Molecular Biology in Cinema: Lorenzo's Oil

Lorenzo's Oil is  the true life story of Augusto and Micheala Odone (portrayed by Nick Nolte and Susan Saradon) who are suddenly faced with the challenge of their child, Lorenzo, being stricken with Adrenoleulzodystrophy (ALD). The film chronicles the affects of the disease and their desperate search for a cure. ALD is an extremely diabilatating neurodegenerative disease that destroys the lipids that form the myelin sheaths of axons in the brain. This reduces the connectivity of the neurons of the brain. It is X-linked recessive, and is fatal in many cases. It mostly affects males, but has been shown to manifest in females. ALD is caused by a mutation in ABCD1, a gene located on the X-chromosome. The disease can cause blindness, paralysis, sexual dysfunction, and dementia.

The film begins with Lorenzo as a normal, active 5 year old boy. He suddenly begins to demonstrate neurological problems such as erratic behavior, loss of hearing, and seizures. He is eventually diagnosed with ALD and given a life expectancy of 2 years. Lorenzo's condition rapidly deteriorates, leading to him completely losing his sight, hearing, and his ability to speak.

Despite his dire prognosis, the Odones fiercely search for a cure, culling through endless amounts of scientific research. They eventually find a therapy that involves a mixture of oils isolated from rapeseed oil and olive oil that contain 2 specific long chain fatty acids. They contact over 100 firms to attempt to find a company who can  synthesize this oil. They find a British chemist who is willing to perform the complicated distillation of the oil, which is later to be found to be erucic acid. Their discovery retards the progression of Lorenzo's ALD and even helps him regain his hearing and some cognitive faculties. Despite its positive effects, erucic acid, later named Lorenzo's Oil, is not able to rebuild Lorenzo's deteriorated myelin sheaths. The film ends with a montage of real-life ALD suvivors who have been treated with Lorenzo's Oil. Lorenzo's Oil is still used today, in conjunction with other methods (stem cell research, gene therapy), as a treatment option for ALD.

Although Lorenzo's Oil was a commercial failure at the time of its release in 1992, it was critically acclaimed. The film garnered 2 Academy Award nominations one for Best  Supporting Actress (Susan Sarandon) and another for Best Original Screenplay.

The Genetic Code

The genetic code is the nearly universal set of rules by which information encoded within genetic material is translated into proteins by living cells. The code consists of a series of codons (a set of nucleotide triplets) that code for specific amino acids which will eventually form proteins. The codon list can be seen below.The genetic code is the basis of all life on planet Earth. Non universal genetic codes are found in some organisms and organelles. The genome of most organisms is inscribed in DNA, and in RNA in viruses.

The genetic code was revolutionized and deciphered by Marshall Nirenberg and his colleagues at the National Institutes of Health. In 1961 Hirenberg and Heinrich J. Matthaei were the first to discover and discern the function of codons. Within five years, the entire genetic code was dechiphered. Hirenberg also explained how RNA is related to protein synthesis.

The genetic code is the recipe for the majority of life on Earth. The RNA codons code for various proteins, which in turn build the structures of the body. The genetic code can be used to determine which areas of the chromosome control specific features and functions. This may also be used in the future to diagnose and cure many genetic and congenital diseases.

Sources:

https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/geneticcode.html

http://www.genomenewsnetwork.org/resources/timeline/1961_Nirenberg.php

The Mitochondrial Eve

In molecular biology and genetics, the Mitochondrial Eve is the most recent matrilineal (maternal descent) common ancestor of all living humans. The mitochondrial eve is also known as mt-Eve or mt- MRCA. The name is derived from the Biblical character Eve, who was the first woman on Earth and is the mother of all humanity. Mitochondrial Eve does not refer to one female, but rather to a hypothesized group originating in the continent of Africa. It is estimated to be 99-148 thousands years old.

This information has been discerned because in most cases mitochondrial DNA (mtDNA) is inherited from mother to offspring without recombination. Therefore, the maternal mitochondrial DNA remains non-mutated, and is carried on unadulterated to the nest generation. The male counterpart to Mitochondrial Eve is the Y-chromosome Adam, the male in which all homo sapiens descended from. Instead of mitochondrial DNA, descendants of Y-chromosome Adam inherited the nuclear Y-chromosome. The Mitochondrial Eve and Y-chromosome Adam are not the first two homo sapiens, but rather the most recent common ancestors of individuals that carry these traits. These two also did not necessarily live at the same time. Mitochondria and Y-Chromosomes did not have originate at the same time at the same place.

