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

Insulin: a point in favour for transgenics

Despite the arguments and positions against transgenics, it is undeniable that insulin is a great transgenic success. It is essential in some types of diabetes; and since it was discovered, the life expectancy of diabetics has increased more than 45 years. Therefore, let’s know in detail.

REMINDER OF GENETIC ENGINEERING

Genetic engineering allows to clone, that is, to multiply DNA fragments and produce the proteins for which these genes encode in organisms different from the one of origin. That is, if in an organism there is an alteration or mutation of a gene that prevents the genetic code from translating it into proteins, with the techniques of recombinant DNA a gene is obtained without the mutation in another organism. Thus, it is possible to obtain proteins of interest in organisms different from the original from which the gene was extracted, improve crops and animals, produce drugs and obtain proteins that use different industries in their manufacturing processes. In other words, through genetic engineering, the famous transgenics are obtained.

They offer many possibilities in the industrial use of microorganisms with applications ranging from the recombinant production of therapeutic drugs and vaccines to food and agricultural products. But, in addition, they have a promising role in medicine and in the cure of diseases.

And is that the result of obtaining a recombinant DNA, from it, will be made a new protein, called recombinant protein. An example of this is the case of insulin.

WHAT IS INSULIN?

Insulin is a hormone produced in the pancreas and with an important role in the metabolic process. Insulin comes from the Latin insulae, which means island. Its name is due to the fact that inside the pancreas, insulin is produced in the islets of Langerhans. The pancreas is related to the general functioning of the organism. It is located in the abdomen and is surrounded by organs such as the liver, spleen, stomach, small intestine and gallbladder.

Thanks to it we use the energy of the food that enters our body. And this happens because it allows glucose to enter our body. This is how it provides us with the necessary energy for the activities we must perform, from breathing to running (Video 1).

Video 1. Insulin, Glucose and You (Source: YouTube)

HOW DOES INSULIN WORK?

Insulin helps glucose enter the cells, like a key that opens the lock on the cell doors so that glucose, which is blood sugar, enters and is used as energy (Figure 1). If glucose cannot enter because there is no key to open the door, as with people with diabetes, blood glucose builds up. An accumulation of sugar in the blood can cause long-term complications. That’s why it’s important for diabetics to inject insulin.

Figure 1. Picture of the funcioning of insulin in cells (Source: Encuentra tu balance)

WHY DO WE USE TRANSGENIC INSULIN?

First, the insulin obtained from animals such as dogs, pigs or cows was used. But although, above all, pork insulin was very similar to human insulin, it was not identical and contained some impurities. This fact caused rejection and, in some cases, allergies. In addition, to be obtained from the pancreas of pigs, for each pancreas only insulin was obtained for the treatment of 3 days (at more than the cost of care of the animal). The result was low performance and high costs.

But with recombinant DNA insulins, more is obtained at a lower cost. For this reason, currently, the original insulin is obtained from a human of genetic engineering, despite the fact that animal insulins are still a perfectly acceptable alternative.

Through genetic engineering, insulin has been produced from the E. coli bacterium. It was in 1978 when the sequence of the insulin was obtained and introduced inside the bacteria so that it produced insulin. This is how E. coli has gone from being a common bacterium to a factory producing insulin. Insulin is extracted from the bacteria, purified and marketed as a medicine.

The advantages of “human” insulin, obtained by genetic engineering, are the easy maintenance of bacteria, a greater quantity of production and with lower costs. More or more, the compatibility of this insulin is 100%, however there may be reactions due to other components.

On an industrial scale, the production of recombinant proteins encompasses different stages. These stages are fermentation, in which the bacteria are cultivated in nutritious culture media; the extraction to recover all the proteins inside, the purification, which separates the recombinant protein from the other bacterial proteins; and finally the formulation, where the recombinant protein is modified to achieve a stable and sterile form that can be administered therapeutically.

Each of the previous phases implies a very careful handling of the materials and a strict quality control to optimize the extraction, purity, activity and stability of the drug. This process can be simple or more complex depending on the product and the type of cell used. Although the complexity of the process would increase the final cost of the product, the value will not exceed the expense of isolating the compound from its original source to reach medicinal quantities, which is what we have shown with insulin. That is, producing human insulin has a lower cost than obtaining insulin from pigs.

Genetic engineering allows numerous potentially therapeutic proteins to be made in large quantities. Currently, there are more than 30 proteins approved for clinical use, in addition to hundreds of therapeutic protein genes that have been expressed at the laboratory level and that studies continue to demonstrate their clinical adequacy.

REFERENCES

• Ramos, M. et al. El código genético, el secreto de la vida (2017) RBA Libros
• Alberts, B. et al. Biología molecular de la célula (2010). Editorial Omega, 5a edición
• Cooper, G.M., Hausman R.E. La Célula (2009). Editorial Marbán, 5a edición
• Naukas
• Vix
• Main picture: UniversList

The reality of mutations

Do you remember the ninja turtles? Leonardo, Raphael, Michelangelo and Donatello were four turtles that suffered a mutation when they were bathed with a radioactive liquid. Fortunately or unfortunately, a mutation cannot turn us into ninja turtles, but it can have other effects. Next, I tell you what mutations are.

WHAT ARE MUTATIONS?

Our body is like a great factory in which our cells are the workers. These, thanks to their internal machinery, make the factory stay afloat with the least possible problems. The constant operation of our cells (24/7), sometimes causes errors in their machinery. This generates imperfections in the genetic code, which generally go unnoticed. It is true that cells do everything possible to fix the failures produced, but sometimes they are inevitable and lead to the generation of diseases or even to the death of the cell.

Mutations are these small errors, it means, mutations are stable and inheritable changes that alter the DNA sequence. This fact introduces new genetic variants in the population, generating genetic diversity.

Generally, mutations tend to be eliminated, but occasionally some can succeed and escape the DNA repair mechanisms of our cells. However, they only remain stable and inheritable in the DNA if they affect a cell type, the germ cells.

