Skip to main content

Personalized Medicine Versus Rats

According to the press release titled Native American ancestry linked to greater risk of relapse in young leukemia patients

Research from St. Jude and the Children’s Oncology Group ties the genetic variation characteristic of Native American ancestry to higher odds cancer will return and highlights a strategy to ease the racial disparities in survival. The first genome-wide study to demonstrate an inherited genetic basis for racial and ethnic disparities in cancer survival linked Native American ancestry with an increased risk of relapse in young leukemia patients . . . This study identified a possible mechanism linking ancestry and relapse. Hispanic patients, who have a high percentage of Native American ancestry, were more likely than other patients to carry a version of the PDE4B gene that was also strongly associated with relapse. The PDE4B variants were also linked with reduced sensitivity to glucocorticoids, medications that play a key role in ALL treatment. "This is just one example of how ancestry could affect relapse risk," said the study's senior author Mary Relling, Pharm.D., St. Jude Pharmaceutical Sciences chair. "It is likely that many other genes are involved."

The article appears in Nature Genetics.

Contrast the above with the following from a news article titled “Rats Redux” that appeared in Science:

Today, most lab cages house mice, but the tenant of choice used to be rats. The reason: Rats are more like us. The human heart, for example, beats about 70 times a minute; a rat's heart, 300 times; a mouse's, 700. Electrical signal patterns in rat and human hearts are also similar. Rats, being more intelligent than mice, might also be better models of human neural diseases such as Alzheimer’s and Parkinson's. And rats are bigger and easier to handle for lab work . . . In August, another group announced a tweak that produced “knockout rats” by the same genetic trick used for knockout mice . . . As a result of such techniques, knockout and genetically modified rats may soon displace their smaller cousins in lab cages around the world. (NewsFocus 2010)

So, while scientists are exploring what causes different ethnic groups to respond differently to cancer treatments, the animal model industry is using rats to model humans in general because the rats have superficial similarities like a heart rate that similar to humans. This would be comical were it not for the fact that people are dying because of nonsense like this.

As I have said many times, industry knows already this. Stephen Minger, Global Director of R&D, Cell Technologies GE:

If one listens to the individuals who are hands-on in the laboratory, working with these cell lines on a daily basis—the biologists, assay developers, screening groups, toxicologists, and compound profilers—it becomes abundantly clear that they need better, more robust and more representative tools. The R&D groups carrying out liver toxicity assays need to perform those assays in human liver cells, and those doing cardiotoxicity studies could produce higher quality and more reliable data if they were able to work with human cardiomyocytes. Similarly, HTS groups cannot assume that the results obtained from an assay run in an animal cell would be the same if the assay were performed in a human cell line. The continued use of these less-than-ideal models as the backdrop for experiments that yield data on which critical decisions are made about which compounds to take forward into drug development sets the stage for failure.

Not only are the cell lines currently in use poor models of human primary cells, moreover, they are far from representative of the huge variability that exists across human populations—differences that can affect how drugs are absorbed, metabolised and excreted, whether they reach their target and how that impacts critical signaling cascades and downstream biochemical pathway, and whether they participate in other, unintended interactions that result in undesirable and sometimes life-threatening side-effects. As the genomic variability between ethnic, racial, and geographically distinct groups are revealed and understood, they will yield the genomic signposts, protein biomarkers and metabolic signatures that will enable truly predictive toxicology, adaptive clinical trial design and repurposing of failed yet promising drug candidates that may be exquisitely effective in one disease subpopulation yet ineffective in other groups of patients with the same disease. It is well-accepted that many, if not most drugs only produce the desired therapeutic effect in a percentage of the patients to whom they are given. Furthermore, some of those nonresponders will suffer negative consequences from taking a drug that offers them little or no therapeutic benefit. (Minger 2010)


Minger, Stephen. 2010. The availability of standardized human embryonic stem cells populations for drug screening will change the course of drug discovery and preclinical drug testing. Drug Discovery World (Summer supplment):8-9.

NewsFocus. 2010. The Runners-Up. Science 330 (6011):1605-1607.


Popular Video