Genetic engineering of human beings is not the same as recombinant DNA research. Genetic engineering is a process carried out on human beings; recombinant DNA methods are ways to purify genes. Such genes might be used in genetic engineering procedures but are much more likely to be used as tools in studies of biological organisation or as elements in a biological manufacturing process. Although genetic engineering is not the same as recombinant DNA research, the two are rightly linked because recombinant DNA work is hastening the day when genetic engineering will be a feasible process for use of certain human diseases. Since recombinant DNA work is also bringing closer the discovery of many other possible new medical treatments and is likely to bring other new capabilities, why is there so much focus on genetic engineering? Genetic engineering, because of its tabloid appeal, has become a symbol to many people of the frightening potential of modern-day technology. Rather than seeing in molecular biology the same complex mixtures of appropriate and inappropriate applications that characterise all powerful sciences, many people have allowed the single negative catch phrase “genetic engineering” to dominate discussions. People worry that if the possibility of curing a genetic defect by gene therapy should ever become a reality, the inevitable result would be “people made to order.” It is argued that unless we block recombinant DNA research now, we will never have another chance to control our fate. Ashoka, in this in-depth research, dispels many misgivings about the subject, in the weekly column, exclusively for Different Truths.
The traditional pact between society and its scientists, in which the scientist is given the responsibility for determining the direction of his work, is a necessary relationship if basic science is to be an effective endeavour. This does not mean that society is at the mercy of science, but rather that society, while it must determine the pace of basic scientific innovation, should not attempt to prescribe its directions.
What we call molecular biology today had its origins in individual decisions of a small number of scientists during the period from the late 1930s through the early 1950s. These people were trained in diverse fields, among them physics, medicine, microbiology, and crystallography. They created molecular biology out of the realisation that the problems posed by genetics were central to understanding the structures of living systems. No one channelled them towards this line of thinking, no one cajoled them to tackle these problems; rather, their own curiosity and sense of timing led them to try to elucidate these mysteries. This history provides a model of how the most effective science is done.
It is partly the successes of molecular biology that have brought on the questioning of whether scientists should be allowed their freedom of decision. It is, therefore, worthwhile tracing the development of concerns about whether certain areas of science should be closed to the investigation. Molecular biology is the science that has revealed to us the nature of one of the most fundamental of all substances of life, the gene. There is a very simple underlying reality to the transmission of characteristics from parents to children: a code based on four different chemicals, denoted by the letters A, T, G, and C, is used to store the information of heredity. The order in which these four chemicals appear in a virtually endless polymer, called DNA, is the language of life.
Knowing that DNA was the physical storehouse of the genes, Watson and Crick, in 1953, first solved the problem of how the DNA is organised to assure that information is transferred with almost perfect reliability from parent cells to progeny cells. They showed that DNA is made of two strands intertwined together into a helix and also that the four subunits in DNA are physically related so that only A and T form a specific pair as do G and C. The two strands are held together by this specific pairing so that the two strands carry redundant information. Each gene is thus really a gene and a mirror-gene; this self-complementarity allows DNA to repair itself–and therefore maintain the fidelity of its information–and also to duplicate itself, sending identical copies into the two daughter cells resulting from a round of cell division.
Following the monumental discovery of the structure of DNA, many scientists have contributed to learning how to make DNA, how to read DNA, how to cut DNA, how to rejoin DNA, and in general, how to manipulate at will the genes of very simple organisms.
What good has all of this new knowledge brought to the average person? First and of great importance is the contribution that scientific advances make to human culture. The continued accumulation of knowledge about ourselves and our environment is a crucial cultural aspect of contemporary life. Science, as well as art, illuminates man’s view of himself and his relation to others. Our knowledge of how we work, how one person differs from and is similar to another, what health is, and what disease, what we need to support health, and so on, helps to set the ground rules for the debates of politics and the productions of art.
Practical Benefits of Biology
The more practical benefits of biology can be expected to come in the future in the form of medical advances, or increases in food production, or in other manipulations of life processes that will be able to provide positive contributions to civilisation. But molecular biology, for all of its power as a basic science, has not been easily translated into tangible benefits. This is a situation that could change very soon. New discoveries are rapidly bringing molecular biology closer to an ability to affect the lives of the general public.
