Five Memorable Animals Who Expanded the Scientific Frontier
Untold numbers of animals have contributed to science, in ways big and small. Studying cows and cowpox helped English doctor Edward Jenner create a smallpox vaccine; Ivan Pavlov's experiments on dogs' reactions to external stimuli heavily influenced modern behavioral psychology.
We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
Scientists still work with rats, rabbits, and other mammals to test cosmetics and pharmaceuticals and to conduct infectious disease research. Most of these animals remain nameless and unknown to the public, but over the years, certain individuals have had an outsize effect. We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
1) LAIKA THE DOG
Laika was the first living creature ever to orbit the Earth. In October 1957, the Soviet Sputnik I ship had made history as the first man-made object sent into Earth's orbit; Premier Nikita Khrushchev was keen to gain another Space Race victory by sending up a canine cosmonaut.
Laika ("barker" in Russian), was a stray dog, reportedly a husky-spitz mix, recruited among several other female strays for the trip. Although the scientists put extensive work into preparing Laika and the other canine finalists—evaluating their reactions to air-pressure variations, training them to adapt to pelvic sanitation devices meant to contain waste, and eventually having them live in pressurized capsules for weeks—there was no expectation that the dog would return to Earth, and only one meal's worth of food was sent up with her.
Laika the dog, with a mockup of her space capsule.
Sputnik II, six times heavier than its predecessor, launched on November 3, 1957. Soviet broadcasts reported that Laika, fitted out with surgically implanted devices to monitor her heart rate, blood pressure, and breathing rates, survived until November 12; the spacecraft stayed in orbit for five more months, burning up when it re-entered the atmosphere.
At the time, the Sputnik II team reassured the world that Laika had died painlessly of oxygen deprivation. It was only decades later, in the 1990s, that Oleg Gazenko—one of the scientists and dog trainers assigned to the mission—revealed that Laika had died 5 to 7 hours after launch from a combination of heat and stress. The capsule had overheated, probably as a result of the rushed preparation; after the fourth orbit, the temperature inside Sputnik was over 90 degrees, and it's doubtful she could have survived much past that. "The more time passes, the more I'm sorry about it. We shouldn't have done it," Gazenko said. "We did not learn enough from the mission to justify the death of the dog."
Yet even the four or five orbits that Laika did complete were enough to spur scientists to press on in the effort to send a human into space.
2) HAM THE CHIMP
Four years after Laika's ill-fated flight, a chimpanzee named Ham entered suborbital flight in the American Project Mercury MR-2 mission on January 31, 1961, becoming the first hominid in space—and unlike Laika, he returned to Earth, alive, after a 16-minute flight.
Even though Ham's flight was not destined for orbit, the spacecraft and booster used on his trip were the same combination intended for the first (human) American's trip later that year. If he came back unharmed, NASA's medical team would be prepared to okay astronaut Alan Shepard's flight.
Ham receives his well-deserved apple.
For approximately 18 months before liftoff, Ham was trained to perform simple tasks, like pushing levers, in response to visual and auditory cues. (If he failed, he received an electric shock; correct performance earned him a treat. Pavlov would have been pleased.)
At 37 pounds, Ham was also the heaviest animal to ever make it to space. His vital signs and movements were monitored from Earth, and after a light electric shock from the ground team reminded him of his tasks, he performed his lever-pushing just a bit slower than he had on Earth, verifying that motion would not be seriously impaired in space.
Less than three months after Ham returned to Earth, on April 12, 1961, Soviet cosmonaut Yuri Gagarin became the first human to complete an orbital flight; Shepard was close behind, successfully crewing the MR-3 mission on May 5. For his part, Ham "retired" to the National Zoo in Washington D.C. for 17 years, before being transferred to the North Carolina Zoological Park; he died of liver failure in 1983 at age 26. His grave is at the International Space Hall of Fame in New Mexico.
3) KOKO THE GORILLA
A western lowland gorilla born at the San Francisco Zoo, Hanabi-ko, or "Koko," became famous in the 1970s for her cognitive and communicative abilities. Psychologist Francine "Penny" Patterson, then a doctoral student at Stanford, chose Koko to work on a language research project, teaching her American Sign Language; by age four, Koko demonstrated the ability both to make up new words and to combine known words to express herself creatively, as opposed to simply mimicking her trainer.
Koko and Penny compare notes.
Koko's work with Patterson reflected levels of cognition that were higher than non-human primates had previously been thought to have; by the end of her life, her language skills were roughly equivalent to a young child's, with a vocabulary of around 1,000 signs and the ability to understand 2,000 words of spoken English.
