Nitrate-cured meats may contribute to mania

Nitrate-cured meats may contribute to mania, study finds

An analysis of more than 1,000 people with and without psychiatric disorders has shown that nitrates-;chemicals used to cure meats such as beef jerky, salami, hot dogs and other processed meat snacks-;may contribute to mania, an abnormal mood state. Mania is characterized by hyperactivity, euphoria and insomnia.

The findings of the Johns Hopkins Medicine study, which was not designed to determine cause and effect, were published July 18 in Molecular Psychiatry. Specifically, it found that people hospitalized for an episode of mania had more than three times the odds of having ever eaten nitrate-cured meats than people without a history of a serious psychiatric disorder. Experiments in rats by the same researchers showed mania-like hyperactivity after just a few weeks on diets with added nitrates.

While a number of genetic and other risk factors have been linked to the manic episodes that characterize bipolar disorder and may occur in other psychiatric conditions, those factors have been unable to explain the cause of these mental illnesses, and researchers are increasingly looking for environmental factors, such as diet, that may play a role.

The researchers say that their new study adds to evidence that certain diets and potentially the amounts and types of bacteria in the gut may contribute to mania and other disorders that affect the brain.

“Future work on this association could lead to dietary interventions to help reduce the risk of manic episodes in those who have bipolar disorder or who are otherwise vulnerable to mania,” says lead author Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at the Johns Hopkins University School of Medicine.

Mania, a state of elevated mood, arousal and energy that lasts weeks to months, is generally seen in people with bipolar disorder, but can also occur in those with schizoaffective disorder. Manic states can lead to dangerous risk-taking behavior and can include delusional thinking, and most of those affected experience multiple hospitalizations in the course of their psychiatric illness.

Bipolar disorder affects an estimated 1 to 3 percent of the population of the United States and costs an estimated $25 billion a year in direct health care costs, according to a studyin the Journal of Affective Disorders.

Yolken, trained as an infectious disease expert, was originally interested in whether exposure to infections such as viruses transmitted through food might be linked to any psychiatric conditions. Between 2007 and 2017, as part of an ongoing study, he and colleagues collected demographic, health and dietary data on 1,101 individuals aged 18 through 65 with and without psychiatric disorders. Approximately 55 percent of the participants were female and 55 percent were Caucasian, with 36 percent identifying as African-American.

Those with psychiatric disorders were recruited from patients receiving care at the Sheppard Pratt Health System in Baltimore. Individuals with no history of psychiatric disorders were recruited from posted announcements at local health care facilities and universities in the region.

A study of their records between 2007 and 2017 showed that, unexpectedly, among people who had been hospitalized for mania, a history of eating cured meat before hospitalization were approximately 3.5 times higher than the group of people without a psychiatric disorder. Cured meats were not associated with a diagnosis of schizoaffective disorder, bipolar disorder in people not hospitalized for mania or in major depressive disorder. No other foods about which participants were queried had a significant association with any of the disorders, or with mania.

“We looked at a number of different dietary exposures and cured meat really stood out,” says Yolken. “It wasn’t just that people with mania have an abnormal diet.”

Nitrates have long been used as preservatives in cured meat products and have been previously linked to some cancers and neurodegenerative diseases, so Yolken suspected they may also explain the link to mood states such as mania.

The dietary survey did not ask about frequency or time frame of cured meat consumption, so the researchers couldn’t draw conclusions about exactly how much cured meat boosts one’s risk of mania, but Yolken hopes future studies will address this.

To get at the roots of the association, Yolken collaborated with researchers studying the impact of nitrates on rats.

Kellie Tamashiro, Ph.D., associate professor of psychiatry and behavioral sciences, and M.D./Ph.D. student Seva Khambadkone, both of Johns Hopkins, and others divided a group of otherwise healthy rats into two groups: one received normal rat chow, and the other received both normal chow and a piece of store-bought, nitrate-prepared beef jerky every other day. Within two weeks, the rats receiving the jerky showed irregular sleeping patterns and hyperactivity.

Next, the team worked with a Baltimore-based beef jerky company to create a special nitrate-free dried beef. They repeated the experiment, this time giving some rats the store-bought, nitrate-prepared jerky and others the nitrate-free formulation. The animals that ate the nitrate-free meat behaved similarly to a control group, while the animals that consumed the nitrates once again showed sleep disturbances and hyperactivity similar to that seen in patients with mania-;increased activity during normal sleep times and in new environments.

The results were then replicated with a specially formulated rat chow that had either nitrate added directly to the chow, or no nitrate.

Importantly, the amount of nitrate being consumed on a daily basis by the rats¾when scaled up to the size of a human-;was equivalent to the amount a person might eat for a daily snack, such as one beef jerky stick or hot dog.

“We tried to make sure the amount of nitrate used in the experiment was in the range of what people might reasonably be eating,” says Yolken.

When the group analyzed the gut bacteria of the different groups of rats, they found that animals with nitrate in their diet had different patterns of bacteria living in their intestines than the other rats. Moreover, the animals had differences in several molecular pathways in the brain that have been previously implicated in bipolar disorder.

While the team also cautions that it’s too early to take any clinical messages from the results, and occasional cured meat consumption is unlikely to spur a manic episode in most of the population, Yolken says the findings add to evidence of the multiple factors that contribute to mania and bipolar disorder.

“It’s clear that mania is a complex neuropsychiatric state, and that both genetic vulnerabilities and environmental factors are likely involved in the emergence and severity of bipolar disorder and associated manic episodes,” says Khambadkone. “Our results suggest that nitrated cured meat could be one environmental player in mediating mania.”

Yolken’s group recently published results of a separate study showing that when people with bipolar disorder are given probiotics-;which can change the composition of gut bacteria-;after a manic episode, they are less likely to be rehospitalized in the following six months. “There’s growing evidence that germs in the intestines can influence the brain,” says Yolken. “And this work on nitrates opens the door for future studies on how that may be happening.”

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How I Confronted My Worst Childhood Memory

How I Confronted My Worst Childhood Memory

Twenty-five years after a chance encounter in a middle school bathroom humiliated him, revisiting the episode—and his tormentor—changed the course of the author’s life.

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Danielle Daly

I was ten years old when I experienced a childhood trauma that would last for years. It was 1993. And I’d recently entered middle school in southern Maine. One afternoon I left Spanish class to pee. I entered one of the stalls in the men’s bathroom, dropped my shorts to my ankles, and relieved myself.

What happened next is hazy. What I can recall is that I became preoccupied with something on or around my genitals—so preoccupied that, without noticing, I backed away from the toilet and out of the stall. I stood by the sink examining my balls.

My shorts were still around my shoes when I heard the metal door slam. Standing in front of me was the toughest eighth-grade boy in school. Brandon [name has been changed] was a football star, handsome, and popular. And now
he was incredulous.

“What the fuck are you doing?!”

I froze.

“Are you some kind of faggot?”

Flight kicked in. I gathered up my shorts and ran. Back in Spanish class, I slid down in my seat and closed my eyes. No. I wished the entire experience away.

After that dayin the bathroom with Brandon, I disappeared. I stayed away from the lunchroom, cut out as soon as classes finished. My grades dived. I came to know that particular prepubescent agony of wondering where I fit in. I was sure I liked girls, but the homophobia that existed among boys in blue-collar Maine was so vicious that news of my pantlessness would mean danger, and I had convinced myself it was only
a matter of time before Brandon told the entire school I was gay.

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Danielle Daly

By age 11, I began wearing T-shirts to the swimming pool, covering my body. For years, I hid my face beneath a low baseball cap. Puberty finally hit, bringing brutal bouts of acne with it. Years later, still struggling with my identity, I escaped into drugs. When I finally got sober in 2017, I was confronted for the first time with the vast, shadowy realm of all the parts of me I’d suppressed. Was that sole incident with Brandon to blame for all my years of childhood pain? No. But it was the day I learned that I would have to hide.

I tried every trick that could help me dig through my basement of hidden memories. I had my head shrunk by Freudian psychoanalysts in New York, I had my soul retrieved by a Topanga Canyon shaman, and along the way I learned something transformative: Every time I worked up the courage to reveal a shameful memory, it lost its power—often instantly.

Adults understand that crappy childhood experiences are as common as chicken pox. But kids don’t. By uncovering all the parts of ourselves we’ve hidden, we soothe the awkward sixth-grader in us who was sure his brand of torture was unique.

One afternoon during a breathing exercise with my therapist in Beverly Hills, I remembered Brandon. I couldn’t believe how long I’d repressed the memory, or how strongly the feelings came back. I felt my whole body go rigid. Hesitantly, I revealed to my doc what had happened that day in the bathroom, and the way the shame had haunted me in the years following.

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Danielle Daly

I went home and Googled Brandon’s name, and a Facebook page came up. Had to be him. I kept searching and found his email address. I typed an email: I was a classmate of his from middle school. I had a memory I wanted to corroborate with him, and would he be willing to talk?

Two hours later, a text arrived: It’s Brandon reaching out to you.

I felt a familiar clenching in my chest.

I pulled off the highway and sucked in deep breaths. I thought I might hyperventilate. In all my fantasies of how this might go down, I’d never gotten to the part where I would actually have to
speak to him.

I spent two hours crafting the perfect text message. That evening, I finally mustered the courage to hit send. Less than five seconds after the text landed, Brandon called. Startled, I picked up.

“Yo.”

It was the same deep voice that’d been replaying in my brain for months.

“Hey, Brandon,” I said. “Thanks for—“

“What’s up?” he asked. Cool, aloof. “Refresh my memory.”

When I finished telling my story, he paused for what felt like an hour.

“I came from home economics,” he said, in what sounded like disbelief. “I came into the bathroom and, yeah, there you were, with your pants down. I was scared. I thought, Jesus, this kid is flashing me!I didn’t know what to do!”

I laughed. He laughed.

“I told the kid who sat next to me in home ec about it,” he said. “But I never spoke or thought about it again.”

Then he asked, “Was I mean?”

When I explained to him what he’d said, his voice dropped. “Man,” he said. “That was wrong.”

Then he asked, “Why were you in therapy?”

I told him about my struggle with addiction.

“No kidding,” he said. “I’ve been
there too.”

With the tension defused, and a bond cemented, we laughed like coconspirators, like brothers. We laughed and laughed.

“Look me up next time you’re in Maine,” he said when we finished. “I’m so glad you called.” I thanked him and hung up the phone, triumphant. It was a feeling better than any buzz, any high.

What happens the day after you face something that’s been haunting you for a quarter century? You wake up at 4:00 a.m., electrified. The most shameful moment of my life resolved. The most epic fear reduced to laughter. Had it really happened? In the weeks and months that followed that phone call, my life was transformed. I smiled more. I obsessed less. Hours I’d spent scrutinizing my skin and body in the mirror were alchemized into time I spent out in the world, lighter, freer. Relationships with the older men in my life—even the tough, macho types I realized I’d always projected Brandon onto—became easier. I experienced the world less as a scared boy and more as an upright man.

In recovery I’ve learned the places within ourselves we dread going are
the places we must go. And sometimes we find something we could never expect. A story, a narrative I’d held on to for years turned out to be just another experience shared by someone who saw it from a different angle. His explanation of that set me free. As Brandon said, “I can’t believe that day haunted you for all this time, and I never thought about it again.”

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How 3 drops of oregano oil and baking soda could heal your lungs

How 3 drops of oregano oil and baking soda could heal your lungs

How 3 drops of oregano oil and baking soda could heal your lungs

Pneumonia is the 6th leading cause of death worldwide, and oregano oil and baking soda could act as another line of defense!

Currently, we use prescription medication to manage respiratory problems. And since the majority of these illnesses are bacterial infections, we use antibiotics to treat them. But Oregano Oil, with its potent antibacterial properties, could offer another tool to shield against the damages of rogue bacteria. Keep reading to find out how.

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The dangers of Pneumonia

Pneumonia can infect one or both lungs. Most of the time it develops through a bacterial, fungal, or viral growth. Before the discovery of antibiotics, 1 out of 3 people who contracted Pneumonia died. And at present, over 3 million patients catch Pneumonia every year, and half a million of them end up in hospital.

Streptococcus pneumoniae represents the most common cause of bacterial pneumonia. As a result of catching this form of Pneumonia, the person may experience a rapid onset of the illness, including with fever, shaking chills, and production of rust-colored sputum. In 20%-30% of the cases, the infection may spread into the blood. This is known as sepsis. And if this occurs, then 20%-30% of those patients will likely die.

The modern Antibiotics solution

The most common Antibiotics treatments include penicillin, amoxicillin and clavulanic acid (Augmentin), and macrolide antibiotics including azithromycin, erythromycin, and clarithromycin.

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Initially, Doctors chose Penicillin as the primary treatment. However, with the arrival and extensive use of more potent antibiotics, drug resistance began to develop. Penicillin may still prove useful in the treatment of pneumococcal pneumonia. But patients should only use it after cultures of the bacteria confirm their sensitivity to this antibiotic.

The ancient Oregano Oil solution

Cultures from the Far East and the Middle East have used Oregano OIl to heal many ailments, including respiratory infections, chronic inflammation, urinary tract infections, dysentery, and jaundice.

Laboratory studies in which the oil was applied directly to foodborne pathogens showed that oregano oil has potent antibacterial properties (Dadalioglu I et al. 2004). In fact, medicinal oregano holds a high mineral content that intensifies its healing advantages, including magnesium, calcium, zinc, copper, potassium, manganese, and boron.

Oregano oil is safe for humans. And patients can combine it with antibiotics to combat bacterial infections (Preuss HG et al. 2005). Many have also used it as an early defense mechanism at the onset of a cold or a sore throat.

How to take Oregano Oil: Take three drops once per day. Mix it into a glass of orange juice. Within a few hours, you should experience positive results. Repeat once per day for up to five days in combination with other treatments you have received.

Combine Oregano Oil with a Baking Soda solution

Many people also use Baking Soda (also known as sodium bicarbonate) as a home remedy. The substance can be found in all living things. And it acts to neutralize acids and break down proteins. Baking soda maintains pH balance in the bloodstream, which is necessary to support life.

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If we hold our body at an alkaline pH within 7.3 and 7.4, we can remain free of disease. Furthermore, by raising pH, we increase the immune system’s capacity to destroy bacteria. Considering the viruses and bacteria that cause colds, bronchitis, and secondary infections such as pneumonia, flourish in an acidic environment. So raising the pH levels could help to destroy this pathogen.

How to take Baking Soda: To reduce symptoms such as a sore throat combine 2 teaspoons of baking soda with 16 ounces of warm water. Gargle and swish your mouth with this solution. And to help with reversing pneumonia, sinusitis, asthma, prepare a nebulizer with water and two drops of liquid sodium bicarbonate. Take 2 to 3 times a day. You can also read this article for more natural baking soda remedies.

Note from Mimi:

Make sure to buy Organic and “Professional Grade” Oregano Oil.  The active ingredient is called Thuja.

