Filled Under: mutation
Is eating DNA safe?
Eating DNA sounds scary but it’s completely safe. I do it every day. Let me explain.
DNA stands for deoxyribonucleic acid. The words “acid” and “nucleic” are in the name so it is hardly surprising that some people are concerned about its effects when eaten.
But the name is nothing to worry about. While DNA is an acid, it’s a very weak one – more like vinegar, or the citric acid in lemons, than a dangerous acid like sulphuric acid.
What about the word “nucleic”? That has nothing to do with nuclear energy – it refers to the nucleus or centre of the living cell. The nucleus is the compartment where, in animals, plants and fungi, the DNA is stored. (In bacteria the DNA just floats around in the cell.)
The third part of the name – “deoxyribo” – also has a chemical sound to it but this just refers to ribose, which is a sugar a bit like glucose but with fewer carbons. The “deoxy” part means the ribose is missing one oxygen atom.
This makes DNA a very stable, non-reactive molecule and ideal for the long term storage of genetic information. It is also a good food.
Why am I so sure that eating DNA is safe?
I am sure because nearly all the food we eat contains DNA and lots of it. The reason is simple. Organisms are not built of continuous matter like plasticine, we are made up of tiny balloons called cells.
Ancient stories describe how people were fashioned from clay but actually it is more like being made of Lego blocks. Bacteria are single-celled organisms, most animals and plants are multi-celled organisms. Cats are bigger than mice because they have more cells.
In a sense, we are all like Lego constructions.
And here’s the amazing part – virtually every cell has its own DNA (its own genetic information or genome) and each cell in your body carries your genome. So each block is more like a smartphone than a balloon – each block has its own computer code or DNA genome.
In complex organisms each cell has the same DNA but interestingly different genes are active in different bodily organs. Think of genes as different apps on a smartphone – so all the smartphones that make up your liver will have one set of apps on, and your muscle cells will be using a different set of apps.
In plants, different apps (genes) are on in leaves and roots but all the cells of a plant carry the same set of genes, i.e. the same genome.
So whether you are a vegetarian who eats lettuce and cauliflower or an omnivore who eats steak and kidney pies, you are eating cells, and each cell contains DNA which in turn contains the entire genetic information or the whole genome of each species you eat.
The only living parts that don’t contain DNA are things like egg whites or filtered milk that are there for energy storage, or blood juices in which our blood cells float.
Carolina Biological Supply Company
DNA is pushed out of hair when it forms so hair doesn’t have much – if any – DNA, but hair roots do, and in mammals red blood cells (but not white blood cells) push out their DNA as they mature so they can squeeze along tiny blood vessels.
But most parts of animals and plants are made up of cells containing DNA. This is why police can identify suspects from either a drop of blood or a hair root at a crime scene. They could also identify a lettuce or a strawberry from a leaf or from the fruit.
If you eat a three course meal – oysters for starters, chicken and asparagus as a main, and fruit salad for dessert, you are eating lots of different DNA.
Can DNA from food get into my own DNA?
Basically, DNA, like proteins and complex carbohydrates, gets broken down into pieces – this is what digestion is all about. Your teeth mash it up and enzymes throughout your digestive tract cut it to pieces.
Enzymes produced by your pancreas called DNases are specially designed to break the DNA into tiny pieces that can be taken up into your blood and then carried around and used by other cells to build new molecular structures in your body – including possibly your own DNA.
Could any of the genes, from any of the organisms you eat, get into your DNA and do you harm? It’s a reasonable question, but the answer seems to be no. Imagine you dropped a smartphone in a blender or ate it (please don’t) – all the components would be mashed up.
When you eat and digest DNA it seems that the long coding sequences, the narratives or the apps that specify gene products, are so cut up that they can no longer function as genetic material. There are few if any sentences left, just letters or fragments of words.
Even if some sentences did survive your digestive system it is unlikely they would enter your cells or harm you in any way.
