Of the CRISPR-Cas9 tools created to date, base editors have gotten lots of attention because of their seemingly simple editing: they neatly replace one nucleic acid with another, in many cases all that should be needed to fix a genetic disease. Scientists have now determined the structure of the latest base editor as it swaps out nucleic acids, showing why it can go off target but also how it can be improved.
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People who laugh frequently in their everyday lives may be better equipped to deal with stressful events - although this does not seem to apply to the intensity of laughter.
from Top Health News -- ScienceDaily https://ift.tt/2CUYLzP
The debate about the origin of SARS-CoV-2 continues, as does the debate over whether the pandemic could have been quashed had Chinese authorities acted and shared information about the outbreak sooner.
According to a Hong Kong whistleblower scientist who has fled to the U.S., the Chinese government and World Health Organization representatives in Hong Kong covered up the Wuhan outbreak, allowing it to spread unchecked around the world.
In the featured Fox News interview, the whistleblower, Dr. Li-Meng Yan — who worked at the University of Hong Kong School of Public Health, a top coronavirus research lab — claims her early investigation into the SARS-like outbreak in Wuhan could have helped prevent a global pandemic from developing, had her supervisors shared her findings.
Yan claims her supervisor, WHO consultant Leo Poon, asked her to, secretly, investigate reports of a SARS-like illness spreading in Wuhan, China, in late December 2019. The Chinese government had refused overseas experts from getting involved, and Poon wanted her to figure out what was really going on.
Human-to-Human Spread Was Recognized From the Start
Yan, who has many professional colleagues in China, turned to a friend who works in the Chinese Center for Disease Control and Prevention and had first-hand information about the outbreak. Yan was told there was likely human-to-human transmission occurring, as they had found family clusters of cases.
The WHO, meanwhile, did not confirm the human-to-human spread potential for several weeks. On the contrary, an official WHO statement said the virus "does not transmit readily between people." In a Tweet, WHO also stated that preliminary investigations by Chinese authorities "found no clear evidence of human-to-human transmission."
January 16, 2020, Yan was again asked to reach out to her contacts in China to see if she could learn more. Her CDC contacts were fearful, but it became clear that patients and front-line doctors were not being properly protected, and that Chinese authorities were trying to keep a lid on the flow of information.
When she updated Poon, he told her to stay silent and not cross the Chinese government, or else they'd both be "disappeared." Yan felt it was crucial to inform the public, but Poon took no action. The co-director of the University of Hong Kong School of Public Health laboratory, professor Malik Peiris, also stayed quiet.
Yan believes WHO colluded with the China Communist Party (CCP) government to prevent information about the virus from coming out. The WHO quite predictably denies her claims.
Yan describes how, since her escape, the CCP has been trying to smear her name and ruin her professional reputation, saying she's been kidnapped by Americans, and even that she has a mental disorder. Her professional webpages and affiliations have been deleted and removed.
Yan Doesn't Provide Any Shocking Revelations
On the whole, though, Yan doesn't really tell us anything we didn't already know. It's been clear that China delayed telling the public about the Wuhan outbreak. She doesn't indicate having any information about the virus' origin, and she certainly does not provide any useful recommendations for how to protect ourselves.
In fact, she parrots the recommendations of most governments — staying 6 feet apart, using alcohol-based disinfectants and wearing surgical masks. Aside from disinfectants, which may be useful for killing viruses on hands and surfaces, social distancing and mask wearing have no basis in actual science.
Of course, the Chinese have been known to wear face masks in public for some time, but they've primarily been worn to protect the wearer against air pollution1,2 — not infectious disease. Just because masks prevent inhalation of dangerous air pollution does not mean they work against viruses.
All of that said, she's certainly correct when saying that the CCP's attempts to keep details of the Wuhan outbreak from the public allowed the virus to spread, not only through China but also across the world.
