetic engineering in agriculture.

Plants Resistant to Herbicides

Weeds can be killed by repeated applications of herbicides (chemical that kill weeds). These chemicals, however, very often kill beneficial plants as well, and even some crops. These are non-specific toxins. Great care is needed to use herbicides properly.

Genes had been identified from bacteria and other sources that code for proteins that break down herbicides. That’s how the bacteria survive to them. These genes had been isolated from the bacteria and put into cotton, corn, soybeans, rice, etc. As a result, these modified crops are now resistant to the herbicide. The herbicide can be applied without any risk of damaging the crop. These crops are in widespread use all over the world.

Nutritionally Rich Rice

Rice grains are deficient in their protein, in terms of their amino-acid balance. There is an ongoing effort to improve that. In addition, rice does not make a substance called beta-carotene. People require beta-carotene, which gets converted into vitamin A, in their diet. Rice plants do not have the gene to make beta-carotene. As a result, about 250000 children go partially blind each year. They are eating rice, and they don’t get enough beta-carotene in their diet.

Other organisms have the genes coding for enzymes that can produce beta-carotene through a biochemical pathway. Ingo Potrykus isolated DNA for each one of these enzymes. One of them was from a bacterium, the other genes happened to be from a daffodil plant. One by one, over a period of a decade, he took each one of these genes and introduced them into a rice plant, along with a promoter that would stimulate gene expression in the developing rice grain.

The result is a rice plant that made grains with beta-carotene. These plants are now being crossed with local varieties all over the world to make the beta-carotene phenotype part of rice that is used in different regions of the world.

Genetic Engineering in Agriculture

Let’s talk about genetic engineering in agriculture. As we know, genetic engineering allows transferring genes from one organism to another. How is this useful in agriculture? We’re faced with a challenge over the next 50 years: feeding an ever expanding human population. According to UN estimates, human population will level off at about 10 billion people. Can genetic engineering in agriculture help?

A real problem in agriculture that existed for millennia is that most plants cannot grow in salty soils. When soil is irrigated, that is when people bring water to dry soils, the water also brings salts. This temporarily allows plants to grow, and normally these small amounts of salts get removed from the soil by rainfall. In dry climates, however, there isn’t much rain. As time goes on, salt builds up.

Salt build up has always been a major problem in agriculture. It led to the fall of civilizations. For example, the Mesopotamians fell as a civilization largely because of salt build up in their soil. Today, it is estimated that up to 65 thousand acres of farmland a day are lost to excess salt build up. The soils are essentially rendered unusable.

Salt is toxic to plants in two ways. First, salt impairs the roots from taking up water. Second, salt blocks several of the enzymes involved in important processes. How does it do that? It alters the way that these proteins fold, and if an enzyme folds incorrectly it won’t be able to do its function. The particular enzymes I’m talking about are involved in making proteins, and also some involved in photosynthesis. Photosynthesis is the process by which a plant converts solar energy into stored energy in the form of sugars.

Few plants in the world can thrive in very salty soils. Certainly, not the major crops (rice, wheat and corn). Finding a gene for salt tolerance in these crop plants is unlikely. If you go to the crop seed bank, it’s likely that you’re going to find a variety of rice that has a mutation that makes it tolerant to salt.

Scientists always use “model organisms” to do research. The model plant is a tiny mustard like plant, called Arabidopsis. Arabidopsis is a model for the genomes of the major crops. Arabidopsis does all the things that the major crops do. It has roots, stems, leaves, flowers and all those things. It is useful to study it because we can grow it in a greenhouse near a laboratory and we know its entire genome.

In the 1990’s, Eduardo Blumwald found that Arabidopsis has a gene that is expresses as a protein which suck ups salt form the soil, and put it into storage depots inside of cells called vacuoles. These particular cells are in the leaves of the plant. This might be a pretty good way to tolerate salt. The salt would never get into the rest of the cell.

The problem comes when the salt build up in the soil is very high, as happens in soils that had been rendered unsuitable for agriculture. There isn’t enough of this protein, so the excess salt leaks out of the vacuoles and gets into the rest of the cells.

Using genetic engineering, Blumwald has added a vector with a very active promoter (a section of DNA that turns on a gene) beside the gene that allows the salt to be stored in vacuoles. So, the expression of this gene would be enhanced. When he made transgenic plants using this vector, the genetically modified Arabidopsis was able not just to withstand salty soil, but to thrive in it. What an amazing thing!

Blumwald didn’t really want to grow Arabidopsis on salty soils, but to get this gene into crop plants. Genetic engineering allows transferring genes from one organism to another. When the active salt-tolerance gene from Arabidopsis was put into a tomato plant, it became very salt-tolerant. A normal tomato plant would wither and die in a salty soil, whereas the modified tomato plants would be just fine. What’s more, the salt was in the leaves, the tomato fruits were just fine.

