135 School of Pathology, Oxford, under the direction of Prof. Henry Harris.’ Just over ten years ago it was discovered that cells from different animal species could be fused to form viable hybrids. At first the hybrid cells are binucleate, but simultaneous mitosis of the two nuclei usually results in daughter cells which contain complete sets of chromosomes from both parent nuclei. Thereafter, chromosomes are progressively lost. In the case of human/mouse hybrid cells, the human chromosomes tend to be lost preferentially. By looking for associations between the loss of particular markers and the loss of particular chromosomes, it is possible to assign genes determining overt phenotypic markers to particular chromosomes. If, before fusion, breaks are induced in the human chromosomes by ionising radiation, analysis of the frequency of disruption of linkage enables one to determine the order of the linked genes on the chromosome and the distances between them. In these ways rapid progress has been made in human genetic carto-
graphy. The ability
a cell to multiply progressively and kill syngeneic host, is a genetic marker of malignancy. Thus, in mice it has been possible to investigate by fusion techniques whether malignancy is a
its
host,
of
or a
dominant or a recessive trait and whether it is associated with the presence or absence of particular chromosomes or genes. A surprising but consistent finding has been that fusion of a malignant cell with a non-malignant one results in suppression of the malignant phenotype: as long as the resultant hybrid cell retains the full combined genetic complements of the two parent cells, it exhibits little or no ability to multiply in immunosuppressed syngeneic hosts. By using "nude" mice as hosts it has been shown that malignancy is similarly lost when human cancer cells are fused with normal human cells. That is the good news. The bad news is that, after a variable period of cultivation in vitro, malignancy almost invariably reappears in the hybrid-cell population. This may well be because chromosomes which neutralise malignancy are lost from hybrid cells, and the search is now on to see whether particular chromosomes are more important than others in this respect. In the mouse it is already clear that chromosome 4 carries some determinant that plays a crucial role in controlling cell growth. However, the loss of both chromosomes 4 does not confer malignancy, so that obviously other factors are involved. Malignancy associated with the presence of an oncogenic virus could be suppressed by fusion with a normal cell, despite continued replication of the virus in the hybrid cell. From this it can be deduced that there is not a direct relationship between expression of viral genetic information and the production of the malignant
phenotype. A feature of
tumour-cell lines is their of non-expression histoincompatible surface antigens. Cell-fusion studies have shown that such non-expression is not necessarily associated with the loss from hybrids of the chromosomes bearing the relevant genes. It may be the result of suppression of surface antigen production even though the genetic information for such production persists. However, fusion with cells showing normal expression of H-2 antigens may restore the ann-
transplantable
genicity of immunoresistant cell lines with reduced expression of H-2 antigens. The development of successful immunotherapeutic procedures may well ultimately depend on an understanding of how to overcome immunoresistance. Cell-fusion techniques promise to be valuable tools in reaching such an understanding.
MICROWAVE HAZARDS NINE months ago’ we commented on the thousandfold between the microwave exposure standards of the U.S. and Western Europe and of the U.S.S.R. and Eastern Europe. Since then Western newspapers have reported continuing exposure of U.S. diplomats in Moscow from microwave beams directed by the Soviet Union at their embassy. This, seemingly, has been going on for many years, but what made it news again was the claim that the health of diplomats and their families was being affected. Dr Kissinger was quoted as saying that the "Moscow Embassy affair ... is a matter of great delicacy that has many ramifications". This was on Feb. 12 and a week later Izvestia countered with an article suggesting that the embassy’s own radio equipment could be responsible for the high levels of microwave radiation. The State Department has belatedly elected to give quantitative information on the level of microwave exposure. Apparently this fluctuates, but as a result of talks between the two countries the level is now 2 uW cm-2 and is further reduced inside the embassy by wiremesh screens. Before the U.S. protests the level had been as high as 30 W cm-2. We therefore have the curious situation in which the U.S. appear to have been complaining on health grounds about microwave exposure levels that are a factor of 300 lower than their (and the British) exposure standard of 10 mW cm-2 and which even the more restrictive Soviet standard would permit for several hours a day. In Soviet usage210 mW cm-2is regarded as high-intensity radiation and they claim that even low-intensity microwave radiation (tens to hundreds of uW cm-2) of man "usually leads to functional disturbances in the nervous system, with a predominantly asthenic condition (clearly due to exhaustion of the central nervous system)". The symptoms of the asthenic syndrome include weakness, depression, impairment of memory and general mental function, and an inability to make decisions, and it has been suggested3 that the Soviet Union may have been trying to induce this syndrome. What seems much more likely in fact is that the Soviet Union have merely been seeking to jam American listening devices intercepting, for instance, microwave radiotelephone conversations. It is certain, however, that the Soviets are firmly convinced of the reality of the asthenic syndrome, and this affair serves to support our previous comment that the additional studies recommended by the World Health Organisation4should be put in hand without delay.
discrepancy
1 Lancet, 1975, ii, 694 2. Gordon, Z. V. Occupational Health
Aspects of R-F Electromagnetic RadiaErgonomics and Physical Environmental Factors. ILO Occupational Safety & Health Series, no. 21
tion in
3 Wade, N. Science, 1972, 177, 778. 1 Cancer Research
Campaign
53rd Annual
Report covering
1975.
