Jan 30 2018


The Human Genome Project was started in 1990 and completed in 2003. It took 13 years, multiple labs around the world, and hundreds of millions of dollars to sequence the human genome – this was more than two years ahead of schedule and millions of dollars under budget.

The reason for exceeding expectations is that the technology for sequence the genome was not static – it progressed throughout the project. DNA contains a code of four letters, the nucleotides indicated by the letters G, T, A, and C. This four-letter alphabet creates 64 different three-letter words, which code for different amino acids or operations that control the conversion of the code into proteins. Sequencing the genome essentially consists of discovering the order of these four letters in the string of a DNA molecule.

In 1997 the movie Gattaca, right in the middle of the genome project, portrayed the near future in which a cheek swab would rapidly yield an individual’s genome. It turns out this is not far fetched at all – we are almost living in Gattaca’s near future, at least in terms of sequencing technology. Scientists have just published a report of the nanopore device, which is a hand-held device capable of sequencing an individual’s genome.

This represents one of the greatest technological advancements in our time – the improvement by orders of magnitude the ability to cheaply and quickly read an entire human genome. The company who makes the device, Oxford Nanopore, claims that the small handheld sequencer, the MinION, can sequence 10-20 Gb per 48 hours (a Gb is a gigabasepair, or billion letters in the genome). In the published study the MinION was used to sequence 91.2 Gb of data to complete the sequence:

The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%.

The device costs $1000. So in a couple decades sequencing a genome went from hundreds of millions of dollars to 1000 dollars, that’s at least five orders of magnitude. Sequencing has also gone from 13 years to a few days (shorter if a larger version of the nanopore is used). They also make the SmidgION, which is even smaller and attaches to a smart phone.

The advantages for research are obvious. With rapid and cheap sequencing technology we can sequence the genomes of many plants and animals. This allows us to study evolutionary relationships, to identify new species, and to “barcode” plant species. Medical applications are also obvious – we can identify genetic diseases in individuals, and researchers can more easily locate specific genes that cause or predispose to certain diseases. There are now over 2,000 tests available for human genetic diseases.

There are also some applications which may not be immediately obvious. For example, researchers can track the spread of an infectious disease more easily if they can trace how strains mutate as they spread. This was done to track the latest ebola outbreak, for example.

The Human Genome Project, in addition to being an example of extremely rapidly progressing technology, is also an example of overhype. It was often overpromised in popular coverage of the project that once we sequenced the genome, there would rapidly be numerous medical applications.  Diseases would start falling one by one. Fifteen years later, this hype has not been realized, although it is starting to be. This is partly because being able to sequence the genome is only one piece to the puzzle. We also have to know what all those genes we are sequencing do.

This has led to the proteome project – the effort to map which proteins all those genes code for. We also have to know what the proteins do, how they are regulated, and what goes wrong in specific diseases.

What the genome project has done, however, is made all this later research faster and cheaper. But still, this kind of research takes years and decades. What often happens is that scientific and technological advances are met with unrealistic hype. However, wait 20 years and the hype eventually becomes a reality (sometimes – I’m still waiting for my flying car). We may be getting close to that situation with the human genome, especially now that CRISPR has given us the technology to rapidly and cheaply alter that genome.

What about the abuses of this technology that was the focus of the movie Gattaca? In the film rapid sequencing was used to identify those who were genetically fit (valids) and separate them from the unfit (invalids). This created a social caste system based on genetics. The situation was also tied to the idea of guided vs unguided conception – having children and just throwing the genetic dice, or guiding conception by choosing the best genes for your children.

While I don’t think it will play out as in the movie, these ideas are not far fetched. Superior genes will likely become one more bit of social and biological capital that the wealthy will be able to transfer to their children. The ability to remove genetic diseases, and even reduce genetic predisposition to disease, is overall a good thing. This technology can lead to a healthier population, and perhaps even reduce health care costs by eliminating expensive lifelong illness. It may even be cost effective for society to pay for such genetic treatments for everyone, rather than assume the health care costs of the otherwise avoided illness.

There are too many variables to predict how this will play out, but it is not too early to start thinking about possible applications of this technology and how it should be regulated. Like many of our advanced technologies, it can be a great thing, but it can also be abused or lead to unintended consequences. The rate at which such technologies are advancing is also both a boon and a challenge. It doesn’t give us much time to adapt to the advancements.

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