Genetic Engineering

Genetic engineering has plunged the world into a stunning technological revolution, one that brings great promise, spurs grave fears, and has unquestionably changed humanity’s relationship with the very blueprint of life and physical existence. The problem with being in the midst of a revolution is that one can have little idea where one will end up when the revolution is complete.

So far, genetic engineering and gene-based knowledge have lifted biological science from a relatively crude state of inexactitude, have allowed humans to crack the genetic code, and have given researchers the tools to alter human, animal, and plant life to serve human goals.

Already the products of genetic engineering and genetic science are common throughout the developed world: gene therapies to treat human disease, genetically modified foods for people and animals, and pharmaceuticals for humans produced through genetically engineered bacteria.

The wave of potential products is stunning: organs from pigs transplanted into sick humans, drugs for humans produced in cow’s milk, plastics produced by plants rather than with fossil fuels, and gene therapies that could extend human life.

Genetic Engineering, Genes, and Genomics

What exactly is genetic engineering? In essence, it involves the manipulation of genes using recombinant DNA techniques to modify what the gene does, either by itself or in combination with other genes. Recombinant means combining genes from different sources in a different manner than occurs naturally. Genes are the units formed by combinations of the nucleotides G (guanine), A (adenine), T (thymine), and C (cytosine), which lie in two equally long and twisting strings (the famous “double helix”) that are attached to each other throughout their length. G, A, T, and C nucleotides combine in pairs across the space between the two strings.

About three billion pairs form the human genome — the string of genes that make up each individual human’s genetic structure. The study of genomes — known as genomics — aims to discover how genome-scale technologies might be applied to living organisms, including human beings. Genomics currently enjoys strong support, both financial and institutional, within the scientific and medical communities and within the pharmaceutical industry.

Other biological life forms have different numbers of genes than the human genome. A gene is a stretch of A-T and C-G pairs that, by their complex arrangement, lay out the instructions for a cell to produce a particular protein. Proteins are the basic agents, formed from amino acids, that determine the chemical reactions in the cell. This long and complex genome is also incredibly small. It is contained in every cell in the body as a microscopic molecule. Although all of the genetic code is included in each body cell, each cell performs only a relatively tiny number of highly specialized functions, with only a comparatively few genes being activated in the functioning of a cell’s production and use of proteins. Each cell may produce thousands of proteins, each the product of a different gene; but most of the genome’s genes will never be employed by each cell. The genome can perhaps be understood as an instruction manual both for the construction of a life form and for its functioning once it has formed. It is like a computer operating system that also contains the information that a tiny piece of silicon could use to build itself into the computer that will use the operating system.

Changing Genetic Function

Because genes determine what cells do within an organism, scientists realized that by altering, adding, or deleting genes they could change the functioning of the larger life form of which the genes are a part. To do so they need to use genetic engineering to alter and switch genes.

What scientists have been able to do with genetic engineering is (1) make it possible to “see” the genes in the DNA sequence, (2) understand the functions of some of those genes, and (3) cut into the DNA and remove or add genes and then reform it all as a single strand. Often the genes that are added come not from members of the same animal, plant, or bacterial species but from entirely different species.

Genetic Engineering Procedure

How is genetic engineering done? Again, there are very simple and exceedingly complex answers to this question, depending on how much detail one wants about the underlying processes.

The recombinant DNA revolution began in the 1970s, led by three scientists from the United States: Paul Berg, Stan Cohen, and Herb Boyer. They knew that certain bacteria seemed to be able to take up pieces of DNA and add them to their own genome. They discovered that even recombinant DNA created in the lab could be taken up by these bacteria. By 1976 scientists had successfully created a bacterium containing a human protein in and later managed to produce human insulin in bacteria. Bacterially produced human insulin, produced using this bacterium-based process, is now the main form of insulin supplied to people suffering from diabetes.

Genetic engineers have discovered ways to isolate a gene in one species that they think could have a useful function in another, insert that gene (with others that make it “stick” to the rest of the DNA strand) into a cell’s nucleus, and then make that cell develop into an entire life form. It is comparatively easy for scientists to introduce genes and comparatively much harder to get the altered cell to develop into a larger life form.

Radical Implications

Many fear the implications of this revolution. Not only is it a radically new science with little proof that its many innovations will be entirely safe but, in addition, no one is in control of it. Like all revolutions of knowledge, once the scientific breakthroughs have been achieved and the information has been widely disseminated, human individuals and societies, with all their virtues and vices, will be free to use the knowledge as they see fit. At present nobody is responsible for saying yea or nay to genetic engineering developments on behalf of the human species. History does not suggest that all human beings are either entirely altruistic or completely competent in embracing the possibilities of radical new technology.

