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About a week ago, the Internet went wild with the announcement that a \u201cfountain of youth\u201d drug had been found that extends life by about 10%.\u00a0 I picked a site at random and read the report, knowing full well what I would find buried somewhere in the story.\u00a0 Sure enough, there it was, tucked at the end of a paragraph halfway down: the study was done on mice.<\/p>\n
The \u201celixir of life\u201d is rapamycin, an immunosuppressant used to prevent transplanted organ rejection.\u00a0 The maximum human daily dose for rapamycin is 5 mg.\u00a0 To receive the same relative amount as the mice were fed in the study, people would have to ingest 200 mg daily. This means that anyone who takes \u201clongevity\u201d doses of rapamycin had better live in a controlled, sterile environment.\u00a0 It also means that they\u2019ll be prone to developing tumors.\u00a0 This is not a problem for mice, in whom cancer can be easily cured.\u00a0 Not so, by a long shot, for humans.<\/p>\n
Mice are extremely useful for dissecting molecular pathways and fairly useful as models for a long list of diseases.\u00a0 Their advantages are many and obvious: they\u2019re mammals, so they share more with humans than the other organisms used in genetics \u2013 yeast, flies, worms, fish.\u00a0 Their generation times are short, their litters large.\u00a0 We can totally control their environment, though this affects their health and behavior.\u00a0 We can alter, delete or insert genes in mice and regulate when and where they express.\u00a0 And mouse research is far less emotionally and ethically fraught than experiments on primates.<\/p>\n
However, as I never tire of saying, the devil\u2019s in the details.\u00a0 Mice are sufficiently different that drug studies, in particular, are better as proofs of principle than one-on-one mappings.\u00a0 Unlike us, mice are fast-metabolizing and short-lived.\u00a0 Drugs, nutrients and hormones are radically divergent in every mammal in terms of bioavailability, activity, metabolism and toxicity.\u00a0 Many drugs that showed exceptional promise in mice fared no better than placebos or essentially acted as poisons in human clinical trials.\u00a0 The social and behavioral wiring of the two species are totally disparate.\u00a0 For example, mouse sexual arousal and mothering behavior depend on smell pheromones.\u00a0 Mouse models of complex diseases are prone to over- or mis-interpretation.\u00a0 Does a compound stop a mouse from jerking uncontrollably because it\u2019s a pain killer — or is it acting as a muscle relaxant?\u00a0 It\u2019s even harder to correlate such complicated responses as learning, anxiety or depression.<\/p>\n
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At the molecular level, many genes that are essential in mice are non-essential in humans and vice versa.\u00a0 Comparisons between the human genome and its recently completed mouse equivalent show that they diverge far more than previously recognized \u2013 close to 20%.\u00a0 Not only are there significant numbers of human-specific genes; equally importantly, genes whose structure is identical in the two species are nevertheless differently regulated.\u00a0 And last but decidedly not least, the two species have distinct regulatory RNAs (miRNAs for the truly curious).<\/p>\n
All this may sound esoteric, but the conclusion is simple: mouse models, especially those based on highly inbred strains, recapitulate only limited aspects of many human functions and diseases.\u00a0 This is particularly true of metabolism, neoplasty, lifespan and that troublesome jewel in the crown \u2013 the brain.\u00a0 Elixirs and panaceas for obesity, cancer, longevity and dementia remain stubbornly species-specific.\u00a0 So next time a brushfire sweeps the Internet with news of yet another miracle cure, the first and last question of non-biologists should be: what were (or when will we know) the results of the human tests?<\/p>\n