Bioscience, Biotech, and Bioethics
It's safe to say — and all the pundits are saying, consistent with the betting on Wall Street — that the coming century will see the flowering of biotechnology. Just as the century now coming to a close witnessed the dawn of the Nuclear Age and the Space Age, the 21st Century will usher in a new Age of Bioscience. We were reminded of the imminence of this new frontier of biology, medicine, and genetics this past June when it was announced that the Human Genome Project, the task of sequencing the 3 billion base pairs of the 24 human chromosomes (22 are paired autosomes, plus the X and Y sex chromosomes) was all but complete.
But this revolution is sprouting from roots that are deep in the 20th Century and, in particular, from a discovery that occurred less than ten years after the end of World War II. It is an amazing story of how humanity came into possession of an understanding that has become key to biology and medicine. And it is a far more astonishing story than someone getting a divine revelation in a dream or vision. Let me sketch the situation.
Although Darwin had made a powerful case for the cumulative impact of biological "variations" that were inherited across generations of organisms and had the ultimate effect of creating new species, no one had any idea of how this could happen. Friedrich Wöhler had synthesized the first organic molecule — urea — from inorganic precursors in 1828. Additional work had shown that living things depended on chemical reactions no different in principle than any other. So there were no "vital forces" or other life "energies" to account for. But just how molecules could actually reproduce themselves and pass traits from parents to offspring remained an enormous mystery. Nobody even knew what sort of molecules were responsible for this seeming miracle.
For a long time, all the betting was on proteins. Linus Pauling won the Nobel Prize in 1954 for his work on chemical bonding and structure. It was he who figured out that proteins, long chains of amino acids, could form complex shapes, helices in particular, through the formation of chemical bonds that involve the sharing of protons — hydrogen nuclei — between different amino acids in the chain.
The only other possibility was deoxyribonucleic acid: DNA. But DNA was composed of only a kind of 5-carbon sugar and four nucleotide base groups: adenine, thymine, guanine and cytosine. Compared to proteins with their 20 amino acids, DNA was boring. If you were going to bet on a molecule that could store information, 20 different constituents looked a lot better than 4. [Hence GATTACA. When you have only four letters to work with, you can't spell as many words!]
But it had to be either protein or DNA, because those were the only constituents of viruses, the simplest life forms known. In 1944 the evidence began to shift towards DNA. That was the year that Oswald T. Avery, Colin MacLeod, and Maclyn McCarty showed that a "transforming principle" that could genetically alter bacteria was, in fact, DNA.
James Watson describes his life as a young scientist during the years from 1951 to 1953 in his book The Double Helix. With remarkable — even embarrassing — candor he recounts his own thinking and that of others during that time. It was surmised that DNA, for example, was composed of either 2 or 3 chains of a sugar backbone with the nucleotide groups attached in sequence. The logical thing to suppose was that the nucleotides were sticking out. How else would the genetic information be revealed? Because of Pauling's work, the idea of helical conformation and hydrogen-bonding was also attractive. But, again, the precise solution was perplexing. Not since the time of Isaac Newton had there been a problem in science quite like this, in which even the general idea of what must be happening presented such a puzzle.
In London, at the Cavendish lab, Rosalind Franklin and Maurice Wilkins were creating images of DNA using X-ray crystal diffraction techniques in an attempt to solve the problem with brute force. Eventually they would have done it, too. This is how, today, 3-dimensional structures of all sorts of complex molecules are determined. Watson described his state of mind when he first learned — by a stroke of luck — of this early work:
Before Maurice's talk I had worried about the possibility that the gene might be fantastically irregular. Now, however, I knew that genes could crystallize; hence they must have a regular structure that could be solved in a straightforward fashion. Immediately I began to wonder whether it would be possible for me to join Wilkins in working on DNA.
Watson didn't join Wilkins. But he did get to London and the Cavendish lab, where he began model-building with Francis Crick. Although Wilkins and Franklin both considered this approach as bordering on the disgraceful, it forced Watson and Crick to narrow down the possibilities. They chose to work on a 2-stranded DNA, for example. The X-ray pictures also pushed them into thinking about a helix, as did common sense, since a helical shape is the best way to pack a large, long molecule into a small shape. But how the nucleotide bases fit in was the difficult part. Watson and Crick eventually decided to put the sugar backbone of the DNA molecule on the outside.
