Diseases And Disorders

"One of the earliest advances with fetal tissue was to use fetal kidney cells to create the first poliovirus vaccines, which are now estimated to save 550,000 lives worldwide every year."

"In the early days of making the vaccine, researchers infected fetal kidney cells in Petri dishes to produce a large amount of virus that they could then harvest, purify and use to vaccinate people. (The virus evolves to become less deadly when it infects cells out of the body, and thus could safely be given to people to prime their immune system for the real thing.) Today manufacturers of the polio vaccine use other types of human cells, which weren’t available in the mid-1900s. They also use monkey cells, which they originally avoided for fear that making the vaccine in animal cells could put people at risk of diseases from other species."

"Some people assume that because diseases like polio have disappeared from the United States, it’s no longer necessary to vaccinate children against them. However, polio is still widespread in other parts of the world, and could easily begin re-infecting unprotected individuals if it were re-introduced to the country."

"In the 1940s, scientists worked on vaccines against influenza, polio, measles, and other viruses deemed critical national security importance. That decade brought vaccines against influenza, which was then understood to be not just one virus, but several types of influenza virus for which different vaccines would be needed. Similarly, polio was understood to be three types of virus in the same group, so a vaccine against one type did not protect against the others."

"Rumors of the current oral polio vaccine having been intentionally contaminated with drugs to cause sterility and “viruses which are known to cause HIV and AIDS” led to local refusals to accept the vaccine in parts of Africa. It’s likely that these rumors are related to the original OPV/HIV accusations. Partially as a result of these refusals, polio flared back up in parts of Africa after vaccination had led to positive steps toward eradication."

"One concern that must be considered is the potential for the vaccine virus to revert to a form capable of causing disease. Mutations that can occur when the vaccine virus replicates in the body may lead to a more virulent strain. This is unlikely, as the vaccine virus’s ability to replicate is limited. However, possible mutations are considered when developing an attenuated vaccine. It is worth noting that mutations are somewhat common with the oral polio vaccine (OPV), a live vaccine that is ingested instead of injected. The vaccine virus can mutate into a virulent form and lead to rare cases of paralytic polio. For this reason, OPV is no longer used in the United States, and has been replaced on the Recommended Childhood Immunization Schedule by the inactivated polio vaccine (IPV). Protection from a live, attenuated vaccine typically outlasts the protection provided by a killed or inactivated vaccine."

"Armed with the knowledge of different virus types of the same virus group, scientists worked on vaccines against all types to prevent all disease. By 1954, after decades of well-funded research, Jonas Salk and his team developed the first killed virus vaccine. It was a vaccine against polio, and it went against the dogmas established at the time: the vaccine had to contain live/attenuated virus, and that a dead virus could not cause an immune response. The work of Isabel Morgan, MD, and other women helped lead the way to a vaccine that saved thousands of children's lives. The 1960s brought the oral polio vaccine as a replacement to Salk's vaccine, after the Cutter Incident eroded the public's trust in vaccines. The oral vaccine, developed by Albert Sabin, was tested in the Soviet Union and Latin America, and then brought to the United States with much success. By the 1990s, polio was eliminated from the United States and much of Europe. By the early 2000s, polio was eliminated from the Americas, Europe, and most of Asia. By the 2010s, polio had receded to local outbreaks in Africa and Central Asia. By the 2020s, types 2 and 3 of polio are eradicated, and type 1 is only present in Central Asia."

"The health benefits associated with relatively recent advances in vaccine therapy are well documented.To mention just a few: in 1921 there were nearly 207,000 reported cases of diphtheria in the United States. In 1991, there were two. In the same year, apart from a small number (five to ten) of vaccine-associated cases, there were no reported cases of poliomyelitis, as compared with more than twentyone thousand in 1952; “The CDC projects that the world will be polio-free by 2003."

"The success of the Nigeria programme hinges on the active participation of everyone to make sure that all children are reached by National Immunization Days (NIDs), Immunization Plus Days (IPDs) and the routine immunization programme, if the country capitalizes on the commitments I've heard in the past two days, Nigeria can lead the way to a polio-free Africa."

"We are in the end game, I'm optimistic that we will be successful. I'm personally very committed."

