Friday, December 18, 2015

The Singular Uniqueness of Tarsiers

South-East Asia draws the attention of many tourists and travelers because of its rich cultural heritage, globally famous cuisine, and picturesque views. But there are a growing number of people who are starting to shift their attention to the native wildlife of the region, both terrestrial and marine. Among others, nature lovers are attracted to small, forest-dwelling animals with huge eyes, jumping enormously long distances: tarsiers. Those tiny creatures are becoming a mandatory part of the travel itinerary of many visitors. Some of the people find them cute, some of them describe them as aliens from another world. But the question remains, what actually are they?

Image by Paige Carter.

Tarsiers are the distinct group among primates. This is an unquestionable fact all scientists agree on. Still, what kind of primate is a much more difficult question to answer. There are a few reasons behind this difficulty in classifying them. Their nocturnal nature and morphology would, at first glance, suggest their close relationship to lemurs, lorises and bushbabies, often referred to as prosimians or strepsirrhine. On the other hand, another set of traits, mainly anatomical and reproductive characteristics, would tempt us to place them together with monkeys, apes and humans, which together are called haplorhine. Despite uniform attempts to clarify their relationship to other primates, scientists remain divided on this issue. Why is this issue so difficult to decide?

First of all, along with characteristics common for strepsirrhine on one hand and for haplorhine on the other, tarsiers possess their own distinctive traits. Those creatures are the most carnivorous primates currently known, preying upon various animals, ranging from arachnids and insects to amphibians, reptiles and even birds.[1] Even though they are considered one of the smallest primates, their eyes are disproportionately big, with just one eyeball being bigger than their brain. This is their adaptation for better vision at night, making them better predators, as they do not have tapetum lucidum, the reflective layer behind the retina, which facilitates night vision in lemurs, lorises and bushbabies. Tarsiers are also the only mammals that can rotate their head by 180 degrees, which significantly increases their vision angle and improves their hunting ability. Furthermore, two of their leg bones, the fibula and tibia, are fused, which is an adaptation for their interesting, long-distance leaping.[1]

In 1918 Pocock proposed tarsiers be classified with haplorhines based on his revision of their anatomy, looking especially into the upper lip and nose, placenta, and postorbital partition. However, many of the traits making tarsiers closer to haplorhines have been discussed as convergence or loss as a result of specialization on visual, rather than olfactory, predation (dry rhinarium to give an example).[1] Because of this and other traits, like postorbital partition, placing tarsiers with haplorhines is still a controversy. Thus, since the findings of Pocock in 1918, some primatologists use “Prosimii” and “Anthropoidea,” classifying tarsiers with prosimians, and the others use “Strepsirrhini” and “Haplorhini,” with the latter including tarsiers, monkeys, apes and humans.

Fossil records also fail to resolve this discussion. The fossils of tarsiers are very rare, and the only certain information derived from them is the fact that they come from the Eocene epoch.[1] Therefore, it is not sure whether early tarsiers should be linked with Omomyidae or Anthropoids.[1] It seems that the tarsiers’ affiliation and origins will not be easily solved.
However, some fossil evidence of past forms of tarsiers is available. This includes mainly teeth, lower jaws, and one postcranial skeleton. Four species of fossil tarsiers were recognized: Afrotarsius chatrathi found in Egypt, Tarsius thailandicus collected in Thailand, and Xanthrorhysis tabrumi and Tarsius eocaenus, both excavated in China, with the latter dating back 45 million years.[2] A comparative study of the teeth and tibiofibula from African specimen with modern species reveal many matches. Although smaller than extant specimen, the fossils do not exhibit any major differences in morphology, indicating that currently living tarsiers have not changed in any aspects which could be evaluated based on the excavated material. The animals are essentially “living fossils.”[2]

We also know at least some about the animal’s evolutionary history. All of the present day tarsiers live in rainforests of South-East Asia, and it is known that the physical structure of the forests and insects guilds living there have not changed substantially from Tertiary period, providing a stable of the environment for tarsiers.[2] Put simply, the rainforest of this region is basically the same as it was at the time of the earliest tarsiers. Thus, we can trace back the evolutionary history to some degree.

In the Eocene epoch the forest composition started forming closer understory vegetation in forms of buttressed trunks, lianas and epiphytes.[2] This created a habitat for many animals, including arthropods. However, only a small part of forest-dwelling animals focused on utilizing invertebrate niches, mostly bats and birds.[2] This is explicable when one considers conditions at the understory where most of the arthropods live and their biology itself. Habitat in lower parts of the forest is harder for travelling, resulting in animal predator adaptations of moving up and down vertical tree trunks, crossing gaps and balancing on thin branches and lianas.[2] Additionally, a large part of arthropods are and most likely were, since the beginning of their evolution, nocturnal, which makes foraging challenging. All of the adaptations the tarsiers developed made them successful in exploiting this kind of niche. Foraging in the dense understory became possible due to leaping as a primary locomotion mode, which is enabled by elongated hindlimbs.[2] They also have low metabolic rates and lower body temperatures to save energy expenditure.[2] This made them very efficient in exploiting niche of nocturnal insectivores and carnivores foraging in rainforest dense understory, which apparently has not changed since its origin.[2]