Almost immediately, the two were led to suppose that the nucleotide bases were hydrogen-bonded to each other in some way on the inside of a double helix. In fact, Watson was prepared to publish the idea that the nucleotides were paired with themselves in just this way. But there was one very big problem: the nucleotides are different sizes. Guanine and adenine are purines, and much bigger than thymine and cytosine, which are pyrimidines. In addition, Watson had used the wrong chemical forms of the molecules in supposing how the hydrogen-bonding worked. There was another wrinkle as well. Crick, in particular, worried about the strange findings of Erwin Chargaff, who had found only a few years before that DNA molecules seemed to always have the same number of purines — guanine and adenine — as the number of pyrimidines — cytosine and thymine. In fact, only the ratio of G-C to A-T nucleotide bases varied from species to species.
Near the end of his book, The Double Helix, James Watson describes the events of one day in early 1953, shortly after another of his hopes had been dashed that he had figured out the structure of DNA:
"When I got to our still empty office the following morning, I quickly cleared away the papers from my desk top so that I would have a large, flat surface on which to form pairs of bases held together by hydrogen bonds. Though I initially went back to my like-with-like prejudices, I saw all too well that they led nowhere. When Jerry [Donohue, "an American crystallographer"] came in I looked up, saw that it was not Francis, and began shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seemed to form naturally; no fudging was required to make the two types of base pairs identical in shape. Quickly I called Jerry over to ask him whether this time he had any objection to my new base pairs.
When he said no, my morale skyrocketed, for I suspected that we now had the answer to the riddle of why the number of purine residues exactly equaled the number of pyrimidine residues. Two irregular sequences of bases could be regularly placed in the center of a helix if a purine always hydrogen-bonded to a pyrimidine. Furthermore, the hydrogen-bonding requirement meant that adenine would always pair with thymine, while guanine could pair only with cytosine. ... Even more exciting, this type of double helix suggested a replication scheme much more satisfactory than my briefly considered like-with-like pairing. Always pairing adenine with thymine and guanine with cytosine meant that the base sequences of the two intertwined chains were complementary to each other. Given the base sequence of one chain, that of its partner was automatically determined. Conceptually, it was thus very easy to visualize how a single chain could be the template for the synthesis of a chain with the complementary sequence.
Upon his arrival Francis did not get more than half way through the door before I let loose that the answer to everything was in our hands. Though as a matter of principle he maintained skepticism for a few moments, the similarly shaped A-T and G-C pairs had their expected impact. His quickly pushing the bases together in a number of different ways did not reveal any other way ... the question then became whether the A-T and G-C base pairs would easily fit the backbone configuration devised during the previous two weeks. At first glance this looked like a good bet, since I had left free in the center a large vacant area for the bases. However, we both knew that we would not be home until a complete model was built in which all the stereochemical contacts were satisfactory. There was also the obvious fact that the implications of its existence were far too important to risk crying wolf. Thus I felt slightly queasy when at lunch Francis winged into the Eagle [pub]to tell everyone within hearing distance that we had found the secret of life."
- James D. Watson, The Double Helix (1968) Chapter 27.
As we now know, though, they had done exactly that. As happens so much in science, though, terminology tends to fix people's attention on the wrong thing. For the secret of life was not so much the discovery that DNA is a double helix. It was the realization that the nucleotide bases were paired in a complementary way — guanine always pairing with cytosine and adenine always with thymine — in an otherwise symmetrical molecule, each half of which determined the structure of the other half. That was the trick that solved the problem not only of how living things can be self-replicating, and of how they can pass their traits to their offspring, but of how those traits can be subtly changed by point-substitutions in the otherwise precise sequence of nucleotides in DNA. This is also why, despite the contribution of Wilkins and Franklin's X-ray studies, it is grossly unfair to accuse Watson and Crick, as some have, of "stealing" their discovery from others. [Incidentally, in Britain "Watson and Crick" is pronounced "Crick and Watson!"]
