This post is in response to a blog post I read titled Dear Parents You Are Being Lied to…
At no time in history have we succeeded in making, in a timely fashion, a specific vaccine for more than 260 million people.
Yes, it may be true that vaccines are one of our greatest public health achievements, and one of the most important things you can do to protect your child. But, the number of young children who are not fully vaccinated for preventable diseases has been steadily increasing over the last decade. More and more, parents are claiming nonmedical exemptions from routine vaccinations. Are they really crazy? Is there a legitimate fear? Can we find a balance? Can parents recognize that no matter which side you are on we all want our children safe?
No matter which team you are on, one things for sure; whether you understand biochemistry or not, we would be crazy not to question the sudden increase in the number of vaccines needed or required despite our innate fear of disease.
Let’s remember that human beings are protected against infectious diseases by various physical and biochemical factors. Our first level of protection against disease is our skin and its acidic secretions, tears and the mucous membranes that line our nose, mouth and other passages connecting our internal and external environments. These factors and others, when functioning properly, keep pathogens at bay.
If an infectious agent, a pathogen, gets past the first line of defense, our bodies have a second tier of defense provided by natural or innate immune mechanisms. In this case, our own cells and the chemicals they produce seek out, identify and eliminate the pathogen. These very general and non-specific responses are critical to the maintenance of good health.
On occasion, a pathogen can get past our bodies’ primary protective mechanisms if it is present in very large numbers or if it has evaded or suppressed these processes. Stronger protection is needed and we respond by mounting an acquired immune reaction specific to the pathogen. These responses involve a variety of types of cells found in the blood and tissues, and can require a week or more to become established. Acquired immunity consists of antibody and cell-mediated responses.
An acquired immune response can result in either short-term or long-term protection against a specific pathogen and, perhaps, against some of its close relatives. In the case of long-term protection, re-exposure to the same pathogen weeks, months or years later reactivates the response mechanisms laid down during the original exposure.
This reactivation leads to rapid, effective elimination of the agent, often without clinical symptoms or signs of infection. When specific immunity results from unintentional exposure to agents in the environment, we refer to the resulting protection as being passively acquired immunity. Intentional exposure to such an agent or its components through vaccination is known as actively acquired immunity.
There’s always been some controversy surrounding vaccines, but in the past that was usually overridden by fear of the disease itself.
Take the polio vaccine, for instance. When it was first tested, families lined up for the trials. These were people who had no idea if the vaccine itself would cause polio. They didn’t even know if they’d receive a vaccine or a placebo. But they were so terrified of polio that they were willing to try anything. Ordinary people were also willing to pay for the development of the vaccine. That’s what got the March of Dimes started; it was an effort to pay for the research privately since the government wasn’t willing to fund it with public money. The point is that when people are terrified of a disease, they are far more willing to take risks.
The idea of inoculating people against disease dates back to 1796 when British doctor Edward Jenner noticed that milkmaids appeared to be immune to smallpox because of their exposure to a mild form of pox carried by cows.
Dr. Jenner took puss from a lesion on the hand of a milkmaid and inoculated a young boy. When the child didn’t become ill with smallpox, Dr. Jenner deduced that a small dose of a disease could protect a person from a more serious illness (the word vaccine is derived partly from “vaca,” the Latin word for cow).
More than two centuries later, making vaccines on a large-scale remains challenging.
Understanding how vaccines work requires some appreciation of the cells and other factors that play a role in the acquisition of immunity. The immune system is a complex network of molecules, cells and tissues that is widely dispersed throughout the body. Each of these entities has a distinct role to play, and all interact in a coordinated and orchestrated manner to generate a timely and specific immune response to a pathogen or to a vaccine.
When a pathogen or vaccine reaches the internal environment through inhalation, ingestion, a wound or injection, the cells in the surrounding tissues release chemicals called chemokines and cytokines that attract various types of white blood cells to the area of injury, leading to the destruction of the pathogen. White blood cells are found in everyone’s blood and are responsible for keeping our bloodstream and tissues free of pathogens, abnormal cells and other unwanted material.
Several types of white blood cells are critical to the natural immune response. One type of white blood cell is called a macrophage. It is among the first of the responding cells to arrive at the site of injury where it engulfs and destroys the pathogen.
