There is a great deal of controversy today about a new and powerful technology called genetic engineering. We talked to a number of scientists, environmentalists and ethical experts about some of the issues in these debates.
Biologist Richard Burgess, former head of the Biotechnology Center at the Univ. of Wisconsin in Madison, puts the issues into perspective. We asked Dr. Burgess just what is genetic engineering?
“Usually I'm asked what is biotechnology? And I say it's not just genetic engineering. Genetic engineering is the ability to isolate individual genes and produce duplicates and to cut and paste the genetic information, the DNA.”
What is biotechnology?
“Biotechnology is a general term that has many definitions but I think the most understandable and straightforward one is that is applied biology. It's using the knowledge that's been gained by basic research in biology to ... for practical purposes. For producing new products, producing new processes, and of course, it's not new.
“People have been domesticating animals, domesticating plants, bringing new plants to improve food production for thousands of years. They've been making wine, and cheese and beer by fermenting, using microorganisms to convert food processes for thousands of years. So applied biology is not new.
What is new then?
“Well I tend to think there have been three major new tools that have been created in the last two decades that give us the ability to do things we couldn't have dreamed of doing in the past. One of them is genetic engineering, the ability to cut and splice DNA. One is cell biology, the ability of tissue culture to grow cells from an organism in a tissue culture. Finally we have seen the development of computers and instrumentation that allows us to analyze proteins and DNA much more sensitively and accurately than we could ever have done in the past.”
Here is an example of how genetic engineers are using these new tools to produce new plant varieties.
What do you do when your beautiful field of barley is being destroyed by a fungus? In the past farmers have tried many methods. Rotating their crops, trying different varieties, adding chemicals.
Today here at the U.S. Dept. of Agriculture Cereal Crops Research unit in Madison, Wisconsin they use gene cut-and-paste techniques and what is called a gene gun to create a new variety of barley plant that will resist the fungus without chemical aid.
First they found a species of oats that was able to resist the fungus. They were able to identify the particular molecular part of the oats plant that gave it this power. This molecular part is a DNA fragment in all the cells of the plant. That DNA fragment is a “gene.” They “cut” this fungus-resisting gene out of an oats plant cell with special newly-discovered chemicals called restriction enzymes.
Once cut loose from its original strand of DNA, the DNA fragment—the “gene”--is “pasted” into a special bacterium plasmid with the help of another special enzyme. They multiply the plasmids using a technique called PCR (Polymerase Chain Reaction). They mix the new bacterium plasmids that now contain the fungus-resistance gene, with gold dust. And now they are ready.
“We have here a small seed. We dissect the embryo right here and we transfer the gene that we want into the little embryo with the help of a gene gun.
“Ok. This is a gene gun. And this is the chamber where the actual bombardment is done.”
They put thousands of copies of the new fungus-resistant gene on the very fine gold dust and then with a burst of pressure, the gold dust with genes attached is shot into the tiny barley embryos. They grow the bombarded embryos on special culture media and select the ones that have taken up the fungus resistant gene.
They are called transgenic plants now and eventually from these transgenic embryos they grow mature barley plants that will be resistant to the destructive fungus and that will be suitable for large scale reproduction in the barley fields of the United States, Canada and northern Europe.
You can use the same process to cut-and-paste useful genes into many other plants and animals. Dr. Burgess explains a project that genetically engineers fungi, a project with broad implications for energy, and the environment.
“How do you make paper? Paper is typically made by taking wood which is made of cellulose fibers that you want for paper and lignin, which is the glue that holds the fibers together.
“The typical process for making paper pulp is to dissolve the lignin with chemicals which requires a great number of harsh chemicals, leads to a loss of fifty percent of the mass of the wood which is just lignin. and that becomes a waste in itself. You have waste streams coming out of pulp mills which are undesirable. You've lost 50 percent of the mass of the wood.
