Genetic screening and democracy: lessons from debating genetic screening criteria in the Netherlands

Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor’s office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When prenatal screening for all pregnant women became conceivable, the potential increase in scale made social and ethical concerns relevant for the whole of society. Whereas genetic testing in clinical genetic practice was widely accepted, prenatal screening at a population level met with unease. Concerns were raised regarding social pressure to screen: the sum of individual choice might result in a ‘collective eugenics’. The government’s involvement also raised suspicion: actively offering screening evoked associations with eugenic population policies from the first half of the 20th century. By reconstructing elements of policy and public debate on prenatal screening in the Netherlands from the past 30 years, this article discusses how the government has gradually changed its role in balancing the interest of the individual and the collective on genetic reproductive issues. Against a background of increasing knowledge about and demand for prenatal screening among the population, governmental policy changed from focusing on protection by banning screening toward facilitating screening in a careful and ethically sound way by providing adequate information, decision aids and quality assessment instruments. In the meanwhile, invigorating democracy in public debate may entail discussing concepts of ‘the good life’ in relation to living with or without impairments and dealing with genetic information about oneself or one’s offspring

Reduction in glomerular heparan sulfate correlates with complement deposition and albuminuria in active heymann nephritis

In a time-study of active Heymann nephritis, the expression of agrin, the main heparan sulfate proteoglycan in the glomerular basement membrane, was analyzed in relation to deposition of IgG and complement in the glomerular capillary wall and the development of albuminuria. Binding of IgG autoantibodies to the glomerular capillary wall could be detected from 2, wk onward, followed by activation of complement after 6 wk. progressive albuminuria developed from 6 wk onward to a level of 274 +/- 68 mg/18 h at week 12. The staining intensity for the agrin core protein decreased slightly, and the staining intensity for the heparan sulfate stubs that were still attached to the core protein after heparitinase digestion remained normal. From week 6 onward, however, a progressive decrease was seen in the staining of two monoclonal antibodies (mAb) directed against different epitopes on the heparan sulfate polysaccharide side chain of agrin (to 35 and 30% of the control level, respectively, at week 12, both mAb P = 0.016). Moreover, albuminuria was inversely correlated with heparan sulfate staining as revealed by these antibodies (r(s) = -0.82 and r(s) = -0.75, respectively, both mAb P <0.0001). This decrease in heparan sulfate staining was due to a progressive reduction of glomerular heparan sulfate content to 46 and 32% of control level at week 10 and week 12 of the disease, respectively, as measured biochemically. It is speculated that the observed decrease in glomerular heparan sulfate in active Heymann nephritis is due to complement-mediated cleavage of heparan sulfate, resulting in an increased permeability of the glomerular basement membrane to macromolecules