Infectious Diseases

From the common cold to more serious infections such as tuberculosis (TB) and Covid-19 that affect the lungs and respiratory system, animal research has been involved every step of the way to bolster our knowledge of these diseases and come up with therapies.  
A variety of mammals have been used to research influenza, which causes seasonal disease epidemics that result in up to five million cases of severe illness a year. Ferrets were the first animals used to study influenza-like illness and observehow it could spread between animals, as their lungs have a similar biological make-up to people. They have also been used for different variants, such as influenza A, for example by confirming that the virus was spread by aerosol transmission (via expelled infectious droplets). 
Ongoing research at Imperial College London, UK, is using ferrets to investigate how the flu virus infects cells, as well as how to reduce flu transmission. For example, a 2020 study showed that a drug called baloxavir can reduce the risk of ferrets transmitting the virus to healthy animals, suggesting it could be used to control flu outbreaks. See also this video on Imperial's research with Prof Wendy Barclay (pictured below). 
Meanwhile, studies in guinea pigs established the distances between two people that flu could be transmitted from, and monkeys infected with influenza have been important for making sense of historical outbreaks by clarifying how the virus spreads, for example.  
The Worldwide Influenza Centre at the Francis Crick Institute, UK, is monitoring the evolution of flu strains so as to create new vaccines as they are needed. The research involves using sheep to develop antibodies, and making antiserum from infected ferrets to analyse the infection properties of a specific virus. Fertilised eggs from chickens are then used to mass produce new vaccines.  

Pigs are emerging as good models for human flu vaccine development because of their similar immune systems, with research at the Pirbright Institute, UK, finding that the animals can mimic the effects of vaccination against human flu, and identifying ways to administer vaccines to provide better disease protection. 
Animals are useful to develop treatments that are more effective than those currently used.  
A study at Yale School of Medicine, USA, found that a nasal influenza vaccine could provide mice with better protection than administering it via injection, as well as demonstrating that it could potentially protect against new Covid-19 variants.  
Monkeys have helped to develop more effective vaccines against TB than the currently-used BCG vaccine, which is not very effective, while research at Duke University, USA, used zebrafish to identify suitable medicines for disrupting the formation of granulomas – aggregates of immune cells that play a key role in the development of TB.  
A study using rats at the EARA member Trinity College Dublin, Ireland, showed the effect a protein has on the immune system and how it hampers the body’s response to TB. 
Historically, guinea pigs, along with mice and chicks, were used for finding the first cure for TB through the testing of the effectiveness of streptomycin, a natural bacteria-killing substance made by microorganisms in the soil. 
Thanks to vaccine developments, polio has been virtually eradicated worldwide. Researchers at the Pasteur Institute, Paris, first replicated polio in monkeys, using spinal cord samples from a patient, and developed a vaccine in the 1950s after decades of work in not only monkeys, but also mice and rats. The Koch Institute for Integrative Cancer Research, at MIT, USA, has tested in rats a ‘self-boosting’ polio vaccine that means multiple vaccination shots are not required.  See also the work of researcher Jonas Salk. 

A universal vaccine targeting a range of strains of meningitis B, which affects the brain, has been developed by EARA member Novartis, Switzerland, which used earlier research in mice and rats. Novartis researchers were able to create the vaccine by searching the genome of the Neisseria meningitides bacterium (the main cause of meningitis) for proteins that could be targeted by antibodies, before producing these antibodies in mice and testing whether they could kill the bacteria. Rats treated with the mouse antibodies confirmed that the vaccine worked and could be rolled out to protect thousands from disability and death.   
Zebrafish have also been used to study meningitis. A study at the Paris Brain Institute, France, and UMC Amsterdam, Netherlands, identified that brain neurons that detect bitter tastes played a role in protecting against bacterial meningitis.  