While tomatoes are important, they are not nearly as important as the major grain crops. So, Blumwald and others are busily trying to transfer this salt-tolerance gene from Arabidopsis to rice, wheat and corn.

This may make salty soils in the world usable for farming. Salt-tolerant transgenic plants may make deserts bloom again.

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Benefits of Genetic Engineering

What are the benefits of genetic engineering? The benefits of genetic engineering are the products we can make with it. Genetic engineering could be used to make products in two ways: we could take the existing organisms and modify them genetically to make them more efficient. We could for example add a promoter that would make the organism produce more of one kind of protein. The second use of genetic engineering is that we can take new genes and insert them into organisms that never had them before.

The first major product of genetic engineering was human insulin. Insulin is a protein that acts as a hormone to stimulate uptake of blood sugar into tissues, such as the liver and the muscles. In diabetes, people don’t make insulin. Previously, insulin came from slaughtered animals. The insulin protein has 51 amino-acids. The insulin from slaughtered animals is similar to human insulin, but very often is one or two amino-acids different. It still has the same function, but the human immune system will recognize these one or two differences. So, in a significant number of diabetics, when taking non-human insulin, their immune system reacts against it.

Here, what we need is human insulin. Insulin is made in very small amounts. So, the only way to get this in reasonable amounts is by amplifying the expression of genes for insulin in recombinant DNA.

At City of Hope Medical Center in California, Keiichi Itakura went into the chemistry lab and made the insulin gene. It wasn’t even then a big deal to make it. Itakura’s colleague, Art Riggs, took this gene and put it into an expression vector, right next to a promoter. The expression vector now had the gene and a marker. The expression vector was then put into bacteria, and the bacteria expressed human insulin. This is about 7 or 8 years after the first emergence of recombinant DNA technology.

The insulin then was extracted, sent to a drug company, and then to physicians. This is the source of all insulin now used to treat type 1 diabetics. This is really the great example of a genetically engineered medication.

Another example is the blood-clotting protein that is missing in hemophilia. This blood-clotting protein can be supplied with genetic engineering. People no longer die of hemophilia thanks to genetic engineering. So, here we have two clear benefits of genetic engineering.

Proteins used to treat diseases

There is a protein called Erythropoietin (EPO). EPO is a hormone-like substance made by the kidneys. It enters the bloodstream, goes to the bone marrow and stimulates the production of red blood cells. Red blood cells only last about 120 days, so they must be constantly replaced. There are many people with kidney failure for various reasons. These people are treated with kidney dialysis, because kidney transplants are limited.

The kidney filters out the poisons and keeps the good things. In this case, all you can do is to filter the bad things with the dialysis machine. Among the things that get filtered out is EPO. So, these people with kidney failure have kidney function restored by dialysis, but they’re not making EPO. They have severe anemia. The only way to get around this is by massive transfusion or to treat them with EPO.

The gene coding for EPO was isolated, EPO was made by recombinant DNA technology, and this is now widely used for people who are undergoing kidney dialysis and also people who are being treated with cancer chemotherapy. Many of the drugs used in chemotherapy destroy bone marrow cells.

EPO is also the first genetically engineered drug of abuse. Athletes found that if they take some EPO they can increase their blood cell count. Increasing the amount of red blood cells by about 10% can give an athlete an edge in competition. There had been great controversies in cycling and elsewhere because of the abuse of EPO.

In Animals

Plants and animals can be genetically engineered to make products useful for us. The great example of this is diary animals. Sheep, goats and cows produce a lot of milk. Biologists found that the expression of genes for the major milk proteins is under the control of a promoter. This promoter is a sequence of DNA that causes the adjacent genes to be expressed in the mammary gland. It is called the lactoglobulin promoter.

This sets up a really nice opportunity for using genetic engineering. You could take the gene you want expressed in milk and put it into a DNA vector. Then you put this vector into a sheep egg cell. If you do this, the egg can then be developed in the laboratory for a couple of days until it becomes an embryo. You can insert the embryo into a mother and the offspring that are born are sheep that would make milk which contains this extra protein. This was actually behind the reason for cloning Dolly the sheep.

There are a significant number of humans that lack adequate amounts of growth hormone. These people are very short in stature. The growth hormone is a protein. So, we can get that protein from the body, but it is made in the pituitary gland in extremely small amounts. So, again, we got to get it through genetic engineering. The gene was isolated, put into a vector, put into cows, and there is a herd in Argentina of ten cows that in their milk will supply the world need for human growth hormone every year. This process is called pharming, and a very promising technology.

In Plants

Plants can be genetically engineered to make useful products. Genetically engineering a plant is a lot easier than animals. We don’t need to inject and expression vector into the fertilized egg of a plant, because plant cells are totipotent. We can take any plant cell grown in a laboratory, put the vector in, and then grow the plant up from that cell.

Plants produce a lot of protein. For example, tobacco plants have been genetically modified to make TPA in their leaves. Tobacco leaves are very large and it is easy to get the TPA from them.

