3066. More Than 76,000 Non-human Primates Are Used in Laboratories, Representing an Uptake

By David Grimm, Science Magazine, November 2, 2018



The number of monkeys used in U.S. biomedical research reached an all-time high last year, according to data released in late September by the United States Department of Agriculture (USDA).

The uptick (see graph below)—to nearly 76,000 nonhuman primates in 2017—appears to reflect growing demand from scientists who believe nonhuman primates are more useful than other animals, such as mice or dogs, for testing drugs and studying diseases that also strike humans.

“I think the numbers are trending up because these animals give us better data. … We need them more than ever,” says Jay Rappaport, director of the Tulane National Primate Research Center in Covington, Louisiana, which houses about 5000 monkeys. The increase also comes amidst a surge in funding from the National Institutes of Health (NIH), which supports much of the nonhuman primate research in the United States.

The figures have surprised and disappointed groups seeking to reduce the use of lab animals. The biomedical community has said it is committed to reducing the use of research animals by finding replacements and using these animals more selectively, says Thomas Hartung, director of Johns Hopkins University’s Center for Alternatives to Animal Testing in Baltimore, Maryland. But the new numbers suggest “people are just blindly running toward the monkey model without critically evaluating how valuable it really is.”

Nonhuman primate research has faced intensifying scrutiny. Harvard University closed its national primate research center—one of only eight in the country—in 2015, after a federal investigation into the deaths of four of its animals. That same year, NIH ended its support of all invasive chimpanzee studies, citing a report that found these animals were no longer essential to biomedical research. And in 2016, Congress directed NIH to hold a workshop on the utility and ethics of monkey research.

Public opposition to animal research has been rising—with a recent Pew Research Center poll finding that a record 52% of Americans oppose such studies. And importing monkeys to the United States has become increasingly difficult as almost all commercial air carriers now refuse to fly the animals.

Yet according to the new USDA figures, scientists used 75,825 nonhuman primates for research last year, up 22% since 2015 and 6% since 2008. In contrast, the number of cats, dogs, rabbits, and other animals recorded by USDA are all being used at lower numbers than they were a decade ago. (Nonhuman primates constitute just 0.5% of all animals used in U.S. biomedical research; about 95% are rats and mice, which are not reported by USDA.) The total number of monkeys in labs—which also includes those bred in colonies and those not currently being used in research—has remained fairly steady for the past decade, with about 110,000 recorded last year (see second graph, below).

The uptick in monkey research “represents both the state of the science and the importance of nonhuman primates,” NIH said in a statement. Nearly two-thirds of the nonhuman primates the agency supports are rhesus macaques, with cynomolgus macaques (15%), baboons (6%), and a dozen other monkey species making up the remainder. The rising demand for rhesus macaques appears to be driven by researchers studying HIV/AIDS, the brain, Alzheimer’s disease, and addiction, according to an NIH report released in September. 

The rise might also reflect the agency’s expanding investment in these studies. NIH gave 249 grants in 2017 that supported nonhuman primate research, up from 171 in 2013. And the agency expects the number of nonhuman primates it supports to continue to grow in coming years.

That forecast frustrates Hartung, who says NIH should launch a review of the need for monkeys, similar to the one that led it to end its support for chimpanzee research. He challenges the idea, for instance, that nonhuman primates are more useful for drug testing than rats or mice. Nonhuman primates are more genetically variable than rodents, he argues, and researchers typically use relatively few monkeys for studies of drug efficacy and safety. As a result, those experiments could yield skewed data on how the drugs will act in humans. Scientists embracing monkey experiments, he says, are at risk of “repeating the mistakes of the past.”

Other animal advocates hope the new statistics will move members of Congress to put greater pressure on U.S. agencies to reduce nonhuman primate use. “I think when Congress sees these numbers, things are going to come to a head,” says Mike Ryan, director of policy and government affairs at the New England Anti-Vivisection Society in Boston. This week, Representative Brendan Boyle (D–PA)—reacting to an investigation into the Food and Drug Administration (FDA) by the Washington, D.C.–based animal activist White Coat Waste Project—sent a bipartisan letter to FDA asking it to review all studies involving the more than 300 nonhuman primates it oversees. “Painful primate testing is shameful, and it has no place in the 21st century,” Boyle tells Science. “It’s clear that federal agencies are still not doing enough to curb this appalling practice.”

In the meantime, Rappaport says nonhuman primate facilities like his are simply struggling to meet the demand. Some scientists are reporting that they have delayed studies by at least 6 months because they can’t obtain animals, the NIH report notes. The growing demand could sharpen the tensions surrounding animal research. “The public wants more cures, but fewer animals,” says Cindy Buckmaster, board chair of the Washington, D.C.–based Americans for Medical Progress, which supports animal studies. “They can’t have it both ways.”

2216. The "Mind Controlling Ability" of a Single-Cell Parasite: Toxoplasmosis gondii

By Carl Zimmer, The New York Times, February 11, 2016

Many of our primate ancestors probably ended up in the bellies of big cats. How else to explain bite marks on the bones of ancient hominins, the apparent gnawing of leopards or other African felines?

