From lab to big screen (II)

As I told you in the previous article on genetics and cinema, there is a wide variety of films that talk about genetics. In the next article we will talk about science fiction, with two well-known films. Beware: spoilers!

GATTACA (1997)

Director: Andrew Niccol

Cast: Ethan Hawke, Uma Thurman, Jude Law

Genre: Science fiction

Story line: Vincent is one of the last “natural” babies born into a sterile, genetically-enhanced world, where life expectancy and disease likelihood are ascertained at birth. Myopic and due to die at 30, he has no chance of a career in a society that now discriminates against your genes, instead of your gender, race or religion. Going underground, he assumes the identity of Jerome, crippled in an accident, and achieves prominence in the Gattaca Corporation, where he is selected for his lifelong desire: a manned mission to Saturn’s 14th moon (titan). Constantly passing gene tests by diligently using samples of Jerome’s hair, skin, blood and urine, his now-perfect world is thrown into increasing desperation, his dream within reach, when the mission director is killed – and he carelessly loses an eyelash at the scene! Certain that they know the murderer’s ID, but unable to track down the former Vincent, the police start to close in, with extra searches, and new gene tests. With the once-in-a-lifetime launch only days away, Vincent must avoid arousing suspicion, while passing the tests, evading the police, and not knowing whom he can trust.

Relation with genetics: GATTACA is the “genetic” film par excellence. Starting with the title, this is formed by the initials of the four nitrogenous bases that make up DNA (guanine, adenine, thymine and cytosine). In addition, the helical shape of the DNA is repeated in several moments of the film, as in the stairs of Vincent’s house.

The main issue is about genetic selection, all children born have been genetically selected, closely linked to bioethics. The idea of ​​this selection is to reach eugenics, that is, to improve the population by selecting the “best” humans. This concept can be related to the Hitler’s Germany, who believed that Germans belonged to a superior group of races called “Aryan”. Hitler said that German Aryan race had been better endowed than the others and that this biological superiority destined Germans to oversee an empire in Eastern Europe.

Although nowadays genetic selection is valid and is used to avoid diseases, it is not applied with the same purposes as those of the film. At present, it is decided to carry out genetic selection after having studied the family and carried out the appropriate genetic counselling. It aims to help patients and their families avoid the pain and suffering caused by a genetic disease and should not be confused with the eugenic objective of reducing the incidence of genetic diseases or the frequency of alleles considered to be deleterious in the population.

This is very related to the genetic discrimination, case also exposed in the film. Gattaca is situated in a possible future in which genetics, trying to improve the quality of life of society, causes a movement of discrimination.

When we talk about discrimination, we tend to think about racial discrimination. This is defined as the different or exclusive treatment of a person for reasons of racial or ethnic origin, which constitutes a violation of the fundamental rights of individuals, as well as an attack on their dignity. Racism has been present throughout the history of mankind, especially in the twentieth century with racial discrimination in the United States and apartheid in South Africa.

For some time now, genetic discrimination has been gaining weight. It happens when people are treated differently by their company or insurance company because they have a genetic mutation that causes or increases the risk of a hereditary disorder. Fear of discrimination is a common concern among people who undergo genetic testing, and is a current problem that concerns the population because your own genome does not have to be a curriculum vitae that opens or closes doors as happens in the film. Vincent goes to work in Gattaca after performing a urine test and a blood test, since in Gattaca they do not choose workers for their ability or ability but for their DNA.

However, the film ends with the sentence “There is no gene for the human spirit”. This means that, although the society in which Gattaca is located is based on genetic modification, it does not affect the morality and final character of people because there is no way to genetically relate to the spirit, only the body has the genetic information.

Video 1. Trailer Gattaca (Source: YouTube)

JURASSIC PARK (1993)

Director: Steven Spielberg

Cast: Sam Neill, Laura Dern, Jeff Goldblum

Genre: Science fiction

Story line: Huge advancements in scientific technology have enabled a mogul to create an island full of living dinosaurs. John Hammond has invited four individuals, along with his two grandchildren, to join him at Jurassic Park. But will everything go according to plan? A park employee attempts to steal dinosaur embryos, critical security systems are shut down and it now becomes a race for survival with dinosaurs roaming freely over the island.

Relation with genetics: In the first film of this saga, from dinosaur’s fossils scientists extract DNA to be able to clone dinosaurs. The cloned dinosaurs will be part of the Jurassic park on which the film is based.

It is true that DNA can be extracted from bones, widely used in forensic genetics. Same as the issue of cloning, which was known by the Dolly sheep, the first large animal cloned from an adult cell in July 1996. But the film goes further and raises the possibility of reintroducing, in today’s world, extinct species and challenge natural selection.

