The growing danger from gene-spliced hormones

The growing danger from gene-spliced hormones

Thomas Murray

My son Peter is twelve, and lately the cuffs of his pants have been racing up his ankles — a sure sign that growth hormone is coursing through his body. He’s on about the same growth schedule I was. By my fourteenth birthday I was already just shy of six feet, and hopeful of four or five inches more. I thought that would be enough to give me a shot at playing basketball in college. Alas, I’d reached my limit. Lacking any notable physical talents, I had to rely on guile; if you can’t shoot over the guy, get him looking one way and then scurry past on the other side. (As we used to say, ”Fake left, go right.”) Recent happenings in genetic engineering make me wonder if something similar, albeit unintentional, is going on there: Is our attention being directed one way while what’s important is slipping by on the other side?

At least since 1980, worries about using recombinant DNA technology to alter ”human nature” have focused on gene therapy — the direct and intentional alteration of genetic material to treat disease. On June 20 of that year the general secretaries of three national organizations, for Protestants, Jews, and Catholics, wrote the President to warn: ”History has shown us that there will always be those who believe it appropriate to ‘correct’ our mental and social structures by genetic means, so as to fit their vision of humanity. This becomes more dangerous when the basic tools to do so are finally at hand. Those who would play God will be tempted as never before.”

Nothing garners attention as quickly as a nice little scandal; within a month of the letter, Dr. Martin Cline of UCLA provided one by experimenting on two patients with beta-zero thalassemia, a genetic condition that causes severe anemia. Cline removed some of their bone marrow, treated it with recombinant DNA containing normal hemoglobin genes, then reinserted it into the bone (after making room by killing some of the remaining marrow cells with radiation). The hope was that the treated cells would multiply and produce normal hemoglobin.

They didn’t. Worse, Cline didn’t have the approval of the UCLA committee that oversees research with human subjects. When the affair became public, the National Institutes of Health (NIH) stripped Cline of $162,000 in grant money and demanded strict supervision of his research. For those suspicious of human gene therapy, the case was proof that scientists couldn’t be trusted to regulate themselves.

Since then, such work has proceeded very cautiously. A presidential commission gave its tentative blessing to gene therapy with somatic cells — those that don’t pass the altered genes on to future generations. The NIH’s watchdog recombinant DNA advisory committee set up a ”human gene therapy subcommittee,” which has suggested ”points to consider” for doctors who propose to tinker with genes. Among them: whether the benefits of the treatment outweigh the risks, how to choose patients fairly, and how to publicize the results of the research. Thanks to the brouhaha over gene therapy, no great threats to humanity are likely to slip by in the near future — at least not on that side.

But there’s another side to genetic engineering that has the power to alter us physically and socially. Rather than directly altering our genes, it can mod- ify our bodies by supplementing the natural supply of important regulatory hormones with genetically engineered ones. A prime example is biosyntheti- cally manufactured human growth hormone — hGH. Except for one additional amino acid — methionine (which appears to have no effect on its action) — biosynthetic hGH is identical to the hormone that promotes normal growth.

Produced in the pituitary gland, hGH plays a key role in determining how tall we’ll become. So-called pituitary dwarfs usually lack an adequate supply of bioactive hGH. To treat them, for more than twenty years we’ve been harvesting pituitaries from human cadavers, each of which yields a minute quantity of hGH. Until recently the supply was barely adequate. In 1979 genetic engineers cloned the gene carrying instructions for making hGH, inserted it into a microorganism, and coaxed the bug to produce the human hormone. Just in time, it appears, because some hGH recovered from human pituitaries seems to have been contaminated with the slow virus that causes Creutzfeldt-Jakob disease (CJD), a degenerative infection of the brain. In April 1985 the Food and Drug Administration (FDA) halted the sale of natural growth hormone, and shortly thereafter approved Genentech’s biosynthetic version. Since no human tissue is used in producing it, there’s no danger of contamination with the CJD virus. Also, we’re no longer limited by the scarcity of cadaver pituitaries, and other uses for hGH can be explored.

Biotechnology came to the rescue of kids deficient in growth hormone. But if hGH injections can make extremely short children a bit taller, what can it do for those who aren’t dwarfs, but just shorter than average? What about the youngster who would have been only of average height? And what about the basketball player for whom a couple of inches more might mean the difference between the schoolyard and the NBA? In short (no pun intended), why not use hGH to give your child the advantages that come with being tall?

Years ago, at an FDA hearing, I speculated that once biosynthetic hGH was approved, people would want to use it for all sorts of non-therapeutic purposes. One member of the FDA committee told me that several parents had already asked her if they could get the drug for their kids, who weren’t hGH-deficient. All, she recalled, were physicians. Rebecca Kirkland, who does clinical tri- als of biosynthetic hGH at the Baylor College of Medicine, recently said she’s had inquiries from five parents wanting to get hGH for their normal children.

Why would parents want to go to such expense (treatment with biosynthetic hGH costs roughly $10,000 a year), cause their children pain (the shots hurt a bit), and risk unknown long-term side effects? Quite simply, because it’s advantageous to be tall — within limits. A modest body of scientific evidence supports the commonsense observation that taller people often get the nod over their shorter counterparts, because they’re perceived as more intelligent, good-looking, likable, extroverted, and attractive. Being very much taller than average is a mixed blessing, to be sure. Bu being a few inches above average seems to help.

A survey at the University of Pittsburgh in 1968 found that starting salaries for graduates varied with height: roughly $300 an inch up to six feet two inches. In a study of men whose heights had been recorded twenty-five years earlier, a graduate student at Washington University in St. Louis demonstrated a ”height bonus” of approximately $400 per inch.

