Recently, former NIH Director, Elias Zerhouni (director from 2002-2008), returned to address NIH and made a startling comment:
"We have moved away from studying human disease in humans," he lamented. "We all drank the Kool-Aid on that one, me included." With the ability to knock in or knock out any gene in a mouse -- which "can't sue us," Zerhouni quipped -- researchers have over-relied on animal data. "The problem is that it hasn't worked, and it's time we stopped dancing around the problem...We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans."
"Evidence-based medicine" is a term used throughout medical practice. Basically, we rely on evidence to support virtually every practice in medicine and medical research -- except one. Despite the fact that millions of animals are used in experiments each year, we have rarely actually scrutinized the data on animal experiments to determine how relevant they are for human diseases and for improving our lives.
Fortunately that's changing. More scientists are now taking a hard look at this question. What the evidence is showing is that we can get much better answers about human health and diseases and develop more effective therapies if we use human-based tests instead of animal experiments.
Again and again, drugs found effective in animals in the laboratory have failed when tried in humans. For example, in my book I discuss how dozens of treatments for spinal cord injury worked in animals, but not one worked in humans. Over one hundred stroke drugs have been found effective in animals in the lab, yet all have failed in humans. Over 85 HIV vaccines that worked in non-human primates failed miserably when tried in humans.
The main reason for these high failure rates? Animal experiments simply don't make good "models" of human physiology and human diseases.
Recognizing this, Merck and other pharmaceutical and biotech companies are creating exciting new testing methods like human organs-on-a-chip, which, having human cells and tissues, are likely to do a far better job at mimicking the human body than animal experiments.
As Merck's Dr. Nicholson says:
"The limitations of animals as stand-ins for human patients are a major reason (for drugs to fail). Animal disease doesn't faithfully replicate asthma, for instance. The condition is uniquely human ... and animal models can't capture the constriction of airways and all of the other characteristics of the disease. We have found great mechanisms that can control asthma in an animal," he says. "And most of them have failed" in humans.
Animal experiments fail because no matter how many physiologic similarities there may be between other animals and humans, there are just too many differences. To make matters worse, we are not even aware of what most of those differences are. The way medicine is practiced today, it seems that the differences -- even the most subtle ones -- outweigh the similarities.
Here's an example. In February, a study published in PNAS reported that the mouse "models" used extensively to study human inflammatory diseases (in sepsis, burns and trauma) have been totally misleading. The authors of the study point out that there have been nearly "150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed."
What the study found was that mice differ greatly from humans in their responses to the inflammatory conditions. Mice differed from humans in what genes were turned on and off and in the timing and duration of gene expression. These different responses cause high drug failure rates.
Essentially, this one study showed that we wasted decades of research using mice as models for human inflammatory diseases because no one thought until recently to actually take a look at how relevant the animal experiments are. Dr. Richard Hotchkiss, a sepsis researcher at Washington University said that the study "... argues strongly -- go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways."
"To understand sepsis, you have to go to the patients," he said.
Similar sentiments have been expressed about Alzheimer's Disease (AD) research. AD is characterized by the presence of some key features in the human brain. For decades now, researchers have tried to create AD mice by altering their genes and inserting human genes. But here's the problem -- each mouse "model" is different and no single mouse "model" shows all the pathologic features of AD. Instead, each model displays bits and pieces of AD and these models often give conflicting results because they differ in regards to the symptoms that develop and the causes behind these symptoms.
Not surprisingly, one of the key messages of the 2007 Inaugural Alzheimer's Drug Discovery Foundation Meeting was that the human patient is the only true model of AD (1).
Susan Fitzpatrick, former Associate Executive Director of the Miami Project to Cure Paralysis and current Vice President of the James S. McDonnell Foundation stated this about the heavy reliance on animal experiments:
"The biomedical model is failing. Even if we know all there is to know about the animal model we don't necessarily know about the disease," because, as Fitzpatrick continues, "the model becomes what we study, not the human disease."
So what's the bottom line? Cut out the animals. If we want to truly improve our lives and find cures for our diseases, wouldn't we be better served if we stop wasting immense time and resources using misleading animal experiments?
Let's refocus our efforts on studying human diseases using ethical human-based tests, such as virtual humans, human organs-on-a-chip, imaging techniques, and many others. By doing so, we will better help our loved ones and ourselves as well as save millions of animals annually from lives of misery.
Please stay tuned! In my next article, I will explore how the stress and distress animals experience in the labs is one major reason why animal experiments fail.
Dr. Akhtar is the author of the book: Animals and Public Health. Why Treating Animals Better is Critical to Human Welfare. You can learn more at her website.
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1. Fallon L. 'Drug Discovery for neurodegeneration -- Inaugural Alzheimer's drug discovery foundation meeting' IDrugs 2007; 10: 233-236.