Essay: Are Genetically Modified/designer Babies the future with the help of CRISPR?

Introduction

Imagine, you could go to the clinic and choose on a menu what kind of traits you would like for your child? Green eyes, brown hair, a high IQ and a kind and generous personality? Is this really possible in the future? Can we edit out bad genes that cause diseases in humans and replace them with healthy ones? Is this ethical and technically possible? Could we engineer animals so they can’t pass on deadly diseases to us?

Is this all ethical and technically possible?

All these questions made me want to choose the topic surrounding genetic modification, and specifically designer babies. it excites me to think about the new technology known as CRISPR- which makes it theoretically possible to change the genes in human-DNA.

I decided to write my PWS in English, because most of the articles that are published about this technology are all in English. On top of this, I liked the opportunity to prepare a project like this in English because we normally don’t get that chance.

1 What is CRISPR?

CRISPR gene editing technology is seen by many scientists as a way in the future to cure cancer, prevent the passing on of inherited diseases and viral infections.

1.1 – DNA info + Definition CRISPR:

Before I explain further to you about CRISPR, I’ll give you some information about DNA, as this is an important part of the whole research. DNA is also known as the molecule, or code of life, called by the name Deoxyribonucleic acid. A complex molecule that guides the growth, development, function and reproduction of everything alive. Information is encoded in the structure of the molecule, 4 nucleotides are pared and form a code that carries instructions, change the instructions and you change the being carrying it.

DNA, code of life

CRISPR’ stands for “Clusters of Regularly Interspaced Short Palindromic Repeats.” The name refers to the way short repeated DNA sequences in the genomes (the complete set of genes or genetic material present in a cell or organism) of bacteria and other microorganisms are organised. The popular term “CRISPR” is short for “CRISPR- cas9.” This “cas9” is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA.

1.2 – How does the process work?

CRISPR technology is made up of two elements, an enzyme and a guide molecule. The guide molecule takes its enzyme (Cas9) to a gene which is selected for modification, the enzyme cuts the gene which can then be repaired or modified in many different ways. By using CRISPR technology it is possible to change the function of the gene, remove the gene altogether or make the gene more active.

How the genome editor works

In this picture you see that The CRISPR-Cas9 system targets precise gene sequences and removes, adds to, or changes them with the help of two components: an enzyme called Cas9 and guide RNA (gRNA). It’s based on the naturally occurring ability of bacteria to recognize and destroy invading viruses via a genetic memory.

If you want to use CRISPR on a genome, you first have to damage the DNA -> this means splitting/cutting the double helix in half -> this causes the normal cell reparation to start -> we then make sure the cell makes the reparation we want, not the natural reparation.

Cas9 acts as the scissor that snips the DNA and the RNA guide is a tailor-made sequence that ensures Cas9 is cutting in the right place. Researchers are able to program the guide RNA with any sequence of the genetic code they desire in order to lead Cas9 to the proper location.

Once the DNA is cut, the cell’s natural repair mechanisms kick in and work to introduce mutations or other changes to the genome. There are two ways this can happen.

According to the Huntington’s Outreach Project at Stanford (University), “one repair method involves gluing the two cuts back together. This method, known as “non-homologous end joining,” tends to introduce errors. Nucleotides are accidentally inserted or deleted, resulting in mutations, which could disrupt a gene. In the second method, the break is fixed by filling in the gap with a sequence of nucleotides. In order to do so, the cell uses a short strand of DNA as a template. Scientists can supply the DNA template of their choosing, thereby writing-in any gene they want, or correcting a mutation.”

A simple explanation of the process

When viruses infect a cell, they inject heir DNA. And in a bacterium, the CRISPR system allows that DNA to be plucked out of the virus, and inserted in little bits into the chromosome, the DNA of the bacterium. And these integrated bits of viral DNA get inserted at a site called CRISPR.

