More than just being of interest to basic research at universities, twin-based research can become a highly relevant part of translational medicine with many benefits to biopharmaceutical R&D. Recent advancements in methodology allow twin studies to play their part in target validation by defining measurements that best reflect genetic influences on health and the detection of underlying genes as well. Furthermore, twin studies can prove small effects in prevention or treatment with nutraceuticals by providing perfectly matched controls. Improved understanding of disease-related physiology can only have beneficial effects on the development of therapeutics. Accordingly, acquiring a deeper knowledge of pathophysiology should become an integrated early part of drug research, as PriceWaterhouseCoopers state in their recent report Pharma2020: The vision.

As genes are involved in pathophysiology as well as in the response of organisms to drugs, genomics is a promising field for drug development. Most of today’s genetics weaponry is used on animal models as remote as fruit flies or zebra fish. If we acknowledge that many findings in mice, for example, are specific to only one strain, why should we be confident that such findings have any bearing on man? In today’s sequential development from target ‘validation’ to clinical trials, it is not before Phase II or III that we obtain confidence in mechanism and safety for target as well as substance in humans. Wouldn’t it be good to get some of that information much earlier, and could the old twin study method help us in achieving this?

CLASSICAL TWIN STUDIES

We study genetics because we want to understand why some of us get a disease and others don’t, why only some patients respond to a drug, or why some have unwanted side effects. Overall we wish to understand human variability. Heritability is an estimate of the fraction of this variation that is due to genetic variability. Simply stated, if LDL cholesterol has an heritability of around 70 per cent, more than half of the differences between people are due to the fact that they carry different versions of genes relevant for that trait and only 30 per cent are attributable to environmental or behavioural differences. This heritability does not of course say anything for a given patient.

Monozygotic twins (MZ) inherit identical genetic material, as they derive from a single fertilised egg. In contrast, dizygotic twins (DZ) develop from two eggs fertilised independently, so they share only half of their genetic material. The systematic analysis of similarities between MZ and DZ twins to determine heritability was introduced by Siemens, a German dermatologist, in 1924. Siemens correlated mole counts in one twin with mole counts in the co-twin and contrasted this correlation between MZ and DZ twin pairs. The correlation for mole count in MZ twins was 0.4. In DZ twins, the correlation was only 0.2. These results indicate the importance of genetic factors for variation in mole count. The larger genetic resemblance in MZ twins is associated with their larger resemblance for the phenotype under study.