Our world is awash with DNA and always has been but there is no clear evidence that eating DNA can harm you.
Genetically modified organisms
So what about genetically modified organisms or GMOs? Are they safe to eat too?
I certainly think so. If you ate a fish with a gene from a strawberry or a strawberry with a gene from a fish, to me it is no different from eating fish for the main course and strawberries for dessert.
I don’t think eating DNA or any combination of different DNAs from different species could do us harm.
To convince yourself that DNA is contained in food you can do a simple experiment at home. You can extract DNA from fresh strawberries.
I wouldn’t eat the DNA alone though. When wet it is slimy and when dry it looks like cotton wool. But when mixed with the other components of strawberries it is undetectable and harmless, and strawberries taste great as they are.
Merlin Crossley works for the University of New South Wales. He receives funding from the Australian Research Council and the National Health and Medical Research Council.
Explainer: what is genomic editing?
Mistakes in the paper version of the Encyclopædia Britannica took a long time to correct – years often passed between revised editions – but these days editing information is much easier. In electronic sources, like Wikipedia, anyone can log on and use simple web-based tools to make corrections or even improvements.
Human genomes also contain various errors or mutations. Many are relatively harmless but some cause life threatening genetic diseases. In a few cases, patients have been treated by conventional gene therapy; new genes have been carried in by viruses. These can then compensate for defective genes. But so far few – if any – patients have had their mutations corrected by genomic editing.
Likewise in the agricultural world, most applications of genetic engineering have involved inserting new genes, termed transgenes, rather than using editing to incorporate desirable genetic variations.
Synchronous technological revolutions
This may all change now that new editing tools have come on the scene. A quiet revolution is occurring in our ability to modify living genomes.
John Jobby/Flickr, CC BY-SA
Most importantly the new editing tools have arrived in the midst of a second revolution – a revolution in our ability to sequence large genomes.
The affordable sequencing of human genomes has allowed the ready identification of myriad harmful mutations. Conversely, in agriculturally important organisms, new beneficial gene variants have been identified. So it is becoming more and more relevant to think about editing such variants in or out.
At the same time the improvements in sequencing also mean that one can readily re-sequence after editing. One can check whether any unintended errors have been introduced.
The big advantage of genomic editing over the addition of new genes by gene therapy or transgenesis is that a defect is corrected, or a desired variation is introduced, via a single, targeted and permanent change. Since the change already exists in nature, it should work effectively, and it should be safe.
In contrast, gene therapy has been severely hampered by the epigenetic silencing of transgenes, as well as by the unwanted insertion of new genes beside important growth control genes – that in one case led to uncontrolled cellular growth and cancer.
Tools for modifying genomes
So what are these new genomic editing tools, where did they come from, how do they work, and why are they not more widely talked about?
As often happens the new tools came from fundamental research – research into DNA-binding proteins or the mechanisms by which bacteria protect themselves from viruses. The key development is that it is now much easier to design DNA-targeting reagents that – at least in theory – can surgically cut a single gene within a complex genome.
Breaks in DNA can be lethal so the cell has in-built machinery that repairs any nick as soon as possible. One strategy is to grab any available spare DNA that seems to match the damaged DNA and to stitch it in as a replacement – just as you might darn a red pair of socks with any red wool that you find lying about in the cupboard. This is called homologous DNA repair.
Genomic editing is carried out by introducing a specific DNA-cutting module along with a piece of repair DNA, carrying the change you want to incorporate. When the original DNA gets cut, the cell replaces it with the donor DNA.
Surgically targetting chosen human genes
Bush 41 Library/Flickr, CC BY-NC-ND
The restriction enzyme EcoRI (that helps the bacterium E. coli protect itself from invading DNA viruses) recognises and cuts sequences of the form GAATTC (a string of DNA subunits or nucleotides and carrying in order a guanine, two adenines, two thymines and a cytosine). This sequence is only 6 units long and it occurs by chance millions of times in the human genome.
