Human genetic engineering. CRISPR/cas9 DNA editing of humans. What is the current status? What are the benefits and risks? Including 3 case studies of DIY and 2 documentary tips!

Genetic enhancement

A method that has been in the media a lot in recent years is genetic modification, also known as genetic manipulation or genetic engineering [link at the bottom]. With CRISPR / cas9 technology you can change the building blocks or operating system of the life of an organism, such as a human, animal, plant, bacteria or virus. Even more far-reaching is that the changes can also be passed on to subsequent generations.

This method reminds of the serie Orphan Black. That’s the picture at the top of this article.


Genetics

Genetics, as the name implies, is all about genes. I’ve previously written an extensive article about this [link at the bottom]. To sum up the essence of it: almost every cell of our body contains 3.2 billion base pairs. These base pairs consist of AC and TG molecules, and they are intertwined in the form of a double helix.

The shape of the double helix, which was discovered by Francis Crick and James Watson together with Rosalind Franklin, is now considered an iconic image of DNA. DNA contains hereditary information: in the case of biological reproduction in humans, you get half of your DNA from your father and the other half from your mother.

Chromosomes

The base pairs are packaged into 23 chromosomes, which in turn construct about 25,000 genes in total. A gene is made up of DNA code, which codes for a particular function or characteristic. For example, the DNA sequence in the HERC2-gene determines the color of the eyes [link at the bottom].

RNA

Because of the double helix structure, DNA code can easily be copied to either new DNA or into RNA. The best known form of RNA is messenger RNA. The mRNA molecule is an important link in the transcription, or reading, of the genetic code. The mRNA is read by the ribosome outside of the cell nucleus, after which the ribosome starts to build one of the twenty possible amino acids.

The amino acids form proteins, which in turn perform all kinds of functions in the cell, such as building, maintaining, decomposing and communicating tissue, transporting amino acids to other cells and much more. This entire process, from DNA to the production of proteins, is also known as the ‘Central Dogma’ of molecular biology.

Phenotype

The genotype is what we call the collection of genetic or hereditary information. The phenotype, on the other hand, is the composite of the organism’s observable characteristics. In a podcast interview with the Flemish comedian and science journalist Lieven Scheire, he gave the following example: ‘If you’re curious about the influence of the genotype on the phenotype, look at identical twins. You could say that what they have in common in terms of appearance and behavior, is encoded in their DNA.’

If you are curious about the influence of the genotype on the phenotype, look at identical twins

Lieven Scheire (comedian and presenter)

Geneticists roughly distinguish three factors that influence a person’s characteristics: genes, the shared family environment, and non-shared environmental factors outside of the family (such as school, friends and unique experiences). The extent to which these factors influence our characteristics varies enormously. For example, my gender is completely dependent on my genes, while the fact that I speak Dutch has nothing to do with my genes.

Mapping DNA

When the Human Genome Project (HGP) was completed in 2003, the expectations were high. The HGP meant that the entire human genome would be mapped. When they presented the project, President Clinton (United States) and Prime Minister Blair (United Kingdom) referred to it as ‘the book of life’.

However, it soon turned out that physical traits, diseases and other characteristics, such as intelligence, speed and empathy, could not be identified that easily within the DNA code. In fact, scientists were amazed by the number of genes each individual has. The total number of genes is now estimated at 20,000 to 25,000, which is similar to that of a mouse [link at the bottom].

Epigenetics

So how is it possible that we as humans are much more complex organisms than a mouse, but that the number of genes we possess is more or less the same? One reason for this is probably the additional layer of code on top of our DNA; the field of study that looks into this, is called epigenetics.

To sum it up: when, to what extent and how genes are expressed, depends to a large extent on cell environment and – on a higher level of abstraction – also on the environment in which the organism is located. In a podcast interview with PhD student Désirée Goubert (whose research focuses on epigenetics), we talked about this in detail [link at the bottom].

DNA sequencing

Research into the relationship between the genotype (the DNA code) and the phenotype can be done through DNA sequencing. This means that the DNA is analyzed and converted into the code of AC and TG base pairs. Researchers then look at the phenotypes: does the piece of genetic code they’ve selected influence the characteristics of an organism?

