The genomic revolution: reading and editing the code of life

By Dries Dury, International & Sustainable equity fund manager at DPAM


“Who thinks their genome will be sequenced at least once in the next 10 years?” With that question DPAM kicked off an internal research meeting about the genomic revolution. Almost half of the analysts and portfolio managers in attendance raised their hand.

Fewer than 0.02% of humans have had their genome sequenced, ever.

The genome is the complete set of genes – stretches of DNA that code for something – present in a cell. DNA can be visualised as a spiralling ladder. The steps of that ladder are made up of 4 different type of chemicals called DNA bases, which scientists have labelled A, C, T and G. DNA tells amino acids how to line up and form themselves into specific protein shapes, which are the building blocks of life(1).

If you look at one side of the DNA ladder, you can actually read its chemical code – or genetic sequence – from top to bottom. In a way, it is like reading a book on a molecular level. The Human Genome Project produced the reference sequence of the human genome in 2003. The project took more than 10 years to complete and cost almost USD 3 billion. The first reading of an actual individual genome cost about USD 20 million in 2006. That price has fallen to USD 1000 today. Current sequencing technology is expected to further lower the price tag to USD 100 within the next couple of years(2).

It is estimated that over 90% of all sequencing data world-wide has been generated through the instruments of one company: Illumina. DNA sequencing is still in its infancy, but Illumina is already generating close to EUR 4 billion in revenue and EUR 1 billion in profits annually, despite investing EUR 700 million in research & development.

In total, there are 3 billion DNA bases (A, C, T and G’s) in each of the tens of trillions cells in the human body. Astoundingly, 99.9% of human DNA sequences are identical to each other. So we still have about 3 million differences between our respective genome sequences that make us unique. As of yet, we only understand the functional value of less than 1% of these variants in the human genome.

With population genomics programs, governments are looking to obtain valuable input by analysing large numbers of DNA sequences from their population. For instance, Genomics England aims to sequence 100,000 genomes from patients with rare diseases and common cancers. In the US, the All of Us program plans to sequence and genotype DNA from a million participants. China announced a Precision Medicine Initiative and plans to invest USD 10 billion to sequence genomes and gather clinical data.

Each one of our cells contains 23 pairs of chromosomes, one set of 23 from mom and one set of 23 from dad. The most important gift your mother and father ever gave you was the pair of three billion letters of DNA that make up your genome. But like anything with three billion parts, it is exceedingly fragile.

Sunlight, smoking, unhealthy eating, traumas or even spontaneous events within a cell can all cause changes to your genome. The most common kind of mutation in DNA is the simple swap of one base, such as C, with a different letter, such as T, G or A.

Most of these point mutations are harmless. But every now and then, a point mutation disrupts an important function within a cell. If you inherited this mutation from your parents or if it happened early on in your development, many or all of your cells would contain this harmful mutation.

Unfortunately, hundreds of millions of people suffer from a genetic disease. Fortunately, the number of genetic diseases – such as sickle cell anaemia, progeria or muscular dystrophy – for which we now know the associated point mutation or gene is growing. Theoretically, by sequencing a blood sample, a single test could one day screen for thousands of genetic diseases at once and quickly identify the root causes of a condition to facilitate medical interventions.

GRAIL, a spin-off of Illumina, is developing a blood test for the early detection of cancer, when it can still be cured. Today, effective screening only exists for a few cancer types, and most cancers are detected at later stages, when survival rates are much lower(3).

Genetic diseases caused by point mutations are particularly frustrating, because we often know the exact single-letter change that causes the disease and, in theory, could cure it. Children with progeria are born with a T instead of a C at a single position in their genome. This unfortunate misplacement causes these kids to age at such a fast rate that they rarely live past the age of 15.

Our medical capabilities have been unable to change that disease-causing T back into a C. Until now. Crispr-Cas9 allows scientists to make targeted changes to an organism’s DNA. CRISPR is a protein that acts like molecular scissors to cut DNA. Amazingly, these scissors can be programmed to search for and cut only a specific DNA sequence. When that happens, DNA coding can be altered(4).

This summer, for the first time, doctors in the US used this gene editing technology to try to cure a woman from sickle cell disease. Prior to this intervention, the sole possible treatment for sickle cell disease was a donor transplant, which only succeeded 10 percent of the time.

The first genetically modified babies, Lulu and Nana, were born in China in October 2018. CRISPR was used to modify the babies’ DNA to attempt to give them a genetic resistance to the HIV virus. This controversial experiment was criticized by many scientists.

Genus, a company from the UK, is creating a genetic change leading to pigs that are resistant to porcine reproductive and respiratory syndrome, a pig disease that is estimated to cost pig farmers some EUR 3 billion annually.

Changes in the DNA have been happening throughout evolutionary history in a natural way, through the process of natural selection. Humans can now read and edit DNA in a fast, cheap and relatively accurate way at their discretion. This is a fantastic opportunity to get rid of diseases, but we need to act prudently, by assessing risks in the best way possible and agreeing to respect clear, ethical standards.




(4)Can we cure genetic diseases by rewriting DNA?, David. R. Liu, TED talks 2019.


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