When a researcher at Eastern Michigan University presented two hypothetical job candidates to recruiters, one eight inches taller than the other, 72 per cent preferred the taller one, 27 per cent said there was no difference, and only one chose the shorter applicant. And much has been made of the fact that the taller candidate for President usually wins. Only two presidents — Madison and Benjamin Harrison — were shorter than the average American male of their eras.

If some parents want to give their child the edge that height seems to confer, what’s wrong with that? If it’s O.K. to spend $2,500 on orthodontics, to buy your kid private tennis and music lessons, or to spend $10,000 a year and up for prep school and private college, what’s a few thousand bucks more to buy a couple of inches? The kid could turn out to be a klutz at tennis, have a tin ear, and major in Michelob, but taller is taller.

In this century, we make a strong presumption in favor of liberty. Before we interfere with the right of parents to bring up their children as they judge best, we demand strong reasons for doing so. Can we find them in the case of hGH?

Let me ask a skeptical question: What’s the disease for which human growth hormone is the cure? Philosophers have a difficult time agreeing on the definition of disease, but most would recog- nize a physiological deficiency in hGH as a genuine disease, and hGH injections as a reasonable treatment. There are some kids, though, who aren’t measurably deficient in hGH but who are very short. Their shortness can be the consequence of any one of numerous medical problems, or they may fall into the category of ”familial short stature” — that is, short like mom or pop. Either way, can their shortness ever be a disability? A disability is a condition that interferes with the tasks of daily living. If people are so short that they qualify for the elevator riddle,* their shortness may well be a disability. Disabilities usually justify medical intervention. But what if a person isn’t suffering from a disease, and isn’t so short that the lack of height becomes a disability? What if it’s merely a disadvantage?

Even if hGH turns out to be physiologically harmless — some experts have warned of possible effects on glucose regulation, as well as an increased risk of atherosclerosis and high blood pressure — there may be psychological consequences to treating children with the hormone. The unmistakable message given to a child is that shortness is a grave enough problem to justify the considerable expense, inconvenience, and discomfort of hGH treatment. It’s likely to increase the child’s self-consciousness about height. And since children rarely grow as much with the hormone as they or their parents hope, disappointment is likely.

A study of hGH-deficient children and their families found that the most psychologically mature kids weren’t those who grew the most but those whom parents and other adults had treated appropriately for their age rather than their size. Kids who were encouraged to pursue interests where their height wasn’t a disadvantage were much happier with themselves.

People differ in so many ways: in intelligence, charm, quicknessof hand and foot, facility with words, wit, etc. But when we put children through hGH treatments, we focus almost entirely on their height (where they don’t ”measure up”) and ignore their other talents and abilities. Un- derstandably, short kids receiving hGH may come to feel that they’re inadequate and inferior.

All other things being equal, taller basketball players are moreeffective than shorter ones. Height is an advantage in basketball and some other sports. In almost all other realms of human endeavor, though, height bears no relationship to the ability to do a job well. But in a culture that regularly imputes desirable characteristics to tall people and undesirable ones to short ones, shortness is surely a disadvantage. (Even our language is laden with ”heightisms”: we look up to people we admire, look down on those we don’t.)

Like other ”isms,” such as racism and sexism, heightism involves making unwarranted judgments about people based on irrelevant criteria. Does anyone believe the solution to racism is to find a drug that lightens black skin? The mind boggles at the possible biotechnological remedies for sexism. And yet those who want to give their kids hGH are proposing just this sort of technological end-run around heightism.

If we choose to allow hGH to be used for non-disease, non-disabling shortness, then we must make a choice. Either we let those who can afford it buy it for their children, or we make it available at public expense to all children whose parents want it.

Suppose we let it be sold. The children of rich parents will have one more leg up, so to speak, on their peers. You could ask, what’s one more advantage in light of all the others available to people with means? But the prospect of two classes — one tall and monied, the other short and poor — is ugly and disquieting. It would allow injustice to be piled upon injustice.

Suppose we take the other route and provide hGH to anyone who wants it. If all parents (short and tall alike) rushed out to get hGH shots for their kids, the average height of the entire population might increase. But in all likelihood the distribution of height in the population wouldn’t change much, if at all. There would still be the taller and the shorter, and since we’re doing nothing to diminish heightism, discrimination against the shorter would continue. Some people would benefit, of course — for example, the stockholders in Genentech (which holds a patent for making biosynthetic hGH) and those who produce fabrics (since everyone will be wearing bigger sizes). Meanwhile, at considerable social expense, kids would get their three shots a week with a little pain and, we hope, minimal side effects.

Inevitably, a few eager parents would want to regain the edge for their kids and try to get bigger doses of hGH, like those athletes who take increasing amounts of anabolic steroids in the hope of obtaining an advantage over their rivals. In both cases, individuals pursue their own inter- ests, only to make everyone worse off.

Whether hGH is available just to those who can pay for it or to everyone, the results would be unfortunate. In one instance, we use biotechnology to reinforce the advantages of wealth; in the other, we incur enormous expense and unknown risks without making anyone better off. The wisest course is to restrict hGH to cases of disease and disability.

Although hGH may be the first biosynthetic hormone to tempt us to improve on human nature, it won’t be the last. Imagine what we might do with a hormone that prompted damaged nerves to regenerate. Someone would wonder whether it would also stimulate growth in the brain. And soon we’d be trying to enlarge our brains, however misuided that might be, scientifically or morally.

It also occurs to me that simply by writing this article I may spur some parents to seek out growth hormone for their child of normal height. I fervently hope not. But the temptation posed by hGH, and by other fruits of biotechnology as yet unripened, will be great. And it will require all our collective common sense to use them wisely.

COPYRIGHT 1987 Discover

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