Let’s look at an example of the HREC2 gene I mentioned before, which occurs in humans [link at the bottom]. The layer of code on this gene, the so-called SNP (single-nucleotide polymorphism), has a significant influence on the color of your eyes – but less on, for example, hair color and whether or not you get sunburned easily.

China

Teams of scientists all over the world are researching these processes and the relationships between them. The Chinese government and Chinese companies in particular are very active in this field. This was captured very well in the documentary ‘DNA Dreams’ by Bregtje van der Haak [link at the bottom].

The company Beijing Genomics Institute (BGI) has plans to genetically examine all organisms in the world. Furthermore, the institute is also looking specifically for the genes that influence positive characteristics such as intelligence. In the documentary you can see how young children undergo all kinds of IQ tests at the company, after which BGI compares the results of the tests with the DNA of the child.


Genetic modification humans

Genetic modification, also known as genetic engineering or genetic manipulation, takes things a step further than just examining and analyzing DNA. I’ve previously written an extensive article about the interesting developments in this field [link at the bottom].

When I give a keynote, I often explain that modifying DNA is something that we as humans have actually been doing for a long time. Think, for example, of how we first started breeding plants and breeding animals. Of course these were initially very unrefined methods, in which there was a large degree of unreliability – after all, at that time we didn’t know what the underlying DNA code looked like.

Modifying DNA in a lab is a lot more accurate and precise. A big scientific breakthrough can be ascribed to the work of Cohen and Boyer in 1973, who were the first scientists to use a technique called recombinant DNA [link at the bottom]. Recombinant DNA refers to artificially combining DNA from multiple sources. In the past few decades, additional methods have been developed, such as TALEN (Transcription activator-like effector nucleases) and Zinc finger nuclease.

The biggest breakthrough took place in 2014, when Jennifer Doudna and Emmanuelle Charpentier presented their discovery of CRISPR/Cas9 in Science Magazine [link at the bottom].

Compared to TALEN and Zinc finger nuclease, CRISPR/Cas9 is much cheaper, faster and more effective. Because of that, the discovery of CRISPR/Cas9 was a huge step for the scientific community and was quickly applied in research on crops, animals and humans.

Orphan Black Netflix

The TV show Orphan Black on Netflix is about genetics and cloning. In the section Fiction, I’ll write about that in more detail.

Modifying human DNA

DNA modification in humans is primarily used in the healthcare sector. A few examples, although the CRISRP/cas9 technique wasn’t used in all of these particular instances:

  • Genetically modifying the white blood cells of leukaemia patients to better target and destroy cancer cells. In 2011, the American Emily Whitehead was the first to be successfully treated using this technique [link at the bottom];
  • In 2017, a British patient who was blind was cured after DNA modification of the retina [link at the bottom];
  • Several biotechnology start-ups are working on gene therapies for the treatment of infectious diseases, hereditary diseases and HIV [link at the bottom].

The vast majority of research using genetic modification techniques concerns crops, bacteria and smaller organisms. There are high expectations of this field; more than ever, we as humans are able to be in charge of biology. The most exciting part is the possibility to apply these techniques to ourselves as well. What possibilities do we have there?


Types of human DNA modification

It’s clear to me: in the future, we (humans) will want to enhance and modify ourselves. The most pressing question, which I will return to later when I discuss the ethical implications, is to which extent we will want to do so. Do we restrict the use of these techniques to, for example, when the health of a patient is at stake? Or will they soon be available to everyone (commercially)? I have roughly divided genetic modification in humans into the following categories:

  1. Somatic modification (editing people’s DNA);
  2. Germline modification (DNA modification in embryos, the so-called ‘designer’ babies);
  3. Epigenetic programming;
  4. Modification of intestinal flora (microbiota);
  5. Virome.

I’ll elaborate on these different categories below and conclude by looking at their proven efficacy. Categories 1 and 2 are already being used in medical and biological research, whereas the ones from number 3 onwards are much more speculative and hardly proven (as of now).


1. Somatic modification

‘Soma’ is a Greek word for ‘the body’. Somatic modification, then, refers to genetically modifying the body. The British patient I mentioned before, with an eye impairment, is a good example of this. In his case, the genes that are responsible for maintaining the light-sensitive cells in the back of the eye, missed half of their DNA code. Researchers were able to reprogram the genes in the lab and then insert them in the right place, behind the eye, using a virus.