Genetic Engineering Pros and Cons

With all the promise and potential, a wave of beneficial products appears set to wash over the human species and make human existence better.

Since the beginning of the genetic engineering revolution, however, some people have been profoundly concerned about the implications and possible dangers of the scientific innovations now occurring in rapid succession.

From its beginning, genetic engineering has prompted concerns from researchers, ethicists, and the public. For example, Paul Berg, the genetic engineering pioneer, called for a moratorium on molecular genetic research almost simultaneously with his team’s early discoveries, so that people could consider the consequences of these new methods. Since then, scientists have debated the positives and negatives of their new scientific abilities while also overwhelmingly embracing and employing those abilities. Many — but not all— of the scientific worries have been alleviated as scientists have improved their knowledge, but the worries of the public and nonscientists conversely have greatly increased.

Some of the concerns of critics about genetic engineering are practical. Is it safe to move genes around from one individual to another? Is it safe to move genes from one species to another? For example, if organs from a pig were genetically altered so that humans could accept them as transplants, would that make that person susceptible to a pig disease? And if that pig disease struck a human containing a pig organ, could that disease then adapt itself to humans in general and thereby become a dangerous new human disease? The actual nuts and bolts of genetic engineering often include many more strands of genetic material than just the attractive characteristic that scientists want to transfer. Diff erent genetic materials are used to combine and reveal changes in genetic structure. What if these elements bring unexpected harm, or if somehow the combination of disparate elements does something somehow dangerous?

Some fear that ill-intended people, such as terrorists or nasty governments, might use genetic engineering to create diseases or other biological agents to kill or injure humans, plants, or animals. For instance, during the years of apartheid, a South African germ warfare program attempted to find diseases that could kill only black people and attempted to develop a vaccine to sterilize black people. During the Cold War, both NATO and Warsaw Pact nations experimented with biological warfare. The program of the Soviet Union was large and experimented with many diseases, including anthrax and smallpox. In one frightening case, an explosion at a Soviet germ warfare factory caused an outbreak of anthrax in one of its cities, causing many deaths. If scientists become able to go beyond merely experimenting with existing diseases to creating new ones or radically transformed ones, the threat to human safety could be grave. Australian scientists alarmed many people when they developed a form of a disease that was deadly to mice. If that disease, which is part of a family that can infect humans, somehow became infectious to humans, science would have created an accidental plague. What if scientists deliberately decided to create new diseases?

This fear about safety is not limited just to humans intentionally creating dangerous biological agents. What if scientists accidentally, while conducting otherwise laudable work, create something that has unexpectedly dangerous characteristics? What if humans simply are not able to perceive all the physical risks contained in the scientific innovations they are creating?

This concern has already gone from the theoretical to the real in genetic engineering. For instance, British scientists got in trouble while trying to develop a vaccine for hepatitis C after they spliced in elements of the dengue fever genome. Regulators disciplined the scientists for breaching various safe-science regulations after some became concerned that a frightening hybrid virus could arise as a result. The scientists had not intended any harm, and no problem appears to have arisen, but potential harm could have occurred, and any victims might have cared little about whether the damage to them was caused deliberately or by accident. Once a disease is out of the laboratory and fl oating in an ocean of humanity, it might be too late to undo the damage.

Responding to this concern, some argue for an approach they refer to as the “precautionary principle.” This suggests that innovations and developments not be allowed out of the laboratory — or even created in the laboratory — until their safety or potential safety has been exhaustively demonstrated. Critics of genetic engineering often claim that the absence of long-term tests of genetic engineering innovations means that they should not be introduced until these sorts of tests can be conducted. This sounds like a good and prudent approach, but if actually applied across the spectrum, this approach would have prevented many innovations for which many humans now are profoundly grateful. If organ transplantation had been delayed for decades while exhaustive studies were conducted, how many thousands of Americans would not be alive today because they could not receive transplants? If scientists were prevented from producing insulin in a lab and forced to obtain it from human sources, how many diabetics would be short of lifesaving insulin? If scientists develop ways to produce internal organs in pigs that could save the many thousands of people who die each year because they cannot obtain human transplant organs in time, how long will the public wish to prevent that development from being embraced? The precautionary principle may appear to be an obvious and handy way to avoid the dangers of innovations, but it is difficult to balance that caution against the prevention of all the good that those innovations can bring.