Chronic myeloid leukaemia (CML) is one such rare cancer that develops slowly over a person’s lifetime, but thanks to medical advances can now be kept under control with the right treatments. Studies in mice were an instrumental part in finding the protein abnormality that causes CML. The precision medicine Gleevec was developed, by Oregon Health & Science University, USA, to just target this protein abnormality in cancer cells in mice (not targeting all cells, like most chemotherapy drugs), and was later used to reduce cancer growth in CML patients. Other species, including dogs, rabbits and monkeys, were also involved in the development of Gleevec (and its rapid approval by the US Food and Drug Administration), by shedding light on how the drug behaved in the body and potential toxicities. 
​There are several different types of rare cancer that start in childhood, including neuroblastoma that mainly affects children under five-years-old and starts in nerve cells called a neuroblast, often in the adrenal glands located on the top of each kidney. Several studies in mice have contributed to improving survival rates and developing treatments with less severe side effects, for example a team at the University of Gothenburg, Sweden, were able to find an effective drug that worked against one of the two gene mutations that cause neuroblastoma.  
Mice were also used in a study of the rare eye cancer retinoblastoma (which mainly affects young children) at the St Jude’s Research Hospital, USA, to confirm that the cancer’s cause was not a series of mutations, like most cancers, but the loss of a single gene – explaining why it develops so quickly.

Animals have been paramount to understanding HIV in terms of the virus itself, and to how to treat AIDS which occurs as a result of the virus attacking the immune system – see also this article. 
Several preclinical studies have paved the way for developing antiretroviral therapy (ART), which involves a combination of medicines that suppress the virus’s replication – the earliest ART was tested in monkeys. 
Simian immunodeficiency virus (SIV) in monkeys is closely related to human immunodeficiency virus (HIV), and a study by EARA member the Biomedical Primate Research Centre (BPRC), Netherlands, discovered that the SIV virus damages the brain and can lead to neurological symptoms. This highlighted how HIV in people could also affect other parts of the body (not just the immune system) and helped identify other possible targets for research and treatments.  
There is also a real possibility of an effective vaccine within reach the next decade, based on the success of trials in animals. In 2019, for example, the virus was eliminated from the genome of a mouse for the first time, by researchers at Temple University and the University of Nebraska Medical Center, both USA. Temple researchers also created a new HIV therapy using CRISPR gene editing that worked to eliminate HIV from infected cells in human cells, mice and monkeys; it is in clinical trials in humans. Meanwhile, another US team at Scripps Research developed an HIV vaccine, which improved the ability of mice, rabbits and monkeys to block the virus. 

As well as using genetically altered mice, other treatments for sickle cell disease hold great potential such as producing cells of interest from human stem cells, which have the ability to develop into any type of cell, and then transplanting these into animals to grow and develop. 

A variation on this approach has been used at the University of Alabama at Birmingham, USA, which also previously developed the first mice that could be used to study sickle cell anaemia. By making mouse skin cells develop into stem cells, the researchers successfully made these mice models produce healthy, functioning blood cells and the diseased animals showed no symptoms.

The blood condition haemophilia, also known as the ‘Royal Disease’ because it ran in the family of certain royal lines, is where the ability of the blood to clot is severely hampered, leading to excessive bleeding. It is now known to be caused by a change in one gene in the X chromosome, that is inherited and passed down through generations. Studies in dogs that naturally had a type called haemophilia B led to the development of a gene therapy that later went to human trials, from research at Auburn University, USA, while a factor from the blood of pigs has historically been used as a treatment for specific types of haemophilia (such as haemophilia A), to successfully stop bleeding episodes in severe cases.

Non-human primates have played a central role in the research and treatment of hepatitis, a group of infections, usually caused by viruses, that affect the liver and result in inflammation. Chimpanzees are the only animal that can be infected with the hepatitis C virus (HCV) – a type that has long confounded researchers. Although other animals can model aspects of HCV infection (mice, for example, share some genes with human HCV), they do not always encapsulate the disease well.  
The use of great apes in research, including chimpanzees, is generally prohibited in the EU, and is only permitted when a condition that endangers humans cannot be studied in other species, as is the case with hepatitis C. The discoverers of hepatitis C, Harvey J. Alter, Michael Houghton and Charles M. Rice, were awarded the 2020 Nobel Prize in Medicine, with chimpanzees being an integral part of the work.  
Mice are more commonly used to study hepatitis B, for example, through the transplantation of human liver; yet,using mice, researchers from the University of North Carolina School of Medicine, USA, found that an oral drug originally intended for hepatitis B could also prevent the hepatitis A virus.  
Other species, such as ducks and groundhogs, are infected by similar viruses, which also make them useful to hepatitis research. 

Many people with another genetic brain disease, Rett syndrome, which causes mental and physical disability, can live to adulthood, but certain complications such as pneumonia and problems with heart rhythms, can mean some die during childhood. Mice have been important for testing gene therapies for Rett syndrome, particularly by allowing researchers to study it in females, since it affects females more than males. 