The experimental CRISPR/Cas9 procedures that are currently being used to treat leukemia patients employ a similar method. Blood is administered, the bloods cells are genetically modified, and the modified blood is interjected into the patient’s body again.

Delivering genes

As both examples illustrate, the greatest challenge is to deliver the modified genes or cells to the right place in the body. We’re still a long way from a scenario in which you can place a syringe of modified cells in your arm, and have the modifications arrive exactly at the right organs, at the right cells and at the selected DNA.

At the same time, this doesn’t stop some people from experimenting on themselves with these methods.

CRISPR biohackers

People who genetically modify themselves are also called biohackers. I personally think of the term ‘biohacking’ as a broader concept though. That’s why I’ll refer to people who experiment with genetic modification on themselves ‘CRISPR biohackers’ for now.

Josiah Zayner

The most well-known CRISPR biohackers are Josiah Zayner and Tristan Roberts. Two other well-known biohackers that I discussed in my article about biohacking, are Brian Hanley and Lizz Parish [link at the bottom].

Josiah Zayner created quite a controversy at the end of 2017, when he injected himself with modified cells. In particular, it was the context of his action that caused a great deal of commotion. He broadcasted it live on video on Facebook, and his goal was to grow extra muscle mass [link at the bottom]. He wanted to gain muscle mass by suppressing the activity of the gene that codes for the muscle growth inhibitor myostatin.

Tristan Roberts

While muscle mass might be more of an aesthetic goal, some people think of do-it-yourself genetic modification as the ultimate way to improve their health. That’s also true for Tristan Roberts. He was diagnosed with HIV and became frustrated with the daily medication regime.

Some time ago, a group of scientists published research on a certain genetic mutation that exists and which protects people from HIV. That’s possible because the body can produce the antibodies against the HIV virus, called N6, itself. Roberts’ idea was to genetically modify himself, so that the fat cells in his belly would also start producing N6 themselves.

I interviewed him for my YouTube channel, so feel free to check out the interview :

https://www.youtube.com/watch?v=EVz5mgCm9pg
My interview with Tristan Roberts

2. Germline modification

Germline modification refers to the modification of genetic material in the embryonic state, the sperm and/or the egg cell. The essential difference compared to somatic modification, is that any modifications in the DNA are passed onto the next generation. So the consequences of such modifications are not limited to an individual, but also extend to the offspring. This type of treatment is done in combination with in-vitro fertilisation (IVF). This means that scientists modify the embryo in the laboratory and then insert it into the uterus. In 2017 such a treatment took place in England, which led to newspaper headlines saying that a three-parent child had been born [link at the bottom].

Replacing embryo DNA

During the treatment, the mother’s mitochondrial DNA in the embryo was replaced by the DNA of another woman. The mitochondria in the cell are responsible for energy supply, have their own DNA, and are passed on exclusively by the mother. In the scenario in England, the mother had a hereditary mutation in her mitochondrial DNA. By replacing this in the laboratory, her child, and then all of their offspring, was relieved of this disorder.

Lulu and Nana controversy

The treatment in England that I described in the previous paragraph, was carefully discussed, debated in politics and enshrined in legislation. The same does not apply to the best-known case (so far) of germline modification. This doubtful honour is reserved for the Chinese scientist Jiankui He [link at the bottom].

In the autumn of 2018, he announced that he had given birth to two babies under the names Lulu and Nana, which had been genetically modified as embryos. The aim of the treatment was to modify the CCR5 gene, which would make the children resistant to HIV. The father of both children was himself a carrier of the virus.

CCR5 gene

You may be familiar with this gene. At the end of 2018, the Chinese scientist He Jiankui was in the news [link at the bottom]. He wanted to change this gene in two Chinese babies, Lulu and Nana. The advantage of this mutation is that it makes them resistant to HIV.

Apart from other problems with the procedure by He Jiankui (among other things that the procedure was not permitted by law, there are doubts about whether the permission of the parents was granted and that the genetic cut probably did not go well), Church has included in his overview that the CCR5 mutation also leads to an increased risk of contracting the West Nile virus [link at the bottom].

Later, however, stories appeared stating that this particular gene also influences the development of one’s cognitive capabilities [link at the bottom]. If that is the case, then there’s certainly a moral, ethical and political discussion about genetic modification, and using it for enhancement purposes, to be had. More on that later.