Putting aside the past, currently there are 10 species of tarsiers inhabiting rainforests of BIMP countries: Brunei, Indonesia, Malaysia and the Philippines.[3] Their habitats stretch from primary and secondary lowland evergreen to mossy upper montane rainforests.[2] Except for different distribution, they also differ from each other by some aspects of their biology, ecology and behaviour.  For example, in some species the sexual dimorphism exist with larger males, while in others it is not existent, without differences between sexes.[4] Few species live in family groups, sharing their sleeping sites, while others are solitary, sleeping separately.[4] In terms of their future survival, the tarsiers situation does not seem that bright as one might expect. All of 10 tarsiers species exhibit decreasing population trend; however, the conservation status assessment differs and they were assigned with different categories: one species is Critically Endangered (CR), two are Endangered (EN), two are Vulnerable (VU) and one is Near Threatened (NT).[3] Three remaining species are Data Deficient (DD), showing an immediate need for studies on them.[3]

One of the most famous but most poorly known of these animals is the Philippine tarsier (Tarsius syrichta). Despite some obvious facts, incorrect myths have accumulated along the years to draw the attention of visitors to this tiny primate. First, completely wrong information about Philippine tarsiers can be found in almost every tourist guidebook and is repeated by local guides immediately upon arrival. Even worse, this information is passed to young Filipinos in textbooks for elementary schools. For example, visitors coming to the Philippines, especially to Bohol, will be bombarded with the offer to see the “smallest monkey on the world.” As already mentioned above, it is not a monkey; moreover it is not the smallest primate (this title is held by Madame Berthe’s Mouse Lemur (Microcebus bertahe)),[5] or even the smallest tarsier (the smallest among tarsier is pygmy tarsier (Tarsier pumilus)).[4]

What, then, do we know about the Philippine tarsier? This species, of weight range 83-183g, occupies few Philippine islands.[6] In addition to Bohol (recognized as subspecies T. syrichta fraterculus), other places where it can be found include Leyte and Samar (T. syrichta syrichta), Mindanao (T. s. carbonarius) as well as Surigao, Basilan and Dinagat.[6] The latter includes tarsiers that, according to the latest genetic findings, may soon be considered as a separate lineage.[7] On the other hand, the natural history of the Philippine tarsiers looks vague. The evidence, especially geological, is scarce, but it is believed that the species immigrated to the Philippines from Borneo between late Miocene to mid-Pleistocene via Sulu archipelago.[6]

The behaviour of tarsiers is very difficult to uncover. However, thanks to radio, telemetry and other technical advancements, some important data on the Philippine tarsier, although limited, was collected in the past several years.[8-12] Studies revealed that this species on average occupies home ranges of 2.45 ha for females and 6.45 ha for males, travels nightly from 260 m to 2284 m and its primary locomotor behaviour is leaping on vertical supports.[8,9] The Philippine tarsiers inhabit mainly secondary lowland rainforest in early to mid-successional stage.[9] Based on recordings from 25 individuals, 8 types of audible calls were distinguished for the species, which are emitted mainly around sunset and a less frequently at sunrise.[10] What is more, it was found that in addition to vocalizations heard by human hearing, the Philippine tarsiers produce ultrasonic vocalizations (USVs).[11] It was also reported that Philippine tarsiers can be predated by cats and monitor lizards, and probably many more.[8,12] Finally, though no one is sure of its exact social system, available evidence suggests that the Philippine tarsiers are rather solitary.[8,9]

The Philippine tarsier was assessed as Near Threatened (NT).[13] This is because while there are still tarsiers in the forest, we do not know the exact or even approximate population estimates. What is more, the particular subspecies are not studied and assessed properly. Finally, the main threats the species faces, which are disappearing forest cover and hunting, still occur.[13] Deforestation in the Philippines is a major problem. Still, the second threat, hunting, due to its faster pace, is the main for the species. Expanding human population encourages development that is closer and closer to the tarsiers’ habitat. It not only increases predation by domesticated cats, more frequent in the area, but increases temptation of relatively easy income in the form of selling captured tarsiers. Based on my observation, it can take place directly, with the primates as the main target to catch, or they can be obtained from the wild as “by-catch,” which occurs when the hunter goes to the forest to collect other animals, for example, birds, but when tarsiers are spotted, they are captured as additional benefit. Later on, they are sold to private owners as pets. Tourism encourages this. Tarsiers are rarely kept in suitable conditions. For example, instead of resting during the day like their biology demands, tarsiers are exposed to crowds of people during the day. In some places visitors can touch them. Under those circumstances, along with inappropriate feeding, they ultimately die, and breeding does not occur, due to challenges in keeping this sensitive species in captivity. However, because of intervention from foreign organizations, the situation has become slightly better.[14]