For some neurological diseases, the fruit fly has proved to be a valuable species, playing a considerable role in not only our understanding of how these diseases work, but also in the discovery of rare diseases. It was thanks to investigating a specific gene mutation generated in fruit flies that researchers at Baylor College of Medicine, USA, first identified Mitchell syndrome(previously a mystery) to understand how it caused progressive loss of various body functions, including movement and hearing, in people with the mutation.

In turn, through investigating potential treatments for the syndrome, again using fruit flies, members of the same team were then also able to apply their insights to other neurological diseases such as multiple sclerosis (which is more common, but includes the common feature of brain inflammation).

Meanwhile, in a study led by EARA member Uppsala University, Sweden, researchers concluded that routinely used blood-thinning drugs could be a hugely beneficial option for people with cerebral cavernous malformations (abnormal groups of blood vessels in the brain that can lead to bleeding, resulting in seizures), by studying mice with mutations that reflected the human condition, as well as human tissues. 

In the last decades, significant progress has been made in treating this mosquito-borne disease, thanks to US research that involved penguins infected with an avian version of malaria, to study how it could be treated with an antimalarial drug, chloroquine. 
However, malaria remains a significant health threat in regions including sub-Saharan Africa and southeast Asia (it caused more than 600,000 deaths in 2021), and what is urgently needed is an effective vaccine that can target the parasite, or the disease itself. The RTS,S vaccine, which entered large-scale trials in 2019 to treat thousands of young children in Africa, was developed with the use of mice in the 1960s. Those studies showed that vaccinating animals against the infective stage of plasmodium can protect against infection, and also identified a specific protein that could be recognised by the immune system – this was incorporated into the RTS,S vaccine and, in 2021, the World Health Organization recommended RTS,S for preventing malaria in children living in high-risk areas.  
More recently, research at EARA member the Max Planck Institute for Infection Biology, Germany, and the University of Bristol, UK, was able to find what caused organ failure in malaria patients by infecting mice with a variant of the malaria parasite (as well as genetically altering mice), to protect against liver damage that is seen in severe cases of the disease. 

In countries, particularly in Africa, such as the Democratic Republic of Congo (DRC), Ebola is a serious ongoing health emergency. However, thanks in part to research involving mice and monkeys, a real breakthrough was achieved in 2019 when two of four experimental treatments cured 90% of patients in a clinical trial. These therapies were pioneered by harvesting the antibodies from humanised mouse models that were exposed to proteins from the virus, which were then studied in combination with monkeys. 
An outbreak in 2020 (the second most deadly to occur) also ended because of a rollout of the first successful vaccine and two antibody drugs developed in monkeys by the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC), USA. 
A more recent NIAID study used monkeys to develop a vaccine against Sudan virus – one of the four types that cause Ebola and is similarly deadly in both monkeys and people, and which is also lacking a treatment.  

Animal research, in species such as monkeys, has also paved the way for human vaccine trials to begin for other viral diseases, such as the one caused by Zika virus, after work by the University of Liverpool and the University of Manchester, both UK.  
At Yale, US, a team used the same blueprint of a Covid-19 vaccine to develop one for Lyme disease, which protected guinea pigs against this tick-borne infection.  
​Meanwhile, research led by Oregon Health & Science University, USA, developed an experimental drug for the Chikungunya virus that, when tested in mice, reduced the amount of virus by up to 1,000 times and stopped joint pain, with hopes to start clinical trials in the future. Chikungunya is a viral disease transmitted via mosquito bites, with one of its key symptoms being joint pain, which can often be severe and last months, or even years.  
The first vaccine for chikungunya is likely to go onto the market in 2023, following ‘imminent’ approval by the Food and Drug Administration (FDA). Developed by the biotechnology company, Valneva, France, monkeys were used to test antibodies that can neutralise the virus, with trials showing that the animals did not develop any symptomatic disease. 

The health of animals, humans and the environment is deeply interconnected. Because many infectious diseases are transmitted to animals and humans alike, monitoring how pathogens are spread in animals can give crucial information to prevent and control the spread of diseases. A large study in Brazil from Fiocruz and the Federal University of Rio de Janeiro (UFRJ) captured 1,714 mosquitoes from 52 species at two nature reserves using light traps and found that mosquitoes in the Brazilian Atlantic Forest are now more likely to feed on humans due to biodiversity loss. 
The World Organisation for Animal Health has as one of its main missions to monitor the emergence and spread of animal diseases so we can take action before they deeply affect animal welfare and animal and public health.  

