Do mutations require a milieu?
‘A mutation is a change in the DNA at a particular locus in an organism.’ Mutation plays an important role in evolution and is the ultimate source of all genetic variation. It is salient as the introductory step of evolution because it creates a new DNA sequence for a particular gene, creating a new allele. Gene mutations occur very rarely but its rate can be artificially increased by mutagenic agents such as mustard gas, x-rays and ultraviolet light to give induced mutations.
Genetic mutations can be classified in two major ways: hereditary and somatic. Hereditary mutations are present virtually in every cell in the body and are inherited from a parent. Due to their presence in the parent’s gametes, the mutations are also referred to as germline mutations. If a mutant gene is passed onto offspring, when growth occurs due to mitosis, the mutation will be present in all cells. The other type of mutations is somatic (acquired). These occur during a person’s life and are therefore present only in some cells. These can be caused by environmental factors such as ultraviolet radiation from the sun, or due to an error made during cell division, which is called non-disjunction. Somatic mutations cannot be passed to offspring due to the mutations not being present in gametes.
A number of regions of DNA possess dominance determining when and where genes are turned ‘on.’ Occurring mutations in these parts of the genome can substantially change the way the organism is built; a mutation in a control gene can cause a cascade of effects in the behaviour of genes under its control. An example of a control gene is hox genes. They are found in a number of animals like humans and designate where the head goes and which regions of the body grow appendages. Such genes assist in the directing of the body’s unit construction eg. segments, limbs, and eyes. Thus evolving an extensive change in basic body layout may not be so unlikely; it may simply require a change in a Hox gene and the favour of natural selection.
‘Mutations can be either beneficial, neutral, or harmful for the organism.’ Though it is said that factors in the environment an influence on the rate of mutation, they are not thought to influence the direction of mutation. This means that exposure to harmful chemicals may increase the mutation rate, but will not cause more mutations that make the organism resistant to those chemicals. In this respect, whether a certain mutation occurs or not is unallied to how serviceable that mutation would be, proving the concept that mutations are random. For example, in the U.S. where people have access to shampoos with chemicals that kill lice, a lot of lice that are resistant to those chemicals are commonly encountered. Two possible explanations can arise for this:
‘HYPOTHESIS A - Resistant strains of lice were always there — and are just more frequent now because all the non-resistant lice died.
HYPOTHESIS B - Exposure to lice shampoo actually caused mutations for resistance to the shampoo.
In 1952, Esther and Joshua Lederberg performed an experiment that aided in showing that mutations are random. They focused on the idea that bacteria grow into isolated colonies on plates. These colonies have the ability to reproduce from an original plate to a new plate by the process of ‘stamping’ (stamping the original plate with a cloth and then stamping empty plates with the same cloth). Bacteria from each colony are picked up on the cloth and then deposited on new plates. This led to Esther and Joshua hypothesising that antibiotic resistant strains of bacteria surviving an application of antibiotics had the resistance before their exposure to the antibiotics, not as a result of the exposure. Their experimental set up is summarised below:
This shows that before the encounter of penicillin the resistant bacteria were present in the population thus did not evolve resistance in response to the exposure of the antibiotic. Moreover, from the evidence available, we can hence deduce that mutations might therefore preferentially form around existing ones.
By Gaya Giritharan, 10F
The Science Behind Glioblastoma
CN: picture of brain surgery
How do brain tumours form?
A brain tumour occurs when brain cells divide and grow in an abnormal and uncontrolled way. When a cell divides, it copies its genes and replicates itself. Sometimes however, mistakes occur in this process, and are known as mutations. Whilst some mutations are harmless, others cause the cell to divide uncontrollably.
The mutation causes the cells to behave as though they are receiving a growth signal or deactivates the checkpoints that would stop the cells from dividing. Therefore, the cells continue to divide uncontrollably, forming a tumour
What is glioblastoma?
Glioblastomas are the most common and aggressive type of brain cancer that forms from cells called astrocytes in the nervous system. They belong to a group of brain tumours called gliomas, which are malignant tumours of the glial tissue. The average age of patients with glioblastoma is 64 years old; its risk increases with age. Whilst glioblastomas are mostly found in the cerebral hemispheres, they can be found anywhere in the brain.