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Rationale for the Design of a Novel Tool for Immunotherapy Based on an Emulsion of Glycosaminoglycan

Rationale-for-the-design-of-imuno-27Sept18

The rationale for the design of a novel tool for immunotherapy based on an emulsion of glycosaminoglycan, Marco Ruggiero* and Stefania Pacini, Silver Spring Sagl, Switzerland

Abstract

In this article, we describe the rationale behind the design of an innovative immunotherapeutic tool designated imuno™ that is an emulsion of microbial, low- molecular-weight chondroitin sulfate non-covalently bound to pure phosphatidylcholine with vitamin D3 intercalated in the ensuing multi-molecular structure. The rationale for this design derives from the decade-old observation that chondroitin sulfate is the active principle responsible for the immune-stimulatory, anti-cancer properties of cartilage extracts and from the more recent observation that a known immunotherapeutic compound, the Gc protein-derived Macrophage Activating Factor (GcMAF), works as an adjuvant similar, in principle, to the incomplete Freund’s adjuvant. From these premises, we designed an innovative tool that uses an ultrapure, low-molecular-weight chondroitin sulfate, thus overcoming all limitations associated with blood-derived or animal-derived non-ultrapure extracts, at the same time guaranteeing constant sulfation profile and charge density. This novel form of chondroitin sulfate is non-covalently bound to pure phosphatidylcholine in a self-assembly manner that is coherent with the principles of negentropy. Vitamin D3 is then intercalated in this structure that resembles protocells made of a phosphatidylcholine bilayer. Such an association reduces the main side effect of vitamin D3 that is the induction of hypercalcemia, at the same time maximizing its immunotherapeutic potential. In addition, we describe the mechanism of action of this immunotherapeutic tool with particular reference to stimulation of innate immunity through a mechanism shared by adjuvants such as Freund’s adjuvant. Finally, we describe an example of a transdermal delivery system and we discuss possible applications.

The term “immunotherapy” encompasses a wide number of treatments that harness the immune system to fight diseases ranging
from cancer [1] to asthma [2] and Alzheimer’s disease [3]. Although
this approach has been implemented with success in a wide variety
of diseases and conditions, immunotherapy of cancer appears to
yield the most promising results, and it is now considered an integral component of the armamentarium for the treatment of patients with advanced tumors [1]. Both the cellular and the humoral components
of the immune system are targets of immunotherapeutic approaches as
well as the innate and adaptive arms of the system, thus leading to an extraordinarily high number of remedies and strategies that differ in
terms of specificity, selectivity, and efficacy. Among the different types of immunotherapy, we recently focused our attention on those approaches
that are based on glycosaminoglycans with particular reference to the
work of Dr. Prudden [4]. Since 1957, Prudden and Colleagues described
how extracts from bovine cartilage exerted a plethora of therapeutic
effects that today would be described as immunotherapy, ranging from accelerated wound healing [5], to decrease of inflammation [6], and successful treatment of advanced cancers [4]. In this specific context,
in 1985, Prudden wrote “Oral and subcutaneous administration of
specific preparations of bovine tracheal cartilage rings (Catrix), a nontoxic agent, has resulted in a high response rate in 31 cases of a
variety of clinical malignancies (response rate 90%, 61% complete). The demonstrated responder includes present therapeutic disasters such as glioblastoma multiforme and cancers of the pancreas and lung. Other
types which were treated with success included cancers of the ovary,
rectum, prostate, cervix, thyroid, and an inoperable squamous cancer of
the nose.” [6]. Three years later, in 1988, Prudden and Colleagues were
able to identify the molecule responsible for the successful treatment of those “present therapeutic disasters” and concluded that chondroitin sulfate, a glycosaminoglycan, was responsible for what they called “immunoaugmenting activity” of the bovine cartilage extract [7].

Dr. Prudden passed away the same year he identified chondroitin sulfate as the active agent of his preparation; his work was well described in layman’s terms in the obituary published in The New York Times that reads “Dr. Prudden also reported research that used cartilage treatment to help osteoarthritis patients and he believed that it could be used to treat cancer and other diseases.” [8]. The results observed by Prudden and Colleagues have been independently replicated, and a recent paper published in 2018 by researchers working at Faculty of Medicine of the American University of Beirut, Lebanon, demonstrates that “bovine cartilage induces tumor cell death through apoptosis and this mechanism of action is the same across different cell lines and species.” [9] thus supporting the notion that chondroitin sulfate exerts general anti-cancer effects not limited to a specific histologic type. Such a universal anticancer effect can be explained by assuming that chondroitin sulfate works on multiple types of immune cells, most notably on cells pertaining to the innate arm of the immune system.

Consistent with these observations, in 2016 we wrote that chondroitin sulfate, in addition to being the active molecule responsible for the anticancer effects of cartilage, was also the molecule responsible for the immunotherapeutic effects of an elusive compound termed Gc protein-derived Macrophage Activating Factor (GcMAF) [10]. Such a concept stemmed from more than thirty years of research in the field of glycosaminoglycans and from the observation that chondroitin sulfate is composed of repetitive units of alternating sugars that are glucuronic acid and N-acetyl-galactosamine, the latter being the active site of GcMAF [11]. Shortly after publication of our paper, this concept was independently confirmed by the observation that chondroitin sulfate inhibits angiogenesis in the chick embryo chorioallantoic membrane [12] that is another anticancer property attributed to GcMAF that we had previously described [13]. In addition, it has been recognized for a long time that heparin, a glycosaminoglycan with a molecular structure closely related to chondroitin sulfate, inhibits cancer cell proliferation [14], even though the anticoagulant effects of this molecule prevent its use as a bona fide anticancer treatment. It is worth noticing, however, that the anticancer effects of heparin are independent of its anticoagulant activity, and a recent study demonstrated how low-molecular-weight heparin may represent a novel therapeutic approach to the prevention of metastases thanks to its effects on the endothelial barrier that are not associated with the anticoagulant activity [15].

Based on these facts and consideration, in 2015 we formulated an emulsion of chondroitin sulfate, vitamin D3 and oleic acid that was intended to modulate the immune system and reproduce the biological and clinical effects attributed to GcMAF. Use of this compound, designated Rerum, yielded encouraging results in the complementary approach to a number of conditions ranging from cancer to autism, to acute and chronic pain [16-18]. Here we describe the rationale for the design of a novel tool for immunotherapy based on our previous experience with glycosaminoglycans, GcMAF and Rerum.

A novel type of chondroitin sulfate

Until recently, chondroitin sulfate was extracted and purified from animal cartilage; because of this, animal-derived chondroitin sulfate is a heterogeneous mixture of high and low-molecular-weight species, with high-molecular-weight species being prevalent, and shows a heterogeneous sulfation profile. Such heterogeneity is well recognized up to the point that the last Revision Bulletin of the United States Pharmacopoeia [19] states that chondroitin sulfate preparations are allowed to have quantities of the glycosaminoglycan ranging from 90% to 105% calculated on the dried basis. In other words, a purity of merely 90% is accepted. In addition, since the process of extraction cannot have a 100% yield and presence of contaminants has to be accepted, the same document states that protein contamination up to 6% has to be accepted. Likewise, the presence of heavy metals up to 20 ppm is accepted as well as the presence of non-specific disaccharides up to 10%. In short, animal-derived chondroitin sulfate is a heterogeneous mixture comprising non-negligible amounts of contaminants. A major breakthrough in chondroitin sulfate research was represented by the recent availability of non-animal chondroitin sulfate, a compound that overcomes the limitations of animal-derived compounds as described above. Such chondroitin sulfate is the result of microbial fermentation with the production of unsulfated chondroitin that undergoes site- selective sulfation, modulated in order to obtain a sulfation profile superimposable to that of human chondroitin sulfate. This patented procedure leads to a product that is 99% pure, has a percentage of typical disaccharides almost identical to that of human synovial fluid and, most importantly, shows consistent low molecular weight with constant charge density and molecular mass parameters [20]. These features represent a significant improvement over animal-derived chondroitin sulfate and such an improvement leads to significantly increased

clinical efficacy. Thus, in a recent study, the pharmacokinetic profile of an oral form of this non-animal, low-molecular-weight chondroitin sulfate was compared to that of animal (bovine)-derived chondroitin sulfate in healthy volunteers. Microbial low-molecular-weight chondroitin sulfate yielded a much greater plasma concentration with increased specific sulfation in the 6-position of N-acetyl-galactosamine in human plasma and, as a consequence, the overall charge density was doubled compared to animal-derived chondroitin sulfate [20]. Such a greater efficacy bears important consequences as far as the known anti-inflammatory, “immunoaugmenting” (to quote Dr. Prudden’s words) activities of chondroitin sulfate are concerned. A recent study demonstrated how the greater therapeutic efficacy of microbial chondroitin sulfate was mainly due to its homogeneous low-molecular- weight. In an animal model of polyarthritis, low-molecular-weight chondroitin sulfate reduced the arthritic score with significantly greater efficiency than high-molecular-weight chondroitin sulfate and, at the same time, decreased gamma-glutamyltransferase activity, plasmatic C-reactive protein levels plasmatic levels of C-reactive protein and the pro-inflammatory cytokines IL-1beta and IL-6 [21]. In summary, microbial low-molecular-weight chondroitin sulfate is a demonstrated significant improvement over animal-derived chondroitin sulfate as it shows much more efficient pharmacokinetics and therapeutic efficacy. Because of these features, we decided to design our next immunotherapeutic tool on the backbone of ultra-pure, homogeneous low-molecular weight chondroitin sulfate that represents a different chemical moiety as compared with animal-derived high-molecular- weight chondroitin sulfate.

Design of imunoTM a multi-molecular complex based on low-molecular-weight chondroitin sulfate, phosphati- dylcholine and vitamin D3

The rationale for the design of imunoTM lays in the observation that glycosaminoglycans in human blood are assembled in multi-molecular complexes comprising phosphatidylcholine, the major constituent of cell membranes. We first observed such an association between phosphatidylcholine and a human blood glycosaminoglycan, heparin, in 1985 when we demonstrated that circulating endogenous human heparin is complexed with phosphatidylcholine in human plasma [22]. In this paper, we described for the first time the two major features of the physiological phosphatidylcholine/glycosaminoglycan interaction that, 33 years later, led to the design of imunoTM.

1. The glycosaminoglycan, a highly hydrophilic molecule, interacts with phosphatidylcholine, an amphipatic molecule constituting the lipid bilayer of cell membranes, through electrostatic interactions between the negatively charged quaternary ammonium groups of its polar head and the sulfate groups of the glycosaminoglycan, with carboxylic acids possibly contributing to electrostatic stabilization. Such an interaction at the plasma level could represent a mechanism of abstraction and storage of a highly active compound.

2. In addition to this mechanism, we demonstrated how the glycosaminoglycan participated in cell signaling by interacting with phosphatidylcholine of the external layer of the membrane, thus modulating transmembrane second messenger formation through polyphosphoinositide metabolism with the formation of calcium-mobilizing inositol 1,4,5-trisphosphate, and protein kinase C-activating diacylglycerol [22,23].

These observations of ours have been recently confirmed and extended as it appears that the supra-molecular assembly we described for human endogenous circulating heparin is a general physiological phenomenon that involves other glycosaminoglycans and, in particular, chondroitin sulfate. In a study published in 2016, it was demonstrated that chondroitin sulfate interacts mainly with the polar groups of phosphatidylcholine in an experimental cell membrane system exhibiting a dynamic adsorption-desorption process. Interestingly, the electrostatic interaction that we had described in 1985 between the polar head of phosphatidylcholine and the sulfated groups of the glycosaminoglycan, proved instrumental in inducing a higher degree of order in the phosphatidylcholine monolayer mimicking the external layer of the cell membrane as assessed by polarization-modulated infrared reflection absorption spectroscopy [24]. In other words, it appears that the phosphatidylcholine/glycosaminoglycan interaction represents a notable example of negentropy that is consistent with the concept delineated by Nobel Laureate Erwin Schroedinger in 1944 [25], and elaborated in a more recent publication where is reported that “… such an occurrence of molecular self-assembly in the absence of genetic information is thought to have been the first step in the origin of life … molecules not pertaining to the flow of information in the classical interpretation of molecular biology since the times of Watson and Crick (DNA → RNA → Proteins) are assembled in our blood following a pattern as archetypical as life itself …” [26]. The concept that glycosaminoglycans help to establish a higher order, or negentropy, in biological structures similar to cell membranes is further corroborated by results reported in a study authored by researchers working at the Department of Pharmaceutical Sciences of the North Dakota State University. In a paper entitled “Glycosaminoglycan-mediated selective changes in the aggregation states, zeta potentials, and intrinsic stability of liposomes” the Authors describe how the organizational states of liposome bilayers are stabilized by the presence of glycosaminoglycans [27]. This observation is consistent with a more recent paper by Mantovani, et al. (2016) who describe the assembly of endogenous chondroitin sulfate in human blood drawing a distinction between plasma and whole blood, and highlight the role of chondroitin sulfate associated with circulating cells of the immune system where the sulfation profile appears essential for such an association, paralleling what we had described in 1985 [22,28]. Interestingly, the sulfation profile of immune cell-associated chondroitin sulfate in human blood is more similar to that of microbial low-molecular-weight chondroitin sulfate than to that of its animal-derived counterpart with particular reference to specific sulfation in the 6-position of N-acetyl-galactosamine [20]. These data were not available in 2015 when Rerum was designed, and it is based on these data and the consideration outlined above that we decided to formulate an immune-modulating supra-molecular complex using microbial low-molecular-weight chondroitin sulfate as the backbone of the novel multi-molecular complex termed imunoTM. In imunoTM, pure phosphatidylcholine is bound to microbial low-molecular-weight chondroitin sulfate through non-covalent, electrostatic interactions between the negatively charged quaternary ammonium groups of its polar head and the sulfate groups with particular reference to sulfated N-acetyl-galactosamine that is the active site of GcMAF [11]. Considering that the sulfation profile of microbial low-molecular- weight chondroitin sulfate is homogeneous, at variance with its animal- derived counterpart, the interactions are more stable, thus favoring a higher level of negentropy that may be superimposable to that observed in the natural assembly of these molecules in the cells of the immune system. In essence, each molecule of microbial low-molecular- weight chondroitin sulfate is coated/surrounded by a high number of molecules of phosphatidylcholine that expose their hydrophilic tails.

In an aqueous environment, this prompts the spontaneous formation of cell membrane-like structures under the form of a homogeneous, single-phospholipid bilayer that resembles protocellular structures with chondroitin sulfate mimicking the role of nucleic acids [29].

