Neuromag November 2017 | Page 26

ance regardless of the medications given. This work caught the field by surprise and brought a long-held be- lief into question, namely whether one type of mouse is representative of all the others (Fig. 4). Jeff Mogil’s com- ment about his own study speaks volumes, “Frankly, we just published a paper that scared the hell out of me.” In the field of pain research, researchers need to be cautious when generaliz- ing the results from one mouse strain to another, let alone to humans. This same group of researchers later dem- onstrated that when male scientists worked with mice or rats a reduced pain response was observed. Howev- er, this effect was not observed when females handled the rodents. Most in- terestingly, the reduced pain response occurred again when females wore male T-shirts revealing that the sex of an experimenter can influence pain responses in rodents [5]. It appears scientific truth is not only obscured by different types of mice, but also by the scientists who interact with them. Figure 5. Four laboratory mouse strains Source: Stanton Short / Jennifer L. Torrance Jax. org The days of debating nature versus nurture are behind us. It is both the interaction of genes and the external environment that produce a given out- come. But what about our internal en- vironment? A recent paper highlighted another aspect of animal research, namely the sterility of it all. Laboratory mice are housed in pristinely clean environments, especially when com- pared to their wild counterparts. Re- cently, there has been growing inter- est in the microbiome and the role that gut bacteria play in health and disease. In a study investigating exactly this, researchers colonized laboratory mice with gut bacteria from that of wild mice and subsequently demonstrated that laboratory mice harboring the ‘wild bacteria’ were more resistant to viral infection and tumorigenesis mod- els [6]. To demonstrate the impact of Figure 6. Amyloid plaques are commonly found in Alzheimer’s patient neural tissue. Source; BrightFocus Foundation this experiment, let’s talk numbers. Of the normal laboratory mice, 17% were alive 18 days after intranasal infection with the influenza virus, while 92% of the bacterial carrying lab mice were still squeaking around! Clearly, our animal models are kept under artifi- cial conditions that appear to have a strong influence on disease suscepti- bility, at least in our rodent friends. Neurology is another field where treatments have not much improved despite the multimillions of dollars, euros, pounds, and other currencies invested in this research area. Alzhei- mer’s disease has frustrated many re- searchers as it still lacks any treatment despite many transgenic mouse mod- els developed to study this disease (although one could argue that a true mouse model of Alzheimer’s does not exist). The most accepted explanation of Alzheimer’s disease is the buildup of a protein in brain cells known as amyloid beta (Fig. 6). Unfortunately, the majority of attempted Alzheimer’s treatments have failed and none have made it to market. Currently, there is not an approved treatment that works on amyloid beta, but there are Phase III clinical trials (the final phase) in pro- cess to test an antibody treatment that reduces the amount of amyloid beta. This study should be completed by 2022. Mice do allow for better science and have helped advance our knowledge of biological processes. In the end though, mice are not humans and their utility as guideposts along the road to developing new medications for humans can be misleading. Our Figure 7. Scientists need to scrutinize all of their tools to conduct the best science possible. Source: labdepotinc.com; shutterstock.com; Jax.org 26 | NEUROMAG | November 2017