Anti bodies

Anti bodies

EVERY year, from August 1-7 during the World Breastfeeding Week, there is considerable hype about the usefulness of breast milk over bottle milk. But what if breast milk is full of pesticides -- as it is in Delhi -- capable of suppressing infants' immune systems?

Scientists have mainly focussed on pesticides as a cause for cancer and neurological disorders. Latest research, several of which have been conducted on animals (see box: Ominous indicators), indicates that these are also highly immunosuppressive, raising serious questions about their role in public health in countries like India; scientists have begun worrying about the impact of chronic exposure to pesticides on human beings. A popular review of these studies published recently by the World Resources Institute in Washington dc -- Pesticides and the Immune System: The Public Health Risks by Robert Repetto and Sanjay S Baliga -- raises some critical issues that should shake up health and environmental officials in developing countries, especially India where human exposure to pesticides is reported to be one of the highest in the world.

Developing nations: sitting ducks Why are people in developing nations most endangered by pesticides? There are diverse reasons for this:
•Poor sanitation and water supply;
•Exposure to communicable diseases like respiratory and gastrointestinal infections;
•younger populations, with many infants and children, whose immune systems are still developing;
•Large proportion of the population suffering from malnutrition, which weakens the immune system.

Infections remain a major cause of morbidity and mortality in developing countries. Pesticide-induced immunosuppression could seriously increase this already high burden of ill-health. In addition, the chances of exposure to pesticides is also higher in the developing world:
•where a large fraction of the population works on farms and the most exposed are agricultural labourers and small farmers;
•where pesticides which have been banned or restricted in the industrialised countries, are still in use;
•where pesticide use is growing more rapidly than in the industrialised world; and,
•where pesticide regulations are weak and farmers lack the training and equipment to handle pesticides.

Baliga and Repetto point out that growth in the pesticides market in Latin America and Asia (excluding Japan) between 1987 and 1993, in value terms, was more than twice the world average. Increasing intensification and commercialisation of agriculture in these regions are bound to lead to a greater demand for these poisons. And, if in the future, industrialised countries were forced in fora like the World Trade Organization (WTO) to cut agricultural subsidies, a lot of the world's agricultural production could move to developing nations.

Even urban populations in developing countries are not spared the health impact of pesticides, exposed as they are chronically to these toxins in the form of residues in food, dairy products and drinking water. This is especially true of places where government food standards are poor and regulatory systems are corrupt, weak or non-existent. Data on exposure levels in a country like India are frightening. Surveys in Delhi have revealed high accumulation of pesticides and ddt in the body fat of human beings and high levels of similar poisons in mothers' milk (Down To Earth, Vol 5, No 13).

What is most disturbing about these findings is that the consequences of pesticide-induced immunosuppression may remain totally undetected because people would, on the face of it, die of measles, pneumonia or stomach disorders -- which are otherwise diseases from which they could have easily recovered if they had an active immune system.

The proof of the matter
Sceptics may well ask how good is the scientific evidence on pesticide-induced immunosuppression. In toxicological research, experimental animal studies are used extensively because chemicals that are toxic to humans are usually toxic to other mammalian species as well. Moreover, it has been found that all mammalian, avian and piscatory immune systems are structurally similar. The us national research council's committee on immunotoxicology has accepted the fact that animals can be used to assess immune dysfunction objectively.

But critics argue that as animal models are fed high doses of toxins and their sample is small, data from lab animals is unreliable for extrapolation to humans who receive much smaller, chronic doses. On the other hand, animal experiments can underestimate the effect of toxins on human populations because lab animals are usually healthy young male adults fed on a nutritious diet, whereas a normal human population also consists of sick and unwell people with already compromised immune systems. Various experts, however, point out that while the arguments of these critics of animal models may be correct, the differences in exposure do not mean that humans are not at risk.

Animal experiments -- including researches done in India, China and Brazil -- have demonstrated that a variety of pesticides, including widely used organochlorines, organophosphates, carbamates and metal-based pesticides, induce immunotoxicity and thus reduce the resistance of the host animal to infections. Besides pesticides themselves, many pesticide solvents, inert ingredients and contaminants cause measurable immunosuppression in several species.

The us government's National Institute of Environmental Health Sciences has recommended that toxicologists use a two-tier battery of tests (see table: Zeroing in) to assess the potential health consequences in humans. This is because, due to the complexity of the immune system, changes in a single immunological parameter may not be adequate.

