Tag Archives: animal research

Chapter 6. The Costs of Animal Experiments

The false-positive and false-negative results of the animal bioassay can be considerable. Ennever and Lave analyzed the data on known human carcinogens with the animal data for cancer predictability. They found a disturbingly large proportion of incorrect predictions, ‘potentially allowing widespread human exposure to misidentified chemicals’. An analysis of the data on 780 chemical agents listed in the International Agency for Research in Cancer database found the positive predictivity of the animal bioassay for a definite or probable human carcinogen to be only around 20 per cent. In addition to placing human lives at risk, the low predictability of this assay is costing us money and wasting time. Each assay requires up to millions of dollars and years of planning. In the meantime, as we continue to rely on this assay, there is a huge backlog of untested chemicals to which we are already exposing ourselves.

Other toxicology and carcinogenicity tests that rely on animals are equally flawed. One study examined the toxicological profiles of rodent and non-rodent (beagles and NHPs) species of 50 compounds. The study found poor correlation of target organ toxicity across species and concluded that ‘simple extrapolation across species is unrealistic’. The study authors called for regulatory agencies to institute an evaluation of tests using animals as predictors of human adverse signs. In 1999 the Health and Environmental Science Institute examined the data on 150 compounds that had produced a variety of toxic effects in people. It found that only 43 per cent of the compounds produced similar effects in mice and rats and 63 per cent did so in other animals. A reviewer of toxicology testing and regulations commented that ‘compelled to act, regulators have chosen animal tests to forecast human cancer risks. To this end, animal data are filtered through a series of preconceived assumptions that are presumed to overcome a host of human/animal differences of biology, exposure, and statistics-differences that in reality are insurmountable.’

Recognizing the immense difficulty in predicting toxicity in one species based on the toxicity data from another is not new. As early as 1978, Fletcher found poor correlation between drug safety tests in animals and subsequent clinical experience with 45 major drugs, including anti-cancer agents, antibiotics, cardiac agents and neurological agents. Fletcher’s survey established that only 25 per cent of the toxic effects observed in animals might be expected to occur in humans. Assessing three decades of data on the subject, toxicologist Ralph Heywood also found that the concordance between animals and humans is only 25 per cent. ‘Toxicology’ he concluded, ‘is a science without a scientific underpinning.’

‘In retrospect,’ Fletcher concluded in his 1978 report, ‘it is a relatively simple matter to determine the correlation between animal and human studies, but prospectively it is difficult to know which particular toxic effects are likely to prove troublesome when it comes to giving the drug to man.’ And that’s the catch: accurately predicting when the animal experimental results are relevant to humans is nearly impossible because of inter-species differences. We can always go (and have often gone) back after clinical trials have been conducted to assess whether the animal experimental results correlated with the clinical results, but retrospective confirmation is not the purported reason for using animals in experimentation. They are intended to predict human results and inform human health care. If we find that the animal experimental results equated with the clinical results, then the research community hails the efficacy of the animal experiments. But when the animal and human results do not match, the proclaimed failure is said to be a result of flaws in experimental design, publication bias or use of young animals for a disease that occurs predominately in elderly humans. Rarely is the use of the animals themselves—not how they are used—questioned.

While most researchers admit the difficulty in extrapolating and applying information obtained from other species to humans, commonly proposed solutions to this colossal obstacle are far from helpful. Neyt et al. suggest that ‘clearly profound differences may exist at the gross, microscopic and genetic level between humans and other mammals, and these differences must be appreciated before extrapolating the results of a given study to human clinical practice.’ Caution in extrapolating data from animals to humans is another common advice given. In fact, ‘appreciation of differences’ and ‘caution’ about extrapolating results from animals to humans is now almost universally expressed in published reports on animal experimental results intended to inform human health.

Yet, in reality, how does one take into account differences in drug metabolism, genetics, expression of diseases, anatomy, behavior, influences of laboratory environments, and species and strain-specific physiologic mechanisms and then discern what is applicable to humans and what is not? There is just no established formula or algorithm to do this. Many scientists have recently acknowledged that modeling human disease in animals is extremely problematic but have still argued for their use, instead, to study basic physiologic mechanisms. But again, if we cannot predetermine what mechanisms in what species and what strain of species and in what caging system and even during what time of day are applicable to humans, then the usefulness of the experiments needs to be questioned.

Why the NFL Needs to Have Its Head Examined

Recently, PBS’s Frontline aired a disturbing documentary chronicling the National Football League’s history of downplaying and distorting the evidence that football-related head injuries cause long-term brain damage. The film included footage from a 2009 Congressional hearing in which lawmakers compared the NFL’s approach to the problem to Big Tobacco’s decades of sham science and lies about the link between smoking and disease. The analogy is spot on.

The NFL borrowed a page from Big Tobacco’s playbook by choosing to dump millions of dollars into experiments on animals that won’t ever help humans, but will allow dangerous activity to continue while giving the public the illusion that they’re being protected.

Read the full article in the Huffington Post

Why Animal Experimentation Doesn’t Work. Reason 3: Animals Aren’t Little Humans

Your child, my father, and all of our loved ones who may be suffering from illnesses are not rats or dogs or monkeys. So why do animal experimenters keep treating them as though they are?

Suppose you are an experimenter and are determining if methylprednisolone, a steroid, will help humans with spinal cord injury. After crushing the spinal cords of many different animals, you test the drug on them. My colleagues and I looked at the published studies (62 in total) and here are the results broken down by species [1]:

  • In Cats: the drug was mostly effective
  • Dogs: mostly effective
  • Rats: mostly ineffective
  • Mice: always ineffective
  • Monkeys: effective (1 experiment)
  • Sheep: ineffective (1 experiment)
  • Rabbits: results were split down the middle

Based on these results, can you determine if methylprednisolone will help humans with spinal cord injury?