It is worth mentioning that the formation of ordered structures made of microbial low-molecular-weight chondroitin sulfate and phosphatidylcholine leads to interesting consequences as far as alternative biological signaling is concerned. Both chondroitin sulfate and phosphatidylcholine are highly charged molecules that are propelled at speeds varying from 40 cm/s in the aorta to 0.03 cm/s in capillaries, thus showing positive and negative acceleration at every heartbeat. Acceleration of an electric charge is invariably associated with an electromagnetic field that, in the case of the structures described above, it is a varying field whose frequency and wavelength depend on a number of variables that are strictly individual such as, for example, heart frequency, hemodynamics, factors of turbulence, and so on. This varying electromagnetic field can be interpreted as a radio signal, and it is tempting to speculate that it may lead to non-chemical signaling between molecules in circulating blood and DNA. Thus, we recently described how DNA, functioning as a fractal antenna, is able to send and receive signals under the form of radio waves and how this may, in turn, regulate gene expression and, ultimately, epigenetics [30]. Since the assembly of microbial low-molecular-weight chondroitin sulfate and phosphatidylcholine is reminiscent of archetypical protocells or, in other words, of structures directly entangled with the origin of life on earth, the radio signal associated with these structures may be considered one of the most fundamental in biologic signaling and it can be conceived that it helps in restoring gene expression, in particular when it is deranged as it is in the case, for example, of cancer cells.

Vitamin D another component of the multi-molecular complex3

here described, is a secosteroid hormone with such a number of health effects that a review on this topic was provocatively entitled “Does vitamin D make the world go ‘round’?” [31]. We have extensively written on the vitamin D axis, a functional signaling pathway that comprises the vitamin D-binding protein, the precursor of GcMAF, vitamin D and its protein receptor (VDR) [32]. We have also proposed the molecular mechanism of interaction between GcMAF and VDR as it derives from the observation that biological responses to GcMAF depend on VDR polymorphisms [33,34]. In the formulation of imunoTM vitamin D3 is incorporated in the protocellular structures described above in a manner similar to that described for liposomes made of phosphatidylcholine [35]. It is worth mentioning that the incorporation of vitamin D3 in liposomes is a strategy to reduce its main side effect that is hypercalcemia [35]. Since incorporation rate of vitamin D3 in phosphatidylcholine liposomes is more than 80%, imunoTM may represent a delivery system much more efficient than the Gc protein/GcMAF where only one molecule of vitamin D3 is bound to one molecule of the protein.

In summary, imunoTM is a multi-molecular complex made of molecules endowed with known healthy properties arranged in such a way as to reproduce archetypical protocells able to send putatively restorative radio signals to DNA. Due to its peculiar molecular design, the function of imunoTM in the context of immunotherapy shows a dual nature. On one side, the known health effects of its components are amplified by their assembly in a multi-molecular structure held together by a higher number of non-covalent bonds. On the other side, the physical-chemical features of the emulsion enable imunoTM to function in a manner superimposable to that of Freund’s adjuvants.

Mechanism of action of imunoTM as a Freund’s adjuvant, indications and ways of administration

The first description of what is now called Freund’s adjuvant can be found in a publication of 1942 where Freund and McDermott described a method of immunization in which the antigen – in that case, horse serum – was emulsified in an oily suspension of heat-inactivated dried mycobacteria. According to their results, a single injection of this emulsion resulted in the development of large amounts of antibodies. After this first report, several publications described the efficacy of this approach in inducing a strong immunological response against a wide variety of antigens and, as of today, there are close to 13,000 peer-reviewed papers listed in PubMed describing the use of Freund’s adjuvant. Among these publications, it is worth mentioning a freely available review written in 1955 that provides an interesting historical perspective on the matter. Freund’s adjuvant exists in two forms, the complete one that comprises inactivated dried mycobacteria (usuallyMycobacterium tuberculosis), and the incomplete form that is only an emulsion of water and mineral oil. Although Freund’s adjuvant was originally intended to boost immune responses, numerous other fields of application have been proposed ranging from diabetes [36] to Parkinson’s disease [37]. As far as cancer is concerned, Freund’s adjuvant has been proposed as an effective tool in cancer vaccines [38] and encouraging results using the incomplete form of the adjuvant have been reported in patients with melanoma [39]. The main limitations of the original Freund’s adjuvant are associated with the use of mineral oil and, for this reason, modern versions of the adjuvant use other types of lipophilic compounds such as squalene or emulsifying agents such as polyacrylic acid [40] thus supporting the concept that it is the physical nature of the emulsion rather than its chemical composition responsible for the stimulation of the immune system. Such a concept is corroborated by the observation that adjuvants induce a variety of immunological responses ranging from synthesis of cytokines and chemokines to recruitment of immune cells and induction of antigen transport to draining lymph nodes. It is accepted that adjuvants primarily stimulate the innate arm of the immune system by favoring a local immuno-competent environment at the site of injection [41]. Since the innate arm of the immune system comprises cell types as different as macrophages, neutrophils, dendritic cells, natural killer cells and mast cells as well as cytokines and molecules of the complement system, stimulation of innate immunity by emulsions such as imunoTM provides a much wider spectrum of immunotherapeutic targets as compared with molecules that activate only one type of cells of the immune system. From the standpoint of a more recent historical perspective, it is interesting to notice that also GcMAF was originally proposed by Yamamoto as an adjuvant for antibody production [42], and it is likely that such an activity is indeed responsible for a number of the effects that have been observed in fields where macrophage activation and immune deficiency play little, if any, role such as autism [43]. In addition, the ascription of the clinical effects of GcMAF to its adjuvant activity would solve many of the inconsistencies that we have described in a recent paper [10]. The adjuvant activity of GcMAF is consistent with the molecular models we recently proposed [34], and may explain the greater efficacy of a GcMAF derivative we invented, where oleic acid was non-covalently bound to the protein [44]. imunoTM, at variance with GcMAF and Rerum, contains neither blood-derived proteins nor animal-derived components that may interfere with features of the emulsion that are required to exert maximal adjuvant activity without side effects. In addition, the peculiar molecular design of imunoTMenables ways of administration that add great versatility to its use and enable a wide spectrum of indications.

Thus, because of its composition, imunoTM can be manufactured as a sterile emulsion for subcutaneous injection that exploits its adjuvant activity. It is worth noticing that such a way of administration was recognized by Prudden as the most effective for bovine cartilage extracts containing chondroitin sulfate [4], and subsequent experiences with Rerum by a number of therapists confirm this assumption [18]. In addition, imunoTM can be compounded under the form of a transdermal delivery system following the concepts that we have recently described in a paper dealing with optimization of HIV DNA vaccines [45], an area where stimulation of the innate immune system may provide significant results. Compounding of imunoTM under the form of a transdermal delivery system (cream) would increase the spectrum of indications that in addition to those recognized for GcMAF and Rerum would thus comprise dermatologic and rheumatologic conditions where the rebalancing of the immune system is sought after. In addition, since the system that we have previously described significantly increases transdermal delivery, it can be foreseen that imunoTM may yield effects at the site of application not too different from those observed with injection. In short, the field of application of imunoTM comprises, but it is not limited to, all conditions and diseases that have been successfully targeted by GcMAF and Rerum ranging from cancer to autism, acute and chronic pain, autoimmune diseases and inflammatory bowel disease [17,18,43,46,47].

In conclusion, design and development of imunoTM represents the culminating point of research in the field of glycosaminoglycans begun in the early eighties as well as the result of years of achievements in the field of immunotherapy with particular reference to GcMAF and Rerum.

Authorship and contributorship

Marco Ruggiero and Stefania Pacini developed the concepts described in this paper and contributed equally to this manuscript.

Competing interests

Marco Ruggiero is the founder and CEO of Silver Spring, a Swiss company dedicated to research, development, and production of supplements and probiotics. No product of Silver Spring is mentioned in this article. Marco Ruggiero has invented a number of products including the product designated imunoTM here described and consults for several companies.

Stefania Pacini has invented the product designated imunoTM here described and consults for several companies.

Advisory

No information in this paper is presented by the authors as medical advice. Caregivers, researchers and interested parties should research all information given. Beginning any significant biomedical or other interventions that may impact physiology or making changes to an established regimen should be discussed with the patient’s physician in advance. Standard of care for each pathology must be followed as well as rules and regulations established by Health Authorities of each Country.

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27. Nyren-Erickson EK, Haldar MK, Totzauer JR, Ceglowski R, Patel DS, et al. (2012) Glycosaminoglycan-mediated selective changes in the aggregation states, zeta potentials, and intrinsic stability of liposomes. Langmuir 28: 16115-16125. [Crossref]

28. Mantovani V, Galeotti F, Maccari F, Volpi N (2016) Analytical Methods for AssessingChondroitin Sulfate in Human Plasma. J AOAC Int 99: 333-341. [Crossref]

29. Yanagawa H, Ogawa Y, Kojima K, Ito M (1988) Construction of protocellular structures under simulated primitive earth conditions. Orig Life Evol Biosph 18: 179- 207. [Crossref]

30. (2015) Ruggiero M, Aterini S. Electromagnetic Fields. In: Schwab M. (Edtr) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. [https://www.springer.com/gp/ book/9783540476481]

31. Wagner CL, Taylor SN, Hollis BW (2008) Does vitamin D make the world go ‘round’?Breastfeed Med 3: 239-250. [Crossref]

32. Ruggiero M, Pacini S (2011) The vitamin D axis in chronic kidney disease: state of the art and future perspectives. Eur Nephrol 5: 15-19.

33. Pacini S, Morucci G, Punzi T, Gulisano M, Ruggiero M, et al. (2012) Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling. J Nephrol 25: 577-581. [Crossref]

34. Thyer L, Ward E, Smith R, Fiore MG, Magherini S, et al. (2013) A novel role for amajor component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages. Nutrients 5: 2577-2589. [Crossref]

35. Merz K, Sternberg B (1994) Incorporation of vitamin D3-derivatives in liposomes of different lipid types. J Drug Target 2: 411-417. [Crossref]

36. Liddi R, Beales PE, Rosignoli G, Pozzilli P (2000) Incomplete Freund’s adjuvant reduces diabetes in the non-obese diabetic mouse. Horm Metab Res 32: 201-206. [Crossref]

37. Armentero MT, Levandis G, Nappi G, Bazzini E, Blandini F (2006) Peripheralinflammation and neuroprotection: systemic pretreatment with complete Freund’s adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson’s disease.Neurobiol Dis 24: 492-505. [Crossref]

38. Huijbers EJ, Femel J, Andersson K, Björkelund H, Hellman L, et al. (2012) The non- toxic and biodegradable adjuvant Montanide ISA 720/CpG can replace Freund’s in a cancer vaccine targeting ED-B-a prerequisite for clinical development. Vaccine 30: 225-230. [Crossref]

39. Slingluff CL, Petroni GR, Smolkin ME, Chianese-Bullock KA, Smith K, et al. (2010) Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete freund’s adjuvant for multipeptide melanoma vaccines. J Immunother 33: 630-638. [Crossref]

40. Lai RP, Seaman MS, Tonks P, Wegmann F, Seilly DJ, et al. (2012) Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund’s adjuvants. PLoS One 7: e35083. [Crossref]

41. Awate S, Babiuk LA, Mutwiri G (2013) Mechanisms of action of adjuvants. Front Immunol 4: 114. [Crossref]

42. Yamamoto N (1996) Structural definition of a potent macrophage activating factor derived from vitamin D3-binding protein with adjuvant activity for antibody production. Mol Immunol 33: 1157-1164. [Crossref]

43. Bradstreet JJ, Vogelaar E, Thyer L (2012) Initial Observations of elevated Alpha-n- Acetylgalactosaminidase Activity Associated with Autism and Observed Reductions from GC Protein-Macrophage Activating Factor Injections. Autism Insights 4: 31-38.

44. Branca JJ, Morucci G, Malentacchi F, Gelmini S, Ruggiero M, et al. (2015) Effects of oxaliplatin and oleic acid Gc-protein-derived macrophage-activating factor on murine and human microglia. J Neurosci Res 93: 1364-1377. [Crossref]

45. Ruggiero M (2017) A Novel Method to Enhance Immune Responses Induced by HIV DNA Vaccination. [https://bioaccent.org/hiv/hiv27.php]

46. Yamamoto N, Suyama H, Yamamoto N (2008) Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF. Transl Oncol 1: 65- 72. [Crossref]

47. Ruggiero M, Ward E, Smith R, Branca JJ, Noakes D, et al. (2014) Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer. Anticancer Res 34: 3569-3578. [Crossref]

Copyright: ©2018 Ruggiero M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Posted in Most Recent | 6,749 Comments

What is the Bravo Yogurt Protocol?

https://www.bravocoop.com/so/7aMQkWHoG?cid=2c8adf3c-ce9d-468f-94ef-fecb028d5303#/main

The GcMAF Healing Protocol

How to be all the way well!

FAQ:    “What do I need to do besides taking the Bravo Yogurt?”

It’s different for everyone but here are some basics to keep in mind.

The Bravo Yogurt is a formula of probiotics, Bifidus, yeasts, colostrum, and kefir.

It isn’t a random placement of ingredients.  Dr. Ruggiero tweaked this formula 324 times to get the right ratio to create a microbiome that can create GcMAF.

GcMAF is the substance that comes out of the Vitamin D metabolic channel.  It is used by the body to kickstart and turn on the immune system.  Ordinarily, this system is open and clear, unless you have nests of microbes such as bacteria or viruses in your body.

Viruses may remain in your body from naturally occurring colds, flu, and childhood diseases like chickenpox, etc.  When the viruses are present, the natural ignition of the immune system is covered with biofilm to intentionally glue the door closed that naturally opens when the immune system is required!! If the viruses are retroviruses it can change the DNA in that area so that your messages are not received!

Thus, it’s important to protect the microbiome that the Bravo Yogurt provides.  Flooding the body with yogurt or kefir can push the formula off balance and is not recommended.  Yogurt, kefir, yeasts, may affect this formula.  Antibiotics will clearly remove the microbiome even though it is essential to our bodies to have it.  Most people report that Bravo feels great and has enhanced their bodies.  However, if anyone has had  “antibiotic excess” or damage they might not feel the benefit for a few months until the body can restore itself.

If you do have a sizable infection, you may want to start with imuno™ first until the infection is resolved.  I also recommend a good quality colloidal silver which served as antibiotics prior to their invention.  I started with Rerum suppositories which I made myself.  I took 3 suppositories, with 3 drops, taken 3 days apart.  I had a huge heavy metal release with lots of aluminum coming out of my brain stem.  It was comfortable except for a tiny bit of “dust” from the transfer. That dust caused a small Alzheimer’s storm and reminded me of the benefit of this work and how grateful I am to avoid these diseases by detoxing them.  It was honestly a trainload of heavy metal coming down my spine and putting it inside my colon for removal.  It was powerful to witness and very rejuvenating to have it gone.

When Rerum was replaced by imuno this fall, Dr. Ruggiero announced that it is twice as effective.  I called one of my Rerum customers who had bought a lot of it.  His friend really pulled him out of a scary condition and within months I got the news that his doctors gave him a clean bone scan!  I called him and asked what he did with the Rerum.  He used a nebulizer and took 11 drops twice per week.

So my husband and I got started on that protocol.  Wow!  The imuno is incredible!  The first time I took my 11 drops into my sinuses and lungs with the nebulizer, it felt like a super clean, shiny spot was made around my sinuses and the center of my lungs.  Every 3-4 days I took 11 drops and the spot expanded each time and the same shiny clean feeling expanded too.  There were a few days where a goo was coming out.  It was as if someone was squeezing a tube of toothpaste and a gooey waste was gone.  I assume it went to the bowels.  I just felt the movement for a few days and was moving.   Then I began to notice that after 3 days of not taking my imuno dose, the edges of that clean spot closed back.  It was 3 steps forward, one half step back.  Taking it again still made a new expansion.