As mentioned above, keeping this sensitive species in captivity is extremely difficult. Efforts to breed the Philippine tarsier were made across Western countries in past decades, without any success. The same is happening in the Philippines. The biggest problem is the very low survival of offspring. The backup captive population for any conservation action is therefore not existent. Recently, an attempt to change the situation has been made by Tarsius Project, which is working on the development of the Tarsier Conservation Center. The core activity of this complex initiative is to establish a viable breeding colony in the country of origin in a purely scientific way. All of the possible causes of failure in Western countries were minimalized by reducing stress due to transportation of animals, providing natural climate and conditions (enclosures are big and planted with natural vegetation providing a miniature habitat for tarsiers live in) as well as providing tarsiers with a variety of natural nutritionally rich food, including crickets, prey mantids, spiders, katydids, grasshoppers, dragonflies, cicadas and moths. Results look promising.

However, it is not enough to secure the survival of tarsiers. To make that happen local people should be knowledgeable about tarsiers and other wildlife, as well as their relationships and dependence on forest. The current situation in this regard is not satisfactory. Thus, staff of the Project created a few educational programs for different school levels, from elementary schools to universities with several institutions already involved in those activities. What is more, to improve environmental awareness among pupils, the traineeship curriculum for teachers has been designed and conducted. Trained teachers are aware about environmental issues and are encouraged to incorporate their gained knowledge in early teaching. Further, the Project tries to involve as many local residents as possible in small livelihood projects, reducing dependence of villagers on natural resources. Those activities provide solutions and ideas which can be easily adopted by other projects or conservation centers in the Philippines. Only this kind of complex initiatives, touching all of the issues related to wildlife conservation are successful to improve the situation and reduce the risk of extinction of any of endemic and interesting species, including tarsiers.

Filip Wojciechowski is a primate lover and holds a Master’s degree in environmental biology, majoring in zoology, obtained from Adam Mickiewicz University in Poland. For a few years, he had assisted in primate husbandry in the Poznań Zoological Garden and conducted fieldwork in Vietnam, contributing to the conservation status assessment of the critically endangered Delacour’s langur. Since July 2014, he is tied up with the Tarsius Project, currently as a Field Manager in charge of research, environmental and conservation education and tarsiers husbandry in developing Tarsier Conservation Center in Bilar, Bohol, Philippines focused on the Philippine tarsier.



  1. Simons, E. L. The Fossil Record of Tarsiers Evolution. 2003. In: Wright, P.C., E.L. Simons & S.L. Gursky (Eds.). 2003. Tarsiers: Past, Present, and Future (Rutgers Series in Human evolution). Rutgers University Press, New Jersey, London: 9-34.
  2. Jablonski, N. G. The Evolution of the Tarsiid Niche. 2003. In: Wright, P.C., E.L. Simons & S.L. Gursky (Eds.). 2003. Tarsiers: Past, Present, and Future (Rutgers Series in Human evolution). Rutgers University Press, New Jersey, London: 35-49.
  3. The IUCN Red List of Threatened species.
  4. Grow, N. & Gursky, S.L. 2010. Preliminary Data on the Behavior, Ecology, and Morphology of Pygmy Tarsiers (Tarsius pumilus). International Journal of Primatology 31, 1174–1191.
  5. Madame Berthe’s Mouse Lemur.
  6. Dagosto, M., Gebo, D. L. and Dolino, C. N. The Natural History of the Philippine Tarsier (Tarsius syrichta). 2003. In: Wright, P.C., E.L. Simons & S.L. Gursky (Eds.). 2003. Tarsiers: Past, Present, and Future (Rutgers Series in Human evolution). Rutgers University Press, New Jersey, London: 237-259.
  7. Brown, R. M., Weghorst, J.A., Olson, K.V., Duya, M.R.M., Barley, A.J., Duya, M.V., et al. (2014). Conservation Genetics of the Philippine Tarsier: Cryptic Genetic Variation Restructures Conservation Priorities for an Island Archipelago Primate. PLoS ONE 9(8): e104340. doi:10.1371/journal.pone.0104340
  8. Dagosto, M., Gebo, D.L. & Dolino, C. 2001. Positional Behavior and Social Organization of the Philippine Tarsier (Tarsius syrichta). Primates 42, 233-243.
  9. Neri-Arboleda, I., Stott, P. & Arboleda, N.P. 2002. Home Ranges, Spatial Movements and Habitat Associations of the Philippine Tarsier (Tarsius Syrichta) in Corella, Bohol. Journal of Zoology 257, 387-402.
  10.  Gursky-Doyen, S.L. 2013. Acoustic characterization of ultrasonic vocalizations by a nocturnal primate Tarsius syrichta. Primates, DOI 10.1007/s10329-013-0349-3
  11. Řeháková-Petrů M., Peške L., Daněk T. 2012. Predation on a wild Philippine tarsier (Tarsius syrichta). Acta Ethologica, 15, 2, 217-220, DOI: 10.1007/s10211-011-0096-7
  12. Řeháková-Petrů, M., Policht, R., Peške L. (2012) Acoustic repertoire of the Philippine tarsier (Tarsius syrichta) and individual variation of long distance calls, International Journal of Zoology, Volume 2012 (2012), Article ID 602401, doi:10.1155/2012/602401
  13. Shekelle, M. & Arboleda, I. 2008. Tarsius syrichta. The IUCN Red List of Threatened Species 2008: e.T21492A9289252. Downloaded on 28 October 2015.
  14. Tarsius Project: Research and Conservation on the Philippine Tarsier (Tarsius syrichta).
  15. Padua, M. A. 1994. Conservation Awareness through an Environmental Education Programme in the Atlantic Forest of Brazil. Environmental Conservation, 21 (2), DOI: 10.1017/S0376892900024577.
  16. Patel, E. R., Marshall, J. J., and Parathian, H. 2005. Silky Sifaka (Propithecus candidus) Conservation Education in Northeastern Madagascar. Laboratory Primate Newsletter, 44 (3): 8-11.

