Which of the following is most likely to have caused a decline in animal research

Learn how animal testing and research has advanced human health.

Aging

Life expectancy in the United States is 78.8 years: For females, it is at 81.2 years; for males, it’s 76.4 years. Scientists have recently begun exploring the aging process. Google even launched an anti-aging development sector, Calico. Researchers have been studying potential drugs to boost immune functions and slow the aging process. Animal research is being used to determine the effectiveness of anti-aging elements.

Researchers have been studying the drug Metformin, which increases the number of oxygen molecules released into a cell, to determine its effects on aging. An old diabetes drug, Metformin is cheap and has been found to stall the aging process in work with mice and the roundworm c. elegans. Researchers observed a substantial increase in the lifespan and vitality of the animals. Subjects lived to the person equivalent of 120 years. In middle-aged mice, a small dose extended their lives, while a large dose shortened them. The proper dosage also resulted in fewer cases of cataracts and weight gain. Metformin improved the life and health span of the mice, leading researchers to further investigate the drug’s potential protective effect against diseases that become more common with age, like cancer, heart disease, and Alzheimer’s.

The results in animals were so compelling, in 2016 the FDA greenlit human clinical trials known as the Targeting Aging with Metformin (TAME) study. 3,000 elderly people will be tracked for 6 years to see how the drug affects their overall health. Depending on the results of the trial Metformin could become the first ever anti-aging drug. If the results transfer to humans not only will life span increase, but humans will be better protected against age-related diseases.

Other anti-aging drugs are being researched with the help of animals. Recently a team at the University of New South Wales have identified the metabolite NAD+ as key in DNA repair. Our bodies natural ability to repair our DNA declines with age, but mice who received an NAD+ booster improved cells repairability so much so, treated old mice cells were indistinguishable from those of young mice. Human trials will begin in late 2017, and if they succeed the drug could be available in as soon as four years. The progress towards anti-aging drugs offers the prospect of not only a greater life span but a world with less age-related diseases resulting in an overall healthier population. Once on the market for humans, these drugs could also be adapted to improve the lifespan of pets. Animal research has been fundamental in the anti-aging drug prospects we have now and will remain fundamental going forward in our quest to prolongate and improve human life.

Alzheimer’s Disease

Alzheimer’s affects an estimated 44 million people and their families. Alzheimer’s is the sixth leading cause of death in the U.S. with more than 5 million Americans currently living with Alzheimer’s. A new study even estimates that including those who are not yet symptomatic, the number of Americans living with Alzheimer’s may be closer to 11 million. With no cure or effective treatment, research is vital. The estimated cost incurred on the American taxpayer to treat Alzheimer’s patients on Medicare and Medicaid for 2017 is as high as $259 billion. If more effective treatments are not developed, by the year 2050, costs will rise to $1.1 trillion. The institutions conducting Alzheimer’s research publicly recognize the continual need for humane and responsible research with animal models for understanding and curing the disease.

Understanding genetic predisposition to the disease is crucial to finding a cure. Non-human primates are essential to our knowledge of the human brain. Studying brain function in healthy monkey brains, researchers can pin point where human brains suffering from Alzheimer’s, dementia, and other neurological disorders are failing. Progress has also been made in the last decade using mice models to determine the genetic factors of Alzheimer’s. Researchers have been able to identify an early-onset mutation for Alzheimer’s, through studies with humans that was then strengthened with mouse models, and recently a rare protective gene mutation that provides more evidence for excessive levels of a normal brain substance, beta amyloid, as a driving factor of the disease. Identifying this gene mutation is a solid starting point to developing a possible drug to slow or prevent the disease’s progression. Though no one model mimics the disease in humans completely, a group of mouse models together, offer insight into the workings of the disease. Mouse models are also being used to pioneer immunotherapy treatments for Alzheimer’s that are currently in clinical trials. Mouse models have also made an at-home test possible for individuals with a history of Alzheimer’s in their family to assess their own risk of carrying the gene.

Mouse models have also been used in an exciting new drug-free prospect to treat Alzheimer’s. Researchers in Australia have been able to use non-invasive ultra-sound technology to break apart the neurotoxic amyloid plaques responsible for memory loss. The team reported that full memory function in 75% of the mice was restored with no damaged done to the surrounding brain tissue. This offers an entirely new avenue of treatment for the disease, changing our approach to possible treatments. Researchers hope to move to higher animal models before human clinical trials within the next few years.

Mice and non-human primates are advancing our progress towards the prevention and curing of Alzheimer’s and other neurodegenerative diseases. They offer invaluable knowledge of the workings of the brain which can help with all neurological conditions, from Alzheimer’s to autism and bipolar disorder. Our understanding of the human brain would be nowhere near to finding a cure to Alzheimer’s without the use of animal models.

Artificial Blood

Fresh blood can only be stored for 42 days, and only a few hours without proper refrigeration, leaving the world in constant need of blood donations. Artificial blood substitutes are being developed for transfusions to save the lives of trauma patients in emergencies, those undergoing lengthy, complex surgical procedures, and those who are injured in a places lacking access to blood. The quest to create an effective blood substitute has proved a challenging one, but with the animal research promising steps are bring artificial blood closer to a life-saving reality.

Rats and mice have been used to understand the components of human blood for decades. In 1968 a blood substitute, perfluorochemicals (PFC), was suggested in experiments with mice. PFC-based blood alternatives are a major faction of artificial blood research. The FDA has approved one PFC-based alternative, but due to the high amount necessary for efficiency, it is not widely used. Improved PFC-based artificial blood continues to be developed using mice and rats, but have not reached human trials yet.

The biggest challenge in the creation of artificial blood is the protein hemoglobin. In red blood cells, hemoglobin delivers oxygen from the lungs to the necessary tissue, but it also can damage tissue and cause blood vessels to constrict if not properly isolated. Hemoglobin-based products are the second major research faction. One group of researchers have encased hemoglobin in a synthetic polymer. Using rabbits, they are studying the reaction of the aorta to new red blood cells to ensure an identical reaction when their artificial blood is added to the body. Their artificial blood must prove successful in continuing animal tests before it is proved safe enough to start human trials.

Stem cell-based blood substitutes are another avenue used to create artificial blood. Our knowledge of stem cells comes from and continues to progress due to animal research. A stem cell-based substitute has been created that in the United Kingdom is entering human clinical trials in late 2017 after proving safe and effective in animal tests.

Cancer

Cancer deaths have been on a continuous decline in the United States since the 1990’s, but according to the American Cancer Society, there are still 1,658,370 new cancer cases and 589,430 cancer deaths in the U.S. each year. Drugs to treat cancer are more effective than ever before thanks, in large part, to animal models involved in oncology research and testing, but there are still improvements to be made. With the help of dogs, rodents and other animal species, scientists are working toward continuing to lowering mortality rates with the development of more effective cancer treatments, namely gene and immunotherapy.

Many of the cancer-fighting drugs today would not be possible without the use of mice. Chemotherapy was first developed by using modified mustard gas to reduce tumors in mice(1). Another influential cancer drug, Herceptin, popular for improving long-term survival in breast cancer patients, was developed with mice. Continuing to play a role in improving current therapies, but also in newly developing therapies, mice remain a vital part of cancer research. They are even part of burgeoning research in the development of gene therapy to reduce tumor size in ovarian cancer, and a possible vaccination against the development of breast cancer. Another promising development made possible with mice researchers in Sweden recently discovered a possible gene switch within cells that could stop the growth of cancer cells. Healthy cells and cancer cells regulate their growth with different gene switches. In mice, researchers were able to remove a regulatory region that is linked to several different forms of cancer and reduce tumor formation in mice without affecting the growth of healthy cells. This is evidence for the possibility of developing highly specific cancer drugs to stop the formation of cancer cells with no damage to the surrounding normal cells. Mice remain an invaluable part of oncology research and our continued improvement in the remission rate.