This story of how the structure of DNA was discovered is at once far more electrifying than any tale of divine revelation. It is also a stunning refutation of the currently popular postmodern-deconstructionist claim that science is nothing but a social construct, and an oppressive one at that. This is the idea that science — or any facts you might care to name — are no more "true" than anything that anyone wants to believe. Now, admittedly, if you read Watson's book you will find many things that reflect the nature and culture of the West, and Europe in particular, in the early 1950's. But the molecular structure of DNA is not one of them.
Another aside: DNA makes a right-handed helix. That is, it's like a right-handed screw of the common kind found in hardware stores. But many representations of the molecule in the media are shown as left-handed for some reason. Pay attention to this the next time you see a picture of the DNA molecule. [But if a politician or other celebrity should change the side their hair is parted on!]
Watson and Crick's discovery became the basis of the science of molecular biology. It was soon after found that genes are written in "codons" of three base pairs which, with four nucleotides to work with in DNA gave 64 possible combinations, far more than the 20 possible amino acids in proteins. Those combinations, and the amino acids they code for, were quickly worked out. All that remained was to decode every DNA molecule of interest and figure out the control mechanisms for its transcription/translation and replication. This is why the decoding of the entire human genome of 3 billion base pairs representing about 100,000 genes is important. People have been looking for the next stage of evolution for a long time. This is it.
As I have pointed out before, the last great genetic revolution was believed to have happened billions of years ago when an "RNA world" of living things based on self-replicating RNA gave way to DNA, with RNA taking up an intermediate position in the "central dogma" of biology: DNA makes RNA makes protein. The Human Genome Project is important because it represents the literal conversion of our genetic code, and, by extension, of that of all other living things, to the sequences of letters that stand for the four nucleotide bases: A, T, G and C. DNA, like RNA before it, is in the process of being relegated to an intermediate role. The new reality will be that we — human thoughts and human ideas — make DNA makes RNA makes protein.
If it hasn't seemed particularly revolutionary to you, consider the fact that just about everything that has dramatically and irreversibly changed the world has taken place in times and places that hardly seemed exciting at the time. A Roman general named Caesar crossed a river. An obscure Jewish mystic named Paul scribbled letters to people. An English King named John was forced by some nobles to sign a piece of paper. A confused Italian sailing in a Spanish ship hauled up on a small island in the Caribbean Sea. A group of upstart political dissidents sent an impertinent "Declaration of Independence" to King George the Third of the British Empire. A short Corsican captain was promoted to brigadier general in the French army. An obscure beer hall demagogue and political activist was named to lead the National Socialist German Workers' Party at about the same time that an unknown physics professor is experimenting with rockets in Massachusetts. All of these things happened in times and places that seemed anything but extraordinary. But all of them set events in motion that inevitably changed the world. And they did so in ways that make it difficult, if not impossible, for us to even imagine what things must have been like before.
Well before the Human Genome Project, bits and pieces of human DNA, and whole genomes of other organisms, had been analyzed. Modern methods in molecular biology, at least in principle, open up possibilities in three key areas: gene-hunting, genetic testing, and gene therapy. Two closely-related technologies are those of cloning and stem cell manipulation.
Although science is not a social construct, it affects society in ways that many people scarcely realize. The work of Freud, and especially of Pavlov, fostered the belief that an organism's environment exerts a major effect on its behavior. "Talking cures" for just about every variety of mental illness, real or perceived, was the result. The broader application was political propaganda. The "dark side" was the idea of "brainwashing" and psychological programming. When all you have is a hammer, everything tends to look like a nail.
When physical attributes of living things did become subject to manipulation it was by surgical means. H.G. Wells' Dr. Moreau was a plastic surgeon in the days before the problems of tissue rejection became better known. But surgery has its drawbacks and does not appeal to everyone.
