Mapping Life Itself
One might argue that the digital revolution enabled the biological one, although it might actually be the other way around. Many of the terms used in the computer world have their roots in biology – viruses, genetic algorithms, neural networks, synaptic web. So by looking at biology, might we be able to see what will come next with computer technology? As Steve Jobs once said, “I think the biggest innovations of the 21st century will be at the intersection of biology and technology. A new era is beginning”.
This new era is nicely illustrated by how algorithms to analyse genomes are being baked into next-gen computer chips. Genomes are our genetic blueprint, built up from three billion DNA letters, and genomics is the branch of molecular biology concerned with the structure, function, evolution and mapping of them.
By using baked-in computer chips, processing a whole human genome takes about 20 minutes, compared to 20-30 hours using classic CPU-based systems. That’s a giant leap since 2003, when the Human Genome Project was completed after (almost) fully sequencing and mapping the genetic code of one human. While that project cost $3bn and took 13 years, the cost to sequence a genome is around $1,000 today.
The recently introduced Oxford Nanopore MinION is a DNA sequencer the size of a Mars bar that generates sequence data in real-time. It can do this in a hospital or at home, near the bedside and with it, a bacterial infection and the proper antibiotic to use can be identified within two hours. Compared with the conventional three days before an intensive care patient with sepsis or pneumonia receives antibiotic treatment (assuming they survive the initial infection) and the clinical disruption of the MinION is abundantly clear.
Although 99.9% of every human’s blueprint is identical, within the remaining 0.1% are the genetic variants and mutations that determine how we look and influence which diseases we are susceptible to. We still don’t understand much about the human genome. 99% of it, the part which doesn’t code for proteins (the building blocks of our body), is only now starting to reveal its first secret, which is that it’s the instruction manual to make sense of the other 1%.
Also, the real impact of genomics will be only be reached once we start to grasp the sequences and profiles of its other layers, the epigenome, the transcriptome, the proteome and the metabolome. These are the true sensors and actuators of our lifestyle and environment, in combination with the DNA content of our microbiome, which are the collective genomes of the microorganisms that reside in and on our bodies.
Novel genomic studies start to provide invaluable insight into the evolutionary mechanisms that were designed by nature to help prevent individuals from developing disease. Nature also created people with a range of ‘superpowers’, from extremely dense, damage-resistant bones or high pain tolerance to a sleeper mutation which leaves the individual feeling energised after just four hours of sleep. These rare genetic outliers are pursued by pharma companies as shortcuts to developing drugs that can address osteoporosis, chronic pain and sleep problems, respectively.
Genomics has already given us medical treatments – over 25 drugs are now prescribed only when a patient has a given mutation. Cancer is no longer treated based on the geography of a tumor but instead on the presence of mutations in the patient’s genome. Recently, the state of Hawaii forced two pharma companies to tailor blood-thinning prescriptions to the unique metabolism of its islands’ population by encoded in three DNA letters that have been inherited from their ancestors and are distinct from the mainland US population. Such decision will spearhead the further development of medicines by using 3D printing to produce tailored doses that match genomic profiles. The first was approved for use in 2017.
For early diagnosis of rare disease, it has been shown that genome analyses helps to identify disease in approximately 50% of cases, six years earlier and ten times cheaper than the conventional tests used today. Genomics starts having a big impact in-utero. Down’s syndrome has, until recently, been difficult to screen for because the test involves extracting amniotic fluid from the womb, a procedure that come with a risk of miscarriage. A Non-Invasive Prenatal Test (NIPT) is now being used to detect most common fetal chromosome anomalies using a sample of the mother’s blood.
We would already be able to identify over 3,000 other hereditary diseases (many of them rare and easy to overlook) if policies were shaped to allow this. In January 2018, researchers took a major step toward one of the hottest goals in cancer research – a blood test to detect tumors prior to any symptoms showing. This is the type of work that has attracted both Amazon’s Jeff Bezos and Microsoft’s Bill Gates to invest massively in GRAIL, a spinoff from genomics powerhouse Illumina. Microsoft, which also invests in testing DNA for computing applications in order to store vastly more data, has taken a stake in another type of universal diagnostic test, which applies genomics to sequence the trillions of trigger mechanics of our immune system.
Who needs to know?
Once the technology exists, not having access to your own genome becomes ethically unacceptable. For while our healthcare systems are set up to treat symptoms, our individual DNA has the potential to become an operating manual which doctors can use to better diagnose, treat and prevent disease.
We are starting to see an evidence-based process to evaluate the clinical utility of genome-based medicine for all. The prospect of universal screening for disease predisposition will lead to some novel jobs, such as ‘genome counselors’, to meet consumer needs to understand their data and to manage expectations. For instance, if you discover that you have a genetic variant or mutation, it’s possible that your siblings or offspring will also have it. But is it your duty to pass on this information? And what if they would prefer not to know? Many people – especially the young – may fiercely protect their right to stay wilfully ignorant of potential risks.
Yet as people get older, they tend to wise up to their own mortality and the value of being informed. Another great example is how genomic diagnosis can be used to predict risk for sudden cardiac arrest. Instead of advising an at-risk patient against physical overexertion, physicians can implant a small cardioverter defibrillator, while smartphone health apps can routinely follow heart function and anticipate an intervention. These ‘guardian angel’ mobile health devices will help to harvest genomics’ impact to the fullest.
Understanding your DNA
Now that people all around the globe are starting to learn the secrets encoded into their own DNA, where do we go from here? During Thanksgiving weekend 2017, personal genomics company AncestryDNA sold a staggering 1.5 million kits to Americans. Each provides insights into people’s ethnicity and familial connections, yet they only look a very small percentage of each genome.