The organisms that reproduce sexually have two types of cells: germinal and somatic. While the former transmit genetic information from parents to children, somatic cells form the body of the organism. Because the information of germ cells, which are what will give rise to gametes (sperm and oocytes) passed from generation to generation, they must be protected against different genetic changes to safeguard each individual.

Most mutations are harmful, species cannot allow the accumulation of large number of mutations in their germ cells. For this reason not all mutations are fixed in the population, and many of these variants are usually eliminated. Occasionally some may be incorporated into all individuals of the species.

The mutation rate is the frequency at which new mutations occur in a gene. Each specie has a mutation rate of its own, modulated by natural selection. This implies that each species can be confronted differently from the changes produced by the environment.

Spontaneous mutation rates are very low, in the order of 10^-5-10-⁶ per gene and generation. In this way, mutations do not produce rapid changes in the population.

THE ROLE OF NATURAL SELECTION

Changes of nucleotides in somatic cells can give rise to variant or mutant cells, some of which, through natural selection, get more advantageous with respect to their partners and proliferate very fast, giving us as a result, in the extreme case, cancer, that is, uncontrolled cell proliferation. Some of the cells in the body begin to divide without stopping and spread to surrounding tissues, a process known as metastasis

But the best way to understand the role of natural selection of which the naturist Charles Darwin spoke is with the example of spotted moths (Biston betularia). In England there are two types of moths, those of white colour and those of black colour (Figure 1). The former used to be the most common, but between 1848 and 1898 black moths were imposed.

Figure 1. Biston betularia, white and black moths (Source: TorruBlog)

This change occurred at the same time that cities became more industrial, in which coal became the main fuel for power plants. The soot of this rock dyed the sky, the soil and the buildings of the cities black. Tree trunks were also affected, where the moths were camouflaged.

The consequence of this fact was that white moths could not hide from their predators, whereas those that were black found a successful exit camouflaging well on the tinted trunks. With the change of colour of their hiding place they had more opportunities to survive and reproduce (Video 1).

Video 1. Industrial melanism, white and black moth (Source: YouTube)

This is a clear example of how changes in the environment influence the variability of gene frequencies, which vary in response to new factors in the environment.

TYPES OF MUTATIONS

There is no single type of mutation, but there are several types of mutation that can affect the DNA sequence and, rebound, the genetic code. However, not all mutations have the same effect.

There are many and different types of mutations, which are classified by mutational levels. These levels are based on the amount of hereditary material affected by the mutation and go up in rank according to the number of genes involved. If the mutation affects only one gene we speak of gene mutation, whereas if it affects a chromosomal segment that includes several genes we refer to chromosomal mutation. When the mutation affects the genome, affecting whole chromosomes by excess or by defect, we speak of genomic mutation.

An example of a point mutation is found in cystic fibrosis, a hereditary genetic disease that produces an alteration in the secretion of mucus, affecting the respiratory and digestive systems. A point mutation affects the gene that codes for the CFTR protein. The affected people receive from both parents the defective gene, which, having no copy of the good gene, the protein will not be functional. The result is that the secretions produced by the human body are thicker than usual, producing an accumulation in the respiratory tract.

REFERENCES

• Ramos, M. et al. El código genético, el secreto de la vida (2017) RBA Libros
• Alberts, B. et al. Biología molecular de la célula (2010). Editorial Omega, 5a edición
• Cooper, G.M., Hausman R.E. La Célula (2009). Editorial Marbán, 5a edición
• Bioinformática UAB
• Webs UCM
• Main picture: Cine Premiere

Rare diseases: fight against oblivion

We are ending the month of February, and this means that the Rare Disease Day is approaching. Marfan syndrome, Williams syndrome, DiGeorge syndrome, Crohn’s disease, Fanconi anaemia, mucopolysaccharidosis, among many others make up the list of these diseases. Why are they called minority diseases or rare diseases?

WHAT ARE MINORITY DISEASES?

A minority disease is that which affects less than 1 in 2,000 people. Although individually they are rare, there are many diseases of this type (6,000-7,000), so there are many affected patients.

Although the definition of minority disease is what I have just said, in the pharmaceutical industry it is that disease in which it is not profitable to develop a drug due to the low number of patients, the limited information available, the poor diagnosis, the lack of clinical studies and the difficult location of patients. It is for this reason that the families themselves create their own foundations to obtain financing for the investigation of these diseases.

A few years ago these diseases were socially forgotten, but, fortunately, they are now socially transcendental and recognized.

As I said, there are around 7,000 minority diseases described and every year between 150 and 250 new ones are described, thanks to new technologies.

A large number of these diseases affects children, that is, they manifest themselves at an early age. It is necessary to know that most have a genetic basis, caused by mutations in specific genes such as cystic fibrosis or several muscular dystrophies. But there are also related to environmental factors, such as some types of anaemia due to lack of vitamins or due to medications. This is the case of malignant mesothelioma, a breast cancer, in which more than 90% of cases are due to asbestos exposure. However, there are still many without knowing their origin or data on their prevalence.

MINORITY DISEASES IN NUMBERS

The fact that these diseases affect few people and the ignorance of their symptoms by the public and professionals, it is estimated that the time that elapses between the appearances of the first symptoms until diagnosis is 5 years. In 1 of every 5 cases, more than 10 years may pass until the correct diagnosis is obtained. This means not receiving support or treatment or receiving inadequate treatment and worsening the disease.

Not all hospitals have the means to treat those affected, for this reason it is estimated that practically half of sufferers have had to travel and travel in the last 2 years out of their province because of their illness, either in look for a diagnosis or treatment.

Minor diseases represent a significant economic cost. The cost of diagnosis and treatment accounts for around 20% of the annual income of each affected family. This means an average of more than 350€ per family per month, a figure very representative of the high cost involved in the care of rare diseases. The expenses to cover in the majority of cases are related to the acquisition of medicines and other health products, medical treatment, technical aids and orthopaedics, adapted transport, personal assistance and adaptation to housing.

TREATMENT FOR MINORITY DISEASES

Only 1-2% of minority diseases currently have some type of treatment, therefore, much remains to be investigated.

