Hepatolenticular Degeneration

Developmental Toxicity of Aluminium and other Metals: Areas Unexplored

Reproduction and developmental damage has irreversible consequences compared to other body functions and may have adverse effects throughout life. In some circumstances, the damage passes from generation to generation. Many environmental agents contribute to developmental toxicities such as toxic metals, insecticides or pesticides, commercial or industrial pollutants, and air pollutants. Increased urbanization and industrialization have led to the accumulation of toxic metals in the environment. Widespread use of heavy metals in different fields such as agriculture, domestic, medical, industrial, and technological applications have resulted in increased exposure of heavy metals to the human population. Environmental exposure to heavy metals is extensively linked to toxic effects on mammalian embryos. Metals such as lead, cadmium, mercury and arsenic are known developmental toxicants that intensely affect fetal and embryonic development and cause certain malformations in developing embryo even at low concentrations. Other metals such as uranium, cobalt, lithium, Aluminium, manganese, and copper are also reported to induce developmental consequences, including neurobehavioral abnormalities, neural tube defects, fetal growth retardation, skeletal deformation, preterm or delayed birth, and still birth or postnatal death. Heavy metal developmental toxicity depends on different factors, including dose, duration, and route of exposure. Hence, heavy metals are known to be toxic to fetal and embryonic tissues and can produce serious teratogenicity in mammals; however, not much attention has been given to this topic. This chapter, therefore, summarizes the developmental toxicity of heavy metals on the mammalian system and their teratogenic mechanism in growing embryos.

Maintenance of Body Composition

The Birth of an Idea

The story began in 1912, but my involvement only began in 1951. In 1912 Dr Kinnier Wilson, working at the National Hospital for Nervous Diseases in London described a new illness affecting youngsters, the principal symptoms being loss of control of movement and contractures of the limbs. This was always associated with scarring of the liver. All these patients died with in a few months of diagnosis.

Dr Wilson's life long ambition was to find a cure for this disease which became known as Wilson's disease, technically hepatolenticular degeneration.. In 1948 Professor John Cumings, working at the same hospital, showed that patients dying of Wilson's disease all had large abnormal amounts of copper deposited in the brain and in the liver. He suggested that the new metal binding drug, British Antilewisite (BAL) might be used to arrest the course of the disease.

In 1951, working in the Metabolic Unit at University College Hospital in London I discovered that patients treated with the antibiotic penicillin excreted in their urine, a breakdown product of the drug, penicillamine. Later, when studying as a Fulbright Fellow in the Liver Unit at the Boston City Hospital, I saw a patient with Wilson's disease being treated, with little, benefit, with BAL. I suggested that penicillamine had the right structural formula to bind copper and promote its excretion and this would be a more effective treatment than BAL and, could be given my mouth and not by painful injection, it would be easier to give over a lifetime.