An especially impactful study in 2012 showed that Koko had learned to play the recorder, revealing an ability for voluntary breath control that scientists had previously thought was linked closely to speech and could only be developed by humans. Barbara J. King, a biological anthropologist, suggested that Koko's immersion in a human environment may have helped her develop such a skill, and that it might be misleading to consider similar abilities "innate" or lacking in either humans or non-human primates.
Koko's displays of emotions also fascinated the public, especially those that seemed to closely mirror humans': she cared for pet kittens; appeared on Mr. Rogers' Neighborhood and untied the host's shoes for him; acted playfully with Robin Williams during a visit from him, and later expressed grief when told about the comedian's death. Koko died in her sleep in June 2018, at age 46. Patterson continues to run The Gorilla Foundation, which is dedicated to using inter-species communication to motivate conservation efforts.
4) DOLLY THE SHEEP
Dolly—named after country singer Dolly Parton—was the first mammal ever to be cloned from an adult somatic cell, using the process of nuclear transfer. She was born in 1996 as part of research by scientists Keith Campbell and Ian Wilmut of the University of Edinburgh.
Dolly the cloned sheep.
By taking a donor cell from an adult sheep's mammary gland, using it to replace the cell nucleus of an unfertilized, developing egg cell, and then bringing the resultant embryo to term, Campbell and Wilmut proved that even a mature cell (one that had developed to perform mammary gland functions) could revert to an embryonic state and go on to develop into any and all parts of a mammal.
Although cloned livestock are legal in the U.S.—the FDA approved the practice in 2008, after determining that there was no difference between the meat and milk of cattle, pigs, and goats—Dolly has had an even bigger impact on stem cell research. The successful test of nuclear transfer proved that it was possible to change a cell's gene expression by changing its nucleus.
Japanese stem cell biologist Shinya Yamanaka, inspired by the birth of Dolly, won the Nobel Prize in 2012 for his adaptation of the technique. He developed induced pluripotent stem cells (iPS cells) by chemically reverting mature cells back to an embryonic-like blank state that is highly desirable for disease research and treatment. This technique allows researchers to work with such stem cells without the ethically charged complication of having to destroy a human embryo in the process.
5) LAIKA THE PIG
Named in honor of the dog who made it to space, the second science-famous Laika was a genetically engineered pig born in China in 2015 as a result of gene editing carried out by Cambridge, MA startup eGenesis and collaborators.* eGenesis aims to create pigs whose organs—hearts, kidneys, lungs, and more—are safe to transplant into people.
Laika the gene-edited pig.
Using animal organs in humans (xenotransplantation) is tricky: the immune system is very good at recognizing interlopers, and the human body can start to reject an organ from another species in as little as five minutes. But pigs are otherwise exceptionally good potential donors for humans: their organs' sizes and functions are very similar, and their quick gestation and maturation make them attractive from an efficiency standpoint, given that twenty Americans die every day waiting for organ donors.
Perhaps unsurprisingly, Dolly the sheep helped move xenotransplantation forward. In the 1990s, immunologist David Sachs was able to use a similar cloning method to eliminate alpha-gal, an enzyme that is produced by most animals with immune systems, including pigs—but not humans. Since our immune systems don't recognize alpha-gal, attacks on that enzyme are a major cause of organ rejection. Sachs' experiments increased the survival time of pig organs in primates to weeks: a huge improvement, but not nearly enough for someone in need of a liver or heart.
The advent of CRISPR technology, and the ability to edit genes, has allowed another leap. In 2015, researchers at eGenesis used targeted gene-editing to eliminate the genes for porcine endogenous retroviruses from pig kidney cells. These viral elements are part of all pigs' genomes and pose a potentially high risk of infecting human cells. (After the HIV/AIDS crisis especially, there was a lot of anxiety about potentially introducing a new virus into the human population.)
The eGenesis lab used nuclear transfer to embed the edited nuclei into egg cells taken from a normal pig; and Laika was born months later—without the dangerous viral genes. eGenesis is now working to make the organs even more humanlike, with the goal of one day providing organs to every human patient in need.
*[Disclosure: In 2019, eGenesis received a series B investment from Leaps By Bayer, the funding sponsor of leapsmag. However, leapsmag is editorially independent of Bayer and is under no obligation to cover companies they invest in.]
[Correction, March 3, 2020: Laika the gene-edited pig was born in China, not Cambridge, and eGenesis is pursuing xenotransplant programs that include heart, kidney, and lung, but not skin, as originally written.]
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.