Reflecting on important topics with unique insights and different perspectives.

CRACKING GENE THERAPY tells the heroic human story behind the licensing of the world’s first major pharmaceutical gene therapy. The moving account of Margaux, a baby girl on today’s groundbreaking trial, is interwoven with a historical journey through the triumphs and tribulations of the field. This takes us back to the first experimental gene therapy in 1990, which famously treated the four-year-old Ashanthi DeSilva at the National Institute of Health, for the same disease.

Comparing these two treatments provides an original story of the 30 years of transatlantic research it has taken to get this product to market. The fascinating human narrative and easily digestible explanations skillfully guide the reader through the mechanics of gene therapy: how it works, the science behind it, the research process and most importantly its healing power. The gene therapy dream has finally become a reality for patients the world over, in a concise 5000 words this story reveals surprising insights into how it happened.

https://www.amazon.co.uk/dp/B074D727TK

Why We Need to Keep Pushing for Newborn Screening for SCID

featured in The Mighty 5th September 2017

Gene Editing: from science fiction to science fact

15 March 2016

by Amelia Vale

The slicing and splicing of human genes attributed to science fiction movies and books are literally becoming science fact.   

Research underway in laboratories around the world using new gene-editing technologies means age-old genetic diseases could become a thing of the past. In the wrong hands, however, these cutting-edge tools could turn a scientific dream into a living nightmare. People have been quick to highlight their commercial prospects enhancing humans, reminiscent of the cult Hollywood movie Gattaca. They could even end up accidentally creating new incurable diseases as depicted in Warner Brothers film I Am Legend.  Worse still the technology could fall into the wrong hands and be used in bio-terrorist attacks  like the threat Dan Brown’s protagonist Robert Langdon  faced in the book Inferno.

If this sounds far-fetched, bear in mind these are all scenarios that rational scientists have been mulling over of late. And why: a formidable new gene editing technology which is proving to be THE hot new piece of kit for genetic modification.

The technology maybe new but scientists have been envisioning moving around our genetic make-up for a long time.  At the turn of the millennium the 25,000 genes, which govern our bodily functions and traits were sequenced, giving scientists the script they needed for some serious engineering. Up until now the idea of creating genetically modified babies was a distant vision but in 2013 it was pulled into sharp focus when Crispr/Cas9 arrived on the scene. Short for Clustered Regularly Inter-spaced Short Palindromic Repeats, its precision search and destroy capability means that specific DNA letters, which form our genes, can be modified (disabled, edited out or inserted) with unprecedented ease, speed and affordability.  

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IN DETAIL: Crispr/Cas9

The Crispr technology is based on an immune response that bacteria use to protect themselves against viruses. When bacteria detect the invading viral DNA they produce two types of short strands of RNA; one of which contains a sequence that exactly matches that of the invading virus.  These two RNAs join forces with a protein called Cas9, which is a molecule that can cut DNA. The RNA molecule guides the Cas9 protein to the target sequence of viral DNA that it then cuts to disable the virus. Scientists have harnessed this system to cut the DNA of any species by programming the guide RNA molecule to hone in on any DNA sequence they want to change.

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The research started out by testing Crispr/Cas9 on diseases that were caused by one faulty gene with the idea of progressing to more common diseases like cancers that have multiple genetic mutations.

However, research teams from around the world leapt on the Cripr/Cas9 bandwagon and this led to an explosion of Crispr experiments. We are already starting to see the results of these; which range from correcting the single gene responsible for the muscle-wasting disorder Duchenne muscular dystrophy to disabling numerous genes involved in cancer cell growth. 

But with the hopes come the fears: while researchers at Duke University in the US were manipulating a gene to boost muscle function in individual mice with Duchenne muscular dystrophy, researchers in China were manipulating a gene to create a new breed of super-muscular dog.

The relative ease and speed at which they did this has psyched up religious and ethical groups. “This is consumer eugenics,” says Dr David King from Human Genetics Alert.  “Gene editing will become an entrepreneurial technology, next it will be used to enhance humans in athletics, then in the army and police force and then in society at large. The consumer market will prevail.  It will be divisive and create greater inequality with those who can afford to pay for it and those who can’t. It will be a disaster for our society.”

Dr King stresses that he has no issues about genetic editing for the purpose of sparing individuals from terrible diseases. But what he finds totally unacceptable is any alteration made to the DNA of human embryos. Crucially, these changes would affect all other cells in the body, including sperm and egg cells, meaning they would be passed on to future generations.

The Chinese researchers genetically modified the embryos of their experimental dogs, and therefore any off-spring will be this new super-muscular variety. The researchers at Duke University, however, chose to directly inject their modified genes into the muscle and blood cells of their mice so these changes are limited to just those individuals. “There is no medical argument for engineering embryos,” Dr King asserts. “Genetically modified babies will just lead to designer babies. There are plenty of other options for parents from prenatal testing [to ultimately select disease-free embryos for those who actually know they carry a genetic mutation] to adoption.” 

Last month the UK was the first country to approve gene-editing on human embryos. Not only was the move seen as “a step too far” by the usual opponents but many leading scientists in the field also disapproved. They met at the first International Gene Editing Summit in Washington last December and recommended a ban on manipulating embryos until the scientific and ethical consequences are better understood.

Edward Lanphier, the founder of Sangamo BioSciences which developed the first gene-editing patient treatment, was amongst those calling for the ban. Without a “robust public discussion” and understanding about the difference between these two gene therapies, he worries there could be a backlash regarding therapies (like Sangamo’s) that are currently treating numerous people on trials. 

According to Prof Don Kohn, a pioneer of both traditional gene therapy and gene editing at UCLA, "Crispr creates so many opportunities for the field. It is an enormously important path of research as for so many diseases adding a gene isn't going to work. But I see editing embryos as a line that shouldn't be crossed. It is crucial that we keep tabs on what is going on and stick the proper protocol," he stresses.  

Other scientists agree but policing countries around the world will not be easy, especially those with laws unto themselves. They were particularly concerned that a different group of Chinese researchers had moved into editing human embryos without informing the scientific community.  Not only did they think that they had been reckless in crossing this ethical line, the Chinese research data proved this to be the case. 

An attempt to replace the single gene responsible for the severe blood disorder beta-thalassemia resulted in such poor uptake of the new gene that the researchers decided to go back to the drawing board. But it got worse when they saw that the technology had made numerous unintended gene mutations as well. If this was to happen in a human treatment the consequences would be disastrous. Scientists could accidentally create new diseases, the likes of which we would be totally unfamiliar with, for generations to come.    

This technological star, however, has not fallen from grace. “The paper from this Chinese group is the first to ask if the methods work, and the answer provided is very equivocal. Yes, they do, but inefficiently and with several problems,” Robin Lovell-Badge, Head of Stem Cell Biology at the Francis Crick Institute in London, states. Researchers realise even the most promising gene editing technology will take time and effort to perfect before it can be considered for human use. If scientists proceed with caution abiding by rigorous practices, safe-guards and regulations; gene editing could simply eradicate numerous devastating diseases -forever.

The most significant result of the first human embryo manipulation was the warning it sounded off, like a loud fog-horn to the world.  The reverberations of this issue, however, are yet to truly reach the general public. It is vital that people voice their hopes and fears and influence the decisions that will be made on the future of the human race.

The gene editing bandwagon is rapidly gathering momentum. Everyone must get on board the debate to ensure that the repercussions familiar to science fiction don’t become a fact of live.