Some of the concerns have been political and economic. Regardless of the possible positive uses of genetic engineering innovations, do they confer wealth and power on those who invent, own, or control them?

Many genetic engineering innovations are immediately patented by their inventors, allowing them to control the use of their inventions and charge fees for access to them. If an innovation makes a biological product such as a crop more competitive than nonengineered varieties, will farmers be essentially forced to use the patented variety in order to stay competitive themselves? Will the control of life forms changed by genetic engineering fall almost entirely into the hands of wealthy countries and big companies, leaving poor countries and individuals dependent on them? If a researcher makes an innovation in an area that other researchers are working in and then gets legal control of the innovation, can he prevent other researchers from developing the science further? The latter is a question American university researchers have often debated.

Positive Progress or Dangerous Development

Genetic engineering can be seen as radically new, but to some it is merely a continuation of humanity’s age-old path of scientific development. Some see it as an unprecedented break with age-old methods of human science and industry and fundamentally different; others see it as the next logical step in development and therefore not fundamentally radical at all.

One’s general outlook on scientific development can also color one’s view as to whether these developments seem generally positive or negative. Do you see scientific progress as opening new opportunities and possibilities for humans to improve their situation and the world, or do you see it as opening doors to dangers against which we need to be protected? To some degree these different perspectives determine whether one is alarmed and cautious about this new science or excited and enthusiastic about it.

As humanity lives through this stunning revolution, the number of details known will increase. Few believe we are anywhere near the peak of the wave of innovations and developments that will occur because of the ability of scientists and industries to use genetic engineering to alter life. Indeed, most scientists consider this to be a scientific revolution that is only just beginning.

Selective Breeding

Humanity began its social evolution when it began manipulating its environment. Hunter-gatherer peoples often burned bush to encourage new plant growth that would attract prey animals. At a certain point in most cultures, early hunters learned how to catch and domesticate wild animals so that they would not have to chase them or lure them by crude methods such as this. The ex-hunters would select the best of their captured and minimally domesticated animals and breed them together and eliminate the ones that were not as good. Eventually the animals became very different from those that had not been domesticated.

The earliest crop farmers found plants that provided nutritious seeds and, by saving and planting some of those seeds, created the first intentional crops. By selecting the seeds from the plants that produced the biggest, greatest number, or nutritionally most valuable seeds, those early farmers began manipulating those plant species to produce seeds quite different from the uncontrolled population.

The plants and animals created by selective breeding were the result of a very primitive form of genetic engineering by people who did not know exactly what they were doing (or even what a gene was): the attractive animals and plants with heritable characteristics were genetically different from the ones that did not have those characteristics, so when they were bred together, the genes responsible for the attractive qualities were concentrated and encouraged to become dominant, and the animals and plants without the genes responsible for the attractive characteristics were removed from the breeding population and their unattractive genes discouraged.

Over centuries and thousands of years, this practice has produced some stunningly different species from their natural forebears, as deliberate selection and fortuitous genetic mutations have been embraced in the pursuit of human goals. For example, it is hard to imagine today’s domestic cattle at one time being a smart, tough, and self-reliant wild animal species capable of outrunning wolves and saber-tooth tigers, but before early humans captured and transformed them, that is exactly what they were. Consider the differences between cattle and North American elk and bison. Even “domesticated” elk and bison on farms need to be kept behind tall wire mesh fences because they will leap over the petty barbed wire fences that easily restrict docile cattle. But in 100 years, after “difficult” animals are cut out of the farmed bison and elk herds, will these animals still need to be specially fenced?

Wheat, one of the world’s most common crops, was just a form of grass until humans began selective breeding. The fat-seeded crop of today looks little like the thin-seeded plants of 7,000 years ago. Under the microscope, it looks different too: although the overall wheat genome is quite similar to that of its wild grass relatives, the selective breeding over thousands of years has concentrated genetic mutations that have made today’s wheat a plant that produces hundreds of times more nutritional value than the wild varieties. Did the farmers know that they were manipulating genes? Certainly not. Is that what they in fact did? Of course. Although they did not understand how they were manipulating the grass genome, they certainly understood that they were manipulating the nature of the grass called wheat.