Reproduction

The example of Lulu and Nana illustrates the rapid pace at which reproductive technology is developing. I spoke about this in a podcast interview with professor Sjoerd Repping of the VU Medical Center in Amsterdam [link below].

For example, there is already talk about making egg cells from skin cells, which makes it possible for two men to also play the role of genetic father and genetic mother [link at the bottom].

During the interview, he talked about the revolution we’ve already experienced with regard to in vitro fertilisation (IVF). IVF is a fertility treatment in which fertilization takes place outside the body. Another term for this is test tube fertilization.

The first treatment using this technique in the Netherlands took place in 1980, but nowadays, an average of one child in every school class was born in this way. In the eighties there was a big commotion about this method. After all, having a baby was a gift from God. These days, the use of IVF is hardly a topic of discussion; could the same apply to the genetic modification of embryos in the future?

Programming superhumans

Politicians and bioethicists all over the world were tumbling over each other to condemn Jiankui He’s action. They argued that the modifications were sloppy, that he didn’t have permission from the government or his research institute, and that there are much easier ways to stop the HIV virus from being passed onto future generations [link at the bottom].

Another reason for the commotion, however, may stem from a primary human reaction: jealousy. At an event organized by the Feather Foundation in Delft, where I also gave a lecture myself, Professor Robert Zwijnenberg of Leiden University suggested this as well. He mentioned that Harvard University (Boston, United States) itself is in the process of modifying sperm cells to reduce the risk of Alzheimer’s [link at the bottom]. The reactions to He’s news are probably affected by a twinge of envy. It’s no coincidence that there seems to be an arms race going on between China and the United States concerning genetics and genetic modification. More about that later.

George Church

Professor George Church is a prominent scientist and pioneer in the field of genetics and genetic modification. Halfway through 2019, he published a list of a number of genes that lead to improved human traits in the correct mutation [link at the bottom].

  • LRP5: stronger bones;
  • MSTN: larger muscles;
  • FAAH-OUT: lower sensitivity to pain;
  • PCSK9: better resistance to cardiovascular disease;
  • GRIN2B: memory improvement;
  • BDKRB2: being able to hold the breath for a long time;

Some genes in his list have remarkable qualities, such as ABCC11. A mutation on this gene is linked to the production of less sweat. He also gives examples of adverse effects of some genes. The mutation on PCSK9 with the advantage of better resistance to cardiovascular diseases can also lead to an increased risk of diabetes.

In short, you will have to make trade-offs here.


3. Epigenetic programming

According to professor Michael Bess, author of the book Make Way for the Superhumans, it is unlikely that germline modification will be used much [link at the bottom]. That’s because it raises all kinds of moral issues regarding the autonomy of the unborn child. With this in mind, he expects more from so-called epigenetic programming.

Changing the DNA of the embryo raises many moral issues regarding the autonomy of the unborn child

Professor Michael Bess

Epigenetics is like a piano. Michael Bess: “The DNA can be compared to the piano. But the pianist plays the piano. You get a different melody and rhythm, depending on which keys the pianist plays. Now that’s actually epigenetics.” Epigenetics is a layer that lies on top of the DNA and influences the DNA expression. I’ve previously written an extensive article about epigenetics.

In the future, scientists will probably find out more and more about the effects of epigenetics and, in due time, how to influence them. This is also called epigenetic programming. Perhaps a scenario would arise where people are allowed to make (epi)genetic changes at a certain age, for example when reaching the age of being a legal adult. In the podcast I did with Désirée Goubert, I talked extensively about epigenetics and its possible future applications [interview at the bottom].


4. Gut flora

In the book Evolving Ourselves, Enriquez and Gullans write about the ‘Omen’ model. This model includes the genome (DNA), the epigenome (epigenetics), the microbiome and the virome [link at the bottom]. The microbiome stands for the composition of the intestinal flora.

Your intestinal flora consists of bacteria (about 700 to 1,000 strains), yeasts, viruses and parasites. Each person’s intestinal flora is unique – as unique as a fingerprint. These microorganisms don’t just live in your gut; they are found on all of our body’s surfaces and form an ecosystem of their own everywhere. It is comparable to a jungle: a huge forest area with plants, herbivores and carnivores.

