Article underestimates challenges of marrying chemical design and toxicology.

Posted by Audrey Moores at Mar 31, 2011 06:00 AM | Permalink

An article entitled “Better by Design“ and published in Science News on March 26th describes the recent progress made by chemists towards the design of safer chemicals. The article features a computer-based study by a group of Yale chemists who demonstrated that toxicity of a molecule is strongly correlated with a small number of chemical and physical properties. This research study suggests that we soon will be able to quickly assess the potential toxic risk associated with a molecule – all from its chemical formula. The hope is to build a predictive tool to design inherently safer chemicals from the moment chemists first start to think about them.

The Science News article does a good job of describing the importance of designing chemicals for everyday use that will not present environmental health problems. It also explains in an approachable fashion, some of the ways molecules can interfere with the body. However, two important aspects of the challenge chemical design represents for chemists may be lost.

First, understanding the potency of a molecule at the design level is achievable, as some of the works highlighted in the article suggest. However it is still difficult and not yet entirely possible for all molecules, especially brand new ones. The chemistry community still regards it as an immense challenge to design molecules possessing biological activity – for drug discovery for instance. It is equally complex to predict a desired absence of biological potency. It goes far beyond simply looking at a molecule’s drawing. It requires specialized computer software and databases, as well as lab and animal tests.

Why? Because a compound may be harmful for many combined reasons. The article accurately lists some of them. A compound may interact with the body, for instance, through binding with a specific protein. When it does so, it may trigger undesired body responses, such as an earlier puberty in the case of BPA. This interaction is like a key-lock interaction, where the global shape of the key and the position of each indentation count. So that when chemists design a new molecule for making a plastic wrap, for instance, they should verify that it is not also a key that unlocks an unwanted protein reaction. This task is gigantic, despite what the article suggests. Only a computer program could achieve it reliably.

Second, chemists have by training a limited knowledge of molecular toxicity. There is a tendency for scientists to specialize, and chemists have followed that path. For example, biology is hardly taught in any chemistry curriculum – which mainly concentrates on chemical reactions with a target product in mind. Students are not taught where starting materials are coming from and where molecules go after use. A true paradigm shift is needed to ensure the next generation of chemists can embrace the complexity of the problem of molecule design. The article completely skipped this issue.

In general, the article would be more powerful, and maybe more approachable, if it had provided a vision of how in the future chemists could use tools to design molecules. When chemists first think about a molecule and draw its structure they could consult the program to get an estimation of how potent it can be. With this information, chemists could refrain from even making a molecule that could prove harmful in the long run.

While the article covers an important development in chemistry, it would be better if the reporter had put this work into perspective. Using computers to predict biological activity is a good step, but is just one of many methods developed.