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).