The scary techniques of Genetic Engineering

For a couple of years now, rumors are that designer babies are just around the corner. The rumors state that it will be possible for parents to literally “design” their kids, much like you would design a website today. Given how nuts this idea sounds, how did it spread so widely in the first place?

The line of thought that led to these rumors is the following: All characteristics that make humans distinct are programmed in their DNA. Hair color, skin color, body dimensions and so on are all determined by a specific piece of DNA. At some point, technology will become sophisticated enough to change DNA however desired. As a consequence, at this point it will be possible to actually design human beings.

Again, this is what the rumors say. But what does science say? How does modern biotechnology really look like and what genetic engineering techniques are available to us?

What is Biotechnology?

It is not easy to formulate a clear definition for what biotechnology is. In most modern contexts it refers to technologies from the field of molecular biology. More specifically, a collection of techniques that are about analyzing and altering the basic building blocks of life. Molecular biology, as a subarea of biology, concerns structure and function of macromolecules. Central to molecular biology is research about DNA and RNA.

So, one way to put it, biotechnology is the notion that molecular biology is not only about understanding nature but increasingly about altering it. 

However, there is a more broad and often cited definition from the US congresses “Office of Technology Assessment”. It says: “Biotechnology includes any technique that uses living organisms or parts of organisms to make or modify products, to improve plants or animals, or to develop microorganisms for specific uses.“

Biotech has been around

If you think about it, the above definition applies to lots of techniques we already use all the time. Most agricultural goods we use today are a product of some form of biotechnology. For example, the process of beer brewing makes use of yeast, a single-cell organism. In short, yeast takes sugars like glucose or maltose and produces alcohol and carbon dioxide. 

Yeast and its role in beer brewing (Source)

This process very well fits the above definition. Which is also true for processes like making bread or cultivating fruits and vegetables. But we are not really interested in techniques that have been around for thousands of years. Instead, we are more interested in modern or future techniques. So, what is modern biotechnology? 

Tampering with DNA

Many modern biotechnology techniques are based on genetic engineering. Genetic engineering or DNA technology is without doubt a rapidly growing field and will most likely open up mind-boggling possibilities in the future. Therefore, we will examine the general pattern and some basic techniques of DNA technology. But first, some prerequisites from the world of molecular biology. Also note that although there are subtle differences between genetic engineering and DNA technology, they are used interchangeably here.

THE FAMOUS DEOXYRIBONUCLEIC ACID

Surely, you are familiar with the famous double helix shape of a DNA-molecule. Most likely, you also know it contains an organism’s genetic information and that all organisms have DNA in their cells – except for some RNA-viruses. In plain words, the information stored in DNA determines a person’s eye color, height, susceptibility for genetic diseases and so on.

Thus, if you want to find out a certain trait about a person, you have to find the respective segment in their DNA. Such a segment that determines one specific characteristic of the organism is called a gene. The entirety of genetic information in a cell is called the genome. Estimates for the number of human genes vary a lot but most agree that there are tens of thousands. Still, genes make up only about three percent of the human DNA. The remaining 97 percent are not as well understood yet. 

Genes in DNA (Source)

The critical function of genes is that they also contain information for the creation of so-called RNA. In a process called transcription, RNA is built from DNA. While there are different types and different functions of RNA, they essentially act as blueprints for proteins. Proteins, which eventually form the characteristics, specified in the DNA.

To me, it is astounding that scientists were able to figure out all of this knowledge! But of course, research does not stop here. Once we understand a system well enough, the idea of tampering with it comes pretty naturally. This is where DNA technology comes into play.

General pattern of genetic engineering

Strongly simplified, the overall goal always is to create recombinant DNA (rDNA). That is, constructing an artificial DNA molecule as desired that would normally not occur in nature. The process includes several steps: First, it is necessary to identify and locate the DNA pieces of interest. We must then extract those pieces from the natural DNA molecule. In a third step, they are incorporated into some plasmid or vector, which we will look at later. Finally, they can be inserted into the chosen host genome and the product is a piece of recombinant DNA. This general pattern is also often referred to as genome editing.

To better understand how this is done, in the following we take a look at techniques of DNA cloning and DNA sequencing. The descriptions are kept very general and brief. Of course, in practice these techniques are highly complex processes and numerous variants of them exist.

