840.119:Human Growth Hormones

Abstract

Microbial biotechnology has been essential in the development and improvement of human growth hormones. This page and project are dedicated to detailed study and research about the technology involved in human growth hormone development. Focusing on the product, Somatropin, we will provide information on the past developmental breakthroughs and current development, which we feel would be an improvement on the research and production of these human growth hormones. Recombinant DNA technology, using Escherichia coli, the importance of microbes, and potential impacts will be considered.

State of the Art

In our review of journal articles, we have come across research about improved techniques to create more cost-effective human growth hormones with fewer health risks involved. We feel that this is information to be considered and further researched as it would be very beneficial...

Prior to the use of recombinant DNA, human growth hormones necessary to help individuals with diseases such as hypopituitarism were obtained only from the pituitary glands of human cadavers. This, naturally, had many negative implications and left a great deal of room for improvement in human growth hormone production. The first commercially available human growth hormone made using microbial biotechnology was produced in 1985 by scientists at Genetech. This led to possible production of an almost endless supply of this very vital pharmaceutical.

Objectives

There are obvious advantages in using biotechnology, and specifically in using microbial biotechnology, to create human growth hormones. These advantages can be made more clearly by exploring the history and the evolution of human growth hormone production. As noted previously, prior to the discovery of microbial biotechnology as a superior method of production, growth hormones were purified from human cadaver pituitaries. When using animal biotechnology, there were several disadvantages. Obviously, this was associated with several health risks. Because so many pituitary glands were necessary to create the needed supply of human growth hormones, there were incredible shortages of this essential medication. These hormones could not be made quickly enough to supply all patients with the pharmaceuticals they needed. There were simply not enough cadavers available. This was a particular problem in the 1970s when autopsy rates in the United States dropped. Using human cadavers was very costly as well. In using microbial biotechnology, lack of resources is no longer a problem. Escherichia coli, the bacteria used in the production of human growth hormones is widely available. This obviously resulted in reduced costs of production as well.

Scientific Approach

Somatropin, the scientific name for human growth hormones, is a protein consisting of 191 amino acids. The approximate weight of this protein is 22,000 dalton. Its primary purpose is the promotion of linear growth in individuals with human growth disorders including, but not limited to, hypopititary dwarfism, somatopause, pediatric growth hormone deficiency, and adult growth hormone deficiency. It can also be helpful in treating other, seemingly unrelated disorders like burns, bone fractures, and bleeding ulcers. Human growth hormones are in the category of biomedical enhancements, meaning that they serve the purpose improving the body, mind, or performance.

(Potential) Impact

The human growth hormone is a protein that is produced by the pituitary gland. Because it is necessary for human growth, growth hormone deficiency exists when this hormone is absent or produced in inadequate amounts. Recombinant human growth hormone makes it possible to produce this protein, resulting in profound benefits and impacts. Human growth hormones have been found to be effective treatment for those suffering from human dwarfism, pediatric growth hormone deficiency, adult growth hormone deficiency, hypopituitarism, and similar conditions. One 1999 study, the North American Pediatric Renal Transplant Cooperative Study, followed children with human growth deficiency to adulthood. For those who had follow-ups at age eighteen, when comparing the final adult height, the delta height standard deviation score was greater in the human growth hormone treatment group than in the group who had not been treated.

Associated Risks

Due to the use of microbial biotechnology in the production of Somatropin, the risks involved in this type of therapy have been decreased significantly. Prior to recombinant human growth hormone availability, when cadavers were the source of this protein, human growth hormone therapy was associated with Creutzfeldt-Jakob Disease, a fatal neurological infection. The use of Escherichia coli has eliminated this as a general risk. However, like all types of medication and medical treatment, there are risks involved.

For each population of patients receiving human growth hormone therapy, the risks tend to differ. For children, for instance, benign intercranial hypertension development is a risk (with an occurence rate of about 0.001), where as adults and elderly rarely develop this disease when using human growth hormones. Elderly, on the other hand, when receiving human growth hormone therapy, are at risk for developing gynecomastia.

Some side effects that have been found to be associated with human growth hormone therapy include: peripheral edema, arthralgias, myalgias, back pain, paresthesias, carpel tunnel syndrome, headache, hypertension, rhinitis, and flulike symptoms. Many of these side effects appear to be dose related and are decreased with the lowering of medication dosage.

Treatment with somatropin may decrease insulin sensitivity, making it necessary for patients being treated to monitor glucose levels periodically. Glucose intolerance has been reported by human growth hormone patient recipients also suffering from a critical illness as well as elderly patients. This is much less of a risk for otherwise healthy children and adults. Diabetes as a concern for those receiving growth hormone therapy tend to be conflicting. One particular review, for instance, of large databases containing more than 35,000 patients on growth hormones indicated no greater incidence of type 1 diabetes than their age-matched counterparts. On the other hand, a recent study of an increased incidence of type 2 diabetes in children undergoing growth hormone therapy with risk factors for diabetes suggests that GH may cause earlier expression of this condition.