This leads to the third major reason in my series why animal experimentation is unreliable for understanding human health and disease:

Read the full article in the Huffington Post

Why Animal Experimentation Doesn’t Work — Reason 2: Animals Don’t Get Human Diseases

My father suffers from diabetic peripheral neuropathy. His diabetes led to nerve damage that causes him severe, constant pain. I want the best medical treatments possible for him and, as a neurologist, I am always on the lookout for good, new drugs, but none of them have effectively slowed down his diabetes and nerve damage. As long as experimenters continue to try to recreate diabetes in animals, instead of studying human diabetes, I have little hope that my father’s pain will end.

Although numerous drugs are available, diabetes remains among the top killers in the U.S. and worldwide. The newest drugs are generally no more effective than the older drugs or are much more harmful. Just recently, two new diabetic drugs, Onglyza and aleglitazar, failed clinical trials after testing in animals.

At first glance, it might seem that if we can recreate diabetes in dogs or mice, we would better understand diabetes. But here’s the problem: we end up better understanding animal diabetes– in dogs and mice– but not necessarily human diabetes.

In this article in my medical research series, I discuss the second major reason (click here for the first reason) why animal experimentation is unreliable for understanding human health and disease.

Read the full article in the Huffington Post

Why Animal Experimentation Doesn’t Work — Reason 1: Stressed Animals Yield Poor Data

Imagine you are a monkey in a laboratory and a person dressed in a white coat walks into the room with a catching net. How do you think you would react? You would probably not be surprised to learn that monkeys in this situation immediately show significant distress.

What may surprise you, however, is that the distress that animals in laboratories experience is one of the main reasons why animal experimentation doesn’t work.

Read the full article in the Huffington Post

Want to Improve Medical Research? Cut Out the Animals!

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.

Read the full article: Huffington Post

NASA’s Wrong Stuff

I am an absolute space geek. The only time I ever skipped high school was to hear a panel of astronauts give a talk about space exploration. I owned a topographical map of Mars before it was ever considered cool (it IS considered cool, by the way). And this past July I was one of the lucky few that joined the team of Apollo 11 to commemorate the 40th anniversary of their moon landing. I have always been a firm supporter of NASA and its space exploration program; it is truly the stuff of dreams (including mine). Yet, for the first time, I am finding myself extremely disappointed by NASA’s efforts to pursue the final frontier. During a time when NASA’s budget is especially tenuous and after the Obama administration essentially put the agency’s human spaceflight plans on hold, I am bewildered by NASA’s plan to squander nearly $2 million in taxpayer money on radiation experiments on monkeys.

NASA has announced it is funding an experiment in which as many as 30 squirrel monkeys will be exposed to harmful ionizing radiation here on Earth. The purported goal of this project is to observe how radiation exposure during extended trips through deep space may affect astronauts’ neurochemistry, cognition, and behavior. Ultimately, the experiments are poorly planned and a far cry from the real life conditions humans would be confronted with in space.

On long trips to space, astronauts are continuously exposed to low levels of radiation, but the monkeys in the NASA experiment will be exposed to a single, large dose of radiation over a period of just a few minutes. The biological effects of these two very different kinds of exposure vary substantially. For example, in small doses over a lifetime, the radiation we are exposed to during diagnostic medical procedures is relatively safe. But if one were exposed to all of that radiation at once, one could suffer from health complications including vomiting, seizures, skin and bone marrow damage, internal bleeding and increased risks of cancer.

According to government documents, after the radiation exposure at the Brookhaven National Laboratory, the monkeys will be taken to a Harvard facility where they will be individually confined to steel cages. They will be strapped into restraint chairs and forced to perform behavioral tasks like pressing levers or touching a computer screen in response to visual stimuli. This will go on for five days a week for at least four years, allowing the experimenters to observe how the radiation exposure causes the animals’ physical and mental health to deteriorate. The monkeys will spend the rest of their lives in cages. NASA says there are no further plans for them at this time, but the radiation study could be renewed in four years or the monkeys may be used in additional experiments later on.

Any cognitive and physical deficits that the monkeys might suffer as a result of being irradiated will be confounded — and potentially magnified — by the debilitating impacts of their confinement and manipulation. In the laboratory, the monkeys will be denied meaningful social interaction, physically tormented, confined to highly unnatural environments, and deprived of everything normal to them. This environment — inherently detrimental to the monkeys’ physical and mental health — will render the results of the experiment extremely difficult to interpret.

Additionally — and here’s the real problem — this experiment will only help tell us how the monkey brain is affected by radiation, not the human brain. While monkeys are intelligent and social creatures and share many characteristics with humans, key differences exist between the neuroanatomy and neurochemistry of monkeys and humans. Not to mention the many differences that we aren’t even aware of yet. These known and unknown differences will make it almost impossible to unravel and determine what results, if any, from the monkey experiment can and cannot be applied to humans. At best we will come away $2 million poorer with information that we won’t know how to safely apply, and at worst, we will be misled by the results of this experiment in ways that can seriously jeopardize the safety of future astronauts.

Four decades of radiation experiments on monkeys have cost thousands of animals their lives and taxpayers millions of dollars, yet have provided hardly any useful information about the effects of space radiation on humans. In fact, the government’s program for conducting these experiments was halted in the 1990’s largely for this very reason. Another one, 100, or 1,000 monkey studies will not tell us how human beings will be affected by space radiation on a trip to Mars, or anywhere for that matter.

NASA’s space program relies on incredibly sophisticated technology and represents a triumph of human ingenuity and imagination. This experiment is a step backwards for a forward-looking organization and contradicts what is best about NASA.

This piece was originally posted in the Huffington Post.