Cheaper than free

In a few years, people will be taught to trade their genome

Yuri Vishnevsky, "Business Capital"

People have long been accustomed to the fact that high technologies are getting cheaper every year and are becoming more widely available. This applies to computers and mobile communications, the Internet and digital television, solar power plants and electric cars, and soon, you see, space flights will also be affected.

Nevertheless, the cheapening of technologies has always meant only a reduction in their price by some times, but it was not a question of it falling to zero or even lower. However, it is precisely this stunning prospect that awaits one of the most advanced biomedical technologies – genome sequencing. This was announced by an outstanding American geneticist, professor at Harvard University and the Massachusetts Institute of Technology George Church in two lengthy interviews: in May – to 52 Insights magazine, in July – to Medium magazine.

52 Insights magazine, talking about Church, noted that he is called "the most interesting scientist on earth," and Medium, introducing the interlocutor, called him "the most influential geneticist of our time." However, Church's forecast deserves attention rather for another reason: he is one of the most active and successful entrepreneurs in this field. The company Veritas Genetics founded by him in March 2016 was the first in the world to lower the price of genome sequencing, including the cost of interpretation and genetic counseling, below $1,000. Church also co-founded Nebula Genomics, which was presented in February 2018. It is she who, according to Church, is going to pay people for sequencing their genome, and not in some indefinite future, but in the coming months. "I've spent a huge part of my career trying to reduce the price of technology," says Church, "and I hope that this year we will reduce the price of DNA sequencing below zero. I hope we will pay people to have their genome decoded."

Professor George Church. Photo: wikimedia.org

Why is it necessary

For the company, the accumulated database of personal DNA is of great value, and the larger it is, the further it is possible to advance in the study of the genetic diversity of mankind and the invention of new genetic therapies. Nebula Genomics notes that the sequencing of the personal genome will make it possible to better diagnose, prevent diseases and personalize therapy. In addition, if genomic data is transferred to researchers, the causes of many diseases will be identified and new drugs will be developed. These opportunities promise to create a billion-dollar genomic data market. Nebula Genomics explicitly admits that it "strives to lead this emerging market."

The following examples give an idea of the scale of transactions already carried out in the genomic data market. In 2012, the American biopharmaceutical company Amgen acquired for $415 million the Icelandic company Decode Genetics, which sequenced the genomes of 2,636 Icelanders in order to detect genetic variations associated with diseases. In 2015, 23andMe received $60 million from another American biotech company Genentech for access to its genetic data bank. In July 2018, the British pharmaceutical company GlaxoSmithKline announced the beginning of cooperation with 23andMe in order to develop new drugs taking into account genetic analysis. The exclusive four-year partnership includes GlaxoSmithKline's $300 million investment in 23andMe equity.

When companies launch their own sequencing projects, it also requires huge investments. For example, in 2016, the British-Swedish pharmaceutical company AstraZeneca, announcing the launch of a project to sequence 2 million genomes, promised to invest "hundreds of millions of dollars" in it over 10 years. In January 2018, the American company Regeneron Pharmaceuticals announced the creation of a consortium with an authorized fund of $50 million for the partial sequencing of 500 thousand genomes from the British Biobank.

Church's companies, in order to overtake competitors, have already begun cooperation with private clinics, offering their patients genome sequencing. So, in January 2018, the Mayo Clinic, which is one of the largest private medical and research centers in the world, became a shareholder of Veritas Genetics in order to make genome sequencing widely available to healthy people in order to prevent diseases.

And in May 2018, Nebula Genomics and Longenesis – a joint venture of the biotech company Insilico Medicine and the blockchain group BitFury – announced cooperation in creating a new industry, which they called the life data economy. According to the partners, they plan to create platforms using blockchain technology to exchange genetic data, medical records and other biological information. Currently, Longenesis uses artificial intelligence to store and share health-related data and results, whereas Nebula Genomics uses blockchain to store genomic data. The partnership plan is to combine both of these technologies. "Nebula Genomics is creating a market that will ensure a fair and efficient genomic data economy. Longenesis has built a similar platform that focuses on long–term health data, so our platforms complement each other very well," Church emphasizes.

