Episode 8

"Bad Sign"

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Episode 8, Development

Section 1

 

In multicellular organisms, such as humans, individual life develops from one single cell (the egg fertilized by the sperm), into complex and rather large multi-system bodies composed of trillions of cells.

To achieve that, the first cell divides, producing new cells that divide themselves, and so forth, until the process of development and growth is complete.

In the womb, and during childhood, we grow and become larger because cells divide at a very fast rate, and organs become larger. However, when we reach adulthood, we stop growing.

For the rest of our lives, cells and tissues will die and shed, and new cells will replace them instead, maintaining a more-or-less steady state between decay and growth for some decades.

As we approach old age, our decay vastly surpasses our maintenance efforts, and so we degenerate, our tissues become ever more un-functional, until we die.

These facts highlight the idea that evolution does not result in a perfect system.

In a perfect system, regeneration would balance out against decay. However, evolution does not produce perfection, only the best compromise available. This compromise involves the regulation of cell cycle and cell death, by molecular mechanisms that are all but infallible.

If a cell does not reproduce, there is no growth, no development.

However, if a cell undergoes seemingly endless cycles of mitosis (cellular division), then an aberrant growth will arise: a tumor.

Inside human cells, a fantastically complex system of specialized proteins (such as enzymes, receptors, and ligands), regulate the pace of cell division vs. cell death.

But this system can and does go wrong from time to time, resulting in mutations that alter our DNA.

Some of these mutations can make cells enter an endless cycle of reproduction, that gets out of control. Inside cancerous cells, the fight to reproduce is winning over the efforts to stop cell reproduction (even if that means the cell has to kill itself, “apoptosis”).

Tumors grow because cancerous cells have mutated into better reproduction machines, they do not confine to the rules of becoming quiet and just slowly dying.

Tumors are successful because cancer is a micro-evolutionary event inside an organism.

Cancerous cells have the upper hand in their competition for resources, against healthy cells.

They evolve so much; they become invisible to the immune system by a process known as “antigen masking”.

A cancer cell is doing badly for the body, but it's doing great for itself! We exemplify these ideas using animation, archive footage, microscopy-imaging and interviews with leading scientists in the field.

We showcase the ideas of “necrosis” and “apoptosis”, two separate mechanisms that result in cell death.

We emphasize overwhelming concepts in the field of cancer biology, such as “oncogenes” (genes that cause cancer), “tumor suppressor genes” genes that fight cancer), “DNA damage” (the source of cancer mutations), “tumorigenesis” (the process of tumor growth), “metastasis” (the process of tumor spreading around the body) and “angiogenesis” (how tumors create blood vessels around them).

We meet with Sir Paul M. Nurse and Sir Tim Hunt, both Nobel Laureates for their work on cell cycle biology at the Francis Crick Institute (London, UK). Prof. John Kerr, discoverer of Apoptosis, at the University of Queensland (Brisbane, Australia) and meet with Prof. Junying Yuan, a world-class expert in Necrosis, from Harvard Medical School (Cambridge, MA, USA).

Finally, cancer as a microevolutionary process is addressed by Prof. Jean Clairambault, at the INRIA Research Center of Paris (Paris, France).

The importance of cancer research for cell biology is showcased through a tour of the National Institute of Cancer headquarters at Rockville (MD, USA).

 

Episode 8, Development

Section 2

 

The knowledge accumulated after decades of biological and medical research into cancer, in all its forms, can be put to use by bio-engineers.

By reverse engineering the events leading to DNA mutation, it is possible to accurately predict the probability of cancer development.

This process is explained with animation, as well as by interviews with Prof. Lawrence A. Loeb, from the Gottstein Cancer Research Laboratory, University of Washington, Seattle (WA, USA)

Another example of reverse engineering is given by showcasing the different methods that exist today to determine whether a certain compound is a carcinogenic (causes cancer), including case-control studies, tumor-induction in lab mice, the “Ames’ test”, etc.

To demonstrate these, we use archives footage and interviews with several top scientists, including: Prof. Bruce Ames, from the University of California, Berkeley (CA, USA) and Dr. Christopher P. Wild, Director of the International Agency for Research on Cancer, Lyon (France).

Next, we move towards the engineering of self-replicating machines powered by artificial intelligence.

This part showcases an in-depth interview with Prof. Freeman Dyson from the Institute of Advanced Study, Princeton (NJ, USA), one of the most influential theoretical physicist of our times.

Will self- replicating machines evolve artificial limitations and regulations on breeding?

Will programmed-death evolve in machines, in a similar way as it evolved in living cells (“apoptosis”), to counteract potential endless self-replication?

Can a mistake in the process of replication, such as cancer, occur in hypothetical societies built on self-replicating artificial intelligence?

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Episode 8, Development

Section 3

 

Say YES to cancer!

The devastating consequences of a cancerous tumor in the body of patients are evidence of the powerful effect that a small group of rogue cells can have on the whole organism.

So much so, that the cancerous outgrowth ends up killing its one and only host organism and originator (the body itself).

This amazing and terrorizing phenomenon has deeply helped scientists, for the last 50 years, to understand and uncover key facts regarding the biology of the individual cell.

By st udying cancer, scientists have uncovered the mechanisms used by cells to repair damaged DNA, and control cell reproduction, aging and death. Several of these fundamental concepts in modern biology, all achieved through cancer research, are thoroughly discussed using animation, archive footage and interviews with Prof. Paul L. Modrich, Duke University at Durham (NC, USA), Nobel Laureate 2015 for DNA repair mechanism; Sir Paul M. Nurse and Sir Tim Hunt, both Nobel Laureates for their work on cell cycle biology at the Francis Crick Institute London, UK. (see also Section 1). Furthermore, as cancer cells refuse to die and continue reproducing out of control, they could hold the key to extending life in an unexpected way.

If we could harness their power of escaping aging and death, but without the detrimental effects of the tumor on the rest of the body, we could potentially enhance the regenerative capabilities of our own tissues, extending life to unprecedented ages and delaying aging in a most significant way.

On this issue, Prof. Judith Campisi, from the Buck Institute for Research on Aging, at Novato (CA, USA) is featured here.

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Episode 8, Development

Section 4

 

Is cancer on its way to become eradicated, such as several infectious diseases?

Two significant developments are analyzed.

• The first is the rise of “immunotherapy” as the ultimate cure for all cancers.
  Is this really the case?
  How does immunotherapy work, and what obstacles does it still need to overcome?

• The second is the search for cancer vaccines.
  For example, the HPV vaccine effectively prevents cervical cancer, but it is possible only because an identified virus (the human papilloma virus – HPV) is the proven cause behind that type of cancer.
  However, this is not the case for many other types of cancer.

Will there ever be a vaccine against cancer that can tackle every type?

What potential technologies could erase cancer forever?

We interview Prof. James P Allison, one of the pioneers of immunotherapy, at the University of Texas MD Anderson Cancer Center, Houston (TX, USA); tour the headquarters of Bristol-Myers Squibb at New York City (NY, USA); and interview Prof. Ugur Sahin from the Johannes Gutenberg University of Mainz (Germany), the first to develop an applicable method to create a universal anti-cancer vaccine.