There are 4 basic types of treatment for rare genetic diseases:

PHARMACOLOGICAL THERAPIES

It consists in the modification of a normal or pathological biochemical reaction by an external chemical agent.

The development of a drug is a very expensive process and difficult to quantify. Currently many millions have to be invested for a new drug to reach the patient.

But what is a medication? A medicine is a small organic molecule, which typically has to be:

• Specific to solve a molecular problem (ex: prevent an abnormal interaction between two proteins)
• Very active and very tuned for your target
• Very little toxic
• Distribute well throughout the body and reach the target tissue
• Cheap to produce or, at least, that can be synthesized in industrial quantities
• Stable
• New (patentable)
• It has to be commercialized

GENE THERAPY

Attempt to correct defective genes responsible for diseases in the somatic (non-sexual) line, either by:

• Loss of function: incorporate the normal gene (ex: phenylketonuria)
• Function gain: eliminate the responsible mutation, eliminating the protein (ex: Huntington)

Limitations:

• Only the reversible characteristics of a genetic disease can be corrected
• The size of the DNA to be incorporated in the patient’s genome
• Immune response against the viral vector (retroviruses, adenoviruses, adenoassociates)
• Inactivation of an essential gene that can cause a problem greater than the disease
• Directionally to appropriate target cells

CELLULAR THERAPY

Describes the process of introducing new cells into an affected tissue, with or without previous gene therapy. It is necessary to introduce many cells because the treatment is effective and, sometimes, these cells can go to unwanted tissues or have some types of abnormal growth.

SURGERY

For example in congenital heart defects.

RARE DISEASE DAY

For rare diseases to cease to be, Rare Disease Day is celebrated on the last day of February, with the aim of raising awareness and awareness among the public about rare diseases; as well as showing the impact on patients’ lives and reinforcing their importance as a priority in public health.

It was established in 2008 because, according to the European Organization for Rare Diseases (EURORDIS), the treatment of many rare diseases is insufficient, as well as in social networks to support people with minority diseases and their families. In addition, while there were already many days devoted to people suffering from individual diseases (such as AIDS, cancer, etc.) before there was not a day to represent people suffering from minority diseases. It was chosen on 29^th February because it is a “rare” day. But it is celebrated on the last day of February in years that are not leap years.

Then I leave the promotional video for the Rare Disease Day 2015:

Video 1. Rare Disease Day 2015 Official Video (Source: YouTube)

REFERENCES

• FEDER
• EURORDIS
• Fundación Mehuer
• Rare Disease Day

Cracking the genetic code

In the same way that Alan Turing decoded Enigma, the encryption machine used by the German army in World War II, several scientists managed to decipher the genetic code. The solution to this framework has allowed us to understand how cells work and make genetic manipulation possible.

INTRODUCTION

A code is a system of replacing the words in a message with other words or symbols, so that nobody can understand it unless they know the system. For example the genetic code.

Although it seems to be a lie, all living beings (except for some bacteria) biologically work in the same way. And it is that Jacques Monod already said, everything that is verified as true for E. coli must also be true for elephants.

From the cells of the blue whale, the largest animal on the planet, to the cells of a hummingbird, passing through humans, are the same. This is thanks to the genetic code, which allows the information of each gene to be transmitted to the proteins, the executors of this information.

This flow of information was named by Francis Crick, in 1958, as the central dogma of molecular biology (Figure 1). In it he claimed that information flows from DNA to RNA, and then from RNA to proteins. This is how genetic information is transmitted and expressed unidirectionally. However, later modifications were added. Crick claimed that only DNA can be duplicated and transcribed to RNA. However, it has been seen that the replication of its RNA also occurs in viruses and that it can perform a reverse transcription to generate DNA again.

Figure 1. Central dogma of molecular biology. Red arrows: Francis Crick’s way. Grey arrows: later modifications (Source: Quora)

THREE LANGUAGES OF CELLS

Inside the cells three different languages ​​are spoken, but they can be related through the genetic code.

The one we already know is the language of deoxyribonucleic acid (DNA), wound in a double chain and composed of 4 letters that correspond to the nitrogenous bases: adenine (A), thymine (T), cytosine (C) and guanine (G).

Another language very similar to the latter is that of RNA. It differs from DNA mainly in three aspects: (i) it is composed of a single chain instead of being double-stranded, (ii) its sugars are ribose instead of deoxyribose (hence the name of ribonucleic acid) and (iii) it contains the base uracil (U) instead of T. Neither the change of sugar nor the substitution of U by T alters the pairing with base A, so that RNA synthesis can be performed directly on a DNA template.

The last language that remains for us to know is that of proteins, formed by 20 amino acids. The amino acids constitute each and every one of the proteins of any living organism. The order of the amino acids that form the chain of the protein determines its function (Figure 2).

Figure 2. Table of 20 amino acids (Source: Compound Interest)

THE GENETIC CODE

As we have been saying, the genetic code is the rules that follow the nucleotide sequence of a gene, through the RNA intermediary, to be translated into an amino acid sequence of a protein. There are several types of RNA, but the one that interests us is the messenger RNA (mRNA), essential in the transcription process.
The cells decode the RNA by reading its nucleotides in groups of three (Figure 3). Since mRNA is a polymer of four different nucleotides, there are 64 possible combinations of three nucleotides (4³). This brings us to one of its characteristics: it is degenerate. This means that there are several triplets for the same amino acid (synonymous codons). For example, proline is coded by the triplets CCU, CCC, CCA and CCG.

Figure 3. The genetic code with the table of 20 amino acids (Source: BioNinja)

The genetic code is not ambiguous since each triplet has its own meaning. All triplets make sense, either encode a particular amino acid or indicate read completion. Most amino acids are encoded by at least two codons. Methionine and tryptophan are the only amino acids that are codified only by a codon. But each codon codes only for an amino acid or stop sign. In addition, it is unidirectional, all triplets are read in the 5′-3′ direction.
The AUG codon serves as the start codon at which translation begins. There is only one start codon that codes for the amino acid methionine, while there are three stop codons (UAA, UAG and UGA). These codons cause the polypeptide to be released from the ribosome, where the translation occurs.
The position of the start codon determines the point where translation of the mRNA and its reading frame will begin. This last point is important because the same nucleotide sequence can encode completely different polypeptides depending on the frame in which it is read (Figure 4). However, only one of the three reading patterns of a mRNA encodes the correct protein. The displacement in the reading frame causes the message no longer to make sense.