Video 2. Trailer Jurassic Park (Source: YouTube)

REFERENCES

• FilmAffinity
• SensaCine
• Fotogramas
• La mano del extranjero
• TeleSur
• United States Holocaust Memorial Museum

Pharmacogenetics: a drug for each person

Sometimes, some people say that the medications prescribed by doctors are not good. Can this be true? Not all drugs work for the same population. Keep reading and discover the secrets of pharmacogenetics.

INTRODUCTION

The same that happens with nutrients, happens with drugs. Another objective of personalized medicine is to make us see that not all medicines are for everyone. However, it does not come again because around 1900, the Canadian physician William Osler recognized that there was an intrinsic and specific variability of everyone, so that each one reacts differently to a drug. This is how, years later, we would define pharmacogenetics.

It is important to point out that it is not the same as pharmacogenomics, which studies the molecular and genetic bases of diseases to develop new treatment routes.

First, we need to start at the beginning: what is a drug? Well, a drug is any physicochemical substance that interacts with the body and modifies it, to try to cure, prevent or diagnose a disease. It is important to know that drugs regulate functions that our cells do, but they are not capable of creating new functions.

Apart from knowing if a drug is good or not for a person, you also have to take into account the amount that should be administered. And we still do not know the origin of all diseases, that is, we do not know most of the real molecular and genetic causes of diseases.

The classification of diseases is based mainly on symptoms and signs and not on molecular causes. Sometimes, the same group of pathologies is grouped, but among them there is a very different molecular basis. This means that the therapeutic efficacy is limited and low. Faced with drugs, we can manifest a response, a partial response, that produces no effect or that the effect is toxic (Figure 1).

Figure 1. Drug toxicity. Different colours show possible responses (green: drug not toxic and beneficial; blue: drug not toxic and not beneficial; red: drug toxic but not beneficial; yellow: drug toxic but beneficial) (Source: Mireia Ramos, All You Need is Biology)

DRUGS IN OUR BODY

Drugs usually make the same journey through our body. When we take a drug, usually through the digestive tract, it is absorbed by our body and goes to the bloodstream. The blood distributes it to the target tissues where it must take effect. In this case we talk about active drug (Figure 2). But this is not always the case, but sometimes it needs to be activated. That’s when we talk about a prodrug, which needs to stop in the liver before it reaches the bloodstream.

Most of the time, the drug we ingest is active and does not need to visit the liver.

Figure 2. Difference between prodrug and active drug (Source: Agent of Chemistry – Roger Tam)

Once the drug has already gone to the target tissue and has interacted with target cells, drug waste is produced. These wastes continue to circulate in the blood to the liver, which metabolizes them to be expelled through one of the two routes of expulsion: (i) bile and excretion together with the excrement or (ii) purification of the blood by the kidneys and the urine.

THE IMPORTANCE OF PHARMACOGENETICS

A clear example of how according to the polymorphisms of the population there will be different response variability we find in the transporter genes. P glycoprotein is a protein located in the cell membrane, which acts as a pump for the expulsion of xenobiotics to the outside of the cell, that is, all chemical compounds that are not part of the composition of living organisms.

Humans present a polymorphism that has been very studied. Depending on the polymorphism that everyone possesses, the transporter protein will have normal, intermediate or low activity.

In a normal situation, the transporter protein produces a high excretion of the drug. In this case, the person is a carrier of the CC allele (two cytokines). But if you only have one cytosine, combined with one thymine (both are pyrimidine bases), the expression of the gene is not as good, and the expulsion activity is lower, giving an intermediate situation. In contrast, if a person has two thymines (TT), the expression of the P glycoprotein in the cell membrane will be low. This will suppose a smaller activity of the responsible gene and, consequently, greater absorption in blood since the drug is not excreted. This polymorphism, the TT polymorphism, is dangerous for the patient, since it passes a lot of drug to the blood, being toxic for the patient. Therefore, if the patient is TT the dose will have to be lower.

This example shows us that knowing the genome of each individual and how their genetic code acts based on it, we can know if the administration of a drug to an individual will be appropriate or not. And based on this, we can prescribe another medication that is better suited to this person’s genetics.

 APPLICATIONS OF THE PHARMACOGENETICS

The applications of these disciplines of precision medicine are many. Among them are optimizing the dose, choosing the right drug, giving a prognosis of the patient, diagnosing them, applying gene therapy, monitoring the progress of a person, developing new drugs and predicting possible adverse responses.

The advances that have taken place in genomics, the design of drugs, therapies and diagnostics for different pathologies, have advanced markedly in recent years, and have given way to the birth of a medicine more adapted to the characteristics of each patient. We are, therefore, on the threshold of a new way of understanding diseases and medicine.