If patients whose medical records are collected in the Longenesis data bank agree to sequencing their DNA to replenish the Nebula Genomics data bank, then a unique array of information will be obtained, the analysis of which will reveal correlations between genetic variations and various pathologies. Thanks to this, the tandem of the two companies will be able to outstrip competitors in this direction for years and become a monopoly supplier of exclusive information to the largest pharmaceutical corporations. This prospect makes paying patients extra for genome sequencing cost-effective.

Benefits for the state

However, governments can benefit even more from reducing the price of DNA sequencing. And if they realize this benefit, then in just 10 years they will be able to accustom people to genetic control. True, the professor himself does not directly say this, but everyone can draw conclusions from his words himself.

Everyone should be able to decode the genome, Church is sure. If such a practice became widespread, we could save hundreds of billions of dollars that are spent on healthcare – due to the fact, for example, that about 5% of babies are born with very serious genetic disorders. People would take this into account and avoid risky alliances when both he and she are carriers of a mutant gene. You can even create software so that potential marriage partners themselves check their genetic compatibility by entering transcripts of their genomes.

Another example of this kind is the incompatibility of medicines. According to Mayo Clinic estimates, more than 7% of drugs approved by the US Food and Drug Administration (FDA) cause an adverse reaction in patients with some genetic variations. In particular, 10 years ago it turned out that warfarin, usually prescribed for blood thinning, can lead to fatal internal bleeding in people who are genetically predisposed to it. Knowledge of personal pharmacogens should help doctors in determining the correct choice and dosage of medications to prescribe to patients.

Prevention of diseases in people with various genetic abnormalities also promises huge benefits. For example, take non–alcoholic steatohepatitis, a chronic inflammatory liver lesion caused by its fatty degeneration. According to the Mayo Clinic, this is the most common form of chronic liver disease in the United States, 80-100 million Americans suffer from it. Recent studies have shown that this disease is genetically determined. If you know about each person, to which diseases he is genetically predisposed, then you can give him recommendations about a diet that will allow you to maintain health for as long as possible.

In short, thanks to genome sequencing, people will be able to find out what food is right for them, what medications should be avoided and who should not have children with. If the sequencing of personal genomes is carried out nationwide, it will dramatically increase the proportion of healthy able-bodied people in the population. As a result, the economy will receive an incentive for growth and, in addition, the demographic situation should improve. So the state interest is obvious, and the time is not far off when governments of different countries will decide to take advantage of this opportunity.

The rate of cheapening

Of course, the implementation of such plans will require considerable costs. But the cost of sequencing a personal genome is decreasing every year, and very sharply. In 2001-2017, it fell by 80 thousand. once – from $95.3 million to $1,150 per genome. Such data is provided by the National Institute for Human Genome Research, part of the system of the National Institutes of Health of the USA. The price of genome sequencing is expected to drop to $100 over the next few years.

At the same time, DNA sequencing methods are constantly evolving. One of the directions is to create a fairly cheap fluorescence technology that will allow DNA elements (nucleotides A, G, T and C) to be colored in different colors for the convenience of genome research. By studying this picture under a microscope and recording it on a camera, it will be possible to quickly and reliably determine in what order the nucleotides are located in the chain. Such fluorescent sequencing can be combined with augmented reality technology to get a more visual and clear image, says Professor Church.

According to him, the development and cheapening of technologies will lead to the fact that they are legally available to individual users. "In the future, I think there will be portable gadgets for decoding the genome – not just your own. They can even be used to analyze the environment for the presence of allergens and pathogens and to obtain information about other people and other living beings near you," Church predicts.

How will geneticists prolong our lives

The professor paints a rather optimistic picture of the future. He never tires of emphasizing the rapid development of technology. What was considered impossible or very expensive yesterday is becoming publicly available today, and tomorrow it will become commonplace. Such promising opportunities include an increase in human life expectancy.