SARS-CoV-2 Did Not Evolve Naturally, Scientists Say
With regard to the origin of SARS-CoV-2, scientists keep finding more clues indicating it's not a naturally-evolved virus. Among them are two recent papers by Norwegian and British researchers Sørensen, Susrud and Dalgleish.
In the first paper,3 "A Candidate Vaccine for Covid-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity," published in the journal Quarterly Review of Biophysics Discovery, they claim to have identified inserted sections in the spike surface that allows it to bind to and enter human cells.
According to the authors, "The SARS-CoV-2 spike is significantly different from any other SARS that we have studied."
The second paper,4 "The Evidence Which Suggests That This Is No Naturally Evolved Virus: A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike," published by the Norwegian periodical Minerva,5,6 July 13, 2020, presents several arguments for why SARS-CoV-2 is likely to have been manipulated in the lab.
As in the first paper, the researchers stress anomalies in the spike protein of the virus. The abstract reads, in part:7
"… SARS-CoV-2 is possessed of dual action capability … The likelihood of this being the result of natural processes is very small. The spike has six inserts which are unique fingerprints with five salient features indicative of purposive manipulation.
We then add to the bio-chemistry a diachronic dimension by analysing a sequence of four linked published research projects which, we suggest, show by deduction how, where, when and by whom the SARS-CoV-2 Spike acquired its special characteristics. This reconstructed historical aetiology meets the criteria of means, timing, agent and place to produce sufficient confidence to reverse the burden of proof.
Henceforth, those who would maintain that the COVID-19 pandemic arose from zoonotic transfer need to explain precisely why this more parsimonious account is wrong before asserting that their evidence is persuasive, most especially when, as we also show, there are puzzling errors in their use of evidence."
US-China Collaborated on Coronavirus Research
Sørensen also highlights open source studies describing the creation of new chimeraviruses that have SARS-coronavirus as a base. For example, researchers have exchanged properties between bat coronaviruses and human SARS viruses. So, there can be no doubt that the technology and know-how exists. Minerva reporter Aksel Fridstrom writes:8
"Furthermore, Sørensen's article points to the fact that Wuhan's Virology Institute again in 2010 took part in gain-of-function experiments with international collaborators, where SARS-coronavirus was provided with additional properties that increase the virus's ability to infect humans."
In that research, an HIV pseudovirus was used to express seven bat ACE2 receptors. The binding properties of these bat ACE2 receptors were compared to human ACE2 receptors in order to determine which one would have the greatest ability to bind to and infect human cells.
The international collaborators in this case included researchers at the University of North Carolina. Five years later, in 2015, the University of North Carolina again collaborated with the Wuhan Institute of Virology, performing gain-of-function research in which bat viruses were manipulated to create a chimeric virus capable of binding to human upper airway cells. That particular virus was called SHC014-MA15.
"Sørensen and his co-authors write that this work created 'a chimeric virus with very high infectivity potential targeted to the human upper respiratory tract' and that what is being described is 'in fact, precisely SARS-CoV-2 properties,'" Fridstrom writes.9
Virus Origin Papers Are Being Shunned by Scientific Journals
One of the reasons Sørensen, Susrud and Dalgleish chose to publish their science paper in a magazine rather than a scientific journal is because of the difficulty getting papers about the virus' origin published. There's tremendous stigma attached to this topic.
The journal Nature was recently caught blocking accounts of people questioning the natural origin of SARS-CoV-2 on Twitter, and several papers discussing the lab origin theory or proposing genetic engineering are languishing on preprint servers, seemingly unable to get accepted for formal publication. Several such papers are mentioned in a July 16, 2020, GM Watch article.10
Sørensen, Susrud and Dalgleish had also already gotten the runaround on their first paper. Both the Journal of Virology and Nature rejected it, stating it was "unsuitable for publication." It was eventually accepted by Quarterly Review of Biophysics Discovery, a journal chaired by Stanford University and University of Dundee scientists.