This really improved my breathing!  At about 4 weeks into this protocol, imuno is slowly clearing my heart, diaphragm, and brain now.  The toxic drip that came through my neck lymph constantly irritating and activating my thyroid has stopped.  That must have been from whatever used to be in my brain.   My shoulders joints also cleared.

I noticed that the back of my brain was clean only up to the brain stem and then it was moving slowly to get through all those layers.  I had an idea and took a few suppositories because the Rerum suppositories cleared out my brainstem last time.  That did the trick. I now have these very, very bright spots where my cells are clear and super bright!  I can think better, I can breathe, and I don’t run out of energy.

Sometimes, I take a breath just to remember how good I feel.   I can recover my energy when I want to.  When I meditate, the Light comes through me in a very vibrant way!   I don’t think I could imagine feeling better,  but I have to do something that I didn’t do before.   I have to rest and not just push.   I am much wiser now!  I have learned to trust that my “imuno Balance”, my “Bravo Balance”, and the shiny Light that moves through me are enough!    This healing protocol which I have outlined here is enoughto get my whole body to be healthy, free of disease and to sparkle!

I still take Bravo Yogurt orally during imuno use but I also take Bravo Yogurt internally and topically.  Be patient while the Bravo restores you and you begin to feel good like everyone reports.  People that take Bravo topically get all the same results.  They feel a shimmer as the microbiome engages the tissue and detoxifies it and a clunk when the immune system turns on at about 2 weeks.  You may miss the clunk but not the good feeling!  It may take a while if there is antibiotic damage.

 

Eventually, with the help of the DNA restoration herbs, the viruses and bad microbes will recede and the microbiome will restore natural function to the body.  This may take some time.  When you stop, the viruses will ooze out of the corners and taint the clean areas again.  It is important to keep using Bravo and imuno to increase immunity and clarity to all areas of the body so it doesn’t come back.  Even when complete, you will see the value of having “the cleaning team” come in regularly!

The Bravo microbiome usually turns on the immune system after the first two weeks of taking it.  Then, the immune system begins to restore power to the body by taking the most vital and important issues first.

Don’t Make this Mistake

Most people are delighted to feel their immune system igniting bit by bit and their bodies being energized.  They feel great so they stop taking Bravo and go on about their lives thinking that they have done something good that will stay with them.  However, the fight between the viral invasion and the body is far from over at that point.  The best course of action is to continue taking the Bravo Yogurt or Non-Dairy Bravo at a rate that allows you to expand and convert your tissues to natural immune ignition.  Also, to continue to detoxify in a nice glide with imuno.   To glide, you don’t work too hard or use too much energy.  We call this the “Bravo Balance”.

The “Bravo Balance” also includes knowing not to push or rush the body to “get rid of something and get it out”.  That is a reactionto not liking your situation and not how the body works.  The body has delicate drains that can get clogged.  It has detox pathways that can get inflamed.  The best way to go about supporting your body is to train yourself not to react and to trust the process.  It is helpful to not eat inflammatory foods and digest completely by bedtime.  If you do this, you will allow the next step to happen, the emotions and thoughts will be digested, completed, and archived.  Now you are at full power, but again, it is not helpful to react because you can still over do it even if you are celebrating feeling good!  Keep an even pace, keep your good habits in place and enjoy knowing how to get all the way to the end of your journey until you feel great.

Continuing “Bravo Balance” and the “imuno Balance” can also be preventative.   There are always more viruses, flu shots, car exhaust, or stinging bugs which can change your DNA.  Now, the doctors have discovered simple herbs which can restore your DNA mutations and give you your “own” transmission back but you must consider being in cooperation with the program to continue and keep taking steps as you can to build your strength and health.

I can’t go back to how I used to be and keep my “Bravo Balance”.  I have changed my food, my timing, and my habits.  I personally move ahead by choosing strength.  But now I am “expanded” and in order to keep my balance.  If I go back to not keeping myself expanded, I won’t be able to do everything I do now.  I have to keep my balance and keep a reserve saved!

When you keep your balance, other things will show up that you didn’t have room for.

You may realize that eating carefully is essential because our food supply is currently tainted with GMO’s and poisonous pesticides, fungicides and herbicides.  You may come to realize that you didn’t know!   Lots of money has been spent by the people who make these chemicals to make sure we don’t know about how dangerous all of this is.  Many of these types of things make it all the more important to keep your “Bravo Balance”!

I am very thankful for the contribution the that Dr. Ruggiero has made and I am grateful for those who support him.  It is indeed a gift of health to us.

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Do your part to make it work:

* Ketogenic Diet– Reduce inflammation & restore food absorption

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A Novel Potential Adjuvant for Cancer Vaccines – Ruggiero & Pacini

From Dr. Ruggiero

imuno: A Cancer Vaccine- Old vaccines go after pathogens.  New vaccines stimulate the macrophage.  Dr. Rugierro and his team were among the first to demonstrate that a low molecular weight acid phosphatase has phosphotyrosine phosphatase activity, thus counteracting aberrant signaling in cancer cells and inhibiting cancer cell proliferation.  They were among the first to highlight the role of macrophage activating colony stimulation factors in human cancer. They designed imuno which has the potential to boost the efficacy of existing cancer vaccines as well as to stimulate the innate immune system.  The “vegan chondroitin sulfate” called imuno has considerable promise as a mucosal immunization for fighting pathogens and cancer at mucosal sites.    . . . more

ISSN: 2638-1966 Madridge Journal of Vaccines Editorial Article Open Access.       Received: September 18, 2018 Accepted: September 24, 2018 Published: September 29, 2018 Citation: Ruggiero M, Pacini S. A Novel potential Adjuvant for Cancer Vaccines. Madridge J Vacc. 2018; 2(1): 58-62.

doi: 10.18689/mjv-1000112

Copyright: © 2018 Ruggiero M, et al. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Published by Madridge Publishers n       n8

Abstract

In this Editorial, I describe a novel potential adjuvant/(vaccine ingredient) for cancer vaccines designated imuno/(new vegan replacement for GcMAF & Rerum), an emulsion of low molecular weight microbial chondroitin sulfate, phosphatidylcholine and vitamin D . The molecules constituting imuno are arranged in cell membrane-like structures under the form of a homogeneous, single-phospholipid bilayer that resembles protocellular structures with chondroitin sulfate mimicking the role of nucleic acids. Phosphatidylcholine and chondroitin sulfate, arranged in protocellular-like structures, have to be interpreted as a universal delivery system with the potential of maximizing the effects of vaccination as we proposed for HIV DNA vaccines; such a molecular arrangement proves essential for the functioning of imuno as a novel type of cancer vaccine adjuvant.

A Novel Potential Adjuvant for Cancer Vaccines

Ruggiero M* and Pacini S

Silver Spring Sagl, 6864 Arzo, Switzerland

Cancer Vaccines

Until recently, vaccines were considered almost exclusively for prevention and cure of infectious diseases based on the century-old observation that attenuated microbes and/or their antigens, stimulate the immune system so to develop adaptive immunity against a specific pathogen. This concept is based on the assumption that a pathogen is recognized by immune cells as “non-self” and, therefore, as a target to be eliminated through one or more of the arms of the immune system. In the context of oncology, the task of the immune system is definitely more difficult since cancer cells have the ability to “conceal” their identity and escape immune surveillance through a variety of strategies. 

When cancer arises as a pathologic entity it is precisely because cancer cells have been successful in avoiding immune surveillance.  The idea of vaccination against cancer is an old one that, in modern times, dates back to the nineteenth century and Dr. William B. Coley with his toxin, often referred to as Coley’s vaccine. It is worth mentioning, however, that in the times of Coley, knowledge of oncology and immunology were rudimentary at best, and Coley’s vaccine was interpreted more as a form of bacterial therapy rather than a form of what today is called cancer immunotherapy. 

Coley had not been the first to observe an association between bacterial infection and cancer regression; even without counting reports from ancient Egypt and Pharaoh Imhotep in 2,600 BC, in the thirteenth century AD, Peregrine Laziosi, later canonized as the Saint Patron of cancer patients, described spontaneous regression of a large tumor in his leg after the tumor became severely infected and, since the eighteenth century, intentional infection of cancers was considered standard of care treatment that yielded significant successes up to complete regression of advanced cancers [1,2]. 

With today’s knowledge of the functioning of the immune system, we may interpret those results as a brutal stimulation of the immune system that, associated with the unavoidable hyperthermia/(fever) due to the severity of the infection, led to cancer cell apoptosis/(normal death) and, eventually, to cancer regression/(lessening of severity).

Cancer vaccines of the twenty-first century are obviously more targeted and less risky than those heroic attempts of the pre-antibiotic era as they try to “educate” the immune system to recognize cancer cells as non-self so to restore immune surveillance and efficiently eliminate abnormally proliferating cells. Modern vaccines against cancer have an unquestionable appeal over treatments such as surgery, radiation therapy or chemotherapy, since they are perceived as much less invasive and, at least in theory, they could protect against a specific type of cancer for life just like a vaccination against microbial infections does. 

Based on these premises, many potential vaccines against specific cancers have been developed, and the phase II/III clinical trials are underway to test their clinical efficacy [3]. At variance with/(different from) the heroic attempts of the past, today’s cancer vaccines are based on antigens derived from self-molecules rather than on infectious pathogens; however, just like in the past, they have been used primarily in advanced, metastatic, cancer with the target of stimulating the immune system so as to slow down the progression of the disease. In other words, until recently, cancer vaccines and, more broadly, cancer immunotherapy, was relegated to those cases where standard of care had failed or was not applicable; it is only in recent years that cancer vaccines and immunotherapy are being interpreted as means to target early cancer and premalignant lesions with the objective of preventing the onset of malignancies [4]. Therefore, two types of cancer vaccines are being developed: therapeutic vaccines that are used in patients who already have cancer, and preventive vaccines aimed at preventing cancer from occurring.

An interesting cancer vaccine that has been licensed for use in clinical practice is Sipuleucel-T (commercial designation, Provenge), a vaccine intended for the treatment of asymptomatic/minimally symptomatic metastatic castration- resistant prostate cancer. This vaccine ultimately relies upon activation of macrophages; to this end, peripheral blood mononuclear cells that are taken from the patient and incubated with a fusion protein consisting of recombinant prostate acid phosphatase and granulocyte-macrophage colony-stimulating factor (GM-CSF) [5].

It is worth noticing that we were the first to demonstrate that a low molecular weight acid phosphatase has phosphotyrosine phosphatase activity, thus counteracting aberrant signaling in cancer cells and inhibiting cancer cell proliferation [6,7]. Likewise, we were among the first to highlight the role of macrophage colony stimulating factors in human cancer [8], and to propose macrophage-based immunotherapy in advanced cancer [9]. It is based on this decade-old, proven expertise in the field of cancer cell signaling and therapy that we developed imuno, a novel tool that has the potential to boost the efficacy of existing cancer vaccines as well as to stimulate the innate immune system in the context of cancer immunotherapy.

Adjuvants for cancer vaccines

Cancer vaccines, just like other vaccines, benefit from the addition of adjuvants, compounds that optimize the immune response by increasing the production of antibodies and offering a longer-lasting coverage, thus reducing the amount of antigen that needs to be injected. In addition to increasing antibody production, adjuvants are used to potentiate cell- mediated immune responses, for example, by activating T-lymphocytes. 

Among different types of compounds, Freund’s adjuvant merits special consideration. It was first described in 1942 when Jules Freund and Katherine McDermott published a study describing the immunological response following injection of a “lanolin-like substance and killed tubercle bacilli suspended in oil” in guinea pigs [10]. There exist two types of Freund’s adjuvant, the complete and the incomplete form. The former consists of inactivated and dried microbes (typically Mycobacterium tuberculosis) in an emulsion of water and mineral oil whereas the incomplete form lacks the microbial component. 

The mechanism of action of Freund’s adjuvant involves stimulation of cell- mediated immunity as well as activation of innate immune responses, thus boosting the efficacy of vaccination. It is worth noticing, however, that use of the original formulation of Freund’s adjuvant in humans is forbidden because of toxicity, mainly due to the presence of mineral oil.  In the context of cancer, adjuvants assume particular relevance because most cancer vaccines are poorly immunogenic/(able to produce an immune response) per se and cancer patients frequently have deficient immune responses, thus making the presence of an adjuvant a mandatory requirement [11]. 

Although the original formulation of Freund is unsuitable for human use, nevertheless the main tenet of Freund’s adjuvant, that is the presence of an emulsion of water and oil, is maintained.  For example, authors from Cambridge (UK) reported in 2012 that a combination of adjuvants based on emulsions of lipophilic compounds elicited immunological responses comparable to Freund’s adjuvant [12]. Even though many adjuvants are based on emulsions of water and oil, or water and lipophilic compounds, also other combinations of molecules are efficient cancer vaccine adjuvants. 

In 2013,  authors from China and the USA demonstrated that polysaccharides may prove useful as cancer vaccine adjuvants with particular reference to advanced, metastatic cancer [13]. Therefore, based on our previous expertise in the field of polysaccharide research in experimental oncology, when we designed imuno we combined the two most effective approaches in the field of adjuvants developing an emulsion of water and a lipophilic molecule complexed with a polysaccharide endowed with immune stimulating properties.

Design of a novel tool for adjuvant immunotherapy

The design of imuno takes inspiration from our long- standing expertise in experimental oncology as well as from the pioneering work of Dr. Prudden who demonstrated, since 1985, that a polysaccharide, the glycosaminoglycan chondroitin sulfate, is the powerful immune stimulating agent responsible for the anticancer effects of cartilage formulations [14]. 

Chondroitin sulfate is composed of alternate units of glucuronic acid and N-acetyl-galactosamine, the latter being the active site of the Gc protein-derived Macrophage Activating Factor (GcMAF) [15], a macrophage activating factor endowed with significant adjuvant activity [16]. 

In 2013, based on molecular modeling, we hypothesized that the immune stimulating properties of GcMAF were due to its association with lipophilic compounds, namely oleic acid, and vitamin D3, thus reinforcing the hypothesis that the physical features of an emulsion were involved in the biological and clinical effects described for GcMAF [17]. 

In 2016, in the attempt to solve a number of controversies surrounding GcMAF and its role in immunotherapy, we hypothesized that chondroitin sulfate was indeed responsible for the biological and clinical effects attributed to GcMAF [18]. Based on these observations, we designed an emulsion of chondroitin sulfate, oleic acid and vitamin D3 designated Rerum®, that proved useful in a variety of conditions where potentiation of the immune system is sought after [19].