Other types of white blood cells, called lymphocytes, also are attracted to the site. These cells, along with the macrophages release other chemokines and cytokines that direct the immune response. The local accumulation of the various types of cells contributes to the inflammation or redness that is often observed at sites of infection and injury. These cells and processes constitute the natural immune response and are often sufficient to clear or eliminate the infection.
Natural immunity is neither specific nor long lasting. This response occurs each time there is a threat of infection, and is virtually identical for each pathogen that gains entry. Natural immunity is also independent of the number of times to which we are exposed to any single agent, that is, even if we are exposed to a single agent many times, our response to each exposure is the same.
Vaccines on the other hand contain a number of substances, which can be divided into the following groups:
1. Micro-organisms, either bacteria or viruses, thought to be causing certain infectious diseases and which the vaccine is supposed to prevent. These are whole-cell proteins or just the broken-cell protein envelopes, and are called antigens.
2. Chemical substances, which are supposed to enhance the immune response to the vaccine, called adjuvants.
3. Chemical substances which act as preservatives and tissue fixatives, which are supposed to halt any further chemical reactions and putrefaction (decomposition or multiplication) of the live or attenuated (or killed) biological constituents of the vaccine.
All these constituents of vaccines are toxic, and their toxicity may vary, as a rule, from one batch of vaccine to another.
The desired immune response to vaccines is the production of antibodies, and adding certain substances to the vaccines enhances this. These are called adjuvants (from the Latin adjuvare, meaning “to help”).
The chemical nature of adjuvants, their mode of action and their reactions (side effect) are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions, which are more or less expected.
There are several types of adjuvants. Today the most common adjuvants for human use are aluminium hydroxide, aluminium phosphate and calcium phosphate. However, there are a number of other adjuvants based on oil emulsions, products from bacteria (their synthetic derivatives as well as liposomes) or gram-negative bacteria, endotoxins, cholesterol, fatty acids, aliphatic amines, paraffinic and vegetable oils.
The discovery of adjuvants dates back to 1925 and 1926, when a doctor showed that the antitoxin response to tetanus and diphtheria was increased by injection of these vaccines, together with other compounds such as agar, tapioca, lecithin, starch oil, saponin or even breadcrumbs.
The term adjuvant has been used for any material that can increase the humoral or cellular immune response to an antigen. In the conventional vaccines, adjuvants are used to elicit an early, high and long-lasting immune response. The issue with the newly developed purified subunit or synthetic vaccines used today using biosynthetic, recombinant and other modern technology are poor immunogens and require adjuvants to evoke the immune response.
To explain the action of adjuvants, we should look into immunology. The theory of vaccine efficacy is based on the ability of vaccines to evoke the formation of antibodies. This is of varying efficacy, depending on the nature of the antigen(s) and the amount of antigenic substance administered.
However, the mechanisms for the diversity of immune reactions are complex, and to this day are not quite known and understood. There are numerous theories, the favored one being antibody response as the sign of immunization (acquiring immunity).
Specific immunity to a particular disease is generally considered to be the result of two kinds of activity: the humoral antibody and the cellular sensitivity.
The ability to form antibodies develops partly in utero and partly after birth in the neonatal period. In either case, immunological competence—the ability to respond immunologically to an antigenic stimulus—appears to originate with the thymic activity.
The thymus initially consists largely of primitive cellular elements, which become peripheralised to the lymph nodes and spleen. These cells give rise to lymphoid cells, resulting in the development of immunological competence. The thymus may also exert a second activity in producing a hormqne-lilce substance, which is essential for the maturation of immunological competence in lymphoid cells. Such maturation also takes place by contact with thymus cells in the thymus.
Stimulation of the organism by antigen results in proliferation of cells of the lymphoid series accompanied by the formation of immunocytes, and this leads to the antibody production.
None of the theories for antibody formation comprehends all the biological and chemical data now available.
With a few exceptions, adjuvants are foreign to the body and cause adverse reactions.
This is where we should be paying attention!
The use of adjuvants enables the use of fewer antigens to achieve the desired immune response, and this reduces vaccine production costs.
So is it reasonable, to consider the aggregate effects of the increasing number of vaccinations given to babies? Are we totally satisfied that aggressive modulation of the immune system in healthy children has no significant risks? We can just keep adding vaccines? The more the better? I’m just wondering out loud. Less is more in almost every other aspect of medicine, just not in infectious disease?