Similarly, dogs play a large role in the developing cancer treatments for humans, but also for the estimated 6 million dogs that will be diagnosed with cancer each year in the United States. Thanks to the NHGRI Dog Genome Project’s successful genome mapping of Tasha the Boxer, we have confirmed that many of the genes involved in human cancer are present in that of dogs as well. This helps the development of translational treatments. Half of the dogs over the age of ten will develop cancer, and new drugs are being tested to help dogs in whom surgery is not an option. A new oral medication KInavet is offering promising result in reducing mast cell tumors in dogs. Once the drug has been refined it could be used as a starting point to develop something similar for humans. Bone cancer and many other types of tumors are almost identical to those same kinds found in humans. They progress faster in dogs, making them the ideal -patients to test the effectiveness of new therapies. For bone, breast and skin cancer dogs are especially important to our discovery of new treatments and therapies due to the similarity in cancer’s behavior in both species. Researchers in Switzerland have studied the surrounding tissue in dogs with mammary cancer, identifying that, like in humans, the tumor can influence the surrounding healthy cells to support cancerous growth. This is further evidence for the immense similarity between human and dog tumors, and the crucial value our efforts to cure cancer in dogs holds for also curing cancer in humans. Another convertible cancer is hemangiosarcoma (HSA) in dogs, angiosarcoma in humans, both are extremely aggressive with only half of humans diagnosed living longer than 16 months, and less than half of dogs will live longer than another 4-6 months after diagnosis. Because it is a vascular cancer, it is difficult to treat without inflicting severe damage on the immune system. Researchers have developed a drug, eBAT, to target the tumor with minimal damage to the immune system. eBAT with traditional chemotherapy extended the life spans of the dogs tested. Researchers hope to continue improvements to fight HSA in dogs and to modify the drug for human trials to aid the fight against angiosarcoma and other tumors.

Pioneering treatments are being developed with the help of dogs, such as immunotherapy and bacteria injections to fight cancer. Researchers have injected tumors in dogs with a bacteria that grows and kills cancer cells. The tumors were effectively reduced or eliminated altogether. One human patient has received this bacterium, and researchers hope to continue research with dogs before widespread human trials. The is significant progress because the bacteria target cancer cells only, however for the injections to be effective researchers need to harness the bacteria to target metastases, as they often prove more fatal than the original tumor. Immunotherapy is another developing technique to cure cancer. With one in eight Rottweilers affected by cancer, The Rottweiler Health Foundation is a major supporter of canine cancer research, and immunotherapy is one that has proved successful. Osteosarcoma, bone cancer, is the most common type that affects dogs, and immunotherapy has been used to save many dog’s lives, and in turn, has been modified to successfully treat cancer in humans. Osteosarcoma is another form of cancer that is remarkably similar in humans, specifically children, so testing cures with dogs is progress towards curing the thousands of dogs and children affected. As our research into canine cancer improves so does our developments to fight cancer in humans- man and man’s best friend are a united front in the fight against cancer.

[1] Adair, F.E. and Bagg, H.J. Experimental and clinical studies on the treatment of cancer by dichloro ethyl sulphide (mustard gas) Am. J. Surg 93:190-199, 1931

Cholesterol

Coronary artery disease is the deadliest disease in the world with an approximate 7.4 million deaths a year. Between 1980 and 2010 the number of CAD deaths has been cut in half due to medical advancements resulting from animal research. Both pioneering surgeries, like coronary artery bypass, and heart medications have been refined to reduce the risk of heart attacks in high risk individuals.

High cholesterol is a major contributing factor in cardiovascular health. The science of cholesterol lowering drugs is grounded in animal research; the second and the nineteenth most prescribed drugs in America, Crestor and Zetia, were tested both on mice, dogs, and rats, and Zetia was also developed with rabbits and monkeys. Mice, rat and rabbit models led to the development of statins, a staple in lowering cholesterol and preserving cardiovascular health. A staggering number of American take statins: half of men, ages to 65 to 74, and 39% of women, ages 75 and older, showing how high a priority perfecting heart medications are. Approximately one in four Americans ages 45 or older, an estimated 32 million Americans, take statins to lower their cholesterol. With these cholesterol medications, we can help prevent at risk individuals from having heart attacks by reducing the strain bad cholesterol adds to the cardiovascular system. In 1973, Dr. Akira Endo identified an enzyme, HMG-CoA, as key in producing LDL, or “bad”, cholesterol, therefore blocking this can help reduce one’s cholesterol level. His theory was supported by studies created to block HMG-CoA activity in dogs, rabbits and monkeys, whose circulating LDL cholesterol levels then lowered. Human trials were initiated, but then quickly halted after dosage problems proved fatal to dogs being tested. More animal studies were conducted to determine a safe and effective dose to reduce cholesterol levels. Cholesterol medications are now a vital medication to help protect individuals from heart attacks. Animal research is even making progress towards a cholesterol lowering vaccine that would provide long-term protection. A candidate has recently entered human clinical trials after proving effective at reducing LDL cholesterol in mice. Researchers hope the vaccine will be a simple way to reduce bad cholesterol and ultimately reduce one’s risk of heart disease.

Other heart medications to reduce hypertension in high risk individuals, like beta blockers and ACE inhibitors, were also developed through animal research. Drugs for high blood pressure would not have been possible without animal research. The sixth most prescribed drug in America, tested on rats, mice, rabbits and marmosets, Diovan, is for high blood pressure. Similarly, drugs reducing hypertension all began with research done on mice, eventually proving safe and effective for mice, dogs, and cats before being used to safely reduce blood pressure in humans. James Black developed the first beta blockers after studying guinea pig heart muscles and monitoring the cardiovascular functions of anaesthetized cats. The first ACE inhibitor, Captopril, was introduced in 1981. It effectively treats hypertension through the peptide, bradykinin potentiating factor (BPF), which neutralizes the enzyme responsible for increased blood pressure. This enzyme was identified after testing its effects on anaesthetized dogs. The neutralizing agent, BPF, was then isolated from the venom of the Bothrops jararaca pit viper by Sergio Ferreira. The discovery of BPF is responsible for many innovative heart medications and drug therapies.

Non-human primates are instrumental in our understanding of blood pressure as “long-term blood pressure regulation is nearly identical in humans, baboons, and other NHPs”, and they frequently develop high blood pressure and hypertension as they age. Their life span and the increased development of heart complications with age make baboons and chimpanzees a keystone in our development of medications and treatments to prevent heart disease.

Pets suffer from heart disease as well, but thanks to animal research there are several medications commonly prescribed by veterinarians to treat heart failure in dogs and cats, for example ACE inhibitors are commonly recommended to treat pets with congestive heart failure. These medications alongside proper diet and exercise can effectively treat their condition, extending their life span just like heart medications in humans. Animal research has resulted in life-changing heart medications to improve and prolong the lives of the humans and animals who suffer from heart disease. While the rate of those afflicted with heart disease has greatly dropped it is still a large concern, but with animal research we can expand our knowledge of cardiovascular disease, and its treatments to continue improving cardiovascular health.

Cystic Fibrosis

A genetic disease which affects the lungs, pancreas, and liver, Cystic Fibrosis (CF) is a progressive disease with varying levels of severity and symptoms. While there is no cure, treatments for CF have drastically improved, raising the median lifespan to age 40, when previously most CF patients didn’t live past childhood. Animal models, especially mice, ferrets, and pigs, have been key in developing treatments for CF.

Mice have played a significant role in Cystic Fibrosis research. However, because mice with CF did not contract the lung infections that humans with CF would, scientists conclude that the main difference between mice and human respiratory systems lies in the airway surface liquid (ASL), which protects the respiratory system. CF patients lack the necessary respiratory shield, leading to lung infections. Recently, researchers in Japan have genetically engineered mice which can now closely reproduce the symptoms found in humans, as opposed to the previous mice models which lacked the infections of humans. This helps researchers understand and develop treatments for CF, and other pulmonary diseases.