"I'd like to start by telling you about my wife Melinda's Aunt Myra. We see her a few times a year. Aunt Myra worked for many years taking reservations for Delta Airlines. She lived in New Orleans until Hurricane Katrina, and then she moved to Dallas, Melinda's hometown. She loves to see our kids. When we all get together, she'll sit down on the floor and play games with them. Aunt Myra also has polio. She's in braces, and she has been ever since she was a little girl. Our children only know what polio is because of their aunt. Otherwise, the disease would just be another historical fact they learn about in school. In fact, even though I was born just three years after one of the worst polio epidemics in American history, I didn't know anyone with polio when I was growing up. That's how far we've come."

"The harsh mathematics of polio makes it clear: We cannot maintain a level of one thousand or two thousand cases a year. Either we eradicate polio, or we return to the days of tens of thousands of cases per year. That is no alternative at all. We don't let children die because it is fatiguing to save them. Our commitment as a foundation is to work with partners until no children die from polio."

"In the last 20 years, thanks to your hard work, polio has declined by 99 percent. In 1988, 350,000 people got polio. By 2008, the number was down to just a couple of thousand."

"Though there hasn’t been a single case of polio in the United States since 1979, a significant number of people are still thought to be living with the after-effects."

"Look, you have some vaccines that are so amazing, the polio vaccine I happen to think is amazing."

"The only human infectious disease to be eradicated through vaccination is smallpox. Polio is on the verge of being eradicated, with cases of the wild (not vaccine derived) strain only found in Central Asia."

"Armed with the knowledge of different virus types of the same virus group, scientists worked on vaccines against all types to prevent all disease. By 1954, after decades of well-funded research, Jonas Salk and his team developed the first killed virus vaccine. It was a vaccine against polio, and it went against the dogmas established at the time: the vaccine had to contain live/attenuated virus, and that a dead virus could not cause an immune response. * Later, other researchers would test various vaccines, including vaccines for polio and measles, in institutionalized subjects. These tests, conducted by Salk, Hilary Koprowski, MD, and others, usually did not deliberately infect subjects with the disease agent."

"The Salk vaccine trial successfully showed that the vaccine helped prevent paralytic polio, and licensure of the vaccine quickly followed. The disease that once paralyzed thousands of children has now been eliminated in the Western Hemisphere."

"For decades, the polio vaccine had been made in cells taken from monkey kidneys, some of which – it was later discovered – were infected with a virus, simian virus 40 (SV40). Though today vaccines are extensively filtered, and don’t contain any material from the cells they’re grown in, between 1955 and 1963, it’s been estimated that up to 30 million people were infected in the United States alone. The contamination is thought to have occurred because the cells were usually grown fresh from monkeys – as opposed to from a stock of laboratory cells – and SV40 is a common infection in the most widely used species, the rhesus macaque. Over the ensuing years, frozen vials of the cells were flown to hundreds of laboratories across the world. Whether the introduction of the virus had any medical consequences is still under question – as is the possibility that it is now spreading to people who were never vaccinated. In the laboratory, the virus has been shown to be carcinogenic, and a possible link between the virus and several types of cancer, from brain cancer to lymphoma, has been investigated, but there isn’t yet definitive evidence either way. Nevertheless, it suddenly became necessary to find an alternative supply of cells."

"Unlike bacteria, viruses do not replicate on their own. To make viral vaccines, large numbers of viruses must be grown in cell cultures specific to each virus. Some licensed viral vaccines (i.e., some formulations of hepatitis A, poliovirus, rabies, rubella, and varicellazoster viruses or combination vaccines containing such component viruses) are produced by growing viruses that infect humans in WI-38 or MRC-5 cell cultures."

"Dr. Peter Salk vaguely remembers the day he was vaccinated against polio in 1953. His father, Dr. Jonas Salk, made history by creating the polio vaccine at the University of Pittsburgh and inoculated his family as soon as he felt it was safe and effective. Cases of polio peaked in the early 1950s, but it arrived every summer disabling an average of more than 35,000 people each year for decades, sometimes causing paralysis and death, according to the Centers for Disease Control and Prevention. Public officials closed swimming pools, movie theaters, amusement parks and other pastimes that naturally came with summer vacation."

"In the early 1900s, children routinely suffered and died from diseases now easily prevented by vaccines. Americans could expect that every year diptheria would kill twelve thousand people, mostly young children; rubella (German measles) would cause as many as twenty thousand babies to be born blind, deaf, or mentally disabled; polio would permanently paralyze fifteen thousand children and kill a thousand; and mumps would be a common cause of deafness. Because of vaccines, all these diseases have been completely or virtually eliminated. But now, because more and more parents are choosing not to vaccinate their children, some of these diseases are coming back."