“Alternatively you can do something called mechanical pulping. which is physically shearing, or breaking down the wood into fibers. The problem there is that it requires a very large amount of energy. And it produces a very weak paper because the fibers are short. And what researchers here have done in the last few years is to demonstrate that you can treat wood chips with a biological treatment. In this case treating them with fungus.
“Fungi grow on dead trees and rot them and allow their material to be recycled in nature. So it is fungi that will degrade lignin. So if we treat wood chips with the right kind of fungi under the right kind of conditions we can tenderize or soften the wood chips ...now we can do mechanical pulping with a very large savings of energy, as much as 50 percent, and at the same time producing longer fibers that can make a stronger paper and avoiding the use of the chemicals in the process. So here is an example of going from a chemical pulping to what we would call a bio-mechanical pulping and it comes by understanding how to grow fungi and how to improve fungi.”
Similar methods are being used around the world in the 21st century to produce transgenic wheat that can resist common parasites, transgenic cotton that will resist the boll weevil, drought-resistant corn with high oil levels, drought-resistant rice with high levels of vitamin A, cottonwood trees that can soak up mercury from polluted soil, potatoes that can make their own pesticides to resist the Colorado potato beetle, soybeans that can resist weed killers and produce higher yields.
Many millions of acres in the United States, Canada, Mexico, China, India and other countries around the world are using transgenic plants today to increase food production, to cut down on the use of chemicals, to prevent soil erosion, to decrease the land needed for agriculture and to increase the areas that can be turned back into wetlands and wilderness.
This new science can potentially be of great help in the world’s poorest continent, Africa, although thus far it has not been used extensively there. Two of the most important foods in Africa, for instance, are cassava and bananas.
Cassava is the staple food for 250 million people not only in Africa but in other countries of Latin America and Asia. Unfortunately the natural cassava plant contains cyanide so it must be pounded and soaked repeatedly to leach out the poison before cooking. Genetic engineers, using cut and paste techniques, are working to create new varieties of cassava that would produce less cyanide and more protein.
Genetic engineers have already produced a banana that can resist a common airborne fungus that right now is causing great destruction to banana trees in Uganda and other African countries. They are also working on a way to add genes to the banana plant so that it will produce molecules that give resistance to Hepatitis B, a deadly disease that kills thousands of Africans every year. A $200 inoculation could prevent Hepatitis B, but few Africans can afford that amount. A new Hepatitis B resistant banana would cost as little as ten cents.
Not only plants, but animals too can be and are being genetically engineered. Malaria and dengue fever are responsible for millions of deaths in Africa every year. Both are carried by mosquitoes. Right now genetic engineers working on ways to block a mosquito’s sense of smell so that it cannot find a human. Others are working on ways to shorten a mosquito’s life span so that it can still reproduce but cannot transmit disease. Still others are working on ways to change the disease-causing virus so it kills the mosquito instead of infecting a human. The Gates Foundation has recently given $437 million dollars to work on these and similar genetic engineering projects for global health.
All well and good, but could the genetically altered organism cause serious problems once released in the natural environment? Many environmental activists think so. Jeremy Rifkin explains.
“I have been on record for years saying we need a moratorium. We should not be releasing any genetically engineered organisms into the ecosystems of this planet at this time simply because we have no risk-assessment science. In the area of petro-chemical technology we have tests that can be done.
“There is a science of toxicology. There is no such science when we come to genetic engineering. We have no predictive ecology that can measure the amounts of risk in placing a microbe, a plant, an animal into a complex ecosystem. And so if we don't have the risk-assessment science, it seems to me foolish to maintain the fiction that we can regulate the environmental questions here.”
“I respect his opinion on this. I don't agree with it. I think there is a substantial body of risk-assessment science. That's how one determines whether a chemical will be a carcinogen. That's how one determines whether a food has the appropriate vitamins and nutritional value and lack of toxic compounds. So in fact a new potato is produced. It is tested for its safety whether it is produced by conventional plant breeding or whether it is produced by genetic engineering.