Vaccines are still made primarily from tiny bits of pathogens, the disease-causing agents of a virus. It can take months to get the formula right, and flu viruses are always changing. The manufacturing process is also clunky and relies on techniques developed 50 years ago in which a virus is injected into chicken eggs to multiply.
Here’s how the process works: Like any virus, flu will only grow in living cells. One of the best places to grow it is in fertilized chicken eggs. (Pigs and humans are also good, but less practical.) Eleven days after the egg is fertilized, a hole is drilled into the eggshell and the virus is injected into the fluid surrounding the embryo. After the virus infects the embryo, it multiplies. Machines then crack open the eggs and the virus-filled fluid is removed.
The virus is chemically inactivated, usually with formaldehyde, and used as the “antigen” of a flu shot. Antigen is short for antibody generator. When injected into the body, it’s the antigen that provokes an immune response that remembers the code of the virus that is attacking the body.
The antigen-making process can take months because the eggs have to be at the right maturity. The virus also grows slowly and it can take as many as three eggs to make one shot of flu vaccine. Then there are the chickens that produce the eggs – they have to be kept in steady supply, and healthy, since producing enough vaccine for an entire country can take millions of eggs.
“It’s very cumbersome to make flu vaccine.”
Heavy regulation and a lack of a broad customer base left many drug companies with little incentive to make vaccines. Why spend time on such a low-margin business as vaccines when a company could make a fortune developing a new blockbuster drug?
But all of that began to change with the first hint of a pandemic on the other side of the world.
The outbreak of H5N1 in Hong Kong in 1997 was relatively small – just 18 people who handled birds – but six of them died. Such a high death rate drew immediate attention from medical experts around the world. Fears of a much bigger death toll began to percolate at government levels.
Like many countries, Canada began working on a pandemic preparedness plan. Led by John Spika, a senior infectious disease official at Health Canada, federal and provincial bureaucrats began drawing up models of a potential outbreak that could kill up to 58,000 Canadians and do $30-billion worth of damage to the economy. The key to fighting such an outbreak, they believed, was securing an abundant supply of vaccine.
Dr. Spika and others in the vaccine community warned that if a serious pandemic broke out, countries would close their borders and hoard vaccine. Governments began setting aside money in federal budgets for pandemic preparations. Ottawa also began negotiating a long-term vaccine supply agreement with BioChem, which had the only flu vaccine facility in Canada.
For Mr. Vezeau at BioChem, pandemic planning was a godsend. Suddenly, he had the attention of government officials. “We were losing money, so we went to the government and said, ‘Listen, for this to be a viable manufacturer, we need to increase the price of our vaccine,” Mr. Vezeau said. They got a higher price.
The government pursued contract negotiations with BioChem on a deal that was potentially so lucrative it began to push the value of the company higher. Before it was even signed, Shire Biologics stepped in and purchased BioChem in 2001. Soon after, the company signed a 10-year pact with Ottawa that would see the Quebec facility responsible for producing flu shots for every Canadian in a pandemic.
Dr. Spika called the deal “a cheap insurance policy” for the country. At a price tag of $300-million, it was more money than the vaccine maker had ever seen before.
Other vaccine companies began to negotiate similar large-scale contracts in dozens of countries, from Switzerland to France and even such smaller nations as Iceland.
However, one problem remained for the vaccine manufacturers as governments around the world began doling out money for contracts. The process was slow and hard to use on a mass scale. “They have to use chicken embryos and there isn’t enough supply of those readily available to be able to make tons of vaccine.
Fighting pandemic flu with vaccine made from eggs alone would be a losing battle, many believed. Companies needed to find a way to increase the amount of vaccine that could be produced in order to capitalize on the growth. And that particular discovery was already in the works.
For years, scientists had tried to find a faster way to make vaccines. They chased a variety of theories, including isolating the DNA of a virus, which many researchers believed would unlock new ways to fight infections. But at its main vaccine facility in Rixensart, Belgium, Glaxo had found a way to make vaccines more potent using another kind of technology: adjuvants.
Like we said, adjuvants are like superchargers for vaccines. They are mild contaminants that cause the body to respond with a more intense immune response. When paired with antigens, the adjuvant liquid can make the vaccine’s impact stronger. This allows for more doses to be produced from less antigen. Not a good long-term strategy but highly profitable.
