Dr. Schund, how can Proctor & Gamble reinvent its Olestra debacle into spreadsheet pecuniary splendor?
Scientific American 278(2) 73 (1998) avows annual US blood transfusion hemoglobin flux is 530,000 kg net, 10.5 million units of blood, and growing every year. As with health care, day care, and presumably Brussels sprouts care, America is skirting a National Blood Supply Crisis. Prodigal demand is projected to exceed donations come 2030. (2030 is the decade when China's Officially skewed birth ratio - 114 boys/100 girls and soaring - implements bridal civil war. Is there a State-imposed harvest-for-export solution here?) Synthetic blood lasting beyond 42 days of refrigeration is a goal. Some clever blood substitute storable like a sack of beans and not triggering ABO/Rh immune response would render Health Maintenance Organizations all giddy with discreet deals and profitability.
Hemoglobin is a four-protein cluster. In humans an alpha-subunit (141 amino acid residues) gets in tight with a beta-subunit (146 amino acid residues), then the pairs dimerize (molecular weight of 64,500). The protein embraces and tunes four heme prosthetic groups (MW = 616.50 apiece) each holding one working Fe(2+) ion (55.845). The final assembly exhibits allosteric interactions such that oxygen is avidly grabbed in the lungs and progressively released vs. local oxygen partial pressure. Upstream tissue does not get flooded with nor downstream tissue starved for oxygen. That justifies the 1200:1 matrix/worker weight ratio.
Human hemoglobin inconveniently requires 2,3-diphosphoglycerate to reversibly function lest it rapidly auto-oxidize to rust. Low concentrations of free hemoglobin will destroy your kidneys, high concentrations will gel your blood. This colorful, nasty, and vital material comes packaged in red blood cells with support metabolism. Bovine hemoglobin is similar stuff save that it does not need 2,3-diphosphoglycerate to function, and is available in biblically proportioned floods from slaughterhouses.
Starting with unpackaged (cell membranes go, ABO/Rh antigens go) steer hemoglobin, do a little chemical crosslinking or mild copolymerization to forestall protein subunit dissociation. Kidneys choke on small proteins but ignore big ones. Decorate the polyhemoglobin molecular surface with poly(ethylene glycol) (PEO) for emphatic humoral and cellular immune compatibility and enhanced chemical stability. It works as an indefinitely storable human blood substitute, though not to Food and Drug Administration satisfaction given "increased mortality."
Physical reality aside, artificial blood needs a more desperate corporate push against the FDA bogeyman. Contemplate a certain multinational company dunked in a $500 million FDA bloodbath: Proctor & Gamble's sucrose polyester (Olestra, Olean) non-caloric grease washes out oil-soluble vitamins (A, E, K) and exhibits anal leakage (skid marks in your shorts). Olestra is table sugar with a fatty acid ester joined to each of its pendant hydroxyl groups. The resulting oleaginous molecule is too big to fit into digestive enzymes' active sites. It passes through the human digestive tract unchanged but not ignored, Officially and personally.
Olestra is a financial cataclysm resistant to repackaging as all-natural crankcase lube and not rectifiable as its pay by the squirt by lubricious squirt delivery in gay bathhouses. Then again, there is no reason why fatty acids must be used to build Olestra-type molecules from sugar. It is chemically forthright to start with sucrose or corn syrup, add ethylene oxide plus catalyst, and grow chains of poly(ethlene oxide) (PEO) onto the sugar cores. Said PEO is attached by robust ether linkages, allowing sugar aldehyde or ketone functionality to be hydrolytically unmasked in acid. Spontaneous Schiff base formation with pendant amino groups on the surfaces of polyhemoglobin molecules is secured by reductive alkylation to irreversibly close the links - Hemolestra(tm)! It sounds like an exciting Spanish dance, doesn't it?
Grafting to ordinary polyhemoglobin links one PEO chain/molecular attachment site on the fly. It requires vigorous reaction conditions perhaps in special (expensive, environmentally hazardous, OSHA-regulated, cancer-causing, FDA not approved) solvent media to achieve dense derivatization. The reaction product must be purified from byproduct and degradation gunk. Hemolestra synthesis fastens up to eight PEO chains/attachment site in a spontaneous reaction in water. The purification simplicities and economic advantages are obvious: Do the aggressive chemistry on cheap sugar. Tickle expensive and delicate polyhemoglobin to obtain the final product.
(Hemolestra would be the first low-calorie artificial blood - just the thing for morbidly obese vampires - but I digress.)
What advantages are to be had? Seriously compromised people would not be dunned up to $200 for a unit of blood, maybe. Hemolestra could be stored in broom closets and administered without regard to blood typing or Rh sensitization of potentially child-bearing women. Transmission of AIDS, various flavors of hepatitis, and other blood-borne diseases would vanish. The military would stockpile tens of thousands of gallons.
The military has a special little blood problem. Sand fleas throughout the Muslim Middle East transmit the protozoan disease leishmaniasis. America's brave young sacrifices for democracy are poxy with it. Skin sores (that progress to chronic skin ulcers); mouth ulcers and tissue erosion (tongue, gums, lips, nose), and inner nose erosion. The military blood donor pool is poxy.
P&G could give the FDA a bloodbath of its own.