Other animals which are valuable to Cystic Fibrosis research are pigs and ferrets, as both have longer life spans than mice and have similar CF gene expressions to humans. In 2010 researchers discovered that pigs with CF contract lung infections shortly after birth, mirroring the human experience. Like humans, pigs also struggle to counteract acidity in the ASL. This raised acidity lowers one’s ability to fight infections. Mice can better regulate the PH of their ASL, which in comparisons to pig tests have helped identify an enzyme which could be used to treat humans. This discovery opens the potential for a drug featuring this enzyme which would raise the patient’s immunity against dangerous airway bacteria. Ferret animal models are also helping progress CF treatments, as CF ferrets experience similar resulting ailments such as liver and pancreatic disease. Due to similarities in lung cell biology, the ferret model has been vital to our continued progress in combatting lung infections and is pivotal in our CF research going forward.

Thanks to the contributions of animal research CF treatments have vastly improved, allowing CF patients to live happy lives into late adulthood, and with continued research a cure is possible.

Diabetes

415 million people worldwide are living with diabetes, affecting 29 million Americans. Almost 95% have type two diabetes, which mainly affects overweight individuals. Our understanding of the disease is constantly growing, largely in part to research with dogs and mice, and with that we are able to prevent and effectively treat diabetes. 3 of the 25 most prescribed drugs are for diabetes, and all have been developed with animals. With the continued use of animal research, significant progress has been made to treat diabetes with hope for a cure on the horizon.

All those with type 1 diabetes require insulin, as do some with type 2. The discovery of insulin would not have been possible without research with dogs. Beginning in 1893, dogs were crucial to identifying the role of the pancreas and the eventual isolation of insulin and successful injection in humans in 1922. First by monitoring blood sugar levels in rabbits, James Collins then successfully used insulin in dogs and then humans, dramatically changing the treatment of diabetes.

Diabetes research has since been developed most commonly using mice. The nonobese diabetic mouse (NOD) is a common model for studying type 1 diabetes and the KK mouse and ZDF rat are used for type 2. Recently mice have produced promising results for a cure to diabetes. Through the growth of mice pancreas cells placed in rat embryos, that were then transferred into mice, diabetes was reversed. Through stem cell technology, scientists injected mice pancreas cells into rat embryos. The pancreas cells remained made up of only mouse cells, later allowing a successful transplant into diabetic mice. This is a breakthrough opening the possibility for human stem cells which successfully produce insulin. Another exciting prospect is the recent use of gene transfer that cured type one diabetes in mice. The immune system of someone with diabetes kills the “beta” cells which make the necessary insulin, but researchers think they have found a way to force other cells to make up for the failing “beta” cells. New insulin-producing cells were injected into mice, successfully curing their type one diabetes. The mice have been diabetes free for one year with no complication, and researchers hope to move to larger animals before then starting human clinical trials. This work could also be used to help treat the more common, type 2 diabetes.

Non-human primates are also instrumental in the fight against diabetes. Recently researchers have been developing an insulin shot that would last an entire month, replacing the weekly or daily shot required by patients with type 2 diabetes. The shots have proved effective at controlling the glucose levels in rhesus monkeys for over 14 days. Monkeys and mice have faster metabolisms than humans making the shot likely to work as effective glucose control for a month or longer in humans. This is another exciting prospect to improve treatments for diabetics.

Our pets can suffer from diabetes as well. The number of diabetic dogs and cats in the United States is growing, but fortunately, diabetic pets can be treated with the same insulin and oral medications that help human diabetics. Research with animals is helping to improve the daily lives diabetics, human and animal, with enhanced treatments helping to prevent the devastating consequences of the disease.

Ebola

The 2014 Ebola outbreak in West Africa claimed 11,310 lives and more than 28,000 people were infected. Ebola causes severe hemorrhagic fever in humans and other mammals. So far, vaccines have shown promise in preliminary safety trials with animals and an effective vaccine is expected. Because Ebola evolved from primate viruses, animal research is essential to the study of disease.

Ebola is a leading cause of death in wild chimpanzees and gorillas, so the role of non-human primates in developing a vaccine cannot be overstated.  In 2013, six chimpanzees received an experimental vaccine which proved safe and effective at inducing an immune response. However, the vaccine protection in monkeys waned over time, making them only partially protected ten months after their vaccine. While the goal is lasting protection, these experiments are still useful going forward especially, with the prospect of developing booster shots. In 2015 an inhalable vaccine neutralized the Ebola virus in rhesus macaques monkeys, by producing an immune response in the respiratory system. Ebola vaccines in the past have been effective on monkeys but not on humans, but each new development in monkeys, while not a guarantee for a cure for humans, is still a positive step forward in understand the disease. An aerosol vaccine like this is especially promising as a vaccine in this form would be easy to administer without trained medical professionals, which are gravely lacking in areas most affected by the Ebola outbreak.

Continued non-human primate experiments are vital in the fight against Ebola. As the disease is constantly evolving, constant monitoring is the only way to stop the spread of Ebola. The use of captive chimpanzees in research is extremely rare, so the use of other non-human primate models is critical. Rhesus and cynomolgus macaques and marmosets exhibit a disease course like that of humans, and are necessary to understand the full progression of the disease. Vaccines and antivirals that are the result of this non-human primate research have promising results, and the eventual eradication of the disease is possible with continued animal research.

Epilepsy

There are currently 20 anti-seizure medicines available to the 3 million people living with epilepsy in the U.S. Surgical treatments for epilepsy are also an option for some. None of these new treatments would be approved for human use unless their safety had been first tested in animals. Continued research for epilepsy is needed as in the United States over a third of those using current epilepsy medications still suffer from persistent seizures.

Instrumental in our understanding of epilepsy, mice are helping to pioneer new therapies and even possible cures. The identification of several gene mutations in mice has allowed a better understanding of the cause of epilepsy. Targeting the exact gene responsible is helping researchers to develop highly specified treatments to eliminate seizures without negative side effects. Drugs which stop the signals of chemical and electrical seizures were tested with animal models before proving effective to prevent refractory seizures in humans.

For those in whom seizures are not stopped by drugs, new treatments are being pioneered. Amino acids have been known to help prevent seizures. Even before medication, an amino-rich diet was recommended, and today scientists are trying to condense the power of amino acids as an alternative therapy.  Mice treated with amino acid showed far greater seizure resistance, providing a starting point to better treat epilepsy. Cell therapy is also emerging as a possible cure for epilepsy. Medial ganglionic eminence (MGE) cells implanted in epileptic mice successfully stopped seizures. This is progress for researchers hoping to use cell therapy to address the underlying cause of the disease, not just control symptoms like the current therapies. Mouse models and humans with the condition share pathological similarities, making mice useful to fully under the neurological processes behind the condition, and, in turn, what must be done to eliminate seizures. The mice used in tests for cell therapy are especially important as they closely model drug-resistant human epilepsy, making them the key to ending seizures in those whose symptoms persist. The developing new treatments are for more than just the control of symptoms and are exciting progress towards a cure.

Eyesight

More than 10 million Americans already have age-related macular degeneration, the leading cause of vision loss in the United States. AMD damages and destroys central vision, which is critical for performing everyday tasks like reading, driving, or simply recognizing the faces of loved ones. Animal research is a crucial step to discovering potential treatments for the millions of humans, and animals, with low vision.

Research with cats gave an important starting point to our understanding of the visual system. Scientist David Hubel studied the visual system of cats to find that all mammals have partially developed visual systems at birth. Studies on the nervous system of kittens, helped Hubel to discover that stimulation of the visual neurons by light is necessary for proper development of the eyes, optic nerve and visual centers of the brain. Cats, alongside monkeys, helped Hubel gain vital insight into visual system, aiding in all future developments to treat blindness and progressive vision loss.

