1856-1863: FATHER OF GENETICS
Austrian monk Gregor Mendel revealed the probability of genes passing from generation to generation. In cross-pollinating pea plants that produce either yellow or green pea seeds exclusively, he found the first offspring generation always had yellow seeds, but that the next generation had a 3.1 ratio of yellow to green.
1869: IDENTIFYING DNA
Swiss doctor Friedrich Miescher, who turned to research because of a hearing problem, became the first scientist to identify DNA as a distinct molecule, thanks to his study of blood cells from the pus of discarded bandages.
1953: DISCOVERY OF DNA STRUCTURE
Cambridge researchers Francis Crick and James Watson revealed that the human blueprint is wrapped in a double-helix structure, like a twisted rope ladder, with three billion rungs or letters. Knowing how DNA is put together helps today’s scientists take it apart.
1961: CRACKING THE DNA CODE
RNA or ribonucleic acid transmits messages encoded in DNA. In discovering how RNA works, American biochemist Marshall Nirenberg revealed how DNA directs the building of proteins and thus of life itself.
1977: DNA SEQUENCING
British biochemist Frederick Sanger invented a method for “reading” the “letters” of the genetic code. He was the first scientist to decode the complete genome of any organism and his approach increased by a thousand times the rate at which scientists can sequence DNA.
1983: COPYING DNA
US biochemist Kary Mullis developed a technique that can produce in a few hours 100 billion copies of DNA from, say, a single human hair, a drop of blood or a 40,000-year-old woolly mammoth frozen in a glacier. Polymerase chain reaction has many uses, from gene analysis to diagnosis of hereditary diseases.
Dutch scientists first coined the term CRISPR.
2003: COMPLETION OF THE HUMAN GENOME PROJECT
The $3-billion, 13-year project enabled scientists to read nature’s complete genetic blueprint for building a person. The number of single gene aberrations known to cause disease jumped from around 100 to nearly 3,000 and more than 200 genes were now linked to cancer, nearly three times the previous number.
2005: DISCOVERY OF CAS9 PROTEIN
Alexander Bolton, of the French National Institute for Agricultural Research, made the discovery while studying bacteria.
2012: CRISPR-EDITING TOOL
Jennifer Doudna, of the University of California, Berkeley, and her collaborator Emmanuelle Charpentier were credited with co-inventing a tool for editing CRISPR. This becomes the subject of a bitter patent dispute, which is ongoing with US bioengineer Feng Zhang.
INSIGHT: GENE EDITING
CRISPR-Cas9 has the potential, in theory, to change the lives of everyone and every living thing on the planet. Enabling scientists to edit our genes with unprecedented precision, ease and efficiency, it has been compared to cut-and-paste text editing. It comprises a chemical “sat nav” – an RNA or ribonucleic acid molecule – which is primed to guide “molecular scissors” – the Cas9 protein – to editing targets.
If it fulfils all its promise, CRISPR-Cas9 will eradicate family lines of hereditary, single gene disorders such as cystic fibrosis, sickle cell anaemia and Huntington’s disease. It is already transforming research into gene therapies and helping to identify new drug targets.
Such is the excitement that one London researcher featured, along with Angela Merkel, Justin Trudeau and Pope Francis, in 2016’s Time 100, which lists the world’s most influential people. Dr Kathy Niakan’s study of human embryos at London’s Francis Crick Institute is taking her to where no scientist has been before.
US biochemist Dr Jennifer Doudna, co-inventor of the CRISPR-Cas9 gene editing tool, says: “Niakan’s work will answer previously unanswerable questions about what makes a healthy embryo, what factors contribute to infertility and what goes wrong when pregnancies don’t progress as planned.”
This could reduce, among other things, the huge tragedy of miscarriage. The Miscarriage Association estimates that more than one in five pregnancies end in miscarriage, probably more than a quarter of a million each year in the UK alone.
But there is concern as well as hope, especially over the possible emergence of eugenics and the prospect of designer babies produced to order with traits such as super strength or hyper-intelligence.
Ironically, CRISPR-Cas9’s ease of use and cost is adding to ethical concern. On line DIY kits cost as little as $120, up to 200 times less than a leading earlier system. stem. But the benefits are stacking up.
Although it was only discovered in 2012, CRISPR-Cas9 has already helped to correct the genetic defect in Duchenne muscular dystrophy in mice, deactivate 62 genes in pigs so organs of animals grown for human transplants won’t be rejected, excise HIV from human cells in a laboratory and from living animals, create therapies that turn off cancer genes, force a gene that kills malaria parasites to spread through a whole population of parasite-bearing mosquitos, and create genetically modified animal models of human disease to study genetic changes that trigger illness or confer protection.
The world’s first human CRISPR-Cas9 trial is underway at Sichuan University in China on ten patients with lung cancer.
CRISPR-Cas9 is not, of course, foolproof. For example, gene edits can occur at the wrong place, which could result in the disabling of a tumour suppressor gene or the activation of a cancer-causing one.
Translocation, the cause of chronic myeloid leukaemia, when pieces from two different chromosomes converge, is another potential problem. So there is currently research by many investigators to establish which regions of the genome could be accidentally “CRISPR’d”. And there could also be unforeseen downstream consequences of unleashing altered organisms into the human gene pool, hence the caution around moving from laboratory to clinical trials.