CRISPR is a mechanism that allows cells to record, over time, the viruses they have been exposed to. And importantly, those bits of DNA are passed on to the cells progeny (offspring). So, cells are protected not only in one generation, but over many generations of cells. This allows the cells to keep a record of infection. As Blake Wiedenheft once said: “the CRISPR locus (the position of a particular gene on a chromosome) is effectively the genetic vaccination card in cells.” Once those bits of DNA have been inserted into the bacterial chromosome, the cell then makes a little copy of a molecule called RNA, this is an exact replicate of the viral DNA. RNA is a chemical cousin of DNA molecules that have a matching sequence. Those little bits of RNA from the CRISPR locus bind to protein called Cas9, and form a complex that functions like a lookout (sentinel) in the cell, to find sites that match the sequences in the bond RNAs.

We can think of the Cas9 RNA as a sentinel complex like a pair of scissors that can cut DNA, it makes a double-stranded break in the DNA helix. And importantly, this complex is programmable. So it can be programmed to recognize particular DNA sequences, and make a break in that DNA at that site.

It was recognized that that activity could be strengthened for genome engineering to allow cells to make a very precise change to the DNA at the site where this break was introduced. This is comparable to the way we use a word-processing program to fix a typo in a document.

The reason that it’s envisioned using the CRISPR system for genome editing, is because cells have the ability to detect broken DNA and repair it.

So, when a plant or animal cell detects a double-stranded break in it’s DNA it can fix that break, either by pasting together the ends of the broken DNA with a little tiny change in the sequence of that position, or it can repair the break by integrating a new piece of DNA at the site of the cut. So, if we have a way to introduce double-stranded breaks into DNA at precise places, we can trigger cells to repair those breaks, by either the disruption or incorporation of new genetic information.

So, if we were able to program the CRISPR-technology to make a break in DNA at the position at or near a mutation causing for example cystic fibrosis, we could trigger cells to repair that mutation.

1.3 – Genome engineering in the past

Genome engineering is not new but has been in developments since the 1970s. There have been technologies for sequencing DNA, for copying DNA, and even for manipulating DNA. These technologies were very promising but the problem was that they were either inefficient, or they were so difficult to use that most scientist h
ad not adopted them for use in their own laboratories or certainly for many clinical applications.
So the opportunity to take a technology like CRISPR and put it into practice has appeal, because of it’s relative simplicity we can think of older genome engineering technologies as similar to having to rewire your computer each time you want to run a new piece of software. Whereas the CRISPR-technology is like software for the genome, we can program it easily, using little bits of RNA.

2 What does this have to do with babies?

In 2017 a study carried out by Dr. Shoukhrat Mitalipov a leading scientist in embryo research in the USA showed that by using the CRISPR technology its possible to alter the genes of human IVF embryos safely. This means that the characteristics or traits of babies can be changed.

2.1 What traits could be changed?

The technology could be used to eliminate inherited diseases from the next generation but it could also be used to determine the following characteristics:

• Gender
• Appearance such as blue eyes and blond hair
• Intelligence
• Athleticism
• Personality

This means that parents would be able to “pick and choose” what type of baby they would like just like buying a customised doll.

Build a baby

2.2 How does this process then work?

How to create a modified baby (picture cut-out from newspaper article)

2.3 Pros and Cons of designer babies

For some people the ability to edit the human gene is regarded as a fantastic opportunity to change and improve the human race. They see this new technology as a revolutionary way to eliminate genetic diseases, create new and improved human beings and ultimately create a better world. On the other side of the argument many people regard this new technology as dangerous as they see it as interfering with nature. They are scared that the technology could get into the wrong hands and be misused particularly if there are no strict controls and rules stating who can use the technology and limiting what it can be used for.

Customise your baby!