Vision studies have historically used rhesus monkeys and cats, but recently a growing number of studies have been conducted with mice to pioneer new ways to treat blindness. While mice have an exceptionally poor vision, our understanding of their genetics allows the opportunity to try new cell therapy techniques to combat blindness. Mice also have a long history of aiding our understanding of the neurological system, which bolsters its potential as a successful visual model. Recently, scientists have regenerated optic nerve cables in mice whose visual condition resembled glaucoma. Cataracts and glaucoma and the two leading causes of blindness, and while cataracts can often be removed with surgery, glaucoma has no known cure. Partial vision was restored in the glaucoma model mice, an exciting step to curing the more than 70 million people worldwide affected by glaucoma.

Vision restoration is the goal for the 285 million people worldwide who are visually impaired, 39 million of whom are blind. Developments like the implantation of retinal stem cells in mice are showing promise for the prospect of stem cells to restore lasting vision. Worldwide, 80% of all visual impairment can be prevented or cured, which would not have been possible without animal research. For those whose vision cannot yet be corrected with existing therapies, continued research with animals is taking exciting steps in new vision restoration techniques.

Flu

Each year in the U.S., roughly 150 million doses of influenza vaccine are distributed annually to prevent outbreaks and reduce the impact of this disease. Certain strains of influenza can have serious consequences, even death, for high-risk persons, especially children, pregnant women and the elderly, and as many as 500,000 people die worldwide from influenza each year. Researchers are working on developing a universal flu vaccine with the help of animal models. Historically, ferrets, mice, and guinea pigs have been important animal models in influenza research. Influenza can also cause lower respiratory infection which is the third most deadly disease in America.

Ferrets have been a crucial part in influenza research and the creation of the flu vaccine. There are three main types of influenza A, B, and C. Types A and B naturally infect ferrets. The infections progress similarly to influenza’s progression in humans making ferrets an ideal model to study the disease. With longer life spans than mice, ferrets are used to study the effects of age on flu susceptibility. Ferrets have helped researchers understand the variants of the virus. The flu virus is constantly changing through antigenic shifts, so continued animal research is important to adapt the vaccine to protect against the current circulating strains. Researchers hope to create a vaccine that could provide life-long immunity to the flu by targeting the genetically stable part of the virus, so no matter how the virus adapts, the core remains neutralized.

Mice are utilized for continued research against the flu and in efforts for a universal vaccine. Mice are the most widely used, due to accessibility, convenience, and our ability to genetically modify them. Initial antivirals were tested on the mouse model, as it allows a large number to be tested, providing robust data in a short time span. While mice exhibit disease symptoms, guinea pigs, though naturally susceptible to influenza, lack visible disease symptoms. The disease in guinea pigs is seen mostly in the upper respiratory track, so while they are not useful for the study of overt disease signs, they are useful to the study of how the disease impacts the respiratory system. The disease also rapidly transfers throughout guinea pig groups, improving our knowledge of influenza transmission.

Progress in creating a universal vaccine is being made. In 2015 universal vaccine proved successful in protecting mice from eight different flu strains. The vaccine proved effective for six months. Older mice were successfully protected as well, which is especially positive as older people are far more susceptible and exhibit harsher, more life-threatening symptoms. The research team wants to move to ferrets, which will be useful in further determining the vaccine’s effectiveness as one ages, before moving on to human trials. The development of a universal vaccine would be a huge step in reducing the impact influenza inflicts every year. Animal models are necessary to effectively combat influenza and reduce the number of deaths that result from infection every year.

Hepatitis B

Approximately 1.2 million people in the United States and over 350 million worldwide have Hepatitis B. Some people after infection can fight off the virus, but for others, the virus leads to a life-long illness. This contagious virus can cause long-term, chronic illness that leads to cirrhosis of the liver, liver cancer, and death. Hepatitis B virus (HBV) infections are spread through bodily fluids, and symptoms can take up to thirty years to develop meaning many do not know they are infected, leading to spreading of the virus. An estimated 600,000 people a year die from Hepatitis B-related liver disease. Fortunately, Hepatitis B can be prevented by vaccination and controlled by precautionary treatments – both of which were developed with the help of animals. Chimpanzees are the only animal model which is susceptible to all 5 main strains of hepatitis, so their contribution has been crucial to understanding the virus.

Because chimpanzees are susceptible to human hepatitis viruses without developing a clinical illness, they are a vital model in the studying HBV. Before treatments and vaccines can be developed, scientists must first understand the biological properties of the virus. The infection patterns in chimpanzees closely resembled that in humans, leading scientists to the current treatments and vaccine. Chimpanzees were instrumental in the development of diagnostic tests for hepatitis A and B, helping to almost eliminate the spread of the virus through blood transfusions. Antiviral drugs are available, but researchers continue to improve treatments for those infected, and transgenic mice models have been useful in studying the origin and development of the disease. There is an acknowledged need for the continued use of adequate mouse models for the development of more potent antiviral therapies. Tree shrews, a mammal closely related to primates, is also proving useful in the treatment of HBV that could prevent liver cancer, hepatocellular carcinoma (HCC), in those infected. Tree shrews’ immune system has immense similarities to that of humans seen in the progression of HBV and subsequent HCC, so tree shrews are a practical model for the development of therapeutic measures to prevent HCC in chronically HBV-infected humans.

The HBV vaccine was developed in 1976, and after proving safe and effective on chimpanzees became commercially available in 1982. Because Hepatitis B significantly increases one’s risk of liver cancer, it can be considered the first cancer vaccine. The vaccine contains a purified antigen of the virus which was extracted from humans, but it’s safety and dosage was tested on marmosets, guinea pigs, grivet monkeys, and chimpanzees. The vaccine has since been administered to over 120 million people, preventing their contraction of the disease and helping to prevent the spread of the virus. With chimpanzee models, scientists are currently working on a new type of vaccine that creates cell-mediated immunity in hopes of improved safety and effectiveness in the vaccination of infants at risk of mother-to-infant transmission. Without the ethical use of animal models, we would have little understanding of how to treat or protect against the virus leaving millions still susceptible to this deadly virus. Animal models are a continued necessity in efforts to treat and prevent all strains of the hepatitis virus.

Hepatitis C

170 million people worldwide are infected with hepatitis C (HCV). A staggering 3.2 million Americans are currently living with chronic hepatitis C infection, with 17,000 Americans becoming infected every year. The Center for Disease Control even estimates that more Americans are dying from hepatitis C infection than from HIV. Like hepatitis B, many living with it are unaware. As many as one in 33 adults aged 45-64 are unknowingly living with the disease.  While there is no vaccine for HCV, beginning in 2012 a series of breakthrough treatments have delivered a cure for what was once a debilitating, lifelong disease. These medicines are not only faster-acting and simpler to take than previous therapies. Previous drugs managed the condition, but today’s can essentially eradicate it in sometimes as little as 12 weeks. The current hepatitis C treatments were developed with the help of mice, rats, and monkeys.

As previously stated, chimpanzees and other non-human primates have been vital in understanding the virus. Chimpanzees enable the discovery of hepatitis C and has been a valuable tool in preclinical analysis of developing antivirals. As chimpanzees are under growing ethical constraints, tree shrews are a suitable rodent alternative to study HCV, but mice remain the most accessible. Rodent models offer insight into agents of early HCV infections, and new mouse models have been genetically enhanced to elicit responses closer to humans. The human-liver chimeric mouse is the only living preclinical model to monitor HCV drug resistance. This model lacks the necessary immune responses to test possible vaccines, but in efforts towards a cure, researchers have developed mice humanized with liver and immune cells. This model is greatly helping with vaccine strategies, for example they have suggested the possibility of a prophylactic vaccine for HCV due to the success the antibodies have exhibited in preventing infection in these mice.