Why COVID-19 Vaccines Are Likely to Fail
Importantly, in "A Candidate Vaccine for COVID-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity,"11 Sorensen et.al. warn that current efforts to develop a COVID-19 vaccine are likely to fail since the etiology of the virus has been misunderstood:12
"These data reveal the biological structure of SARS-CoV-2 Spike and confirm that accumulated charge from inserts and salt bridges are in surface positions capable of binding with cell membrane components other than the ACE2 receptor.
We have also looked at the naked coronavirus spike protein as a concept for the basis of a vaccine, which we have rejected because of high risk of contamination with human-like epitopes.
Analysis of the Spike protein of SARS-CoV-2 shows 78.4% similarity with human-like (HL) epitopes. For the avoidance of confusion, a standard protein blast searches for functionalities and homologies to other proteins.
However, antibodies can only recognize 5-6 amino acids and therefore a 6 amino acid rolling window search for antibody epitopes was performed.
A search so tailored to match against all human known proteins will give a 78.4% human similarity to the SARS-CoV-2 Spike protein, i.e if all epitopes on the 1255 amino acid long SARS-CoV-2 Spike protein can be used by antibodies then there will be 983 antibody binding sites which also could bind to epitopes on human proteins.
This is what we did and found … [I]n the present context, any vaccine design based on the whole Spike protein of SARS-CoV-2 may not be immunogenic due its high human similarity compared to a vaccine with specifically selected NHL epitopes, such as Biovacc-19 does — and is.
COVID-19 candidate vaccines designed without appreciating these problems may run similar risks to those experienced with HIV vaccines that failed to show protection.
The possibility of inducing autoimmune responses or antibody-dependent enhancements, needs to be carefully guarded against because there is published evidence that an HIV candidate vaccine has actually enhanced infectivity:
'Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time.'
Such antibody-dependent enhancement (ADE) has been observed for coronaviruses in animal models, allowing them to enter cells expressing Fc𝛾R. ADE is not fully understood: however, it is suggested that antibody-dependent enhancements may come as a result of amino acid variability and antigenic drift."
They also point out that choosing an adjuvant after the primary vaccine design work has been completed, which is how vaccine development is typically done, may be yet another serious mistake that could make a COVID-19 vaccine really dangerous.
Many Different Lab Origin Hypotheses Have Been Presented
Another scientist who questions the natural evolution theory is Jonathan Latham, Ph.D., a molecular biologist and virologist. In a June 2, 2020, Independent Science News article,13 Latham and Allison Wilson, Ph.D., a geneticist, dissect the zoonotic origin theory, showing the research simply does not support this claim.
While they do not dispute the idea that SARS-CoV-2 started out as a bat coronavirus at some point, they dispute the mechanism by which it supposedly gained the ability to infect humans. In his article, Latham lays out several different lab origin hypotheses, which are also reviewed in my interview with him, featured in "Cover-Up of SARS-CoV-2 Origin?"
Is SARS-CoV-2 Really a Novel Virus?
Latham and Wilson continue their search for the truth in a July 15, 2020, Independent Science News article.14
"… enormous scientific attention has been paid to the molecular character of the SARS-CoV-2 virus, including its novel genome sequence in comparison with its near relatives," Latham writes.
"In stark contrast, virtually no attention has been paid to the physical provenance of those nearest genetic relatives, its presumptive ancestors, which are two viral sequences named BtCoV/4991 and RaTG13."
According to Latham, SARS-CoV-2 may not be an entirely novel virus after all. A highly conserved close ancestor, BtCoV/4991, has been listed in the database for seven years and has been featured in the published literature. When the Wuhan lab later resequenced this sample, they simply renamed it, thereby obscuring its history.
As Latham explains in his article15 — which I encourage you to read in its entirety — BtCoV/4991 was found in samples collected in a mineshaft in Yunnan province, China in 2012-2013.