Figure 4. Possible frameshifts (Source: marcoregalia.com)

 

As we said at the beginning, one of the main characteristics of the genetic code is that it is universal, since almost all living beings use it (with the exception of some bacteria). This is important because a genetic code shared by such diverse organisms provides important evidence of a common origin of life on Earth. The species of the Earth of today probably evolved from an ancestral organism in which the genetic code was already present. Because it is essential for cellular function, it should tend to remain unchanged in the species through the generations. This type of evolutionary process can explain the remarkable similarity of the genetic code in present organisms.

Although the human being itself continues to be an enigma for science, the revolution of the deciphering of the genetic code has allowed us to delve into the functioning of our body, specifically that of our cells, and cross borders to genetic manipulation.

 

REFERENCES

• Alberts, B. et al. Biología molecular de la célula (2010). Editorial Omega, 5a edición
• Cooper, G.M., Hausman R.E. La Célula (2009). Editorial Marbán, 5a edición
• Gotta Love Cells
• BioNinja
• Main picture: eldiario.es

Prions: special proteins

Do you remember mad cow disease? Some years ago it caused media hype because this illness, which affected animals, affected people too. Then, it was discovered that prions were the cause. So, I will discuss what prions are and the diseases that they produce.

WHAT ARE PRIONS?

Prions are proteins, but with different characteristics. Proteins are molecules formed by amino acids, which are bound by peptide bonds. All proteins are composed by carbon, hydrogen, oxygen and nitrogen. They are localized in all cells of the body and they participate in all biological processes that are produced. While DNA carries genetic information of the cell, proteins execute the work led by this information.

Proteins are the most varied macromolecules. In each cell there are miles of different proteins, with an extended range of functions. Between them: to be structural components of cells and tissues, to act in the transport and storage of little molecules, to transmit information between cells and to proportionate a defence in front of an infection. However, the main function is to act as enzymes, which catalyse most of chemical reactions in biological systems.

Prions are proteins with pathogenic and infectious characteristics (Video 1). They are not virus nor alive organisms; they are proteins without nucleic acid, it means, without DNA. They are localized in the surface of the central nervous system, especially in neurons; although they are also located in other body tissues of adult animals. Significant levels have been detected in the heart and skeletal muscle, and to a lesser extent in other organs except the liver and pancreas.

Video 1. What are prions? (Source: YouTube)

THE CELLULAR PRION PROTEIN

There is a change in the configuration of the cellular prion protein PrPc (Figure 1) in the diseases caused by prions. This protein has a protector role for cells and helps them respond in front of lack oxygen. The consequence of prions on this protein is the alteration of its functionality, producing a protein PrPSc with altered configuration. However, both configurations have the same sequence of amino acids. The secret of the different behaviour is the wrong folding, it means, the wrong conformation.

Figure 1. Left: normal protein (PrPc). Right: protein with altered configuration (PrPSc)(Source: Searching for the Mind with Jon Lieff, M. D.)

PRION DISEASES

Prion diseases are neurodegenerative processes produced by abnormal metabolism of a prion protein. These affect humans and animals and have a fatal clinical evolution, with the death as final.

There are various prion diseases, however, symptoms and clinical features are shared (Table 1). Some of these clinical features are dementia, ataxia (discoordination in the movement of body), insomnia, paraplegia and abnormal behaviors. The brain acquires a spongiform aspect, it means, an aspect like a sponge. This is due to accumulation of prion proteins in neurons, where amyloid plaques are formed.

Amyloid plaques are caused by accumulation of amyloid peptide, an essential protein for cellular function of the body. This accumulation in the brain can generate toxicity for nervous cells.

Until today there is any treatment to cure, improve or control symptoms and signs of these diseases.

Tabla 1. Prion diseases and its clinical features (Source: Rubio, T. & Verdecia, M. Enfermedades priónicas. MEDISAN 2009; 13(1))

DISEASE	SYMPTOMS	AGE	DURATION
Creutzfeldt-Jakob	Dementia Ataxia	< 60 years	1 month – 10 years (average 1 year)
Kuru	Ataxia Dementia	40 years (29-60)	3 month – 1 year
Fatal familial insomnia	Insomnia No autonomy Ataxia Dementia	45 years (35-55)	1 year

CREUTZFELDT-JAKOB SYNDROME

During 18^th century, European farmers described a neurodegenerative disease that affected sheep and goats, called scrapie. The affected animals will compulsively scrape off their fleeces against rocks, trees, or fences. Furthermore, its brain looked like a sponge. So, this is the birth of the word spongiform.

However, until 20^th century, in 1920, neurologists Creutzfeldt and Jakob described the first cases of spongiform encephalopathy in humans (Figure 2) and called the disease with their names.

Figure 2. Comparison of two brains: a brain affected by Creutzfeldt-Jakob disease (left) and a healthy brain (right) (Source: Health & Medical Information)

In this disease, there is a loss of memory, lack coordination and damage of mental abilities. The balance problems are common and, sometimes, are manifested in the beginning. Many patients lose autonomy and are unable to take care of themselves in later stages of the disease.

Due to prion nature of the disease, any symptom is possible and it depends on the area of the brain that is being affected.

KURU

It is a rare disease, localized in New Guinea. The main risk factor to suffer the disease is the intake of brain human tissue, which can contain infectious particles.

It is the reason that it is associated with people who practice a form of cannibalism, in which the brains of dead people are eaten as part of a funeral ritual. Although this practice ended in 1960, cases of kuru have been reported years later.

