LRI conducts experiments on animals; currently, in particular, mice. We believe that this is worthwhile -- that is, we believe that whether a drug makes mice live longer tells us something meaningful about whether it will make people live longer.
But is that a valid assumption? We know, after all, that most drugs that “work” in mouse experiments don’t go on to succeed in human clinical trials. Only 14% of drugs that are tested on humans succeed in demonstrating effectiveness[1], and all of these are drugs that have been found efficacious in animals, so successful animal studies are very far from a guarantee by themselves. Why do we trust them at all?
First of all, it should be noted that the overall clinical trial success rate is brought down by cancer drugs, which have only an 8% success rate in clinical trials. The success rate for trials of all non-oncology drugs is 20%.
Curing cancer in a laboratory mouse is very different from curing it in a person. In particular, these aren’t animals that got old and developed tumors spontaneously; they’re mice that have been made to get cancer, either by breeding a cancer-prone strain of mice, or by exposing the mice to a carcinogen, or by grafting a tumor into the mouse directly. None of these processes works exactly the same as developing spontaneous tumors, and in particular they may be easier to reverse than spontaneous tumors. Part of what makes humans get cancer is that, with age, we lose the ability to fight cancer off, through weakened immune systems and other dysfunctions; we’d expect it to be easier to eradicate tumors implanted in a young, healthy mouse than the ones acquired by an old, unhealthy one. Similarly, mutant tumor-prone mice may have genetically simpler forms of cancer than mice who develop cancer in old age, and their genetic defects may thus be easier to counteract with drugs. This means that the animal experiments are “playing on easy mode”, and many drugs that pass them would not pass the “hard mode” of a human study.
The same argument goes for many other so-called “animal models” of disease. We induce Parkinson’s-like symptoms in animals with a poison called MPTP -- but this produces only a narrowly targeted form of brain damage, while real Parkinson’s disease, naturally acquired in elderly humans, includes more types of damage to more areas of the brain. It is easier to reverse MPTP symptoms than Parkinson’s disease. Animal models of age-related disease generally do not wait for the diseases to be naturally acquired, but induce them artificially in young animals, which we’d expect to be overall more resilient than the elderly humans who normally get these diseases.
This flaw doesn’t apply to lifespan studies of mice -- we’re not simulating aging, we’re observing natural aging, and how drugs modify it.
by Sarah Constantin, LRI | Read more:
But is that a valid assumption? We know, after all, that most drugs that “work” in mouse experiments don’t go on to succeed in human clinical trials. Only 14% of drugs that are tested on humans succeed in demonstrating effectiveness[1], and all of these are drugs that have been found efficacious in animals, so successful animal studies are very far from a guarantee by themselves. Why do we trust them at all?
First of all, it should be noted that the overall clinical trial success rate is brought down by cancer drugs, which have only an 8% success rate in clinical trials. The success rate for trials of all non-oncology drugs is 20%.Curing cancer in a laboratory mouse is very different from curing it in a person. In particular, these aren’t animals that got old and developed tumors spontaneously; they’re mice that have been made to get cancer, either by breeding a cancer-prone strain of mice, or by exposing the mice to a carcinogen, or by grafting a tumor into the mouse directly. None of these processes works exactly the same as developing spontaneous tumors, and in particular they may be easier to reverse than spontaneous tumors. Part of what makes humans get cancer is that, with age, we lose the ability to fight cancer off, through weakened immune systems and other dysfunctions; we’d expect it to be easier to eradicate tumors implanted in a young, healthy mouse than the ones acquired by an old, unhealthy one. Similarly, mutant tumor-prone mice may have genetically simpler forms of cancer than mice who develop cancer in old age, and their genetic defects may thus be easier to counteract with drugs. This means that the animal experiments are “playing on easy mode”, and many drugs that pass them would not pass the “hard mode” of a human study.
The same argument goes for many other so-called “animal models” of disease. We induce Parkinson’s-like symptoms in animals with a poison called MPTP -- but this produces only a narrowly targeted form of brain damage, while real Parkinson’s disease, naturally acquired in elderly humans, includes more types of damage to more areas of the brain. It is easier to reverse MPTP symptoms than Parkinson’s disease. Animal models of age-related disease generally do not wait for the diseases to be naturally acquired, but induce them artificially in young animals, which we’d expect to be overall more resilient than the elderly humans who normally get these diseases.
This flaw doesn’t apply to lifespan studies of mice -- we’re not simulating aging, we’re observing natural aging, and how drugs modify it.
Image: uncredited
