Symposium focuses on immune system Advances in immunological treatment of cancer and the possibility of an "an-tipregnancy vaccine" were among de­velopments described in a wide-ranging all-day symposium at the San Francis­co AAAS meeting that focused on re­cent inquiries into the human body's immune system.

The possibility that the body's im­mune defenses can be rallied to fight off or destroy various types of cancer cells has been enhanced by work car­ried out by Dr. Donald Morton, chief of the division of oncology at the Univer­sity of California, Los Angeles, school of medicine. His apparently successful use of immunotherapy in advanced cancer patients evolves from the obser­vation that the surfaces of cancer cells contain specific antigenic sites that are susceptible to attack by antibodies and the body's cellular immune defenses. On the other hand, similar cells that are not cancerous do not contain the surface antigens.

Even before the discovery of surface antigens, the fact that the body might have immune defenses against cancer cells was suggested by the observation that, in about 200 known cases, malig­nant tumors have regressed with no clear explanation as to how or why they did, Dr. Morton notes. In the re­cent UCLA work, the cancer patient's immune system is "revved up" by in­jections of BCG, an attenuated form of a bacterium that causes tuberculosis in cows. It long has been known that BCG can increase the ability of the immune system to react against bacteria, vi­ruses, fungi, and other disease agents. But until recently it never had been tried against cancer.

Earlier experiments with guinea pigs showed that an injection of BCG, along with cells from the animal's own tumor, caused the tumor to regress, Dr. Morton explains. Later work showed that the same thing occurred with BCG injections alone and prompted him to try the bacterial agent in humans with cancer that had resisted all other available techniques, including surgery and chemotherapy. In one case of a 52-year-old man with malignant melanoma (skin cancer) characterized by 15 cancerous lesions on his forearm, Dr. Morton injected BCG into half of the tumors, and left the others alone. In three weeks, most of the lesions had regressed—indicating that BCG also had a systemic effect— and in two and a half years there was no trace of the disease. After six years the patient still survived.

Since then, many other patients with advanced, otherwise untreatable, mela­noma have been treated successfully with BCG, with an indication that it also may be effective in recurring breast cancer, Dr. Morton points out. In addition, he has found that BCG is

effective even when it is injected at a site some distance from the tumor site. This indicates to him that BCG may have a double-barreled effect in which it can induce the production of anti­bodies in the blood stream in addition to enhancing the activity of immunity-conferring cells in the immediate vicin­ity of the tumor.

Dr. Morton notes that the best can­didates for BCG immunotherapy are those who show an immune sensitivity to dinitrochlorobenzene (DNCB), a test that indicates that the patient's immunity-conferring cells are still in good working order. In 19 patients who gave a positive DNCB test, all re­sponded to treatment with BCG, he says. No regressions occurred in pa-

Behrman: antipregnancy vaccine

tients who showed no reaction to DNCB.

In comparing the effectiveness of BCG therapy in patients to the effects of surgery and chemotherapy in other patients who had advanced to the same state of the disease, Dr. Morton found that cancer recurred in 20% of BCG-treated patients in two years, com­pared to a 60 to 70% recurrence in the other patients.

The UCLA surgeon cautiously notes that his apparent success with BCG still gives "only presumptive evidence" that the technique is effective. He ex­pects that within two years, after a more elaborate and comprehensive study is completed, a better evaluation will be possible.

The possibility of developing an "an­tipregnancy vaccine" was hinted at by Dr. Jan Behrman of the department of obstetrics and gynecology at the Uni­versity of Michigan. He was able to cause abortions in rhesus monkeys by injecting females with an antiserum produced against specific protein anti­gens associated with the sperm of the male monkey. The fetus was aborted at any stage of development between 39 and 80 days of pregnancy, he explains.

The work leading to this develop­ment goes back to the theory that the inability of some women to have chil­

dren may be based on some type of im­munologic incompatibility between the egg and the sperm. Following up that lead, Dr. Behrman has found that when sperm is injected into the uteri of rabbits, they become immunized and produce a series of immunoglobulins including IgG, IgM, and IgA. By label­ing the last with fluorescent thiocy-anate, Dr. Behrman concluded that the immunoglobulin localized in the head of the sperm, suggesting that it sought out a specific reaction site.

Dr. Behrman then found that if he took the blastocysts (very early stages in the development of embryos) from pregnant rabbits, incubated them with uterine fluid from sperm-immunized rabbits, and then implanted them in normal females, only 19.4% of the pregnancies took. On the other hand, when blastocysts were incubated with the uterine fluid of rabbits that had not been sperm-immunized and then reimplanted, 86% of the pregnancies took. "Obviously the presence of the immunoglobulins had reduced the abil­ity of the blastocyst to survive," Dr. Behrman says.

In the rhesus monkey experiments, Dr. Behrman used electrophoresis to separate proteins produced in the pla­centas of the monkeys. Because these materials cross-reacted with the pro­teins of monkey sperm, he inferred that they were involved in promoting the immune response. Then when he injected the placenta tissue into a goat, antibodies were produced in the ani­mal's blood serum. It was this antise­rum that produced the abortions in fe­male monkeys.

"It now appears that it is possible to produce specific antibodies to sperm proteins which can be given to an indi­vidual to prevent pregnancy," Dr. Behrman explains. "Our experiments with animals also indicate that when an animal treated in this way mated again, it had no difficulty in getting pregnant or in sustaining that pregnan­cy."