While a vaccine is not yet possible, new drug treatments cure hepatitis C in 90% of patients. These current antivirals would not be possible without non-human primate and rodent models. Targeting the host molecules rather than the virus proved successful in non-human primates. This knowledge was a breakthrough in improving antivirals. Sovaldi (sofosbuvir) tablets were approved in 2013 for the treatment of chronic hepatitis, and, in most patients, cures the disease in a few months. Before approval Sovaldi proved safe and effective in preclinical rodent and non-human primate models. While effective, the drug is very expensive so animal testing no only continues to be integral in developing a vaccine, but also in finding a cheaper alternative for the cure of HCV. Tests in mice have recently suggested that an allergy medicine may be the alternative, as in mice it prevents an early stage of the infection. Developments are in the early stage, but with further animal research the drug could be improved and eventually certified for HCV treatment.

Hepatitis A and B can be prevented with a vaccine, but there has yet to be a vaccine that can prevent hepatitis C. Non-human primates and mice have been crucial to the research that has created HAV and HBV vaccines, as well as the current treatments for HBV and HCV. Animal research’s results can be seen in the development of a cure for HCV that was found in 2012. Cures helps the millions already effected, but a vaccine is the only way to truly stem the number of infections and work towards ending the epidemic, especially in the developing world. With continued animal research a vaccine is in sight for hepatitis C and will be a major step in greatly reducing the rate of infection.

HIV

There are an estimated 1.2 million Americans living with HIV and an estimated 36.7 million people affected worldwide. Over the course of the global HIV/AIDS epidemic, nearly 78 million people have been infected and 39 million people have died. When the epidemic began in the 1980s, HIV/AIDS was universally fatal. Today, there are 31 FDA-approved drugs available to treat HIV infection. With proper treatment, those infected with the disease are living normal lifespans. Researchers are currently working on an HIV vaccine with hopes to eradicate the disease in our lifetime. Animal models, especially monkeys, have been critical to the development of existing and future treatments for HIV/AIDS.

The first antiretroviral was developed in 1986 through research with monkeys and mice. The first of its kind, the drug greatly improved the life expectancy of patients. With non-human primates, researchers were better able to understand the virus and identify a similar virus, SHIV. This discovery was vital to the development of ARVs and their expansion and improvement, allowing patients to live longer, healthier lives. Recently, research has pioneered new ways to prevent and treat infections. High-risk populations can take a daily antiviral drug, pre-exposure prophylaxis (PReP), which reduces one’s risk of infection by up to 92%. This prevention was made possible through efficiency tests with mice. After exposure to HIV, antibodies will develop and become detectable within three weeks. This process can be stopped with a post-exposure prophylaxis (PEP) treatment regimen if started within 72 hours of exposure. Made possible by mouse and non-human primate models, PEP allows people to stay HIV-negative even if the virus has entered their bloodstream. Effective treatments and prevention is an effective step towards reducing new infections and premature deaths due to the disease, however, the only way to stem the global pandemic is a vaccine.

With animal research, exciting steps are being taken towards the creation of an HIV vaccine. Building upon the identification of SHIV in non-human primates, recent studies with monkeys have led to the development of SAV001, a safe and well-tolerated vaccine. Expected to go into its second phase of clinical human trials later this year, this vaccine offers hope that researchers are close to a cure, and in turn, an HIV/AIDS-free future worldwide. Teams worldwide are developing vaccine candidates with animal research. To be an effective vaccine, it must protect against the multiple strains of the virus; Scientists at The Scripps Research Institute have developed an immunogen from the protein of subtype C, the most rapidly spreading strain. This immunogen could be incorporated in future vaccine research to combat several strains of HIV. The developing vaccine candidate has proved effective in non-human primates, eliciting an immune response which neutralized the C strain of the virus. Another team of researchers has recently had promising developments by engineering a vaccine which boosts the immune system for more efficient defense. With traditional vaccines, the immune system is unable to completely eliminate the virus, this vaccine would bolster the immune system for total removal of the virus. So far this new vaccine strategy was developed with mice, and has recently proved effective at controlling SHIV in monkeys. Researchers continue to refine the strategy with animals and hope to later move to human trials.

HIV research has been grounded in animal research from the start; research into feline leukemia and the immunosuppression created by the virus led to the isolation of the HIV virus in the early 1980’s. Now, with continued animal research, a cure for HIV is in sight. Researchers hope to end the global HIV pandemic in our lifetime, and new clinical trials are offering hope that this devastating disease could soon be systematically eliminated. Staggering progress in treatment and prevention has already been made with animal research, but continued research with animals is necessary for an effective and safe HIV vaccine.

Joint Replacements

Hip and knee replacements allow many patients to move more freely with significantly less pain. Dogs are also increasingly receiving successful joint replacements. There are over 2.5 million Americans living with a hip replacement, and 4.7 million with an artificial knee. Joint replacements greatly increase one’s quality of life, relieving pain and returning mobility. Joint replacements are techniques are being improved with animal research for the recipients of the 300,000 hip replacements and the 600,000 knee replacements performed each year.

Themistocles Glück was the first attempted hip replacement in the late 19th century. Using animals, he was able to find safe and effective ways to fix joint replacements to the bone. Today researchers are still improving joint replacements with animals to improve upon the life span of the standard metal replacements. Researchers are experimenting with a cementless fixation, a biological implant which allows the bone to grow onto the implant. This is being researched with dogs and rabbits to pioneer implants which would be reabsorbed by the host tissue. Cementless knee replacements are also being developed with animals before it is ready for use in human patients. Rabbits are essential in this work on biological implants. With tissue engineering, researchers have successfully created a moving joint in rabbits. These technologies for joint replacement have yet to move to humans, but with continued research could be useful solutions for younger joint replacement patients to avoid the 10-15 year replacements necessary with metal hip replacements. Longer-lasting hip replacements are the main concern of current joint replacements, as several research teams are attempting to connect the artificial joint with the living femur. These efforts for a durable hip replacement must first prove effective in animals before they will be able to be tried in humans. Osteoarthritis is a prominent area of joint research and using animal models. Knee replacements are commonly used to treat advanced cases of osteoarthritis. Knee osteoarthritis affects an estimated 27 million, with animal models acting as significant research tools to treat all stages of the disease including those who require joint replacement. As with hip replacements, canine models are the optimal animal model for osteoarthritis and knee replacements. Their joints are remarkably similar to ours, so they experience joint problems just like we do.

Routine hip surgeries have been performed on big dogs since the 1970’s, and much of our knowledge on the surgery comes from the veterinary practice. Canine hip dysplasia is very common in big dogs, so for decades, vets have been treating joint issues in larger dogs. As we continue research into ways to improve joint replacement in humans we are now able to perform micro-joint replacements for cats and small dogs. Animal research, specifically with canines, has been central to the development of joint replacements, and today are helping to improve techniques for more effective surgeries for both us, and our pets. Joint replacements are an apt example for the benefits animal research has for humans and animals.

Kidney Disease

Fifty years ago, kidney disease was considered fatal and took the lives of 20,000 Americans annually, making it the fourth leading cause of death among young adults. Today kidney disease can be treated and managed for a long, happy life. Virtually all the recent improvements in the care of patients with kidney disease, including shunts, blood pressure management, immunosuppression drugs, and kidney stone removal, have resulted from basic research involving the use of lab animals. Improving our kidney disease treatments helps not only the over 661,000 Americans with kidney failure but also the thousands of pets suffering from kidney disease.

A common treatment for kidney failure is dialysis. Those suffering from chronic kidney failure must receive dialysis a few times a week to remove toxins from the blood. The invention of dialysis would not have been possible without dogs. Dogs and rabbits were the first animals dialysis was tested with, then testing moved to monkeys before it was used to save the lives of the millions who have suffered from kidney failure. Currently, other treatments are being pioneered with the help of mice.