"Thirteen years after Sabin and Olitsky’s success with growing poliovirus in brain tissue, researchers at the lab of John Enders at the Children’s Hospital in Boston successfully grew the virus in a culture of skin and muscle tissue from a human embryo—in a fortunate happenstance. At the time, the researchers were focused on trying to isolate and grow varicella, the chickenpox virus. They had already succeeded in growing mumps and influenza viruses, and had moved on to varicella, which they knew grew in human cells. After preparing flasks with human embryonic tissue, they inoculated four flasks with throat washings from chickenpox patients. Another four flasks were inoculated with a strain of poliovirus as a control group. The chickenpox virus did not grow in this case, but to the researchers’ great surprise, poliovirus did. They went on to grow two other strains of poliovirus, and in many types of human embryonic tissue, without using nervous system tissue. They were able to grow the virus rapidly and to very high concentrations using the “roller tube” apparatus created by researcher George Otto Gey in the 1930s."

"For demonstrating that poliovirus could be reliably grown without using nervous tissue, Enders and his colleagues Thomas Weller and Frederick Robbins were awarded the Nobel Prize in Physiology or Medicine in 1954. Their discovery proved to be the breakthrough needed to develop a polio vaccine. In 1951, Jonas Salk and his colleagues at the University of Pittsburgh found that poliovirus could also be propagated on a large scale in monkey kidney cells. Over time, most vaccine development efforts shifted to cell strains—cultures made up of only a single type of cell. These strains can be derived from tissue cultures, which contain multiple types of cells. While viruses can be grown in tissue cultures, cell strains allow continuous observation and control that may not be possible in cultures containing multiple types of cells. This same transition was made in the development of polio vaccines. A monkey kidney cell strain is used to grow poliovirus for the inactivated polio vaccine made today."

"In 2003, the European Council of Fatwa and Research issued a fatwa finding the permissibility of using oral poliovirus vaccine produced with porcine-origin trypsin. Their decision centered on lack of similarity between pork and purified trypsin, physical removal during processing, dilution of any residual, necessity, and lack of alternative."

"Numerous examples of vaccine-preventable outbreaks among religious schools, congregations, and communities illustrate how clusters of vulnerable people can enable epidemics, even spreading beyond those foci to neighboring, well-immunized communities. Published examples include diphtheria, Haemophilus influenzae type b, hepatitis A, measles, mumps, pertussis, poliomyelitis, and rubella."

"Opposition to immunization programs among selected Muslim communities has occurred during poliovirus immunization programs in Nigeria, Pakistan, and Afghanistan. The opposition within northern Nigeria, notably in the state of Kano, was particularly long-lasting and an impediment to the global eradication effort. Detailed consideration of the Nigerian situation revealed that what was described as ostensibly religious objections and assertions that vaccines spread the HIVvirus or were vehicles for sterilization programs masked deeper struggles related to political power, inadequate health services, and a controversial clinical trial of an investigational antibiotic. While the boycott was centered within Islamic social networks, most of the objections raised related to social issues, rather than theological issues. Eventually, the Nigerian government sent religious representatives to South Africa, Indonesia, and India to observe quality-control tests of poliovirus vaccines to be used in their areas and then sourced the vaccine from manufacturers they trusted."

"During the early efforts to develop a vaccine against polio, researchers discovered that the virus could cause disease not only in humans, but also in monkeys. This led to early field trials in the 1930s of vaccine candidates developed using material taken from polio-infected monkeys, such as monkey spinal cords. These candidates proved dangerous, sometimes causing paralysis in the limb where the vaccine was administered. Vaccines derived using nervous system tissue have a higher side effect profile than those developed using other methods (the myelin in the vaccine material can stimulate an adverse neurological reaction). The trials ceased, and researchers moved on to find another way to grow the virus for vaccine development."

"Viruses for some vaccines are grown in laboratories using animal cell cultures. This is because viruses will only grow in human or animal cells. In the UK schedule this applies to these vaccines: *The polio part of the 6-in-1 vaccine (Infanrix Hexa), the pre-school booster vaccines (Repevax, Infanrix IPV and Boostrix-IPV) and the teenage booster vaccine (Revaxis) *The Rotavirus vaccine (Rotarix) * One of the Inactivated flu vaccines (QIVc) Viruses for these vaccines are grown on Vero cells. This is a cell line started in the 1960s using kidney cells from an African green monkey."