Some of the risks involved in human growth hormone therapy, particularly the long term risks are currently being studied. Recent data indicate that increased levels of human growth hormone treatments may be related to an increased risk for the later development of prostate cancer. This potential risk is currently being looked into in population-based case-control studies.

Another long term concern being watched closely is the risk of cardiac enlargement. In short-term studies, it has shown that this has no short term effects on patients, but the long term risks are yet to be fully understood. Long-term surveillance plans for late-onset side effects are essential and are an important part of keeping this drug safe for patients.

Compared to most pharmaceuticals, the risks involved are fairly low. Most of the risks that are of concern are physiological and psychological. Years of injections has negative effects on the patients, as it does with diabetic patients as well.

One concern has been that injections may actually serve to enhance the negative self-image and stigmatization that already exist for many children with human growth deficiency.

Controversial Topics

Medical Challenges

A growing and challenging debate in the area of human growth hormone therapy is the diagnostic criteria for those with the need to be treated with growth hormones. Human growth hormone therapy is not only effective for patients with classic growth hormone deficiency, but for many other patients as well. Girls with Turner ’s syndrome and children with idiopathic short stature respond to growth hormone treatment. Children who are particularly short in height due to genetics have shown to have increased heights when receiving human growth hormones as well. Because this drug is so effective for so many, physicians are given the task of assigning growth hormones to individuals who do not fill the criteria for classic growth hormone deficiency at their own discretion. Due to the fact that there will always be an overlap between normal children and those with growth hormone deficiency, there becomes a definite and not yet established need for an analysis and agreed upon set of standards for physicians to reference when prescribing this medication.

Economic Matters

Unfortunately, those in need of this drug are burdened by the recent cost increases and in medical care and prescription drugs. the recent cost increases and in medical care and prescription drugs. These trends have had an enormous impact on all prescription medication, but human growth hormone patients are feeling the effects even more so. The Human growth hormone is a high-profile, small market medication, making it very expensive for the population in need. The product can cost up to $18 000 to $30 000 per year of treatment. Beneficence is the ethical principle establishing the need to “do good.” With such high costs, making the product unavailable to many, this bioethical principle is being violated. This results in need for a change in the process by which this hormone is made or enormous changes in healthcare as a whole.

Legal Issues

A legal issue involved in human growth hormones that is becoming increasingly prominent is the inappropriate use of this drug. The most common misuse of this drug is for antiaging purposes. As we grow older, growth hormone levels in our body decrease. Someone older than 60 has growth hormone levels half that of young adults. Because of this, human growth hormones are appealing greatly to older individuals. However, where there is no deficiency, human growth hormone therapy will artificially raise blood levels of the hormone above normal levels, something not recommended. Though many physicians seem unaware or unconcerned, the United States Code Title 21 Section 333 prohibits the distribution of human growth hormones to humans for any use other than recognized medical reasons unless authorized by the Secretary of Health and Human Services.

This issue is not a concern for physicians alone. Distributors of human growth hormones, promoting its antiaging benefits, are targeting older consumers. These older consumers sometimes are willing to pay tens of thousands of dollars annually, a cost not covered by health insurance, to reap these benefits. Though its antiaging effects have yet to be proven, consumers are willing to pay these large amounts of money for a more youthful appearance. Distributors are profiting in this industry, which is estimated to be worth billions of dollars.

References

• Berlin, C. (1997) Considerations related to the use of recombinant human growth hormones in children. Pediatrics (99)1, 122-129.

• Blanchard, M. (2004). Pause before writing that prescription: physicians jumping on the growth hormone wagon should consider serious liability risks. Cosmetic Surgery Times (7)14, 24.

• Committee on Drugs and Committee on Bioethics. (1999). Considerations Related to the Use of Recombinant Human Growth Hormone in Children. Pediatrics (99)1, 122-129.

• Conrad, P., & Potter, D. (2004). Human growth hormone and the temptations of biomedical enhancement. Sociology of Health & Illness (26), 184.

• Cook, D., Owens, G., & Jacobs, M. (2004). Human Growth Hormone Treatment in Adults: Balancing Economics and Ethics. The American Journal of Managed Care, S417-S419.

• Microbial Biotechnology. United States Department of Agriculture: Cooperative State Research, Education, and Extension Service. September 6, 2006 <http://www.csrees.usda.gov/nea/biotech/in_focus/biotechnology_if_microbial.html>

• McNerney, T., Watson, S., Sim, J., & Bridenbaugh, R. (1996) Separation of recombinant human growth hormone from Escherichia coli cell pellet extract capillary zone electrophoresis. Journal of Chromatography (A)744, 223-229.

• Salomon, F., Cuneo, R., Hesp, R., & Sonksen, P. (1989) The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. New England Journal of Medicine (321) 1797-1803.