2. Viruses don't cause cancer ? | Virology Series

In medical training, the idea that viruses can cause cancer is taught as fact. Unfortunately, that claim is devoid of historical context, biological plausibility, as well as confirmatory evidence.

2. Viruses don't cause cancer ? | Virology Series
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Background Information

For decades we have been looking for ways to blame cancer on viruses. The discovery of viruses began as vectors for infectious disease, but slowly morphed into a field of unproven conjectures.

At first, we used viruses to account for acute illness that seem to coexist in space and time. They clustered around a geographic location, at a similar point in time. Deadly outbreaks first, then novel pathogens, then seasonal pathogens. Eventually we got to harmless skin lesions. As infectious diseases became far less prevalent, thanks to the advent of sanitation and access to clean water...there was less and less for virology to diagnose & treat.

So, the post-polio era virologists were looking for a new game to stick their beak into. Cancer was on the rise...which looked like a good option. So, they began applying their tools to find the hypothetical cancer-causing virus.

In the Beginning

In 1905, there was a reception for Robert Koch (of Koch's Postulates) who had been awarded the Nobel Prize. German Emperor Wilhelm II addressed Koch and said:

My dear professor, now you must get the cancer-bug.

...but in german.

Virologists faced two major obstacles:

  1. Cancer is not contagious, but viral disease is.
  2. Viruses reproduce by entering a cell, using its resources to replicate, then break out of the cell - destroying it.

Cancer is a disease in which cells continue to live. These cells change their behavior to become more aggressive, less cooperative, and invasive of boundaries. Once these cells consume your body, like insatiable parasites, the patient dies.

But, if a virus kills your cells to succeed, how could it possible cause them to become immortal & cancerous?

Think about this another way:

If the evolutionary objective of viruses is to replicate successfully and propagate across time...why would a virus evolve to induce a cellular state (cancer) that is so consumptive (by endless replication of host DNA), there would be no resources left for the viral genes that are trying to self-propagate.

In fact, you could make the case that once a cell becomes cancerous - unrestricted growth & replication - it marks the end of the virus. The cancer would deplete the resources required to propagate the virus. So any virus that did cause cancer would take itself out of the evolutionary tree.

As biotechnology got more sophisticated, the virologists began experimenting with them in their hunt for cancer. This seemed to solve their problem (of irrelevance) and enabled them to seize control of the field of cancer research.

They claimed that:

  1. If you wait long enough, the virus would progress from infection to cancer. Anywhere up to 50+ years after the initial infection.
  2. They postulated a defective virus that was unable to multiply (keeping the cell alive), but still able to cause cancer... a unique class of non-cytocidal viruses.

Cancer virology reached great success in the 1980s.

To their credit, the virologists made a perfectly legitimate observation of a rare event. Apparently, some special virus caused tumor growth in some extraordinarily rare instance, in a susceptible animal.

Rous Sarcoma Virus

One of our silkie chicks we hatched this spring! Sola was the first baby girl to hatch <3
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The first tumor-virus was observed in 1908.

Vilhelm Ellerman & Oluf Bang discovered that something tiny enough to pass through a bacterial filtration system - assumed virus - caused leukemia in newly infected chickens. Peyton Rous isolated some filtrate from a chicken with a solid tumor, and discovered that it caused rapidly growing tumors in other chickens within days of infection - named this Rous Sarcoma Virus (RSV)

RSV is a retrovirus. Retroviruses propagate through the continued existence of the host cell lineage. The more harmless they are, the more successful - because, the host lives the longest. And, the continued survival of the host cell opens the possibility of potential carcinogenic activity, if even through random mutation.

But, it was mostly ignored. We could not find it in humans because human cancers are not contagious - unlike some animal cancers. These viral isolates would only affect special strains of mice that had been intentionally weakened by generations of inbreeding. This can cause disease & cancer spontaneously - no need for the virus.

Furthermore, these viruses could not cause cancer in mice from nature.