The samples were collected after six miners contracted a strange respiratory illness that sound remarkably similar if not identical to COVID-19. Three of them died. While the disease had only been described in a Chinese thesis written by the doctor who treated the miners, Latham had the thesis translated into English.
"The evidence it contains has led us to reconsider everything we thought we knew about the origins of the COVID-19 pandemic," Latham writes.16"It has also led us to theorize a plausible route by which an apparently isolated disease outbreak in a mine in 2012 led to a global pandemic in 2019.
The origin of SARS-CoV-2 that we propose below is based on the case histories of these miners and their hospital treatment. This simple theory accounts for all the key features of the novel SARS-CoV-2 virus …"
Key features Latham and Wilson believe can be explained by their theory include:
The origin of the novel furin cleavage site on the virus' spike protein that enhances its spread in the human body
The "exceptional affinity of the virus spike protein for human receptors"
The virus' lack of evolution since the pandemic began
The reason SARS-CoV-2 targets the lungs
While they do not claim SARS-CoV-2 was genetically engineered, they believe gain-of-function research performed at the Wuhan Institute of Virology played "an essential causative role in the pandemic."
The Mojiang Miners Passage Hypothesis
Latham and Wilson go on to explain their hypothesis, which they've dubbed the Mojiang miners passage (MMP) hypothesis. Again, I recommend reading the original article, but for your edification, I've chosen to quote a larger than usual section to summarize it for you:
"We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2, that escaped from the WIV in 2019 …
Passaging is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host's immune system vanquishes the ill-adapted virus.
But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique … intensively selects for viruses adapted to the new host or cell type …
We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalized miners favored a very high rate of evolution inside them.
The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution. Furthermore, according to the Master's thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus …
In support of the MMP theory we also know something about the samples taken from the miners. According to the Master's thesis, samples were taken from patients for 'scientific research' and blood samples (at least) were sent to the WIV …
The logical course of such research would be to sequence viral RNA extracted directly from unfrozen tissue or blood samples and/or to generate live infectious clones for which it would be useful (if not imperative) to amplify the virus by placing it in human cell culture. Either technique could have led to accidental infection of a lab researcher …
We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.
Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic. In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic."
As discussed in "Bioweapon Labs Must Be Shut Down and Scientists Prosecuted," the COVID-19 pandemic should be a wake-up call for the world to reconsider the wisdom of gain-of-function research. Lab escapes are guaranteed to occur, sooner or later. We got lucky this time, in the sense that SARS-CoV-2 is far less deadly than initially feared. But the government response to the pandemic has been devastating.
Global shut-downs have taken a massive toll on mental and financial health, not to mention the global economy as a whole. Could we survive as a species if something with a really high lethality were to get out? These are crucial questions that deserve public discussion and close scrutiny by lawmakers.
The benefits of vitamin D have been well-documented over the years. I believe that getting your vitamin D status optimized to between 60 ng/mL and 80 ng/mL is one of the best things you can do to help protect yourself against the fall infectious disease season, which is expected to include both flu and COVID-19.
Health authorities are warning of a second wave of COVID-19, which means the time to start addressing your vitamin D level is now. But, as important as it is to get your level optimized by fall, it's just as important to keep it there throughout the year.
Ideally, your body makes vitamin D when your skin is exposed to sunlight. This is why it's also called the sunshine vitamin.1 The best indicator of your vitamin D level is a blood test measuring the concentration of 25-hydroxy vitamin D, also called 25-OH vitamin D.2
In addition to the crucial role it plays in your immune system, researchers have also found that it's integral to optimizing leptin levels, which in turn are linked to obesity.3 In one study, researchers measured vitamin D and metabolic markers in two age- and gender-matched groups.4
They learned that individuals with deficient or insufficient vitamin D had a higher risk of metabolic syndrome. The results from several studies have also revealed a link between low levels of vitamin D and nonalcoholic fatty liver disease, although the results have not been consistent.