Of the advances that have occurred, a critical one has been the development of a process called recombinant DNA research. This is a technique whereby different pieces of DNA are sewn together using enzymes; the chimeric DNA is then inserted into a bacterium where it can be multiplied indefinitely. Because the method allows genes from any species in the world to be put into a common type of bacterium, there is a theoretical possibility of hazard in this research. The potential for unforeseen occurrences led a number of scientists, including me, to issue in 1974 a call for restraint in the application of these new methods. We were addressing a limited problem, whether there could be a recognisable hazard in the performance of certain experiments. That limited question opened a floodgate; other questions came pouring out and are still coming. They have led to front-cover stories in weekly magazines, to serious attempts at federal legislation, to a demoralisation of some of the community of basic research biologists, and, most significantly, to a deep questioning of whether further advances in biology are likely to be beneficial or harmful to our society
Much of the discussion about recombinant DNA research has centred on whether the work is likely to
create hazardous organisms. The mayor of Cambridge, Massachusetts, raised the spectre of Frankenstein monsters emerging from MIT and Harvard laboratories, and speculations about the possibility of inadvertent development of a destructive organism like the fictitious Andromeda Strain have been much in the news. I am personally satisfied that most of such talk is simply science fiction and that the research can be made as safe as any other research. The people who understand infectious diseases best make the arguments most strongly that recombinant DNA research is not going to create the monsters. But rather than defend my judgment that the safety issue has been blown out of proportion, I want to consider some of the more general issues that have been raised by the controversy.
If safety were the most important consideration behind the debate about recombinant DNA, then we might expect the debate to focus on the hazards of doing recombinant DNA experiments. Instead, many of the discussions that start considering such questions soon turn to a consideration of genetic engineering
Two techniques labelled genetic engineering exist. Both originated because not everybody’s genes are perfectly designed for the job of being a functioning human being, so that many instances of blood disorders, mental problems, and a host of other disabilities are traceable to a malfunctioning gene. It would be a triumph of medicine if the effects of such genes could be countered, and two approaches for countering them have been considered, both of which are called genetic engineering. One approach involves altering some cells of the body so that they can carry out the needed function. A patient could, for instance, be treated in this way for a blood disease caused by an abnormal protein made by a mutant gene. A normal gene would be inserted into the precursor cells–immature bone marrow cells that ultimately develop into functioning blood cells.
The Malfunctioning Gene
In this way, a normal protein could be made in place of, or along with, the aberrant protein. The genetically altered blood cell precursor could then cure the patient’s disease. But the malfunctioning gene would still be transmitted to the patient’s offspring. Because this form of genetic engineering would not change the gene pool of the species and because it may prove an effective medical treatment of disease, it does not present the same moral problem as the other form. It is likely to be the first type of genetic engineering tried on human beings, and might be tried within the next five years.
The second type of genetic engineering presents more of a dilemma because it could change the human gene pool. This would involve replacement of genes in the germ cells, cells that transmit their genes to our offspring. Such a change would represent a permanent alteration of the types of the genetic information that constitutes our species. Replacement of germ cell genes would be very difficult and is, I suspect, at least twenty years away. It presents no theoretical problems, only formidable logistic problems.
Both forms of genetic engineering, but especially the engineering of germ cells, present two very deep and perplexing problems: who is to decide, and how shall they decide what genes are malfunctions? Decisions about which genes are good and which bad truly represent decisions of morality and are therefore highly subjective. Fear that dictators will decide which genes should be suppressed and which promoted, and that their criteria for the decision will be how best to maintain their own power, has made the phrase “genetic engineering” symbolic of the moral problems that can be created by modern biology.
Genetic engineering of human beings is not the same as recombinant DNA research. Genetic engineering is a process carried out on human beings; recombinant DNA methods are ways to purify genes. Such genes might be used in genetic engineering procedures but are much more likely to be used as tools in studies of biological organisation or as elements in a biological manufacturing process. Although genetic engineering is not the same as recombinant DNA research, the two are rightly linked because recombinant DNA work is hastening the day when genetic engineering will be a feasible process for use of certain human diseases. Since recombinant DNA work is also bringing closer the discovery of many other possible new medical treatments and is likely to bring other new capabilities, why is there so much focus on genetic engineering? I believe that genetic engineering, because of its tabloid appeal, has become a symbol to many people of the frightening potential of modern-day technology. Rather than seeing in molecular biology the same complex mixtures of appropriate and inappropriate applications that characterise all powerful sciences, many people have allowed the single negative catch phrase “genetic engineering” to dominate discussions. People worry that if the possibility of curing a genetic defect by gene therapy should ever become a reality, the inevitable result would be “people made to order.” It is argued that unless we block recombinant DNA research now, we will never have another chance to control our fate.