Mitochondrial Eve and Y-Chromosome Adam do  not only exist in humans. These two are present in nearly all living things on Earth. "They are the ancestors of dinosaurs, trees, butterflies, (even) Donald Trump". Mitochondrial DNA can be used to build phylogeny, determine geographical places of origin, and find common ancestors. It may be possible in the future to find even older Mitochondrial Eves and Y-Chromosome Adams.

Sources:

https://www.smithsonianmag.com/science-nature/no-mitochondrial-eve-not-first-female-species-180959593/

https://en.wikipedia.org/wiki/Mitochondrial_Eve

CTE Biochemical Markers and Their Implications on Professional Sports

There has been quite a bit  of news recently about the long term effects of CTE on professional athletes. Most recently with the announcement of a lawsuit filed by the widow of former NFL player (and convicted murderer) Aaron Hernandez. She claims that head injuries the Hernandez sustained during his NFL tenure led to his homicidal and suicidal behaviors. Also, last year the NFL paid a $1 Billion settlement to former players who had sustained concussions while playing. The future implications of CTE could be monumental on not just the NFL but all of professional sports.

CTE (Chronic Traumatic Encephalopathy) is a neurodegenerative disorder that is found in individuals that have recieved multiple brain injuries.These injuries can ranged from minor to significant. It has been found to affect individuals that have participated in contact sports such as American Football, MMA, Boxing, and Soccer as well as soldiers that have been exposed to blasts from IEDs (Improvised Explosive Devices). CTE can affect individuals as young a middle school aged and can be triggered by insignificant head trauma. The pathology of CTE manifests in four steps...
           Stage 1:  Attention Deficit Hyperactivity Disorder (ADHD), confusion, dizziness, headaches
           Stage 2: Memory loss, anxiety, impulsive behavior, poor judgement
           Stage 3: Vertigo, movement disorders, speech impediments
           Stage 4: Dementia, depression, deafness, suicidality

Normally, an individual must be deceased before that can be properly diagnosed with CTE. A biopsy of their brain tissue must be performed and PET image must be obtained. However, there have been breakthroughs in CTE diagnosis and research. Analysis of cerebrospinal fluid proteins and plasma are potential alternatives to standard detection methods. CCL11 (a protein coded by genes on chromosome 17) may be a potential biomarker for individuals with CTE, Alzheimer's Disease, and other neurodegenerative diseases. CLL11 is a protein that is associated with age-related cognitive degeneration and it has been observed in the brains of individuals with CTE and Alzheimer's. Elevated levels of CCLL11 can be found in their CSF and plasma, and these levels could be used to diagnose indivduals with these diseases. These tests could be used to diagnosed athletes who currently play in these sports, and when faced with the risks of acquiring CTE may decide to end their careers prematurely.


Sources:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185541

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249716/

https://en.wikipedia.org/wiki/Chronic_traumatic_encephalopathy

Molecular Biology in Cinema: Gattaca

In my attempt to make this as interesting and tolerable as possible  I will try to connect Molecular Biology to one of my biggest interests, movies. One of my favorite genres of film is science fiction. Although the vast majority of science fiction films that are made are based in fantasy, they can be very predictive of future scientific breakthroughs. Just take a look one episode of the original "Star Trek" and you will see many devices that look like the ones we use today.

One movie that may be very predictive is the 1996 film "Gattaca". The title is composed of the nucleotide base pairs G, A, T, C. Long story short, it is about a future dystopian society that has attained the ability to genetically alter its future offspring and select the best hereditary traits.   Parents are able to change their children's physical and psychological traits by simple altering the embryo's genetic code. The film tackles the issues of eugenics, class systems, and genetics.

Could this be replicated in real life? According to NPR, scientists have been able to successfully edit DNA in human embryos. They were able to do so without causing any harmful mutations. Research of this nature could have monumental implications in eugenics and family planning. But, if left unchecked this could lead to a generation of irresponsibly genetically modified humans

Sources:

http://www.npr.org/sections/health-shots/2017/08/02/540975224/scientists-precisely-edit-dna-in-human-embryos-to-fix-a-disease-gene

https://en.wikipedia.org/wiki/Gattaca