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August 19th, 2017 at 9:30 am

The code of life

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Centuries ago we were writing on clay tablets.

In this century we will write the stuff of life.

At the most basic level, we’re all biological machines, designed not only to pass on information to create future generations, but also to conserve and amplify the information best suited to our current environment. These are the fundamentals of evolution. Our genes are what allow us to do this – they’re software programs. This is not a metaphor. Genes are made up from the code of life. It’s just that the sequences of data are made up of Gs, Cs, Ts and As, rather than 1s and 0s.

One generation ago, at around the same time as the birth of the modern internet, a group of scientists embarked on one of the most ambitious scientific projects of all time: an attempt to decipher the entire human genome, the code that makes us from the bottom up. In 2003, after 13 years of hard work and billions of dollars later, they pulled it off. The story of how they did that is one of greed, ingenuity, ambition, big egos and dazzling technological breakthroughs. Someone should definitely make a movie about it.

But that’s not the story we’re telling in this blog post. Instead, we want to tell you what’s happened since then.

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Today, 14 years later, we can read the code of life in high fidelity. Genome sequencing is commonplace in the fields of biology and medical research (I’m speaking from personal experience – I do this stuff every day in the lab). It costs around $1000 per genome and takes about a week. A decade ago it cost $300,000. And according to Francis deSouza, the chief executive of the world’s biggest sequencing company, it’s on its way to taking an hour and costing about $100.

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This is an Illumina gene chip. You can fit the code of life for 5 human beings on this thing.

Genome sequencing is getting better all the time. A company called Oxford Nanopore has a device the size of a Snickers bar that connects to a laptop via USB, and works by passing strands of DNA through a tiny hole at hypersonic speeds and measuring the corresponding change in electric current. This is orders of magnitude faster and means you can take genome sequencing into the field. Two months ago they sequenced the whole genome of a human for the first time, putting them on a level playing field with the biggest players. Another company called Helix has plans to sequence and store your entire exome, every letter of the 22,000 genes that code for proteins in your body.

This newfound ability to read our genome gives us a much better understanding of what makes us healthy and what makes us sick as individuals. Because we’re all unique, we differ in how we develop diseases and respond to treatments, nutrition and lifestyle. As the technology gets faster and more sophisticated it’s getting easier to determine the best treatment based on the genetics of both the disease AND the individual.

This is not sci-fi. It’s happening right now.

Here in Melbourne, my team recently completed a world first with a simple, cheap non-invasive test to detect blood cancer using genetic sequencing. Over in Boston, a company called Veritas Genetics is offering a $1,500 baby genome sequencing test that will report back on 950 serious early and later life disease risks, 200 genes connected to drug reactions, and more than 100 physical traits.

That means that for the scientific and medical professions, heavy data-mining and computation are now a big part of what they do. The sequencing is only part of it. Quality checks, pre-processing of sequenced reads and mapping to a reference genome require powerful computing facilities, efficient algorithms and skilled staff that know how to analyse data. It’s a time-consuming process. The Broad Institute in Massachusetts recently said that during one month it decoded “the equivalent of one human genome every 32 minutes. That translated to about 200 terabytes of raw data.” While that’s smaller than what’s handled daily by big tech companies, it far exceeds anything biologists and hospitals have ever dealt with, and means they’re having to completely rethink hiring practices, training and infrastructure development.

Data isn’t just the new oil.

It’s the new lifeblood of the medical profession.

Remember too, those three billion letters of code are an extraordinary treasure trove of information. There are large-scale genome projects underway in the US, the UK, France, Canada, Austraila, Qatar, Japan, Iceland, Ireland, Malaysia, India and Estonia. In 2010, the BGI Genomics Institute in Shenzhen was probably hosting a higher sequencing capacity than that of the entire United States, and they’re now aiming for a million human genomes. We can also sequence the DNA of animal, plant and microbial species. Earlier this year a group of US and Chinese researchers announced their intent to sequence “all life on Earth.” Their plan, dubbed the Earth BioGenome Project, will start by focusing on eukaryotes; the group of organisms that includes all plants, animals and single-celled organisms such as amoebas.

