For the next few science posts, I’m going to talk about some breakthroughs that use CRISPR-Cas9. So take this as an intro post to CRISPR technology.
The CRISPR-Cas9 system is a mechanism used by bacteria to defend against viral attack: an immune system, if you will. CRISPR is a short segment of DNA that matches a viral or plasmid DNA. The CRISPR locus is transcribed into a guide RNA. When the guide RNA binds to the complementary sequence, Cas9 (an endonuclease) is able to cut the DNA at that specific point and inactivate it.
Jennifer Doudna and Emmanuelle Charpentier in 2012 described a simplified method of the CRISPR where a synthetic guide RNA could be used. In 2013, Feng Zhang and George Church first described that CRISPR-Cas9 can be used for genome editing in eukaryotic cells.
Essentially, instead of the guide RNA being used to target viral DNA, it could be used to target a gene (in a human!). If a scientist wants to study a loss of function gene in a cell or animal, they would design a guide RNA introduce it and Cas9 into a cell and the Cas9 would remove the gene. This is an extremely targeted way of editing genes. Before, scientists would have to use radiation and other mutagens and screen hundreds of millions of cells before getting the exact mutation they want. This system can also be used to correct gene mutations! So, infinite potential.
In the scientific community, there is basically a consensus that this technology will win a Nobel Prize. (The Nobel Prize can only be shared between a maximum of three people: no one knows what combination of Doudna, Charpentier, Zhang, and Church will get it.) But recently, the East Coast Team™ (Zhang and Church) won the patent over the West Coast Team™ (Doudna and Charpentier), so that’s a big win for them.
Rita Levi-Montalcini was born in Turin, Italy in April 22, 1909 to a Jewish family. Her father believed that higher education would interfere with a woman’s role as a wife and mother and discouraged her and her sisters from attending university. However, Rita was able to convince her father otherwise and graduated the University of Turin with a degree in medicine and surgery.
Come the rise of fascism in Italy, Mussolini issued the “Manifesto of Race” which prohibited the professional and academic careers of non-Aryan Italian citizens. Undeterred, Rita converted her bedroom into a research lab and studied nerve growth in chicken embryos.
World War II caused her to move twice; eventually ending up in Florence where she served as a doctor for the Allied health service. After the war, she went to St. Louis to continue her experiments in chicken embryos. She eventually isolated nerve growth factor from observations of tumors that were transferred into chicken embryos that caused rapid embryonic nerve growth.
She received the Nobel Prize in Physiology or Medicine in 1986 for her work in growth factors.
World’s first “three parent” baby born. (parent as in the biological sense, not the social sense)
Dr. John Zhang of the New Hope Fertility Center helps a woman with Leigh’s syndrome give birth to a healthy baby.
Basically, mitochondria (the powerhouse of the cell) has its own DNA. And we get all of our mitochondria from our mothers. So if your mitochondrial DNA has a mutation (which this woman had), it will cause really big problems for your children (which it did). The mutation in her mitochondria killed her two previous children.
Dr. Z took out the nucleus of her egg, plopped it into a donor egg (with nucleus already removed), and then fertilized it with the father’s sperm. And voila. Healthy baby with healthy mitochondria. Whoopee!!
This also opens a new can of worms (that everyone saw coming from miles away) about gene editing in humans. This technique is actually only legal in the UK.
Here is the original paper for all of you who like primary sources
Ethanol is a renewable source of transport fuel made from plant material and, thus, is a valuable alternative to fossil fuels. Although ethanol has a lower energy content than the same amount of fossil fuel-based petrol and increases the chance for corrosion, it does have its advantages. Its higher octane content can be used to make the engine more efficient, which is also why ethanol blends have been a favourite race fuel for decades.
Burning ethanol reduces harmful exhaust emissions and – depending on the carbon-foot print of the production process - green-house gases. So, what is the catch?
Making large amounts of fuel from plant material has proven a challenging and costly process. Its production requires multi-step processes to release sugar from the plant material, which can then be fermented and distilled to yield pure ethanol. Unfortunately large-scale production has so far been more expensive and much less convenient than just drilling a little deeper for oil.
Nonetheless, there is a global effort to increase production and consumption of bioethanol. Brazil has been leading the field – closely followed by the USA - since the 1970s, when the Brazilian government made ethanol-petrol blends up to 25 per cent (E25) mandatory. Together, the two countries produced over 80 per cent of the world’s ethanol fuel in 2011. In the EU, current obligations require that 10 per cent of the European transport sector should be powered by renewable sources by 2020.
However, these elaborate government mandates have caused farmers to divert land, water and capital into growing corn and other crops for fuel rather than food. Most of the ethanol produced globally is ‘first generation bioethanol’ made from starchy plants, which could otherwise be used as food for people or livestock. 40 per cent of the corn produced in the USA currently goes into ethanol production. This has led to the ‘food vs fuel debate’.