"Hopes of growing poliovirus in the lab without the use of live animals drove many researchers in the 1930s and 1940s. Cell cultures involve growing cells in a culture dish, often with a supportive growth medium like collagen. They offer a level of control unavailable using live animals, and can also support large-scale virus production. (For more about cell cultures and cell lines, as well as cell lines made using human cells, see our article “Human Cell Strains in Vaccine Development.”) Early efforts to grow poliovirus in culture, however, repeatedly ended in failure. In 1936, Albert Sabin and Peter Olitsky at the Rockefeller Institute successfully grew poliovirus in a culture of brain tissue from a human embryo. The virus grew quickly, which was promising, but Sabin and Olitsky were concerned about using this as starting material for a vaccine, fearing nervous system damage for vaccine recipients. They tried to grow poliovirus in cultures using tissue taken from other sources, but were unsuccessful."

"When I was around six years old, I woke up one morning and couldn’t get out of bed. My legs wouldn’t move. I was paralyzed from the waist down. This was during the polio era, in the early 1950s. My mother came in because I wasn’t ready for school. I remember the alarm in her eyes. In those days, doctors made house calls, and he entered my room carrying his black physician’s bag, sat on the edge of the bed, stuck a thermometer under my tongue, and checked my pulse. There was little else he could do. The terror of polio haunted children and parents everywhere. It was common to see young people in leg braces or wheelchairs; those imprisoned in iron lungs we only heard about. I was lucky. It wasn’t polio; it was possibly a severe allergic reaction to a tetanus shot I had had a few days before, caused by the tetanus antitoxin, which is harvested from horse blood. Horses were so important to the production of antibodies that many of the great pharmaceutical companies began as horse farms. It might also have been a dangerous disease called Guillain-Barré syndrome, an autoimmune disorder sometimes associated with infections such as influenza, Zika, and dengue fever—but so far not Covid-19. After a day or two, I could move my legs, but the memory was searing."

"The first written account of variolation describes a Buddhist nun (bhikkhuni) practicing around 1022–1063 CE. She ground scabs taken from a person infected with smallpox (variola) into a powder, and then blew it into the nostrils of a non-immune person to induce immunity. Continuing this tradition, the 14th Dalai Lama participated in poliovirus immunization programs personally."

"Omar Kasule, professor of Islamic medicine at the Institute of Medicine University of Brunei Darussalam noted that polio immunization is obligatory (wajib) when disease risk is high and the vaccine shown to have benefits far outweighing its risks. Muslims will be interested in issues of vaccine safety, Professor Kasule explained, because immunization to prevent disease should not lead to side effects of the same magnitude as the disease. He based this judgment on the purpose of the law to protect life, the principle of preventing harm (izalat aldharar), and the principle of the public interest (maslahat al-ummah). He noted that the Qur’an¯ uses the concept of wiqaya in multiple situations to refer to taking preventive action (e.g., against hell-fire, punishment, greed, bad acts, harm, heat) and concludes that prevention is one of the laws of Allah, ¯ with obvious application to medicine."

"Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance."

"While the etiology and pathogenesis of Parkinson’s disease (PD) is still obscure, there is evidence for lifestyle factors influencing disease risk. Best established are the inverse associations with smoking and coffee consumption. In other contexts there is evidence that health effects of lifestyle factors may depend on gut microbiome composition."

"All patients with Parkinson's disease learn tricks of various sorts—to "unfreeze" themselves, to initiate and control motion, to transfer tremor and rigidity from limb to another, etc, etc. Such tricks or strategies, were analysed in detail by A R Luria in the 1920s and by James Pardon Martin (especially in his 1967 book, The Basal Ganglia and Posture), but these analyses would not have been possible without the aid of patients."

"The International Parkinson and Movement Disorder Society Evidence‐Based Medicine Committee's recommendations for treatments of PD were first published in 2002, updated in 2011, and now updated again through December 31, 2016. … The evidence base for treating a range of nonmotor symptoms in PD has grown substantially in recent years. However, treatment options overall remain limited given the high prevalence and adverse impact of these disorders, so the development and testing of new treatments for nonmotor symptoms in PD remains a top priority."

"Intestinal inflammation has been suggested to play a role in development of Parkinson’s disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD and MSA, we performed a nationwide population-based cohort study. ... This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent basic scientific findings of a potential role of GI inflammation in development of parkinsonian disorders."