DNA CLONING

In essence, the purpose of DNA cloning is to make multiple copies of a piece of DNA, for example a gene. The challenge of extracting the particular piece of DNA is done via so-called restriction enzymes. These enzymes are able to cut DNA at a specific location, a restriction site.

After cutting out a piece of DNA, it needs to be “pasted” into a plasmid, which usually is a circular DNA molecule – the host genome. For this part, we can make use of DNA ligase. DNA ligases are also enzymes which can string together pieces of DNA. This ability is useful to insert pieces into a plasmid.

It is important to understand that this is not done for one single DNA molecule. You would rather just put together lots of DNA and restriction enzymes and plasmids. So many that there is a high probability for the reaction to happen a certain number of times.

Cloning process (Source)

There is one more step: To replicate the copied piece of DNA, typically it is inserted into bacteria, for example “E. coli” (Escherichia coli). Then the offspring of the modified bacteria also contains the plasmid.

You might wonder what the benefit of all of that is? It very much depends on the function of the “cloned” piece of DNA. For example, it could be a gene that effectuates production of insulin. Often times the purpose might also be to conduct experiments. 

DNA SEQUENCING

The beneath image takes a closer look at the structure of DNA. As you might remember from school, central parts of a DNA molecule are the so-called nucleobases. They build base pairs inside the double helix and there are four types of them. If you view an organism as a computer program, then the order in which the nucleobases appear would be the source code. DNA sequencing techniques concern the task of determining this order of nucleobases.

Internal structure of DNA (Source)

One basic DNA sequencing technique is called Sanger Sequencing. Here is how it works: 

The first step is to split the molecule into two single strands. This can be done by heating it up, a process known as denaturation. In a second step the mixture cools down and a short molecule – a primer – attaches to the DNA single strands at a specific location. It builds a short piece of double-strand molecule. With the use of an enzyme – DNA polymerase – the missing piece is added to receive a double-stranded molecule of a specific length. Because this happens not ten or twenty times but lots of times, at the end the mixture contains double-stranded molecules of every possible length. Meaning, every possible length within the scope of the piece DNA that should be sequenced. This makes it possible to reconstruct the exact sequence of nucleobases from the original piece of DNA.

Brief remark on bioethics

Obviously, the things made possible by biotechnology raise lots of ethical questions. Questions like, how should a particular technology be used? Is it wrong to use it at all? Who even has a right to debate those subjects? These questions are important to discuss by all means. When you modify the genetics of an organism, the modifications will also be inherited by all of its offspring. Hence, you are potentially creating a new race. But the issues of bioethics are not discussed here, since this blog focuses on technologies themselves. 

Future outlook

Less than a decade ago, scientists discovered CRISPR gene editing – the CRISPR-Cas9-method. Arguably, CRISPR is the most advanced genome editing technique known today, basically promising arbitrary, fast and easy gene editing. This might have led to unrealistic expectations for genetic engineering. So, what would be a realistic outlook on future technologies and their applications?

Technologies like CRISPR will without doubt change the lives of millions of people for the better! How? Here are some examples: 

Medicine

Obviously, medicine can benefit hugely from modifying DNA. It is not at all unrealistic that a variety of genetic diseases will be cured by this technology. Also, personalized medicine will drastically advance to a point where drugs are individually adapted to a patient.

Agriculture

More applications lie in agriculture. It is not a new technique to genetically modify plants for an increased crop yield. In the future this trend will likely accelerate with possibly entirely new kinds of food or food produced in a lab (in vitro).

Environment

But manipulating plants can have bigger purposes. Climate change is one of the most pressing issues of our times, and we have not found a solution yet. Maybe, someday genetically modified plants will play its part in solving this too.

While there are so many beneficial use cases, there are also potential risks. Some would even say biotechnology poses existential risks for humanity. Analogous to other disruptive technologies, as available techniques become more powerful, it will be crucial to sustain a strong ethical framework. Altogether, genetic engineering can be applied in so many ways that it is hard to tell what its impact on our lives will ultimately be. However, one thing is for sure. It is a rapidly evolving field, you should definitely keep paying attention to.

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Victor Shibut
17.04.20, 15:30
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