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  • Writer's pictureKirk Hartley

In Silico and Bio-CAD – Terms For Future Daubert Hearings

(Image courtesy of Cray Supercomputing – more than 270 Cray supercomputers are now being deployed in the Blue Waters Project ongoing at the University of Illinois Center for Supercomputing Applications – the resulting supercomputer will be one of the world’s fastest, and will be used for scientific research.)


Two new terms for the lexicon: In silico testing and bio-CAD design.

In vivo testing of a creature measures and observes conditions within a living creatures. In vitro testing of a creature measures and observes part of a creature within the glass of dishes and tubes. Now, in silico testing has matured to the point that an entire, existing creature has been measured, modeled and accurately operated inside a computer using algorithims and data built from over 900 traditional studies. Does the model work in ways that conform to real world observations ? Yes. The research findings were published in Cell in July – the outcome also is explained in a press release from Stanford and a ScienceDaily summary is here.

The results ? Excellent. The abstract for the paper states the results in the understated style of science:


An entire organism is modeled in terms of its molecular components

Complex phenotypes can be modeled by integrating cell processes into a single model

Unobserved cellular behaviors are predicted by model of M. genitalium

New biological processes and parameters are predicted by model of M. genitalium


Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery." (underling added)

The press release is not understated:

"In a breakthrough effort for computational biology, the world’s first complete computer model of an organism has been completed, Stanford researchers reported last week in the journal Cell.

A team led by Markus Covert, assistant professor of bioengineering, used data from more than 900 scientific papers to account for every molecular interaction that takes place in the life cycle of Mycoplasma genitalium, the world’s smallest free-living bacterium.

By encompassing the entirety of an organism in silico, the paper fulfills a longstanding goal for the field. Not only does the model allow researchers to address questions that aren’t practical to examine otherwise, it represents a stepping-stone toward the use of computer-aided design in bioengineering and medicine.

"This achievement demonstrates a transforming approach to answering questions about fundamental biological processes," said James M. Anderson, director of the National Institutes of Health Division of Program Coordination, Planning and Strategic Initiatives. "Comprehensive computer models of entire cells have the potential to advance our understanding of cellular function and, ultimately, to inform new approaches for the diagnosis and treatment of disease."

The research was partially funded by an NIH Director’s Pioneer Award from the National Institutes of Health Common Fund."

Relevance for lawyers ? Sooner than we may imagine, it seems there will be Daubert hearings involving findings generated from all three types of research – in vivo, in vitro and in silico.

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