Although both GcMAF associated with oleic acid, and Rerum® have shown remarkable effects in immunotherapy [9- 20], the extractive nature of their main components has prevented their widespread use. Thus, GcMAF is synthesized from a blood protein, whereas, until recently, chondroitin sulfate was extracted from animal cartilage and it is well known that compounds extracted from complex matrices suffer from less than optimal homogeneity, purity, and consistency. Because of this, in the design of imuno we took advantage of the recent development of a novel form of chondroitin sulfate that derives from microbial fermentation and shows a degree of purity and homogeneity far superior to that of the animal-derived counterpart [21]. 

Microbial chondroitin sulfate shows a homogeneous sulfation profile that is much closer to that of human chondroitin sulfate and features a homogeneous low molecular weight whereas animal-derived chondroitin sulfate is a heterogeneous mixture of species with different molecular weights. This feature is of utmost importance as it has been widely demonstrated that low molecular weight glycosaminoglycans are much more effective than their high molecular weight counterparts as it is the case, for example, of heparin [22]. 

Consistent with this concept, Volpi et al. recently reported that low molecular weight microbial chondroitin sulfate shows far superior bio-availability and pharmacokinetics with a significantly greater clinical efficacy as compared with the animal-derived counterpart. Therefore, imuno is constituted by an emulsion of low molecular weight microbial chondroitin sulfate complexed with phosphatidylcholine and vitamin D3. At variance with Rerum®, phosphatidylcholine rather than oleic acid was chosen to provide the lipophilic moiety of the supramolecular assembly. The rationale for this choice lays in our decade-old observation that circulating glycosaminoglycans are associated with phosphatidylcholine and this association may be responsible for a number of biological effects [23]. 

In this way, the molecules constituting imuno are arranged in cell membrane-like structures under the form of a homogeneous, single-phospholipid bilayer that resembles protocellular structures with chondroitin sulfate mimicking the role of nucleic acids [24]. In a broader context, phosphatidylcholine and chondroitin sulfate, arranged in protocellular-like structures, have to be interpreted as a universal delivery system with the potential of maximizing the effects of vaccination as we proposed for HIV DNA vaccines [25]; such a molecular arrangement proves essential for the functioning of imuno as a novel type of cancer vaccine adjuvant.

As a matter of fact, despite the use of adjuvants in billions of doses of human and animal vaccines with indisputable efficacy, their mechanism of action at the molecular level remains the “immunologist’s little dirty secret” [26].  Many different mechanisms have been proposed to solve the “secret” consisting in the fact that exposure to a foreign antigen per se is insufficient to mount an efficient immune response and rather non-specific substances such as mineral oil, killed mycobacteria, or even metals – aluminum – have to be added in order to activate T- and B-lymphocytes. 

The question (of what to use) is central to understanding the functioning of the immune system; thus, lymphocytes are able to recognize non-self antigens without the need of any adjuvant, but, in the absence of this, the immune response to vaccination is rather inefficient as if these crude extracts were essential for initiating the body’s immune response. This being the case, even the noun “adjuvant”, from Latin adiuvare (to help) seems inadequate as it appears that rather than merely “helping” adjuvants are indeed essential. Among the different mechanisms proposed to elucidate the role of adjuvants at the molecular level, we wish to highlight activation and maturation of antigen presenting cells (APC) that migrate to the draining lymph nodes and activation of inflammasomes [27]. These mechanisms bear clinical relevance in the context of cancer vaccines where adjuvants similar in principle to imuno are considered. 

Thus, it can be hypothesized that the most efficient way to take advantage of activated lymphocytes and cells of the innate arm of the immune system, could be intradermal injection of the cancer vaccine together with its adjuvant in an anatomical location where the flow of lymph would carry the activated immune cells toward the malignancy.

It is worth noticing that intradermal delivery of vaccines is considered one of the best ways to achieve immunization as it has been demonstrated that it generates a higher response with lower dose when associated with a suitable adjuvant [28]. In addition, it has been highlighted that intradermal vaccines containing adjuvants similar in principle to imuno offer the advantage that they could be self-administered and sent through the mail since there is no need for long needles or technical expertise to achieve effective immunization. 

According to Authors from USA, Israel and Canada in reference to an intradermal flu vaccine containing a new adjuvant based on 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine – a type of phosphatidylcholine – in the event of a pandemic outbreak, intradermal self-administration of vaccines sent by mail “could alleviate the congregation of patients in health centers and thus reduce the potential of these centers to enhance the spread of lethal infection” [28]. In the case of the study quoted above, 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine was conjugated with a Toll-like receptor 4 (TLR4) ligand. 

In the case of imuno, phosphatidylcholine is complexed with low molecular weight microbial chondroitin sulfate and vitamin D3 and it is known that vitamin D3 regulates human dendritic cell response synergistically with Toll-like receptor agonists [29]. Because of this similarity, it can be hypothesized that imuno may be compounded in intradermal preparations that can be sent through the mail and self-administered in analogy with the strategy proposed by Carter et al. [28].

Conclusions

It is foreseeable that cancer vaccines will become an essential tool in the oncologist’s armamentarium and, in analogy with traditional vaccines designed to prevent infectious diseases, effective adjuvants will be required to maximize the effects of vaccination. With the design of imuno for the first time, we have in a single supramolecular structure the features of Freund’s-like water and oil emulsions and those of polysaccharide-based adjuvants. 

In addition, imuno can be considered a delivery system analogous to that proposed for HIV DNA vaccines [25], thus performing several functions, all aimed at optimizing immunization. Considering its role as a delivery system, we propose that imuno may also be considered in the context of mucosal immunization that is a promising novel strategy for fighting pathogens and cancer at mucosal sites [30].

Authors’ contribution

The Authors contributed to the genesis and development of the project described in this study and to the writing of the manuscript.

Ethics

This article is original and contains unpublished material.

Conflict of interest

Marco Ruggiero is the founder and CEO of Silver Spring, a Swiss company dedicated to research, development, and production of supplements and probiotics. No product of Silver Spring is mentioned in this article. Marco Ruggiero has invented a number of products including the product designated imunoTM here described and consults for several companies. Marco Ruggiero is a member of the Editorial Board of The Madridge Journal of Vaccines; he receives no remuneration for his editorial work. Stefania Pacini has invented the product designated imunoTM here described and consults for several companies.

Advisory

No information in this paper is presented by the authors as medical advice. Caregivers, researchers, and interested parties should research all information given. Beginning any significant biomedical or other interventions that may impact physiology or making changes to an established regimen should be discussed with the patient’s physician in advance. Standard of care for each pathology must be followed as well as rules and regulations established by Health Authorities of each Country.

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13. Li X, Min M, Du N, et al. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine. Clin Dev Immunol. 2013; 2013: 387023. doi: 10.1155/2013/387023

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19. Peter T, Ruggiero M. Ketogenic Diet and Immunotherapy in Cancer and Neurological Diseases. 4th International Congress on Integrative Medicine, 1, 2 April 2017, Fulda, Germany. Am J Immunol. 2017; 13: 158- 164. doi: 10.3844/ajisp.2017.158.164

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Madridge Journal of Vaccines

22. Robert F. The potential benefits of low-molecular-weight heparins in cancer patients. J Hematol Oncol. 2010; 3: 3. doi: 10.1186/1756-8722-3-3

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30. Nizard M, Diniz MO, Roussel H, et al. Mucosal vaccines: Novel strategies and applications for the control of pathogens and tumors at mucosal sites. Hum Vaccin Immunother. 2014; 10(8): 2175-2187. doi: 10.4161/ hv.29269

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How Extreme Weather Is Shrinking the Planet

California is currently ablaze, after a record hot summer and a dry fall set the stage for the most destructive fires in the state’s history. Above: The Woolsey fire, near Los Angeles, seen from the West Hills.

Photograph by Kevin Cooley for The New Yorker

Thirty years ago, this magazine published “The End of Nature,” a long article about what we then called the greenhouse effect. I was in my twenties when I wrote it, and out on an intellectual limb: climate science was still young. But the data were persuasive, and freighted with sadness. We were spewing so much carbon into the atmosphere that nature was no longer a force beyond our influence—and humanity, with its capacity for industry and heedlessness, had come to affect every cubic metre of the planet’s air, every inch of its surface, every drop of its water. Scientists underlined this notion a decade later when they began referring to our era as the Anthropocene, the world made by man.

I was frightened by my reporting, but, at the time, it seemed likely that we’d try as a society to prevent the worst from happening. In 1988, George H. W. Bush, running for President, promised that he would fight “the greenhouse effect with the White House effect.” He did not, nor did his successors, nor did their peers in seats of power around the world, and so in the intervening decades what was a theoretical threat has become a fierce daily reality. As this essay goes to press, California is ablaze. A big fire near Los Angeles forced the evacuation of Malibu, and an even larger fire, in the Sierra Nevada foothills, has become the most destructive in California’s history. After a summer of unprecedented high temperatures and a fall “rainy season” with less than half the usual precipitation, the northern firestorm turned a city called Paradise into an inferno within an hour, razing more than ten thousand buildings and killing at least sixty-three people; more than six hundred others are missing. The authorities brought in cadaver dogs, a lab to match evacuees’ DNA with swabs taken from the dead, and anthropologists from California State University at Chico to advise on how to identify bodies from charred bone fragments.

For the past few years, a tide of optimistic thinking has held that conditions for human beings around the globe have been improving. Wars are scarcer, poverty and hunger are less severe, and there are better prospects for wide-scale literacy and education. But there are newer signs that human progress has begun to flag. In the face of our environmental deterioration, it’s now reasonable to ask whether the human game has begun to falter—perhaps even to play itself out. Late in 2017, a United Nations agency announced that the number of chronically malnourished people in the world, after a decade of decline, had started to grow again—by thirty-eight million, to a total of eight hundred and fifteen million, “largely due to the proliferation of violent conflicts and climate-related shocks.” In June, 2018, the Food and Agriculture Organization of the U.N. found that child labor, after years of falling, was growing, “driven in part by an increase in conflicts and climate-induced disasters.”

In 2015, at the U.N. Climate Change Conference in Paris, the world’s governments, noting that the earth has so far warmed a little more than one degree Celsius above pre-industrial levels, set a goal of holding the increase this century to 1.5 degrees Celsius (2.7 degrees Fahrenheit), with a fallback target of two degrees (3.6 degrees Fahrenheit). This past October, the U.N.’s Intergovernmental Panel on Climate Change published a special report stating that global warming “is likely to reach 1.5 C between 2030 and 2052 if it continues to increase at the current rate.” We will have drawn a line in the sand and then watched a rising tide erase it. The report did not mention that, in Paris, countries’ initial pledges would cut emissions only enough to limit warming to 3.5 degrees Celsius (about 6.3 degrees Fahrenheit) by the end of the century, a scale and pace of change so profound as to call into question whether our current societies could survive it.

Scientists have warned for decades that climate change would lead to extreme weather. Shortly before the I.P.C.C. report was published, Hurricane Michael, the strongest hurricane ever to hit the Florida Panhandle, inflicted thirty billion dollars’ worth of material damage and killed forty-five people. President Trump, who has argued that global warming is “a total, and very expensive, hoax,” visited Florida to survey the wreckage, but told reporters that the storm had not caused him to rethink his decision to withdraw the U.S. from the Paris climate accords. He expressed no interest in the I.P. C.C. report beyond asking “who drew it.” (The answer is ninety-one researchers from forty countries.) He later claimed that his “natural instinct” for science made him confident that the climate would soon “change back.” A month later, Trump blamed the fires in California on “gross mismanagement of forests.”

Human beings have always experienced wars and truces, crashes and recoveries, famines and terrorism. We’ve endured tyrants and outlasted perverse ideologies. Climate change is different. As a team of scientists recently pointed out in the journal Nature Climate Change, the physical shifts we’re inflicting on the planet will “extend longer than the entire history of human civilization thus far.”

“His last words were ‘Yodel-ay-he-hoo.’ ”

The poorest and most vulnerable will pay the highest price. But already, even in the most affluent areas, many of us hesitate to walk across a grassy meadow because of the proliferation of ticks bearing Lyme disease which have come with the hot weather; we have found ourselves unable to swim off beaches, because jellyfish, which thrive as warming seas kill off other marine life, have taken over the water. The planet’s diameter will remain eight thousand miles, and its surface will still cover two hundred million square miles. But the earth, for humans, has begun to shrink, under our feet and in our minds.

“Climate change,” like “urban sprawl” or “gun violence,” has become such a familiar term that we tend to read past it. But exactly what we’ve been up to should fill us with awe. During the past two hundred years, we have burned immense quantities of coal and gas and oil—in car motors, basement furnaces, power plants, steel mills—and, as we have done so, carbon atoms have combined with oxygen atoms in the air to produce carbon dioxide. This, along with other gases like methane, has trapped heat that would otherwise have radiated back out to space.

VIDEO FROM THE NEW YORKER

The Flames Engulfing California

There are at least four other episodes in the earth’s half-billion-year history of animal life when CO2 has poured into the atmosphere in greater volumes, but perhaps never at greater speeds. Even at the end of the Permian Age, when huge injections of CO2 from volcanoes burning through coal deposits culminated in “The Great Dying,” the CO2 content of the atmosphere grew at perhaps a tenth of the current pace. Two centuries ago, the concentration of CO2 in the atmosphere was two hundred and seventy-five parts per million; it has now topped four hundred parts per million and is rising more than two parts per million each year. The extra heat that we trap near the planet every day is equivalent to the heat from four hundred thousand bombs the size of the one that was dropped on Hiroshima.

As a result, in the past thirty years we’ve seen all twenty of the hottest years ever recorded. The melting of ice caps and glaciers and the rising levels of our oceans and seas, initially predicted for the end of the century, have occurred decades early. “I’ve never been at . . . a climate conference where people say ‘that happened slower than I thought it would,’ ” Christina Hulbe, a New Zealand climatologist, told a reporter for Grist last year. This past May, a team of scientists from the University of Illinois reported that there was a thirty-five-per-cent chance that, because of unexpectedly high economic growth rates, the U.N.’s “worst-case scenario” for global warming was too optimistic. “We are now truly in uncharted territory,” David Carlson, the former director of the World Meteorological Organization’s climate-research division, said in the spring of 2017, after data showed that the previous year had broken global heat records.

We are off the literal charts as well. In August, I visited Greenland, where, one day, with a small group of scientists and activists, I took a boat from the village of Narsaq to a glacier on a nearby fjord. As we made our way across a broad bay, I glanced up at the electronic chart above the captain’s wheel, where a blinking icon showed that we were a mile inland. The captain explained that the chart was from five years ago, when the water around us was still ice. The American glaciologist Jason Box, who organized the trip, chose our landing site. “We called this place the Eagle Glacier because of its shape,” he said. The name, too, was five years old. “The head and the wings of the bird have melted away. I don’t know what we should call it now, but the eagle is dead.”

There were two poets among the crew, Aka Niviana, who is Greenlandic, and Kathy Jetnil-Kijiner, from the low-lying Marshall Islands, in the Pacific, where “king tides” recently washed through living rooms and unearthed graveyards. A small lens of fresh water has supported life on the Marshall Islands’ atolls for millennia, but, as salt water intrudes, breadfruit trees and banana palms wilt and die. As the Greenlandic ice we were gazing at continues to melt, the water will drown Jetnil-Kijiner’s homeland. About a third of the carbon responsible for these changes has come from the United States.