It is not only human health that benefits from infectious disease studies in animals, but such research is also important to help minimise or prevent transmission between humans and other species, as well as protect farm animals. Diseases that can pass between people and animals are known as zoonotic diseases, such as Covid-19 and rabies, or the recent outbreak of the monkeypox virus. 
The global EU-funded consortium, VACDIVA, involving EARA member the Complutense University of Madrid, Spain, is at the forefront of developing a vaccine for African swine fever (ASF) – a high contagious disease affecting pigs that has resulted in millions of the animals being culled.  
Research at The Roslin Institute at the University of Edinburgh, UK, found that vaccinating calves against bovine TB in their first few weeks of life boosted the level of protection against the disease, which presents a major health challenge in cattle, but can also be spread occasionally to humans.  

As the most common species of animals used in research around the world, rodents are indispensable to the understanding and treatment of infectious diseases. Animals more closely related to us, such as monkeys, catch more of the same diseases as humans, however rats and hamsters have many of the same health problems that are common to the human condition – they can also easily be given characteristics of a disease through genetic alterations.  
Attaching cells or tissues derived from humans into mice – a technique called a xenograft – is another useful way to make the animals more ‘human-like’ so that they better reflect human diseases and pathology. Immune cells have been xenografted and applied to the study of several types of infectious disease, such as viral haemorrhagic fevers, that include dengue, yellow fever and Ebola. Research at the German Centre for Infection Research showed that by transplanting human stem cells into mice, the animals exhibited features akin to Ebola, such as liver impairment.  
By analysing mouse stem cells, researchers at the Francis Crick Institute, UK, found that the ‘machinery’ needed to build an antiviral protein could protect the body against both the Covid-19 and Zika virus. 

The fact that mice can be easily genetically manipulated to carry specific genes, or have their genes edited, has paved the way for treating various diseases, including familial hemophagocytic lymphohistiocytosis (FHL), a disease of the immune system commonly affecting young children.

Research led by EARA member the Max Delbrück Center (MDC), Germany, used CRISPR gene editing to repair the defective immune cells in mice as well as in blood samples taken from two babies with FHL, to dampen the immune response and return it to normal.

Meanwhile, scientists at ICVS, University of Minho, Portugal, studied Machado-Joseph disease (MJD) – also called spinocerebellar ataxia type 3 – that affects muscle control and in the severest cases limits life expectancy to around 35 years. The team genetically engineered mice to express a protein that is responsible for the rare genetic disorder, and by using these mice to test possible treatments, found that an existing drug for depression could reduce the severity and slow the progression of MJD. 

"The animal models provide essential information regarding nervous system function that is not possible to obtain in cell culture systems and allow us to evaluate the effect of treatments on the organism as whole, namely on the movement problems associated with the disease," said​ Dr Patrícia Maciel, ICVS Minho, Portugal.

Mice can also be engineered to study cystic fibrosis (CF), a condition that results in thick mucus building up in the lungs and digestive system. The mice used have the CTFR gene that is responsible for the condition and this allows researchers to investigate the faulty mechanisms that cause the mucus to thicken abnormally, as well as ways to prevent common features such as lung damage. 

In a study at Yale School of Medicine, USA, researchers were also able to correct some of the mutations in CTFR in multiple tissues in mice, using gene editing, and found that this treatment led to CTFR partially gaining back its normal function. This has the potential to treat not only CF, by addressing its numerous gene mutations, but other genetic conditions. 

Humanised mice can shed light on the gene defects that affect the health and function of the muscles, such as muscular dystrophy and spinal muscular atrophy (they can display similar symptoms to the human condition). Researchers at Harvard University, USA, explored a different approach by successfully transplanting human muscle stem cells into mice with muscular dystrophy, to improve their muscle function and help repair future muscle injuries. 

