AN EMBARRASSMENT OF RICHES (C)1999 Alan M. Schwartz R&D alpha geeks (with luck, otherwise degreed poseurs who did not scare Personnel much during job interviews) cause Management no end of heartache. Discounted cashflow/return on investment projections demand spreadsheets whose only entries are money. Sales generates revenue and Marketing hypes Sales. R&D sucks cash and returns nothing resembling folding green. Researchers dress badly, have ugly wives, do not play golf... and their kids attend public schools. One scenario worse than a clique of freaks sporting plastic pocket protectors is their stumbling onto some preposterous world-shaking discovery. Management then exercises damage control and assumes full credit. Vancomycin is the antibiotic of last resort against Gram-positive bacteria (Staphylococcus aureus). Deadly pathogens have evolved (despite Fundamentalist Christian protests) resistance to everything else. Vancomycin binds to terminal D-Ala-D-Ala residues to prevent their crosslinking into peptidoglycan cell wall armor. Osmotically-challenged bacteria then rupture. Resistant bugs make D-Ala-D-Ala-Lac lactide to which vancomycin binds 1000 times less strongly. The drug is rendered powerless and patients die of 1900s' diseases. Vancomycin has a molecular weight of 1449.27. It is a polycyclic nightmare compote of polyphenyl ethers multiply connected to an oligopeptide, with a disaccharide topping it all off. Synthetic approaches to vancomycin and analogues are tortuous and noisomely expensive. We join a herd of alpha geeks assaulting Korporate Kulture and Official truth by asking if that heady concatenation of chiral molecular crap is necessary to kill bugs. Holy mackerel! (and not the ones on Christ-besotted automobile bumpers). Science 284(5413) 507 (1999), Chemical & Engineering News 77(16) 12 (1999), and J. Am. Chem. Soc. 120 11014 (1998). Take the disaccharide plus a small lump that tethers it in vancomycin, stick a 4-chloro-p-biphenylmethyl group on its other end. Desperate chemists commit "umpolung." When goop goes sour reverse its properties and hope you are very clever for doing so. Sugars like water. Hang some serious grease onto the vancosamine residue because its amine is the easy place to do it, aldehyde plus cyanoborohydride. 56% of vancomycin's molecular weight, less the complicated stuff, delivered ten times the killer punch! The halfling molecule anchors itself to bacterial cell membranes via its grease spike and liquidates pathogens via bimodal inhibition of glycosidation and peptidoglycan polymerization, whether bugs are vancomycin- resistant or not. Having saved the world from Staphylococcus, the chemists plan to diddle the disaccharide and foment some serious molecular honking re destroy all Gram-negative pathogens. Management is not amused. Growing vancomycin in huge culture vats of mutant Streptomyces orientalis is big business, and few countries have the infrastructure or custom fungus to pull it off. Vancomycin is the antibiotic of *last* resort. Drug companies can pretty much charge what they want for it lest eager lawyers start whispering "malpractice" to nervous doctors. Any fool can hang a couple of lumps off a disaccharide and call it a done deal. It could be an undergrad lab assignment. Merck paid for the work, Lilly holds the fundamental vancomycin patent. Middle managers and vice presidents in Rahway, NJ expect fat performance bonuses and abundant tax-exempt perquisites. As for Dr. Daniel Kahne, one imagines his calloused ass is back in the lab lest corporate downsizing enhance his efficiency right out the door. Why, they could hire an undergrad and give him the assignment! (In the People's Republic of Canada it is called work-study. The kid gets minimum wage and also pays full tuition toward his five-year BS/Chem - a taste of what lab niggers' lives are all about.) Dr. Kahne is even a traitor to his (under)class! A whole village of highly educated drones is worrying the herculean task of vancomycin aglycone synthesis at the Scripps Research Institute amidst butt-flossed sweet young things playing in Pacific beaches' sun-warmed sand, J. Am. Chem. Soc. 121 3226 (1999). The aglycone, the big fancy lump, is the part Dr. Kahne showed was irrelevant (detrimental!) to antibiotic activity. Susumu Miyasaki, Seong Heon Kim, Jason H. Wu, Olivier Loiseleur and others may be deported as redundant, forced back into the agricultural manure pits of their impoverished childhoods. Third World reproductive warriors do not receive vancomycin. They die - and good riddance. Politicians and First World elitists sucking Gaia dry of her resources luxuriate in exorbitant medical care. Crass class warfare whose opening volley was penicillin is advanced another notch. Dr. Kahne's terrorist cabal must be tried at the Hague for crimes against all Coloured humanity, and executed. His invention must be confiscated and awarded in compensation to poor people everywhere (who will proceed to kill each other over the spoils).