2008 saw a spike in food prices that was thought to be linked with the increased production of biofuels and diversion of agricultural land for their production. However, in March 2010 a report by the UK’s Department for Environment, Food and Rural Affairs found that ‘available evidence suggests that biofuels had a relatively small contribution to the 2008 spike in agricultural commodity prices.’ The World Bank also reviewed their 2008 suggestion that biofuels were playing a large role in higher food prices and found that ‘the effect of biofuels on food prices has not been as large as originally thought’ in a 2010 analysis.
This may be true. Nonetheless, the large scale diversion of land from the production of food crops to the production of ‘feedstocks’ for biofuels has placed the industries’ ‘sustainability’ at the centre of controversy. The increasing demand, driven by US and EU policies, has promoted the production of biofuels in developing countries. This is further supported by views that poverty in developing countries is best alleviated by creating local employment opportunities. Research at the University of Bath has found that even though intentions may have been only the best by governments and companies alike, the reality is a far cry from secure jobs and secure provision of food. In fact, production of biofuels in sub-Saharan Africa has led to increased poverty and local food insecurity, as jobs are temporary, ‘idle’ fields are converted into biofuel feedstock plantations even though fallow land is important for future food security, and compensation for farmers is insufficient. This can only be alleviated by responsible and balanced production in these areas.
The fact is that these mandates have turned the ethanol fuel market into a big mess. And there is no stopping them. The US Renewable Fuel Standard (RFS), which was created by the Environmental Protection Agency (EPA) in 2005, originally required 7.5 billion gallons of renewable fuel to be blended into gasoline by 2012. This was extended in 2007 under the Energy Independence and Security Act (EISA) to 36 billion gallons by 2022.
The result is that the fuel industry is about to hit a ‘blend wall’, as mandates demand more ethanol to be blended into petrol than the market can absorb. Recent changes in life-style habits and advances in technology have led to a decrease in fuel consumption that is unlikely to recover. In the US, compliance with the mandates is implemented through the use of tradable RIN (Renewable Identification Number) credits; so rather than purchase an excess of ethanol, refiners meet their quotas by buying RIN credits.
Since the spark of the ‘food vs fuel debate’, governments have realised the drawbacks of first generation biofuels. Second generation bioethanol may be able to alleviate some of these limitations. It is produced from cellulosic feedstocks, such as agricultural and brewery waste and non-food plants, such as grasses and wood chips.
Commercialisation of this advanced bioethanol has been extremely challenging technically and financially. Cellulosic plant material requires chemical and enzymatic pre-treatment to release sugars from cellulose and lignin, which can then be converted to fuel using thermochemical processes (high temperatures and pressure) or biochemical processes (natural or engineered bacteria, yeasts or algae). Industrial-scale plants are still small compared to corn-ethanol plants, and the ethanol produced is too expensive to be competitive with first generation ethanol.
The ethanol fuel market is already saturated, so again policies and mandates were introduced to create a market for second generation bioethanol. The EPA envisioned the US supply to be 21 million gallons by 2022. Production challenges have caused supply to fall short, so the EPA has cut the mandate for cellulosic ethanol from 14 million to 6 million gallons this year.
Earlier in September this year the EU parliament voted in favour of introducing a cap of 6 per cent on first generation biofuels and a swift transition to second generation renewable fuels in order to fulfil the 10 per cent renewable fuel quota required by the Renewable Energy Directive. While this has thrown a lifeline to start-up companies producing second generation biofuels, it has put producers of first generation biofuels under pressure. This vote also strengthened the accountability for indirect land usage change and greenhouse gas emission in future analysis of the carbon-foot print of biofuel production. However, the vote was not as strong as was hoped and a second reading of the legal text has been called for, so a final decision may be delayed until later next year.
With a mandated lifeline and market created, up-scaling highlights another challenging limitation in the production of second generation ethanol: the availability of appropriate waste generation sources. A factory with 140 million litres ethanol output per year requires 350,000 tonnes biomass to operate. Organic waste is abundant, but generally thinly spread. Getting it to one location will be costly. And just as with diverting land for food crops to ethanol feedstocks, diverting wasteland will be controversial. Perhaps, we will see a ‘biodiversity vs fuel debate’ if this is not managed carefully.
So what does the future hold? It seems the most successful strategy will be the collocation of a waste producer – this may even be a first generation ethanol plant - with a waste-to-ethanol plant. In this model, second generation bioethanol will fill a commercial niche and create more profit while also reducing waste. This is already being trialled in Brazil.
As for the UK, for now we remain in the bottom three of the EU renewables league table, but we are working hard to expand sustainable renewable energy opportunities. Even the University of Bath has several research groups in a variety of departments working on commercially viable and sustainable solutions. So perhaps there is hope for a way out of the mandate mess.