What's changed over the last 50 years, ever since Watson and Crick figured out the molecular basis of reproduction, heredity, and what Darwin called "modification," there has been a growing tendency to suppose that there is a gene for everything. Things are going to turn out a good deal more complicated than this, just as they have in behavior modification and transplant surgery. But it's almost certainly a good thing that, after many years of supposing that the "right" nurture can overcome just about any nature, and of blaming the "wrong" nurture for every bad thing that can't be obviously explained by heredity, we are finally moving in the opposite direction. This will have — is already beginning to have — a profound effect.
The old way of thinking in criminal justice, for example, is that under some circumstances things are going on in our brains that prevent us from acting as we ordinarily would. This is the basis of the familiar "insanity defense." The truth is, of course, that but for what's going on in our brains under any circumstances we would not think and act as we do. This gets into the free will conundrum that we've addressed before — and will again, no doubt — but it shows that our legal system is far behind the curve. What ought to happen — and I think what will eventually happen — is that criminal proceedings will first determine whether an accused actually did or did not do something illegal beyond a reasonable doubt. Guilt or innocence — in a moral sense — can be left until later.
In fact, morality can and should be left out of criminal justice entirely, at least in principle. As the saying goes, locks are for honest people. Or, as Ayn Rand put it, "morality ends at the point of a gun." Not only can Humpty-Dumpty not be put back together again, but psychological methods of rehabilitating criminals have not been very successful. But maybe — just maybe — with both behavioral and physical/genetic methods it will be possible to fix every kind of broken mind. That is, if we can sort out the genetic contributions to antisocial behavior — if various groups who feel they are being unfairly targeted will allow such studies — and if effective corrective actions can be devised.
Those are very big if's. But it's typical of how our minds work that we race ahead with speculation while the more likely scenarios are mostly ignored. Larger-scale social and political considerations usually get more attention than closer-to-home and seemingly more trivial matters that may not affect us personally. What if there is a gene for homosexuality, after all? So what? What does that have to do with whether some people should be denied their civil rights? What does that have to do with the question of whether things that consenting adults do among themselves should be labeled "immoral" or held to be illegal?
The greater challenge, and the likelier next beach-head in gene hunting, is going to be figuring out the genetic basis of a number of relatively rare hereditary disorders about which we still know less than we'd like to. Then, looming over these is a whole range of chronic diseases from obesity and diabetes to heart disease and cancer. We already have good reason to believe that many of these conditions have a genetic component. They have an environmental component, too. But let's be reasonable. Medications that lower cholesterol are a better choice for most people than a 5% or 10% fat diet. Likewise, when all the genetic and environmental factors that contribute to chronic and degenerative diseases are teased apart, it's often going to be the case that a pill is going to be the best solution for many, if not most people.
Don't be surprised when this clashes with religious ideologies. The idea that if you're overweight or have a heart attack that it's your fault because you didn't "eat right" is not going to go away. Rather, the pattern is usually one of denial, anger, and an even stronger commitment to the old understanding, but this time as a matter of faith instead of fact. If understanding how the human body works on a molecular level allows us to come up with a pill that supplied many of the benefits of regular aerobic exercise, what sort of person would have a problem with that? It's the same kind of person who today pontificates against all the dangers of blood transfusions, birth control pills, and abortion [and now the recently-approved RU-486 or mifepristone], while ignoring their benefits and not paying the least amount of attention to why people need and/or want such things. It's the same kind of person who today insists that the only way to be healthy is to eat and exercise a certain way, eat "organic" foods, and take one or another of various "nutritional supplements."
[I hesitate to paint with such a broad brush but just consider what Ohio Congressman Dennis Kucinich had to say about the matter: "Everyone who goes to a health food store does so because they have — a consciousness, which revolves around a certain philosophy of food choices." I think he's wrong, by the way. I think a lot of people try things out of curiosity and I think a lot of people are doing their level best to make sense of a lot of confusing and self-serving published material on the subject of health and nutrition. But the modern-day philosophical heirs of the Old Testament food fetishists are still among us as well.]