The word itself comes from the Latin “adjuvare” which means to help or aid. But adjuvants, like so many scientific discoveries, were stumbled upon almost by accident.
Testing on different batches of vaccines often found that some worked better than others. In cases where there was a slight contaminant present in the mix – something as simple as using dirty lab materials – researchers found there was an enhanced immune response from the body to that dose of vaccine.
Thus the adjuvant industry was born, with contaminants such as oils, salts and virosomes (which are bits of influenza virus that do not replicate) added to vaccines.
“It allows us to decrease the antigen content, which allows us to multiply the capacity,” said Philippe Monteyne, senior vice-president of global vaccines development at Glaxo. “And of course, multiplying the capacity has some impacts on the business side,” boosting profits.
Adjuvants allowed companies to pump out more, but it is also a higher-margin business than antigens.
Significantly more than half the price of a dose of flu vaccine is attributable to the adjuvant, though Glaxo doesn’t disclose the exact figures. “That’s why vaccines became so attractive,” Mr. Monteyne said. “Most of the value in our case is put on the adjuvant technology.”
For the drug companies, the new interest in vaccines by governments looking to get as many flu shots as they could buy, and the scientific advances of adjuvants, came at an opportune time.
Many drug makers were starting to worry about the long-term viability of mega drugs like Lipitor, a cholesterol fighter, and Zantac, an ulcer treatment, that have a finite period of patent protection. When the patents expire, the market is flooded with cheaper generic versions. The big drug companies needed a new source of revenue, and the advent of large-scale vaccine manufacturing looked promising.
With the value of vaccines on the rise with the fears of avian flu, the drug companies also liked something else about the resurgent business: they had it to themselves.
Because vaccine making is so expensive – a new plant can cost up to $1-billion (U.S.) – companies like Glaxo, Novartis and Sanofi-Aventis didn’t have to worry about a rash of new entrants cutting into the flu vaccine business as governments ordered millions of doses.
“The barriers to enter the market are extremely high,” said Mr. Monteyne in Belgium. “You don’t become a vaccine maker over night. That’s why we have a few big players, and very few only.” That meant the giants could push hard to increase prices. And they did.
Sanofi-Aventis expects to earn close to $6-billion (U.S.) in vaccine revenue next year and double its sales by 2013. This quarter, sales of H1N1 vaccine alone will top $500-million. It is suddenly a good time to be a flu shot maker.
“Vaccines, vaccines, wonderful business,” Chris Viehbacher, the Canadian-born CEO of Sanofi-Aventis, told investment analysts on a conference call a few months ago.
It didn’t take long for such calculations to be made in other boardrooms around the globe. The companies began acting quickly to expand: Novartis spent $5-billion to buy U.S.-based flu vaccine maker Chrion. Britain’s Astra Zeneca paid $15-billion for Medimmune, and Glaxo purchased the old BioChem vaccine operation in Quebec for $1.4-billion.
With 22 per cent of the market, Glaxo was now the global leader in vaccines. And with that clout came the power to influence governments, who were already fearful about not having enough vaccine supply in the event of a pandemic.
In the summer of 2008, Canadian Finance Minister Jim Flaherty’s staff prepared a briefing note for an upcoming meeting with the head of Glaxo’s Canadian operations, Paul Lucas.
Glaxo had been lobbying several governments around the world to get higher vaccine prices and access to massive cash reserves countries were setting aside to cope with a pandemic threat.
“We understand that Mr. Lucas would like to discuss how GSK could further contribute to Canada’s pandemic preparedness, including [Ottawa] setting aside $400-million as a contingency fund,” the note said, according to documents obtained by Ottawa researcher Ken Rubin.
Mr. Flaherty held the purse strings on any national pandemic plan and subsequent vaccine purchase from Glaxo. The company had a message for the minister: “GSK has been critical … contending that the proposed vaccine price is too low,” Mr. Flaherty’s staff told him.
Indeed, the company had already been lobbying governments well before then. Since the late 1990s, prices for flu vaccine in North America have soared from $2 per dose to as high as $12 in 2007. The price has recently fallen back to about $8 as buying volumes increased in the face of H1N1. But that’s still a healthy margin, as some analysts estimate it costs about $1 to make each dose.