"For the past 15 months we have been engaged in a long-term study of the effects of levodopa on 60 severely disabled patients with Parkinson's disease, half postencephalitic and half idiopathic, who have been institutionalized for many years in our chronic disease facility. In common with published reports (summarized in an editorial in Brit Med J 1:446-447, 1970) we have found that the drug was effective, though to a varying degree, in the majority of our patients. However, in contrast to these reports we have observed that the period of benefit has been of limited duration and has been followed in all cases by adverse effects, the latter often progressive, sometimes serious, and occasionally dangerous."

"Parkinson’s disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. ... This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson’s disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein."

"The intestine is one of the first affected organs in Parkinson’s disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon. ... In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasser subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD. ... The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD."

"The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). … In addition to increased local inflammatory activity in the intestine, there is also evidence of increased systemic inflammatory activity in Parkinson’s disease. Thus, the working group around Williams-Grey and Bordacki detected increased levels of proinflammatory cytokines such as TNF-α, INF-gamma, IL1-β, IL-2, IL-4, IL-6 and IL-10 within the blood of PD patients … In this context, it has already been suspected that proinflammatory cytokines lead to a disruption of the blood-brain barrier and consequently are indirectly involved in the activation of glial cells … in a mouse model of PD transplantation of the microbiome of patients with PD into receptive mice led to motor symptoms as opposed to the transplant sample of healthy individuals … Furthermore, recently it has also been shown that gut-associated bacteria differ in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases in the proximal small intestine and thereby influence the levodopa dosages needed for symptom control … In this regard, a conserved tyrosine decarboxylase (TyrDC) has been detected within Enterococcus faecalis … In addition, a negative correlation between the frequency of Firmicutes and the use of entacapone has been reported … These data suggest that in future the microbiome might be a crucial component in the management of side effects as well as in the therapy of PD."

"We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson's Disease that could be used in clinic"

"As a person with Parkinson's, it's hugely frustrating to think that one decision can actively hold back research that holds promise to transform lives. Patients with neurodegenerative diseases dream of the day when disease-modifying treatments are found, instead of therapies that simply mask symptoms. Disease-modifying therapies create the possibility of newly diagnosed patients never having to experience full-blown disease. The Michael J. Fox Foundation has long championed the scientific freedom to pursue all promising paths to finding these treatments. Biomarker discovery and stem cell science are among the innovative areas of biomedical research that hold potential to speed progress. So while our foundation gears up to launch its most ambitious biomarker discovery project to date, the Parkinson's Progression Markers Initiative, with ADNI as a precedent, we'll also be standing with Parkinson's patients, their loved ones and the majority of Americans who want us to move beyond political agendas and advance the promise of stem cell research."

"It has been established (Inaudible) for example, for Parkinson disease, you can use fetal brain cells from an abortus(?), or for treating diabetes, you can use eyelet cells from corpses. That works, this cure to the patients. The problem is, you need for one patient, for one Parkinson patient, the ... six abortuses, fetal brains, and there are not enough corpses to supply the needy patients with eyelet cells. The conclusion from all this is that only embryonic stem cells could provide the cells needed for an effective medical application."

"The propensity to lean forward becomes invincible, and the patient is thereby forced to step on the toes and the fore part of the feet, whilst the upper part of the body is thrown so far forward as to render it difficult to avoid falling on the face."

"Epilepsy is one of the most common serious brain conditions, affecting over 70 million people worldwide. Its incidence has a bimodal distribution with the highest risk in infants and older age groups. Progress in genomic technology is exposing the complex genetic architecture of the common types of epilepsy, and is driving a paradigm shift. Epilepsy is a symptom complex with multiple risk factors and a strong genetic predisposition rather than a condition with a single expression and cause. These advances have resulted in the new classification of epileptic seizures and epilepsies. A detailed clinical history and a reliable eyewitness account of a seizure are the cornerstones of the diagnosis. Ancillary investigations can help to determine cause and prognosis. Advances in brain imaging are helping to identify the structural and functional causes and consequences of the epilepsies. Comorbidities are increasingly recognised as important aetiological and prognostic markers."

"Neurosurgery is an underutilized treatment that can potentially cure drug‐refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery."

"Following an episode of autoimmune encephalitis, patients experience a variety of neurocognitive sequelae and are at risk for seizures; however our understanding of the true impact of these are limited to case series and retrospective studies ... Not only are seizures a common initial presentation of autoimmune encephalitis, but many patients develop post encephalitis epilepsy ..."

"... microcephaly is only one possible adverse outcome among a spectrum of conditions that may be part of congenital Zika syndrome. A population-level increase in central nervous system anomalies has been observed in both French Polynesia and Brazil."