U.K. Approves First Studies of CRISPR on Human Embryos

In my last blog post, I detailed the legal battle currently taking place over the biggest scientific breakthrough of 2015, a controversial gene edited technology called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats.) On February 1st, the United Kingdom’s Human Fertilization and Embryo Authority (HFEA) announced that it has now approved biologist Kathy Niakan’s request to use CRISPR to alter DNA in a human embryo for the first time.

So far, CRISPR has been has been used to attempt to splice genes from cells and eliminate mutations responsible for sickle cell anemia and HIV.  But this is the first time in the U.K.’s history that CRISPR will be allowed to be applied on germline cells in a live human embryo. The technology will help Niakan and her team of scientists from the Francis Crick Institute to attempt to cut out and replace parts of DNA that prevent an embryo from developing properly.

CRISPR has proven to be a cutting-edge technology that allows researchers to make impressively precise, targeted changes in DNA. Moreover, CRISPR’s process is so simple that many molecular biology labs and IVF clinics already have the right equipment to use the technology. But as beneficial and progressive as CRISPR may sound, some researchers fear the effects that the powerful technology will eventually have over the level of control we have on the human genome.

The biggest concern is that if CRISPR is able to permanently change genes in a human embryo, it also has the potential to forever alter the human gene pool, thus posing a threat to the diversity of our gene pool – something that is extremely important in order to keep a species healthy. If we begin to manipulate the pool, we will most likely face dire threats to our existence such as our ability to fight disease, life expectancy, etc.

Another controversial aspect of CRISPR is the fact that the technology is so precise that scientists worry about how far this kind of intervention can and should go. It’s one thing to use CRISPR to tackle disease and infertility, but another thing to employ CRISPR to design customized babies – a fine line that people are concerned would lead to scientists playing God.

In the case of Niakan, group leader at the Crick Institute Robin Lovell-Badge assures that her use of CRISPR will be exclusively geared towards answering questions about infertility. So far, researchers have a lot of information on how the early mouse embryo develops, specifically on how cell lineages promote the development of the embryo and the tissue that make up the placenta. But they don’t have that much information on how it happens in a human embryo. She will use CRISPR to snip each gene of interest and then study what happens to the embryos. If she’s able to track which types of cells continue to develop, she will be able to determine which genes are critical to specific tissues in the early embryo, thus getting one step closer in understanding and reducing infertility in women.

In places like the United States, federal laws prohibit the National Institutes of Health from funding human-embryo-based research that uses CRISPR, but studies on human embryos with private funding are left unregulated. However in the U.K., research conducted by both HFEA and private IVF clinics are strictly regulated by laws that would prohibit them from getting too carried away with the use of CRISPR. So even though some scientists may see the U.K.’s approval of the use of CRISPR on human embryos as a big mistake, the reality is that these studies are being conducted in a very controlled and safe way.

Even if Niakan’s study pans out as being successful, the embryos will be discarded after 14 days and more importantly it still remains completely illegal for any scientist to implant the altered embryos into a woman.

Mickael Marsali is a Senior Consultant for Arterial Capital Management. This post was originally published on Mickael’s financial blog.

Who invented CRISPR? A look at biotech’s most promising breakthrough.

Named the biggest scientific breakthrough of 2015, the gene-editing technology called CRISPR has the potential to allow us to one day delete the HIV virus from infected patients cells, create organs for transplants, and even produce better crops. Around the world scientists are trying to perfect new ways of using this technology every day.

But this week, biotech’s most promising breakthrough has been submersed in controversy, mostly because no one can seem to figure out who actually invented it.

Two big time research institutions are now facing off with hundreds of millions of dollars on the line: the University of California Berkeley and the Broad Institute in Cambridge (affiliated with MIT and Harvard.)