FATAL FAMILIAL INSOMNIA

It is a familial and inherited disease, which people affected suffer progressive insomnia. The human brain needs to sleep and rest, so permanent insomnia (there is not treatment with drugs) causes the death of patients.

Insomnia is due to a permanent and irreversible alteration of the sleep-wake cycle, which is characterized by the inability of the patient to develop REM and non-REM sleep.

REFERENCES

• Alberts, B. et al. (2016). Biología molecular de la célula. Barcelona: Omega.
• Rubio, T. & Verdecia, M. Enfermedades priónicas. MEDISAN 2009; 13(1)
• Wemheuer, W. M. et al. Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types. Am J Pathol. 2009; 175(6): 2566–2573
• Manual MSD
• Early Clinical Trial
• MedlinePlus
• Main picture: Canal44

Biology and extraterrestrial life

Frequently we can read on the news newly discovered planets that could harbor extraterrestrial life. Often we have new information about Mars, other worlds with water and extremely resistant living beings, like tardigrades. But is life possible outside the Earth? What is life? What is needed to sustain life? Astrobiology tries to answer this questions. Do you want to find out more?

ASTROBIOLOGY AND EXOBIOLOGY

Astrobiology is a set of different scientific disciplines that studies the existence of life in the universe. To achieve this it combines knowledge of biology, physics, chemistry, astronomy, ecology, geography, geology, planetary science and molecular biology. Within astrobiology, exobiology studies the possibilities of life outside our planet. It should not be confused with ufology, a pseudoscience. Astrobiology tries to answer such exciting questions as:
– What is life?
– How did life appear on Earth?
– How does life evolve, and what is its adaptability?
– What is the future of life on Earth and other places?
– Is there life in other worlds?

No, neither is this a Martian nor is it astrobiology. Source: Quo

WHAT IS LIFE?

Although it seems like a banal question, life is not easy to define. Apparently, we can recognize if something is alive or not if it can perform certain functions and has certain features. Living beings have vital functions:

• Nutrition: they can obtain energy from the environment to grow, survive and reproduce.
• Reproduction: they can create copies similar to themselves.
• Interaction: they can perceive what is going on the environment and inside themselves.
• Organization: living beings are formed by one or more cells
• Variation: variability between individuals allows species to evolve.

Problems begin when with beings that don’t have all the characteristics. The most classic example would be viruses: they are unable to reproduce on their own and lack cellular structure. Another example would be erythrocytes (red blood cells) of mammals, cells without genetic material or mitochondria.

Microphotography of the Ebola virus under electronic microscope (Public photo of the CDC)

WHAT IS NEEDED FOR LIFE TO EXIST?

We only know one type of life: the terrestrial one. This is why astrobiologists need to take it as a reference to know what to look for elsewhere. Could there be other forms of life different than terrestrial? Maybe, but it would be almost impossible to recognize them. If you do not know what you are looking for, you may find it but do not realize it.

It is considered that in order for life to appear and develop, it is necessary:

• A liquid where chemical reactions take place: on Earth, it is water.
• An element with ease to form stable compounds: on Earth, it is carbon.
• A source of energy: on Earth, it is the Sun.

We are looking for planets or satellites with these characteristics, although other possibilities such as liquid methane (in the case of Titan, a satellite of Saturn), ethane, sulfuric acid, ammonia or acetic acid as solvent are being considered. Life-based on other elements such as silicon, it is a recurring topic in science fiction stories.

Artistic representation of Titan’s methane lakes. Credit: Steven Hobbs

WHAT IS NEEDED TO SUSTAIN LIFE?

The celestial body has to fulfill a series of characteristics so that life can be sustained:

• An abundance of chemical elements such as carbon, hydrogen, oxygen, and nitrogen to form organic compounds.
• The planet/satellite has to be within the habitability area of its star (orbiting at a distance that allows a temperature suitable for life).

Habitability area (green) according to the temperature of the star. Red: too hot, blue: too cold. Source: NASA / Kepler / D Mission. Berry

• A source of energy enough to maintain the temperature and allow the formation of complex molecules.
• An appropriate gravity to keep an atmosphere and not crush the living beings of the planet.
• A magnetic field to divert the radiation incompatible with life.

The Earth’s magnetic field protects life from the solar wind. Source: ESA

In our Solar System, the candidates that possibly fulfill these characteristics are Mars, Europe and Ganymede (satellites of Jupiter), Enceladus and Titan (satellites of Saturn) and Triton (satellite of Neptune).

WHY CARBON?

Living beings are formed by cells, and if we reduce the scale, by molecules, and atoms (like all matter). Why is life-based on carbon?

In fact, in the constitution of organisms 26 elements are involved, but 95% of living matter consists of carbon (C), hydrogen (H), nitrogen (N), oxygen (O), phosphorus (P) and sulfur (S). We can imagine them as the “bricks of life”: by combining these building blocks, we can obtain complex organisms. These bricks can be joined to others by covalent bonds. Metaphorically, atoms can be imagined as spheres with hands which can be grasped by other hands. For example, the main energy source molecule for all living things is ATP (Adenosine triphosphate, C₁₀H₁₆N₅O₁₃P₃).

Schematic representation of carbon, hydrogen, oxygen, nitrogen and phosphorus atoms and their valences (possible bonds). Own production based on figure 6.3 of “Life in space” (see references)

The candidate element to sustain life would have to be an abundant element able to form a great amount of bonds with itself and with other elements. The 5 most abundant elements in the universe:

• Helium: does not form compounds
• Hydrogen and oxygen: they have 1 and 2 hands: they can only form very simple compounds
• Nitrogen: can bind to 3 atoms, but no chains of several nitrogen atoms are known.
• Carbon: it has 4 hands so it can be strongly bonded to other carbons with single, double, or triple bonds. This allows it to form long chains and three-dimensional structures and can still join to other atoms. This versatility allows constructing molecules chemically active and complex, just the complexity that makes life possible.

DNA chemical structure where we can see the importance of carbon bonding to form rings and chains. Source

Could there be life in another place based on a different atom?