And this occurs at a time when you want to leave behind the world of patients who, in the face of illness or discomfort, are treated and diagnosed in the same way. By routine, they are prescribed the same medications and doses. For this reason, the need has arisen for a scientific alternative that, based on the genetic code, offers to treat the patient individually.

REFERENCES

• Goldstein, DB et al. (2003) Pharmacogenetics goes genomic. Nature Review Genetics 4:937-947
• Roden, DM et al. (2002) The genetic basis of variability in drug responses. Nature Reviews Drug Discovery 1:37-44
• Wang, L (2010) Pharmacogenomics: a system approach. Syst Biol Med 2:3-22
• Ramos, M. et al. (2017) El código genético, el secreto de la vida. RBA Libros
• Main picture: Duke Center for Applied Genomics & Precision Medicine

 

From lab to big screen (I)

A little more than a month for the great gala of the cinema, the Oscars, I present some films related to genetics. There is a variety of feature films, especially sci-fi. For this reason, this is the first of several articles about cinema. In this article I will focus on films based on genetic diseases.

WONDER (2017)

Director: Stephen Chbosky

Cast: Jacob Tremblay, Julia Roberts, Owen Wilson

Genre: Drama

Story line: A 10 years-old boy born with a facial deformity is destined to fit in at a new school, and to make everyone understand he is just another ordinary kid, and that beauty is not skin deep.

Relation with genetics: Auggie suffers Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. This condition affects an estimated 1 in 50,000 people. In most cases, it is due to a genetic mutation of chromosome 5. Specifically, in the gene TCOF1, involved in the development of bones and other tissues of the face.

Video 1. Wonder trailer (Source: YouTube)

JULIA’S EYES (2010)

Director: Guillem Morales

Cast: Belén Rueda, Lluís Homar, Julia Gutiérrez Caba

Genre: Terror

Story line: It tells the story of a woman slowly going blind, the death of her twin sister tries to uncover the mysterious.

Relation with genetics: Both Julia and her sister suffer from retinitis pigmentosa. This disease causes the progressive loss of vision, affecting the retina, which is the layer of light-sensitive tissue in the back of the eye.

The first symptoms tend to be the loss of night vision and difficult to guide in low light. Later, the disease produces the appearance of blind spots in the lateral vision. With the passage of time, these blind spots come together producing a tunnel vision (Figure 1). Finally, this leads to blindness.

Figure 1. Comparison between normal view and view wtih retinitis pigmentosa (Source: EyeHealthWeb)

The inheritance pattern can be autosomal dominant, recessive or linked to the X chromosome. In the first case, a single copy of the altered gene in each cell is sufficient to cause the disease. Most people with autosomal dominant retinitis pigmentosa have an affected father and other family members with the disorder.

Video 2. Julia’s eyes trailer (Source: YouTube)

MY SISTER’S KEEPER (2009)

Director: Nick Cassavetes

Cast: Cameron Díaz, Abigail Breslin, Alec Baldwin

Genre: Drama

Story line: Sara and Brian Fitzgerald’s life with their young son and their two-year-old daughter, Kate, is forever altered when they learn that Kate has leukaemia. The parents’ only hope is to conceive another child, Anna, specifically intended to save Kate’s life. Kate and Anna share a bond closer than most sisters: though Kate is older her life depends on Anna. Until Anna, now 11, says “no. Seeking medical emancipation, she hires her own lawyer, initiating a court case that divides the family and that could leave Kate’s rapidly failing body in the hands of fate.

Relation with genetics: Leukemias are the first type of cancer in which genetic alterations were described, such as translocations, which are the most frequent (more than 50% of cases). In addition, these have high prognosis and diagnostic value. There are many types of leukemias, therefore it is a diverse group of blood cancers, which affect blood cells and bone marrow. It is the most frequent type of cancer in children; however, it affects more adults than children.

A first classification is based on the lineage: lymphoid (blood-forming cells) or myeloid (cells of the bone marrow). At the same time, you are (lymphoid or myeloid) also classified according to the clinical presentation: acute (symptoms in short period of time and severe symptoms) or chronic (the time is longer).

In adults, acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) are more frequent, while in children it is acute lymphoblastic leukemia (ALL).

Video 3. My sister’s keeper trailer (Source: YouTube)

LORENZO’S OIL (1992)

Director: George Miller

Cast: Nick Nolte, Susan Sarandon, Peter Ustinov

Genre: Drama

Story line: The story concerns 5-years-old Lorenzo, suffering mightily from an apparently incurable and degenerative brain illness called ALD. His parents, an economist and a linguist, refuse to accept the received wisdom that there is no hope, and set about learning biochemistry to pursue a cure on their own. The film becomes an intriguing scientific mystery mixed with a story of pain, grief, and the strain on the two adults.

