Episode 4

"The Weakest  Link"

 

Episode 4,  Development

Section 1

 

The immune system is a complex collection of organs, cells, and molecules that protect the body from intruder micro-organisms.

For these micro- organisms, we are just fertile feeding and reproductive grounds.

The microscopic army that defends us from them, is divided into two main brigades:

• The “innate” immune system

• The “adaptive” immune system.

The innate system is composed of hard-to-breach barriers, preventing microbes from entering our bodies to begin with.

The adaptive system deals with what happens if these barriers are non-the-less breached, and is composed of a convoluted and hierarchical organization of tissues, spanning many different cell types (neutrophils, basophils, macrophages, lymphocytes T, lymphocytes B, and more).

Each cell type and subtype has a specific role and a
predetermined target. Some are programmed to kill infected cells, others produce and release specific antibodies that can last for a whole lifetime.

For all the awe this sophisticated defense system inspires, it is far from perfect.

On one hand, our immune system evolved as the result of an arms race with the microbial enemy.

This arms race has not ended yet, and it is currently more explosive than ever before.

On the other hand, even in the absence of the enemy, our defense system can malfunction and turn on ourselves (“autoimmune diseases“).

The immune system is the best weapon we have, yet it has many flaws.

We demonstrate how this arms-race takes place by showcasing the different ways in which micro-organisms can beat the immune system and  overcome its defenses.

The episode opens with archive footage from the 80's depicting the HIV-AIDS epidemic.

With animation and microscopy-images, it is made clear how HIV
infects T-lymphocytes and turns the immune system on itself, destroying
the body's defenses (use the enemy’s weapon against itself).

Prof. Robert Gallo, Institute of Human Virology & University of Maryland (USA), who discovered that AIDS is caused by HIV, is featured here.

The next sequence deals with the bacterium that causes Tuberculosis (“mycobacterium”), and how it can render completely useless its attacker, the bacteria-eating human cell known as “macrophage".  

The reasons behind the need for a new flu shot every winter are discussed along the explanation as to why last year's shot is not good anymore.

We show how the Influenza virus rapidly evolves to create new surface molecules, forcing the immune system to develop new antibodies every time, making antibody memory useless.

We visit the Pasteur Museum in Paris, France, to learn how Louis Pasteur developed the first vaccine against Anthrax in 1881.

Anthrax is the ultimate killer, it shields itself rendering the immune system useless, but it also attacks by releasing toxins that rapidly spread and destroy human tissue.

The section is focused around a coordinated visit to the headquarters of the Centers for Disease Control (CDC, Atlanta, GA, USA).

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Episode 4, Development

Section 2

 

Here we deal with how engineers and scientists design attack and defense systems.

First, we showcase the field of Artificial Immune Systems (AIS) in which biological principles are used to device computational systems that can solve problems and develop artificial intelligence.

We emphasize the limitations of such techniques based on the same limitations that the immune system has in our bodies.

Prof. Jon Timmis from the University of York (England, UK) helps us to understand how robots and anti-virus software are based on the core biological principles behind the activity of the immune system.

Military defense system is showcased using footage and animation.

Anti-missile technologies that allow intercepting incoming missiles in mid-air and how they detect their target are presented (e.g., radar, satellite).

Then the same principle is exemplified by the immune system: how cells of the immune system detect their target (a mechanism called “chemo-kinesis“).

Intercepting a missile is compared with intercepting a virus, and engineers and biologists demonstrate what are the principles behind each.

Using animation, we get into the details of each example.

Footage and interviews obtained from visits to the Lockheed-Martin R&D headquarters in Palo Alto (CA, USA), The Salk Institute in San Diego (CA, USA), and the lab of Prof. Bruce Beutler (a Nobel Prize Laureate immunologist) at the University of Texas, Dallas (TX, USA) are presented. When spelling out the different strategies used by the immune system to detect a microbe, we emphasize the weak points, and how the system can be tricked.

The concept is that the arms race between microbes and our immune system is still ongoing, and so, by definition, if the process is still going on, there is no winner or loser.

The question still is: will this arms race ever end?

 

Episode 4,  Development

Section 3

 

In this section, we focus on answering the question formulated by the end of the previous section, emphasizing mainly the topic of vaccines and vaccinations.

We discuss the diseases that have been eradicated from the planet, and those for which we still do not have an effective vaccine.

Past diseases are featured using archive footage and animation montages (e.g., polio, tetanus).

Diseases that have become part of the past along those that have almost completely disappeared are presented.

We showcase the recent development of a 100% effective Ebola vaccine by Merck & Co. in Kenilworth (NJ, USA).

The goal is to explain why there is no vaccine for HIV at all; why the vaccine against the flu is seasonal; and why the vaccine against polio is permanent. Finally, we move to recent developments in antibiotics and anti- viral drugs. The biological mechanism behind the reason why antibiotics kill bacteria but not viruses is fully animated.

The issue of “antibiotic resistance” (dangerous types of bacteria that develop immunity against antibiotics) is emphasized as a major challenge for modern science and medicine.

However, as we seem to lose the fight against bacteria, we might be on the brink of a major win against viruses. In recent years, antiviral drugs took a significant leap forward.

The recent development of Harvoni (a cure for Hepatitis C) and anti-retroviral drugs that allow HIV carriers to live long lives are featured here.

The principles behind how these drugs work, are demonstrated using animation, while showcasing the intricate complexities of anti-viral treatments and virus-host relationships.

Footage and interviews are obtained from The Division of HIV/AIDS at San Francisco General Hospital (CA, USA), Gilead Sciences, Inc. at Foster City (CA, USA), the lab of Prof. Ada Yonath, (Nobel Prize Laureate in chemistry) at the Weizmann Institute of Science, Rehovot (Israel), the Emory Antibiotic Resistance Center at Emory University, Atlanta (GA, USA), and the lab of Shirit Einav at Stanford Medicine, in Palo Alto (CA, USA).

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Episode 4, Development

Section 4

 

Will the arms race, between our immune system and harmful microbes, ever be over?

Will humans eventually persevere over microbes, or vice versa?

A future scenario in which humans undergo extinction but bacteria and viruses prevail is not far-fetched.

On the other hand, new developments in antibiotic and antiviral treatments may signify the end of the arms race, with humans winning over microbes. Prof. Rotem Sorek, from the Weizmann Institute of Science (Rehovot, Israel), Prof. Richard Dawkins, from Oxford University (Oxford, UK), and Prof. Curt Lively from Indiana University at Bloomington (IN, USA) are featured here. “The Red Queen” hypothesis as proposed by Leigh Van Valen in the 70’s is featured while illustrating the major ideas of this hypothesis using archive footage as well as animation.