ALTERNATIVES TO CARBON

SILICON EXTRATERRESTRIALS

Since establishing 4 links is so useful, silicon is the first candidate for biologists and science fiction writers, even if it is not as abundant as carbon. Silicon (Si) can also form 4 bonds and is abundant on rocky planets like Earth, but …

• The Si-Si bond is quite weak. In an aqueous medium, life based on silicon would not be sustained for a long time as many compounds dissolve in it, although it could be possible in another medium, such as liquid nitrogen (Bains, W.).
• It is very reactive. Silane, for example (one silicon atom bonded to 4 hydrogens) spontaneously ignites at room temperature.
• It is solid at most temperatures. Although it can easily form structures with oxygen (silica or silicon dioxide), the result is almost always a mineral (quartz): too simple and only reacts molten at 1000ºC.
• It does not form chains or networks with itself, due to its greater size compared to carbon. Sometimes it forms long chains with oxygen (silicones), that perhaps could be joined to other groups to form complex molecules. The alien of the movie Alien has silicone tissues. The beings formed by silicones would be more resistant, which leads to speculate what kind of extreme conditions they could withstand.

Horta, a silicon-based form of life featured in the science fiction series Star Trek. Source

NITROGEN AND PHOSPHORUS EXTRATERRESTRIALS

Let’s look at some characteristics of nitrogen and phosphorus:

• Nitrogen: can only form 3 bonds with other molecules and is poorly reactive.
• Phosphorus: its bonds are weak and multiple bonds uncommon, although it can form long chains. But it is too reactive.

By combining the two, stable molecules could be obtained, but the beings based on nitrogen and phosphorus would have other problems: the nitrogen compounds, from which they would have to feed, are not abundant in planets and the biological cycle would not be energetically favorable.

BORON, SULFUR AND ARSENIC EXTRATERRESTRIALS

The most unlikely biochemistries could be based on these elements:

• Boron: can form long chains and bind to other elements such as nitrogen, hydrogen or carbon
• Sulfur: can form long chains, but because of its size is highly reactive and unstable.
• Arsenic: is too large to form stable compounds, although its chemical properties are similar to those of phosphorus.

In 2010, the journal Science published a scientific research in which researchers claimed to have discovered a bacterium (GFAJ-1) capable of living only in arsenic, lethal to any living being. It broke the paradigm of biology by not using phosphorus (remember ATP and DNA structure) and opened up new study lines for astrobiology. In 2012, two independent investigations refuted the theory of researcher Felisa Wolfe-Simon and his team. Phosphorus remains essential for organisms to live and develop on Earth.

GFAJ-1 bacterium. Source

At the moment, these hypothetical biochemistries are nothing more than speculations, so astrobiologists are still looking for carbon-based life, although we already know that science never ceases to amaze us. Although we could identify life based on other elements if we ever find extraterrestrial life (or vice versa) the revolution will be so great that it won’t matter if they are carbon-based beings.

REFERENCES

• Mix, L.J. 2010. La vida en el espacio. Ed. Crítica
• Giménez A., Gómez, J., Rodríguez E. , Martín, D. (Coordinadores). Astrobiología: sobre el origen de la vida en el universo. 2011, CSIC.
• MOOC notes Astrobiology and search for extraterrestrial life. Edimburgh University.
• Superlife: el silicio orgánico
• Cover picture (Face hugger based in Alien movie)

 

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White, brown or red?

For many people summer is synonymous of beach and tan. But there are people who are not tan during winter. Some people prefer to use UVA tanning booths a few months before, and others take the sun without protection to catch some colour. What consequences can this have? Then I will talk about the skin and the effect of radiation on it.

OUR SKIN

The skin is the largest organ of our body, has an area between 1.5 and 2m² of surface and a weight around 3.5-5kg. Their functions are:

• Protection: protects the internal organs from trauma and prevents the loss of water and electrolytes from the inside.
• Thermoregulation: the blood vessels increase or decrease the temperature of the skin. When it is very hot the sweat refreshes the skin surface.
• Sensitivity: the perception of touch, pressure, temperature, pain and itching is done through the skin.
• Secretion: the skin protects the body from dehydration.
• Excretion: through the skin we eliminate about 350ml per day of water, which we have to recover by moisturizing. In certain diseases you can get rid of a lot of protein and sulfur.

The skin has two basic cells: keratinocytes (80%) and melanocytes (10%). The melanin, which gives the tan, is found inside the melanocytes and accumulates in some bags (melanosomes). When it does not touch the light it remains in deep strata, whereas when it touches the sun goes up by the keratinocytes (Figure 1).

Figure 1. Melanin (arrows) rising towards the keratinocytes (Source: Salud del Siglo XXI)

Tan is the synthesis of new melanin. Not all people produce the same amount of melanin. We all have the same number of melanocytes, but the difference is in the number of melanosomes.

Our skin is formed by 3 layers that are, ordered from superior to inferior, epidermis, dermis and hypodermis (Figure 2).

Figure 2. Skin layers: A) epidermis, B) dermis and C) hypodermis (Source: MedlinePlus)

The tanning process passes into epidermis, which is the top layer of the skin. Epidermis is 0.2mm thick and subdivided into 4 or 5 layers, depending on the body part. For example, the palms of the hands and soles of the feet are formed by 5 layers, where the extra layer gives more resistance. The thickness of the skin in these areas is 1-2mm, in contrast, in other areas, as in the eyelids, is lower (0.004mm). In the inner or deep layers, the cells are younger and more active, and along the cycle, they ascend to the outer or superficial area, becoming dead cells, without nucli and formed basically by keratin (dead skin).

Below, there is dermis that gives elasticity to the skin, where you find the nerves and blood vessels and is where the hairs and nails grow. Finally, hypodermis is below everything and is where the glands are.

RADIATION FROM OUR SKIN

The sun emits radiation with wavelengths ranging from 0.1 to 17,000nm. But only the radiations between 280 and 3,000nm arrive to the Earth (the others remain in the ozone layer).

Radiation that affects living organisms involves spectrum of 280-800nm (UVB, UVA, visible light and a part of infrared) (Figure 3).