EcoRI is a useful tool when cutting and joining short pieces of DNA in the lab – pieces that only have one or two GAATTC motifs – but it is useless in terms of trying to surgically cut and repair a single human gene within our vast genome.
To get an idea of the importance of specificity, think of the Google search engine. If you typed in the word “editing” you might never find this article, but if you type in “genomic editing” you may. To be safe you could type in this whole sentence, or any other long sentence. The unique sequence of letters should be enough to take you right here.
A better toolbox
The first breakthrough in designing reagents that could target longer sequences came from the study of DNA-binding proteins in the model organism, the African clawed frog (Xenopus laevis).
Thomas Splettstoesser/Wikimedia Commons
His work showed that TFIIIA bound DNA via a series of short domains he called “zinc fingers” – because they curled around a zinc ion to form a shape that could stretch out to fit into the major groove of DNA.
He realised that each zinc finger could bind three nucleotides, and that by linking two zinc fingers together you could bind six. A protein of six zinc fingers can bind 18 base pairs, and so on. Like the long sentences mentioned above, 18-base pair sequences are sufficiently long to identify individual human genes.
These days many different artificial zinc fingers are available and can be linked together to target virtually any 18 base pair motif.
Artificial zinc finger proteins were then hooked up to DNA-cutting enzymes, or nucleases, to generate zinc finger nucleases. These have already proved effective in carrying out genomic editing – see the video below.
But they have also turned out to be more difficult than expected to make – the rational design approach did not always lead to the desired specificity in practice and a certain amount of trial and error and screening of random variants was required to achieve acceptable specificity and tightness of binding.
Consequently, a few companies, such as Sangamo Biosciences, offered a service in making zinc finger nucleases but few laboratories adopted the technology themselves.
Now things have really changed since two new DNA-binding modules have come on the scene:
1. Transcription activator-like effector nucleases (TALENs): these are based on DNA-binding proteins found naturally in bacteria that infect certain plants.
Like zinc finger proteins they are made up of repeated modules, and in this case each module binds to two bases. By linking nine domains together, scientists can make a protein that recognises 18 base pairs.
Most importantly the rules of binding have proved to be robust so that scientists can make modules to recognise any chosen doublet and these can then be stitched together. Many laboratories have eagerly adopted this technology to target their chosen genes.
2. Clustered regulatory interspaced short palindromic repeats (CRISPRs): these are similarly attractive.
Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute, CC BY-NC-SA
They occur naturally in bacteria and, like restriction enzymes, are involved in protecting their hosts from viruses. But unlike ZFNs and TALENs, they use a guide ribonucleic acid (RNA) to find their target genes and they team up with a bacterial nuclease, Cas9, to execute the cutting.
This use of a guide RNA is important – RNA can base pair with DNA, using the well understood rules of base pairing.
It is now a simple matter to design CRISPRs against any desired sequence and many labs have swung into action and are doing just that.
So why isn’t this revolution being talked about?
The revolution has crept up on us because the breakthrough really revolves around better and cheaper tools rather than new ideas or concepts. Homologous recombination and genomic editing was already possible in simple organisms and it was feasible but expensive to make knock-out and knock-in mice. But it was slow and laborious. Now it is easier.
The other point concerns specificity. We know we can make the desired changes but we do not know how many other unintended changes are also being introduced.
In agriculture, if the sum of all changes results in the desired outcome, other unintended changes may not matter. But before anyone embarks on human genomic editing we will want to know about any off-target effects. With the availability of affordable genomic sequencing this should be possible and it is reasonable to be optimistic that refinements in specificity and nuclease delivery will, one day, make genomic editing a useful new therapeutic tool.
We will have to think carefully, however, before encouraging everyone to dive in to be a biological Wikipedia editor at home.
Merlin Crossley receives funding from the Australian Research Council and National Health and Medical Research Council.