One should not think, says Church, that there is some universal solution to the problem of prolonging life - some kind of food, diet or medicine to achieve this. You can count almost a dozen ways in which research in this area is going on. In particular, it is the fight against inflammatory processes, the repair of mitochondria – cellular power plants (in both cases, special proteins can be used), the restoration of telomeres – the end sections of chromosomes that shorten with age, etc. Many of these methods have been tested on mice, experiments have shown their effectiveness.

Another direction is genetic therapy. Currently, about 2,000 gene therapies are undergoing clinical trials. If a person lacks a particular protein or its functions are disrupted, then this protein itself or the gene that encodes it can be delivered to the body. In addition, it is possible to design new proteins that will do something new in the body, and with the help of gene therapy, teach the body to create them. You can also find rare people with exceptionally interesting proteins. For example, there are people who have defeated HIV-AIDS even without treatment. And if you find out thanks to which proteins they succeeded, then with the help of gene therapy, you can teach other people's organisms to create such proteins.

Church emphasizes his disagreement with some of the "red lines" that are proposed in genetic research, for example, with the rejection of genetic modification of embryos and reproductive cells. If such a modification helps to get rid of a hereditary genetic mutation, then why not use it. This is much more acceptable and much safer than standard medical practice – abortion.

Is it possible to build brains

Church's professional interests are very extensive. It also includes research on artificial cultivation and transplantation of various tissues and organs to patients, including brain tissues.

"In our experiments on growing brain tissue from stem cells," says Church, "we have achieved the creation of structures with a volume of about half a billion cells, which is more than the brain of a mouse. We can grow cells of various brain tissues. In the future, they can be used to analyze the effects of certain genetic disorders, to test new drugs or new treatments, including gene therapy."

In the future, the tissues grown in this way can also be used for transplantation to replace areas of the brain affected by diseases. It is hoped that this will help to cope, for example, with Parkinson's disease and epilepsy. Another possible use is the regeneration of areas of the brain that have suffered damage or ruptures (such injuries usually cause paralysis).

This suggests that some of the healthy people will want to add brain tissue to themselves. This requires confidence in the safety of the technology, but, according to the professor, this is possible.

Brain fragments grown in the laboratory can also be used as a basis for artificial intelligence. After all, the human brain is far superior to computer systems in many respects and at the same time spends much less energy. It is possible that in the future there will be a computer that will use human brain tissue.

And this is not the only promising direction of biocomputer technologies. Now, for example, technologies for storing information in DNA are being developed. This promises about a million times more information density than that which can be achieved in traditional silicon or other inorganic media. Perhaps purely biological artificial intelligence systems will prove more promising than inorganic or even hybrid systems.

A superbrain instead of a supercomputer

Of course, all this may seem fantastic. But do not forget that Church is engaged in those studies for which he finds money, and a lot of it. And not only his group is engaged in such research, but a number of teams (albeit with varying success) in different countries. And if computer technology boasts exponential growth, then biotechnology, as Church notes, is growing even faster – superexponentially. Therefore, they may soon become no more expensive than computer ones and start competing with them in their field.

And here we return to the topic we started with – genome sequencing. A complete description of the human genome takes at least 200 gigabytes. If the genomes of, say, 1 billion people are decoded, then 200 exabytes will be required to store this information. This means that genomic data banks will surpass any video and text databases in their volume. In addition, genomic banks will be replenished with data on gene editing. All this information must not only be stored, but also processed. So from this point of view, we again come to the inevitability of the appearance of a biocomputer.

There have already been many prophecies about a supercomputer "big brother" – artificial intelligence that will monitor everything and everyone. Now such soothsayers look like naive simpletons. If such a supercomputer appears, it will be biological and will be able to control us not only from the outside, but also from the inside – through our genes.

However, Church did not go so far in his forecasts, but only noted that experiments on human-like artificial intelligence are unethical. However, as history shows, everything that can be created necessarily appears, and no ethics is an obstacle here.

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