Figure 3. Electromagnetic spectrum (Source: J. E. Martin Cordero. Agentes Físicos Terapéuticos (2009))

Not all radiation penetrates in the same way on our skin. Table 1 shows the level of penetration:

Table 1. Penetration according to the different radiation.

Type		Wavelenght	Level of penetration
Ultraviolet	UVC	100-280nm	–
	UVB	280-315nm	Epidermis
	UVA	315-400nm	Dermis
Visible light	VL	400-700nm	Dermis
Infrared	IR	>700nm	Hypodermis

It is important to know that prolonged exposure, without taking precautions, can not only produce skin cancer, but can also have other effects. UVB radiation is the most common cause of sunburn, erythema or redness. It is also the most common cause of skin cancer. In contrast, UVA radiation rarely causes burns, but is responsible for most photosensitization (abnormal increase in skin sensitivity to UV radiation) and may be carcinogenic in the presence of certain substances that enhance its effect. In addition, it causes aging of the skin (Figure 4).

In tanning booths 30% of the radiation is UV. Mostly it is UVA radiation, but there is also UVB radiation (albeit to a lesser extent). The remaining percentage is infrared radiation and visible light.

Figure 4. UVA (aging) and UVB radiation (burns) effects (Source: Antirughe.info)

The amount of irradiation is greater when the more near is the Earth of the Sun (zone of the Equator, between the Tropics of Cancer and Capricorn, or between 12 and 16 hours). This irradiation can damage our DNA, causing breaks in the DNA strand that can cause mutations.

UV rays easily pass through clouds and water vapor, but are partially absorbed by atmospheric pollution. It has been seen that in areas where there are holes in the ozone layer the incidence of skin cancer is higher. This is because the damage caused in the ozone layer allows the passage of more amount of UVB rays. Here the importance of not damaging the ozone layer, as it protects us from these rays.

WE NEED TO PROTECT OUR SKIN

Since the light can be reflected by several substances, it is necessary to take into account that, to direct rays of the sun, can be added those that arrive tangentially on a bright day and that are reflected by sand, water, soil, gel, snow…

Radiation doses are cumulative and may add to the effects of ionizing radiation (X-rays). The presence of skin cancer can be observed many years after an acute burn. This has been observed in American sailors who were in the Pacific during World War II, and who were exposed for months or years to high intensity solar radiation. These sailors have developed over the years different types of skin cancer.

For this reason it is very important to take the correct sun protection measures: use photoprotectors, avoid long periods in the sun, especially in hours of maximum solar intensity; and moisturize often.

REFERENCES

• MedlinePlus
• Onmeda.es
• AEMET – Agencia Estatal de Metereología
• The Tech – Museum of Innovation
• American Cancer Society
• Canal Salut Gencat

DNA: the solution to combat the dog mess

You are walking quietly and suddenly you smell an unpleasant odour. You look from side to side and you see nothing, but the smell continues there. Then, you lift your foot and, effectively, you have stepped a dog poop. You cannot deny it because everybody has happened it. However, DNA can finish with the lack of public spirit. If you do not believe it, I suggest you to continue reading.

THE CONSEQUENCES OF THE LACK OF PUBLIC SPIRIT OF SOME DOG OWNERS

To have a dog is not only feed up it and play with it, but its owners are the person responsible to duck and clean the dog mess and deworming it. However, few people do it.

In the street, in playgrounds or in front of the home’s door you can find the dropping of a dog because its owner has not cleaned it. Although there are many campaigns against the lack of public spirit of some dog owners and there are also economic sanctions, today is an unresolved issue.

To leave dog droppings is not only an unsightly problem, but it goes beyond because parasitized stools are a public health issue. If the stools are not cleaned soon, eggs or cysts presents in them may become infectious forms and represent a risk to people or children who play in the playground. The rain dissipates the stools and people do not see them, but the parasites are still there.

Intestinal worms cause diseases to dogs and cats and people, especially in children and immunocompromised (HIV, transplant patients or with some types of cancer subjected to long immunocompromised therapies).

Parasites can cause health affect to stomach and intestines, but the worst is in the eyes. The parasite Toxacara canis can cause the total loss of vision of the eye that infects.

CAN-ID PROJECT

Oscar Ramírez is the person responsible of the Can-ID project (Figure 1), developed by the Catalan company Vetgenomics SL to combat stools in public spaces. This is a system of canine identification by DNA, based on a chip of 128 markers (SNPs).

Figure 1. Logo of Can-ID (Source: Vetgenomics SL)

The aim of Can-ID is identify all dogs of a municipality with a chip to get a census of dogs. When a council’s technician finds a dog mess, he will pick up a sample and he will send it to analyse. Then, if the DNA removed of the sample coincides with the chip of some registered dog, it will know who the dog owner is. Finally, the council could fine this person.

This project is based on two phases:

Phase 1: genetic identification of all dogs of municipality

• Involvement of vets in the collection of blood or saliva samples
• Identification plate with QR code, which the owner can activate in case of loss of the dog
• Transport with custody system of samples
• Analysis of the samples and obtaining the genetic profiles
• Creation, management and conservation of the database with the genetic profiles of dogs in the municipality

Phase 2: identification of owners with a lack of public spirit

• Non civic owner does not pick up his dog’s stool from the street
• Collection of samples in the presence of members of the local police
• Transport with custody system of samples
• Analysis of stool samples in a laboratory specialized in non-invasive samples
• Comparison of the genetic profile of the stool with the database. Identification of the dog

In order to realize the first phase, the municipality has to modify the municipal ordinances so that, in addition to force the registration of the dogs and an identification by a chip, their owners also submit them to a blood test that will help to make a database.

Unlike what many people think, genetic identification has not a great cost. Moreover, the cost of cleaning the municipality is higher. The first phase has a cost of 35€ per sample and includes the extraction of a sample by a vet and its custody for analysis. The second phase is also around 30€ and the amount of the fine is around 300-600€, depending the city. Therefore, the municipalities that implement this system would recover the investment.