Relation with genetics: Lorenzo suffers from adrenoleukodystrophy (ADL) or also known as Schilder’s disease. It is a disease that mainly affects boys, since it has a pattern of inheritance linked to the X chromosome. It is in this chromosome where the ABCD1 gene is located, involved in the transport of very long chain fatty acids in peroxisomes (organelles involved in the metabolism of fatty acids).

It mainly affects the nervous system and the adrenal glands, which are small glands located in the upper part of each kidney. In this disorder, myelin deteriorates, the coating that isolates the nerves in the brain and spinal cord, reducing the ability of the nerves to transmit information to the brain. In addition, damage to the outer layer of the adrenal glands cause a shortage of certain hormones, resulting in weakness, weight loss, changes in the skin, vomiting and coma.

Video 4. Lorenzo’s oil trailer (Source: YouTube)

REFERENCES

• FilmAffinity
• SensaCine
• Fotogramas
• Genetics Home Reference
• OMIM
• Asociación Nacional del Síndrome de Treacher Collins
• Asociación de Afectados de Retinosis Pigmentaria de Euskadi
• EcuRed

What is gene therapy?

In the last years we have heard discuss gene therapy and its potential. However, do we know what gene therapy is? In this article, I want to make known this promising tool that can cure some diseases that therapies with conventional drugs cannot it. I discuss approaches of gene therapy and their key aspects, where we find animal models.

INTRODUCTION

A clinical trial is an experimental study realized in patients and healthy subjects with the goal to evaluate the efficiency and/or security of one or various therapeutics procedures and, also, to know the effects produced in the human organism.

Since the first human trial in 1990, gene therapy has generated great expectations in society. After over 20 years, there are a lot of gene therapy protocols have reached the clinical stage.

Before applying gene therapy in humans it is necessary to do preclinical studies; these are in vitro or in vivo investigations before moving to clinical trials with humans. The aim of these is protect humans of toxic effects that the studied drug may have.

An important element in preclinical studies are animal models. First, tests are made with small animals like mice. If they are successful, then tests are made with larger animals, like dogs. Finally, if these studies give good results then they are passed to higher animals: primates or humans.

WHAT IS GENE THERAPY?

Gene therapy represents a promising tool to cure some of those diseases that conventional drug therapies cannot. This therapy consists in the transfer of genetic material into cells or tissues to prevent or cure a disease.

Initially gene therapy was established to treat patients with hereditary diseases caused by single gene defects, but now, at present, many gene therapy efforts are also focused on curing polygenic or non-inherited diseases with high prevalence (Video 1).

Video 1. Explanation about what gene therapy is (Source: YouTube)

APPROACHES IN GENE THERAPY

There are two types of approaches in gene therapy (Figure 1):

• In vivo gene therapy: introduce a therapeutic gene into a vector which then is administered directly to the patient. The vector will transfer the gene of interest in the target tissue to produce the therapeutic protein.
• Ex vivo gene therapy: transfer the vector carrying the therapeutic gene into cultured cells from the patient. After, these genetically engineered cells are reintroduced to the patients where they now express the therapeutic protein.

Figure 1. Differences between the two types of approaches in gene therapy (Source: CliniGene – Gene Therapy European Network)

KEY ASPECTS OF GENE THERAPY

When designing a gene therapy approach there are some key aspects to be considered:

1/ THERAPEUTIC GENE

The gene of interest is that which is introduced into the body to counteract the disease. For the one hand, for the diseases are caused by the lost or dysfunction of a single protein, the gene to be transferred is more identifiable, being that only a correct copy of the gene whose dysfunction causes the diseases will be introduced. For the other hand, for the diseases whose origin is more complex the choice of the therapeutic gene may be more difficult and will have to make several studies and know well the disease.

2/ VECTOR

Vehicle by which the gene of interest is transported to the target cells. The perfect vector should be able to transduce target cells without activating an immune response either against itself or the therapeutic gene. But there aren’t a universal vector to treat any disease.

2.1/ VIRAL VECTORS

These type of vectors derives from viruses, but this is not a problem because much or all of the viral genes are replaced by the therapeutic gene. This means that the viral vectors do not cause pathogenic disease because the gene was deleted.

2.2/ NON-VIRAL VECTORS

These type of vectors does not derive from viruses, but the therapeutic gene is part of a plasmid.

3/ TARGET CELLS

Any cell that has a specific receptor for an antigen or antibody, or hormone or drug… The therapeutic gene must be directed to target cells in specific tissues.

