What is a mutation? How do carcinogens work? What role does DNA play? How are mutants made?: Understanding cancer is a key step in preventing and controlling it. The following article tries to answer these key questions using simple explanations and pictures.
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These days the media is full of news about how genetic engineering is being harnessed to create new ‘designer’ medicines and how we will soon be able to conquer certain genetic diseases. Do you really understand what this involves? Do you know precisely what a mutant is or how it is made? What is DNA and what is it about DNA that causes mutations and genetic diseases? In this article I hope to provide answers to some of these questions.
First of all let me explain my background. My career started many years ago in research making mutations in bacteria for the UK’s largest chemical company. I had previously qualified from Manchester University Medical School’s Bacteriology and Virology Department. My bacteria used methanol – a simple alcohol made from natural gas – as their source of energy and food.
The bug had a rather long name (Pseudomonas methylotrophus) which, for ease of communication, I shortened to ‘Psodomy‘. I tried to make mutations that would make Psodomy produce ‘essential‘ amino acids. We need amino acids as our building blocks for proteins – humans can make lots of amino acids themselves. However we can’t make a few amino acids and therefore we need them in our diet – these are the essential amino acids. The strategy was to use Psodomy to turn natural gas into essential amino acids – my chance to help solve World hunger.
We grew Psodomy in a large fermentation vessel – this meant we could put methanol in one end and drain off our protein (called ‘single cell protein‘) using a tap at the other end. Actually our fermentation vessel (see photo below) was so large it received the ‘Erection of the Year‘ award when it was installed near our labs in Billingham (North of England). This was in 1979 (here’s the link to the mega erection story in New Scientist magazine – its on page 840 at the bottom).
Let me now explain some basic facts that will help you to understand what mutants are and how we can make them. Put very simply a mutant is a living thing that has a mutation. A mutation is a change in the DNA of the organism. DNA is what our genes are made of – it is passed down from generation to generation. Things that can change this DNA can cause mutations (and therefore make mutants). These things are called mutagens. So what is this DNA?
DNA is simply a very, very, very long molecule. If you didn’t do chemistry at school all you need to know is that everything in the world is made up of atoms (think of these as incredibly small bits of ‘stuff’). These atoms can join together to make molecules – for example plastics are very long molecules or chains of the same repeating group of atoms. Although we think we are clever because we can make plastics evolution beat us to it – all living things contain lots of very long chains of atoms joined into molecules.
Whereas plastics have identical repeating units of atoms along their chains living things build much more variety into their molecular chains. If you think of plastics as chains of identical glass beads – then the molecules in living things would be made up of beads of many different colours, sizes and shapes. A typical living molecular chain is a protein and by combining its ‘beads’ (called amino-acids) in different ways each protein has a unique shape which helps it do some very useful jobs. This is why proteins make up the machinery used by every cell in our body. For example they help us break down foods (enzymes), carry oxygen in the blood (haemoglobin), cause muscle cells to contract, transmit electrical signals down nerves and identifying harmful microbes (antibodies).
DNA is also a living long chain molecule but its shape is more fixed than most proteins. If we could see a DNA molecule (we can’t – it is too small) we would see what looks like a twisted ladder – each leg of the ladder is a long molecular chain of DNA. This structure is referred to as a double helix (‘double’ because it involves two very long chains of DNA). This structure is very important because each rung on this ladder contains the ‘letters‘ of DNA’s simple 4 letter alphabet.
Why does DNA need an alphabet? This is because DNA is the instruction manual for everything that goes on in a living organism. It doesn’t matter whether you are a bacteria, a plant or an animal – the instructions for making everything you need to live is stored in this DNA instruction manual. The instructions are written using DNA’s simple 4 letter alphabet – and every word in the manual is precisely 3 letters long (the DNA letters are called ‘bases‘).
Evolution was much more organised than humans when it designed its language – humans have loads of languages, loads of alphabets and our words can be almost any number of letters long. In nature all instructions are written on DNA using the same alphabet of only 4 letters and the same vocabulary of 3 letter words. No need for Google Translate here! This means we can put DNA words from humans into bacteria and they can be read by the bacteria to make human proteins (…and viruses can insert their words into human cells and these cells read them and make the ‘virus’ proteins – by using the same language the viruses ‘hack‘ into the cell’s software and hardware systems).
So what do these 3 letter DNA words mean? Well I mentioned above that proteins are made from amino acids (the ‘beads‘). There are over 20 amino acids – and this same pool of amino acid beads is used in all living things. Each of DNA’s 3 letter words signifies one amino acid. Going back to the description of a protein being a chain of many different kinds of beads (amino acids) – the precise names and order of these amino acids is written in the DNA instruction manual (along the ladder) using the 3 letter words. For example:
DNA word TAC instructs a cell to add amino-acid Tyrosine when it makes a protein (in TAC the T, A, and C are abbreviations for the DNA letters, or bases, Thymine, Adenine and Cytosine).