Parets del Vallès (Barcelona) is the first town to implement this system. In the first 3 months, the municipality pays for the collection of samples and their custody, through an awareness campaign.

WHY CHOOSE CAN-ID?

This system has a greater number of markers respect to other identification systems (Table 1), but it also has internal pollution controls.

This system allows to exclude the false positives. A dog may urinate on a stool in the street. This would contaminate the sample, but this system is able to identify if the sample contains more than one DNA. If so, the sample would be excluded.

It can also happen that the dog is not registered or is from another population. But you can obtain a robot portrait and put stronger pressure on dog owners who comply the characteristics of the robot portrait (example: hair colour).

Table 1. Comparision of the Can-ID system respect others identification systems (Source: Oscar Ramírez, Comparative Genomics programme from Master’s Degree in Cytogenetics and Reproductive Biology in UAB)

In addition to identify these people, Can-ID can be applied for genetic identification and paternity tests or monitoring of wild-wolf populations from non-invasive samples too (stools, hair, urine).

We hope that more municipalities will join this initiative and reduce the lack of public spirit of some people, which may affect public health.

REFERENCES

• Vetgenomics SL
• Interview to Oscar Ramírez in the program Catalunya Migdia, of Catalunya Ràdio (04/11/2016)
• El Periódico
• Campaign citizenship Parets del Vallès
• ADN perros

Abrahim’ story: the child with 3 people’s DNA

On last 27^th September media echoed with the news of the first birth of a child with DNA from three people, through the experimental technique, called spindle nuclear transfer. What is this technique? Is it possible to have DNA from other people besides our parents? Then, I will explain the news in detail.

THE FAMILY

We need to know well his parents. They are a couple from Jordan, whose wife is a 36-year-old woman with a gene mutation in her mitochondrial DNA. It is right: mitochondrial DNA. A part of the nuclear DNA, where is found in our cell’s core and we currently mean, there is also DNA in our mitochondria. Mitochondria are double membrane-bound organelles found in all eukaryotic organisms and play a crucial role in energy production. They are necessary for our cells breathe and produce energy.

Like nuclear DNA, mitochondrial DNA can suffer mutations caused inherited diseases. For example Leber’s hereditary optic neuropathy (LHON), a rare inherited disease that causes blindness due to degeneration of the optic nerve.

Well, the mutation suffered by the protagonist of the story in their mitochondrial DNA cause Leigh syndrome. It is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. Clinical symptoms depend on which areas of the central nervous system are involved.

Mitochondria are inherited only from mothers, a pattern known as maternal inheritance. This is the reason that they need to find a solution and avoid to transmit mitochondrial DNA (with mutations) to offspring. Previously, she had 4 pregnancy losses and 2 deceased children at age 8 months and 6 years from Leigh syndrome. The percentage of mutant DNA in mother’s mitochondria is enough for her to have no symptoms of the disease and only be a carrier. However, the probability of transmitting the mutation to offspring is very high.

THE TECHNIQUE: SPINDLE NUCLEAR TRANSFER

The couple sought out the help of John Zhang and his team at the New Hope Fertility Center in New York City. They work researching techniques to prevent diseases caused by mutations in mitochondrial DNA.

Currently, there are two methods for mitochondrial replacement: pronuclear transfer or transfer of the mitotic spindle. In both cases a donor is needed, who has not any mitochondrial DNA mutation.

The first technique is called pronuclear transfer (Figure 1) and involves fertilising both the mother’s egg and a donor egg with the father’s sperm. Before the fertilised eggs start dividing into early-stage embryos, each nucleus is removed. The nucleus from the donor’s fertilised egg is discarded and replaced by that from the mother’s fertilised egg.

But this technique wasn’t appropriate for the couple for religious reasons (they are Muslims). And this method involves the destruction of two embryos.

Figure 1. Pronuclear transfer. An egg from the mother (yellow) and an egg from the donor (purple) are fertilized with sperm from the father (yellow). When the pronucleus is formed in each egg, its is eliminated from the donor and the mother’s pronucleus is inserted in the donor’s egg (Source: A Scientist’s Guide to Making Babies…)

So Zhang’s team took a different approach, called spindle nuclear transfer (Figure 2). They removed the nucleus from one of the mother’s eggs and inserted it into a donor egg that had had its own nucleus removed. The resulting egg (with nuclear DNA from the mother and mitochondrial DNA from a donor) was then fertilised with the father’s sperm.

Figure 2. Spindle muclear transfer. The red egg corresponds to the mother, and her mitotic spindle is removed and inserted into the donor’s egg (orange), which previously has been extracted her mitotic spindle. Later, the egg is fertilized with sperm from the father (blue) (Source: Revista Genética Médica, modification)

In either methods the new egg is 100% free of maternal mitochondrial DNA (mitochondrial DNA with mutations) because it is estimated that about 1% of the mitochondrial DNA can be entrained with the nuclear genetic material. However, it is considered that the levels are low enough to cause Leigh syndrome.

THE CRITICS

The procedure is not legal in the United States, so it was done in Mexico, where rules around human embryo manipulation are more lax than in the United States, which has declined to greenlight the experimental procedure.

The technique has gained notoriety because it leaves the baby with three genetic parents. But there is a part of the scientific community that is not quite agree because he fears are not complied with all ethical codes. The limited information in the abstract left many wanting more.

Zhang’s team created 5 embryos and only one had a normal karyotype (46,XY). It was implanted into the mother and 9 months later Abrahim was born (Figure 3). He is a boy and there is no risk to transmit his mitochondria (donor’s mitochondria) to his offspring.

Now, this Jordanian family enjoys their healthy baby at home, and for the moment the mutation was detected in less than 1% of mitochondria

Figure 3. Fertility specialist John Zhang with the newborn baby Abrahim (Source: Science)

REFERENCES

• Revista Genética Médica
• New Scientist
• OMIM
• Science
• J. Zhang et al. First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome. Fertility and Sterility. 2016
• Cooper, G.M., Hausman R.E. La Célula. Editorial Marbán, 5a edició
• Main picture: MaxiSciences