Foot Pain Associated With Knee or Hip Osteoarthritis
Recently, insufficient levels of vitamin D have been associated with foot pain linked to knee osteoarthritis (OA). Before delving into the results of the research, it's important to understand the relationship between low back pain and foot pain associated with severe knee OA.
In a study from 2010, researchers found that those who had OA in the knee and had pain in other joints in the body, were more likely to experience more intense knee pain.5,6 More specifically, the researchers found that when pain was present in the lower back, foot and elbow on the same side as the affected knee, the individual rated their knee pain as more severe than those who did not have pain in other joints.
The study was led by a physician from Harvard Medical School and involved the use of data from the Osteoarthritis Initiative, a study of knee OA involving people from several locations in the northeastern area of North America. The researchers included 1,389 participants who were between 45 and 79 years of age. The results showed that 57.4% had pain in their lower back, and those same individuals had a higher pain score in their knee.
Another group of participants from the same initiative and in the same age range were gathered for a second study.7 Researchers evaluated 1,255 individuals who had symptoms of knee pain related to OA. They noted that 25% of them had foot pain and the majority of those had pain in both feet.
After adjusting for confounding variables, they discovered that people who had foot pain also had lower scores on other health measures compared to those who did not have pain. Those who had bilateral or ipsilateral pain had lower health scores. This suggested that the side of the body where the foot pain occurred was important.
In a third study published in the Journal of the American Podiatric Medical Association, scientists also evaluated the side of the body where foot pain occurred and compared it to the presence of knee OA.8 One author commented about the importance of this identification:9
"The study shows that a physician evaluating a patient for foot pain should also ask about possible hip or knee pain, and vice versa, so we can address all of a patient's issues. In medicine, many times it comes down to 'what does your MRI look like or what does your x-ray look like?'
But it's really important to conduct a thorough medical history and physical exam. A comprehensive orthopedic evaluation may prompt a broader treatment strategy and possibly a referral to another specialist."
Vitamin D May Reduce Pain Level
People with knee OA may experience mild, moderate or severe pain.10 The Arthritis Foundation compares pain medications used for osteoarthritis listing nonsteroidal anti-inflammatories (NSAIDS), acetaminophen and injections of steroids or hyaluronic acid as treatments.11
In some cases, antidepressants are used to treat chronic pain, such as Duloxetine (Cymbalta).12 In all cases, the medications have a long list of side effects. In one study, comparisons were made between NSAIDs and opioids, a drug with known addictive properties, to relieve OA pain. Researchers found that both types of medication reduced pain and the effects were nearly identical.13
When the use of opioids use has been measured across counties, researchers have found that where there is a higher prevalence of disability and arthritis, there is also a higher rate of opioid prescriptions.14
In a recently published study, researchers sought to determine whether sufficient levels of vitamin D could lower foot pain in those with knee OA.15 Using data from a randomized, double-blind placebo-controlled study they undertook a post-hoc data analysis.16
Members of the group were randomly assigned to receive either a monthly dose of vitamin D3 or a placebo for two years. The participants had a mean age of 63.2 years. Of the 413 who were enrolled, 340 completed the study. The researchers used the Manchester Foot Pain and Disability Index (MFPDI) to rate the patients' perceived pain. At the start of the study 23.7% had disabling foot pain.
The data showed greater improvement in people receiving vitamin D and in those who maintained a sufficient level of vitamin D. They concluded that "supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA."17 In an article published in Rheumatology Advisor, it was noted that the study had several limitations, one of which may have significantly underestimated the results:18
"The study had several limitations, including those secondary to a post-hoc analysis, lack of data on the clinical importance of the differences in MFPDI scores, and potential underestimation of the benefits of vitamin D, as >60% of patients in placebo group had sufficient vitamin D levels at the end of follow-up."