Big cats still pose a threat to primates. In one study of chimpanzees in Ivory Coast, for example, scientists estimated that each chimp ran a 30 percent risk of being attacked by a leopard every year.

A new study suggests that the big cats may be getting some tiny help on the hunt. A parasite infecting the brains of some primates, including perhaps our forebears, may make them less wary.

What does the parasite get out of it? A ride into its feline host.

The parasite is Toxoplasma gondii, a remarkably successful single-celled organism. An estimated 11 percent of Americans have dormant Toxoplasma cysts in their brains; in some countries, the rate is as high as 90 percent. Infection with the parasite poses a serious threat to fetuses and to people with compromised immune systems. But the vast majority of those infected appear to show no serious symptoms. Their healthy immune systems keep the parasite in check.

Mammals and birds can also be infected. But cats in particular play a crucial part in the life cycle of the parasite: When a cat eats an infected animal, Toxoplasma gondii ends up in its gut. It reproduces there, generating offspring called oocysts that are shed in the cat’s feces. The oocysts can last for months in the environment, where they can be taken up by new hosts.

In the 1990s, scientists discovered that mice and rats infected with Toxoplasma gondii lose their natural fear of cat odors — and in some cases even appear to become attracted to them. It was possible, researchers speculated, that the parasite had evolved an ability to influence the behavior of its rodent hosts, to raise the chances they might be eaten by cats.

Subsequent studies have shown that the parasite can change the wiring of fear-related regions of the rat brain. Robert M. Sapolsky, a biologist at Stanford University, said that these findings led many researchers to see Toxoplasma gondii as a parasite exquisitely adapted to rodents. According to this view, he said, “Toxo being able to infect a zillion nonrodent species is just some sort of irrelevant evolutionary dead end.”

Even so, Toxoplasma gondii can cause intriguing changes in our brains as well. In a 2015 study, for example, researchers found that women infected with the parasite are more aggressive than those without it; infected men behave more impulsively than parasite-free men.

Clémence Poirotte, an evolutionary biologist at the Center for Functional and Evolutionary Ecology in Montpellier, France, wondered if our understanding of Toxoplasma might be limited by the paltry number of species in which its manipulations had been studied. She and her colleagues decided to focus on chimpanzees, running an experiment on 33 apes at a primate research center in Gabon, nine of which had Toxoplasma infections.

Instead of testing the reactions of chimpanzees to the odor of house cats, Ms. Poirotte and her colleagues turned to leopards, their natural predators. A veterinarian at a Gabon zoo supplied them with leopard urine, and they poured drops of it on the fence enclosing the space in which the chimpanzees lived.

Stepping back from the fence, the scientists observed the apes to see how they responded. They also ran the same experiment with urine from three species that are not chimpanzees’ natural predators: humans, lions and tigers.

Sometimes, the chimpanzees would approach the fence and investigate the smell; other times, they would ignore it. Ms. Poirotte and her colleagues found that chimpanzees not infected with Toxoplasma investigated the smell of leopard urine less than the smell of humans.

That’s the sort of behavior you would expect if the smell of leopard urine alarmed the chimpanzees — a healthy instinct that could keep them out of leopard territory and reduce their chances of getting killed.

The Toxoplasma-infected chimpanzees, on the other hand, checked out the leopard urine more often than that of humans, not less. They appeared to have developed the same recklessness observed in Toxoplasma-infected rodents.

“It’s so interesting to see that Toxo seems to have evolved the same manipulation ability in an ape with respect to its natural feline predator,” said Dr. Sapolsky, who was not involved in the new study.

Other experts were also intrigued by the report. But Michael B. Eisen, a biologist at the University of California, Berkeley, said he didn’t think it was powerful enough to rule out other explanations for how the chimpanzees behaved.

There might be innate differences in how the chimpanzees respond to odors, for example, that have nothing to do with being infected with Toxoplasma. “I’d have to file this, at best, in the ‘interesting but nowhere near convincing’ file,” Dr. Eisen said.

Ms. Poirotte acknowledged that it might be possible to tease apart these different possibilities by testing the chimpanzees before and after being infected with Toxoplasma. That would be a very challenging experiment to set up, however.

But the current study provided another piece of evidence that the parasite really was manipulating the chimpanzees. “It works only with leopard urine, and not with other felines which aren’t their natural predator,” Ms. Poirotte said.

That’s the kind of precision you’d expect from a parasite that has evolved a strategy for getting into one particular animal. “It’s so specific that it suggests it’s Toxoplasma causing the behavior modification,” Ms. Poirotte said.

She added that it would be useful now to study Toxoplasma’s effects on other primate species. It may even turn out that our primate ancestors were once the primary targets of the parasite.

When domesticated cats emerged several thousand years ago, the parasite might have expanded into a new host population that favored rodents rather than primates.

“It certainly suggests that Toxo’s behavioral effects in humans may be less of an irrelevant dead end than was always assumed,” Dr. Sapolsky said.