You’ve probably heard the term antibody. Antibodies are what the immune system makes to fight diseases. A “plantibody” is a plant is making a human antibody. We can use genetic engineering to have a plant make a vaccine. For example, the vaccine against bacterial meningitis has been expressed in the fruit of plant, a banana plant. The people still have to eat the fruit, but it doesn’t have to be refrigerated and you don’t need health professionals to administer it.

We can create plants with new capabilities. For example, a major component of detergents is lauric acid. This molecule is made in a biochemical pathway in tropical plants, such as coconuts and palm trees. A major source of it is palm kernel oil. Scientists pinpointed one of the key enzymes that is in the biochemical pathway for making lauric acid. Scientists pinpointed the gene in palm trees, they cloned the gene into an expression vector and put it vector into rapeseed plant that produces canola. Normal canola produces oil that is 0% lauric acid. This particular transgenic canola makes 60% lauric acid.

There is a viral disease caused by the tobacco mosaic virus. This is a major pest of tobacco. It doesn’t kill the plant, it kinds of destroys leaf tissues and spreads very rapidly. This virus reproduces in the cells but doesn’t kill the entire plant. The viral genome can be replaced with other genes; in this case, with genes for vaccines. Now, instead of making a lot of proteins in viral particles, these tobacco plants are making large amounts of a vaccine. This may be a new use for what is widely grown crop around the world.

These are just a few benefits of genetic engineering. I’m sure more are coming in the future, as we discover more and more about genes and proteins.

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What is Genetic Engineering

What is Genetic Engineering? Genetic Engineering is the manipulation of microbes, plants and animals to make products that are useful to people. As such, genetic engineering is not new. It began a long time ago. I would say that genetic engineering, or biotechnology, began with agriculture. Agriculture I define as the harvesting, planting of cultivation of plants for food and fiber. This was the first biotechnology. Estimates are that agriculture probably began about 10000 years ago, in what is now the region near Iraq.

We have evidence that Sumerians living there at the time learned that barley plants growing around their homes made seeds that could be used to make bear and bread. They started growing these seeds near their settlements. They would use some of the seeds to make bear and bread, and then they would grow the rest of the seeds nearby.

In ancient Egypt, the hieroglyphic symbol for food is a picture of bear and bread. You may ask, why bear? Just to have a good time? Answer is no. When people began to live in settled places, they realized by trial and error that water purity was a big issue. As they would be going to the bathroom in the same water they were drinking, people would become sick. Alcoholic beverages kill most of the bad things that are in water. It’s not surprising that they were invented quite early on by humans.

The process of making alcohol from seeds is actually carried by yeast cells that live in the grain or grapes. This process is called fermentation, and it is a form of biotechnology. Modern genetic engineering, however, refers to the use of a technique called recombinant DNA. To illustrate what is genetic engineering and what are its uses I’d like to tell a story:

As Tom drove home from work, he felt his face twitching and had a really bad headache. Tom was one of the several million people who have a stroke each year in the United States. A blood clot was blocking an artery leading from the heart to his brain. This deprived brain cells of oxygen, and irreversible damage to the brain could occur quite quickly. When you think of blood clots, you got to consider that they do go away eventually. “Go away” is not a really good biochemical term. We say that the clot dissolves, but this happens rather slowly. The way this happens is the following: as the wound is healed, a series of cells that is healing the wound make a substance called TPA (Tissue plasminogen activator), which activates the blood clotting system. The clot then dissolves.

The time factor is important biologically speaking. If the clot dissolved the minute it was formed it wouldn’t do much good. The blood would flow out and you’ll lose it all. Slow dissolving of the clot is a good thing, but not for Tom. Tom was having a stroke, and that’s not a situation in which we want a blood clot for a long time. Every minute the blood flow to the brain is blocked is harmful.

Luckily for Tom, he was near a hospital. He drove to the parking lot; the emergency stuff got him and immediately injected a drug right on the surface of the blood clot. The clot dissolved right away, blood flow was restored and there was minimum damage to the brain. Tom was home the next day and he was fine.

The drug that the emergency room stuff had injected was TPA. This drug is also called PLAT in medical terms. This is the protein that initiates the clot-dissolving process. Without using TPA, the clot would have gone away, but his brain would have gotten damage in the meantime. Adding this substance right away to the site of the clot activated the clot-dissolving system right there.

TPA is made in very small amounts and only when it is needed. The bad thing is that if we want to use that as a medication, we’d better get a lot of it. It’s virtually impossible to get enough TPA from the cells of a body to store in the emergency room. This is when genetic engineering enters the scene.

First, DNA was extracted from human cells. The gene coding for TPA was isolated and inserted in hamsters. This allowed to produce TPA in amounts far greater than you could ever extract from blood. The TPA is then purified and sat on the shelves ready for a patient like Tom.

The scenario of using a gene to produce a useful protein, by this genetic engineering technology, has now been played out for dozen of products. This is part of a revolution. The revolution of genetic engineering.

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