Sunday, December 6, 2015

Is Human Morality a Product of Evolution?

Nearly 150 years ago, Charles Darwin proposed that morality was a byproduct of evolution, a human trait that arose as natural selection shaped man into a highly social species—and the capacity for morality, he argued, lay in small, subtle differences between us and our closest animal relatives. “The difference in mind between man and the higher animals, great as it is, certainly is one of degree and not of kind,” he wrote in his 1871 book The Descent of Man.

For the last 30 years, the psychologist Michael Tomasello has been studying those differences of degree, trying to determine how our species’ social nature gave rise to morality. The co-director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, Tomasello has spent much of his career conducting experiments that compare the social and cognitive abilities of chimpanzees, our closest relative in the animal kingdom, and human toddlers. In his forthcoming book A Natural History of Human Morality, he draws on decades’ worth of work to argue for the idea that humans’ morality, unique in the animal kingdom, is a consequence of our tendency to collaborate and cooperate in ways that other great apes do not.

China Photos / Reuters

Beginning in the early 20th century, research on non-human primates—like chimpanzees, bonobos, and orangutans—has shown that they are capable of many things once considered uniquely human, like tool-making, empathy, discerning the intentions and goals of others, and forming friendships. But humans also have language, laws, institutions, and culture. For a long time, the dominant explanation for these uniquely human concepts was our raw intelligence—the human brain is three times larger than the chimpanzee brain—but in recent years, some scientists have also argued that our more social nature may be what’s allowed us to advance so much further than the apes.

But as Tomasello argues in his book, this “social intelligence hypothesis” is something of an understatement. A social nature isn’t enough to fully distinguish between humans and chimpanzees—male chimpanzees can form political alliances, for example, and sometimes work together to hunt, both of which require advanced social skills. Humans are not just socially intelligent, then; as Tomasello and others have put it, we’re “ultra-social” in ways that the great apes are not, with an enhanced capacity for cooperation that arose somewhere along our species’ evolutionary path.

“It is inconceivable that you would ever see two chimpanzees carrying a log together.”

Tomasello has conducted dozens of studies to support this idea. In one study published in 2007, he and his colleagues gave 105 human toddlers, 106 chimpanzees, and 32 orangutans a battery of tests assessing their cognitive abilities in two domains: physical and social. The researchers found that the children and the apes performed identically on the physical tasks, like using a stick to retrieve food that was out of reach or recalling which cup had food in it. But with the social tests—like learning how to solve a problem by imitating another person, or following an experimenter’s gaze to find a treat—the toddlers performed about twice as well as the apes.

Related to this enhanced social ability is a greater tendency to work together, even on tasks where collaboration isn’t necessary. In a 2011 study by Tomasello and his Planck Institute colleagues, 3-year-old children and chimpanzees were given an opportunity to obtain a reward either on their own or by collaborating with another member of their species. The experiment was set up so that the children and the apes knew a) that they would get the reward regardless of whether they worked with a partner, and b) that working with a partner would mean both of them got the same reward. Children, the researchers found, were much more likely to collaborate than chimpanzees.

There are many theories for why humans became ultra-social. Tomasello subscribes to the idea that it’s at least partly a consequence of the way early humans fed themselves. After humans and chimpanzees diverged from their common ancestor around 6 million years ago, the two species adopted very different strategies for obtaining food: Chimpanzees, who eat mostly fruit, gather and eat the majority of their food alone; humans, by contrast, became collaborative foragers. The fossil record shows that as early as 400,000 years ago, they were working together to hunt large game, a practice that some researchers believe may have arisen out of necessity—when fruits and vegetables were scarce, early humans could continue the difficult work of foraging and hunting small game on their own, or they could band together to take home the higher reward of an animal with more meat.

