THE CHEMICAL WORLD THIS WEEK
"Ouch " says the little fellow. But h i s pain may be well worth while if the pains of polio are checked by .
The G a m m a Globulin Stop-Gap \
STAFF REPORT
"C IGHT biological processing plants in the "*"* nation are now working round the clock in an eflfort to produce as much gamma globulin (more correctly: polio immune globulin) as possible during the coming summer months. Despite this fact, of the 40 million children in the country who will b e most susceptible to the strange polio virus, only about one million will be able to receive the temporary protection gamma globulin affords. The simple answer to this is that there is just not enough globulin to go around. E v e n if far greater amounts of blood were available, or if more plants could fractionate gamma globulin from whole blood, ii is doubtful if enough could be produced to protect the entire susceptible population throughout all of the summer months. This is because gamma globulin only affords protection from polio for five
3060
weeks, at most. After that the susceptible patient is once again just as apt to contract the virus as not. T o be completely protected, a child, would have to receive periodic shots of gamma globulin every five weeks. Again, during the first a n d last weeks globulin merely lessens the severity of paralysis; in fact, it is not always certain that it gives complete protection to all in this five-week interval. However, if negotiations under way with the Department of Defense are successful, the Office of Defense Mobilization (the gamma globulin distributing agency) may shortly have enough additional globulin for another quarter million children. The Department of Defense has on hand 2 million cc. of dried globulin, used for prevention of epidemics of measles and hepatitis (the original use of gamma globulin). This has been held in reserve in case an epidemic of hepatitis should break out among the troops in oriental countries. It could be processed in a short time for use against polio. O D M hopes to obtain this extra globulin and then to distribute it to all epidemic areas this summer. The
CHEMICAL
large number of epidemics that have occurred so* far made it doubtful at first whether t h e dwindling supply would last past the uniddle of August, especially if epidemics kept occurring at t h e same rate. At present, 3 3 % of the gamma globulin now b e i n g processed is released b y O D M to state health officers w h o in turn release their portion t o individual doctors in thenstates. Another 57% is kept in reserve by ODM for epidemics. As soon as t h e y receive w o r d o f an epidemic, a certain amount, depending upon t h e community size invohved a n d the amount of gamma globulin o n hand, is released for widespread disrtribixtion in the community having the epidemic. Another 10% is kept in reserve for special contingencies, such as an emergency occurring at summer camps. Gamma globulin is actually nothing more t h a n a particular type of protein?'* not too well defined as yet. It is part of the plasma or serum found in the blood stream -with red and white blood cells and blood platelets. Gamma globulin by no means forms the major part of the
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ENGINEERING
NEWS
plasma, rather, something like V? of the total 7% of plasma found in whole blood. It is an antibody w i t h the ability to fight viruses such as polio, which have a harmful effect to the human system. Polio Virus Develops In Three Types of Strains Polio virus develops in three types of strains, representatively called Brunhilde, Lansing, and Leon, any one of which can cause polio in the human system. Each polio strain must have a specific gamma globulin antibody to fight it. There is no w a y of telling which of the three strains a person has contracted; therefore, there must b e three forms of gamma globulin antibody in each portion of serum injected into a child in order to give him complete protection. T h e greater percentage of the population can produce the polio antibodies in their systems naturally and in sufficient quantity to resist one or more strains of polio. A 25-year-old individual has probably an 8 5 % chance that he has at one time or another had polio, although he may never have been aware of the fact DT showed any symptoms. Since there is no accurate, cheap, and rapid diagnostic test for the presence of one or more of these antibodies, the entire group of children most susceptible to the disease must be given all three types of gamma globulin without knowing whether they definitely need the globulin or not, or even without knowing whether they need only one or more of the globulin types. Since individuals can either develop none, one, or all of the three antibodies, it is questionable just which antibodies, and to what amount, exist in any given pint of whole blood. T o ensure an adequate mixture of all three types in the gamma globulin serum, donated blood is mixed in large lots from blood banks throughout the country. This is also one reason "why every batch of gamma globulin is given such stringent tests by the National Institutes of Health before it is released for use. If researchers could find simple, quick tests for polio and its strains, or for amount and type of antibody, much of the heavy demand for globulin could b e cut down, and in turn the treatments could b e approached more effectively. Today, by the time a biological test could be run, the child would b e past help before t h e tests would show whether h e had polio or the antibodies to combat it. So far, gamma globulin is the only thing which will halt polio in any degree. Research workers emphasize that it is only a stop-gap measure. All gamma globulin in use today is produced b y the alcohol fractionation process. T h e eight laboratories doing the processing^are: Sharp & D o h m e , Cutter, Lederle, ET R. Squibb and Sons, Pitman-Moore, Armour, Massachusetts Public Health, and t h e Michigan department of health. The last t w o distribute only on a state-wide basis. T w o laboratories in California may V O L U M E
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soon be processors—Cortland Laboratories and Hyland Laboratories. W . G. Workman, National Institutes of Health, has said that the present supply of globulin is limited, not so much b y the ability of the present plants to process i t fast enough, but b y the amount of blood that the American public wants to give. Dr. Workman also indicated that by fall, or January at the latest, there will b e enough fractionation plants established t o handle all the blood as rapidly as it can be procured. In the Works: Metal Salt Fractions Alcohol fractionation takes from 1 2 t o 14 days. Another m e t h o d of fractionation developed by a Harvard group ( E d w i n J. Cohn, Douglas M. Surgenor, and W . M. Batchelor) may h a v e certain advantages over the alcohol process. This process, metal sales precipitation, uses barium sulfate to remove prothrombin and yields plasma that is relatively, heat stable (C&EN, May 26, 1952, p a g e 2 2 1 8 ) . Zinc is then used to precipitate the bulk globulin from the plasma proteins. The yield is about the same as in t h e alcohol process but the time for t h e complete operation has been reduced to less than eight days. T h e metal salts process, now in semipilot plant stages at Sharpe & Dohme, under the direction of Robert B. Pennell, has the further advantages of requiring less equipment and being more economical in operation. Metal salts globulin is believed
to be more nearly like the original protein in the blood as shown b y its gelling time. Whereas alcohol globulin gels in 10, hours, metal salts globulin has stood 2ft^fiours without gelling. In one sense, m(SallsSlts globulin is less harsh in that i t can safely b e injected intravenously to become effective immediately; alcohol globulin has to be introduced intramuscularly. Indications from work n o w under way give hope that the gamma globulin fraction may again be refractionated into its three component antibody proteins. Dr. P«nnell feels that the metal salts process offers so many advantages that it could replace all of the alcohol operations n o w in use if it is approved as safe and effective as alcohol globulin by the various health agencies. Metal salts processing plants cannot b e built before next summer; according to D r . Pennell, because the process i s still in the stages of clinical testing and must pass months of rigid biological testing before it can b e considered safe for public use. One hope in regard to the short lived gamma globulin now being used is that it may stimulate the patient to produce active antibodies on his own. On the other hasid, as chemistry advances toward the synthesis of proteins, perhaps some day chemical plants will be able to arrive at an end product identical with the protein called g a m m a globulin. Both of these ideas are far in the future in the minds
Dl I SO BUTYL CARBINOL CH3CHCH2CHCH2CHCH3
I CH3
I OH
I CH3
b.p. 178.3° C.
TRIMETHYL N O N Y L ALCOHOL CH3CHCH2CHCH2CHCH2CHCH3 ssss,
CH 3
*
