Sep 26

Sep 26 GMO? OMG! The history of genetic modification

100 Ideas, Genetic engineering, History of genetics

Photo by University of Michigan School for Environment and Sustainability (CC BY 2.0) . Via Flickr

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“Genetically Modified Organism” or GMO is a loaded term. Thanks to all the misinformation swirling around on the internet and in the wider media, there’s a lot of confusion about what GMOs are, why they’re created, and whether they’re safe or even a good idea at all.

But while misleading headlines about ‘Frankenfoods’ may grab attention, there’s a much richer and more nuanced story about the history and uses of genetic engineering that deserves to be told.

For as long as humans have domesticated plants and animals, they’ve tried to shape them through selective breeding, either to perpetuate, improve or lose particular characteristics. Today’s chunky dairy cows with their huge, milk-packed udders are world away from their daintier counterparts from the earlier half of the 20th century, for example.

Then there’s mutation breeding, which involves deliberately exposing seeds to DNA-damaging chemicals or radiation in order to induce potentially beneficial new traits.

Thousands of new plant varieties have been generated in this way since the 1930s - many of them foods that are commonly grown and eaten around the world today.

But when we talk about genetic engineering, or genetic modification, what we really mean deliberately altering genes - whether that’s fixing, changing or breaking them - or introducing new DNA into an organism (a process known as transgenesis). And that really started in the 1970s.

In 1971, Kathleen Danna and Daniel Nathans at Johns Hopkins University in Baltimore published a paper detailing their research on bacterial proteins known as restriction enzymes, first discovered in the 1950s. These enzymes are like little scissors for DNA, and are produced by bacteria in order to protect themselves from viral infection by chopping up invading viral genes.

Danna and Nathans showed that one of these enzymes, ‘endonuclease R’, cut up DNA in a highly reproducible way, always chopping a particular virus into exactly the same fragments, suggesting that it recognised and chopped a specific sequence of DNA.

So, if these enzymes would cut viral DNA at specific points, then why not DNA from anything else?

Add in DNA ligases - enzymes that paste these cut fragments of DNA back together again, which had been discovered just a few years earlier, and you have the makings of a genetic engineering revolution.

This meant that scientists now had the ability to chop up DNA extracted from any organism and pop it into a virus or a plasmid - a small circle of DNA that can be grown in bacteria. And if that DNA contains a gene encoding a protein, then those bacteria might start making that protein (if you’re lucky).

One of the first people to do this was Paul Berg - a biochemist at Stanford University in California. In 1972, he cut and spliced DNA from two different viruses together with a short sequence from bacteria, with the intention of putting this hybrid DNA back into bacteria.

However, he initially stopped short of taking that final step, for fear of what might be produced and whether it could be safely contained in his lab.

It wasn’t just Berg who was concerned. Many people were worried about the potential of these new molecular tools to be used for harm rather than good, including many of the scientists working with them.

In 1975, Berg and a number of the leading lights of the field convened a meeting at the Asilomar Conference Centre in California to discuss the power and potential of this so-called recombinant DNA technology. Together with lawyers and doctors, they drew up guidelines on what these new tools should - and shouldn’t - be used for.

They also outlined the safety measures required for working with genetically modified cells and organisms, and made efforts to communicate the risks and benefits of this technology to the public. And from that point on, biotechnology boomed - not just in academic research labs but on an industrial scale.

Scientists used genetic engineering tools to isolate the genes encoding vital biological molecules and put them into bacteria, allowing large-scale safe production of life-saving medicines such as insulin, which was previously made from dead cows or pigs.

This wasn’t without controversy, and activists in the 1970s pushed back hard against GMO human insulin - a move that seems shortsighted and almost cruel today, but was driven by understandable fears and uncertainty.

Today, genetically modified bacteria, yeast and laboratory-grown cells are used on a grand scale for all kinds of purposes and products - a field now known as synthetic biology.

There are GM bugs that make drugs, produce green fuels or environmentally-friendly rubber and other materials, eat oil spills, sense diseases and much, much more. And the applications of genetic engineering technology don’t stop there.