As well as being very biologically similar to people, monkeys are also natural hosts of many of the same pathogens that infect us, such as the parasite that causes malaria. Studying infections that progress naturally, and occur from wild-type pathogens that have not been altered in some way, has the advantage of being more reflective of human disease – monkeys are the best animal to study Ebola, for instance, because the virus causes serious illness that is akin to what happens in people.  
Assessing how well a vaccine works (or at all) is especially crucial, and the use of research monkeys has led to the introduction of antiretroviral therapy for HIV and the approval of all Covid-19 vaccines. Studies in monkeys also serve to improve our understanding of how diseases may affect the body long term – the hidden effects of ‘long Covid’ was revealed in a study in macaques by EARA member the BPRC, which showed that even with no obvious signs of infection, the animals still had evidence of lung damage and active virus in the lymph nodes. Watch this BPRC video on testing a Covid-19 vaccine.  

Zebrafish have therefore contributed to the study of various genetic diseases, including Batten disease, an incurable disease that results in several symptoms, such as vision sity of Warwick, both UK, zebrafish were edited to have a so-called GATA2 deficiency – a hallmark of a rare bone marrow disorder that is tied to the development of blood cancer – to shed light on how this deficiency increases the risk of the cancer. 

EARA member the Luxembourg Centre for Systems Biomedicine (LCSB), at the University of Luxembourg, was able to identify three possible early markers of Batten disease, using zebrafish larvae which had advantages over using mice or other mammals, which do not develop the disease until adulthood.e. For example, in a study at the University of Birmingham and University of Warwick, both UK, zebrafish were edited to have a so-called GATA2 deficiency – a hallmark of a rare bone marrow disorder that is tied to the development of blood cancer – to shed light on how this deficiency increases the risk of the cancer. 

"Our new model may also facilitate drug screening to identify compounds that could slow or halt disease progression, a breakthrough that the 14,000 patients living with this still uncurable disease are eagerly waiting for," said Dr Carole Linster, LCSB, Luxembourg.

Meanwhile in work at Sidra Hospital, in Qatar, researchers are using genetically modified zebrafish to gain key insights into the biology and symptoms of a range of rare childhood diseases (including inherited blood disorders such as sickle cell anaemia), in turn paving the way for precision medicines. 

Another benefit of zebrafish larvae is their transparent bodies which makes them particularly suited to renipulation has led to zebrafish that have specific gene changes linked to the disease. For example, in a study at the University of Birmingham and University of Warwick, both UK, zebrafish were edited to have a so-called GATA2 deficiency – a hallmark of a rare bone marrow disorder that is tied to the development of blood cancer – to shed light on how this deficiency increases the risk of the cancer. 

For cancer, the benefit of genetic manipulation has led to zebrafish that have specific gene changes linked to the disease. For example, in a study at the University of Birmingham and University of Warwick, both UK, zebrafish were edited to have a so-called GATA2 deficiency – a hallmark of a rare bone marrow disorder that is tied to the development of blood cancer – to shed light on how this deficiency increases the risk of the cancer. 

Dogs share several similar features with people, such as in their anatomy (they have most of the same organs), which makes them suitable for studying human-relevant diseases. They also naturally catch some of the same infections we do, such as rabies.  
Research in dogs was responsible for both veterinary and human rabies vaccines, by vaccinating them using weakened samples of the virus (made from rabbits). Vaccinating dogs means people and animals are also much better protected from its spread, as found by a study led by Imperial College London and the University of Glasgow, both UK, and Ifakara Health Institute, Tanzania.  

"Lots of neurological phenotypes in humans can be assessed in fruit flies, including seizure, motor skills, aging and neuroinflammation," said Dr Hyunglok Chung, Houston Methodist Hospital, Texas, USA.

The causes of the rare neurodevelopmental disorders, Harel-Yoon syndrome and Yoon-Bellen syndrome, were both identified as due to specific genetic mutations thanks to studying fruit flies, by researchers at Baylor College of Medicine, USA. Although this gene mutation had been linked to neurological symptoms in humans, it was only by determining the effect in fruit flies that researchers could confirm the cause – paving the way to targeted treatments. 

Meanwhile, in a fruit fly study at the University of Sydney, Australia, researchers were able to pinpoint howter the cancer has spread to other parts of the body. This resulted in the same tumour development as seen in humans, and was the first time the disease was modelled in an animal, after failed attempts to do so in mice. 