“The National Academy of Science formed a number of major committees to look into this. And their conclusion quite simply is that there is no more danger associated with an organism produced by genetic engineering than there is from one produced by more conventional means.”
We asked Jeremy Rifkin how using genetically engineered organisms differs in risk from bringing in non-native plants and animals.
“Well I think it is very similar. We've been arguing that since we brought the first lawsuit back in 1982 that held up the release of organisms for about 5 years. The fact is non-native organisms provide a good analogy. We have brought many non-native organisms into this continent over the last 200 years. Many of them have fit into the ecosystem. Some of them have died out. A few of them have overwhelmed their environment and created a powerful niche and have caused billions of dollars in damage.
“The gypsy moth is one such example. Dutch Elm disease, chestnut blight. These are all non-native organisms. We brought them here and now we can't get rid of them. Now you have to understand the scale of introduction.... In the 21st century the industry would like to introduce thousands of genetically engineered microbes, plants, and animals in massive commercial volume in ecosystems all over the world.”
Mr. Rifkin made this prediction in the late 1990s. It turned out to be true as to the scale. More than half the soybeans grown in the United States today are genetically engineered. One-third of the corn grown in the U.S. is genetically engineered. And around the world genetically engineered plants and animals were indeed produced in massive volume in 2005. As to dangers, however, so far at least, environmental problems have been minimal. Dr. Burgess suggests why he thinks this is so.
“There is a tremendous diversity of life. And new organisms and variations on organisms are being created all the time. And they have been since the beginning of life. Many of these are problems. “They are problems where they arise and they are problems when they are moved into a new environment. That's a concern. But it's no more of a concern ... what about the organisms that are brought in inadvertently on shoes of people who come in from other countries? Do we want to put a moratorium on travel because you might introduce a harmful organism. I really consider it to be in the same category as putting a moratorium on travel.
“When we put out an engineered organism that's been engineered say to help fix nitrogen. to produce natural fertilizer for alfalfa and soybeans. We know what we're working with. It's been tested in the laboratory first. It's gone through extensive review and in fact these things are much more carefully controlled and understood than what one brings in on a banana or an orange when you bring it in from a foreign country that you've been traveling in. There truly are dangers, and undesirable plants and animals and bacteria but there already there ...
“I don't think ... this really gets to the question of relative risk and I think I'd like to say something about that. Every single thing you can think of has associated with it risks and benefits. You know people are happy to have paved roads. Driving cars is extremely dangerous. Because it is convenient. There are some risks and there are some benefits. The same thing is true with genetically engineered organisms.
“If we want to avoid using chemical pesticides, for example, on our plants, we may want to go to using plants that have engineered into them natural resistance to those pests. So you don't have to put pesticides on them. So there's a risk and there's a benefit.
“There's a risk of some unknown thing happening. It's not a big risk and as more and more experience is gained it can be assessed. The benefit is you can avoid using chemicals that are known to be dangerous.”
Genetic engineering of plants continues to spark controversy. Genetic engineering of animals—and especially of human beings—is equally controversial.
Transgenic plants and animals, insulin, BGH (Bovine Growth Hormone), are all examples of products already developed by genetic engineering and being used today by farmers, doctors, and ordinary people. In the last two decades rapid advances are being made in the most controversial of all genetic engineering projects, investigating and controlling the genetics of human beings.
Dr. Lloyd Smith, for instance, heads the team at the University of Wisconsin-Madison that made rapid progress in the biggest biological quest of all time, the Human Genome Project. The Human Genome is nature’s four-letter code written in unpunctuated sentences on human chromosomes. It is the blueprint for making a human being that took nature three and a half billion years to create. Dr. Smith along with hundreds of colleagues in laboratories around the world took 15 years to learn to read and record the entire code.(It will take much longer to understand it, but that effort has also begun.) By 2003 biologists and genetic engineers did have in computer memory, however, all of the details of the code. And this detailed information offers many new possibilities as well as many new risks.
