May 2007 | Back to Table of Contents
Editor's Note
Molecular Mind
The following paragraph in a recent New England Journal of Medicine article entitled “JAK2 Mutations in Polycythemia Vera—Molecular Mechanisms and Clinical Applications” stopped me in my tracks:
Normally, JAK2 activation involves tightly regulated cytokine-induced phosphorylation of tyrosine residues in the kinase and negative regulatory JAK homology domains JH1 and JH2, respectively. JAK2 V617F, resulting from a point mutation (1849GT) in exon 14, causes the substitution of phenylalanine for valine at codon 617 in the JH1 domain. This change in a single amino acid renders the JAK2 enzyme constitutively active. The four JAK2 mutations described by Scott et al. are in-frame deletions or tandem point mutations in exon 12. Both JAK2 V617F and the exon 12 JAK2 mutations induce cytokine-independent proliferation of cell lines that express erythropoietin receptors and cause these cells to become hypersensitive to cytokines. Moreover, the transfection of hematopoietic stem cells with a mutant JAK2 gene causes a polycythemia vera–like phenotype in mice.*
*Tefferi A. N Engl J Med. 2007;356(5):444-5.
Although I am a clinically oriented primary care internist, I have nurtured a commitment to learning basic science since medical school and have struggled to keep up. Convinced that medical science is galloping toward exciting revelations about disease at the cellular and subcellular level, I have read books about the Human Genome Project and gone to lectures and conferences about advances in molecular biology and bioengineering. I even bought an anchor of a textbook, The Cell.
Perhaps I am more likely to skim over basic science updates in journals than I used to be, but I thought I was at least partially plugged into the genetic/cellular biology revolution. Yet here was a paragraph about a potentially ground-breaking advance in the understanding of a major disease that read to me like a Sanskrit codex. Homology domains, in-frame deletions, tandem point mutations, transfection, and the cryptic characters JAK2 V617F, JH2—Where was the key to unlock this cipher?
This month’s Minnesota Medicine is a start. We have included an explanatory guide to available clinical genetic tests that should help demystify some of the new alphanumeric jumbles (see p. 33). We have a primer on stem cells, those cellular factories that simultaneously evoke the glow of promise and shadow of controversy (see p. 36). And we describe a sampling of other ways DNA and cell biology are influencing the real world (see our cover story, “Code You,” on p. 26). You may not be able to decipher the polycythemia vera paragraph after reading this issue, but I hope you’ll catch a glimpse of the revolution it epitomizes.
Like many scientific revolutions, molecular biology introduces new language to describe new ideas. Medicine has always had its own language, and much of what we physicians grappled with in medical training was learning the lexicon and syntax of a tongue notorious for its polysyllables and abbreviations. Conquering that lingo prepared us for layering on future knowledge. If you know the basics of DNA and RNA, hopefully, you should be able to integrate the concepts of SNPs or reverse transcriptase.
Learning the language does take patience. The terms are new and not particularly user-friendly. The rate of change is vertiginous, making my Cell textbook obsolete almost before I finished the introduction. Yet the exhilaration of delving into the shrinking mystery that is the cell is worth the effort.
Charles R. Meyer, M.D., editor in chief
Dr. Meyer can be reached at
cmeyer1@fairview.org