In the overview below are included a list of the pros and cons surrounding the use of CRISPR genome editing on embryos

2.3.1 Pros:

• Reduces risk of genetic diseases such as Down syndrome, Alzheimer’s, Huntington’s disease, blindness and many more.
• Reduces risk of inherited medical conditions such as cancer, diabetes, anemia, obesity, and many more.
• Prevent next generation of family from getting characteristics/diseases
• Better chance the child will succeed in life and allows a parent to give their child a healthy life.
• Installs a better understanding of genetics amongst scientists
• Increased life span up to 30 years
• Can give a child genes that the parents do not carry
• Modifying your baby is not a requirement but it’s an option. If you’re against the idea, you don’t have to engineer your child. Parents should be allowed to decide and can set the limits.
• If you think about it, parents already engineer their child/children in many ways. For example: religion, morals and education.
• If the technology is banned it could mean that people will go to unauthorized biologists to get the same treatment which is riskier.

2.3.2 Cons

These can be split between the ethical and technical issues:

Ethical

• Modifying your embryo is not cheap, so not everyone could afford it. This could create a big gap in society. Because the modified babies would get preferred treatment at, for example, jobs.
• A baby has no choice in the matter. That’s why some people think its wrong because they say the parents do not “own” their child. It could also be that parents use it for superficial reasons, as they specifically want their child to have brown hair and green eyes for example.
• Loss of individuality. The majority of the people who will modify their baby will want an intelligent, good-looking and a kind baby with lots of other good qualities. This will decrease the uniqueness of the population.

Technical

• The embryo could be accidentally terminated if not done properly.
• Geneticists are only human, and it doesn’t always work out exactly as they want it to (and they can make mistakes)
• Possibility of damage to the gene pool could cause difficulties later on throughout the baby’s family tree.
• Genes don’t have just one use but could own more. This could mean that a child has a gene that controls athleticism but also has a gene that controls emotion. This could lead to a child that’s very athletic but who can’t control his/her emotions.

2.4 How realistic is it that there will be designer babies in the next 20 years?

The reality, however, is that with the CRISPR technology we are a long way away from being able to design babies to control or determine their personalities and intelligence. While CRISPR may be used to determine physical characteristics such as the sex of a child or its hair and eye color current techniques such as PGD (Pre-implantation genetic diagnosis) are already able to achieve these characteristics through the pre-selection of embryos during IVF.

It is far too early and simplistic to say that this new genetic engineering technology will mean that CRISPR will or can be used to create the “super human”. Much more research still needs to be done to see what human characteristics can and should be changed. The people involved in the CRISPR technology see the application of CRISPR for making designer babies much less scientifically interesting than the possibility to use the technique to create ways of understanding and curing genetic diseases as well as to understand the purpose of many genes for which, based on current genetic research, there is no obvious purpose. This is why a major use of CRISP is to find out what certain genes actually do. While there is plenty of data in the scientific area of genetics which means that the sequence of the entire genome of certain organisms is known to actually identify what each gene does is not easy and still needs more research. CRISPR can be used by researchers to remove and/or change parts of a gene and see what the results are. With 3 billion base pairs of the human genome this technology has a long way to go before scientists are able to say what gene influences human characteristics such as for example an introvert or extrovert personality.

This is where the focus is now, given that the technology is still very new as well as the fact that there are a lot of unknowns, meaning that the possibility to make designer babies is not the priority for the scientists.

2.5 Commercial developments:

However, companies are already using this technology to make a profit. For example, the company 23andme promotes itself as a “personal genetics company” where you can buy a baby genetic predictor tool that they have created. Using this tool, women can choose from various options of preferences and screen through the sperm that potential donors have, in order that your baby will possess those particular traits that you are looking for. You can opt for a particular shade of eye colo
r and a level to which you want to reduce your baby’s risk to being affected by certain types of diseases.