Dr. Smith explains one example of the present-day use of this information to diagnose a serious disease, cancer.
"A good example of that is another company I work with called Visible Genetics has been doing sequencing of the retinal blastoma gene. That is a gene that's involved in the generation of cancer of the eye. And it turns out that if you're in a family that has that gene and you don't do any genetic testing then you don't know which of your children have that gene and which don't. And it turns out since you don't know what you have to do is end up having to do these examinations of the eye under general anaesthesia which are pretty expensive and they have to do them every six months on young children to detect if there is going to be an early occurrence of cancer. So you can try to avoid it by laser surgery at an early stage.
“So it's a very expensive test. It's very stressful for the children, for the whole family. And everybody's sort of sitting on a bomb and they don't know when it's going off.
“Visible Genetics put out this test that allows them to go in and rapidly sequence those genes from the affected members of the family. Once they do that they can find out what the mutation is in the gene that's causing the problem and that allows them to go and very quickly and easily test the children and find out which children have the bad gene and which don't. The ones that don't are right away free and clear. They're out of it. No test. No general anaesthesia. No anxiety. And the ones that do, you can also begin building up a data base to look at what the prognosis is based on different types of mutations and also try to tailor treatment that is specific for those mutations. So in general that's just one interesting example of the social payoff for this, and the social payoff is really going toward targeted treatment for people based on their genetic type ... on their genotypes.”
Besides the already proven use Dr. Smith explained, genetic engineering research is also making promising strides in curing cancers. The standard cancer treatments today are surgery, radiation and chemotherapy. Unfortunately these treatments are often unsuccessful and can cause severe or even lethal side-effects because they destroy many healthy cells as well as cancer cells. Building on the new insights into genetic differences between healthy and cancerous cells, new methods are being developed now to attack cancer cells directly, leaving the healthy cells of the body untouched.
In 2005 J. Craig Venter, one of the leaders in the Human Genome Project, announced a new, even more revolutionary research venture. “This is a step we have all been talking about,” he claims. ”We’re moving from reading the genetic code to writing it.”
He is heading up a new privately funded project to create an entire set of genes from scratch. In other words to create life itself ... from scratch. From chemicals. At the beginning they hope to build enough artificial DNA to make up a complete bacterium genome. Then they will introduce this artificial genome into a bacterium cell whose own genome has been removed. By creating this wholly new kind of life form they hope to be able to produce totally new species of bacteria.
They predict that these new human-created organisms will be useful in an unknown but potentially unlimited set of new applications. Cleaning up polluted soil and water, for instance. Or changing plant cellulose into ethanol. Or producing hydrogen for a new source of energy to power automobiles. Or destroying cancer cells.
Information gained in the Human Genome Project is fast becoming useful in many other promising fields of genetic engineering, especially in cloning and in stem cells.
In cloning, DNA material is taken from body cells of an animal, and then inserted into an oocyte (a female egg cell) after the original DNA material has been removed. The new altered egg cell is stimulated to divide. First it divides into stem cells and then after a few days these stem cells begin to differentiate into nerve cells, muscle cells, bone cells, and finally into a complete new organism, a cloned reproduction of the original animal.
A sheep in Scotland, Dolly, was the first mammal ever cloned in this way from the cell of an adult. By now in the early 21st century, many thousands of cloned mammals--sheep, cows, mice, cats, monkeys, pigs—testify to the success of this kind of engineering.
The hope is that some of these cloned mammals will be of great use in new efforts to test drugs, to produce food, to provide organs for transplantation into humans and to solve some of the mysteries of disease and health.
Dr. Neil First helped prepare the way for Dolly by being the first one to clone cattle from an embryonic cell. Here he explains a benefit of cloning animal cells that has received little notice.