These same kinds of people will be in for an even bigger surprise if and when gene hunting turns up a "greasy food loving" gene or a "second helping" gene or "take the elevator instead of the stairs" gene. But if the past is any guide, we are guaranteed that, if such things are discovered, and if medical science can find a way to exploit how they work, there will be people objecting that it's "playing God." Or, as the most up-to-date denunciation goes, it will be condemned for not being "natural."
Another issue with respect to gene hunting is that of gene patenting. A lot of people are worrying about this and there must be at least a few dozen articles out there with the same title of something like, "Whose Genes Are They, Anyway?" Well, the fact is that genes are natural-occurring products and can't be patented. What people are patenting are sequences of nucleotide base pairs that have been removed and inserted into bacterial chromosomes [plasmids] or otherwise removed from their source in nature. As such, they can be patented just as new arrangements of aluminum or other substances can be patented. [This is also why the government's funding of the Human Genome Project doesn't stop anyone from patenting a DNA sequence. If the government came up with a new alloy of some kind, people would also be free to patent things made of it, including that it is made of the alloy.]
To my way of thinking — not being a patent lawyer — the problem is that patents are being awarded for pieces of DNA about which people know very little or nothing, much less what use can be made of them. Or, when it is known what the piece of DNA is, rights are being claimed for the RNA's and the proteins that such genes give rise to. Much of what is actually being patented, the DNA sequences that have been isolated and inserted into something else, are not useful. This is like patenting a whole lot of different but particular shapes of aluminum on the chance that they might be useful for something and, then, if and when one or another does prove useful, claiming that impressions, shadows, or other projections and modifications of those bits of metal are also covered by the patent. If the patent office and the courts allow such impostures, then the blame lies with those institutions.
Arguments run both ways as to whether gene patenting is helpful or harmful for scientific and medical progress. On the one hand, patents do provide an important incentive without which many new products might never be developed at all. On the other hand, patents can certainly increase the cost of these products and the difficulties of engaging in any kind of work or business that may — even plausibly — infringe on them. In the case of large numbers of patents being awarded for DNA sequences of dubious value or application but which are broadly enforced, it may give us the worst of both worlds. It may reduce interest in studying these genes or possible genes while the patent runs, followed, once the patent eventually expires, by little incentive to study and develop applications for them.
The nature of DNA — complementary strands of nucleotide bases — is such that if you want to detect a particular sequence, which is to say, test for a gene, the best way is to "probe" for it with a piece of DNA that is complementary to what you're looking for. This has serious implications with respect to the gene patenting controversy, though. Because it means that if you patent a DNA sequence and then I discover that it causes a disease and want to test for it, I have to pay you to do my test. That might very good for you, but it's not good for me or my patients. Nor is it good for the argument that such patent claims are important incentives that are necessary for progress in biotechnology. After all, you didn't invent the fact that the structure of DNA is distinguished by the unique base pairing that occurred to James Watson that winter morning in 1953.
Improved and expanded genetic testing is by far the most fertile area for the near-term exploitation of what we already know about the human genome and of new discoveries in gene hunting. Using ordinary chromosome analysis — looking at the microscopically visible collections of genes in the nuclei of cells — it has been possible for many years to diagnose a variety of genetic disorders. In other cases, perfectly normal individuals have been identified who are at high risk of having abnormal — even very abnormal — children. The newer tests are for sickle-cell anemia and other blood disorders, enzyme deficiencies like phenylketonuria (PKU), Tay-Sachs and cystic fibrosis, and for especially frightening disorders like breast cancer and Huntington's Chorea. Testing for these diseases present similar opportunities — and dangers.
The opportunities are obvious. Or are they? People today have grown quite used to expecting two things from medical care: a diagnosis and an effective treatment. A prognosis — an idea of what to expect in the future given the diagnosis and other circumstances — is not usually thought of in the same way. It's perceived more as a sentence, or even a punishment, especially given the prevalent belief that every disease is preventable.