Precision genetic engineering is an incredibly useful research tool used in labs all over the world to create modified cells and organisms, from fruit flies and nematode worms to zebrafish, frogs, mice and more.

Rather than just hoping for interesting mutations to turn up that mimic your disease of interest or hit your favourite gene, genetic engineering allows scientists to create precise changes that alter, enhance or completely eradicate the activity of certain genes - something that has got a lot easier in recent years with the advent of gene editing technologies such as CRISPR.

Genetic engineering tools are also used to insert markers that flag up when and where in the body genes are active, particularly during embryonic development. One of the most famous is GFP - a gene encoding a fluorescent protein originally isolated from jellyfish, which fluoresces green under ultraviolet light.

These tools have brought huge advances in understanding how genes work in normal situations and in disease. For example, there are ‘oncomice’, which mimic the development of human cancers in the body much more accurately than cells growing in a Petri dish. And in recent years they’ve brought significant steps towards gene and cell therapies with potential for treating diseases that were previously thought to be incurable.

It’s hard to argue that using these genetic engineering tools to understand the biology of life and improve human health is a bad thing - although we’ll save the discussions about genetically engineered humans and adventurous biohackers for another day.

But one area where genetic technology gets a lot more controversial is when these tools go out of the lab and into the foods we eat.

Back in episode 5 we dug into the story of the failed FlavrSavr GM tomato - the first time a genetically modified food was stocked on UK shelves. Since then, many genetically modified crops have been approved around the world - mostly soybeans and maize - with modifications including herbicide resistance, pest resistance, drought tolerance and increased levels of vitamins.

Livestock are more tricky, and to date the US FDA has only approved one genetically modified animal for human consumption - that’s the growth-enhanced AquAdvantage salmon.

But there are others waiting in the GM barnyard, including the wonderfully-named ‘Enviropig’™ which produces less polluting waste than its unmodified counterparts. Maybe not the Green Ham that Dr Seuss was thinking of...

However, there are serious questions to be asked about the benefits of GM foods, and we have to be able to trust the food on our plates.

Using genetic technologies to modify agricultural plants and animals raises issues around food safety and potential risks to wildlife and unmodified species, as well as possible harms to the modified organisms themselves.

It was recently discovered that a line of cows that had been genetically modified to remove their horns also carried an antibiotic resistance gene that had been accidentally left behind by the modification process.

There are also bigger questions about the impact of large-scale monoculture farming - which is an issue whether it’s with GM organisms or those generated through regular breeding - as well as potential reduction in diversity of crops and equitable, affordable access to food.

But at the same time, these risks need to be balanced against the benefits. Genetic technology can create more nutritious food, as well as animals and plants that are resistant to potentially devastating diseases.

There’s the potential for generating crops that will withstand drought and other impacts of climate change, with higher yields and a reduced need for water and pesticides which may be very slow or even impossible through conventional breeding.

Personally speaking, blanket opposition to any genetic engineering techniques in agriculture or farming is unhelpful, in my opinion.

In the face of a growing global population and a changing climate, food security is a major issue - particularly in many of the poorest parts of the world - and we owe it to our fellow and future humans to figure out how to use these tools responsibly, safely and fairly.

Finally, there’s one GMO-based foodstuff that most of us probably eat on a regular basis without even realising. That’s chymosin - the enzyme used for making most of the cheese produced in many parts of the world.

Chymosin or FPC is the major component of rennet, a substance traditionally made from the ground-up stomach linings of young cows and is used to thicken milk as part of the cheesemaking process.

That’s not sustainable on the scale of today’s industrial cheese production, so FPC is now grown and purified from a genetically modified mould known as Aspergillus, which carries the chymosin gene.

The enzyme itself is not technically a GMO, as there are no traces of Aspergillus left once it’s been purified, but the cheese made using it is still technically the byproduct of a GMO.

If you want to eat cheese that has no associations with GMOs, then your best bet is ‘organic’ cheeses, which still contain rennet made from cows. And if you’re a vegetarian who wants to avoid calf stomachs and doesn’t like the idea of GMOs then it’s hard cheese - or rather, no cheese - for you.

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