We’re also starting to understand how genetic data actually becomes a biological reality. This is the science of epigenetics. It’s about how your body takes information from the surrounding environment, and then creates biological machines that cause transformation. The best way to think about this is that a caterpillar and a butterfly both have the same genetic code. It’s their environment that tells that code what to do and when – leading to metamorphisis. Epigenetics is revolutionary because it shows that that the age-old ‘nature versus nurture’ debate is meaningless. Experience and environnment can alter gene activity, so the either/or thinking mode no longer applies.

Hold tight, I’m only just getting going here…

If the big medical breakthrough from the last generation was our ability to collect and read the code of life, then the big one of this generation is our ability to actually edit it. In 2012, two biologists, Jennifer Doudna and Emmanuelle Charpentier, invented a technology called CRISPR-Cas9, which allows us to take our DNA and reverse-engineer it, to simulate it, reprogram the parts that are outdated, the ones that give us diseases, or make us age. Incidentally, as a sign of the changing times we always find the symbolism of this pretty satisfying. When you see the old pictures of the Human Genome Project, it’s all middle aged guys in lab coats. These days, no old men or lab coats in sight.

Thanks to these two women, the code of life isn’t read-only anymore, it’s now write, too. In the last 18 months doctors have used CRISPR to cure luekemia, reverse blindness and engineer Salmonella bacteria to attack brain cancer. Agronomists have used to used it to give cows increased resistance to bovine tuberculosis, and stop mushrooms and bananas from rotting. Bioengineers have genetically engineered the malaria parasite to be safe for human beings, and were able to inject it into people, creating a foolproof vaccine.

For agronomists in particular, CRISPR is a godsend because its ability to add or remove plant traits is faster, more precise, easier and cheaper than traditional breeding techniques or old school forms of genetic modification. Although scientists can use CRISPR to add genes from other species, many labs are working to exploit the vast diversity of genes within a plant species, which contain the most valued traits anyway. In tomato growing for example gene editing can separately modify fruit size and weight, the branches that make flowers, the amount of flowers and the architecture of the plant from compact bush to vines and creepers. It’s a better, safer and more sustainable form of genetic modification. And for those of you still freaking out about GMOs, remember that gene editing means that what was done can be undone.

The era of human gene editing is also now well underway. Scientists in Portland recently succeeded in creating the first genetically modified human embryo in the United States. Their results follow two trials, one last year and one in April this year, by Chinese researchers who injected genetically modified cells into cancer patients. This is usually the point where we’re supposed to say how important it is to consider the moral and ethical implications. The problem is that the pace of technological change doesn’t care about our high minded sentiments. Barriers to mass use are falling rapidly and regulators have no chance of keeping up. Dog breeders looking to improve breeds suffering from debilitating maladies are actively pursuing gene hacking. A former NASA fellow in synthetic biology now sells functional CRISPR kits for $150 from his online store.

That doesn’t mean we should be worrying about designer babies quite yet. In the short to medium term, gene editing will probably work more like a powerful vaccine, giving us the ability to remove any one of the 4,000 hereditary diseases caused by a single genetic defect. Scientists are already planning clinical trials to edit human genes linked to cystic fibrosis and other fatal hereditary conditions. In the longer term though, we could edit genes and build new ones to eradicate all hereditary diseases. With genetic alterations, we might be able to withstand anthrax attacks or epidemics of viruses released from the Arctic tundra. We might revive extinct species such as the woolly mammoth. That’s when stuff starts getting really interesting…

Centuries ago we were writing on clay tablets. In this century we will write the stuff of life. Within the lifetimes of most children today, genetic and epigenetic modification will allow us to change our physical appearance and capabilities, and tweak some of the more intangible aspects of our being such as emotion, creativity or sociability. It’s going to transform the societal role of medicine from the treatment paradigm that has prevailed for 5,000 years to one of transforming organisms to give them overwhelming natural advantages against disease and ageing.

It’s a big moment in the story of humanity, comparable to things like the invention of the plough, the printing press, the steam engine and the microchip. It means that lifespan, intelligence and other basic human characteristics may quickly evolve beyond ranges that we consider normal. As they develop, these technologies will raise the most difficult ethical questions that science has ever presented society.

Via Future Crunch

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