As kidney disease often exhibits no symptoms, it is hard to diagnose. Kidney failure is especially dangerous for people with diabetes. Research with mice has created a potential blood test to identify whether a person with type 1 diabetes is releasing a protein which indicates a damaged kidney. The test has successfully identified early signs of kidney damage in mice and then humans. This test could facilitate early treatment, slowing the course of the disease. While stem cells are a possible alternative to kidney replacement or dialysis for those with kidney failure, in mice researchers have identified that kidney cells without stem cell capabilities can still multiply several times to repair the damage. This indicates the possibility of a model to program kidney cells to repair themselves, fixing existing kidney and potentially curing kidney disease.

Pets suffer from kidney disease too, so animal contribution to kidney disease research helps both people and their pets. Abby the Golden Retriever puppy, who received life-saving dialysis, is an example of the widespread benefit of our continued research into kidney disease.

Leukemia

There are currently nine different types of leukemia according to the Leukemia and Lymphoma Society. Accounting for 85% of all leukemia cases are 4 types: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Leukemia is the most common type of childhood cancer, making up one-third of childhood cancer cases. Treatments have advanced so that children have an eight out of ten chance of survival. About 98% of children with acute lymphocytic leukemia go into remission within weeks of starting treatment, and about 90% of those children can be cured. An integral part of this life-saving progress is animal research.

Research using mice has made crucial steps in understanding and tackling leukemia. In the 1970’s mice were used to determine that all malignant cells must be destroyed and that the earlier treatment begins the higher likelihood of eliminating the cancer are; this knowledge has since been used in treating all types of cancer. Today, by introducing a human immune system in mice and observing their response to transplanted cells, the possibility of bone marrow transplants in patients with leukemia is improving. Mice are also being used to pioneer gene therapy as a way to attack leukemia cells, and immunotherapy, an emerging treatment which shows promise against leukemic cells that have already resisted other treatments. While these experimental treatments are being developed, in most cases of leukemia chemotherapy remains the main treatment, which also would not be possible without animal research. In the 1960’s thanks to research on mice, a more aggressive chemotherapy regimen increased the remission rate from 25% to 60% by the end of the decade(1). The remission rate is even greater now at 85%, thanks to animal research furthering our knowledge of chemotherapy and other cancer treatments.

Cats also benefit from leukemia research. They offered insight into the disease after the feline leukemia virus (FeLV) was identified in 1965. A vaccine for FeLV was developed and this knowledge that has allowed leukemia to be prevented and treated in cats can also offer valuable understanding into cases of leukemia in humans. Research into FeLV even resulted in the identification of the first human leukemia virus, HTLV-1. Animal research has helped reduced the fatality of feline leukemia and raised the survival rate of childhood leukemia from 30% to 80%, helping humans and pets alike.

(1) Frei E III. Potential for eliminating leukemic cells in childhood acute leukemia. Proc Am Assoc Cancer Res1963; 5: 20 (abstract)

Malaria

Malaria is a chronic, sometimes fatal disease caused by a parasite in red blood cells that is transmitted to humans by mosquitoes. In 2015 there were an estimated 214 million cases of malaria worldwide with an estimated 438,000 deaths. Malaria intervention since 2000 has helped reduce mortality, but in regions of Africa malaria is still a large problem. 90% of all malaria deaths occur in Africa. With prevention and treatment, there has been a 21% global decrease in malaria cases and a 29% decrease in mortality between 2010 and 2015. The World Health Organization has developed the Global Technical Strategy for Malaria 2016–2030 which hopes for a malaria-free world by 2030. If their goal is to come to fruition, non-human primate and rodent models are essential. They have been instrumental in our knowledge of the disease so far and remain so as researchers work towards a vaccine.

Malaria is preventable and treatable. Drugs to prevent malaria should be taken before, during, and after trips to areas with high malaria rates like Africa and the South Pacific. Chloroquine is a common drug to both prevent and treat malaria, but certain strains of infection can resist the drug and require combination medications. Artemisinin-based combination therapies (ACTs) are treatments for various strains of malaria and can be used alongside injectable artesunate to cure cases of severe malaria. Continued research into treatment is still necessary as the disease is increasingly adapting to be drug resistant. Chloroquine was developed with rodent models and is continually tested alongside new drugs in comparative studies to gauge effectiveness with rodent models. Rodent models have become especially prominent into severe malaria to ensure treatments adapt alongside the disease strains, by tracking the progression of the parasite in rodents. Drug resistance is the biggest challenge in curing malaria, but new drugs have hope for long, clinical use and higher efficacy at lower doses than current medication. With such success in mice, the drug will soon progress to human clinical trials.

While treatments are effective, a malaria vaccine has not yet been possible, but researchers are working to develop one with the help of rodents and non-human primate. Efforts to develop a vaccine are deeply entrenched in animal research. Over 20 years ago, with rodent models, a certain protein called CSP proved to be highly prone to produce an immune response. Building on this work has resulted in a partially effective vaccine with encouraging results for progress towards complete protection. Researchers are also exploring the toxin released by the parasite. Inoculation with the toxin GPI protected mice from the signs of the disease. Recently, an experimental vaccine protected four out of eight monkeys from malaria. In three of the remaining four, the vaccine delayed the appearance of parasites. With continued animal research, scientists hope to improve the vaccine for eventual humans use, bringing us another step closer to universal protection against malaria.

Mental Health

Improving upon those of the past, anti-psychotics of today block less dopamine than before, improving the negative symptoms common in the older generation of drugs. Animal testing has helped understand the doses necessary to properly control symptoms while minimizing unpleasant side effects. Animal models have played a crucial role in the development of these drugs and are used to further understand mental illnesses for most effective treatment possible.

More than 7 million American are living with bipolar disorder and schizophrenia. Through anti-psychotic medications they can live greater quality lives. One such drug, Abilify, is the fourteenth most prescribed drug in America. It was tested on rats, dogs, monkeys, and rabbits to ensure its safety and efficiency in managing the symptoms of schizophrenia and bipolar disorder. Neuroscientists in California are researching the ways lithium can be incorporated into bipolar treatments by injecting lithium into mutant mice. These injections have helped restore dendritic spines, connections between excitatory neurons and nerve cells, to healthy numbers, and reduced symptoms that mimic bipolar disorder in humans. This bolsters the belief that theses synapse abnormalities are the cause of behavioral disorders, and will help progress towards better treatments of various behavioral disorders, such as autism and schizophrenia. A research team has also recently identified, through the study of mice, the cellular protein Phospholipase Cγ1 (PLCγ1) as a possible gene responsible for bipolar disorder. Identifying the gene responsible offers a vast number of possible treatments to reduce and even eliminate the symptoms of chronic mental illness.

Pets also benefit from our continued research into mental illness. Dogs and cats can suffer from schizophrenia, anxiety, and depression. Vets can now prescribe small doses of medication to help treat a pet’s mental illness, allowing one’s dog or cat to live a happy life with minimized symptoms. With animal research, behavioral pharmacology continues to improve, increasing the quality of life for both humans and our animal companions.

Organ Transplants

The lives of thousands of kidney, liver, and heart transplant recipients have been prolonged and enhanced thanks to surgical advances and the development of effective immunosuppressive drugs that prevent organ rejection. In 2016, 33,606 organ transplants were reported, an 8.5% increase from 2015, proving the importance of organ donations and the developments that make organ transplants successfully accepted. The first successful human transplant occurred in 1905, after research with rabbits helped Eduard Zirm successfully complete the first cornea implant. Because corneas normally do not have a blood supply, rejection is typically not an issue. However, for other organs the bulk of transplant research has been in how to suppress the immune system so the body does not identify the organ as “foreign” and attack or reject it. Dogs, rabbits, and mice have been instrumental to the development of surgery techniques and anti-rejection drugs, allowing for successful organ transplants in both humans and animals.

