How can LEGO production affect the world's synthetic DNA output?

Yes, we are talking about acetonitrile - an innocuous-looking and sounding organic solvent highly important in the pharmaceutical and analytical chemistry industry. In fact, the world consumed 113 kilotons of acetonitrile in 2018 (think 45 Olympic swimming pool filled with this stuff). Acetonitrile is used as a starting material to synthesize vitamins A and B1, and in the mobile phase in high-performance liquid chromatography (HPLC). In a conventional DNA synthesizer such as ÄKTA oligopilot plus, consumption of acetonitrile per oligo synthesis cycle is about 72% of the total aqueous volume. 

What's the connection to LEGO? Turns out that acetonitrile is a byproduct in the production of acrylonitrile, a key ingredient (25%) in the polymer, acrylonitrile butadiene styrene (ABS), that made into the LEGO bricks - more than 75 billion bricks every year. ABS is a type of plastic you encounter every day - think computer keyboard, car dashboard, and the electric sockets and drain pipes at your home. It is no surprise then the world consumed over 6,000 kilotons of acrylonitrile in 2019 (now that is more than 2,600 swimming pools).

As only 2-3% of the acrylonitrile production is harvested into acetonitrile (see chart below), one can imagine a knock-on effect if all the LEGO fans decide to turn against them and stopped buying LEGO. But this is a wider issue, as exemplified by the "Great Acetonitrile Shortage" of 2008/2009. There are two main causes of the shortage: 1) The global economic recession in 2008 drove the demand for new houses and cars down, thus reducing the demand for acrylonitrile, and therefore reduced production of acetonitrile. 2) China shut down acetonitrile factories during the 2008 Beijing Olympics to improve local air quality, and US acetonitrile factories in the Gulf Coast were closed due to Hurricane Ike. 

You may wonder, what's the big deal? Markets fluctuate all the time, and we haven't seen this kind of shortage in a decade. I am not often an alarmist, but two major driving forces are just around the corner. 

The first is the rise of antisense oligonucleotides (ASO) in the pharmaceutical industry. ASOs have finally shown clinical effectiveness has in recent years, from Nusinersen (Spinraza), the first medicine approved to treat spinal muscular atrophy, to hyper-personalised medicine such as Milasen. But the production of these oligos remains a big challenge. An example is the manufacturing of Mipomersen (Kynamro), an antisense oligonucleotide used to treat homozygous familial hypercholesterolemia. Although the current production of Kynamro theoretically uses only 0.2% of the world's supply of acetonitrile, if Kynamro is used to treat heterozygous hypercholesterolemia, the consumption of acetonitrile can jump to as high as 13% of the world's annual supply (see picture below)! Kynamro is just one out of nine FDA-approved oligonucleotide-based medicines in the market. What's more - there are over 180 other oligonucleotide-based medicine undergoing clinical trial (data from Thomas Rupp). An alternative production method will be necessary. 

Besides heightened demands for acetonitrile, macroeconomic forces in recent months stemming from the Coronavirus outbreak in China will likely send the world into an economic recession. The Western economies have relied so heavily on supply chains from China that a "supply shock" will introduce extensive challenges to all industries. An example to the point: China is not only the largest consumer of acetonitrile but also one of the largest producers

This "perfect storm" is not imminent, but the consequence can be felt without any advanced warning. If all the DNA manufacturers can switch to a more sustainable way to synthesize DNA, such as an enzyme-mediated method, the industry that will face downturn will be the petrochemical industry. 

But is the world ready to go green yet? LEGO is pledging to make all its blocks from plant-based or recycled materials by 2030. And recently, with the world's largest investment management company BlackRock bringing the topic of climate change front and centre, perhaps we will finally take collective actions. 

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