To see the form of the argument against recombinant DNA research most clearly and to highlight its danger to intellectual freedom and creativity, we should realise that similar arguments have been put forward relative to other areas of basic biology. One of the most respected critics of recombinant DNA research, Robert Sinsheimer, has, for instance, made comparable analyses of two other research topics, research on ageing and attempts to contact extra-terrestrial beings. He argues that if research on ageing were to be successful, people could live too much older ages and the changed age structure of the population would bring serious stresses to society. His fear about searching for extra-terrestrial beings is, again, that we could be successful, and he considers that the discovery of civilisations much more advanced than ours would have effects on us like those the Europeans had on Native Americans after the discovery of the New World. In the case of recombinant DNA research as well as the other topics, Dr. Sinsheimer says we should avoid studying these areas of science. Rather, he believes, we should put our resources into investigating areas of proven need, such as fertility control.
These examples – and I could choose many others, especially outside of biology – have the same general form: certain people believe that there are areas of research that should be taboo because their outcome might be, or in some scenarios will be, detrimental to the stable relationships that characterise contemporary society. I have heard the argument in a different and more pernicious form from members of a Boston area group called Science for the People. They argue that some research in genetics should not go on because its findings might be detrimental to the relationships they believe should characterise a just society. Such arguments are reminiscent of those surrounding the eugenics movements that developed in Germany and Russia, in the 1920s. After a period of intense debate, these countries with opposing ideologies settled on opposing analyses of the role of genetics in determining human diversity. German scientists and politicians espoused a theory of racial purification by selective breeding, while Russia accepted the Lamarckian principle of transmission of acquired characteristics. In both cases, science was forced into a mould created by political and social ideology, and in both cases the results were disastrous.
As I see it, we are being faced today with the following question: should limits be placed on biological research because of the danger that new knowledge can present to the established or desired order of our society? Having thus posed the question, I believe that there are two simple, and almost universally applicable, answers. First, the criteria determining what areas to restrain inevitably express certain socio-political attitudes that reflect a dominant ideology. Such criteria cannot be allowed to guide scientific choices. Second, attempts to restrain directions of scientific inquiry are more likely to be generally disruptive of science than to provide the desired specific restraints. These answers to the question of whether limits should be imposed can be stated in two arguments. One is that science should not be the servant of ideology because ideology assumes answers, but science asks questions. The other is that attempts to make science serve ideology will merely make science impotent without assuring that only desired questions are investigated. I am stating simply that we should not control the direction of science and, moreover, that we cannot do so with any precision.
Before trying to substantiate these arguments I must make a crucial distinction. The arguments pertain to basic scientific research, not to the technological applications of science. As we go from the fundamental to the applied, my arguments fall away. There is every reason why technology should and must serve specific needs. Conversely, there are many technological possibilities that ought to be restrained.
To return to basic research, let me first consider the danger of restricting types of the investigation because their outcome could be disruptive to society. There are three aspects of danger. One is the fallacy that you can predict what society will be like even in the near future. To say, for instance, that it would be bad for Americans to live longer assumes that the birth rate will stay near where it is. But what happens if the birth rate falls even lower than it is now? We might welcome a readjustment of the life span. In any case, we have built the world around a given human life span; we could certainly adjust to a longer span, and it would be hard to predict whether, in the long run, the results would be better or worse
The Error of Futurism
In a general form, I would call this argument for restricting research the Error of Futurism. The futurist believes that the present holds enough readable clues about the future to provide a good basis for prediction. I doubt this assumption; to think that the data of today can be analysed well enough to predict the future with any accuracy seems nonsensical to me.
The second danger in restricting areas of scientific investigation is more crucial: although we often worry most about keeping society stable, in fact, societies need certain kinds of upheaval and renewal to stay vital. The new ideas and insights of science, much as we may fight against them, provide an important part of the renewal process that maintains the fascination of life. Freedom is the range of opportunities available to an individual–the more he has to choose from, the freer his choice. Science creates freedom by widening our range of understanding and therefore the possibilities from which we can choose.
Finally, attempts to dictate scientific limits on political or social considerations have another disastrous implication. Scientific orthodoxy is usually dictated by the state when its leaders fear that truths could undermine their power. Their repressive dicta are interpreted by the citizens as an admission of the leaders’ insecurity and may thus lead to unrest requiring further repression. A social system that leaves science free to explore, and encourages scientific discoveries rather than trying to make science serve it by producing the truths necessary for its stability, transmits to the members of that society strength, not fear, and can endure.