4/ ROUTES OF ADMINISTRATION

The therapeutic gene must be administered through the most appropriate route. The type of route depends, as like as vector, the target tissue, the organ to manipulate or the disease to be treated.

5/ ANIMAL MODELS

Are used to find out what happens in a living organism. They are mainly used in research to achieve progress of scientific knowledge, as many basic cellular processes are the same in all animals and can understand what happens to the body when it has a defect; as models for the study of a disease, because humans and animals share many diseases and how to respond to the immune system; to develop and test potential methods of treatment, being an essential part of applying biological research to real medical problems and allowing the identification of new targets for the intervention of the disease; and, finally, to protect the safety of people, animals and environment, researchers have measured the effects of beneficial and harmful compound on an organism, identifying possible problems and determine the dose administration.

Gene therapy represents a promising tool to cure some of those diseases that conventional drug therapies cannot. The availability of animal models is key to preclinical phases because it allows thorough evaluation of safety and efficacy of gene therapy protocols prior to any human clinical trials.

In the near future, gene therapy will be an effective alternative to pharmacological efforts, and enable treatment of many diseases that are refractory or not suitable for pharmacologic treatment alone. Thus, gene therapy is a therapeutic tool that gives us virtually unlimited possibilities to develop better and more effective therapies for previously incurable diseases.

REFERENCES

• Ramos Muntada M. “Animal Models for Gene Therapy of Glycogenosis” Final Degree Project. UAB, Genetics Bachelor’s Degree 2015
• Bosch F, Roca C, Anguela X and Ruzo A. “Gene Therapy, a new tool to cure human diseases” CliniGene-NoE. CBATEG-UAB 2011, CliniGene – Gene Therapy European Network
• Gene Therapy Technology Explained
• Australian Clinical Trials
• Main picture: Genetic Literacy Project

21st March: world Down syndrome day

21st March is the World Down Syndrome Day. This syndrome is a chromosomal combination that has always been part of the human condition. It exists in all regions of the world, and usually it has variable effects on learning styles, physical characteristics or health. It affects 1 in 700 children, making it the most common chromosomal abnormality and the first cause of mental disability. With this article I want to introduce a little more this syndrome.

WHY IS IT CALLED THAT?

Its name comes from the English doctor John Langdon Down who described a group of patients with intellectual disabilities and similar physical characteristics, in 1866. These patients had Down syndrome.

However, already existed artworks with people with Down syndrome (Figure 1), but Langdon Down was the first one to group them in a subcategory within individual with cognitive impairment.

Figure 1. “The Adoration of the Christ Child” (1515). This oil painting, made by a follower of Jan Joest van Kalkar, shows two people with Down syndrome (Source: Arte y síndrome de Down)

It is called syndrome because the affected people express a known set of symptoms or signs that they may appear together, although its origin is unknown. Even though physical features are common, each person with Down syndrome is a unique individual and can present the characteristics in different degrees or not.

WHAT ARE THE FEATURES THAT CHARACTERIZE THEM?

• Diminished muscle tone
• Small ears
• Slanting eyes
• Short nose
• Flat back of head
• Single crease in the palm of the hand: simian crease: complete fusion between heart line and headline (Figure 2)
• Tendency to obesity

Figure 2. (1) Common lines, like M, and (2) simian crease, complete fusion between heart line and headline (Source: Incidencia de nacimientos pretérmino y de término con peso bajo al nacer y existencia de línea Sydney)

When they are children present retardation in reaching capabilities as sitting independently, wandering, first words…

WHICH IS THE ROLE OF GENETICS?

In 1959, Jérôme Lejeune, a French doctor, saw that people with Down syndrome had 47 chromosomes in each cell instead of 46. This extra chromosome was 21 (Figure 3). The article  Why I look similar to my parents? reminds us what a chromosome is.

Figure 3. Male karyotype, person with Down syndrome (Source: Mireia Ramos, Cerba Internacional SAE)

So, Down syndrome or trisomy 21, is a result of an extra chromosome. But having and extra copy of chromosome 21 can be given by three phenomena.

NONDISJUNCTION

It is the major cause and represents 95% of cases. It is produced by an error in the process of cell division. It means that when parent’s cell divides there is an error, and the son inherits two copies of chromosome 21 instead of one.

Then the son has 3 chromosomes 21: 1 comes from one parent and 2 come from the other parent, which are transmitted together.

TRANSLOCATION

During the process of cell division of one parent, a chromosome 21 joins with other chromosome, usually a chromosome 14.

Then the son has 3 chromosomes 21: one comes from one parent and two come from the other parent.

It represents 4% of cases, and it is important to identify it to avoid passing the translocation to another child, if the couple wants another child.