We think we are clever because we have made computers with software (instruction manuals) using a binary (2 letter) code which can produce useful programmes for word processing, spread sheets, graphics etc. Well evolution has gone much further – it goes straight from the software (written on the DNA) to making 3 dimensional machinery parts (proteins). DNA also stores the instructions for putting these machinery parts together and controls when to turn the machines on and off and how quickly they need to run.
You will appreciate from this that the precise instructions contained along the DNA molecule are very important. Any mistakes in how these instructions are written could really mess up our ‘living’ machinery and all the processes that control it. These mistakes are what we call ‘mutations’ and a typical result of a mistake in the DNA’s instruction manual can totally screw-up a cell’s control system and lead to uncontrolled cell growth or cancer (and a huge number of other diseases).
As I explained above the first word in the DNA word TAC is the base Thymine:
Using the example above if we change the word TAC into GAC the wrong amino acid is added to the protein. This happens when the letter T (DNA base Thymine) is replaced by the letter G (DNA base Guanine).
TAC = amino acid Tyrosine
GAC = Aspartic Acid – A very different kind of Amino Acid
As a result of this single letter ‘spelling mistake’ the protein will have a different shape and different chemical properties. The machine may not work well, it may not work at all or it may do something completely different. Think of a cog in a piece of clockwork if one of its teeth is bent it will probably not perform properly. In our day-to-day life we see many results of mutations in DNA (and therefore in the operation of proteins) – one common example is colourblindness:
To make a mutant you change the words on the DNA molecule. This can be done as above by just changing single letters or by changing several words. The changes can be replacements with different letters or words or they can be deletions – a bit like when you cut and paste or delete in your word processing programme. The body has its own very sophisticated repair systems which it uses to fix mistakes when they occur in DNA. These mistakes may happen at random, or be caused by chemicals (mutagens/carcinogens), radiation (like when we lie out in the sun) or viruses. Viruses take over the cell’s systems when they infect it and sometimes they can ‘insert’ their own DNA into our DNA. This happens, for example, in some cancers.
When we try to make mutants of bugs in the lab we use the same kind of approaches. We can, for example, use mutation causing chemicals, radiation or even viruses (there are special viruses called bacteriophages that attack bacteria). When I worked with Psodomy I used UV radiation – effectively forcing the bugs to lie under a very powerful sun lamp. The idea was to create so many mutations that the bugs’ own DNA repair systems couldn’t fix the damage.
The rather crude strategy was to take a load of mutants and then grow them in a food bath that didn’t contain a specific essential amino acid. If the bug could grow in this bath it meant it could make the amino acid itself and then we tried to find the ones that produced even larger quantities of the essential amino acid. Once we had a bug that made lots of the amino acid we could grow it in our fermentor (our famous ‘erection of the year’ vessel) and hey-presto you turn on the tap and out comes a broth containing the essential amino acid (clearly I have simplified things a bit!).
Today’s scientists are much more sophisticated. They use (for example) viruses into which new genes (=DNA words) have been cut and pasted (instructions to make new proteins). These viruses inject the new genes into the bacteria’s DNA and with lots of technical wizardry the bacteria can be made to produce the new products (including things like drugs/antibiotics and chemicals that are essential to health like insulin and other hormones).
You will hear lots in the press about the CRISPR/Cas9 genome editing system. This is a very powerful genome cut and paste system that was discovered recently in bugs and has been harnessed as the go-to DNA editing system for genetic engineers (more info about that and how it is used in Gene Drives in my article here).
So that, in a nutshell, is a summary of how mutants can be made. If you wish you can make some mutants of your own – just lie out in the strong sunlight and the radiation will create mutants from your own body’s cells. Some of these mutants may overcome the systems the body uses to control the cells. For example a mutation may damage a control protein that stops your cells from growing and multiplying uncontrollably.
Such a cell will then divide many times and could develop into a carcinoma/melanoma and – with help from the sun – you have made mutants and given yourself skin cancer. It could take many years to get this result. Alternatively you might try to be careful about over exposing yourself to the sun – just get enough sunlight to produce the vitamin D you need (or take a supplement).
Interestingly vitamin D helps to protect us from cancer so as always with health advice – it is best to avoid extremes in either direction (not too much and not too little sun exposure). Vitamin D does its magic because it is an antioxidant – this means it can neutralise chemicals (oxidants) that damage the letters in your DNA instruction manual. Every cell has a copy of this manual so every cell is a potential source of cancer. UV radiation from sunlight turns harmless chemicals into these deadly oxidants.
Oh and it you fancy a slightly less ‘academic’ video about making mutants click on the box below (to download it from iTunes use the link here) :
If you found this article interesting please consider taking a look at some of my other recent reports on similar subjects.
Just click on the titles below:
…starting with some more serious stuff:
and now some articles with a slightly humorous angle:
You can also find some of my more humorous reports in the Alpine Press section of my personal site using the link here.
…for even more about me please visit chrisduggleby.com.