Chimps show no signs of this ability. “It is inconceivable,” Tomasello has said, “that you would ever see two chimpanzees carrying a log together.” In one of the earliest studies of chimpanzee cooperation, published in 1937, chimpanzees only worked together to pull in a board with food on it after they’d been extensively trained by an experimenter—they showed no natural ability to do it on their own. (Even when chimpanzees do collaborate, there’s been no evidence to date that they have the ability to adopt complementary roles in group efforts or establish a complex division of labor.)

But collaboration didn’t just change the way early humans procured food, Tomasello argues; it also changed how humans understood themselves in relation to others. Specifically, people came to think of themselves as part of a larger unit whose members worked together for mutual gain. They began, in other words, to have what Tomasello calls “shared intentionality.” This, he says, is the subtle cognitive capacity—that difference of degree Darwin wrote about—that sets humans apart from the great apes, the reason why we have developed cultural institutions and engage in large-scale collaborative activities. Sharing intentions means that two minds are paying attention to the same thing and working toward the same goal, but each with its own perspective on that shared reality.

This shared intentionality, Tomasello believes, is the basis of morality. Some psychologists and philosophers break morality into two components: sympathy, or concern for another individual; and fairness, the idea that everyone should get what they deserve. Many animals are capable of the former—a chimpanzee, for example, will behave in altruistic ways, like retrieving an out-of-reach object for another chimp—but only humans, it appears, have a sophisticated understanding of fairness.

To illustrate this point, Tomasello uses the example of two people working together to pick fruit from a tree: The first person boosts up the second to get to the top of the tree, where he picks fruit for the both of them. The underlying assumption in this interaction is that each person will fulfill the duties of his unique role, and that, once the fruit has been collected, it will be divided fairly. If one person abandoned the task, or gave in to the impulse to take more than his share, the mutual benefit of their partnership would be negated.

A similar scenario has played itself out in Tomasello’s lab: In one experiment, pairs of chimpanzees were brought into a room and given the opportunity to work together to get some fruit. When the fruit was already pre-divided into equal portions, both primates took only their share. But when they had to divide it up themselves, the dominant chimpanzee generally took most or all of it.

When toddlers were faced with a similar task of collaborating to obtain food or toys, and then dividing up those toys, they generally split them up equally. If the two children each worked separately on the same task, though, and one obtained more toys that the other, the luckier child generally didn’t share with the unluckier one. Through their actions, the researchers concluded, the children in the study seemed to believe that fairness was the equal division of spoils when both parties worked together to obtain them—that sharing was fair only in the context of collaboration.

In The Descent of Man, Darwin wrote: “I fully subscribe to the judgment of those writers who maintain that of all the differences between man and the lower animals, the moral sense or conscience is by far the most important.” By extension, then, our enhanced ability to cooperate may be the most significant distinction between us and our closest evolutionary relatives.


Friday, December 4, 2015

Open Season Is Seen in Gene Editing of Animals

SIOUX CENTER, Iowa — Other than the few small luxuries afforded them, like private access to a large patch of grass, there was nothing to mark the two hornless dairy calves born last spring at a breeding facility here as early specimens in a new era of humanity’s dominion over nature.

But unlike a vast majority of their dairy brethren, these calves, both bulls, will never sprout horns. That means they will not need to undergo dehorning, routinely performed by farmers to prevent injuries and a procedure that the American Veterinary Medical Association says is “considered to be quite painful.”

Instead, when the calves were both just a single cell in a petri dish, scientists at a start-up company called Recombinetics used the headline-grabbing new tools of gene editing to swap out the smidgen of genetic code that makes dairy cattle have horns for the one that makes Angus beef cattle have none. And the tweak, copied into all of their cells through the normal machinery of DNA replication, will also be passed on to subsequent generations.

A calf, left, approximately the same age as the first two genetically modified calves to have their DNA edited so that they do not grow horns, right.
Credit: Jenn Ackerman for The New York Times

“It’s pretty cool,” said Micah Schouten, the calves’ caretaker, looking at his charges.

The uproar over the new ease and precision with which scientists can manipulate the DNA of living things has centered largely on the complicated prospect of editing human embryos. But with the federal government’s approval last week of a fast-growing salmon as the first genetically altered animal Americans can eat, a menagerie of gene-edited animals is already being raised on farms and in laboratories around the world — some designed for food, some to fight disease, some, perhaps, as pets.

Just this week, researchers reported having edited mosquitoes so that they will no longer carry the parasite that causes malaria. And the power to reshape other species, scientists and bioethicists say, raises questions that are both unique to animals and may bear on the looming prospect of fiddling with our own.