But this is something peculiar to our age, thanks to medical science and technologies that have vanquished the most dreaded diseases of the past, at least in developed nations. Most of the adult population of the United States think of doctors as people who cure disease. That, after all, has been their personal experience through ear and bladder infections, strep throats, the occasional laceration or toothache, appendicitis, and all the other multitudes of illnesses that people tend to experience in their childhood, youth, and early adulthood. Thanks to antibiotics and other effective medications, innovative surgical techniques, as well as immunizations and public health measures, few people alive today have had to see a parent, a sibling, or even a friend or neighbor die prematurely. Now that the population is aging, it seems especially unfair to many when they discover that medical science has no cure for what ails them and, worse, that what ails them today may kill them tomorrow.
But this is how things were for most of human history. At worst, physicians were magicians, or charlatans, taking credit or seeking to avoid blame for the natural course of diseases they scarcely recognized, much less understood. But at their best they were prognosticators: prophets of health and disease, reading the auspicious or ominous signs in their patient's bodies. Perhaps a good many people in ages past, when they got sick, didn't care to know whether they were likely to recover or not. As we know, "God's Will" was then an even more popular way of evading and avoiding reality than it is today.
The only new wrinkle is health insurance. I think this is, without a doubt, a very serious issue, the main concern being that health insurance companies "might" — I think they definitely would — do their best to exclude anyone with any genetic tendency to serious illness. But the flip side of this is that people who found out that they were especially likely to live long and healthy lives might very well forego buying insurance. Isn't the situation with respect to HIV the same? There is a test, but no cure, and the available treatments are expensive. So people who become HIV+ naturally would like to be insured and have someone else pick up the bill. But the insurance companies don't want to get burned either so they require everyone who applies for coverage to be tested for HIV. Wouldn't it work the same way for syphilis or a bladder infection were it not for penicillin? Consider it this way: if you don't think someone who's unlucky enough to be born with "bad genes" should be penalized financially for it, then you must think that someone who's lucky enough to be born with "good genes" should not be allowed to benefit financially from it. It's not hard to understand. It's just that some people don't want to understand.
That's the promise of a greater understanding of how our genes work and of methods of testing for genetic problems. The claims of finding out that one is destined to die of a stroke on a given date are ridiculous. But the day is not far off when it will make sense for most people, if not everyone, to be tested for one or another common gene that is known to affect their risk of future illness. The real challenge is not the alleged "ethical issues" of the new knowledge itself. As always, it's going to be a matter of understanding both the power and the limitations of that knowledge and of applying it in rational ways that enlarge our ability to make choices on our own behalf. "God's Will," what's "natural," and what self-appointed authorities or elected ones may think best for everyone have no place in these considerations. Each one of us has our own unique perspective, and it is only in that context that such knowledge can have its full meaning.
To even touch on how this feeds into the abortion controversy would be too much to get into today. So I won't.
There are other interesting possibilities with respect to genetic testing. What if, for example, I apply for a job and my prospective employer wants to test me for a genetic marker that increases the likelihood of my contracting a work-related illness of some kind? Can I refuse? Or can the employer insist? Obviously, the employer's concern is being held liable if I develop the illness. So can I sign a release to the effect that I won't hold him liable? Would such a release hold up when I later get the disease and sue? Or, if I sign such a release, and especially if I sign it knowing that I have the gene in question, will the employer suspect that I don't plan on keeping the job for long if hired?
Or how about this? Suppose I am surreptitiously tested for one or more genetic traits. In the extreme, suppose someone has my chromosomes completely analyzed so they know my genes down to the molecular level. Should I be concerned? Or, if I am concerned, how would it differ from the superstitious tribesman who objects to having had his picture taken on the grounds that his soul has been stolen by the camera?
There are already many drugs that are manufactured by recombinant DNA techniques. The genes for insulin and many other substances have been identified, inserted into bacteria, and produced in large quantity and with high purity by this means. There are also growing numbers of drugs that were deliberately developed to act on specific proteins coded for by known genes.
But real gene therapy is the replacement of a missing or defective gene, for example, in an individual suffering from a genetic disorder. There were reports of this being done back in the 1970's, using injected DNA. But the documentation was poor and the effects uncertain.
