Category Archives: Environment & The Human Body

Understanding Biology through Computational Models

The Human body is the most complex machinery known to man. From the genetic material to the tissues and organs, every part of the machine works in absolute synergy on a daily basis.

However, the body also faces daily assaults from a host of chemicals and agents in the environment, be it at home, in school, or in the workplace. Some of these chemicals are in our food or drugs that we take, and some others get in our body inadvertently through the air we breathe, or the things we touch. Sometimes, these chemicals cause unwanted outcomes in our bodies – either short terms or long term. Even the drugs we take or the food we eat for beneficial effects might have unwanted reactions which might affect our health.

Biological and health research has come a long way in giving us many of the answers we seek regarding deleterious health effects. However, with new chemicals, drugs, and cosmetics entering the market every day, the problem of understanding human health risks is a constant one, which changes with every new challenge. Computational and mathematical models help in leveraging existing biological knowledge using fast computers and efficient algorithms to produce novel insights into these complicated problems.

Toxicokinetic Modeling

PBPK Modeling

PBPK-CCLPhysiologically Based Pharmacokinetic (PBPK) Modeling is being applied more and more to provide whole-body level insights to chemical absorption-distribution-metabolism-extraction (ADME) within the body. PBPK models (often referred to as PBTK models when applied to toxic chemicals) are widely used in the pharmaceutical industry for Model Based Drug Development as well as for chemical risk analysis by regulatory agencies like the EPA and the FDA.

Historically, PBPK models were first developed by chemical engineers who saw the human body as analogous to the network of pipes and reactors which they were accustomed to.  PBPK models bring together knowledge of biology, chemistry, mathematics to often produce models of immense complexity.

Specific projects utilizing PBPK models:

 

Figure reference: Xue et al., Probabilistic Modeling of Dietary Arsenic Exposure and Dose and Evaluation with 2003-2004 NHANES Data, Environ. Health. Perspect. (2009); 118, 345-350.