Recent advances in Biotechnology have lead to a revolution in the field of gene editing, including human gene editing. In this blog post, I will talk about one of the most important advances in this area, the CRISPR/Cas9 system, what it is, what it's used for and what its potential and risks are for the future, as well as talking about some of the controversy surrounding it and human gene editing in general.

CRISPR/Cas9 is a part of the natural human immune system. To understand what it is and how it works, it's useful to give a brief overview over how viruses and infections work in organisms. 

As we all know, DNA (deoxyribonucleic acid) is the blueprint for the basic building blocks of life. It is copied to RNA (ribonucleic acid) in cells which is in turn used to produce proteins, which make up most of the structures in an organism. Viruses hijack this mechanism by inserting their own RNA or DNA into a cell and tricking the cell into producing more copies of the virus. A special class of viruses, retroviruses like HIV, even insert their genetic code into the DNA of the cell they are invading, which allows them to hide undetected for a long time and make them, very hard to fight.

Bacteria have developed a method of fighting these kinds of viruses, the CRISPR/Cas systems. CRISPR (Clustered regularly interspaced short palindromic repeats), are long sequences of repeating DNA in the bacteria's genetic code. Detected virus DNA is inserted into these sequences to build up a "library" of virus DNA for future use. The Cas (CRISPR associated system) proteins then use that stored DNA to build up a pattern to match virus DNA in the cell's DNA, and if they find an offending sequence of DNA, they cut it, effectively killing and removing the virus. There's several different Cas proteins, which are numbered, and Cas9 is one of them that works particularly well for gene editing.

For a more visual and accessible explanation, you can watch this excellent video explaining the process:

There's countless research projects and medical trials currently going on, some in animal studies with the goal of later human application, and some already being done on humans. Here are just a few of the more noteworthy ones to give you an idea:

• Curing HIV: Whereas traditional antiviral treatment of HIV focusses on eliminating active viruses from the bloodstream and preventing the virus from reproducing, current research in animals has shown CRISPR/Cas9 to be able to completely remove all traces of the virus from the hosts, with over 50% success rate so far.
• Curing Cancer: Scientists have extracted T-Killer cells (a part of the human immune system that neutralizes foreign bacteria and other pathogens) from humans, reprogrammed them with CRISPR/Cas9 so they can target cancer cells and reinjected them into the patients to enable the bodies own immune system to fight cancer. How efficient this technique is still remains to be seen, though.
• Curing hereditary disease: Scientists have also used CRISPR/Cas9 to edit the DNA of human embryos to fix hereditary genetic defects successfully, though the embryos were terminated after 7 days for ethical reasons.
• Sickle-Cell Anemia: A painful and debilitating disease that leads to malformed blood cells, most common in sub-saharan africa, has been successfully treated in mice, though it will probably be several years before there are any human trials
• Countering Antibiotics Resistant Bacteria: CRISPR/Cas9 shows a lot of potential in treating the growing problem of antibiotics resistant bacteria, effectively being able to remove the resistance from them or just outright killing them directly. It promises to be an important tool in the current fight against resistant bacteria and also in finding new antibiotics to replace the old ones.

These are just some of the research projects currently being done or awaiting approval, but they should serve to give you an idea on the possibilities of CRISPR/Cas9.

While all this sounds very promising, of course CRISPR/Cas9 isn't without it's downsides and negatives:

• Inaccuracies: While CRISPR/Cas9 is very accurate and specific, it's not perfect. It has been shown to insert DNA at unwanted locations in some occasions, ranging from 1-5 off-target changes or more in some cases. The consequences of off-target insertions are difficult to judge and since they depend on the DNA being inserted, have to be tested for every application. Especially editing of germline cells, meaning cells that are passed on to children, poses some risks, since negative effects might only be noticed after several generations.
• Ethical concerns: One of the biggest risks with CRISPR/Cas9 is that it's so good and efficient. The sheer amount of research being done makes it difficult for legislators to regulate, and its potential for any kind of gene editing also means it might be used for ethically questionable uses. While most would agree that curing debilitating hereditary diseases in babies is a good thing, removing genes linked to obesity, changing someones haircolor, improving athletic potential etc. are very questionable territory.
• Nefarious use: Since CRISPR/Cas9 makes gene editing so easy and accessible, with a small laboratory being enough to perform it (there are some DIY kits available, though they can't be used in a general fashion), this also means that it's more accessible for people with bad intent, like terrorists or rogue states, enabling them to engineer bioweapons more easily. And since there's not a lot of infrastructure needed for CRISPR/Cas9, detecting clandestine laboratories could prove difficult.
• Regulatory issues: The pace and breadth of current research makes it difficult for governments to react and adapt, making it more likely that irresponsible and risky research will be done, and currently oversight is done in a large part by scientists themselves

With all the research going on, including fundamental research into making CRISPR/Cas9 more effective and even cheaper, as well as a lot of startups popping up that focus on applications of CRISPR/Cas9, it is difficult to say where cheap gene editing will lead in the future. It has the potential to revolutionize the field of medicine, enabling truly personalized treatments, curing genetic diseases, treating cancer, fighting viruses and bacteria and possibly even being used to treat the effects of aging. Outside of humans it's applications in genetic engineering of crops or fighting pests are even more numerous. But once the technique becomes more common-place and accepted, it will also lead to a lot of debate about whether it's ethical to use it for more cosmetic and less health-related changes, for instance designer babies. The discussion surrounding CRISPR/Cas9 is currently still largely hidden from the public eye, with debate taking place mostly between scientists, but this is likely to change in the near future. 

And while the debate on genetic modifications has been going on for several decades, these recent improvement make it more pressing for the public and law makers to deal with these rapid changes, before it is too late. And with the generally slow pace that law makers deal with new regulations, they will have a difficult task ahead. Outright banning of the research is not an option, since it would just move to a different country, so trying to establish a framework to conduct it responsibly and reliably is something that needs to be done in the coming years.

What is certain right now is that it will lead to a lot of breakthroughs and an acceleration in research in the fields of Bio-Technology and Medicine, fundamentally changing many aspects of our lifes and possibly eliminating a whole swath of diseases that are just accepted as a part of being human right now.

We certainly do live in interesting times!

Whats your opinion on the recent advances in human gene editing?