Modern gene therapy work has focused on using viruses as "vectors." Viruses are basically molecular hypodermics that attach to cells and inject DNA that codes for the production of more virus particles. [And you thought the movie Alien was a ground-breaking concept! Nature is not just "red in tooth and claw," it's back-to-back horror flicks in real life!] So the idea of gene therapy is to replace the viral DNA with the DNA containing the genes you want to supply or replace. Often, a virus can also be chosen or modified to preferentially "infect" some cells and not others.
One problem — among many — for gene therapy is that, except for sickle cell anemia, there aren't many well-understood and simple genetic disorders that are very common. So much attention has been directed at altering the genetics of cancer cells in order to make them easier to treat. Several different kinds of viruses have been or are being used to get tumor suppressor genes into cancer cells, for example. Certain kinds of cancers — thyroid cancers, for example — can also be targeted to express genes that cause the cells to take up higher concentrations of chemotherapy drugs, or drugs that make the cells more sensitive to radiation treatment, or even genes that express a toxin within the infected cells and kill them directly.
There are some genetic diseases that are being directly addressed with gene therapy. One is a kind of neurofibromatosis, a condition in which the risk of both benign and malignant tumors is greatly increased. Another is severe combined immune deficiency — SCID, or the "bubble boy" disease &dmash; that leaves its victims essentially without any immune protection. There are now two cases &dmash; in France &dmash; in which this disorder was treated with gene therapy that has not only worked but in which the effects of the treatment appear to be long-lasting, almost a year so far.
Gene therapy is very much in its infancy. There are many worries with it, particularly with the fact that, when given to a person, as opposed to cells that are removed, treated, and replaced, the viral vectors are recognized by the immune system just as the real virus would be. So, in a sense, these forms of gene therapy are also crude vaccines. The death of a young man in Pennsylvania a year ago only a few days after receiving this kind of gene therapy appears to have been the result of a reaction to the virus used. This was a severe blow to this kind of gene therapy in the U.S. Hopefully, work with animals will proceed. That is, if the "animal rights" religious fanatics can be kept at bay.
As for the more speculative possibilities for gene therapy, I think there will be plenty of time until the day when we are able to more or less alter our genes at will. Not that it isn't fun to speculate. If there is a gene for homosexuality, for example, should parents try to "fix" it in their offspring? Or, if that would be a bad thing, how about if parents wanted to make sure that a child had a genetically-determined homosexual gender preference? What if a homosexual wanted to be heterosexual, or a heterosexual homosexual? One can imagine it being considered a recreational activity to have one's genes altered temporarily. Or cosmetically: one might change one's skin, eye or hair color by gene therapy. And if all of these things are wrong, what does this amount to but acceding to "God's Will" or to the order of "nature?"
Would it be OK to manipulate the genes of embryos so that they grow into people who are tall, smart, athletic, musically inclined, blond, light-skinned or dark-skinned? Might there be genes for leadership, criminality, loyalty, recklessness, and generosity? Should we — would it be acceptable for us to — tweak the genomes of ourselves and others to our satisfaction? And, if not, if that would be "immoral," what about the "morality" of doing the same thing, in a much more clumsy way, by choosing a mate that is tall, or smart, or athletic, or generous and loyal and so on? What about plastic surgery? Conversely, what about criminals and people with other "undesirable" traits who are nevertheless free to have children if they choose to or, what may be more accurate, if they don't choose not to?
These speculations, like good science fiction, should make us think about things that we take for granted every day. No one need wonder whether gene therapies for SCID or other very serious genetic disorders should be studied and, when appropriate, used. But at what point do our physical limitations become something that we ought not to struggle against? Is there such a point? Or is the discomfort that this subject engenders like that of the Pope when he thinks about contraception: that arithmetic is OK but that the line must be drawn at chemistry?
Even today, gene therapy can depend on how "therapy" is defined. Genetic manipulation for worthy or merely desirable ends — as opposed to "necessary" interventions [We could argue about what is necessary!] — is very much at issue when it comes to agricultural applications of biotechnology and genetically modified organisms (GMO's). Here again, in many instances genetic engineering amounts to not much more than accomplishing in a day or a week or a month what typically takes years or decades to do with older selective breeding methods. This is especially true with plants as they are much more genetically variable and flexible than animals. [Did you know that peppermint did not exist prior to 1696, when it was discovered as a new mutant growing in a field of spearmint in England? Yet the novel chemical constituents that give it its unique flavor apparently failed to destroy the global ecosystem!]