GenePeeks is another company which is coming out with more advanced options in the field of genetic mutation and design. It has developed a technology known as MatchRight, which is currently available at certain fertility clinics. It will help you to screen the sperm from various possible donors to see what the result is when that particular sperm is matched with yours. As a result, you will know exactly what type of characteristics your baby will have. The tool has a search option, which will also let you look for any predictable diseases that your baby might be at risk of in the future as well as any specific traits that your baby may pick up or have. Once you finish the designing process, your to-be baby will then go through a series of production steps. Some of these steps may also be carried out in a laboratory, and not inside the womb.

Another thing that is really interesting is that currently, scientists are also trying to create artificial wombs through various laboratory assisted techniques, which will allow you to have a designer baby without even having the baby inside your womb.

2.6 What the experts say …

Expert opinion on this subject further demonstrates the differing opinions that exist in relation to genetic editing and embryo selection. Here are some examples of these differences of opinion:

Biochemist Henry Greely of Stanford University in the USA spoke in an article in the Guardian of “ the possibility of the designer baby fantasy” and stated “ I don’t think we are going to see superman or a split in the species any time soon” he said, “because we just don’t know enough and are unlikely to for a long time-or maybe for ever”.

Bioethicist Ronald Green of Dartmouth College in New Hampshire thinks that technology such as CRISPR will make “design” more of a reality. He thinks that in the next 40-50 years ““we’ll start seeing the use of gene editing and reproductive technologies for enhancement: blond hair and blue eyes, improved athletic abilities, enhanced reading skills or numeracy, and so on.”

He warns that this could also result in other negative developments with the new technology only being available to the richer in society “as the well-to-do exploit technologies that make them even better off increasing the relatively worsened health status of the world’s poor”. Greely states that the impact of other genetic developments such as from PGD, which could give rise to a worldwide improvement in health for all it has only added to the comparable advantage, that wealth already brings. Further progress, which CRISPR brings, could lead to an increase in the health gap between rich and poor, both inside and between countries.

Law professor and Bioethicist R. Alta Charo of the University of Wisconsin has a different opinion. She does not think that there will be any great demand for embryo selection or genetic modification especially if there are doubts about the ability of the technology. She states: “Where there is a serious problem, such as a deadly condition, or an existing obstacle, such as infertility, I would not be surprised to see people take advantage of technologies such as embryo selection. But we already have evidence that people do not flock to technologies when they can conceive without assistance.”

The poor take-up of sperm banks offering “superior” sperm, she says, already shows that for most women, “the emotional significance of reproduction outweighs any notion of ‘optimisation’”. Charo says that “our ability to love one another with all our imperfections and foibles outweighs any notion of ‘improving’ our children through genetics”.

3 What are the important considerations?

CRISPR-Cas9 is not without its drawback. It’s not only got technical issues, but there are also a lot of ethical issues that we should be aware of. Some of these issues have already been mentioned in the pros and cons. These are more specifically explained below:

3.1 Technical issues

“I think the biggest limitation of CRISPR is it is not a hundred percent efficient,” George Church, Robert Winthrop Professor of Genetics at Harvard Medical School. told Live Science. In his view the genome-editing efficiencies can vary. There is also the phenomenon of “off-target effects,” where DNA is cut at sites other than the intended target. This can lead to the introduction of unintended mutations. Furthermore, Church noted that even when the system cuts on target, there is a chance of not getting a precise edit. He called this “genome vandalism”.

In recent research done in China on injecting CRISPR-Cas9 components into the one-cell zygotes only three of the six embryos were genetically modified by CRISPR and two of these three failed develop further which suggested that the gene editing did not take place fast enough before the cell divided into two. However Dr. Mitalipov’s study is a more substantial than the Chinese work. The difference was that his study got CRISPR in at an earlier stage of the fertilization process as the CRISPR was injected at the same time as the sperm before fertilization. This difference is shown in the picture below.

Molecular biologist, Ellen Jorgensen said: “The problem with getting the system (CRISPR) into the cell, in a petri dish it’s not that hard, but if you’re trying to do it on a whole organism, it gets tricky.