Slow Osteoarthritis Progression With Omega-3 Fats
A second nutrient the body uses to prevent or slow the progression of OA is omega-3 fat. Dietary fat is essential to good health. While eating too much or not enough is damaging, without healthy fat your body does not work properly.19
Polyunsaturated fats (PUFA) are one type of essential fat, which means you must eat them since the body doesn't make them. The two main types of PUFAs are omega-3 and omega-6.
Both must be consumed in the right amounts or you may develop chronic inflammation. You'll find high concentrations of omega-6 in processed food, and corn, safflower and sunflower oils. While the ideal ratio is 1-to-1, most who eat a Western diet are getting 16 times more omega-6 than is considered healthy.20
As I've written recently, one of the problems with chronic inflammation may be that it promotes the damaging and dangerous cytokine storm found in those with severe COVID-19. The omega-3 index is a measure of omega-3 fat in the blood, or specifically in the red blood cell membranes. It is given as a percentage, with 8% or higher being ideal, putting you in the lowest risk zone.21
In a global meta-analysis of past studies measuring omega-3 levels, the researchers found areas with "very low blood levels (less than or equal to 4%)" included North, Central and South Americas, Europe and Africa.22
This is important since the balance of omega-3 and omega-6 can help regulate inflammation23 and slow the progression of OA after an injury,24 as demonstrated in animal studies. In naturally occurring OA, animals fed a diet rich in omega-3 reduced OA by 50% over those fed a standard diet.25
In a human trial, researchers found that supplementing with fish oil did not change the cartilage volume in knee osteoarthritis, but it did reduce the participants' pain scores over two years.26 Additionally, researchers have discovered a link between OA and metabolic syndrome.27
While metabolic syndrome increases the risk for OA, balancing your omega-3-to-omega-6 ratio can help reduce the potential risk of metabolic syndrome. The authors of one recent meta-analysis concluded:28
"The present meta-analysis indicates that higher intakes of omega-3 PUFAs, but not omega-6 PUFAs, was associated with lower MetS risk; adding to the current body of evidence on the metabolic health effects of circulating/dietary omega-3 PUFAs."
In a second paper, the authors wrote:29
"Lately, an inverse relationship between omega-3 fatty acids, inflammation, obesity and CVDs has been demonstrated … Omega-3 PUFAs have been shown to decrease the production of inflammatory mediators, having a positive effect in obesity and diabetes mellitus type-2. Moreover, they significantly decrease the appearance of CVD risk factors."
Based on these studies, it's apparent that omega-3 has an impact on OA pain and that it can slow the progression of OA as well as help prevent metabolic syndrome, which also raises the risk of OA.
Number of People With Osteoarthritis Has Doubled
The authors of a study published by Harvard University found that people currently living in America were more than two times more likely to have knee osteoarthritis than those who lived there before World War II. They looked at more than 2,000 skeletons with the goal of determining the age of the disease.30
Interestingly, there was a rise in disease after confounding factors were accounted for, such as longer life and the meteoric rise in rates of obesity since 1940.31 The researchers controlled for age and body mass index and still found a significant rise in people with OA. One author was quoted in the Harvard Gazette, saying:32
"We were able to show, for the first time, that this pervasive cause of pain is actually twice as common today than even in the recent past. But the even bigger surprise is that it's not just because people are living longer or getting fatter, but for other reasons likely related to our modern environments. Knee osteoarthritis is not a necessary consequence of old age. We should think of this as a partly preventable disease."
In the skeletons of people over the age of 50, the data showed knee osteoarthritis was 2.6 times more common in those who were born in the post-industrial age, as compared to those born in the late 1800s.33 The researchers also found the rate of OA in both knees in the post-industrial era was 1.4 times higher.
If you are among those who have OA, consider using vitamin D3 supplements to raise your serum levels. It is important to include vitamin K2 MK-7 for reasons I discuss in "What Are the Health Benefits of Vitamin K2?", including reducing your risk of atherosclerosis.
