This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison
Popular Press Review
Carol Ezzell’s article, “Gene therapy for rare cholesterol disorder - familial hypercholesterolemia” explains the approval of a new gene therapy treatment for familial hypercholesterolemia (FH) (1). This treatment, developed by James M. Wilson and colleagues, was shown to reduce cholesterol levels in hyperlipidemic Watanabe rabbits (2). The article contains a reasonably comprehensive outline of the procedure Wilson used to lower LDL levels in Watanabe rabbits. At the time of publishing, this article only needed FDA evaluation and official approval by the National Institutes of Health (NIH) director in order for the therapy to be used on humans. Ezzell writes optimistically about the potential success of this gene therapy, an optimism that seemed to be shared by the experts that were quoted within the article. This outline of the treatment was simple enough to be understood by the reader, however the term “crippled retrovirus” should have been defined. This term would be somewhat foreign to the reader and considering the importance of the virus for the treatment, it needed to be better explained.
Within the article, Ezzell provides simple, yet important general information on symptoms of FH caused by abnormally high LDL cholesterol levels, like early onset heart attack and xanthomas. By stating that individuals with the most devastating forms of FH usually die from heart attacks in their teenage years, Ezzell is able to highlight the severity of FH and potentially keep the reader interested in the subject of the article. Established medical treatments for FH sufferers are also accurately listed within the article. The listed symptoms and treatments for FH give the reader a sufficient understanding of the clinical manifestations of the disease.
In attempting to explain the genetic and molecular components of FH, the author comes up short. Ezzell incorrectly states that individuals with FH “are born lacking both of the usual two copies of the LDL receptor gene.” This implies that FH is the result of not having an LDLR gene. FH occurs from numerous mutations within the DNA that encodes the LDLR gene, and these mutations variably impact the function of the LDL receptor protein. Depending on the mutation, the efficiency of LDL internalization is reduced or the LDL receptor can be completely non-functional. Therefore, the varying increase in blood LDL levels correlates to the degree of debilitation of the receptor protein, which depends on the mutation within the LDLR gene. Surprisingly, mutations are not mentioned anywhere within the article. Ezzell fails to explain that small base substitutions or deletions that affect pertinent amino acids within the LDL receptor protein cause this disease, not entire deletion of the gene. This mistake in the article reflects the misnomer that the general public tends to believe: genetic disease is caused by the lack of certain genes. Normally in genetic disease, genes are not lost; the products they encode do not function normally or are not expressed because of mutation within the DNA of the gene.
Carol Ezzell’s article, overall, completes its purpose of informing the reader about the causes, symptoms, and treatments of FH. She also effectively explains the new gene therapy treatment method succinctly but thorough enough. Methodology is often the most lacking part of popular press articles written about scientific research. Ezzell successfully summarizes the methods of the gene treatment, which enhances the knowledge of the reader.
Within the article, Ezzell provides simple, yet important general information on symptoms of FH caused by abnormally high LDL cholesterol levels, like early onset heart attack and xanthomas. By stating that individuals with the most devastating forms of FH usually die from heart attacks in their teenage years, Ezzell is able to highlight the severity of FH and potentially keep the reader interested in the subject of the article. Established medical treatments for FH sufferers are also accurately listed within the article. The listed symptoms and treatments for FH give the reader a sufficient understanding of the clinical manifestations of the disease.
In attempting to explain the genetic and molecular components of FH, the author comes up short. Ezzell incorrectly states that individuals with FH “are born lacking both of the usual two copies of the LDL receptor gene.” This implies that FH is the result of not having an LDLR gene. FH occurs from numerous mutations within the DNA that encodes the LDLR gene, and these mutations variably impact the function of the LDL receptor protein. Depending on the mutation, the efficiency of LDL internalization is reduced or the LDL receptor can be completely non-functional. Therefore, the varying increase in blood LDL levels correlates to the degree of debilitation of the receptor protein, which depends on the mutation within the LDLR gene. Surprisingly, mutations are not mentioned anywhere within the article. Ezzell fails to explain that small base substitutions or deletions that affect pertinent amino acids within the LDL receptor protein cause this disease, not entire deletion of the gene. This mistake in the article reflects the misnomer that the general public tends to believe: genetic disease is caused by the lack of certain genes. Normally in genetic disease, genes are not lost; the products they encode do not function normally or are not expressed because of mutation within the DNA of the gene.
Carol Ezzell’s article, overall, completes its purpose of informing the reader about the causes, symptoms, and treatments of FH. She also effectively explains the new gene therapy treatment method succinctly but thorough enough. Methodology is often the most lacking part of popular press articles written about scientific research. Ezzell successfully summarizes the methods of the gene treatment, which enhances the knowledge of the reader.
References
1. Ezzell, C. (1991). Gene therapy for rare cholesterol disorder - familial hypercholesterolemia. Science News, Retrieved February 3, 2010, from: http://findarticles.com/p/articles/mi_m1200/is_n15_v140/ai_11494683/?tag=content;col1
2. Chowdhury, J. R., Grossman, M., Gupta, S., Chowdhury, N. R., Baker, J. R., & Wilson, J. M. (1991). Long-Term Improvement of Hypercholesterolemia After ex Vivo Gene Therapy in LDLR-Deficient Rabbits. Science, 254(5039), 1802-1805. doi: 10.1126/science.1722351
2. Chowdhury, J. R., Grossman, M., Gupta, S., Chowdhury, N. R., Baker, J. R., & Wilson, J. M. (1991). Long-Term Improvement of Hypercholesterolemia After ex Vivo Gene Therapy in LDLR-Deficient Rabbits. Science, 254(5039), 1802-1805. doi: 10.1126/science.1722351