MOSAICISM

It is the least common cause because it represents 1% of cases. After fertilization nondisjunction occurs, but not in all cells. This causes cells with 46 chromosomes and cells with 47, forming a mosaic.

Cells with 47 chromosomes have an extra chromosome 21.

HAVING A CHILD WITH DOWN SYNDROME

It has been found that the age of the mother is related to have a child with Down syndrome, i.e., the risk of having a baby with Down syndrome is greater among mother age 35 and older.

Trisomy 21 is the most trisomy accepted by nature, so in pregnancy test doctors always study it. If they detect a foetus has Down syndrome, the couple can choose to go ahead or to stop pregnancy.

People with Down syndrome are increasingly integrated into our society. Their IQ is 45-48, when the standard range is around 100, but with a special school integration support is highly beneficial and IQ can go up to 70.

Nowadays, more and more companies offering workplaces for them and this should not surprise us, because after all they only have an extra chromosome (Figure 4).

Figure 4. Keep calm it’s only and extra chromosome (Source: Pinterest)

REFERENCES

• Naciones Unidas: Día Mundial del síndrome de Down
• World Down Syndrome Day
• National Down Syndrome Society
• Medline Plus
• Down España

 

Why I look similar to my parents?

The reason of the similitude with our parents is genetics. This science studies the inheritance; it means how offspring resemble their parents, the diseases that are transmitted from generation to generation… It is biology’s discipline growing quickly and it affects biology, healthy and society in general. In this article I am going to talk about what is genetics and the DNA’s discovery.

HOW GENETIC INFORMATION IS INHERITED?

The genetic information is inherited to the offspring by genes, which are the storage unit of this information. They are located inside the chromosomes and they occupy specific positions. The number of chromosomes is constant inside species, but different between other species.

In humans the number of chromosomes is 46. In each cell we have 46 chromosomes, which 44 are autosomal, i.e., not a chromosome sexual and 2 chromosomes sexual. The total of 46 chromosomes is the human genome.

Our genome consist of 2 sets of 23 chromosomes counterparts. This means that each set have the same characteristics respect the other set and one comes from our mother by ovum and the other one comes from our father by sperm (Figure 1). Inherit each set of our progenitor is the reason why we resemble they, but also is via that we inherit some genetic diseases.

Figure 1. Human female karyotype, i.e., the graphical representation of chromosomes. They are placed in pairs sorted and size, from the largest to the pair smaller, plus the sex chromosomes (Source: Mireia Ramos, Cerba Internacional SAE)

CHEMISTRY OF GENES

Genes are parts of DNA (deoxyribonucleic acid), comprising by the join of small molecules that called nucleotide. These nucleotides contain a pentose (compound of 5 carbon), a phosphate and a nucleobase (organic compound with an atom of nitrogen) (Figure 2). There are 4 nucleobase: two purines (adenine and guanine) and two pyrimidines (thymine and cytosine). These nucleobases distinguish each nucleotide and their arrangement constitutes the genetic code.

Figure 2. Details of the chemistry of DNA (Source: Eduredes: Los ácidos nucleicos)

But all knowledge about DNA and genes is recent. The structure of DNA was discovered by James Watson and Francis Crick in 1953 in Cambridge (Figure 3). Previously, other scientists had done studies to try to determine the similarity between relatives, but it was not until this discovery it was understood that there was chemistry behind it.

Figure 3. Francis Crick (right) and James Watson (left) with the construction of the structure of DNA (Source: The DNA store)

THE BEGINNING OF THEIR STORY

Watson, an American 23 year-old biologist, and Crick, an English 35 year-old physicist, worked in the Cavendish Laboratory in Cambridge. They spent many months building models of molecules and comparing them to the information they had, but still they couldn’t find the correct structure of DNA.

In the King’s College of London, the physicist Maurice Wilkins and Rosalind Franklin, another physicist with knowledge in crystallography. She took X-ray pictures of DNA (Figure 4).

Figure 4. The four people who contributed to the discovery of DNA (Source: Biology: The people responsible for the discovery of DNA)

Watson and Crick, after present a wrong model of the triple helix, told Maurice Wilkins about what they were trying to do and he showed them a new and better X-ray picture of DNA, which had been taken by Rosalind Franklin, without her permission. This was the picture number 51 to help them solve the mystery (Figure 5).

Figure 5. Explanation of picture 51 that used Watson and Crick (Source: Seguramente estaré equivocado: La “fotografía 51”)

When the university’s Cavendish Laboratory was still at its old site at nearby Free School Lane, the pub was a popular lunch destination for staff working there. Thus, it became the place where Francis Crick interrupted patrons’ lunchtime on 28th February 1953 to announce that he and James Watson had “discovered the secret of life” after they had come up with their proposal for the structure of DNA. This day is called for someone the 8^th day of Creation.