"Well, there's another kind of transplant that is not so commonly thought about and that is the transplantation of cells. And the best example of this is research on HIV now. One of the more highly promising things on HIV is to engineer blood cells. We call them stem cells, but these are stem cells for the blood lineage and are different from stem cells of the embryonic lineage. So we have embryonic stem cells that will make any and all cells of the embryo. But these are blood cells lineage that will make any and all blood cells. And by starting at that stage and engineering the cells properly... Now what cloning does is provide the possibility for an animal, or even a human I suppose, to multiply these cells, engineer the cells and then using those cells in a transplant and with that transplant interfering with the tumor. Now that might be a blood-born tumor or it might be a solid state tumor perhaps, if you can get it delivered to the tumor. The prospects are very exciting and that's what people are really referring to when they talk about transplantation. And that more than the organ transplant.”
Many scientists think that no research today offers more promise for breakthroughs in human disease and treatment than work with what are called embryonic stem cells. These are the cells that are formed in the first 5 or 6 days after fertilization in the mammalian reproduction cycle. In 1998 James Thomson at the University of Wisconsin-Madison was the first scientist able to culture these early embryonic cells from humans in culture dishes in the laboratory.
One of his close colleagues, Dr Timothy Mulcahy, explains.
“Well, I think the simplest way to explain that is to think of stem cells as a pretty much a blank cell. It is a cell that has the potential to do anything that any cell in the body does, but it hasn’t received specific instructions yet as to which particular program to follow. So the beauty of stem cells is in the potential they offer for medicine, for example, is if we can understand the signals that will tell the cells which programs to follow we could then develop cells to replace cells that are injured in heart attacks, or we could make neural cells that could replace deficits that people suffer in Parkinson’s disease and others. So unlike any other cell in the body which is already following a preordained program, these cells are sitting there waiting to be told what to do and if we can understand the science of how to do that we have a very powerful tool to treat disease.”
The signals that tell the embryonic cells which programs to follow are given by proteins created in cells using the DNA information on human genes. Much of this information is now available thanks to the completed Human Genome Project.
“Many of those proteins are going to be the critical triggers for deciding which way this blank cell is going to go when the time comes and we are already working with investigators on campus to try to look at what genes are uniquely expressed in these cells at their earliest stages, what genes are turned on or turned off when we decide to try to make heart cells from the embryonic stem cells. Having a blue print available is going to be an invaluable tool to help us sort that out.”
Once scientists learn just which genes influence the stem cells to turn into nerve cells they will have potentially a very powerful tool to treat spinal injuries, Parkinson’s and Alzheimer’s Diseases, and other nerve-centered maladies. When they learn which genes influence the stem cells to turn into heart cells they will have a powerful tool to test new drugs to prevent heart attacks as well as a new tool to regenerate heart muscle destroyed in a heart attack.
Another research direction is the biology of aging. Ordinary human cells when taken from the body and cultured in the laboratory dish grow and divide about 50 times, and then lapse into old age and death. Embryonic stem cells, on the other hand, when cultured in the laboratory, divide indefinitely and do not seem to age. If and when biologists figure out the triggers that make ordinary differentiated cells age (and they already have some strong hints) they may be able to devise gene-based strategies to slow or stop that aging.
Any use of stem cells is controversial because it does involve the destruction of early embryos which have the potential to grow into newborn babies. Most of the ethical objections to stem cell research come from people who feel strongly that the human embryo, even at its earliest stages, is a human person and entitled to the same protections that all human beings have whatever their age, abilities or disabilities.
Dr. Robin Alta Charo is an international expert on legal and ethical issues of stem cell and other research involved in reproductive studies. She has recently worked on a national committee appointed by the President to look into these questions. Here is her insight into this ethical issue.
