Promising but Scarce
Of all the drugs that physicians now use totreat various forms of cancer, by far the most promising is the enzyme"L"-asparaginase. It is the first that has been found todeprive some types of cancer cells of a substance that they cannot makebut must have.
This substance is the amino acid, "L"-asparagine. Normal cellsalso use it, and can apparently make it themselves.
So, unfortunately, can certain cancer cells, which explains whyasparaginase cannot be effective against all kinds of cancer. But ithas the enormous ad vantage that whereas other anticancer drugs maydamage normal cells as well as cancer cells, asparaginase is highly selective. It deprives only some vulnerable cancer cells of asparagine,doing no harm to normal cells.
Tests so far show that the enzyme works best against certain forms ofleukemia. But research physicians treating patients with asparaginaseare laboring under grave handicaps. For one, much of the availablesupply is too impure to be given safely to patients already sufferingfrom acute leukemia.
For another, asparaginase is still forbiddingly expensive, and scarce.
One Optimal Dose. The impurities, which cause fever and allergic reactions, are not the manufacturers' fault, says Dr. Harold Campbell, whois working on improved purification methods.
They are produced by the colon bacteria from which asparaginase isextracted. Expense and scarcity result from the fact that a 400-gallonfermenter such as those used by New Jersey's Worthington BiochemicalCorp. produces 44 Ibs. of "wet-weight" E. coli bacteria.From this only 1/30 of an ounce of asparaginase can be extracted. Suchan amount, says Dr. Lloyd J. Old of Manhattan's Memorial Sloan-Kettering Cancer Center, is enough totreat two children or one adult for only three weeks. Of 81 patientswith various kinds of cancer treated so far at Memorial withasparaginase, none have received what the doctors believe may be theoptimal dose.
Despite the limited supplies, early results are encouraging. Dr.Herbert F. Oettgen reports that of 27 patients with acute lymphocytic leukemiatreated by Memorial physicians, 16 have hadfavorable responses followed by relapses. The same is true of leukemicmice; if they receive doses in the same proportion ashuman patients get, their disease is arrested for a while, then itrecurs. But if mice are given hundredfold greater doses, some arecured, says Dr. Ed ward A. Boyse. The Memorial doctors want to getenough asparaginase to try such massive doses on humans. In a few casestreated for some other forms of leukemia and in different types ofcancer, the response rate is near zero, with one striking exception. Aman who had several melanoma deposits under his skin was givenasparaginase for three weeks; now, four months later, he appears freeof this virulent disease. In four other melanoma cases there was noresponse.
Two Enzymes. Why asparaginase is effective against some cancer cells andnot others has just been explained by a research team in thebiochemistry department at Cornell University Medical College and atSloan-Kettering. All cells need the amino acid asparagine, and to makeit they need the enzyme asparagine synthetase. If they lack this, theyare dependent on borrowing asparagine from other cells, andasparaginase knocks out the floating supply, leaving none to beborrowed. Cancer cells that happen to have the synthetase enzyme arenot affected by asparaginase, so the chemical would be wasted inattempts to treat patients with cancerous cells of this type.
How many cancers of different types could be usefully attacked can bedetermined only by elaborate additional testing. To boost asparaginaseresearch directly, the National Institutes of Health has put up$571,000 in grants, including $450,000 to E. R. Squibb & Sons;Sloan-Kettering is spending $450,000 a year, almost half of which comesfrom NIH. Worthington Biochemical has increased its production byconverting a new building to E. coli fermentation and asparaginaseextraction. It has also licensed Merck & Co. to use its processes intheir bigger facilities, and companies in Europe and Japan have begunexperimental production and purity testing.
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