And it’s a crowded jungle too. There are 10 times more bacteria than cells in your body. Your intestinal flora weighs an average of 2.5 to 3 kilos and contains 360 times more DNA than the rest of your body. This has led some scientists to say that we as humans are carriers of bacteria. But what kind of influence do these bacteria have, and how do they work?

Role of intestinal flora

The intestinal flora breaks down molecules from the food we eat, and produces biologically interesting molecules that are useful to our bodies. Like short-chain fatty acids, for instance, which serve as a signalling agent for the metabolism. The bacteria also produce vitamins (K, B12 and folic acid) and amino acids.

The intestinal flora also plays an important role in maintaining your immune system. In addition, more and more knowledge has become available in recent years that shows that the role of the intestinal flora is much greater than we initially thought. At the beginning of 2019, for example, the Catholic University of Leuven published a study in which it demonstrated that two types of intestinal bacteria, Dialister and Coprococcus, occur less frequently in people who report that they are depressed [link at the bottom]. The researchers haven’t fully made up their minds about this though: it could also be the case that people with a depression eat differently and therefore have a different intestinal flora.

I had my intestinal bacteria tested myself, and I’ve also interviewed an expert on the subject: Tom van den Bogert of MyMicroZoo. You can find a link to the article about my own intestinal flora and to the interview at the bottom of this article (available in Dutch).

Gut flora transportation

The intestinal flora has a huge influence on our health (especially in chronic conditions, from obesity to rheumatism and depression), although there experts have different opinions experts about the degree of this influence and whether there is a causal link there. However, multiple patients have successfully been treated with intestinal flora transplants, i.e. faecal transplants. According to an article in Dutch daily the Volkskrant such transplants have occurred in China since centuries ago, in Western countries since the 1950s and within a medical and scientific setting since the past few years [link at the bottom].

The operation is simple: the patient receives part of the intestinal flora from a healthy donor. The donor can also be the patient himself, for example when the intestinal flora is stored before the patient starts a heavy antibiotic treatment. In the Netherlands, this technique is only used for very specific medical situations, which is why patients often have to go into the alternative circuit. In the article in de Volkskrant, the patient went to the Taymouth clinic in England to get their treatment.

DIY transplantations

Josiah Zayner, whom I mentioned earlier when I described how he applied genetic modification on himself, went one step further. In 2016 he prepared his own intervention, which was described in an extensive article on the website of The Verge [link at the bottom]. He collected the faeces of a (healthy) friend, with the aim of adjusting the composition of his intestinal bacteria for the better.

It remains somewhat unclear whether – and if so, to what extent – it has helped him, but he has noticed some other effects. For example, he’s mentioned that after the transplantation he is much more inclined to eat sweets, even though he had never had such a sweet tooth before.

Since he hasn’t immediately reported huge improvements (and it seems a bit gross to me anyway), I wouldn’t be quick to have such an operation. However, I do try to keep my intestinal flora in good condition by eating well: enough fiber from vegetables and whole grain products, fermented food such as kefir and sauerkraut, and occasionally special supplements in the form of pro- and prebiotics.


5. Virome

The human virome consists of all viruses in and on the body. Compared to the microbiome, the virome constitutes an additional step in the order of magnitude. It’s estimated that the virome consists of 380 trillion viruses [link at the bottom]. The vast majority of the virome is made up of bacteriophages. A bacteriophage (or ‘phage’ for short) is a small virus that only infects a specific bacterium.

Viruses are not considered to be living organisms, unlike bacteria. That’s because a virus is actually a piece of floating DNA. The only purpose of the virus is to inject itself into a bacterium, then duplicate and spread. Because of this mechanism, viruses are often used in molecular biology to introduce foreign DNA into bacteria.

Bacteriophages

Another technique that is currently being studied, is the use of bacteriophages as an alternative to antibiotics in bacterial infections. Specific bacteriophages can then infect and destroy the bacteria. The advantage of this method is that bacteria cannot become resistant to bacteriophages by mutation, because the phages also mutate themselves. This is the so-called evolutionary arms race.

At the moment, little is known about how all of the different viruses in our bodies work. We do know, however, that there is no point in destroying all viruses. Although viruses have a bad reputation, think of Ebola and Dengue for instances, they also play a vital role in symbiosis with bacteria in and around the body.

