An iGEM of an idea?
While "An iGEM of an idea" points out that it takes an average age of 42+ to win one's first NIH grant,
I do not wish to disparage iGEM by any means. The problem with science careers is that they are increasingly restricted to those who can afford to live at financial levels below those in business, law, and medicine, and who are immune to a life of rejection (1 in 20 NIH grant proposals are funded). We'll have more scientists (and similarly, K-12 teachers, by the way) if the career opportunities for...
A striking and often overlooked statistic is that about 8% of undergraduates are enrolled in baccalaureate colleges (a category which includes liberal arts colleges) but 17% of the PhDs in STEM fields receive their degrees from such schools, in many cases with no engineering programs to add to the numbers.
University of the South
References1. R. Gallagher, "An iGEM of an idea," The Scientist, 21(12):13, December 2007. 2. T. Cech, "Science at liberal arts colleges: A better education?" Daedalus, 128:195-216, 1999.
The article "MRSA: RIP?" 1 celebrates a very extensive but deeply flawed body of work authored entirely by Naomi Balaban and her colleagues. Despite its claimed importance, no independent confirmation of any of it has yet been published.
This work was initiated in my lab when I asked Balaban, then a new postdoc, to analyze staphylococcal culture supernatants for substances which would affect the expression of agr, an important regulator of bacterial virulence. Balaban confirmed the existence of an activator, which she called RAP, and identified a peptide inhibitor, which she called RIP, in the supernatants. The Balaban group has assiduously propounded a nouveau model in which the protein RAP (ribosomal protein L2) activates a second protein, TraP, which activates RNAIII expression, independently of the agr signaling module. RIP blocks the RAP-TraP pathway, interfering with RNAIII expression and thereby inhibiting biofilm formation and attenuating staphylococcal infections.
Unfortunately, several labs have synthesized RIP and found it to have no significant effect on agr function at concentrations up to 50 micromolar. In my lab, one tested strain produced a peptide inhibitor of agr activation. Although this peptide turned out to be the agr-encoded autoinducing peptide (AIP) of strain RN833, we initially (and naively) designated it "RIP'' (for RNAIII-inhibiting peptide). Balaban later obtained the sequence, YSP-TNF, for the peptide and arbitrarily inserted tryptophan (W) for the indeterminate central amino acid. Yet other research suggests the amino acid is cysteine, and Balaban et al. have never confirmed (e.g., by mass spectroscopy) that RN833 produces YSPWTNF, although at the concentrations that they use for testing, it should be readily detectable.
As is the case with RIP, there has been no independent confirmation of the reported signaling role of RAP. In fact, contrary to the report that RAP is secreted by an agr-negative strain, we have failed to demonstrate any agr-RNAIII activator in culture supernatants of this same strain. Balaban et al. have likewise never provided genetic confirmation of the supposed linkage between TraP and its purported phenotype. Three recently reported studies, independently and carefully performed, have demonstrated conclusively that TraP mutations have no phenotype in otherwise wild-type strains. In other words, TraP does not regulate staphylococcal virulence or agr signaling. 2-4
However, although the RIP-RAP-TRAP model is clearly incorrect, it is possible that RIP affects biofilm formation by some other mechanism.
New York University Medical Center
New York, NY
*We have no financial conflicts of interest or legal involvement with Dr. Balaban. However, we have a joint patent with Rockefeller University on a novel method of producing the agr-activating thiolactone peptides.
Richard Novick has made similar assertions in the past, which are not supported by the numerous peer-reviewed reports that RIP does indeed suppress MRSA infections and that the technology is indeed effective. 5-7
Virulent staph enter an open skin puncture in rather limited numbers and, unless promptly inactivated or killed locally, will colonize the wound and establish highly resistant encapsulated cell clusters known as biofilms.
Once formed, such biofilms tend to be resistant to most small molecule antimicrobials, probably including the proposed large molecule RIP and antibody therapies. The proposed peptide-based therapies furthermore may have short half lives due to proteolytic in vivo destruction, hence their effectiveness may well be limited, except as a possible last resort therapy in disseminated toxemia.
References1. A. Gawrylewski, "MRSA: RIP?" The Scientist, 22(1):19-20, January 2008. 2. R. Adhikari, et al., "A nonsense mutation in agrA accounts for the defect in agr expression and the avirulence of Staphylococcus aureus 8325-4 TraP::kan," Infect Immun, 75:4534-40, 2007. 3. L.N. Shaw et al., "Inactivation of TraP has no effect on the Agr quorum sensing system or virulence of Staphylococcus aureus," Infect Immun, 75:4519-27, 2007. 4. L.H. Tsang, et al., "Mutation of TraP in Staphylococcus aureus has no impact on expression of agr or biofilm formation," Infect Immun, 75:4528-33, 2007. 5. N. Balaban, Ed. Control of Biofilm Infections by Signal Manipulation, Springer: New York, 2008. 6. N. Balaban, et al. "Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP," Antimicrob Agents Chemother, 51:2226-9, 2007. 7. G. Dell'Acqua, et al., "Suppression of drug-resistant Staphylococcal infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide," J Infect Dis, 190:318-20, 2004.
Should we mandate masks?
Once the media aired concerns over the safety of several cold medicines for infants, everyone went into a panic and started calling their doctor because they've been giving their child this medication. What has become of our human nature? Suddenly, everyone has become a doctor or a critic. I'm not saying that I disagree with the idea that people who are sick should probably wear a mask, but I think they should have a choice, not do it out of some mandated law.
Riverside Community College
Moreno Valley, CA
I agree that we should make masks mandatory to protect against airborne diseases, and I would also suggest that doctors give these to patients they have diagnosed as having such a communicable disease. They probably already have these in their office; why not give them to patients as an added incentive and encouragement for the patient to wear while out in public?
References1. J. Woodall, "Let's mandate masks," The Scientist, 21(12):61, December 2007.
I was not amused by this article, 1 which chronicles scientists' spontaneous efforts to study whether nightjars have "evolved" street smarts. Do we really want automobiles to select those species able to survive? Could the scientists have used the hours and their combined brain power to design better ways to collect data so the extent of the problem could be known? Identify factors making different species more or less susceptible? Think up ways to prevent roadkills?
US Environmental Protection Agency
References1. B. Borrell, "Operation roadkill," The Scientist, 21(12):19-20, December 2007.
PhDs and parishioners
Darwinism has changed over the last 150 years with the significant contributions from genetics and other disciplines. But the basic tenants remain intact. Religion is also an evolving discipline, and its basic tenants are also intact. As the article "PhDs and parishioners" points out, 1 a contradiction does not exist between Darwinism and religion - they are distinct disciplines that address quite different issues. Darwin Day exemplifies a reconciliation: Darwinism is not a threat, it is a fundamental truth compatible with religious thought.
University of Calgary
As a self-described scientist of faith I often shock people and students when I tell them that I accept that evolution is the best scientific explanation to account for the diversity of life on earth but that I do not "believe" in evolution. For me a "belief" is something that I accept on faith and without a requirement of proof. Science is just the opposite. Always being challenged, always being either supported or refuted by data, by proof, not one's beliefs.
There is therefore no conflict between these two very different views of the world and it is why I am happy to be a scientist in support of the Clergy Letter Project.
University of Georgia
References1. A. Gawrylewski, "PhDs and parishioners," The Scientist, 21(12):22-24, December 2007.
In our January issue, Matthew Wallenstein was incorrectly identified as Mark Wallenstein ("A sensitive reaction," [22(1):38]). The Scientist regrets the error.