Glioblastoma is a ‘diffuse’ tumour, meaning they are infiltrate and able to spread into healthy tissue in other parts of the brain, and therefore is very fast growing and fast spreading. This makes it very difficult to pinpoint precisely where the tumour starts and ends. Particularly aggressive glioblastoma are able to even spread to the opposite side of the brain through connection fibres, known as corpus callosum. Gliobastoma’s ‘diffuse’ property is particularly problematic when tumours spread near to important regions of the brain that are essential to functions such as movement and coordination.
Symptoms and side effects of glioblastoma
Due to mass swelling from the fluid surrounding the glioblastoma (edema), patients develop symptoms very quickly. The most common symptoms are nausea, vomiting and severe headaches, and are predominantly due to the increased pressure in the brain as a result of the tumour and swelling. Neurological symptoms are also not uncommon, for example, weakness, sensory changes, difficulties with balance, and neurocognitive or memory issues.
Treatment of glioblastoma
Mark Gilbert, director of the Neuro-Oncology Branch in NCI’S Centre for Cancer Research said, “Glioblastoma is one of the hardest to treat in the history of oncology.” Despite continued efforts to develop promising treatments for glioblastoma, none have proved successful, with only 3.3% of patients living for longer than 2 years. The usual treatment for patients with glioblastoma is a surgery to remove most of the tumour, followed by chemotherapy and radiation.
Commonly, surgery would take place in an attempt to remove as much of the tumour as possible- a procedure known as debulking. It is difficult to remove the entire tumour because glioblastoma is a diffuse tumour, which means it can spread into the rest of the unaffected brain, and so it is difficult to tell the difference between affected and unaffected brain tissue.
There have been recent advances, which have improved the extent to which the tumours can be removed in surgery. Prior to surgery, patients are given a drink containing the substance 5-ALA, which causes the affected cells to glow pink under violet light. This makes it less difficult to tell the affected and unaffected cells apart, and so more of the tumour can be removed.
Surgery is also used for palliative treatment in cases where the tumour cannot be removed- intracranial pressure is reduced to relieve symptoms.
Radiation involves the use of high precision high-energy beams, for example X-rays, gamma rays or protons, to kill the affected cancer cells. An immobilization mask is worn by the patient to hold their head in the same position and limit movement. Intensity-modulated radiation therapy is an advanced mode of radiotherapy that uses computer-controlled liner accelerators to deliver precise radiation doses to a malignant tumour. It allows for the radiation dose to conform more precisely to the 3D shape of the tumour by controlling the intensity of the beam in small volumes. The treatment is planned specific to the tumour using the CT and MRI images of the tumour in conjunction with computerized dose calculations to determine the dose intensity pattern that is best suited for the tumour.
Chemotherapy is a technique that uses cytotoxic drugs to kill the affected cancer cells. Temozolomide, Iomustine and carmustine are the most commonly used drugs in chemotherapy. Temozolomide works by preventing the tumour cells from making new DNA, which prevents them from making new cells and therefore growing. It also makes the affected cells more sensitive to radiation, so chemotherapy and radiation treatments are often used together. Whilst radiation acts on the affected tumour cells, chemotherapy acts on all dividing cells, but healthy cells are able to repair themselves easier than the tumour cells, so few healthy cells die after treatment. The various ways in which chemotherapy can be given are:
Tablets- chemotherapy drugs can be taken in tablet form and are absorbed and carried around the body in the bloodstream to reach the affected tumour cells.
Injection/drip- chemotherapy drugs can be injected into a vein or into the spinal fluid. A drip may be used to insert the drug into the bloodstream, where it is absorbed and carried around the body to the affected cells.
Wafers- drugs can be put inside a polymer wafer and inserted into the brain during surgery. The wafers are made of a biodegradable material so they can dissolve over a few weeks, releasing the drug into the brain to kill the tumour cells.
Whilst several immunotherapy-based treatments have proved unsuccessful in facing glioblastoma, vaccinations has been considered to be one of the more promising approaches.
A particular advance in the use of vaccines for glioblastoma was made by Dr Jason Adhikaree from the University of Nottingham, who proposes to use dendritic cells, a type of white blood cell, to create the vaccine. The dendritic cells would be taken from the patient’s body and ‘taught’ to recognise and kill the glioblastoma-affected cells. They will then be injected back into the patient’s body, in which they can attack the tumour cells.
By Maheria Rashid