In the past few centuries, selective and complex forms of breeding have become much more complex and more exact sciences. (Look at the stunning yield-increasing results of the commercialization of hybrid corn varieties beginning in the 1930s.) But it was still a scattershot approach, with success in the field occurring because of gigantic numbers of failed attempts in the laboratory and greenhouse. Scientists were able to create the grounds for genetic good fortune to occur, but they could not dictate it. They relied on genetic mutations happening naturally and randomly and then embraced the chance results.

This began to change after the existence and nature of deoxyribonucleic acid (DNA) was revealed by scientists in the 1950s. Once scientists realized that almost all life forms were formed and operated by orders arising from DNA, the implications began to come clear: if elements of DNA could be manipulated, changed, or switched, the form and functions of life forms could be changed for a specific purpose.

Milk, Crops, and Cloning

It took decades to perfect the technology and understanding that allows genes and their functions to be identified, altered, and switched. But by the 1990s, products were rolling out of the laboratory and into the marketplaces and homes of the public. In animal agriculture the first big product was bovine somatotropin (BST), a substance that occurs naturally in cattle but is now produced in factories. When it is given to milk-producing cows, the cows produce more milk.

Farmers got their first big taste of genetic engineering in produce when various “Roundup Ready” crops were made available in the mid-1990s. Dolly, a cloned sheep, was revealed to the world in 1997. Generally, cloning is not considered genetic engineering because a clone by definition contains the entire unaltered gene structure of an already existing or formerly existing animal or cell. The genes can be taken from a fully developed animal or plant or from immature forms of life. Genetic engineering is generally considered to require a change in or alteration of a genome rather than simply switching the entire genetic code of one individual with another. Although not fitting the classic definition of “genetic engineering,” cloning is a form of genetic biotechnology, which is a broader category.

Disney and Shelley

Humanity has had grave concerns about new science for centuries. These concerns can be seen in folk tales, in religious concepts, and in literature. Perhaps the most famous example in literature is the tale of Dr. Victor Frankenstein and the creature he creates. Frankenstein, driven by a compulsion to discover and use the secrets to the creation of life, manages to create a humanoid out of pieces of dead people but then rejects his living creation in horror. Instead of destroying it, however, he fl ees from its presence and it wanders out into the world. The creature comes to haunt and eventually destroy Frankenstein and those close to him. The story of Frankenstein and his creature can be seen as an example of science irresponsibly employed, leading to devastating consequences.

Another tale is that of the sorcerer’s apprentice. In order to make his life easier, the apprentice of a great magician who has temporarily gone away uses magic improperly to create a servant from a broomstick. Unfortunately for the apprentice, he does not have the skill to control the servant once it has been created, and a disaster almost occurs as a result of his rash employment of powerful magic.

Both of these tales — popular for centuries — reveal the long-held uneasiness of those hesitant to embrace new technology.

Finding Balance On a practical and utilitarian level, many people’s concerns focus on a balance of the positives versus the negatives of innovations. They are really a compilation of pluses and minuses, with the complication of the known unknowns and unknown unknowns not allowing anyone to know completely what all the eventual pluses and minuses will be.

Balancing complex matters is not an easy task. Innovations in life forms created by genetic engineering can have a combination of positive and negative outcomes depending on what actually occurs but also depending on who is assessing the results. For instance, if genetically altered salmon grow faster and provide cheaper and more abundant supplies of the fish than unaltered salmon, is that worth the risk that the faster-growing genetically engineered salmon will overwhelm and replace the unaltered fish?

A helpful and amusing attempt at balancing the pluses and minuses of genetic engineering’s achievements was detailed in John C. Avise’s 2004 book The Hope, Hype and Reality of Genetic Engineering. In it he introduces the “Boonmeter,” which he attempts to use to place genetic innovations along a scale. On the negative extreme is the “boondoggle,” which is an innovation that is either bad or has not worked. Closer to the neutral center but still on the negative side is the “hyperbole” label, which marks innovations that have inspired much talk and potential but little success so far. On the slightly positive side is the “hope” label, which tags innovations that truly seem to have positive future value. On the extreme positive pole is the “boon” label, for innovations that have had apparently great positive effects without many or any negative effects.

Throughout his book Avise rates the genetic engineering claims and innovations achieved by the time of his book’s publication date using this meter, admitting that the judgments are his own, that science is evolving and the ratings will change with time, and that it is a crude way of balancing the positives and negatives. It is, however, a humorous and illuminating simplification of the complex process in which many people in society engage when grappling with the issues raised by genetic engineering.