Decades later, the virologists would seize upon these scattered experimental observations as precedent to claim that harmless viruses cause cancer.

Funding starts rolling in...

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In the late 1930s, 24 grants were distributed by the National Cancer Institute (NCI) in its first 5 years in existence - only 2 went to virus research. Over the next several decades, the NCI kept cancer virology alive. As the virologists took senior positions at the NCI, they used the Rous Sarcoma virus as justification for funding this line of work.

Ludwik Gross took a position at the Bronx VA, and began doing part-time research on a virus that causes leukemia in mice. He stumbled upon the same problem - it caused cancer in the sick inbred lab-mice, not the healthy wild mice. In one experiment he found a virus that caused salivary gland tumors.

By then the NCI had become a branch of the NIH. Other researchers quickly began replicating Gross' work. Sarah Stewart discovered a second virus that caused tumors throughout the body - named polyomavirus.

Several others followed their lead, and the challenge became self-evident:

Find a virus that causes cancer in humans.

Connection to Polio

When the Sabin polio vaccine was undergoing large-scale trials, scientists found a new virus in the monkey kidneys that were used to replicate the poliovirus used for the vaccines. This was the 40th virus isolated from monkey kidney cells.

Unfortunately, the virus caused cell death in kidneys of newborn hamsters. They named it Simian Virus 40 (SV40). By the time this was discovered, millions of children globablly had been injected with a vaccine with a potentially cancerous virus. Soldiers had received a similar contaminant, but for a different disease.

In response, they funded studies to track the recipients for longer periods than the vaccination campaigns that preceded them. Thus, they secured growing funding for the study of cancer-causing viruses.

This digitally-colorized, negative-stained transmission electron microscopic (TEM) image depicted a number of Influenza A virions.
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By the 1970s, over a dozen viruses were isolated from mice with leukemia...all of which were as meaningless as the first. Nonetheless, the NIH kept distributing the funds. This had the effect of drawing a lot of attention from virologists and grad students. At some point, people suggested that if they could create a vaccine for the virus, they could prevent cancer!

Wendell Stanley was the first Nobel Prize winner for the study of viruses. He led the first virology lab in the US, at UC Berkeley. In the 1956 National Cancer Conference he stated:

...we should assume that viruses are responsible for most, if not all, kinds of cancer...design and execute our experiments accordingly ...many more human viruses than we know what to do with...no reason to shy away from giving consideration to viruses as causative agents in cancer...

However, oncologists knew all too well that tumors rarely contained detectable virus. Why would it? It's not expressing anything other than what the cell needs to replicate & grow without restriction. That's what cancer does.

1. Birth of the Latent Virus | Virology Series
I am not a virologist. But, recent events have motivated me to explore the field I thought I understood - at least clinically.

Carleton Gajdusek became popular in the 1960s because the cancer-virus crowd found so enticing his unproven concept of an 'unconventional' latent virus. It really helped their virus-cancer case. They needed to rationalize the absence of detectable virus. Gajdusek responded in kind. At a 1964 NIH conference he suggested nine human tumors as caused by a 'slow' virus.

Andrew Lwoff suggested the possibility of a 'dormant' virus. He was challenged to prove his hypothesis. Thus, he got a grant from the NCI and got to work. Both Lwoff & Gross popularized the idea of cancers caused by viruses.

Unfortunately, scientists could find no active virus in tumors.

The fundamental problem remained that, even in the lab situations of viruses inserting themselves into specific cells - by the very nature of resource competition described above - these viruses would shortly cease to exist. So, how could one ever prove this hypothesis?

First Human Cancer-Virus (?)

Virologists attempted to use the animal models above to study human viruses and cancer. Unfortunately, they could not find such cancer-causing viruses. So, they developed yet another leap in logic. According to their new framework, the virus could cause a tumor...long after the initial infection...and without ever reactivating (latent).