A few days after the boat trip, the two poets and I accompanied the scientists to another fjord, where they needed to change the memory card on a camera that tracks the retreat of the ice sheet. As we took off for the flight home over the snout of a giant glacier, an eight-story chunk calved off the face and crashed into the ocean. I’d never seen anything quite like it for sheer power—the waves rose twenty feet as it plunged into the dark water. You could imagine the same waves washing through the Marshalls. You could almost sense the ice elevating the ocean by a sliver—along the seafront in Mumbai, which already floods on a stormy day, and at the Battery in Manhattan, where the seawall rises just a few feet above the water.

When I say the world has begun to shrink, this is what I mean. Until now, human beings have been spreading, from our beginnings in Africa, out across the globe—slowly at first, and then much faster. But a period of contraction is setting in as we lose parts of the habitable earth. Sometimes our retreat will be hasty and violent; the effort to evacuate the blazing California towns along narrow roads was so chaotic that many people died in their cars. But most of the pullback will be slower, starting along the world’s coastlines. Each year, another twenty-four thousand people abandon Vietnam’s sublimely fertile Mekong Delta as crop fields are polluted with salt. As sea ice melts along the Alaskan coast, there is nothing to protect towns, cities, and native villages from the waves. In Mexico Beach, Florida, which was all but eradicated by Hurricane Michael, a resident told the Washington Post, “The older people can’t rebuild; it’s too late in their lives. Who is going to be left? Who is going to care?”

In one week at the end of last year, I read accounts from Louisiana, where government officials were finalizing a plan to relocate thousands of people threatened by the rising Gulf (“Not everybody is going to live where they are now and continue their way of life, and that is a terrible, and emotional, reality to face,” one state official said); from Hawaii, where, according to a new study, thirty-eight miles of coastal roads will become impassable in the next few decades; and from Jakarta, a city with a population of ten million, where a rising Java Sea had flooded the streets. In the first days of 2018, a nor’easter flooded downtown Boston; dumpsters and cars floated through the financial district. “If anyone wants to question global warming, just see where the flood zones are,” Marty Walsh, the mayor of Boston, told reporters. “Some of those zones did not flood thirty years ago.”

According to a study from the United Kingdom’s National Oceanography Centre last summer, the damage caused by rising sea levels will cost the world as much as fourteen trillion dollars a year by 2100, if the U.N. targets aren’t met. “Like it or not, we will retreat from most of the world’s non-urban shorelines in the not very distant future,” Orrin Pilkey, an expert on sea levels at Duke University, wrote in his book “Retreat from a Rising Sea.” “We can plan now and retreat in a strategic and calculated fashion, or we can worry about it later and retreat in tactical disarray in response to devastating storms. In other words, we can walk away methodically, or we can flee in panic.”

But it’s not clear where to go. As with the rising seas, rising temperatures have begun to narrow the margins of our inhabitation, this time in the hot continental interiors. Nine of the ten deadliest heat waves in human history have occurred since 2000. In India, the rise in temperature since 1960 (about one degree Fahrenheit) has increased the chance of mass heat-related deaths by a hundred and fifty per cent. The summer of 2018 was the hottest ever measured in certain areas. For a couple of days in June, temperatures in cities in Pakistan and Iran peaked at slightly above a hundred and twenty-nine degrees Fahrenheit, the highest reliably recorded temperatures ever measured. The same heat wave, nearer the shore of the Persian Gulf and the Gulf of Oman, combined triple-digit temperatures with soaring humidity levels to produce a heat index of more than a hundred and forty degrees Fahrenheit. June 26th was the warmest night in history, with the mercury in one Omani city remaining above a hundred and nine degrees Fahrenheit until morning. In July, a heat wave in Montreal killed more than seventy people, and Death Valley, which often sets American records, registered the hottest month ever seen on our planet. Africa recorded its highest temperature in June, the Korean Peninsula in July, and Europe in August. The Times reported that, in Algeria, employees at a petroleum plant walked off the job as the temperature neared a hundred and twenty-four degrees. “We couldn’t keep up,” one worker told the reporter. “It was impossible to do the work.”

This was no illusion; some of the world is becoming too hot for humans. According to the National Oceanic and Atmospheric Administration, increased heat and humidity have reduced the amount of work people can do outdoors by ten per cent, a figure that is predicted to double by 2050. About a decade ago, Australian and American researchers, setting out to determine the highest survivable so-called “wet-bulb” temperature, concluded that when temperatures passed thirty-five degrees Celsius (ninety-five degrees Fahrenheit) and the humidity was higher than ninety per cent, even in “well-ventilated shaded conditions,” sweating slows down, and humans can survive only “for a few hours, the exact length of time being determined by individual physiology.”

“Right now, they think they have amouse.”

As the planet warms, a crescent-shaped area encompassing parts of India, Pakistan, Bangladesh, and the North China Plain, where about 1.5 billion people (a fifth of humanity) live, is at high risk of such temperatures in the next half century. Across this belt, extreme heat waves that currently happen once every generation could, by the end of the century, become “annual events with temperatures close to the threshold for several weeks each year, which could lead to famine and mass migration.” By 2070, tropical regions that now get one day of truly oppressive humid heat a year can expect between a hundred and two hundred and fifty days, if the current levels of greenhouse-gas emissions continue. According to Radley Horton, a climate scientist at the Lamont-Doherty Earth Observatory, most people would “run into terrible problems” before then. The effects, he added, will be “transformative for all areas of human endeavor—economy, agriculture, military, recreation.”

Humans share the planet with many other creatures, of course. We have already managed to kill off sixty per cent of the world’s wildlife since 1970 by destroying their habitats, and now higher temperatures are starting to take their toll. A new study found that peak-dwelling birds were going extinct; as temperatures climb, the birds can no longer find relief on higher terrain. Coral reefs, rich in biodiversity, may soon be a tenth of their current size.

As some people flee humidity and rising sea levels, others will be forced to relocate in order to find enough water to survive. In late 2017, a study led by Manoj Joshi, of the University of East Anglia, found that, by 2050, if temperatures rise by two degrees a quarter of the earth will experience serious drought and desertification. The early signs are clear: São Paulo came within days of running out of water last year, as did Cape Town this spring. In the fall, a record drought in Germany lowered the level of the Elbe to below twenty inches and reduced the corn harvest by forty per cent. The Potsdam Institute for Climate Impact Research concluded in a recent study that, as the number of days that reach eighty-six degrees Fahrenheit or higher increases, corn and soybean yields across the U.S. grain belt could fall by between twenty-two and forty-nine per cent. We’ve already overpumped the aquifers that lie beneath most of the world’s breadbaskets; without the means to irrigate, we may encounter a repeat of the nineteen-thirties, when droughts and deep plowing led to the Dust Bowl—this time with no way of fixing the problem. Back then, the Okies fled to California, but California is no longer a green oasis. A hundred million trees died in the record drought that gripped the Golden State for much of this decade. The dead limbs helped spread the waves of fire, as scientists earlier this year warned that they could.

Thirty years ago, some believed that warmer temperatures would expand the field of play, turning the Arctic into the new Midwest. As Rex Tillerson, then the C.E.O. of Exxon, cheerfully put it in 2012, “Changes to weather patterns that move crop production areas around—we’ll adapt to that.” But there is no rich topsoil in the far North; instead, the ground is underlaid with permafrost, which can be found beneath a fifth of the Northern Hemisphere. As the permafrost melts, it releases more carbon into the atmosphere. The thawing layer cracks roads, tilts houses, and uproots trees to create what scientists call “drunken forests.” Ninety scientists who released a joint report in 2017 concluded that economic losses from a warming Arctic could approach ninety trillion dollars in the course of the century, considerably outweighing whatever savings may have resulted from shorter shipping routes as the Northwest Passage unfreezes.

Churchill, Manitoba, on the edge of the Hudson Bay, in Canada, is connected to the rest of the country by a single rail line. In the spring of 2017, record floods washed away much of the track. OmniTrax, which owns the line, tried to cancel its contract with the government, declaring what lawyers call a “force majeure,” an unforeseen event beyond its responsibility. “To fix things in this era of climate change—well, it’s fixed, but you don’t count on it being the fix forever,” an engineer for the company explained at a media briefing in July. This summer, the Canadian government reopened the rail at a cost of a hundred and seventeen million dollars—about a hundred and ninety thousand dollars per Churchill resident. There is no reason to think the fix will last, and every reason to believe that our world will keep contracting.

All this has played out more or less as scientists warned, albeit faster. What has defied expectations is the slowness of the response. The climatologist James Hansen testified before Congress about the dangers of human-caused climate change thirty years ago. Since then, carbon emissions have increased with each year except 2009 (the height of the global recession) and the newest data show that 2018 will set another record. Simple inertia and the human tendency to prioritize short-term gains have played a role, but the fossil-fuel industry’s contribution has been by far the most damaging. Alex Steffen, an environmental writer, coined the term “predatory delay” to describe “the blocking or slowing of needed change, in order to make money off unsustainable, unjust systems in the meantime.” The behavior of the oil companies, which have pulled off perhaps the most consequential deception in mankind’s history, is a prime example.

As journalists at InsideClimate News and the Los Angeles Times have revealed since 2015, Exxon, the world’s largest oil company, understood that its product was contributing to climate change a decade before Hansen testified. In July, 1977, James F. Black, one of Exxon’s senior scientists, addressed many of the company’s top leaders in New York, explaining the earliest research on the greenhouse effect. “There is general scientific agreement that the most likely manner in which mankind is influencing the global climate is through carbon-dioxide release from the burning of fossil fuels,” he said, according to a written version of the speech which was later recorded, and which was obtained by InsideClimate News. In 1978, speaking to the company’s executives, Black estimated that a doubling of the carbon-dioxide concentration in the atmosphere would increase average global temperatures by between two and three degrees Celsius (5.4 degrees Fahrenheit), and as much as ten degrees Celsius (eighteen degrees Fahrenheit) at the poles.

Exxon spent millions of dollars researching the problem. It outfitted an oil tanker, the Esso Atlantic, with CO2 detectors to measure how fast the oceans could absorb excess carbon, and hired mathematicians to build sophisticated climate models. By 1982, they had concluded that even the company’s earlier estimates were probably too low. In a private corporate primer, they wrote that heading off global warming and “potentially catastrophic events” would “require major reductions in fossil fuel combustion.”

An investigation by the L.A. Times revealed that Exxon executives took these warnings seriously. Ken Croasdale, a senior researcher for the company’s Canadian subsidiary, led a team that investigated the positive and negative effects of warming on Exxon’s Arctic operations. In 1991, he found that greenhouse gases were rising due to the burning of fossil fuels. “Nobody disputes this fact,” he said. The following year, he wrote that “global warming can only help lower exploration and development costs” in the Beaufort Sea. Drilling season in the Arctic, he correctly predicted, would increase from two months to as many as five months. At the same time, he said, the rise in the sea level could threaten onshore infrastructure and create bigger waves that would damage offshore drilling structures. Thawing permafrost could make the earth buckle and slide under buildings and pipelines. As a result of these findings, Exxon and other major oil companies began laying plans to move into the Arctic, and started to build their new drilling platforms with higher decks, to compensate for the anticipated rises in sea level.

The implications of the exposés were startling. Not only did Exxon and other companies know that scientists like Hansen were right; they used his nasaclimate models to figure out how low their drilling costs in the Arctic would eventually fall. Had Exxon and its peers passed on what they knew to the public, geological history would look very different today. The problem of climate change would not be solved, but the crisis would, most likely, now be receding. In 1989, an international ban on chlorine-containing man-made chemicals that had been eroding the earth’s ozone layer went into effect. Last month, researchers reported that the ozone layer was on track to fully heal by 2060. But that was a relatively easy fight, because the chemicals in question were not central to the world’s economy, and the manufacturers had readily available substitutes to sell. In the case of global warming, the culprit is fossil fuel, the most lucrative commodity on earth, and so the companies responsible took a different tack.

A document uncovered by the L.A. Times showed that, a month after Hansen’s testimony, in 1988, an unnamed Exxon “public affairs manager” issued an internal memo recommending that the company “emphasize the uncertainty” in the scientific data about climate change. Within a few years, Exxon, Chevron, Shell, Amoco, and others had joined the Global Climate Coalition, “to coordinate business participation in the international policy debate” on global warming. The G.C.C. coördinated with the National Coal Association and the American Petroleum Institute on a campaign, via letters and telephone calls, to prevent a tax on fossil fuels, and produced a video in which the agency insisted that more carbon dioxide would “end world hunger” by promoting plant growth. With such efforts, it ginned up opposition to the Kyoto Protocol, the first global initiative to address climate change.

In October, 1997, two months before the Kyoto meeting, Lee Raymond, Exxon’s president and C.E.O., who had overseen the science department that in the nineteen-eighties produced the findings about climate change, gave a speech in Beijing to the World Petroleum Congress, in which he maintained that the earth was actually cooling. The idea that cutting fossil-fuel emissions could have an effect on the climate, he said, defied common sense. “It is highly unlikely that the temperature in the middle of the next century will be affected whether policies are enacted now, or twenty years from now,” he went on. Exxon’s own scientists had already shown each of these premises to be wrong.

On a December morning in 1997 at the Kyoto Convention Center, after a long night of negotiation, the developed nations reached a tentative accord on climate change. Exhausted delegates lay slumped on couches in the corridor, or on the floor in their suits, but most of them were grinning. Imperfect and limited though the agreement was, it seemed that momentum had gathered behind fighting climate change. But as I watched the delegates cheering and clapping, an American lobbyist, who had been coördinating much of the opposition to the accord, turned to me and said, “I can’t wait to get back to Washington, where we’ve got this under control.”

“I hope this visit from your king has brightened your outlook on things.”

He was right. On January 29, 2001, nine days after George W. Bush was inaugurated, Lee Raymond visited his old friend Vice-President Dick Cheney, who had just stepped down as the C.E.O. of the oil-drilling giant Halliburton. Cheney helped persuade Bush to abandon his campaign promise to treat carbon dioxide as a pollutant. Within the year, Frank Luntz, a Republican consultant for Bush, had produced an internal memo that made a doctrine of the strategy that the G.C.C. had hit on a decade earlier. “Voters believe that there is no consensus about global warming within the scientific community,” Luntz wrote in the memo, which was obtained by the Environmental Working Group, a Washington-based organization. “Should the public come to believe that the scientific issues are settled, their views about global warming will change accordingly. Therefore, you need to continue to make the lack of scientific certainty a primary issue in the debate.”

The strategy of muddling the public’s impression of climate science has proved to be highly effective. In 2017, polls found that almost ninety per cent of Americans did not know that there was a scientific consensus on global warming. Raymond retired in 2006, after the company posted the biggest corporate profits in history, and his final annual salary was four hundred million dollars. His successor, Rex Tillerson, signed a five-hundred-billion-dollar deal to explore for oil in the rapidly thawing Russian Arctic, and in 2012 was awarded the Russian Order of Friendship. In 2016, Tillerson, at his last shareholder meeting before he briefly joined the Trump Administration as Secretary of State, said, “The world is going to have to continue using fossil fuels, whether they like it or not.”