Old vs new

It’s okay to do blood or bone marrow; those are the targets of a lot of researches now. There was a great story of a little girl who they saved from leukemia, by taking the blood out, editing it, and putting it back, with a precursor of CRISPR. If you want to get it into the whole body, you’re probably going to have to use a virus. You take the virus, put the CRISPR into it and you let the virus infect the cell. The problem that could accrue is that you’ve got the virus in the cell and we still don’t know what the long-term effects of that are. CRISPR has some off-target affects, a small percentage but still there.”

3.2 Ethical issues

The ethical questions which the gene editing technology throws up is also a major factor in slowing the process of selecting superior traits for your baby and may even stop it completely. Scientifically this is also very complex as characteristics such as intelligence, personality and temperament are not caused by a single gene but by a combination of genes as well as the environment and experiences that the child is exposed to in its early life. It is an accepted fact that a babies’ or persons’ genes alone do not determine who they are but this is a combination of genes and environment.

4 Research

4.1 What do the people think of modified babies using CRISPR?

To find out what people in the Netherlands think about the idea of modified babies I created a survey in which I asked several question surround the topic so that I could get an idea of what the general public think of this technology as opposed to the scientists. I received 100 responses to my survey and the findings are summarised below:

Q1: What is your gender?

The results you see here indicated that the respondents were 75% women and 25% men.

Q2: What is your age?

The most common age group of the respondents was the category of 0-17 and 18-25 years. I was very pleased that this age group responded in such numbers as this is the age group
that I wanted to get the opinion from. The reason for this is because this is the generation that are
most likely to be confronted and affected by this development.

Q3: What is your level of education?

As you can see in the pie chart above, the educational level of the respondents is predominantly higher educated people.

Q4: Are you familiar with CRISPR?

The majority of respondents had not heard of CRISPR, which surprised me given the fact that it’s been in the news a lot recently. I would have thought this subject would have had more impact given the possibilities.

Q5: If so, how did you become aware of it?

As I already expected, news and television have the highest percentage. The reason I did expect this is because its had a high profile in the media in the last six months following the publication of the findings of Shoukrat Mitalipov.

Q6: What do you think of the idea of modifying babies using this technology?

The percentages of the two choices, critical and interesting but sceptical, are very close. There is a thin line between agreeing and disagreeing.

Q7: Do you see this technology being implemented in the future?

Even tough most people are critical about modifying babies, more than half of the respondents see this happening in the future.

Q8: Would you consider using CRISPR on your own embryo?

More than half of the respondents are unsure, and first want to know more about CRISPR and what sort of consequences there could occur. I understand this response as the majority of the people surveyed are not even aware of what CRISPR is or what it is capable of.

Q9: If so, for what reason?

As expected the majority of the respondents selected using CRISPR on their embryos for medical reasons. What surprised me was that more people wanted to have a say in what their child would look like instead of what they were capable of.

Q10: Having completed the survey, would you be interested in finding out more about CRISPR and specifically the possibility for designer babies?

I’m pleased to see that just over half of the respondents want to know more after my survey.

Conclusion

The question I have asked myself in this project is; Are genetically modified/designer babies the future with the help of CRISPR?

Even though gene modification technology has progressed significantly in the last couple of years, particularly with the recent work done by Dr Shoukrat Mitalipov, this still is a difficult question. While the technical issues of successfully making a genetically modified baby look like they are a step closer, the ethical issues remain the biggest barrier to make this a reality.

As seen in the survey, the general public is interested but sceptical about the idea of having designer babies in the future. This, I think, is understandable as was also shown in the survey that few people know what CRISPR is and what it is capable of. My last questions in the survey however is if they could see this happening in the future. More than half of the respondents say yes. This is a different outlook on what scientist think. They think it is possible but it would take about 40-50 years to actually see this happening.

The conclusion I thereby have made is; Yes, genetically modified/designer babies are the future with the help of CRISPR! Although the timeframe for this is still uncertain.