The company does not discuss its costs, but Mr. Monteyne said the cost of a flu shot is flexible depending on whether the buyer can pay more. “We have a tiered pricing strategy,” Mr. Monteyne said. “It is mainly based on the level of income of the country.”
Beyond just selling crates of vaccine, Glaxo also wants to sell full-service protection – pandemic readiness packages. And the industry’s desire to build a stable business out of vaccines, along with the emergence of adjuvants, has led to perhaps the most significant shift the industry has seen in decades: the creation of vaccine stockpiles.
Switzerland was the first country to jump in. In October 2006, with fear over H5N1 at fever pitch, the Swiss signed a contract with Glaxo on a stockpiling deal that called for 8 million doses of avian flu vaccine, slightly more than one shot for every citizen.
Then, in a new kind of move for the industry, the Swiss reserved future space on the production line for another 8 million doses if needed. That meant Swiss health authorities had priority in line at Glaxo’s factories if a second dose were needed.
This emerging business – pre-pandemic treatment – was rounding into shape. Glaxo began trademarking the names of vaccines along those lines, registering its vaccines as Prepandrix.
Other nations soon followed the Swiss with deals of their own, locking up huge sales for Glaxo.
There was just one problem: the H5N1 pandemic never happened. The virus stayed mostly with animals. The Swiss were left with one of the world’s largest stockpiles of unused H5N1 flu vaccine. Glaxo’s sales of avian flu vaccine fell 54 per cent in 2008, as countries realized their stockpiles weren’t needed.
This was a problem for the vaccine makers, who were looking to build an enduring revenue stream rather than simply capitalizing on flu fears to gain a temporary spike in sales. Glaxo’s new CEO, who had been elevated from the ranks of the company’s vaccine division, understood this.
Barely a year into his tenure as Glaxo’s chief executive officer, Andrew Witty outlined the company’s achievements during a conference call in October. Quarterly profit was up 30 per cent from a year earlier, orders for H1N1 flu vaccines had topped 400 million doses and the company was close to becoming the world’s largest vaccine maker.
“I think the momentum of this business is going in the right direction,” Mr. Witty told analysts. In short, Glaxo’s big bet on vaccines was bearing fruit. And perhaps most surprisingly, the Swiss were buying again, despite having spent millions on H5N1 vaccine it never used.
This, Mr. Witty explained, was the brilliance of the new vaccine market. Glaxo had turned the Swiss situation into an opportunity to sell more vaccine.
Because adjuvant could be paired with any antigen, the leftover stockpiles could be used for other outbreaks by simply plugging in a different antigen, depending on which virus looked most threatening.
Once a country bought a large supply of adjuvant, it was locked in as a buyer for Glaxo’s antigen for years to come. Countries were not just vaccine buyers now; they were subscribers, coming back annually to the company for more and different types of shots.
“If you go with an adjuvanted technology, you can actually keep a stockpile of your adjuvant and then simply rotate a new antigen in at the last minute,” Mr. Witty said.
That is basically what the leading countries like Switzerland did.
“The real business is a business of stockpiling. It is not a reactive market. It is something that is proactively being built with governments,” Mr. Monteyne said.
Other countries, including Canada, took notice of what the Swiss were doing. In the past 12 months, the number of countries using such stockpiling methods has grown to 60 from less than 10. When H1N1 broke out and temporary vaccine shortages occurred, Canadians learned that the federal government has become a big buyer of adjuvants.
As far as the vaccine makers are concerned, adjuvants are the future because they encourage countries to stockpile what they’ve bought from the drug companies. Asked by an analyst whether the company could keep generating the record vaccine profits it saw in 2009, Mr. Witty didn’t hesitate: Yes, it could.
“What’s been created this summer is essentially a stockpiling marketplace, which over a period of time will have to be refreshed,” Mr. Witty told analysts. “And that’s exactly where we see there being some kind of steady state” for the vaccine industry.
New fears over H1N1 were the catalyst to a completely new way of buying and selling vaccines that many countries are expected to follow. Flu shots are now a product for the masses. Non-seasonal flu shots such as H1N1 could become a yearly norm.
Soaring vaccine sales are also pushing companies to chase profit in other types of shots. The race is now on to develop blockbuster vaccines, defined as those that bring in more than $1-billion annually. Two recently developed vaccines – Prevnar for pneumonia and Garasil for cervical cancer – have become blockbusters, selling close to $2-billion a year.