4.
Hlth Phys 1975, 28, 69.
graphy. The ability
a cell to multiply progressively and kill syngeneic host, is a genetic marker of malignancy. Thus, in mice it has been possible to investigate by fusion techniques whether malignancy is a
its
host,
of
or a
dominant or a recessive trait and whether it is associated with the presence or absence of particular chromosomes or genes. A surprising but consistent finding has been that fusion of a malignant cell with a non-malignant one results in suppression of the malignant phenotype: as long as the resultant hybrid cell retains the full combined genetic complements of the two parent cells, it exhibits little or no ability to multiply in immunosuppressed syngeneic hosts. By using "nude" mice as hosts it has been shown that malignancy is similarly lost when human cancer cells are fused with normal human cells. That is the good news. The bad news is that, after a variable period of cultivation in vitro, malignancy almost invariably reappears in the hybrid-cell population. This may well be because chromosomes which neutralise malignancy are lost from hybrid cells, and the search is now on to see whether particular chromosomes are more important than others in this respect. In the mouse it is already clear that chromosome 4 carries some determinant that plays a crucial role in controlling cell growth. However, the loss of both chromosomes 4 does not confer malignancy, so that obviously other factors are involved. Malignancy associated with the presence of an oncogenic virus could be suppressed by fusion with a normal cell, despite continued replication of the virus in the hybrid cell. From this it can be deduced that there is not a direct relationship between expression of viral genetic information and the production of the malignant
phenotype. A feature of
tumour-cell lines is their of non-expression histoincompatible surface antigens. Cell-fusion studies have shown that such non-expression is not necessarily associated with the loss from hybrids of the chromosomes bearing the relevant genes. It may be the result of suppression of surface antigen production even though the genetic information for such production persists. However, fusion with cells showing normal expression of H-2 antigens may restore the ann-
transplantable
genicity of immunoresistant cell lines with reduced expression of H-2 antigens. The development of successful immunotherapeutic procedures may well ultimately depend on an understanding of how to overcome immunoresistance. Cell-fusion techniques promise to be valuable tools in reaching such an understanding.
MICROWAVE HAZARDS NINE months ago’ we commented on the thousandfold between the microwave exposure standards of the U.S. and Western Europe and of the U.S.S.R. and Eastern Europe. Since then Western newspapers have reported continuing exposure of U.S. diplomats in Moscow from microwave beams directed by the Soviet Union at their embassy. This, seemingly, has been going on for many years, but what made it news again was the claim that the health of diplomats and their families was being affected. Dr Kissinger was quoted as saying that the "Moscow Embassy affair ... is a matter of great delicacy that has many ramifications". This was on Feb. 12 and a week later Izvestia countered with an article suggesting that the embassy’s own radio equipment could be responsible for the high levels of microwave radiation. The State Department has belatedly elected to give quantitative information on the level of microwave exposure. Apparently this fluctuates, but as a result of talks between the two countries the level is now 2 uW cm-2 and is further reduced inside the embassy by wiremesh screens. Before the U.S. protests the level had been as high as 30 W cm-2. We therefore have the curious situation in which the U.S. appear to have been complaining on health grounds about microwave exposure levels that are a factor of 300 lower than their (and the British) exposure standard of 10 mW cm-2 and which even the more restrictive Soviet standard would permit for several hours a day. In Soviet usage210 mW cm-2is regarded as high-intensity radiation and they claim that even low-intensity microwave radiation (tens to hundreds of uW cm-2) of man "usually leads to functional disturbances in the nervous system, with a predominantly asthenic condition (clearly due to exhaustion of the central nervous system)". The symptoms of the asthenic syndrome include weakness, depression, impairment of memory and general mental function, and an inability to make decisions, and it has been suggested3 that the Soviet Union may have been trying to induce this syndrome. What seems much more likely in fact is that the Soviet Union have merely been seeking to jam American listening devices intercepting, for instance, microwave radiotelephone conversations. It is certain, however, that the Soviets are firmly convinced of the reality of the asthenic syndrome, and this affair serves to support our previous comment that the additional studies recommended by the World Health Organisation4should be put in hand without delay.
discrepancy
1 Lancet, 1975, ii, 694 2. Gordon, Z. V. Occupational Health
Aspects of R-F Electromagnetic RadiaErgonomics and Physical Environmental Factors. ILO Occupational Safety & Health Series, no. 21
tion in
3 Wade, N. Science, 1972, 177, 778. 1 Cancer Research
Campaign
53rd Annual
Report covering
1975.
4.
Hlth Phys 1975, 28, 69.