“We’re going to see a stream of edited animals coming through because it’s so easy,” said Bruce Whitelaw, a professor of animal biotechnology at the Roslin Institute at the University of Edinburgh. “It’s going to change the societal question from, ‘If we could do it, would we want it?’ to, ‘Next year we will have it; will we allow it?’ ”

A genetically engineered salmon, top, and a regular one.
Credit: Paul Darrow for The New York Times

Animal breeders have for centuries scoured species for desirable traits and combined them the old-fashioned way, by selective mating. But that process can take decades to achieve a particular goal, like cows that are both resistant to disease and produce a lot of milk. And until recently, genetic engineering techniques used to manipulate DNA had been so imprecise as to make them too expensive and difficult to perform in many animals.

But the new techniques, collectively called “gene editing” to reflect the relative ease of their use, have made all manner of previously impossible or impractical goals sufficiently fast and cheap for many to find worth pursuing. Using enzymes that can be directed to cut DNA at specific locations, they allow scientists to remove and replace bits of genetic code more or less on demand. “It’s like a find-replace function in the genome of these animals,” said Scott Fahrenkrug, the chief executive of Recombinetics, based in St. Paul. “It allows us to find the natural variation that exists across a species and quickly bring it under one hood.”

At Roslin, for instance, Dr. Whitelaw has changed three genes in domesticated pigs vulnerable to African swine fever, which can devastate herds, to resemble those from wild pigs that are resistant to the disease. He is now breeding them to put them to the test.

With a tool called Talens, Recombinetics says it has created gene-edited pigs that can be fattened with less food and Brazilian beef cattle that grow large muscles, yielding more meat that may also be more tender. Others are working on chickens that produce only females for egg-laying and cattle that produce only males, since females are less efficient at converting feed to muscle.

Pig26, which was genetically modified as part of the research by the University
 of Edinburgh’s Roslin Institute to develop resistance to African swine fever.
Credit: Norrie Russell/The Roslin Institute

Chinese researchers have produced meatier cashmere goats that also conveniently grow longer hair for soft sweaters, miniature pigs lacking a growth gene to be sold as novelty pets and bulky beagles lacking a muscle-inhibiting gene, an edit that could make for faster dogs.

Using the most powerful of the new tools, called Crispr-Cas9, in pursuit of treatments for human disease, researchers are also altering pigs in hopes of making them grow human organs and creating “gene drives” that would ensure that the edit to make mosquitoes malaria-proof, for instance, would spread through the whole population.

An Accelerating Pace

But the rapid advent of gene-edited animals threatens to outstrip public discussion of their risks and benefits, some scientists and bioethicists have warned.

“This essay is, in essence, a plea — let’s not ignore the nonhuman part of the biosphere,” Alta Charo of the University of Wisconsin and Henry T. Greely of Stanford University cautioned in an article titled “Crispr Critters and Crispr Cracks,” to be published in The American Journal of Bioethics next month. “Not only is it much larger than the human part, but it is much more susceptible to unobserved or unfettered — but not unimportant — changes.”

The discussion of gene-edited animals in farming, in particular, will most likely be colored by the existing debate over the merits of genetically engineered food, which for decades has largely centered on corn and soybeans, altered with older technology to resist pests and tolerate herbicides. Opposition to such crops, known as genetically modified organisms, or GMOs, has prompted some retailers to decline to sell food made with them, and efforts to pass legislation to label them, even as farmers have widely embraced them and scientific organizations have said they are as safe for human health and the environment as conventional crops.

Many of the new generation of edited animals do not contain DNA from another species, a frequently cited concern among opponents of genetically engineered foods, which incorporate genes from bacteria. But some consumer advocates say it may be even more difficult to reach consensus on what, if anything, should be done to the DNA of animals.

“Animals on some level will always be more controversial,” said Greg Jaffe, director of biotechnology for the Center for Science in the Public Interest, a nonprofit consumer advocacy group. “If only because people think of them as closer to humans.”

Beagles bred to build more muscle.
Credit: Zhiwei Wu

Advocates of the technology argue that it can make farming more efficient to help feed a growing world population with less of a toll on the environment. One projection published in a leadinganimal breeding journal, Genetics Selection Evolution, suggests that genome-editing could significantly increase the efficiency the livestock industry is able to achieve through conventional breeding within the same time period.

Today’s chickens, for instance, produce nearly 80 percent more meat for the same amount of feed as the chickens of the 1950s; if chicken breeders had had access to genome technology over that time, said John Hickey, a quantitative geneticist and a co-author of the paper, farmers would have been able to achieve that increase and also be able to grow chickens on half the land.

Others say the technology could benefit human health. The National Science Foundation is underwriting an effort to create dairy cattle that can resist a parasite that causes sleeping sickness in sub-Saharan Africa, a blight often treated with an antimicrobial drug that ended up making its way into the meat consumed by humans.

Several projects underway to edit genetic resistance to a variety of diseases in livestock could theoretically reduce the overuse of antibiotics, which has made it harder to treat human bacterial infections. With funds from the United States Department of Agriculture, Bhanu Telugu, a University of Maryland researcher, is trying to design pigs so they can no longer serve as a reservoir for the flu virus. He argues for genome editing on behalf of animal health, too. “If we know we can eliminate the disease and we don’t, it is in my mind animal cruelty,” he said.