The last remaining rules of disease and rationality had disappeared. Viruses could now:

  • infect a new host
  • remain latent for any length of time
  • then cause cancer without ever being present

Virologists could now claim that any cancer is infectious by blaming any virus that they could find a trace of...either fragments or antibodies (a sign of immunity). How would you disprove this?

In the 1950s, the surgeon Dennis Burkitt was working in Uganada. He noted large numbers of children with lymphoma. Lymphoma seemed to afflict people in central Africa. Noticing a correlation of disease with climate, he proposed that it was contagious.

In London, M. A. Epstein requested tissue samples to be flown back for study. Epstein began the hunt for the virus. Epstein and his lab associate, Yvonne Barr, tried to grow the tumor cells in lab conditions, and also searched with electron miscroscopy.

They found one previously unknown herpes virus - now known as the Epstein-Barr Virus (EBV). Initially thought to be the causative agent of lymphoma...we now believe it causes mononucleosis (the kissing disease).

But, EBV causes mono before the immune system has mounted a neutralizing response against it. In the case of Burkitt's Lymphoma, it is claimed to occur over 10 years after EBV has been neutralized.

Epstein could only find EBV in lymphoma cells cultured outside of the body, under laboratory conditions. In other words, the virus would reactivate only in the absence of an immune system.

Molecular Sleight of Hand

Brindar siempre lo mejor de ti.
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Since patients with lymphoma rarely had detectable EBV, the virus-hunters had to perform another magic trick to convince people of their hypotheses.

When your immune system encounters a novel pathogen, it generates long-lasting immunity in several fashions. One component of this is to generate immunoglobulins (antibodies) - some of which act acutely and others remain for longer periods of time. In either case, the presence of IgG antibodies is indicative of robust long-term immunity.

Since they could not detect the virus itself in patients with EBV - they decided that a test for the antibody against EBV would be sufficient to diagnose EBV-related cancer. It is completely consistent with their fictitious claims:

  • virus has infected the host, and remains dormant
  • so dormant in fact, it is not detectable
  • by their own definition, latent viruses need not reactivate to cause cancer
  • thus, we can use any indicator of prior infection to confirm that the virus causes cancer decades later...

What a mess.

This proved to be rather promising for the virologists, because they soon found that almost everyone with Burkitt's Lymphoma had antibodies to EBV. Unfortunately, they slowly realized that entirety of the central African population, with or without cancer, also had antibodies to EBV. In the USA, roughly half of the population has been exposed to EBV - but an exceedingly small number of people have Burkitt's Lymphoma.

The virologists generated more problems than they solved:

  1. Why did the vast majority of EBV+ people never get lymphoma?
  2. Why is the lymphoma less common than mono?
  3. Why is a central African that is EBV+ almost 100x more likely to get lymphoma compared to an American who is EBV+?

Epstein and his colleagues then decided that there was a cofactor in Africa, that made it more likely for EBV to lead to lymphoma - malaria. Since once infection was insufficient to explain the occurrence of cancer, they figured two infections would certainly plug the holes in their story.

Momentum continues

As the years progressed, several scientists began suggesting that EBV also caused another cancer: this time nasopharyngeal carcinoma - though only in some eastern countries with high EBV antibodies. Just as with Burkitt's Lymphoma, many of the patients with nasopharyngeal cancer had never been infected by the virus...and it was dormant in others.

The EBV-cancer hypothesis accelerated grant-funding for cancer-causing viruses. It is worth noting that EBV as a causative agent of Burkitt's Lymphoma and Nasopharyngceal Carcinoma are taught as fact in college & medical school.

One would struggle to find a single doctor who knows the history of these assertions.

Since then, several viruses have been blamed for the occurrence of human cancers:

Viruses that Can Lead to Cancer
Several viruses are linked with cancer in humans. Find out what we know about viruses and cancer risk here.

The real question is rather simple:

If the bedrock of virus-cancer research is as shakey as has been outlined above...then what else is wrong?

What else did a bunch of nerds in a lab lie about to garner attention and funding?


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