So what if we could all start to share all of this genetic data, from ancestry tests to the data being generated by a growing number of IoT medical devices? Such a large-scale aggregation and comparison of millions of people’s genomes could well be medicine’s next great leap forward. So far, genome sequencing has been largely detached from the internet, so organisations such as MatchMaker Exchange and Genes for Good represent something new – a way of automating DNA comparison from sick people around the world. Fast-growing companies such as BlueBee and DNAnexus already offer cloud solutions which will facilitate such large scale genomics projects.
But let’s look one step further ahead than even that. Theoretically, we will be able to start combining our genome and social profiles. Social media sites such as Facebook will then be able to build an AI suicide-prevention tool that alerts a team of staff trained to reach out to any user contemplating self-harm. Similar tools can be used to collate people’s alcohol usage – as documented on their social media posts – with a genetic predisposition for addictive behaviour and how badly they rate their hangover. A genetic insight could prompt a friendly suggestion to drink in moderation.
The power to make change
The next generation should get sequenced at birth because we are now developing the tools to make sense of, adjust or rewrite their genomes.
In less than five years, the gene-editing technology known as CRISPR has revolutionised the face and pace of modern biology. CRISPR evolved in bacteria as a primitive defense mechanism to find enemy viral DNA and cut it up until there was none left. In July 2017, researchers genetically modified human embryos using CRISPR, editing the DNA of one-cell embryos to demonstrate that it’s possible to safely correct defective genes that carry inheritable diseases.
A similar tool was applied to a living human four months later, when a patient suffering from a rare genetic condition had his genome edited using a treatment developed by Sangamo Theraputics. The patient suffered from a metabolic disease, Hunter syndrome, so was missing an enzyme to break down certain carbohydrates. We’ll find out within the year whether his body can now produce it thanks to the corrected gene.
CRISPR is being used to treat cancer in dozens of Chinese patients by modifying their immune system. This year, there will also be in clinical trials to cure genetic diseases such as sickle cell anemia and beta thalassemia, with inherited hearing loss to follow.
One exciting version of CRISPR will allow genes to be toggled on and off without altering the DNA sequence. This kind of epigenetic editing could be used to tackle conditions that arise from what we eat, how much or how little we exercise, or the pollution or stress we’re exposed to. Lifestyle and environment stressors introduce epigenetic changes to our genome, traces of which can be passed on, potentially making our children more prone to conditions such as mental illness and obesity. With this newest versions of CRISPR, we change our genome at the level where wrong lifestyle decisions can be reversed and ‘status healthy’ restored.
Gene-editing recently took an interesting new twist. Until now, recreating a dead person or animal’s DNA has required that DNA be extracted from the remains of that individual, but a new study has shown that may not be the only way. The DNA of a man who died nearly 200 years ago has been recreated from his living descendants rather than his physical remains. Jurassic Park, anyone?
We can but should we?
Of course, genomics brings quite a number of challenges. Though genetic testing is still in its infancy, it will become more routine in medicine and beyond, amplifying patients’ fears about breaches of confidentiality. These fears range from discrimination to the uneasiness that comes with a loss of privacy. Throughout history, we have seen people excluded because of their religion, disabilities or sexual preference. What if this happens because of their genome? Consider an expectant mother who is found to be carrying a child with Down’s syndrome and how, in the hands of employers, such genetic information could lead to workplace discrimination.
But it’s impossible to completely de-identify genetic information, so since complete privacy is a myth, I’m saying that you better get used to dealing with your genome. You can never anonymously share DNA information – it literally defines who you are!
I believe that in time, our notions of privacy will shift and maybe even disappear. I think genomics could help to move our society to a new model of radical transparency. So I will eventually send my genome along with my CV, or it will be generated at a job interview from a saliva sample.
A classic concern is whether my insurer will be able to use my genome against me. Insurance companies are warming up to the idea of using genomics to encourage preventive health, with insurance plans to cover the hereditary cancer risk test if they meet the criteria. We’re also seeing the first companies providing financial incentives in the form of lower premiums if people reduce risks revealed by genome testing. It’s the same as companies that pay me rewards if I exercise properly, based on data from my wearables. By the time we find out we all have certain disease predispositions, insurance companies that do not want to insure me, will outcompete themselves. That is what disruption is about.
Tools such a blockchain will be of big help here. Blockchain technology is becoming the gold standard ledger and database tool in practically every corner of the global industry. Late 2017, the first companies surfaced linking genomics to the blockchain. Geens, LunaDNA, EncrypGen, and Nebula Genomics all want people to profit by sharing their genomic data, with contributors receiving a virtual currency and partial ownership of the database. Such companies hope that this combination of data security, privacy and monetary incentives will encourage people to share their individual genomic results from consumer genomics players 12andMe, AncestryDNA, Helix and others.
This data will certainly be attractive for pharma companies looking for individuals with a certain match to be recruited in a trial. Using blockchain, they can search and purchase patients’ anonymised data and pay each individual for the right to use it. This is getting extremely relevant if you realise what your DNA is worth. A few years ago, pharma giant Pfizer paid 23andme $60 million for access to 3,000 samples of people with Parkinson’s disease. This one transaction as part of ongoing research finally gave the value of (a tiny part of) one’s genome – $20K !
Finally, genomics could constitute the launchpad for our personal digital twin – a precise visualisation of a physical object. With technological advances in data sciences, one can start to envision a detailed software model of a person – a human digital twin. If one is created at the moment of our birth, the first data point to upload could be our genome. That digital twin will then become a predictive analogue, a simulation for people’s bodies that can be used to and test modifications in lifestyle, behaviour and even genome.
I believe the genomic revolution will stand on the shoulders of that other giant, the digital one. The genomic revolution promises to help us build the foundations, figuratively and literally, of a world where people get ill no more and get paid for that. Take that for disruption.
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