22 November 2018
ZeClinics and its ZeGenesis platform rely on the power of CRISPR/Cas9, a gene editing technique affected by a controversial European Court ruling. Last week ZeClinics had the honour of speaking about the value of CRISPR to the UK Parliament's All-Party Parliamentary Group (APPG) for Life Sciences. Read on for our colleague Dr Albert Pineda's full speech:
"I would like to thank the BioIndustry Association and EuropaBio for inviting me to speak to the illustrious MPs of the Life Sciences All-Party Parliamentary Group. I am Dr Albert Pineda, Director of Business Development at ZeClinics, a biopharmaceutical SME headquartered in Barcelona, Spain. I speak both on behalf of ZeClinics as well as from personal experience; having a cross-sectorial background in pharma, food and chemicals; having worked in the UK and the EU and representing a small SME specialized in drug development services with CRISPR/Cas9, one of the new gene editing technologies now labelled as GM after the recent ruling by the European Court of Justice. Let it be known that the impact of the ruling on biopharma firms like ours is limited because our gene-edited lines are only used in preclinical trials; never released into the environment or in contact with patients. For all these reasons what you will hear today is nothing but my honest professional opinion, free of any conflict of interest. I only hope to bring value to the discussion.
A Crash Course in CRISPR/Cas9
Let´s begin by putting CRISPR/Cas9 in context. I will invite you to imagine the entire genome of an organism as a vast manual with detailed instructions on how to build a living being… such as yourselves. Picture the entire 32 volumes of the original Encyclopædia Britannica, only times a billion. The manual contains entire chapters, sections, paragraphs and any minor change could potentially alter the meaning of entire sentences, if not pages. In the same way a single point mutation in a base pair within a gene (the genetic equivalent of a letter) can determine the difference between health and sickness. So where does CRISPR fit in this example? I will now ask you to imagine CRISPR as a pair of very intelligent scissors that could do your bidding. Imagine that you would send them to that instruction manual to search for the single mention of the word “duck”, target the letter "D" and replace it with another letter. I’m sure you can all think of alternative spellings and understand how drastically meanings could change. In the real world we tweak genes the same way, only not for fun but for research purposes: By switching genes off and on we can learn about their functions, their interactions and their roles in, for instance, a particular disease. And all thanks to that pair of clever scissors: CRISPR/Cas9.
Homology: From Gene to Law
As a doctor in genetics I have been involved in gene editing work with microorganisms, plants, vertebrates and I can tell you that, small differences aside, molecular genetics work is pretty much the same among species: Some will carry out homologous recombination, others will have a cell wall, but plainly speaking a cell is a cell and what applies to one organism is often valid for another. This translatability also is the foundation of preclinical drug assays which aim to predict the safety and efficacy of new drugs in the treatment of human diseases, only the assays are carried out with cell cultures, laboratory rats, zebrafish, etc (aka in vitro and in vivo models). My point is that since gene editing with different organisms is similar, EU legislation regulating its different applications across life science sectors should be comparable as well. But unfortunately, things aren’t that simple: There is the matter of context.
Context versus Consistency
Back in 2016 I was talking about new technologies with an officer from the European Medicines Agency (EMA). She acknowledged differences in GMO regulation between EMA and EFSA but did not see the need for further alignment between both regulatory bodies because the context, the balance between risks and benefits, is radically different: Assessing a GM medicinal product to deal with a deadly disease (such as recombinant insulin) is not the same as assessing a GM flavour or additive for the food industry. In her opinion that justified the divergent approaches followed. But such criteria based on “context”, “risk” or “novelty” can lead to inconsistent legislation where genetically-edited strains with identical phenotypes and genotypes (isogenic organisms) are regulated differently depending on the technique used for their generation. In my opinion we should focus on the outcome, not the process.
The Sharpest Tool in the Shed
A major drawback of the discussion triggered by the ECJ ruling is that it places fundamentally different gene editing techniques under the same umbrella. But comparing classical random mutagenesis with CRISPR/Cas9 is like comparing a large-calibre cannon with a surgeon’s scalpel. State-of-the-art CRISPR technology allows for site-directed mutations within the DNA of any organism with a level of precision that just 10 years ago would have been considered downright impossible. Mark my words: I am not saying we are now doing a better job; I am claiming we can now do things we could not just 5 years ago. Previous techniques (viral flanking regions, artificial chromosomes) are clumsy in comparison, bringing about unexpected effects which render high-precision research of some diseases impractical or virtually impossible. It is crucial to understand CRISPR’s clinical precision when comparing this technique to classical mutagenesis, as it holds the key to the countless breakthroughs in disease research and drug development we have witnessed in the recent past.
We could now give you detailed explanations about CRISPR/Cas9’s technical advantages but I doubt it would help reel in the general public. Let me instead highlight the value of such new technologies to the healthcare sector and to individual patients: In our daily work at ZeClinics, we rely on the high precision of CRISPR/Cas9 to develop new therapies against life-threatening diseases such as Alzheimer’s, heart failure or cancer (to name a few). CRISPR technology targets genes with minimum disturbance and reproduces mutations linked to specific symptoms, allowing us to explore disease mechanisms and potential treatments. I’ve already mentioned our work on Alzeimer’s but not that one year ago I lost my grandmother to Alzheimer's after a five-year-long struggle. It is difficult to express with words how proud I am to be part of the battle against this terrible disease, just like it is difficult to express how I feel about a ruling that casts a negative light on the very technique that makes all of it possible. The industrial biotech and Agrotech sectors will be hit harder by the new rules, but pigeonholing CRISPR/Cas9 technology under the now highly stigmatized “GMO” umbrella will undoubtedly have negative long-term implications for us all.
The Voice of Reason
I hardly have the chance to make a difference in this fight: We live in turbulent times where the loudest often steal the scene and I am just an individual representing a small SME. You, on the other hand, are among the most influential people in one of the most influential nations in Europe. Within these very walls your predecessors passed ground-breaking legislation such as the Slavery Abolition Act (1833) or the Women’s suffrage Acts (1918-28); all of them ahead of their time. So which side to pick? I think I have made it plain I do not agree with the ECJ ruling on gene editing and many within the Commission share my opinion: Just last week the EC’s Science Advisory Mechanism (SAM), in a quite unprecedented move, recommended the thorough revision of the ruling. For my part I will always side with science and fact, as the value of CRISPR in disease research is not going to change because of an European Court rulings or even Brexit. Looking at the larger picture, I believe the EU will remain UK’s closest business partner. I also believe the British biotech and pharmaceutical sectors will need to retain an open, friendly market for their products. The best way to reverse legislation which affects us all will be, obviously, to work together. What I am asking you today is to embrace my message, make it yours, and remain the voice of reason, if not within the European Union then certainly in Europe."