Year 11 Colloquium: Manipulating genomes
Over the course of two lectures on manipulating genomes, biology teacher Dr Henry Nicholls introduced the Year 11 Colloquium students to the exciting fields of synthetic biology and gene editing.
In the first talk on synthetic biology, the students were quick to work out that with a biological toolbox of 20 amino acids, there would be 20n different ways to arrange them into a protein built from n amino acids. So for an average protein with 300 amino acids, there would be 20300 different theoretical sequences, most resulting in their own unique three-dimensional structure and maybe function. This is vastly more combinations than have ever been tinkered with by natural selection in the 3.7 billion years of evolution. But our understanding of protein synthesis is such that scientists can now build and express any sequence they want and use software like Google’s AlphaFold to predict its likely 3D structure and anticipate myriad exciting applications. By writing the instructions for these manmade proteins into the genomes of bacteria, it is now possible to build entire new organisms from the bottom up.
In the second talk, the students learned about the allied technique of gene editing, discovered following pure research into the defence systems that bacteria have evolved to protect themselves against attack from viruses. Bacteria, it turns out, have the molecular machinery to recognise foreign DNA, cut it up and thereby disable it. By incorporating fragments of the viral DNA (known as clustered regularly interspaced short palindromic repeats, or CRISPRs for short) into its own genome, the bacteria are better able to identify and dismantle the same virus in the event of a future infection.
But this natural bacterial defence system is of more than just academic interest. In 2020, Jennifer Doudna and Emmanuelle Charpentier shared the Nobel Prize for Chemistry for their work on the CRISPR system and for realising that it could be harnessed to locate a specific DNA sequence in any genome and (in concert with an enzyme called Cas9) make precise changes to the genetic code.
The CRISPR-Cas9 tool has so many exciting applications: it can help researchers to “knock-out” genes to help infer their function; it can alter existing genes and enhance the function of the proteins they encode; it is likely to bring about a revolution in agriculture; it has even been used to correct genetic mutations in patients, as in the case of a young Syrian refugee with junctional epidermolysis bullosa, a rare but potentially lethal condition in which skin cells do not stick to the underlying connective tissue. In 2017, a team of international researchers reported how they had used CRISPR-Cas9 to edit the DNA from a stem cell taken from the boy, grow him an entire new skin in the laboratory and then carry out a successful transplant. Were it not for this procedure, he would almost certainly not be alive today.
Of course, the technology has the potential to be abused, as demonstrated by the now-infamous case of the CRISPR babies. In 2018, Chinese Scientist He Jiankui created the first genetically edited babies, using CRISPR-Cas9 to disable the CCR5 gene, a surface protein on white blood cells that the HIV virus requires to gain entry. The resulting twins may not be able to contract HIV, but the experiment caused an outcry amongst scientists, resulted in a suspension of He’s research activities, a stint in prison and a hefty fine.
The Colloquium students entered into a lively discussion over the pros and cons of using the CRISPR-Cas9 technique to make changes to the human genome. In 2021, the WHO published a position paper on human genome editing and a framework for governance. This month, the UK’s Human Fertilisation and Embryology Authority (HFEA) has made recommendations for changes to the Human Fertilisation and Embryology Act (1990), seeking to improve the authority’s ability to handle rapidly changing scientific developments like gene editing.
