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Rebuttal from Dr. Snider

Let us also examine the effects of his discarding the definition of pathogenesis of disease based on cell and molecular biology. The antileukotriene drugs were the first novel class of asthma therapy introduced in more than 20 years (1, 2). Without cell and molecular biology, we would not have these agents or many of the new drugs introduced in the last 50 years. We would also be foreclosing our understanding of many diseases.

Cystic fibrosis (CF) was discovered in the 1950s. The CF transmembrane conductance regulator (CFTR) gene was identified in 1989 (3). Since then more than 1,000 mutations have been identified. In the United States, two-thirds of CF patients carry at least one copy of the F508 mutation and about 50% are homozygous for this mutation. Atypical, "mild" mutations in the CFTR gene have been linked to late-onset pulmonary disease, congenital bilateral absence of the vas deferens, and idiopathic pancreatitis. Different mutations in the gene have different effects on the function of CFTR protein. The correlation between genotype and phenotype is imprecise and there is evidence of both environmental and genetic disease modifiers (4). Specific therapy has not yet emerged, but it is evident that changed concepts of disease will be critical in deciding which patients to treat.

Many people denigrate cell and molecular biology research because progress in disease understanding is tortuously slow. As illustrated by CF, disease pathogenesis is sufficiently convoluted that human imagination cannot begin to fathom it without engaging in scientific investigation, which often yields surprises. Small wonder that patients and physicians become impatient with the research process! Progress, including improved symptomatic therapy, is possible with research using the other branches of science. But only research using cell and molecular biology can provide fundamental information on pathogenesis and lead to specific therapies.

REFERENCES

1. Holgate ST, Sampson AP. Antileukotriene therapy: future directions. Am J Respir Crit Care Med 2000;161:S147–S153.[Free Full Text]
2. Leff AR. Discovery of leukotrienes and development of antileukotriene agents. Ann Allergy Asthma Immunol 2001;86(6 Suppl 1):4–8.[Medline]
3. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245:1066–1073.[Abstract/Free Full Text]
4. Noone PG, Knowles MR. ‘CFTR-opathies’: disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations. Respir Res 2001;2:328–332.[CrossRef][Medline]

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