At the same time, Dr. Behrman adds, birth control is not the chief ob­jective of his research: "Even though this technique presents itself as a con­traceptive means, I am much more in­terested in obtaining evidence that will clarify how the maternal system devel­ops its own inscrutable mechanism to accept or reject foreign proteins."

5/?-Cholanic acid found in plant source The group of stable natural products whose origins can be traced to exclu­sively plant sources or exclusively ani­mal ones is rather small. But the chemicals are useful to paleontologists and others who study the distribution of plant and animal life at earlier peri­ods in the earth's history. One useful chemical of this group has been 50-

16 C&EN March 18, 1974

cholanic acid, the dehydration product of certain bile acids that are found in all animals but not in plants.

This steroidal acid has been found in trace amounts in petroleum samples believed to be more than 10 million years old and its presence has been used as evidence of the partial animal origin of these petroleums (C&EN, June 25, 1973, page 13). Now, however, its status as a natural product of exclu­sively animal origin is being revoked. Scientists at the Agricultural Research Center of the U.S. Department of Agri­culture have isolated 5β-cholanic acid from a plant source—the embryo of the jequirity bean.

Dr. Nagabhushanam Mandava and coworkers found the compound while

The poor economics of desalination to produce drinkable water has been a hard technological nut to crack. But that hasn't prevented desalination plants from being built.

These two faces of desalination tech­nology are evident in a newly issued survey made by the department of eco­nomic and social affairs of the United Nations Secretariat in New York City. The survey, second of a series, covers operation of desalination plants throughout the world in 1968. A first survey, issued in 1969, covered the sit­uation three years earlier.

The current survey shows that large-scale use of desalination plants in the world's arid regions has increased rap­idly in recent years. However, the study indicates, there has been no dra­matic breakthrough in costs. In fact, a report on the survey notes that no sig­nificant changes in the economic or technological situation had become ap­parent since the previous survey and suggests that the rate of development isn't great enough to justify a survey every three years.

Excluding plants with capacity of less than 10,000 gallons pet5 day, the survey covers 94 plants in 22 countries; there were 23 plants in the earlier sur­vey. Total capacity of the plants is 61.5 million gallons per day.

Of the plants reporting total water costs, the least expensive operations— two plants in Saudi Arabia—produced potable water for 53 cents per 1000 gal­lons. However, fixed charges on invest­ment in these cases were at a rate of only 5% (compared to the 10% the sur­vey considers a minimum rate under normal economic conditions) and fuel cost was only 8 cents per 1000 gallons.

For most of the plants, total costs amounted to more than $1.̂ 00 per 1000 gallons. However, about 50% of the total water produced cost less than

attempting to isolate a growth-inhibit­ing hormone from jequirity bean em­bryos. In the March 1974 issue of Ste­roids they explain that the compound was separated by ion exchange chro­matography and converted into the methyl ester for analysis. Mass spectral and nuclear magnetic resonance analy­ses, as well as melting point and opti­cal rotation, were used to identify the product as the methyl ester of 5/3-cho­lanic acid. 5a-Cholanic acid—which differs from the 5/3-acid in that it is trans at the A/B steroid ring junction whereas the 5/5-acid is cis—is quite common in plants. Dr. Mandava ran his sample along with known samples of both the cis and the trans cholanic acid methyl esters in mass spectral and

$1.00 per 1000 gallons and more than 80% of the total produced cost less than $2.00 per 1000 gallons.

Other gleanings from the survey pro­vide a profile of worldwide desalination technology in place:

• Of the 94 plants, 55 use multi­stage flash distillation. Although used in only 60% of the total number of plants in the survey, the process ac­counts for 88% of the total production capacity.

• Multieffect distillation is used in 17 plants, but total capacity is only 1/10 that of multistage flash.

gas chromatographic analyses to con­firm that he had isolated the 5β-acid.

Whether 5/?-cholanic acid is unique to the jequirity bean or can be found in other members of the Leguminosae family or perhaps other related plant families has not been determined yet. As yet there is no clear reason why it should benefit the jequirity bean to have such an unusual plant acid, al­though Dr. Mandava hopes that fur­ther studies on this question will be conducted. But it is clear that 5/?-cho-lanic acid no longer may be considered a chemical trademark certifying the prehistoric presence of some type of animal. If one contemporary plant can produce this acid, then perhaps its an­cestors could also.

• Vapor-compression distillation is used in seven plants but accounts for only about 1% of the total water out­put.

• Only one plant uses reverse osmo­sis, and brackish water is the feed.

• Electrodialysis, on the other hand, is used in 14 plants, but mainly for small-capacity plants and always with brackish water as feed.

• No plants use freezing. • Of the thermal distillation plants

in the survey, 75% are dual-purpose plants, combining water production with generation of electricity.

March 18, 1974 C&EN 17

Big rotary kiln will process Baltimore solid waste With Baltimore rising behind it, a 20- by 100-ft. kiln arrives in Baltimore harbor en route to incorporation into a pyrolysis system that will process 1000 tons per day of that city's solid waste. When it goes on stream in the third quarter of this year, the Landgard system, developed by Monsanto Enviro-Chem Systems, Inc., will recover, for sale, useful metals and a glassy aggregate that will be used by the city for road building. The sys­tem, which will cost $15 million, also will generate 200,000 pounds per hour of steam that will be used for heating and cooling buildings in down­town Baltimore.

Technology

Survey profiles worldwide desalination