Fallout in the Food Chain

Still, some consumer advocates urge caution in applying techniques that are still so new to animals that will be consumed as food. Gene-editing tools are known to sometimes make changes to genes other than their intended targets, raising flags about how the changes might affect an animal’s health or the composition of milk or meat.

“You are reducing the universe of potential risks by moving into these techniques,” said Doug Gurian-Sherman, a senior scientist at the Center for Food Safety, a consumer advocacy organization that has been at the forefront of opposition to genetically engineered plants and animals. “But that is not to say we should not still proceed with great caution.”

And some animal rights advocates say gene-editing is simply a means to prop up an industry that causes animals to suffer.

The calves who were modified to not grow horns. “It’s pretty cool,” said Micah Schouten, their caretaker.
Credit: Jenn Ackerman for The New York Times

“Even if they can point to good intentions, it’s just exacerbating the problem,” said David Byer, a spokesman for People for the Ethical Treatment of Animals. The organization, which has urged the dairy industry to stop the practice of dehorning cattle, does not support gene-editing as a solution.

“People should stop consuming dairy or meat or eggs, not further manipulate animals by playing with their DNA,” Mr. Byer added.

The Food and Drug Administration has not said how or whether it will regulate the gene-edited animals to come. But even with the government’s stamp of approval, biotechnology advocates know that farmers are unlikely to embrace technology if they fear consumers will reject it.

And it has not helped the popularity of genetically engineered crops that their chief benefits so far — easier control of weeds and pests for corn and soybean farmers — are not terribly compelling to the eating public.

That is one reason Recombinetics has begun to show off its hornless calves.

Dehorning, which involves burning off horn-buds to stop the flow of blood to the horn tissue, has already garnered a degree of popular concern. Videos of the burning procedure carried out on Holsteins, the black-and-white breed largely responsible for the nation’s milk supply, and circulated by animal rights groups, draw long strings of critical comments.

“We know there’s a negative public perception of dehorning, and it’s certainly not a fun chore for the farmers,” said Lindsey Worden, the executive director for genetics at the Holstein Association.

A small fraction of Holsteins are naturally hornless, and several companies, including General Mills, Dannon and Walmart, have encouraged their dairy suppliers to increase their population through conventional breeding. Farmers have made some headway, with the population of hornless Holsteins climbing to about 4 percent last year from 3 percent in 2013.

But it is slow going. That is why several dairy breeders say they are keeping tabs on Recombinetics’ two hornless calves, which have just been shipped to the University of California, Davis, to be monitored for their health. There, in a few months, their sperm will be harvested, each with edited DNA, which will be used to create a new generation of hornless cattle.

Whether they will become commonplace or remain curiosities may depend largely on how the public comes to view gene editing and its various applications.

“Sometimes you can have nice benefits for animals and farmers and society but still have controversy among consumers,” said Jamie Jonker, vice president for sustainability and scientific affairs at the National Milk Producers Federation. “I think dairy farmers are going to want to see how this is interpreted by the general public.”


Wednesday, December 2, 2015

Apocalypse Pig: The Last Antibiotic Begins to Fail

I mentioned on Monday that this past week was intended by the CDC, WHO and other health authorities to be a global awareness week for antibiotic resistance. Alarming news that came out of China at the end of the week certainly created new awareness of resistance, but possibly not what the organizers had in mind.

On Thursday, researchers from several Chinese, British and US universitiesannounced in the journal Lancet Infectious Diseases that they have identified a new form of resistance, to the very last-ditch drug colistin—and that it is present in both meat animals and people, probably comes from agricultural use of that drug, can move easily among bacteria, and may already be spreading across borders.

A pig being home-raised for a festival in China. PHOTOGRAPH BY CLEMSON, FLICKR (CC).

This is very bad news.

To understand why, it’s necessary to know a little bit about colistin. It is an old drug: It was first introduced in 1959. It has been on the shelf, without seeing much use, for most of the years since, because it can be toxic to the kidneys. And precisely because it hasn’t been used much, bacteria have not developed much resistance to it. It remains effective.

That neglect turned out to be very fortunate a few years ago when several different resistance factors—NDM, OXA, KPC—started hopscotching around the globe. All of them made bacteria invulnerable to a group of drugs called carbapenems that had been considered a last line of defense: They were the last drugs that were in common use and were able to take care of complex infections that happen in hospitals, caused by E. coli, Klebsiella, Acinetobacter and similar gut-dwelling organisms. Once those bacteria became resistant to carbapenems (earning them the general name of “carbapenem-resistant Enterobacteriaceae,” or CREs), colistin was all that was left—and colistin use began rising.

(From around that time: Here’s a great story that Jason Gale of Bloomberg wrote about colistin, and one I wrote for Nature about CREs. A long series of posts I wrote for WIRED about the discovery of NDM and the bitter political fights over its apparent origin in India can be found here. Of note, one of the discoverers of NDM is one of the authors of this new research.)