The Soviet state: basket case
The sharpest information on the effect of pesticides on human beings as yet has come from studies in the former Soviet Union where very high levels of pesticides were used in several agricultural areas (Down To Earth, Vol 4, No 12). One of the worst affected areas was Uzbekistan where cotton -- a crop which calls for heavy use of pesticides -- is grown intensively. Scientists have reported that exposed populations in cotton-growing areas suffered markedly higher rates of respiratory, gastrointestinal and acute inflammatory kidney infections than did residents of other regions where pesticide use was lower but other conditions were similar. For instance, in non-exposed urban Samarkand, the incidence of infectious and inflammatory kidney diseases was only 1.6 per cent whereas in pesticide application zones, residents had an incidence of 7.9 per cent. Among people living near pesticide storage facilities, this rate went up to 12.5 per cent. Another study reported that after four months of aerial spraying of pesticides, the incidence of respiratory and gastrointestinal disorders in people living near the sprayed fields went up by 51 per cent and 28 per cent respectively. Yet another study found a close correlation between pesticide use and gastrointestinal disorders amongst children living near cotton fields.

Pesticide exposure has also been found to exacerbate pre-existing infections like tuberculosis. This could be owing to pesticide-induced immunosuppression effects. Repetto and Baliga point out several studies by scientists from the former Soviet Union that show that t-cell counts and functions were suppressed after pesticide exposure (see box: Autoimmunity). For instance, in the cotton growing areas of Karakalpakstan (in Uzbekistan), people had reduced t-cell counts as compared to control populations; also, they suffered from higher rates of infectious diseases compared to the general population. According to other Soviet studies, children seem to be particularly susceptible to the suppressive effects of pesticides on t-cells.

Inuits: studies into a tragedy
However, the retrospective nature of the Soviet studies -- in them, populations long exposed to pesticides and now diseased have been studied -- creates several problems. For instance, former Soviet Union researchers could not test the immune status of ill individuals because the illness itself would have influenced their immune status. So they had to study healthy individuals exposed to pesticides to get an understanding of what impact pesticides were having on the immunological status of local populations. The results of such tests may underestimate the impact of pesticides on the general population.

Repetto and Baliga, therefore, point out the significance of the only prospective study that is being done in the world -- on the Inuits (Eskimos) of Arctic Canada. Studies have shown that the Inuits exhibit rates of death and illness worse than some of the poorest countries in the world. Studies carried out in the '80s showed that Inuit children in Hudson's Bay were 30 times more likely to suffer from meningitis than us children. Chronic otitis (infection of the inner ear) was endemic among Inuit children in northern Quebec, resulting in high rates of hearing impairments. Around the same time, studies comparing the immunological status of healthy Inuit children with that of healthy children from southern Canada showed "significant differences in... immunity... in both normal and recurrently ill Inuit infants."

It is now widely believed by scientists that the pesticides used in other parts of the world get transported to Arctic ecosystems through atmospheric winds, rivers and ocean currents and accumulate there in human and animal organisms (Down To Earth, Vol 4, No 10). The Inuits mainly depend on fish and the meat of bears and marine mammals like the seal and walrus for their diet, all of which accumulate toxins like pesticides and industrial chemicals. In the early '90s, pcbs, dde (an extremely hazardous metabolite of ddt) and mirex (an organochlorine pesticide) were found in high concentrations in Inuit breast milk. As these compounds can cross the placental barrier in the mother's womb, scientists became concerned about the health effects on Inuit children.

A prospective cohort study has thus been set into place to monitor a group of Inuit infants born in 1989-90. The study has already found that breast-fed babies that had accumulated higher doses of organochlorines were significantly more likely to suffer from acute otitis. Bottle-fed babies had better immune responses; those of breast-fed babies were correlated with the duration of breast-feeding and organochlorine levels in breast milk. In addition, Inuit babies were hard to vaccinate, as many failed to generate a primary antibody response to usual vaccines. Scientists are, therefore, coming to the conclusion that increased infection rates in Inuit children are related to the suppression of host resistance.

Pesticides and cancer
Studies in industrialised nations have reported increased risk of certain cancers associated with immune suppression. Most tumours associated with immunosuppression have been lymphomas and leukaemias. Oncologists have found that people who have received a kidney transplant and are on regular immunosuppressive drugs are at a disproportionately high risk of contracting soft tissue sarcomas, melanomas and squamous carcinomas of skin and lip; those with bone marrow transplants have an elevated risk of brain and skin cancers. Patients who have been treated with the immunosuppressive drug, Cyclosporin a, have a 100-fold risk of lymphatic tumours .