“I think that what constitutes a morally significant form of life is one that has gone on for centuries and is not likely to be resolved anytime in our lifetime. At face it touches on things that cannot be proved, on things that cannot be explored through experimentation. For example, whether you think that the essence of moral significance lies in potentiality, or you think the essence of moral significance lies in a kind of experiential view of life, that is, if you believe that the real potential to develop under the right circumstances into a baby means that this form of life must be protected, in other words the acorn should be protected as if it were already an oak, then you are making this value judgment based upon a vision of the world that could transcend time in which we see life as part of a continuum across time. “On the other hand, there are people for whom that is not a relevant factor and they ask only do we have an entity that can experience itself and can feel disappointment and pain, in other words, can be harmed. And they look at an embryo and say no, it doesn’t even have the biological substrate to be self aware and to have formed a desire to continue to exist, and so it is in no way wrong to harm it. These are very different views about moral significance and they can’t be brought together..”
How can we as a society then decide such irreconcilable differences? Should we simply put them up to a vote, and let the majority rule?
“Well, I personally think there is a lot of guidance within the philosophy of our Constitution. The United States is not governed by pure popular majority. Instead we have a mix. On topics of rather ordinary concern we allow the popular will to prevail. .. On the other hand, there are areas of life that we have said are so central to a personal identity that even when popular sentiment would suggest that things should be restricted, we will permit them until the most compelling arguments have been made for restriction and until we have been shown that there is no other way to handle the concern other than restricting the activity.
“Those are things that are listed in the Bill of Rights, the freedom of association, of speech, of practicing your own religion, and it is also a set of things that have been identified by the Supreme Court as implicit within the Constitution and Bill of Rights such as the freedom to marry.
“Now one of the areas that we need to examine is the freedom of scientific inquiry. There have been suggestions over the years that this is something akin to free speech that just as free speech insures the long term stability of a civic society by providing an outlet for dissent, so we don’t have violent revolution, so scientific inquiry insures the continued development of new knowledge which helps to stabilize society. In my mind that is a very important question because if we see it as fundamental to the long term stability of a civic society than it is something that needs to be protected even if it is against the popular will.”
What about the future? What will happen 10 to 20 years from now with stem cell research, scientifically and ethically. At present the legal status of stem cell research in the United States is a mixed story. Some states have passed laws to ban both reproductive and therapeutic cloning for stem cell research. Other states are considering such bans. On the other hand some states, like California, have passed popularly supported referendums to give generous support to stem cell research in all its variations.
On the federal level there are no laws at present restricting stem cell research. The US government, however, has ordered the National Institutes of Health to refuse federal funding for any stem cell research using embryonic stem cell lines created after Aug. 9, 2001. This restriction is being contested by many scientists as well as many scientific, religious and political groups.
There are similar conflicts about the ethical and legal status of stem cell research, as well as other forms of genetic engineering, in Central and South America and in some western European countries. In 1998 environmental activists in Switzerland sponsored an national referendum that would have banned the production and distribution of transgenic animals, field trials with genetically modified organisms of any sort, and the patenting of genetically modified animals and plants. The referendum was voted down by two-thirds of the Swiss voters.
Countries in Asia like China, Japan, South Korea, Singapore and Taiwan, on the other hand, place few or no restrictions on embryonic stem cell research nor on genetic engineering. And scientists there are making rapid progress on many frontiers of genetic engineering and cutting-edge biology.
How fast will progress take us in the 21st century? No one can be sure.
Dr Mulcahy gives voice to the majority view of scientists today about stem cell research.
“I would say 10 to 20 years from now I fully expect that we will have a number of effective treatments using embryonic stem cells, I also would predict that much like what happened in the case of in-vitro fertilization, which at its inception was a real hot button, it will evolve into a much more accepted and appreciated medical tool..”
So too, most scientists predict that in the many other varied fields of genetic engineering—-food production, environmental protection, disease prevention and cure, species preservation, energy production, poverty alleviation, climate control, reproduction help, pollution clean-up, and more—as the benefits become well-known, public acceptance will follow.
The 19th and 20th centuries are known as the centuries of the industrial revolution. Most experts predict that the 21st century will be the century of biological revolutions.