Ethical concerns are very difficult to place along something as simplistic as the boonmeter. How does one judge the ethics of a notion such as the creation of headless human clones that could be used to harvest organs for transplantation into sick humans? Is that headless clone a human being? Does it have rights? Would doctors need the permission of a headless clone to harvest its organs to give to other people? How would a headless clone consent to anything? This sounds like a ridiculous example, but at least one scientist has raised the possibility of creating headless human clones, so it may not be as far-off an issue as some may think. Simpler debates about stem cells from embryos are already getting a lot of attention.

Conclusion

As genetically engineered innovations create more and more crossovers with science, industry, and human life, the debates are likely to intensify in passion and increase in complexity. Some biological ethical issues do appear to defl ate over time, however. For example, in the 1980s and 1990s, human reproductive technology was an area of great debate and controversy as new methods were discovered, developed, and perfected. Notions such as artificial insemination and a wide array of fertility treatments — and even surrogate motherhood — were violently divisive less than a generation ago but have found broad acceptance now across much of the world. Although there is still discussion and debate about these topics, much of the passion has evaporated, and many young people of today would not understand the horror with which the first “test tube baby” was greeted by some Americans.

Some of these concerns, such as that regarding in vitro fertilization, appear to have evaporated as people have accepted novel ideas that are not fundamentally offensive to them. Other debates, such as those surrounding sperm and egg banks, remain unresolved, but the heat has gone out of them. Other concerns, such as surrogate motherhood, have been alleviated by regulations or legislation to control or ban certain practices. Whether this will happen in the realm of genetic engineering remains to be seen. Sometimes scientific innovations create a continuing and escalating series of concerns and crises. Other crises and concerns tend to moderate and mellow over time.

Even if genetic science is used only to survey life forms to understand them better — without altering the genetic code at all — does that allow humans to make decisions about life that it is not right for humans to make? Some are concerned about prenatal tests of a fetus’s genes that can reveal various likely or possible future diseases or possible physical and mental problems. If the knowledge is used to prevent the birth of individuals with, for example, autism, has society walked into a region of great ethical significance without giving the ethical debate time to reach a conclusion or resolution? A set of ethical issues entirely different from those already debated at length in the abortion debate is raised by purposeful judging of fetuses on the grounds of their genes.

A simple, non–genetic engineering example of this type of issue can be seen in India. Legislators have been concerned about and tried to prevent the use of ultrasound on fetuses to reveal whether they are male or female. This is because some families will abort a female fetus because women have less cultural and economic value in some segments of Indian society. Similar concerns have been expressed in North America. Humans have been concerned about eugenics for a century, with profound differences of opinion over the rights and wrongs of purposely using some measure of “soundness” to decide when to allow a birth and when to abort it. These issues are yet to be resolved, and genetic engineering is likely to keep them alive indefinitely.

One area of concern has less to do with the utilitarian, practical aspects of genetic engineering than with spiritual and religious questions. The problem is summed up in the phrase playing God: by altering the basic building blocks of life — genes — and moving genes from one species to another in a way that would likely never happen in nature, are humans taking on a role that humans have no right to take?

Even if some genetic engineering innovations turn out to have no concrete and measurable negative consequences, some people of a religious frame of mind might consider the very act of altering DNA to produce a human good to be immoral, obscene, or blasphemous. These concerns are often raised in a religious context, with discussants referring to religious scriptures as the basis for moral discussion. For example, the biblical book of Genesis has a story of God creating humans in God’s image and God creating the other animals and the plants for humanity’s use. Does this imply that only God can be the creator and that humans should leave creation in God’s hands and not attempt to alter life forms? If so, what about the selective breeding that humans have carried out for thousands of years?

On the other hand, if humans are created in God’s image and God is a creator of life, then is not one of the fundamental essences of humanity its ability to make or modify life? Because God rested after six days of creation, however, perhaps the creation story suggests there is also a time to stop creating.

The advent of the age of genetic engineering has stirred up a hornet’s nest of concerns about the new technology. Some of these concerns are practical and utilitarian. Some are ethical and some are religious in nature. Regardless of whether one approves of genetic engineering, it is doubtless here to stay. The knowledge has been so widely disseminated that it no government, group of governments, or international organizations is likely to be able to eliminate it or prevent it from being used by someone somewhere. The genie is out of the bottle, and it is probably impossible to force it back in.

If they wish to find acceptable approaches before changes are thrust upon them rather than being forced to deal with ethical crises after they have arisen, scientists, politicians, and the public at large will have to develop their ethical considerations about genetic engineering as quickly and profoundly as these new discoveries surface and expand.

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Bibliography:

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