Ready or Not, Gene Therapy is Here

Performance Enhancement taken to the next level

Gene therapy is coming soon here. And the genetically modified are already walking among us.

How did we get here?

As soon as we discovered that every process and protein in our bodies is governed by DNA, a 4 letter programmable code, one clear idea entered the mind of the astute: we can edit ourselves.

And in decades since Watson and Crick discovered the structure of DNA, this was the exact goal. Editing the DNA of bacteria, viruses, and other organisms such as lab rats happens in almost every major university lab across the world. But ethical and safety concerns have made this a slower process when it comes to human DNA editing.

What are the ethical implications of a genetically modified human species? Are we now governing our own evolution? Will those who can afford it make the rest of us a sub-superhuman, enslaved species? What nefarious actions will be taken with this technology? Will it turn into a weapon?

This has been the topic of many science fiction movies, like Gattaca which explore what the gene-edited vs normal human being interactions may be. Only now, it’s no longer science fiction: the genetically edited humans are already here.

The Case of Jesse Gelsinger

The first goal application for genetic editing was to help treat those with severe genetic diseases like sickle cell anemia or lethal metabolic disorders ornithine transcarbamylase deficiency syndrome, which Jesse Gelsinger had. He was enrolled in genetic therapy through an Adeno-Associated Virus (AAV) approach.

image from askbio.com

Essentially, the genetic material that was missing or broken in the patient would be loaded onto a virus and then the virus would infect the individual and insert the DNA into the individual, giving them the code to make whatever protein or enzyme was missing.

The excitement was colossal, however the horror was more colossal as Jesse unfortunately was the first person to die from genetic engineering in 1999.

The problem with this method of gene therapy is the viral vector itself. It can cause off target effects and well as cause a massive immune response and send the patient into shock, which is what happened to Jesse.

This process dampened excitement about gene therapy and set the field back. That is, until now, over 20 years later when gene therapy is taking a new approach

Plasmid Gene Therapy

Instead of using viruses, new gene therapy approach are using plasmids, which are extra pieces of DNA that bacterial hold. The desired gene is placed on the plasmid as recombinant DNA, then the bacteria multiple millions of times, creating tons of copies of the desired gene.

In fact, this is how many drugs, including insulin are made. But now, instead of making a drug, the actual plasmid is purified and injected into the patient. The plasmid is then taken up by your own cells and your cells now make whatever protein, peptide or enzyme is desired.

This is a fascinating technology to use to treat disease, but what is application being that is currently generating a lot of excitement across the internet? You guessed it: getting people as buff as possible.

Introducing Follistatin Gene Therapy

The company making headlines is called MiniCircle (named after the circular plasmid mentioned above, I have no affiliation to the company). They are enhancing individuals with the gene for follistatin, a human peptide that inhibits another protein named myostatin. (note: the word statin in biology means to block something).

Follistatin blocks follicle stimulating hormone (will be key for side effect discussion later) activin and myostatin. Myostatin inhibits the amount of muscle (myo = muscle, statin = to block) an individual makes. Inhibit the inhibitor of muscle growth and you get: more muscle.

The company’s website claims:

“Follistatin binds to and inactivates two proteins in your blood: myostatin and activin a. Myostatin is a protein in your blood which decreases your muscle mass and bone density. Follistatin’s ability to improve body composition is dependent on both myostatin and activin inactivation (Gilson, et al., 2009). Follistatin’s ability to decrease inflammation is dependent on inactivation of activin (Hedger, et al., 2011).”

Additionally they report, in mice studies, this treatment is reported to extend lifespan by 32.5% (Jajyan, 2021).

By increasing the amount of muscle and decreasing the amount of inflammation, the idea is that the individual would become healthier and more robust. Muscles release myokines, which are beneficial signaling molecules while fat releases adipokines, which are inflammatory signaling molecules. Improve the ratio of myokine/adipokine and you get a healthier individual.

Aren’t we scared of what happened to Jesse Gelsinger? According to MiniCircle, this isn’t a concern as the “highly expressive DNA plasmids to add genes to the human body without altering your pre-existing genome. Our reversible plasmid platform is completely non-inflammatory (unlike AAV) and non-heritable. It is designed as a universal gene therapy protocol.”

I spoke to someone who received the treatment, these are the bullet points of what they told me:

• Single injection of the bacterial plasmid into subcutaneous fat tissue

• Lasts 1.5-2 years until the plasmid DNA is degraded

• They became significantly leaner and more muscular despite not changing diet nor training program. Reports feeling “stronger neurologically” with better and muscle contraction and force

• De-aged approximately 7-9 years based on longevity blood tests (not too confident in how reliable these are, for what its worth)

• Done in Mexico, Japan, and Dubai by a doctor Adeel Khan, MD (not done in USA of course)

• Clinical trials in place for other gene therapies such as klotho for kidney disease and HIV treatments

• Gene therapy for testosterone in the pipeline

• The therapy costs $25,000 USD

Safety and Side Effect

What about the safety? The plasmid has a kill switch attached to it in case it needs to be reversed. If someone wants to reverse the treatment, all they have to do is take an antibiotic called tetracycline and the plasmid will no longer be expressed. Additionally, based on their reports the plasmid does not become attached to your own DNA, rather remains in the cell to be transcribed. As such, this should only last 1.5-2 years and should have no long term effects. Of course, this is all very new and we will see how this plays out. According to the companies website, less than 250 people have received the gene therapy as of October 2023.

Side effects? They report very little in their first patient cohort. According to the company LDL levels went up by 10 points (unclear how significant this will be). Given that follistatin inhibits FSH, which is involved in fertility for both men and women, there is a concern that this treatment will inhibit fertility. However they claim that there are two forms of follistatin and the version they use has less of an effect. This is what their company FAQs report:

We will see if this remains safe and I, like most of you reading this am optimistic however cautious about where this may go wrong. Only time can tell as the first batch of genetically modified people are being studied.

Implications and What Comes Next

Famous biohackers and celebrities are already lining up to receive this (Bryan Johnson, Tony Robins, and Dave Asprey) are all reported to have already received this gene therapy. And some sources report that athletes have already been enhanced by this treatment, which opens up a can of ethical worms about gene doping and cheating. It is possible that the last Olympic Games outcomes were already influenced by gene therapy, with no real way to tests for this and rule out cheating existing. Performance enhancement is always one step ahead of regulatory testing agencies.

After spending most of the last few days researching this field, all I can say is the health and fitness space is going to change forever. Next in the pipeline is gene therapies to increase levels of peptides/hormones like BPC157, GHK-cu and testosterone.

The genetically enhanced already walk among us. Those who can afford this therapies and have early access will have an edge on everyone else. Good luck…