The Washington Post
GROWTH HORMONE FOR HEALTHY TEENS: TREATING SHORTNESS
WITH SHOTS
July 6, 1992
Author: David Brown; Washington Post Staff Writer
Is being short a problem for which medicine is the solution?
A group of scientists at the National Institutes of Health believes the answer may be yes, and has embarked on an experiment to boost the height of very short but otherwise healthy children by giving them human growth hormone throughout their teenage years.
A watchdog group in Washington, however, has petitioned the government to halt the research, saying it is unethical, violates federal regulations governing experiments on children and threatens to ring in a brave new world in which genetically engineered drugs are used to enforce society's prejudices.
"This is the big fear that we've always had about genetic engineering -- that it would be used for social purposes and not medical purposes," said Jeremy Rifkin, whose organization, the Foundation on Economic Trends, plans to sue if NIH does not voluntarily halt the four-year-old experiment.
But the scientists directing the study also claim a high moral purpose in their effort to evaluate a treatment that is increasingly demanded by parents of short children -- and prescribed by physicians -- despite its unknown effects.
"If the study were to get shut down, we would lose the opportunity to find out when, or if, it is a helpful thing to do," said Susan R. Rose, a pediatrician affiliated with NIH who wrote the research protocol. "If it doesn't work, we may save thousands of children from unnecessary treatment."
Study to Have 80 Subjects
There are now 36 children in the study; ultimately there will be 80. They must be between age 9 and 15 on entry, and at least 2.25 "standard deviations" -- a statistical measure of variation from a mean -- below the average height for their age. For example, in the case of children entering the study at 12 1/2 years old (the age at which both sexes average 5 feet tall) girls would have to be shorter than 4 feet, 6 inches, and boys shorter than 4 feet, 4 inches.
Half the children receive injections of growth hormone three times a week. However, in what to many is the most controversial part of the protocol, the other half receive

"placebo" injections that contain no active ingredient. The study is expected to last about
10 years, with all children treated until the growth plates of their bones close, signaling skeletal maturity.
But some parents and doctors have already made up their minds that human growth hormone (HGH) is effective. Of the families who inquire about the study and are found eligible, only one in five chooses to enroll, often because they do not want to take the chance that their children will be in the placebo group, Rose said. In addition, she said, about a quarter of those who decline find a pediatrician who will prescribe HGH -- which is approved only for use in treating genetic defects or disease.
The HGH experiment debate has focused in one place some of modern medicine's thorniest issues: What constitutes a "disease" and a "successful" treatment; which experiments involving children are permissible; how much attention scientists should pay to consumer and commercial pressure for research; and whether there may be important questions forever beyond the reach of ethical study.
These questions are likely to come up again in other contexts as medicine and biotechnology gain the ability to manipulate physical, and possibly mental, traits that are not obviously linked to disease. That is the possibility that worries Rifkin, who has been nagging the scientific establishment about presumed hazards of recombinant DNA technology for more than a decade.
"What about fat people? What about people with different skin pigmentation? What about young girls whose breasts won't grow to the size that society desires? This experiment moves us onto a very, very dangerous journey that starts with 'enhancement' and ends up with eugenics," he said last week.
Human growth hormone, among the first natural products manufactured through recombinant DNA technology, is normally produced by the pituitary gland. It stimulates skeletal growth and has numerous other physiological effects. Small amounts are secreted even after a person stops growing.
In 1985, the Food and Drug Administration approved HGH for use in the roughly 20,000 children with hormone deficiency, either of unknown cause or from damage to the pituitary. With a year's treatment costing $10,000 to $20,000, HGH's two manufacturers,
Genentech Inc. and Eli Lilly and Co., together have annual sales of more than $200 million. A much bigger market, however, would exist if HGH were found to increase the final height of otherwise healthy children who have adequate levels ofHGH in their bloodstreams but nevertheless are very short.
Benefit Is Uncertain
It is far from certain, however, that such children will end up taller if they are given growth hormone. (African Pygmies, for example, do not grow much taller when given extra HGH. Their stature is believed to stem from a relative lack of "receptors" for the

hormone.) Most studies involving short children with adequate HGH have lasted less than two years, with many suggesting that hormone supplements simply shorten the time it takes to reach adult height. It is possible that HGH treatmentmay even be harmful.
The Department of Health and Human Services has regulations saying, in effect, that trials subjecting children to risky procedures must offer them the prospect of direct benefit. Rifkin's organization -- along with the Physicians Committee for Responsible
Medicine -- argues that NIH's experiment violates these regulations on many counts, including that the placebo group stands to gain nothing. The treatment group of the trial should also be closed, they argue, because those children are not ill.
But even if the HGH experiments are successful, is being "constitutionally short" a disease? And if it isn't, why should NIH be interested in studying "treatments" for it?
"I would not call it a disease," said Arthur S. Levine, scientific director of the National
Institute of Child Health and Human Development, which is running the HGH trial. "But in our society, height is generally seen as a positive characteristic, and extremely short stature is seen as a negative characteristic. If a child becomes so disabled by anxiety and worry about his short stature, it becomes tantamount to a disease."
Effects of Short Stature
Susan Rose contends that in extreme cases, short stature can be physically handicapping.
Very small adults can have trouble driving cars, using standard-size furniture or finding suitable clothing. But she also stressed the psychological effects.
"What I see most often is that {very short} children underrate themselves, and people around them expect less of them, because they look younger than their age. They grow up working below their capacity."
In fact, psychological studies suggest some differences between very short people and people of average height, but none fulfilling the usual criteria for a "disease."
Short children tend to score slightly lower than their peers in intelligence tests, though, in statistical terms, height only "accounts" for between 1 and 5 percent of the normal variation in scores. On personality tests, very short children tend to be more introverted and less willing to express aggressive drives. Many researchers also have found that very short adults have "adjustment" problems, with higher rates of unemployment, lower rates of marriage and poor self-esteem when compared to taller people.
Psychological Concerns
For Rifkin, the disease lies elsewhere: "There is nothing wrong with these children. What is wrong is society, the biases, the discrimination. But don't address the biases of society by changing the physiology of the individual."

Even in more sympathetic quarters, there is serious question whether giving placebo injections to healthy children is ethical.
Genentech is running a trial of HGH in 150 very short children without a placebo group because "we didn't think it was either justified or acceptable to the patients," said Joseph
M. Gertner, one of the investigators and a pediatrician at Cornell Medical Center. Several years ago, the University of Nebraska rejected a proposed HGH study, in part because injections posed a "psychological risk" to children in the placebo group.
NIH's review board approved the use of a placebo, and Rose said that many children gain self-confidence when they learn to give themselves injections, feeling "that they have taken charge of something in their lives." (Even if this is true, critics respond, injections serve to "medicalize" a natural condition and send an unconscious message that something is wrong.) In any case, placebo-controlled trials are the sine qua non of clinical investigation, Rose argues; and they are the only way
"Children deserve to have as good quality science done for them as for adults," she said.
But Joel Frader, a pediatrician and ethicist at the University of Pittsburgh, contends the research may lie on the wrong side of an ethical divide. "There may very well be a line that you draw and say, yes, there is good information that may come from this," he said,
"but getting the information is not worth the cost.
Copyright 1992 The Washington Post