In adult medicine, a common problem is poly-pharmacy. Each individual drug may be reasonably safe and effective for its intended disease. But given together, with 5 or 6 or more other chemicals, there are likely to be important interactions. The NY Times covered a study that persuasively suggested muscle side effects from statin drugs might be related to drug interactions.
Is it possible? Absolutely!
Cellular sensitivity, also known as delayed or cellular hypersensitivity, depends on the development of immunologically reactive or “sensitive” lymphocytes and possibly other cells which react with the corresponding antigen to give a typical delayed-type reaction after a period of several hours, days or even weeks.
Cellular hypersensitivity depends on the original antigenic stimulation and a latent period, and is specific in its response. Delayed-type hypersensitivity is characteristic of the body’s response to various infectious agents such as viruses, bacteria, fungi, spirochetes and parasites. It is also characteristic of the body’s response to various chemicals, such as mercury, endotoxins, antibiotics, various drugs and many other substances foreign to the body.
The induction of a hypersensitivity reaction requires the presence in the tissues of the whole organism or certain derivatives of it, in addition to the specific antigen such as a lipid in addition to tubercle bacillus protein. Sensitization to a non-infectious substance must be mediated through the skin or mucous membranes, which probably provide further necessary co-factors.
A delayed hypersensitivity reaction may be enhanced experimentally by the employment of the antigen in a mineral oil adjuvant with added Mycobacterium tuberculosis or by injection of the antigen directly into the lymphatics. The delayed hypersensitivity response is accompanied by mild to severe inflammation, which may cause cell injury and necrosis. The inflammatory response, which occurs in delayed-type hypersensitivity, may not be protective, and in many instances may even be harmful (e.g., rejection of grafts is directly linked to delayed hypersensitivity).
To make a point. Since the end of the Gulf War, tens of thousands of American, Canadian and British soldiers who participated in that war have claimed to be suffering from a variety of incapacitating symptoms which are generally termed as Gulf War Syndrome (GWS). The symptoms are multiple but mainly consist of excessive tiredness, muscle and joint pain, loss of balance, sensory symptoms, neurobehavioural manifestations, diarrhoea, bladder dysfunction, sweating disturbances, and respiratory, gastrointestinal, musculoskeletal and skin manifestations.
These veterans have been exposed to a variety of damaging or potentially damaging risk factors including environmental adversities, pesticides such as organophosphate chemicals, skin insect repellents, medical agents such as pyridostigmine bromide (NAPS), possible low-levels of chemical warfare agents, multiple vaccinations in combinations, depleted uranium, and other factors.
A large number of basic research findings, clinical epidemiological studies, and case control studies are reviewed to try and link them together to produce a coherent picture and to demonstrate the complexity of the interaction of biological systems, environmental and genetic factors, combinations of drugs and toxins with human health.
The findings of these studies so far have demonstrated that many of the previous assumptions made about the ‘safety’ of certain drugs and toxic substances or vaccines must be radically reviewed.
Many of the findings have far reaching implications not only in terms of explanation of what might have gone wrong during the Gulf War, but also have wider implications for many occupational groups who are exposed daily to some of these risk factors. More open-mindedness and much less prejudice are required concerning the basic biology of interactions of the above factors and their effects on cell functions and wider intelligent research is urgently required with high priority.
So, Hep B vaccine in babies? I have yet to hear a convincing reason to mandate vaccinating a newborn for Hepatitis B–a blood/body fluid transmissible disease. (I looked through 6 pages of a Google search. It yielded recommendations, associations and speculations.)
It’s not really because we think 5-year-olds will be exchanging body fluids on a bloody sports field, is it? It’s not for convenience or adherence. Because surely we aren’t saying that we think parents can’t be relied on to bring their older children in for a beneficial treatment. No misunderstandings please.
I’m not suggesting Hep B vaccine is dangerous or that it is a bad idea–I am glad I am protected–but is it wrong to question the net clinical benefit of giving Hep B vaccine to a newborn who lives in non-endemic suburbia and was born to an HBV-negative mom? I’m just asking.
Maybe someone has a convincing scientific explanation; it’s just not on the first 6 pages of Google.
Live and Learn. We All Do.
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