Surveys in us, Canada, Europe, Australia, China and the Philippines have found that male farmers, who as an occupational group experience lower risks of overall mortality, heart disease and cancers, experience elevated risk of many of the same cancers that immune-deficient patients develop. According to an assessment of these surveys, farmers have significantly higher risks for Hodgkin's disease, melanoma, multiple myeloma, leukaemia (all are cancers of the immune system), and cancers of the lip, stomach and prostate. Other cancers with elevated risks were non-Hodgkin's lymphoma, and cancers of the brain and connective tissue. Scientists at the National Cancer Institute, us have concluded that exposure to pesticides are associated with cancers of the lymphatic and haematopoietic system and brain. Studies in several countries have linked phenoxyacetic acid herbicides to non-Hodgkin's lymphoma (Down To Earth, Vol 5, No 13).

Pesticides enhance the risks of cancer in two ways:
•the direct way -- by acting as carcinogens themselves; and,
•the indirect way -- by suppressing the immune system which has the ability to destroy the process of tumour creation in the body.

A review of laboratory studies on animals concludes that pesticides are capable of altering the "functions of the immune system which may otherwise partially or completely abrogate the processes of tumorigenesis". Other scientists conclude that "pesticides could affect a variety of cancers through an immunological mechanism."

A strategy for the developing world
There is growing concern in industrialised nations about the continuing use of pesticides -- especially organochlorines like ddt -- by many developing countries which have yet to ban them. Recent evidence also points to the fact that rivers, seas and winds carry them to polar regions where they affect local tribal populations and also enter food chains of people in Europe and North America because of bioaccumulation in fish. There is, therefore, wide recognition of the need for a new international treaty to force all countries to phase out the use of these toxic substances. The un Environment Programme is already involved in this debate. Repetto and Baliga also argue that the World Health Organization should develop an international research programme to monitor the immunosuppressive effects of pesticides.

But as the issue is of significant health importance to people in developing countries themselves, it is important that their policy-makers develop their own strategies to deal with the problem. To argue that we must use pesticides because we have to feed a growing population is like saying we must find ways of feeding you properly even if it means poisoning you to death. India's current agricultural strategy, for instance, is precisely of this ilk. A two-pronged strategy -- with short-term and long-term components -- is what is required.

The short-term strategy can concentrate on moving towards greater regulation of pesticide use, including implementation of safe food and drinking water standards, safer use of pesticides and use of safer pesticides. This would mean
•better and more elaborate testing of pesticides for their immunotoxicity
•a periodic review of all registered pesticides, based on updated scientific knowledge
•a transparent process for both review and registration of pesticides
•a periodic report from environmental officials on the health and environmental hazards posed by use of pesticides with regularly updated data from the field and from scientific research
•production programmes and regulations to switch to safer pesticides
•programmes for protection of agricultural workers and
•programmes for protection of the general population from chronic exposure to pesticides

The major role here would have to be played by environmental officials, by agricultural officials who regulate and promote the use of pesticides and by state and municipal personnel who are responsible for implementing food quality standards and supply of clean drinking water.

The long-term strategy should, of course, aim to phase out use of pesticides. This would involve
•developing research programmes for non-pesticide-based agriculture
•promotion of integrated pest management and
•development of organic farming and markets for organic produce
The key role here would have to be played by agricultural researchers and policy-makers working together with farmers and farmers' organisations.

It is a task that can be achieved, but will require politicians who really care for those who elect them. Or, a dynamic civil society which does not let them rest easy.

--- This article is based on Robert Repetto and Sanjay Baliga's recent publication called Pesticides and the Immune System: The Public Health Risks, published by the World Resources Institute, US

Research without change

It is indeed strange that public consciousness of the problem in India is almost non-existent. I am reminded of Omar Khayyam's Rubaiyyat -- "Dust into dust and under dust to lie; sans wine, sans singer and sans end" --which, for Indian scientists, can probably be paraphrased into "From journal to journal and under journals to lie; sans purpose, sans change and sans end". But nonetheless, their findings are worthy of attention.

•A 1991 study in Delhi found DDT and HCH residues in urban water, soil and fauna. Even though DDT use had been banned for agricultural uses earlier, human breast milk samples showed DDT and HCH levels had not declined substantially over the past decade, and were comparable to levels found in Punjab, an area of intensive farming (A Nair and M K K Pillai, 1992, 'Trends in Ambient Levels of DDT and HCH Residues in Humans and the Environment of Delhi, India', The Science of the Total Environment, 121:145-157).