Joseph E. Murray, recipient of the Noble Prize for his work on organ transplants, and Thomas E. Starzl, known as “the father of modern transplant”, both acknowledge the importance of dogs in the study of immunosuppressive therapies for transplanted organs to be successfully accepted. Kidney transplants make up over half of the organ transplants performed in the U.S. every year.  As part of dialysis research, dogs were the obvious choice to better understand kidney transplants. Beginning in the 1950’s dogs have helped our understanding of the immunosuppressive drugs necessary for successful transplant and the techniques of kidney transplant, helping the 19,061 people who received kidney transplants in the U.S. in 2016. Heart transplants research also was conducted with dogs at the forefront. Dr. Christiaan Barnard performed the first successful heart transplant in 1967, after years of research in which Barnard and his colleagues performed nearly 50 dog heart transplants.

Mice remain a staple in the continued research into organ transplants. The rat model in the study of transplants started in the 1960’s leading to the prominent rise of the mouse model in the ‘90’s. Rats are simpler models due to their larger size, but now all the transplants that can be performed in rats have high success rates in mice as well.  Currently, researchers at UCSF are genetically modifying immune cells in mouse models to inhibit immune responses. They are also attempting to create immune tests to assess one’s rejection risk. While our transplantability has greatly improved, rejections still unfortunately occur, but this research is a valuable step to eliminating organ rejections. Mice and monkeys are also a part of an ongoing effort to train the immune system to recognize the transplant as its own. This ongoing work could eliminate the need for most organ recipients to take immunosuppressant drugs for the rest of their lives. In this work to eliminate the continual need for immunosuppressants, blood stem cell infusions have allowed some mice and monkeys to be weaned off the drugs. Neither of these techniques is yet effective enough to be trialed in humans, but with continued research with animals, organ transplants will have a higher success rate and the sometimes-dangerous drug regiment following transplant could be reduced or even eliminated.

Companion animals benefit from the continued animal research into organ transplants. While most organ transplants are not yet possible for dogs and cats, kidney transplants are increasingly common. In cats, all that is required is a blood test to find a match, but dogs’ immune systems prove more difficult. Research into organ transplants is translational, helping both humans and dogs. Recently vets have been pioneering dog transplants, finding that if the bone marrow is transplanted alongside a kidney rejection is far less likely. The continued animal research into organ transplants is helping to both increase and improve humans lives as well as the lives of our furry friends.

Paralysis

Approximately six million people in the United States are living with paralysis. Spinal cord injury is the leading cause of paralysis. With the use of animal models, researchers are able to develop potential spinal cord therapies to regrow neuron connections, enabling recovery of sensations and motor functions. Rats are integral to the study of spinal cord injuries, offering promising new therapies, and hope for a cure for paralysis. Researchers at Johns Hopkins University, through the injection of embryonic stem cells, allowed paralyzed rats to move their limbs. The cells spent three months re-growing the injured spinal cord until it once again connected to the rats’ muscles allowing movement. This reconnection between the signals of the brain, the spinal cord, and the muscles is a crucial starting point to expanding research until this therapy is viable in humans with paralysis. Other paralysis developments that researchers have made with rats include the electrical and chemical stimulation of paraplegic rats, allowing them to walk again. Chemical injections began spinal growth, which was then further encouraged by electrical stimulation and an exercise regime. Spinal cord stimulation on rats is another avenue that offers promise for the millions suffering from paralysis.

Non-human primates offer researchers valuable insight into treatments and possible cures for paralysis. Due to the similarity between human and non-human primate nervous systems, they are essential to paralysis studies. Epidural electrical stimulation (EES), first successful in restoring function in rats has since been successful in restoring movement in paralyzed monkeys. Researchers at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland developed a wireless device which stimulates muscle movement in Rhesus Macaque monkeys. Two implants facilitate communication between the brain and the muscles, bypassing the spine region that would have inhibited this signal. The monkeys were paralyzed in one leg, but thanks to this device could fully walk again within two weeks. These developments offer strong hope that with animal research we will eventually be able to offer life-changing treatments for those suffering from paralysis.

Companion animals play a role in our understanding and treatment of paralysis. Cats have helped study acute facial paralysis or Bell’s palsy. The facial nerve of cats and humans have been found to be extremely similar. This allows feline research to aid humans with facial paralysis as well as cats with facial nerve paralysis, a common disease in long haired domestic cats. Dogs afflicted with idiopathic laryngeal paralysis (ILP), and degenerative myelopathy (DM) greatly resemble ALS (Lou Gehrig’s disease), offer the opportunity to develop translational treatments. Sharing a version of the ALS genetic mutation these larger animal models allow greater understanding of ALS, as well as the DM, paralyzing dogs. With these dogs, researchers can work toward ALS treatments as well as treatments for dogs with ILP and DM.

Animal research offers valuable insight into later treatments for humans, but also provides cures for pets. The study of paralysis is one in which animal research is invaluable. Through animal models we are better able to understand paralysis, improving treatments and offering hope for an eventual cure.

Parkinson's Disease

As many as 1 million Americans have Parkinson’s disease, with approximately 60,000 Americans diagnosed each year leading to a total of over 10 million people worldwide living with Parkinson’s. It is a progressive disease, and symptoms affect individuals differently. The exact cause of Parkinson’s is also unknown, a combination of both genetic and environmental factors. Animal research is a staple in the current treatments available for Parkinson’s and the ongoing research to treat and possibly cure the disease.

Animal models are the most effective way to study the development of Parkinson’s and have been instrumental for the current treatments. Though no medications yet reverse the disease, there are still several medications to manage one’s symptoms. Monkeys and mice are the most popular animal models for the study of the disease, but rabbits have also helped revolutionize the treatment of PD. Nobel Prize-winner Avid Carlsson discovered the role of dopamine in the brain’s ability to control movement through tests with rabbits whose movement was restored with injections of the drug L-dopa. L-dopa is an effective drug for some, but its effects wane over time. Monoamine oxidase (MAO) inhibitors, developed with rats and marmosets, increase dopamine levels and can be used in early stages or alongside L-dopa to increase effectiveness in later stages.

Deep brain stimulation (DBS), a surgical technique to regulate the nerve circuitry which creates symptoms is an effective treatment for some people living with Parkinson’s whose symptoms cannot be managed with drugs. DBS improved the movements of monkeys with Parkinson’s before it was trialed on humans and approved by the FDA in 2002. MPTP monkey models were central to the development of DBS which has helped over 80,000 patients manage their symptoms. This model is also part of innovative gene therapy to increase an enzyme in the brain which alleviates symptoms in rats and monkeys.

Exciting new developments in Parkinson’s research focus on the alpha-synuclein, a protein which has become prominent in pioneering therapies. An abnormal form of alpha-synuclein is present in people with Parkinson’s. This protein was identified in monkeys and then humans and now our knowledge of it is being used to create a blood test for Parkinson’s to allow earlier treatment.

A cure has not yet been found for Parkinson’s but symptoms can be alleviated or improved. Animal research is continuing to improve treatments and is working towards prevention and an eventual cure. Parkinson’s is a disease that researchers are confident can be conquered with animal research, alleviating suffering for the millions who are affected worldwide.

Polio

In the 1940s and 1950s, approximately 35,000 people were diagnosed with polio each year. Polio, one of the most horrifying diseases of the 20th century, was not known to be contagious until 1905 when Swedish scientist Ivar Wickman investigated and tracked the spread of infections. This was extremely controversial until 1908 when scientists Karl Landsteiner and Edward Popper proved the specific cause of the disease through the infection of monkeys. These early developments activated the forty-year course of research to create the polio vaccine with the help of monkeys, mice, and cows.

Dating back thousands of years, polio was a perplexing and devastating disease. The disease circulated in low levels until the beginning of the 20th century when it reached epidemic proportions prompting vigorous research into how to stop the virus. Several vaccines were attempted but unsuccessful. In 1935 two research teams, after tests with mice trialed a vaccine that was discontinued after harming test subjects, both chimpanzees, and humans. In 1954 the first inactivated polio vaccine was produced by American, Jonas Salk. Growing the virus in monkey kidney cells, he then inactivated them using the chemical formalin, similar to formaldehyde. This vaccine proved effective on the nearly 2 million children enrolled in the trials and became widely available in 1955. In 1960, Polish-American scientist Albert Sabin created an oral polio vaccine with the help of “approximately 9,000 monkeys, 150 chimpanzees, and 133 human volunteers.” Due to its ease of administration over the injection, Salk’s vaccine was phased out in 1968 in favor of the oral vaccine.