A patent judge found that a recent patent application exhibited a conflict knows as “interference,” meaning that one patent application and another patent or application seem to contradict each other. The patents in question come from Feng Zhang, a scientist at the Broad Institute in Cambridge who was granted patents in 2014 and 2015 and a new patent application filed by Doudna, a scientist at Berkeley, and Emmanuelle Charpentier, director of the Max Planck Institute for Infection Biology in Berlin, filed this week.

As patent specialist at George Mason University School of Law Adam Mossoff told the Washington Post, “These types of actions typically arise only in the context of very successful, very valuable patents. This patent, in particular, is… a significantly huge advance in gene-editing technology, and this type of technology is the core of what has made the biotech revolution.”

CRISPR as an acronym stands for “Clustered Regularly Interspaced Short Palindromic Repeats” which refers to the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms. CRISPR sequences are a crucial component of the immune system. Bacterial cells, just like us, can be invaded by viruses (small, infectious agents.) When a viral infection threatens a bacterial cell, the CRISPR immune system thwarts the attack by destroying the genome of the invading virus. That genome held the genetic material necessary for the virus to continue replicating. Thus, by destroying the viral genome, the CRISPR immune system protects bacteria from continuing the viral infection.

The CRISPR immune system learns what to attack by first processing the DNA of the invading virus, that DNA is copied into RNA (a process call transcription), and then that RNA (which are an exact copy from the viral DNA) can seek out and destroy that specific viral material.

Basically, you use the way bacteria naturally defends itself against infection to create very precise means of eliminating specific invading viruses.

The reason scientists are so head-over-heals for CRISPR is that previously when working with genome editing, researchers first had to spend countless hours identifying which genes were important in the disease, creating animal versions of a disease to test, etc in order to truly target the disease in the first place. With CRISPR, these issues disappear, as scientists can introduce multiple genetic changes in one relatively simple step. What was once so complex it was almost unimaginable to perfect, is now simple to the point of becoming routine.

While there has been a lot of excitement about CRISPR’s potential, we actually have no idea what specifically will come about from this technology first because not even a single clinical trial has had the chance to get started yet.

As Church hypothesizes, “I think genetics is going to be the source of lot of big decisions that are made by stock analysts, politicians, and so forth, and it’s about time we got excited about genetics. If there weren’t a race to sequence the human genome, the human genome would have gotten less attention. If CRISPR didn’t have a race for the technology, there would have been less attention.” Church currently holds CRISPR patents that have not been challenged.

Thus far, the technology has been freely available to academics using it for basic research, and both sides of the dispute agree that they have no intention of limiting the technologies availability to future projects. However, companies that plan to commercialize the technology will need to license the patents from whichever institution wins its rights.

Hundreds of millions of dollars have all ready been raised from investors with the expectation that in the next few years, scientists can develop real-world CRISPR drugs and treatments to manage or even eliminate a myriad of life-threatening diseases better than we ever have been able to do before.

With so much money on the table, the race to a real world applications is on. Editas Medicine has raised $163 million and recently announced that it will have a $100 million initial public offering as they begin clinical trials in 2017 for a rare genetic disease that causes blindness. CRISPR Therapeutics has raised $89 million and announced partnerships with two major drug companies, Bayer and Vertex Pharmaceuticals. Intellia has raised $85 million and partnering with Novartis. Caribou Biosciences has raised $11 million and is partnering with DuPont.

As you can see, whichever institution gets the patent will also be getting a pretty hefty revenue stream. In the mean time, with the uncertainty of who will win the patent, many companies are actually stepping back from investing until they see how things play out. So the amount of money at play is only expected to grow as this issue gets resolved.

Now we just have to wait for the inevitably drawn-out, bureaucratic process of deciding who wind. Recently, the U.S. changed its policy on patent law, now awarding patents based on who files the application first. Unfortunately for Doudna, her patent was filed before this policy change went into affect, which means this case is still subject to the older rules, which means: the patent goes to the first inventor. We’ll have to wait and see who makes the better case.

Mickael Marsali is a Senior Consultant for Arterial Capital Management. This post was originally published on Mickael’s financial blog.