•Pesticides of many chemical classes are immunosuppressive in most laboratory animals (R P Sharma, 1978, 'Environmental Immunotoxicity: An Overview', in I M Asher (ed) Inadvertent Modification of the Immune Response: The Effects of Foods, Drugs and Environmental Contaminants -- Proceedings of the Fourth FDA Science Symposium, US Food and Drug Administration, Maryland; R P Sharma and R S Tomar, 1992, 'Immunotoxicology of Anticholinesterase Agents', in B Ballantyne and T C Marrs, Clinical and Experimental Toxicology of Organophosphates and Carbamates, Butterworth-Heinemann Ltd, Oxford).

•Pesticides may render "people more prone to new or existing diseases by causing immunosuppression" (A Bhatia and J Kaur, 1993, 'Recent Advances in Immunomodulatory Effects of Some Chemical Pollutants -- A Review', International Journal of Environmental Studies, 45: 61-70).

•Among Indian cotton field workers, pesticide exposure has been found to be associated with chromosome damage (D S Rupa, P P Reddy and O S Reddi, 1991, 'Clastogenic Effect of Pesticides in Peripheral Lymphocytes of Cotton-Field Workers', Mutation Research, 261:177-180); other studies have also shown similar effects (D S Rupa, P Rita, P P Reddy and O S Reddi, 1988, 'Screening of Chromosomal Aberrations and Sister Chromatid Exchanges in Peripheral Lymphocytes of Vegetable Garden Workers', Human Toxicology, 7: 333-336; P Rita, P P Reddy and S V Reddy, 1987, 'Monitoring of Workers Occupationally Exposed to Pesticides in Grape Gardens of Andhra Pradesh', Environment Research, 44: 1-5; R C Sobti, A Krishan and C D Pffafenberger, 1982, 'Cytokinetic and Cytogenetic Effects of Some Agricultural Chemicals on Human Lymphoid Cells in Vitro: Organophosphates', Mutation Research, 102: 89-102).

•Chronic bronchitis, asthmas and pneumonitis have been associated with exposure to agricultural and industrial chemicals with high volatility and small mass, like pesticides (S K Rastogi, B N Gupta, T Husain, N Mathur and N Garg, 1989, 'Study of Respiratory Impairments among Pesticide Sprayers in Mango Plantations', American Journal of Industrial Medicine, 16: 59-538).

•Among Indian factory workers chronically exposed to several pesticides, blood lymphocyte levels decreased by as much as 66 per cent in a maximally exposed group. But when a group was asked to take time off from work, immune parameters returned to normal within three months. The study concluded that the pesticide "exposure induced deviations...were time related and cessation of exposure or its withdrawal resulted in achieving normal levels" (S A Khan and S A Ali, 1993, 'Assessment of Certain Haemotological Responses of Factory Workers Exposed to Pesticides', Environmental Contamination and Toxicology, 51: 740-747).

•Several Indian studies show that malnutrition affects the immune system. Protein-energy malnutrition atrophies the thymus (an immune system organ), reduces the number of mature lymphocytes (especially helper T-cells) and impairs cell-mediated immune responses (R K Chandra, 1992, 'Protein-Energy Malnutrition and Immunological Response', Journal of Nutrition,122:597-600); Vitamin-B malnutrition reduces antibody production and immune surveillance by natural killer cells (A D Kulkarni, F B Rudolph and C T VanBuren, 1994, 'Nucleotide Nutrition Dependent Immunosurveillance: Natural Killer Cell Cytotoxicity, Gamma Interferon Production and Polynuclear Cell Function', in R A Forse, S J Bell, G L Blackburn and L G Kaebbash (ed) Diet, Nutrition and Immunity, CRC Press Inc, Boca Raton, Florida); phagocytic mechanisms are suppressed in anaemic patients because enzymatic reactions that destroy foreign organisms require iron and, as a result, anaemia increases infectious morbidity and mortality (P Bhaskaram, 1988, 'Immunology of Iron-Deficient Subjects', in R K Chandra (ed) Nutrition and Immunology, Alan R Liss Inc., New York)); and, zinc deficiencies also lead to reductions in circulating T-cells, delayed hypersensitivity reactions and reduced enzymatic activity in respiratory burst, a process by which phagocytic cells destroy foreign bacteria in the respiratory passages (A S Prasad, 1993, 'Acquired Zinc Deficiency and Immune Dysfunction in Sickle Cell Anaemia', S Cunningham-Rundles (ed) Nutrient Modulation of the Immune Response, Marcel Dekker Inc., New York).