The other argument I mentioned in opposing the imposition of orthodoxy on science is the practical impossibility of stopping selected areas of research. Take ageing as a prime example. It is one of the mystery areas of modern biology. The questions are clear. Why do we get older? Why do organ systems slowly fail? Why one species of animal lives three years and another for lives for one hundred? These seemingly straightforward questions are unapproachably difficult for modern biology. Not only can we not understand events that occur over years, but we even have difficulty understanding questions about events that require minutes to transpire. In fact, molecular biologists are really only experts in the millisecond range of time. Such times are those of chemical reactions; to understand events in longer time frames probably requires knowing how individual reactions are integrated to produce clocks that measure time in seconds to years. Clues to the great mysteries of biology–memory, ageing, and differentiation – lie in understanding how biological systems tell time.
There are a few hints about where answers to the puzzle of ageing might be found, but they are only the vaguest suggestions. In such an area of science, history tells us that successes are likely to come from unpredictable directions. A scientist working on vitamins or viruses or even plants is just as likely to find a clue to the problem of ageing as is a scientist working on the problem directly. In fact, someone outside the field is more likely to make a revolutionary discovery that someone inside the field.
Another example will help to show the generality of this contention. Imagine that we were living at the turn of the last century and had wanted to help medical diagnosis by devising a method of seeing into the insides of people. We would probably have decided to fund medical scientists to learn how to use bright lights to see through patients’ skin. Little would we have guessed that the solution would be revolutionary and would come, not from a medical research scientist, but from a physicist, who would discover a new form of radiation, X-Rays.
Major Breakthroughs are Unpredictable
Major breakthroughs cannot be programmed. They come from people and areas of research that are not predictable. So if you wanted to cut off an area of fundamental research, how would you be able to devise the controls? I contend that it would be impossible. Instead, disruption and demoralisation would follow from attempts to determine when a scientist was doing work in approved directions and when he was not. Creative people would shun whole areas of science if they knew that in those areas their creativity would be channelled, judged, and limited. The net effect of constraining biologists to approved lines of investigation would be to degrade the effectiveness of the whole science of biology
Put this way, the penalty for trying to control lines of investigation seems to me greater than any conceivable benefit. I conclude that society can choose to have either more science or less science, but choosing which science to have is not a feasible alternative. I must repeat a qualification of this broad generalisation: the less basic the research area in which controls are imposed, the less general disruption will be caused by the controls. The development of a specific sweetener, pesticide, or weapon could be prevented with little-generalised effect
While it seems necessary that scientific research to free of overt restraints, it would be naive to think that science is not directed at all. Many crucial decisions are made about general directions of science, usually by the control of available resources. Again, the formula I used before is applicable: the less basic the area of research, the easier it is to target the problems. A fallacy behind some of the hopes for the “War on Cancer” was the assumption that the problems to be solved were sufficiently well defined to allow a targeted, applied approach to the disease. Some problems could be defined and those were appropriate targets for a war on the disease, but the deeper mysteries of cancer are so close to the frontiers of biology that targets are hard to discern.
I have painted a picture of inexorable, uncontrollable development of basic scientific knowledge. The response of many people to such a vision might well be “If we can’t put any controls on research, maybe we shouldn’t have any research.” I see the rationale in this criticism because it is conceivable that the rate of accretion of knowledge could become so high that a brake might be needed. A way exists to produce a slowdown, that is, by controlling the overall availability of resources. A nonselective brake on fundamental biology would decrease productivity without the disruptive and dangerous effects of trying to halt one area and advance another.
Because such a brake was applied in the late 1960s, today we have less basic research, measured in constant dollars spent on it, than we had then. As a result of the slowdown, the danger seen by many is not that we have too much basic research, but rather that we are living on our intellectual capital and that an infusion of funds into basic areas of research is needed before these scientific resources are exhausted. It must also be realised that our commitment to the solution of problems like cancer requires that we develop much more basic knowledge
Let me quote from the most eloquent analyst of contemporary biology, Lewis Thomas, the president of the Memorial Sloan-Kettering Cancer Center in New York. Writing in the New England Journal of Medicine about the recombinant DNA issue, Dr. Thomas ended with this analysis of the role of scientific research in the life of the mind:
Is there something fundamentally unnatural, or intrinsically wrong, or hazardous for the species, in the ambition that drives us all to reach a comprehensive understanding of nature, including ourselves? I cannot believe it. It would seem to me a more unnatural thing, and more of an offense against nature, for us to come on the same scene endowed as we are with curiosity, filled to over-brimming as we are with questions, and naturally talented as we are for the asking of clear questions, and then for us to do nothing about it, or worse, to try to suppress the questions. This is the greater danger for our species, to try to pretend that we are another kind of animal, that we do not need to satisfy our curiosity, exploration, and experimentation, and that the human mind can rise above its ignorance by simply asserting that there are things it has no need to know.
©Ashoka Jahnavi Prasad
Photo from the internet.
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