The 25^th April 1953 it published their article with 900 words in Nature (Figure 6). Three years earlier had published law Chargaff, which was one of the foundations to apply the theory of the double helix of DNA. This law establishes the complementarity of the bases in DNA, i.e., adenine (A) pairs with thymine (T) and the same with guanine (G) and cytosine (C) (Figure 2). So the amount of purine (A and G) is equal to the amount of the pyrimidine (T and C).

Figure 6. Article published in the journal Nature, which shows the picture 51 (Source: The DNA store)

THE IMPORTANCE OF GENETICS

It has been argued that the discovery of DNA as well as our understanding of its structure and function may well be the most important discovery of the last century. The effect of the discovery of DNA on scientific and medical progress has been enormous, whether it involves the identification of the genes that trigger major diseases or the creation and manufacture of drugs to treat these devastating diseases. In fact, the identification of these genes and their subsequent analysis in terms of therapeutic treatment has ultimately influenced science and will continue to do so in the future.

While the discovery of DNA has been a significant one in the twentieth century, it will continue to revolutionize medicine, agriculture, forensics, paternity and many other important fields in society today. DNA research encompasses an evolving area of progress and continued funding and interest in its relevance will likely fuel new discoveries in the future.

REFERENCES

• Course notes of Genetics, Bachelor’s Degree (UAB)
• Universitat Autònoma de Barcelona: Genetic’s Degree
• Proyecto Biosfera: La materia viva
• The Guardian: DNA double helix
• Explore DNA

Evolution for beginners

Biological evolution is still not well understood by general public, and when we speak of it in our language abound expressions that confuse even more how mechanisms that lead to species diversity work. Through questions you may have ever asked yourself, in this article we will have a first look at the basic principles of evolution and debunk misconceptions about it.

IS EVOLUTION REAL? IT IS NOT JUST A THEORY OR AN IDEA WITHOUT EVIDENCES?

Outside the scientific field, the word “theory” is used to refer to events that have not been tested or assumptions. But a scientific theory is the explanation of a phenomenon supported by evidence resulting from the application of the scientific method.

The scientific method. Image by Margreet de Heer.

Theories can be modified, improved or revised if new data don’t continue to support the theory, but they are always based on some data, repeatable and verifiable experiments by any researcher to be considered valid.

So few people (sic) doubts about the heliocentric theory (the Earth rotates around the Sun), or the gravitational theory of Newton, but in the popular imagination some people believe that the theory of evolution made by Charles Darwin (and Alfred Russell Wallace) is simply a hypothesis and has no evidence to support it. With new scientific advances, his theory has been improved and detailed, but more than 150 years later, nobody has been able to prove it wrong, just the contrary.

WHAT EVIDENCE WE HAVE THAT EVOLUTION IS TRUE?

We have many evidences and in this post we will not delve into them. Some of the evidence available to us are:

• Paleontological record: the study of fossils tell us about the similarities and differences of existing species with others thousands or millions old, and to establish relationships respect each other.
• Comparative anatomy: comparison of certain structures that are very similar between different organisms, can establish whether they have a common ancestor (homologous structures, for example, five fingers in some vertebrates) if they have developed similar adaptations (analogous structures, for example, the wings of birds and insects), or if they have lost their function (vestigial organs, such as the appendix).

Homologous organs in humans, cats, whales and bats

• Embryology: the study of embryos of related groups shows a strong resemblance in the earliest stages of development.
• Biogeography: The study of the geographical distribution of living beings reveals that species generally inhabit the same regions as their ancestors, although there are other regions with similar climates.
• Biochemistry and genetics: chemical similarities and differences allow to establish relationships among different species. For example, species closely related to each other have a structure of their DNA more similar than others more distant. All living beings share a portion of DNA that is part of your “instructions”, so there are also found in a fly, a plant or a bacterium, proof that all living things have a common ancestor.

IS IT TRUE THAT ORGANISMS ADAPT TO THE ENVIRONMENT AND ARE DESIGNED FOR LIVING IN THEIR HABITAT?

Both expressions, frequently used, mean that living beings have an active role to adapt to the environment or “someone” has designed them to live exactly where they are. It is a typical example of Lamarck and giraffes: as a result of stretching the neck to reach the higher leaves of the trees,  currently giraffes have this neck for giving it this use. They have a necessity, they change their bodies to success. It is precisely upside down: it is the habitat that selects the fittest, nature “selects” those that are most effective to survive, and therefore reproduce. It is what is known as natural selection, one of the main mechanisms of evolution. It needs three requirements to act:

• Phenotypic variability: there must be differences between individuals. Some giraffes necks were slightly longer than others, just as there are taller people than others, with blue or brown eyes.
• Biological fitness: this difference has to suppose an advantage. For example, giraffes with a slightly longer neck could survive and reproduce, while the others don’t.
  