The Global Polio Eradication Initiative began in 1988, to help stop the disease in developing countries. Global polio incidences have been 99% eradicated. In 2016, polio circulates in just Afghanistan and Pakistan. The Initiative is still working on eliminating polio these last few places where the disease still occurs. Children worldwide are still recommended to get the vaccine to protect against imported cases. Eradicated in the Western Hemisphere, it is easy to forget the ravages polio-inflicted. Polio would still be a global health threat today if not for animal research. Mice and especially non-human primates were crucial to the development of the vaccine that has eliminated 99% of polio worldwide. The World Health Organization hopes to eliminate the last 1% by 2019. Because of research with animals and human ingenuity and perseverance, the world could soon be completely free of polio.

Small Pox

One of the worst pandemics the world has seen, smallpox, was eradicated in 1980 through worldwide vaccination. The World Health Organization is prepared should the virus ever reemerge or should this ever be used by terrorists as a biological weapon, mass vaccination could resume immediately. This vaccine was derived from a cattle virus known as cowpox. Smallpox is an example of the how closely humans and animal health is reliant upon one another.

Smallpox ravaged the development of Western civilization, spreading throughout the world by merchants and explorers. In the 18th century, smallpox claimed an estimated 400,000 lives a year, and a third of the survivors were left blind. As early as 430 BC, survivors were called upon to nurse those newly infected, showing early knowledge of the survivors’ immunity. Variolation, giving people material from smallpox sores through scratching the material into one’s arm or inhalation, was the first effort to stem the disease. The technique came to England from Istanbul in the early 18th century, and while patients would still develop the symptoms of the disease, it was weak and less life-threatening. A vaccine was first developed by Edward Jenner in 1796. Jenner, after noticing that milkmaids who already had cowpox never developed the typical smallpox symptoms after variolation. Jenner took material from a cowpox sore and injected it into a young boy. Months later after multiple exposures to the smallpox virus, the boy remained smallpox-free. After more tests vaccination began spreading as Jenner distributed the inoculant among fellow doctors. Research and development in the 19th and 20th centuries involved cowpox material being extracted from calves and then purified to produce the vaccine. However, global eradication took almost two centuries due to lack of funds and commitment. Finally, on May 8, 1980, the 33rd World Health Assembly officially declared the world free of smallpox. This vaccine and its mass distribution would not have been possible without the use of calves to harvest cowpox material.

The smallpox vaccine was the first ever vaccination and began live, attenuated vaccines with living microbes as a possible cure for other diseases like measles and chickenpox. Vaccines like these are so widespread now that they are easy to take for granted, but without the use of animals in research they would not be a possibility. Without animal research, smallpox would still be a disease affecting masses of people rather than a not-so-distant memory.

Stem Cells

Stem cells hold immense therapeutic potential for diseases such as cancer, Alzheimer’s and Parkinson’s disease. Because cells have the ability to renew themselves, researchers can use these cells to repair internal damage. Embryonic stem cells are unspecialized, but they can acquire the features of a specialized cell through a process called differentiation. This process is still one which scientists are trying to fully understand, but, through animal research, stem cells can become tissue or organ-specific cells, which is vital to combat the internal damage inflicted by diseases such as diabetes and heart disease.

Animal research has been crucial to our understanding of stem cells; rodents especially have played a continual role in its development. Dating back to 1961, researchers have been using animals to understand stem cells, beginning with the identification of nerve cell replication in rats. In 1981 embryonic stem cells were derived from mouse embryos, which then led to the ability to derive stem cells from human embryos in 1988. To better harness stem cells vast potential, scientists inject human embryonic stem cells into mice with suppressed immune systems to study the differentiation process as well as identifying whether the cells are pluripotent, meaning that a single cell can become specialized to any tissue of an organism. Being able to direct the transformation of embryonic cells into specific cell types would be able to treat vision and hearing loss as well as diseases like diabetes.

The first successful isolation and culture of primate pluripotent stem cells occurred in 1995 at the Wisconsin Regional Primate Research Center. This was the beginning of a greater understanding of pluripotent cells and led to developments in how scientists can best utilize these cells for therapeutic purposes. Primate research in stem cells has continued to progress, and in 2013 researchers Qiang Shi and Gerald Shatten programed baboon embryonic cells to restore a damaged artery, offering hope in the future that human stem cells will be able to directly target and repair the damage. Stem cell manipulation with animal models allows a better understanding of diseases, facilitating the discovery of new drug treatments, and more effective clinical trials.

Adult stem cells are unspecialized cells found among already specialized cells. They repair and protect the tissue they are found in. Scientists are trying to discover how to fully harness the potential of these cells, by increasing their quantity to regrow their tissue of origin. A common test to identify adult stem cells is extracting cells from one animal and placing them into another, isolating adult stem cells as those which repopulate the tissue after transfer. Cancer cells share many properties with adult stem cells, so these stem cells hold immense potential for effective cancer therapies. Questions remain regarding adult stem cells, and, in turn, how best to apply them for the treatment of disease, but through animal research models significant progress is being made on utilizing the full capability of adult and embryonic stem cells.

Stem cell trials using companion animals are also taking place to help combat and treat disease in dogs and cats. The study of tumors is one in which there are more similarities between humans and companion animals than humans and rodents, yet the utilization of companion animal disease models is lacking. Companion animal stem cell research has the potential to transform regenerative medicine. Millions of pets will develop a disease in their lifetime which correspond to human diseases, such as arthritis and kidney disease, so companion animal trials offer researchers the opportunity to both better treat and heal pets as well as humans.

Surgery

Lifesaving procedures such as open-heart surgery, coronary artery bypass, valve replacement and the repair of congenital heart defects are now common practice, thanks to their development with lab animals. Beginning in the 1920’s, with the use of animals, researchers attempted to develop the heart-lung machine, now a cardiopulmonary bypass. Without the cardiopulmonary bypass to mimic the functions of the lungs and heart, heart surgery would not be a possibility. Research with canines made the machine possible, and in turn, made all heart surgeries a possibility.

Our understanding of the heart is dependent on animal research. The echocardiography which allows doctors to safely investigate the functions of the heart was first pioneered with calf hearts. This technology is still being improved today with the use of rodents, dogs, and pigs to improve the detection of heart problems. Congenital heart defects affect 40,000 births a year and would be invariably fatal without the heart surgeries developed with animal research. The two most common congenital heart defects are Atrial Septal Defect (ASD) and Ventricular Septal Defect (VSD). Both can be repaired with a surgery to close the hole in the heart with synthetic material. Tetralogy of Fallot is the third most common CHD and can repaired with a Blalock-Taussig procedure, a procedure developed with and performed on dogs with congenital heart conditions. Pig models have also been developed to stimulate CHD and are helping improve procedures and medications to treat CHD. Animal research is helping babies born with CHD to live long, healthy lives into adulthood.

Coronary artery bypass is the most common heart procedure, another procedure which was developed through experimental canine surgeries. The canine aorta has many similarities to human aortas, making it a relevant and effective model to develop heart surgery techniques. Both humans and dogs benefit from the use of animals in heart disease and surgery research and development. The first dog to undergo open heart surgery was a Doberman-German Shepard mix named Taylor in 2015, fixing a rare congenital heart defect. In a recent year, the estimated number of heart surgeries performed was as high as 500,000; Taylor and other pets can join in this number of successful heart surgeries that have changed many lives for a healthier, happier future.

Why is there a decline in animal research?

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What is the biggest reason we use animal in research?