A thing about colistin, which no one seems to have connected the dots on: Because it is an old drug, it is cheap. And because it is cheap, it is an affordable addition to animal feed for all the uses I’ve talked about before: to make animals put on muscle mass faster, and protect them from the conditions of intensive farming.

Which, apparently, is how it is being used in China—but not only in China. From the paper:
China is… one of the world’s highest users of colistin in agriculture. Driven largely by China, the global demand for colistin in agriculture is expected to reach 11,942 tonnes per annum by the end of 2015 (with associated revenues of $229·5 million), rising to 16,500 tonnes by the year 2021, at an average annual growth rate of 4·75%. Of the top ten largest producers of colistin for veterinary use, one is Indian, one is Danish, and eight are Chinese. Asia (including China) makes up 73·1% of colistin production with 28·7% for export including to Europe.

Where sampling for the MCR resistance study took place.Where sampling for the MCR resistance study took place. GRAPHIC FROM LIU ET AL, LANCET INFECTIOUS DISEASES; ORIGINAL HERE.
The findings reported this week originate in an ongoing project in which the Chinese authors were looking for resistance in the E. coli that reside in the guts of food animals. (It’s encouraging that such a project exists.) They say they first perceived a colistin-resistant E. coli in 2013, in a pig from an intensive farm near Shanghai, and then noted increasing colistin resistance over several years. They expanded their research to include, not just samples from animals as they were slaughtered, but sampling of retail meat from supermarkets and street markets, and testing of samples previously taken from patients in two hospitals. The samples were collected between 2011 and 2014.

Here’s what they found. The gene they discovered, which directs colistin resistance and which they dubbed MCR-1, was present:

  • in 78 (15 percent) of 523 samples of raw pork and chicken meat
  • in 166 (21 percent) of 804 pigs in slaughterhouses
  • and in 16 (1 percent) of 1,322 samples from hospital patients with infections.
That last is important: The bacteria possessing this resistance were not, as sometimes happens, merely gut bacteria that had acquired the necessary DNA but were hanging out quietly in the intestines and not causing trouble. They are already causing human infections.

And, of most concern: The MCR-1 gene that creates this resistance is contained on a plasmid, a small piece of DNA that is not part of a bacteria’s chromosome. Plasmids move freely around the bacterial world, hopping from one bacterium to another; in the past, they have transported resistance DNA between bacterial species, facilitating resistance’s rapid movement around the globe. This gene, the authors predict, will be able to do that as well.

The rapid dissemination of previous resistance mechanisms (eg, NDM-1) indicates that, with the advent of transmissible colistin resistance, progression of Enterobacteriaceae from extensive drug resistance to pan-drug resistance is inevitable and will ultimately become global.

“Pan-drug resistance,” to be clear, means that nothing at all will work—that infections are untreatable by any known compound.

It’s worth noting that not every dire superbug prediction comes true. In the early 2000s, physicians were very alarmed when resistance to vancomycin—like colistin, another last-resort antibiotic preserved from the 1950s—moved via a plasmid fromEnterococcus into Staphylococcus aureus, or staph. At the time, people were already worried about the better-known form of drug-resistant staph, MRSA; the emergence of VRSA, as it became known, ratcheted worries way up. In the end, though, VRSA turned out not to be much of a threat: In 15 years, there have been only 14 such infections in the United States.

How plasmids (the blue loops) move among bacteria.
How plasmids (the blue loops) move among bacteria. 

It’s worth noting that not every dire superbug prediction comes true. In the early 2000s, physicians were very alarmed when resistance to vancomycin—like colistin, another last-resort antibiotic preserved from the 1950s—moved via a plasmid fromEnterococcus into Staphylococcus aureus, or staph. At the time, people were already worried about the better-known form of drug-resistant staph, MRSA; the emergence of VRSA, as it became known, ratcheted worries way up. In the end, though, VRSA turned out not to be much of a threat: In 15 years, there have been only 14 such infections in the United States.

But what makes MCR, this new colistin resistance, different from VRSA is the role that agriculture seems to be playing in its evolution and dispersal. There are two problems here. First, that thousands to millions of animals are getting the drug, which exponentially expands the opportunities that favor resistance. And second, that projects such as the Chinese one that allowed the new gene to be discovered are rare—so colistin resistance could begin moving, from animals and into people, without being noticed.

And, in fact, it may be on the move now. The authors note that, while they were writing up their findings, the European Molecular Biology Laboratory received five submissions of bacterial data that appeared to contain the MCR gene—but not from China; from Malaysia.

What will happen next? Unfortunately, we have to wait and see—and hope that systems are built that will perceive this new resistance if it arrives. Meanwhile, I especially appreciate the reaction of Mike the Mad Biologist, who knows a great deal about resistance in his real life and can be counted on to be exasperated and blunt. He said, about this discovery:

If this doesn’t convince people to get serious about the agricultural side of the problem, I don’t know what will.