It’s by no means clear whether Exxon’s deception and obfuscation are illegal. The company has long maintained that it “has tracked the scientific consensus on climate change, and its research on the issue has been published in publicly available peer-reviewed journals.” The First Amendment preserves one’s right to lie, although, in October, New York State Attorney General Barbara D. Underwood filed suit against Exxon for lying to investors, which is a crime. What is certain is that the industry’s campaign cost us the efforts of the human generation that might have made the crucial difference in the climate fight.

Exxon’s behavior is shocking, but not entirely surprising. Philip Morris lied about the effects of cigarette smoking before the government stood up to Big Tobacco. The mystery that historians will have to unravel is what went so wrong in our governance and our culture that we have done, essentially, nothing to stand up to the fossil-fuel industry.

There are undoubtedly myriad intellectual, psychological, and political sources for our inaction, but I cannot help thinking that the influence of Ayn Rand, the Russian émigré novelist, may have played a role. Rand’s disquisitions on the “virtue of selfishness” and unbridled capitalism are admired by many American politicians and economists—Paul Ryan, Tillerson, Mike Pompeo, Andrew Puzder, and Donald Trump, among them. Trump, who has called “The Fountainhead” his favorite book, said that the novel “relates to business and beauty and life and inner emotions. That book relates to . . . everything.” Long after Rand’s death, in 1982, the libertarian gospel of the novel continues to sway our politics: Government is bad. Solidarity is a trap. Taxes are theft. The Koch brothers, whose enormous fortune derives in large part from the mining and refining of oil and gas, have peddled a similar message, broadening the efforts that Exxon-funded groups like the Global Climate Coalition spearheaded in the late nineteen-eighties.

Fossil-fuel companies and electric utilities, often led by Koch-linked groups, have put up fierce resistance to change. In Kansas, Koch allies helped turn mandated targets for renewable energy into voluntary commitments. In Wisconsin, Scott Walker’s administration prohibited state land officials from talking about climate change. In North Carolina, the state legislature, in conjunction with real-estate interests, effectively banned policymakers from using scientific estimates of sea-level rise in the coastal-planning process. Earlier this year, Americans for Prosperity, the most important Koch front group, waged a campaign against new bus routes and light-rail service in Tennessee, invoking human liberty. “If someone has the freedom to go where they want, do what they want, they’re not going to choose public transit,” a spokeswoman for the group explained. In Florida, an anti-renewable-subsidy ballot measure invoked the “Rights of Electricity Consumers Regarding Solar Energy Choice.”

Such efforts help explain why, in 2017, the growth of American residential solar installations came to a halt even before March, 2018, when President Trump imposed a thirty-per-cent tariff on solar panels, and why the number of solar jobs fell in the U.S. for the first time since the industry’s great expansion began, a decade earlier. In February, at the Department of Energy, Rick Perry—who once skipped his own arraignment on two felony charges, which were eventually dismissed, in order to attend a Koch brothers event—issued a new projection in which he announced that the U.S. would go on emitting carbon at current levels through 2050; this means that our nation would use up all the planet’s remaining carbon budget if we plan on meeting the 1.5-degree target. Skepticism about the scientific consensus, Perry told the media in 2017, is a sign of a “wise, intellectually engaged person.”

Of all the environmental reversals made by the Trump Administration, the most devastating was its decision, last year, to withdraw from the Paris accords, making the U.S., the largest single historical source of carbon, the only nation not engaged in international efforts to control it. As the Washington Postreported, the withdrawal was the result of a collaborative venture. Among the anti-government ideologues and fossil-fuel lobbyists responsible was Myron Ebell, who was at Trump’s side in the Rose Garden during the withdrawal announcement, and who, at Frontiers of Freedom, had helped run a “complex influence campaign” in support of the tobacco industry. Ebell is a director of the Competitive Enterprise Institute, which was founded in 1984 to advance “the principles of limited government, free enterprise, and individual liberty,” and which funds the Cooler Heads Coalition, “an informal and ad-hoc group focused on dispelling the myths of global warming,” of which Ebell is the chairman. Also instrumental were the Heartland Institute and the Koch brothers’ Americans for Prosperity. After Trump’s election, these groups sent a letter reminding him of his campaign pledge to pull America out. The C.E.I. ran a TV spot: “Mr. President, don’t listen to the swamp. Keep your promise.” And, despite the objections of most of his advisers, he did. The coalition had used its power to slow us down precisely at the moment when we needed to speed up. As a result, the particular politics of one country for one half-century will have changed the geological history of the earth.

We are on a path to self-destruction, and yet there is nothing inevitable about our fate. Solar panels and wind turbines are now among the least expensive ways to produce energy. Storage batteries are cheaper and more efficient than ever. We could move quickly if we chose to, but we’d need to opt for solidarity and coördination on a global scale. The chances of that look slim. In Russia, the second-largest petrostate after the U.S., Vladimir Putin believes that “climate change could be tied to some global cycles on Earth or even of planetary significance.” Saudi Arabia, the third-largest petrostate, tried to water down the recent I.P.C.C. report. Jair Bolsonaro, the newly elected President of Brazil, has vowed to institute policies that would dramatically accelerate the deforestation of the Amazon, the world’s largest rain forest. Meanwhile, Exxon recently announced a plan to spend a million dollars—about a hundredth of what the company spends each month in search of new oil and gas—to back the fight for a carbon tax of forty dollars a ton. At a press conference, some of the I.P.C.C.’s authors laughed out loud at the idea that such a tax would, this late in the game, have sufficient impact.

The possibility of swift change lies in people coming together in movements large enough to shift the Zeitgeist. In recent years, despairing at the slow progress, I’ve been one of many to protest pipelines and to call attention to Big Oil’s deceptions. The movement is growing. Since 2015, when four hundred thousand people marched in the streets of New York before the Paris climate talks, activists—often led by indigenous groups and communities living on the front lines of climate change—have blocked pipelines, forced the cancellation of new coal mines, helped keep the major oil companies out of the American Arctic, and persuaded dozens of cities to commit to one-hundred-per-cent renewable energy.

Each of these efforts has played out in the shadow of the industry’s unflagging campaign to maximize profits and prevent change. Voters in Washington State were initially supportive of a measure on last month’s ballot which would have imposed the nation’s first carbon tax—a modest fee that won support from such figures as Bill Gates. But the major oil companies spent record sums to defeat it. In Colorado, a similarly modest referendum that would have forced frackers to move their rigs away from houses and schools went down after the oil industry outspent citizen groups forty to one. This fall, California’s legislators committed to using only renewable energy by 2045, which was a great victory in the world’s fifth-largest economy. But the governor refused to stop signing new permits for oil wells, even in the middle of the state’s largest cities, where asthma rates are high.

New kinds of activism keep springing up. In Sweden this fall, a one-person school boycott by a fifteen-year-old girl named Greta Thunberg helped galvanize attention across Scandinavia. At the end of October, a new British group, Extinction Rebellion—its name both a reflection of the dire science and a potentially feisty response—announced plans for a campaign of civil disobedience. Last week, fifty-one young people were arrested in Nancy Pelosi’s office for staging a sit-in, demanding that the Democrats embrace a “Green New Deal” that would address the global climate crisis with policies to create jobs in renewable energy. They may have picked a winning issue: several polls have shown that even Republicans favor more government support for solar panels. This battle is epic and undecided. If we miss the two-degree target, we will fight to prevent a rise of three degrees, and then four. It’s a long escalator down to Hell.

“Oh, yes. Definitely a forgery. Hope it didn’t cost you much.”

Last June, I went to Cape Canaveral to watch Elon Musk’s Falcon 9 rocket lift off. When the moment came, it was as I’d always imagined: the clouds of steam venting in the minutes before launch, the immensely bright column of flame erupting. With remarkable slowness, the rocket began to rise, the grip of gravity yielding to the force of its engines. It is the most awesome technological spectacle human beings have produced.

Musk, Jeff Bezos, and Richard Branson are among the billionaires who have spent some of their fortunes on space travel—a last-ditch effort to expand the human zone of habitability. In November, 2016, Stephen Hawking gave humanity a deadline of a thousand years to leave Earth. Six months later, he revised the timetable to a century. In June, 2017, he told an audience that “spreading out may be the only thing that saves us from ourselves.” He continued, “Earth is under threat from so many areas that it is difficult for me to be positive.”

But escaping the wreckage is, almost certainly, a fantasy. Even if astronauts did cross the thirty-four million miles to Mars, they’d need to go underground to survive there. To what end? The multimillion-dollar attempts at building a “biosphere” in the Southwestern desert in 1991 ended in abject failure. Kim Stanley Robinson, the author of a trilogy of novels about the colonization of Mars, recently called such projects a “moral hazard.” “People think if we fuck up here on Earth we can always go to Mars or the stars,” he said. “It’s pernicious.”

The dream of interplanetary colonization also distracts us from acknowledging the unbearable beauty of the planet we already inhabit. The day before the launch, I went on a tour of the vast grounds of the Kennedy Space Center with nasa’s public-affairs officer, Greg Harland, and the biologist Don Dankert. I’d been warned beforehand by other nasa officials not to broach the topic of global warming; in any event, nasa’s predicament became obvious as soon as we climbed up on a dune overlooking Launch Complex 39, from which the Apollo missions left for the moon, and where any future Mars mission would likely begin. The launchpad is a quarter of a mile from the ocean—a perfect location, in the sense that, if something goes wrong, the rockets will fall into the sea, but not so perfect, since that sea is now rising. nasa started worrying about this sometime after the turn of the century, and formed a Dune Vulnerability Team.

In 2011, Hurricane Sandy, even at a distance of a couple of hundred miles, churned up waves strong enough to break through the barrier of dunes along the Atlantic shoreline of the Space Center and very nearly swamped the launch complexes. Dankert had millions of cubic yards of sand excavated from a nearby Air Force base, and saw to it that a hundred and eighty thousand native shrubs were planted to hold the sand in place. So far, the new dunes have yielded little ground to storms and hurricanes. But what impressed me more than the dunes was the men’s deep appreciation of their landscape. “Kennedy Space Center shares real estate with the Merritt Island Wildlife Refuge,” Harland said. “We use less than ten per cent for our industrial purposes.”

“When you look at the beach, it’s like eighteen-seventies Florida—the longest undisturbed stretch on the Atlantic Coast,” Dankert said. “We launch people into space from the middle of a wildlife refuge. That’s amazing.”

The two men talked for a long time about their favorite local species—the brown pelicans that were skimming the ocean, the Florida scrub jays. While rebuilding the dunes, they carefully bucket-trapped and relocated dozens of gopher tortoises. Before I left, they drove me half an hour across the swamp to a pond near the Space Center’s headquarters building, just to show me some alligators. Menacing snouts were visible beneath the water, but I was more interested in the sign that had been posted at each corner of the pond explaining that the alligators were native species, not pets. “Putting any food in the water for any reason will cause them to become accustomed to people and possibly dangerous,” it went on, adding that, if that should happen, “they must be removed and destroyed.”

Something about the sign moved me tremendously. It would have been easy enough to poison the pond, just as it would have been easy enough to bulldoze the dunes without a thought for the tortoises. But nasa hadn’t done so, because of a long series of laws that draw on an emerging understanding of who we are. In 1867, John Muir, one of the first Western environmentalists, walked from Louisville, Kentucky, to Florida, a trip that inspired his first heretical thoughts about the meaning of being human. “The world, we are told, was made especially for man—a presumption not supported by all the facts,” Muir wrote in his diary. “A numerous class of men are painfully astonished whenever they find anything, living or dead, in all God’s universe, which they cannot eat or render in some way what they call useful to themselves.” Muir’s proof that this self-centeredness was misguided was the alligator, which he could hear roaring in the Florida swamp as he camped nearby, and which clearly caused man mostly trouble. But these animals were wonderful nonetheless, Muir decided—remarkable creatures perfectly adapted to their landscape. “I have better thoughts of those alligators now that I’ve seen them at home,” he wrote. In his diary, he addressed the creatures directly: “Honorable representatives of the great saurian of an older creation, may you long enjoy your lilies and rushes, and be blessed now and then with a mouthful of terror-stricken man by way of dainty.”

That evening, Harland and Dankert drew a crude map to help me find the beach, north of Patrick Air Force Base and south of the spot where, in 1965, Barbara Eden emerged from her bottle to greet her astronaut at the start of the TV series “I Dream of Jeannie.” There, they said, I could wait out the hours until the pre-dawn rocket launch and perhaps spot a loggerhead sea turtle coming ashore to lay her eggs. And so I sat on the sand. The beach was deserted, and under a near-full moon I watched as a turtle trundled from the sea and lumbered deliberately to a spot near the dune, where she used her powerful legs to excavate a pit. She spent an hour laying eggs, and even from thirty yards away you could hear her heavy breathing in between the whispers of the waves. And then, having covered her clutch, she tracked back to the ocean, in the fashion of others like her for the past hundred and twenty million years. ♦

This article appears in the print edition of the November 26, 2018, issue, with the headline “Life on a Shrinking Planet.”

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How someone feels about using imuno™

Using imuno has raised the bar in my mind about how clean a body can be!  imuno is cleaning my body to a higher level than I expected and with each dose I take, that brightness keeps manifesting.  It’s so hopeful! I can’t wait to get more clean to see what that is like!

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Quick Start Instructions:

  • Shake before using & refrigerate after opening
  • Extract each use with a sterile needle syringe so the jar will last for 6 months after opening
  • Imuno™ is a sterile injectable solution. It can also be applied topically, sublingually, or with a nebulizer for systemic issues.
  • Start slowly to make sure detox pathways are open. At first, take 1-3 drops 1x per week. Work up to your dose! More is not better.
  • When your dose is sufficient, the product provides a lift.
  • Uncomfortable detox is rare.  Reduce or spread out doses & take more protein.
  • if you have severity health conditions consult a practitioner for assistance on how to detoxify.

Using imuno – The Solution®

imuno – The Solution® is a sterile solution which comes in a 3 ml vial. Individuals who are appropriately licensed, can injections of imuno – The Solution® into the body:

  1. To put the solution into a specific congested area of tissue
  2. To apply to a specific tissue subcutaneously and put small amounts of the solution as a reservoir under the skin.

It can also be applied topically, sublingually, or with a nebulizer for systemic issues.

  • The adult serving size: 0.2 ml (4 drops) daily.
    • (maximum dose 0.5 ml daily)
  • The child serving size: 0.1 ml (2 drops) once per week.
    • (maximum dose .25 ml daily)

Each 3 ml vial contains 15 x 0.2 ml servings

Precautions:

Chondroitin Sulfate, an ingredient in imuno which has a blood thinning effect similar to the drug heparin.  Take precautions when taking large doses that it may have an anti-coagulant effect and medical supervision is advised.