• Heredity: these characters must be transmitted to the next generation, the offspring will be slightly different to that feature, while “short neck” feature transmits less and less.

The variability in the population causes individuals with favorable characteristics to reproduce more and pass on their genes to the next generation, increasing the proportion of those genes. Image taken from Understanding evolution

Over the years these changes are accumulated until the genetic differences are so big that some populations may not mate with others: a new species has appeared.

If you thought that this is similar to artificial selection that we do with the different breeds of dogs, cows who give more milk, trees bearing more fruit and larger, congratulations, you think like Darwin as it was inspired by some of these facts. Therefore, living beings are mere spectators of the evolutionary process, depending of changes in their habitat and their genetic material.

WHY ORGANISMS ARE SO DIVERSE?

Genetic variability allows natural selection act. Changes in the genetic material (usually DNA) are caused by:

• Mutations: changes in the genome that may be adverse or lethal for survival, indifferent or beneficial to survival and reproduction. If they have benefits, they will pass to the next generations.
• Gene flow: is the motion of genes between populations (migration of individuals allows this exchange when mate with others in a different population).
• Sexual reproduction: allows recombination of genetic material of different individuals, giving rise to new combinations of DNA.

Populations that have more genetic variability are more likely to survive if happen any changes in their habitat. Populations with less variability (eg, being geographically isolated) are more sensitive to any changes in their habitat, which may cause their extinction.

Evolution can be observed in beings with a very high reproduction rate, for example bacteria, since mutations accumulate more quickly. Have you ever heard that bacteria become resistant to our antibiotics or some insects to pesticides? They evolve so quickly that within a few years were selected the fittest to survive our antibiotics.

ARE WE THE MOST EVOLVED ANIMALS?

Theory of Evolution has various consequences, such as the existence of a common ancestor and that therefore, that we are animals. Even today, and even among the young ones, there is the idea that we are something different between living beings and we are in a special podium in the collective imagination. This anthropocentric thinking caused Darwin mockery and confrontations over 150 years ago.

Caricature of Darwin as an orangutan. Public domain image first published in 1871

We use our language to be “more evolved” as a synonym for more complex, and we consider ourselves one species that has reached a high level of understanding of their environment, so many people believe that evolution has come to an end with us.

The question has a mistake of formulation: actually evolving pursues no end, it just happens, and the fact that millions of years allows the emergence of complex structures, it does not mean that simpler lifeforms are not perfectly matched in the habitat where they are. Bacteria, algae, sharks, crocodiles, etc., have remained very similar over millions of years. Evolution is a process that started acting when life first appeared and continues to act in all organisms, including us, although we have changed the way in which natural selection works  (medical and technological breakthroughs, etc.).

SO IF WE COME FROM MONKEYS, WHY DO STILL MONKEYS EXIST?

The truth is that we don’t come from monkeys, we are monkeys, or to be more rigorous, apes. We have not evolved from any existing primate. As we saw in a previous post, humans and other primates share a common ancestor and natural selection has been acting differently in each of us. That is, evolution has to be viewed as a tree, and not as a straight line, where each branch would be a species .

First scheme of the evolutionary tree of Darwin in his notebook (1837). Public domain image.

Some branches stop growing (species become extinct), while others continue to diversify. The same applies to other species, in case you have asked yourself, “if amphibians come from fish, why are there still fish?”. Currently, genetic analyzes have contributed so much data that they make so difficult to redesign the classical Dariwn’s tree.

Classification of live organisms based on the three domains Archaea, Bacteria and Eukarya, data of Carl R. Woese (1990). Included in Eukarya there are the Protista, Fungi, Plantae and Animalia kingdoms. Image by Rita Daniela Fernández.

Evolution is a very broad topic that still generates doubts and controversies. In this article we have tried to bring to uninitiated people some basics, where we can delve into the future. Do you have any questions about evolution? Are you interested into a subject that we have not talked about? You can leave your comments below.

REFERENCES

• Darwin’s Tree of Life is a Tangled Bramble Bush
• Algunas reflexiones sobre la clasificación de los seres vivos
• Museos vivos. Evidencias de la evolución
• Las ideas en la ciencia: Teoría, hipótesis y leyes
• Frequently asked questions about evolution
• Brock et. al. 1999. Biología de los microorganismos. Ed. Prentice Hall.
• Massa, Renato. El origen de la vida. La evolución de las especies. Ed. Susaeta.
• Cover image