Fruit flies reach adulthood in just two weeks, so using them in research opens doors to exploring the long-term effects of a disease and how it progresses over a lifetime, which is more difficult to achieve in larger animals and humans. For example, research at the Institute for Research in Biomedicine and SJD Paediatric Cancer Center Barcelona, both Spain, engineered fruit flies to express a variant of a cancer gene that causes a rare bone cancer called Ewing sarcoma, which has a survival rate of only just over 50% in teenagers, and less than 30% after the cancer has spread to other parts of the body. This resulted in the same tumour development as seen in humans, and was the first time the disease was modelled in an animal, after failed attempts to do so in mice. 

Rabbits have played an important role in the study of some infectious diseases, particularly the S. pneumoniae bacteria that cause pneumococcal disease, which are a diverse range of infections, from those of the ear to the bloodstream, and is spread through direct contact.  
Rabbits have helped to identify new types of the disease in studies on how the bacteria infect, survive and progress, while also being central to developing and testing a range of candidate drugs. For example, US research, led by the University of Buffalo, New York, used rabbits along with mice to test a vaccine that was effective against more than 70 types of S. pneumoniae. 
The first type of papillomavirus was also discovered in rabbits, and research into human papillomavirus (HPV), which can cause various types of cancer and is the main cause of cervical cancer, has benefited from the use of various animal species. 

A rare disease that dogs can get is Batten disease – called neuronal ceroid lipofuscinoses in the canine version. Here, studies in dogs by a US team led by the University of Pennsylvania, have led to new findings about how best to deliver gene therapy to slow the development of the disease in children and in dogs. Studies at the University of Missouri have also looked at how to preserve the function of the retina – a common hallmark of Batten disease is vision loss. 

It was from a study at EARA member the University of Helsinki, Finland, that researchers found that the canine version of hypophosphatasia (impaired mineralisation of the bones and teeth) closely resembles the disease in human babies, and also marked the first report of this condition naturally occurring in dogs. The findings then allowed the team to develop a gene test for the specific dog breed they investigated, to identify the defect before birth. 

"Although hypophosphatasia has been extensively studied in humans, the results of the canine study are significant, as they provide the first spontaneous animal model for the disease, which may also open new avenues for the development of novel therapies," said Prof Hannes Lohi, University of Helsinki, Finland.

Dogs can also suffer from the blood disorder haemophilia. Another condition that is shared with dogs includes muscular dystrophy (MD), because the gene mutation in human MD matches that in golden retrievers with MD. In an unexpected development of studying a version called Duchenne MD in this breed, researchers at the University of São Paulo, Brazil, discovered a new gene mutation that can protect against muscle degeneration and weakness from the disease, opening new avenues to treatment.

Infectious disease research benefits from studying a range of other animals, such as ferrets and guinea pigs which naturally catch strains of human flu, for example, and therefore display similar symptoms.  
Meanwhile, the embryos of chickens develop in a way that is comparable to human foetuses and are therefore useful for studying early infection in diseases like Zika.  
More unconventional species such as insects – from moths to mosquitos to honeybees – are also emerging as valuable models, since they can be easily manipulated, for example at the genetic level, to help understand the factors that contribute to infection mechanisms, disease progression and much more. Insects have additional value because certain pathogens (such as the plasmodium parasite for malaria) use insects as a host to infect other organisms, and can also be used to better understand antibiotic resistance. 

While pigs do not naturally get cystic fibrosis (CF) they can be bred to develop very similar symptoms to the condition, such as lung disease which can naturally develop as a result – the lungs of pigs have been shown to be affected in a very similar way to those of humans. This means that interventions can be tested at an earlier stage than in a patient, in turn allowing researchers to come up with measures that could help to ease symptoms or detect the condition earlier on.

Pigs have also been geneticalms to people with the condition compared to rodents, such as difficulties with walking and running with age. In addition, certain brain changes were similar, such as the loss of specific neurons and immune responses. 

Meanwhile, the same similarities in body make-up to humans have also meant that pigs have been used to model Huntington’s disease, a rare disorder where the brain’s nerve cells are damaged, and that can affect movement, behaviour and communication, among other effects. 

In a study from Emory University, USA, and Jinan University, China, the genome of pigs was edited using CRISPR to insert the human gene that causes Huntington’s. This approach resulted in pigs that showed very similar symptoms to people with the condition compared to rodents, such as difficulties with walking and running with age. In addition, certain brain changes were similar, such as the loss of specific neurons and immune responses.