We know even less about the effects of viruses in the body than we do about the microbiome – especially in combination with bacteria, the epigenome, the genome and situational factors such as nutrition and lifestyle. Nevertheless, I do expect that as we learn more about the virome, we will also see other uses of bacteriophages in the future. Not just in the healthcare sector, e..g. as an alternative to antibiotics, but perhaps also as a method to keep the condition of the microbiome (and so the health of the body) in order.


Artificial selection?

It is therefore possible to replace natural selection with artificial selection. A development that has been going on for some time, but is now becoming more focused and specific. In some cases this is reasonable. For example, there are (hereditary) disorders that are caused by a mutation on one gene, such as Huntington’s disease, sickle cell anemia and cystic fibrosis. The social consensus at the moment is that it is good to use CRISPR / cas9 for this, if safe to do so.

Human Genetic improvement

It is different when we decide to start using this technology to remedy conditions that are not life threatening. Think of changing the color of the eyes, improving intelligence or making sure that you are less likely to become bald. It becomes even more exciting when you think of social intervention: switching off the genes that are related to alcoholism or violence.

That is again the difference between healing and improving. Sometimes that is a gray area, take body height. For example, footballer Lionel Messi received injections of human growth hormone from an early age to help his body to grow [link at the bottom].

Is that under healing or improvement?


Future genetic improvement

A common mechanism within human enhancement is that a method is initially developed in (medical) science to help patients. The next step is that it is used by non-patients to improve themselves.

The question is whether this also plays a role in the editing of genes. Scientific progress continues to help patients (or their future offspring) with a genetic disorder. The gray area is to determine when there is healing and when there is improvement. Take the earlier example of the height of Lionel Messi. Is changing genes so that your child becomes taller a form of healing or improvement?

These questions are difficult to answer unambiguously. As I have argued before, the answers we provide are time-dependent and culturally determined.


Chimera

A special application of genetics and biotechnology are chimeras. A chimera is a cross between two organisms. This is different than crossing organisms, such as a mule (a baby of a donkey stallion and a horse mare) or a mule (a baby of a horse stallion and a mare). In a cross, all cells contain the same DNA, while a chimera contains the DNA of both one organism and the other.

The chimera also appeared in Greek mythology, although it was written slightly differently (as Chimaera). This was an animal that was put together by humans. The chimera was usually depicted with the head of a lion, the body of a goat and the tail of a snake.

Although chimeras with human elements still seem far-fetched, interesting developments are taking place in scientific research. For example, the Japanese government broadened the rules in this regard in 2019 [link at the bottom].

The idea is once again to strictly apply it for medical research. Examples of this are the cultivation of human brain cells in the brain of an animal or the placement of human organs in an animal.

On an even more fundamental level, scientists are curious about molecular biology and the interaction between cells of various organisms on top of each other. For example, it was also announced in 2019 that scientists in China had created an embryo made up of cells from a human and a monkey [link at the bottom].

Xenotransplantation

Under the term xenotransplantation, they investigate whether it is possible to grow a liver, kidney, heart or even lungs in sheep or pigs [link at the bottom]. Pigs are certainly a good candidate for such interventions, since this species is genetically almost identical to humans [link at the bottom].

When the technology is ready, the same moral and social questions play a role here as I have outlined earlier. What if companies can make livers that can break down alcohol even better, lungs with extra capacity and a heart that can effectively spread this extra oxygen to the muscles?


Best documentaries

What are the best documentaries about human genetic engineering? I like Human Nature and the serie Unnatural Selection. You can find both on Netflix.

The documentary Human Nature is about the discovery and applications of CRISPR/cas9.

The documentary Human Nature explains the discovery and applications of CRISPR/cas9.

The documentary serie Unnatural Selection is about biohackers applying genetic modification on themselves:

Documentary serie Unnatural Selection

If you have another documentary or film tip, please leave a comment down below!


Hire me!

Do you want to know more about human enhancement?

Please contact me if you have any questions! Like if you want to invite me to give a lecture, presentation or webinar at your company, at your congress, symposium or meeting.

Or if you want to book a session with me as an expert consultant on this area.


Reading list

I previously wrote these related articles about human enhancement:

These are the external links:


How do you view the genetic engineering of humans? Leave a comment!