Certainly, there should be concerns about the introduction of novel DNA sequences into crop species. But these should be considered on a case-by-case basis. Nor should it matter how incongruous such innovations may sound. Novel combinations of genes in an agricultural product need not worry us in principle any more than having our beans and potatoes and meat touching each other on our plates. As parents everywhere tell their children, "it's all going down into the same stomach!" Labeling of everything that has undergone any kind of genetic manipulation — as has been proposed in Congress [by Mr. Kucinich!], including even the pork from pigs that ate genetically modified corn — is unnecessary, impractical, and irrational.
I have to say that I can't get very excited about cloning humans. Cloning animals is just a faster and better way of creating an inbred strain of genetically uniform individuals. So in animal husbandry it makes sense. But to clone people presupposes that there is some purpose in it other than vanity, because vanity just doesn't seem sufficient motivation for cloning more than very small numbers of people to whom it may appeal. And what other purpose could there be? I haven't heard of any persuasive ones.
When it comes to human reproduction, I think mixing it up is more interesting. Every one of us is an ongoing experiment in genetic recombination. It would have been nice for the process to have undergone some intelligent supervision, perhaps. But that will come in time.
Finally, there is stem cell manipulation. Stem cells are developmentally intermediate between the cells of the early embryo and the differentiated cells of, say, the liver or brain or skin or stomach. They are no longer "programmed" to grow into an entire organism. But they are not committed to be one of the specialized cells of the fully-formed organism either. They retain the ability to grow into many different kinds of cells. There are all sorts of profoundly important questions about cell biology, the molecular biology of the genome and gene control, and developmental biology that work with stem cells may one day answer. The potential for important clinical applications, including the regeneration of aged or diseased tissues, the production of whole organs for transplant, and much more is also there. As with genetic testing, though, political controversies — in this case the abortion controversy — threatens to thwart the promise of this new area of research.
I hope this brief tour of Bioscience, Biotech and Bioethics has been interesting to you. The challenge for was to cover the main points of interest without being either too elementary or getting too technical. Many readers are already well-read on technical subjects. But others aren't.
The important thing about this subject is that in almost every instance where there are serious doubts or ethical issues — real or alleged — it often comes down to the same problem. It comes down to whether it is better, through fear and inaction, to allow "God's Will" or "nature" to determine what's best for us, or whether we ought to think our way through what we know, do all that we can to learn more, and do our best to make wise choices knowing that we can never be certain that we won't come to have some regrets. For Freethinkers the subject can be especially troubling because there are so many arguments out there both for and against a multitude of ideas and proposals, few of which sound like the usual religious irrationalism. The Precautionary Principle, the Prevention Principle, the Principle of Future Generations, and many other arguments can be and are being made to appear soundly based in facts and reason when they are really more like Pascal's Wager.
Of course, no ideas should be dismissed out of hand. But a sense of perspective is needed. The benefits of automobiles, for example, outweigh such harmful things as the pollution they create, our national dependence on foreign oil, and the grisly carnage and ruined lives caused by car accidents. And the way to deal with these problems is not to say that Henry Ford should never have been allowed to build his factories. A similar analysis could be made for air travel, for natural gas pipelines, for electricity, and for just about every other technological advance made by human beings in recorded history, right back to fire and the wheel.
Let us be careful, yes. Let us take care to have a proper humility both about what we know and what we don't know. Let us strive to always learn more and to anticipate problems. But let us never make the mistake of supposing that progress will not come at a cost, or that that fact makes progress unaffordable. Life means change. We can either embrace change and learn to manage it responsibly or we can allow our fears and uncertainties to paralyze us and hold our destinies hostage to the whims of chance and circumstance. In either case, we cannot know what the future will bring. The only question is whether we will go forward to meet it or wait for it to find us.