See the pamphlets and box inserts:

  1. Box Insert
  2. Health Flyer
  3. Beauty Flyer
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Vegetable compound could have a key role in ‘beeting’ Alzheimer’s disease

Vegetable compound could have a key role in ‘beeting’ Alzheimer’s disease

Note to journalists: Please report that this research will be presented at a meeting of the American Chemical Society.

A press conference on this topic will be held Tuesday, March 20, at 9 a.m. Central time in the Ernest N. Morial Convention Center. Reporters may check-in at the press center, Great Hall B, or watch live on YouTube http://bit.ly/ACSLive_NOLA. To ask questions online, sign in with a Google account.

NEW ORLEANS, March 20, 2018 — A compound in beets that gives the vegetable its distinctive red color could eventually help slow the accumulation of misfolded proteins in the brain, a process that is associated with Alzheimer’s disease. Scientists say this discovery could lead to the development of drugs that could alleviate some of the long-term effects of the disease, the world’s leading cause of dementia.

The researchers are presenting their work today at the 255th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 13,000 presentations on a wide range of science topics.

“Our data suggest that betanin, a compound in beet extract, shows some promise as an inhibitor of certain chemical reactions in the brain that are involved in the progression of Alzheimer’s disease,” says Li-June Ming, Ph.D. “This is just a first step, but we hope that our findings will encourage other scientists to look for structures similar to betanin that could be used to synthesize drugs that could make life a bit easier for those who suffer from this disease.”

More than 5 million Americans have Alzheimer’s disease, according to the National Institute on Aging. Its incidence rises with age, affecting one in 10 Americans 65 and older, and one in three by age 85. Scientists are still trying to figure out what causes this progressive and irreversible brain disorder. But one prime suspect is beta-amyloid, a sticky protein fragment, or peptide, that accumulates in the brain, disrupting communication between brain cells called neurons. Much of this damage occurs, Ming says, when beta-amyloid attaches itself to metals such as iron or copper. These metals can cause beta-amyloid peptides to misfold and bind together in clumps that can promote inflammation and oxidation — a process similar to rusting — in nearby neurons, eventually killing them.

Previous research conducted by other scientists suggests that beetroot juice can improve oxygen flow to the aging brain and possibly improve cognitive performance. Building on this work, Ming, Darrell Cole Cerrato and colleagues at the University of South Florida wanted to find out if betanin, a beet compound used in commercial dyes that readily binds to metals, could block the effects of copper on beta-amyloid and, in turn, prevent the misfolding of these peptides and the oxidation of neurons.

In laboratory studies, the researchers conducted a series of experiments involving 3,5 di-tert-butylcatechol, or DTBC, a compound that is used as a model substance for tracking the chemistry of oxidation. Using visible spectrophotometry, the scientists measured the oxidative reaction of DTBC when exposed to beta-amyloid only, beta-amyloid bound to copper, and copper-bound beta-amyloid in a mixture containing betanin.

On its own, beta-amyloid caused little or no oxidation of DTBC. However, as expected, beta-amyloid bound to copper induced substantial DTBC oxidation. But when betanin was added to the copper-bound beta-amyloid mixture, the researchers found oxidation dropped by as much as 90 percent, suggesting that misfolding of the peptides was potentially suppressed.

“We can’t say that betanin stops the misfolding completely, but we can say that it reduces oxidation,” Cerrato says. “Less oxidation could prevent misfolding to a certain degree, perhaps even to the point that it slows the aggregation of beta-amyloid peptides, which is believed to be the ultimate cause of Alzheimer’s.”

Ming acknowledges funding from the National Science Foundation.

The American Chemical Society, the world’s largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

This is something I just ‘picked up’ when reading “The Week” news magazine!  There was a short write-up that suggests new breakthroughs in medical brain studies (April 6, p. 21) to help ward off Alzheimer’s disease.  The article states that:

     Scientists at the University of South Florida found that betanin,
     the compound that gives the beet root vegetable its rich red color,
     could help prevent protein pieces called beta-amyloid from forming           harmful plaque in the brain—a hallmark of the neuro-degenerative             disease.  This plaque usually occurs when beta-amyloid binds to               metals in the brain such as iron and copper; these metals cause the         protein to form clumps that can trigger inflammation and oxidation,
     which destroys nerve cells.  In a series of esperiments, the           researchers found that when beta-amyloid bound to copper was exposed       to betanin, oxidation dropped by up to 90 percent.
They are hopeful that other scientists look further into thisl
Now my footnote!  I have always had an appreciation of pickled beets and keep an open jar in my frig.  Very often I will eat a few—almost as an appetizer while cooking dinner, as Andy doesn’t care for beets!  This might be a glimmer of a reason why I have been spared up to this point!!
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Vectors for healing fibromyalgia

This is a communication on email with someone who has concerns.  I thought I would publish it for those who want to know about how to heal the deepest parts of their energy dysfunction.  I touch on the points as bullet points but I get through it to show you how to do it.  With a little study and elbo grease you could get yourself started.
Check out www.bravocoop.com and www.imunothesolution.com
Hello Mimi,
I have a few more questions for you as I am going along in my treatment. I am still using the yogurt only topically 1 tsp twice a day. I have continually adjusted the dosage sometimes higher and sometimes lower because it does seem like I have some reactions if it is too high.

Well done.  This is a very good lifetime health habit that will clear many things over time.

I am wondering how to determine the correct dosage.

Your correct dosage is determined by finding how much energy you have to heal yourself.  You need energy to run your body and your life, and to have fun.

Budgeting energy can come from your various accounts.
If it is life threatening, then you use more and take more rests on the couch.
But in general your dosage is best when you are moving, in an upward path and feeling great.
I find that I get in trouble only when my general nutrition is low.  If I crave or get bad microbes, if I increase the quality of my food and supplements, I am back on course.
It seems as though I may have some die-off from candida or something.

Very possibly.  Usually under the candida is some sort of parasitic condition.  Again, good habits will pull you through.

I have some itchiness on my skin and even in my intimate areas and constant draining down my throat (sometimes it’s even green or yellow which makes me think there is some infection or something?)
I would say that you are detoxing!  Make sure that your protein is high enough to keep you grounded and you should be able to “slow down” the rate of detox by digesting that protein.  (Lighter food will make you go too fast.  Like a light sled on ice.  This is not advisable unless you want to put yourself at risk.  Bobsledding can cause other damage to yourself in the area of not being safe on your feet.). so grounded, safe and feeling great.
Minerals are also important.
Meanwhile beside the detox, you also have two symptoms.
Itching is the removal of heavy metals.  This is held in place by bad habits.  They will be reflected by the type of metals that get caught inside.  Like ironing filings on a magnet, there are many different types of magnets that are in the body.
The best way to release heavy metal is let go of your bad habits.  Like the seven deadly sins.
Greed, lust, averse, sloth, anger, etc.  the list is long and it is not something we want to do or know we do.
But regardless of the bind, taking good care of ourselves and letting go of what we used to “hold on to” and getting “better friends” is the key.
I call them good habits.
You will want to take lots of greens specifically cilantro and chlorella to bind the heavy metals.
Also, if you “meditate or pray” and consciously release the electro magnetic charge from the metal particles, it will stop the itching and it will leave through proper channels.  This being the spine to the end and then it is passed through the colon and out the feces.
When it is coming out of everywhere, it is too much detox and not enough exit.
That’s why we go slowly and condition the exits before we start going on the “double diamond” runs.
Slow down your dose and increase meat.
If you are a vegetarian, you still need to increase your protein so that you stay grounded.
Minerals.  Lots of them.  This will help the spine to build containment for your heavy load.
You probably want to keep this email and make an appt with me to figure out how to work this all out.
What minerals, greens and proteins  work and how many.  You can pick up on the accessories page.  It is called an energetic healing session.
It’s not required, and I am not licensed to “tell you what to do”. But I can help with over the counter type choices and save you lots of time and money.

Green would be infection.

and some headaches.Are these normal detox reactions?

No.  You shouldn’t be having headaches.  This is an indication of the parasitic condition.  If the headache is a low dull throb in the back of the head, near the neck area.

If not, describe headache.
I have found that on this dose I feel more energetic but I still have pain from the fibromyalgia.

One thing at a time.  The FM is from loss of energy in the cell cycle.  That can be too many things and it is best to get some of these layers off before we can get that whole picture into scope.

It’s kind of like layers of lasagna.  Yeast candida on top. Then parasitic condition, if there is a lack of oxygen the cells will turn blue.
Look under your tongue.  AT mirror, look at your tongue and lift it up.  Are the blood vessels blue?  That is a good reading of your gut under there.  Get yourself breathing and exercising so that you are getting oxygen to your body.  Detox baths help but breathing is the best way to get your pH, hormones, and oxygen cycles balanced.  It also cuts through the layers and gets you closer to the FM.
There are also things you can do that will bring the cells back into balance faster.  You can login to the site and look in the search for Yew capsules.  Or just Yew and pick the capsules.  This is a very good way to get the cells into balance as quickly as possible.  It clears the heavy metals out of the cells and then the imuno can turn on the energy.
Again, how and when and how much need to be designed.
I am unsure if I should up the dose and risk more detox symptoms.

No.  You are already releasing, more will only release potentially magnetized metals and make you miserable

Or kill more parasites than you can get out the door.
They would be dead and start to become septic before you released it causing infection that is harder to deal with than what you are doing.
Go slowly, get some movement.
Remove the carbs from diet to not invite them to relocate and have food.
Go into the burning oil diet with a few tablespoons of oil per day.  FRESH ORGANIC oils.  Not too much.  Just enough to make a light oil/water emollient lotion out of your body.  One that is delicious and happy to live in.
Think of oil as clothing, it needs to be comfortable, breathable and healthy.  The body uses it as soap to clean the cells.  It has been reviewed and rewritten that healthy fats actually cause you to loose weight and gain clarity but it has to be right.  Not too much or too little.
It can do a lot of good on all levels since we can use it for fuel and our hitchhikers cannot.  They go elsewhere.
Or go dormant
I also began taking the psyllium husk powder and bentonite which seems to be aiding in the detox.

Not too much pls.

How can I aid the detox in the most painless way so that I feel the best I can from a fibro point of view?

Follow what I am saying here.  Make your own notes.

Track how you feel about each of these baselines and see what your adjustments do to you.
Keep watching for your break in power.  Most of it for the FM is that people are doing too much.  There is so much work piled on top of them that they can’t do it and don’t see that.  They use it to distract from feelings of emptiness, etc.
It is far better to have the feelings than use all your life energy to distract and then wallow in the uncleaned up mess.  It is better to have the feelings, get them out, and then use all the newly recovered energy for healthy habits and getting through your housework so you can live a clean happy, well adjusted life.
It seems that when I was taking more I had less fibro pain

That’s important to track and find those balances.

Do you understand tracking.  1-10 on a scale and check a box everyday.
Do it on a spreadsheet with the symptom on the vertical and the dates across the top.
You will have to test al the things I am talking about
Including grounding, how much pain, how clean your house is, how happy you are.  All the habits you are building, etc.
but I am scared I will unleash some scary virus or something.

You probably do have a scary virus that wants to come out of you.  It is scary because your body takes lots of energy to contain it.

Stop feeding it.  No carbs.  Then it will at least weaken and you won’t be scared.
Oil pulling as a consistent habit will be the eventual area where you handle this.
Don’t judge about being scared.
It’s like getting old, it will happen.  But if you build your habits to take care of the viruses then less fear and more happiness.
Is that something I should be concerned about?

Ask yourself again after reading what I have begun to build for you.  You let me know if you can shift into confidence.

Your immune system can’t take out a virus if you have built it stronger than it by eating sugar and carbs.
It will get too big to get it out.
You have to get it to go dormant,  put it in jail and then do the prisoner transport to get it out.
The fear and concern is from letting it get too powerful and not containing it.
Containing it is not eating sugars and carbs.
Balancing your food, water and supplements, oils
And movement and breathing.  Track it all.
Soon, you will see the tool Good habits and taking very good care of yourself and letting the feelings out from underneath that you are distracting yourself from.
We all do this.  I am not singling you out.
I also was wondering about taking probiotics seperately since I am only taking the yogurt topically at the moment? Would there be a conflict?

Yes.  The probiotics could alter the formula since it is built on a ratio.  Besides, more probiotics are not necessary.  If they are, take more topically and soon you will want to take some internally as well.  That’s fine but once you get your tracking going, you will begin to understand what is too much.  You will see it multidimensionally since all these things relate.

It is more work but very, very enlightening.
I have seen some food intolerances come back since I took the antibiotics in August

Yes. The antibiotics will damage the digestion because you don’t have what you need to digest your food.

If you are done with the need for antibiotics, consider rebuilding your good gut flora with Bravo internally at very small doses, like put a spoon into the yogurt and swish it in water.  It is a very, very small amount but your shouldn’t react to it.
That and all the other things here to look at.  This is when I can best help you.  When you start turning all the systems into the right direction and stop resisting the simple feeling that we all repress, we can get the wind back into our sails.
and I can tell my gut has regressed and I feel the need to give it some attention. I am worried to use the suppositories because I don’t want to have a detox reaction to it. Is that a concern I should have?

Maybe…. We know your gut is in need of rebuilding.

We know. You are already at your rate of detoxing.
Suppositories can be a good idea if
They are very gentle and low in potency
Not used very often
You see, they are a different place than skin.
So you can take a little bit and not rock the boat.
With FM it’s all about balancing the boat and you wanting to rock it really hard to distract from things that you don’t want to feel.
And usually, there is a spiky defense.  Meaning you will bite anyone who wants to get near those hurtful feelings.  You want a life, in this lifetime?  Deal with the painfulness.  It is a much more direct, fully lined up way to deal with the symptoms than anything else.  It is dead on.  The feelings are hurtful but once you connect with them they clear in a few minutes and you are free.
You have let go of all the energy that was used to hold them down and keep them “safe”.
“Safety”/defensive patterns take the place of healthy patterns.  If you can really find the courage to connect and let them up, you will “know”.
It’s a reckoning inside but all the tracking will help.
Here is an incomplete example:
Yes, you put more energy into the right direction and all things start to level out and head up.
It keeps you honest.
It keeps you focused on where you want to be.
It acknowledges where you are.
But there is one thing that happens that is unexpected:
You start to realize that you ARE changing.
Usually we aren’t paying enough attention so this becomes a vital redirection of the energy into NEW GROWTH.
🙂
Mimi
The vectors of Tabatha’s healing
Sun 9/29/18
1-10
10 highest
Transient things that are popping up right now
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Abnormalities
green mucus in throat
4
Headaches
Strengtheners in the food department
dark green leafy vegetables. (percentage of goal. goal = 10 oz)
4
meats or proteins (percentage of goal. goal = 10 oz)
5
Strengtheners in the supplement department
Amino Acids
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Minerals
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vitamins
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The emollient cleansing
Water (percentage of goal. goal = ? oz)
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Oil (also known as cellular soap) (percentage of goal. goal = 1 oz)
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Stress
Holding of repressed emotion
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amount of work piled on top of repressed emotions
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defensive patterns that hide the hurt
?
energy used to provide safety from defended territory
?
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