A few weeks ago I wrote an article about the Earth BioGenome project in which I suggest that the idea of the project collecting and sequencing all of life was aimed at working towards being able to ‘de-extinct’ species that may be lost in the coming years.

Well this week the Guardian UK newspaper has run an article specifically about de-extinction, leading with the title Firm Raises $15m to Bring Back Woolly Mammoth from Extinction.

Now headlines don’t tell the whole story as we know, and what the article appears to be saying is that scientists (and I will come back to who) want to create an elephant-mammoth hybrid by making embryos in the laboratory that carry mammoth DNA. The plan is to begin by taking skin cells from Asian elephants and reprogram them into more versatile stem cells that carry mammoth DNA.

This could lead to the hybrids having long hair, larger fat depositis and other characteristics that would allow the animals to live in cold environments, rather like a mammoth.

The article has a subtitle though that makes for even more interesting reading: Reintroducing large animals can help restore ecosystems.

This is actually a link to an article that talks about the introduction of wolves and other non-extinct species into environments that suit their lifestyles, although the scientists proposing to do this with mammoths argue that their introduction may help to restore the degraded arctic tundra habitat and help in fighting global warming.

As we might imagine however none of the above comes without criticism, with other scientists arguing that these environmental claims might be baseless and the problems of producing such a hybrid aminal should not be underestimated (in technological terms).

George Church

Now to come back to the scientists. The money has been raised by bioscience and genetics company Colossal, co-founded by Ben Lamm, a tech and software entrepreneur, and George Church, a professor of genetics at Harvard Medical School who has pioneered new approaches to gene editing. I don’t know much about Lamm, but George Church is a very interesting character. He has been at the forefront of all types of genetic research for many decades, raising plenty of controversy along the way.

He is a pioneer who has pushed scientific boundaries, and I had the pleasure of meeting him and sharing lunch back in 2012. I have to admit I was a bit frightened though. What do you say in such presence? There doesn’t appear to be any box to think out of for him!

This seems like an incredible project to me, to the point that I don’t know what to think. I grew up in the era of the Jurassic park films! Will I one day look out to see a pterodactyl fly past?

How does the UK Approved COVID-19 vaccine work?

Synthetic Biology Technology has brought us to the point today that the UK has accepted one of the COVID-19 vaccines for distribution, with the promise that distribution will begin soon. This result has taken just 10 months, how have the pharmaceutical researchers managed to do this? Through advances in technology.

In reality, there are different types of COVID-19 vaccine currently in trials:

1: Live attenuated vaccines

Some well-known vaccines for other infectious diseases are based on weakened versions of a virus.  These are known as live attenuated vaccines.
The viruses are weakened to reduce virulence by culturing cells in a laboratory, and then processed into a vaccine. After people come into contact with these attenuated viruses through vaccination, the virus will not be able to replicate easily in humans. As a result, our immune system has enough time to learn how to fight against this weaker form of the virus. This approach enables us to become immune without getting sick.

2: Inactivated vaccines

Inactivated vaccines contain viruses or bacteria that have been killed, which are either whole or in pieces. When our immune system detects these dead viruses or bacteria or their fragments, it can learn to recognise the fragments. After this, we are protected. If we are infected by the live version of the virus or bacteria in the future, our immune system will recognise the virus or bacteria and respond more quickly to protect us from infection – so we will not become ill.

3: Subunit vaccines

If the vaccine only contains particular pieces of a virus or bacteria, it is known as a subunit vaccine. When that subunit can be recognised by the immune system, it is referred to as an antigen.
Extensive research is being carried out on subunit vaccines for protection against COVID-19. An important subunit of SARS-CoV-2 is the spike protein or S protein, which is attached to the exterior of the virus. The virus uses the S protein to make contact with another protein which is located on the exterior of the cells in our lung vesicles. If the virus attaches itself to a human cell via the S protein, the virus can penetrate the exterior and enter the cell. Then the cell is infected.  Because the S protein plays such an essential role in the infection process, it is targeted by many vaccine developers. If we are infected by the live version of the virus in the future, our immune system will immediately recognise the virus and we will not become ill.

4: mDNA and mRNA vaccines (m stands for messenger)

DNA and RNA vaccines add a new piece of genetic material – deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) – to specific immune cells in our body. The targeted cells are often a particular type, which absorb and break down a virus or bacteria. The immune cells that have broken down a virus or bacteria then show a piece of the virus or bacteria (a subunit known as an antigen) to other immune cells so they learn to recognize the antigen. That is why these immune cells are also referred to as antigen-presenting cells. The cells that learn to recognize the antigen are called lymphocytes. DNA and RNA vaccines allow the antigen-presenting cells to detect a piece of the pathogen without the cell first having to absorb and break down the live version of the virus or bacteria. If we are then infected by the live version of the virus or bacteria in the future, the lymphocytes will recognize the antigen for the pathogen, neutralize the virus or bacteria, and we will not become ill.

There are also DNA and RNA vaccines that use ‘normal’ body cells instead of immune cells. These cells also present the antigen to our immune system, which ensures that we will not become ill if we do get infected. 
These DNA and RNA techniques are new, and a DNA or RNA vaccine has not yet been approved for any human disease. A number of DNA vaccines have already been used successfully for animals.

5: Vector vaccines

Researchers can modify existing viruses to act as vaccines. Once that happens, they are no longer viruses, but vectors. The viruses have been adapted in such a way that they do not display exactly the same behaviour as unmodified viruses. The difference compared to the real viruses is that vector viruses:

  • can no longer make someone ill;
  • (often) cannot replicate themselves, and;
  • not only contain their own RNA or DNA, but also have a piece of RNA or DNA from another virus within them. All pieces of RNA or DNA can work as an antigen, so the cells in our immune system will react to the vector virus as well as to part of the vaccine virus. This is how immunity is developed.

A category of viruses that are often adapted into a vector are the adenoviruses. Adenoviruses are a group of viruses to which people are often exposed, but which cause no or only mild illness. Because adenoviruses are so common, our immune system is very good at dealing with an adenovirus infection.

This article in Nature goes into further detail.

The vaccine approved today in the UK from Pfizer/BioNTech is an mRNA vaccine. This is cutting-edge technology, and the first time such a vaccine has been approved!

To produce an mRNA vaccine, scientists produce a synthetic version of the mRNA that a virus uses to build its infectious proteins. This mRNA is delivered into the human body, whose cells read it as instructions to build that viral protein, and therefore create some of the virus’s molecules themselves. These proteins are solitary, so they do not assemble to form a virus. The immune system then detects these viral proteins and starts to produce a defensive response to them.

Synthetic Biology!

What actually is GM Food?

Last week I gave some statistics about GM food production both in the USA and worldwide, and this week I wanted to consider what genetic modification actually is. It appears to me that confusion reigns when addressing issues surrounding GM, so I would like to try and clarify a few issues.

GM exists in plants but also in animals as the salmon link showed last week (not currently approved for consumption), but we tend to associate it mainly with crops, so what does it entail?

In relation to the biggest crops that I mentioned last week, soybean, cotton and corn, there are 2 distinctly different approaches. The first is herbicide tolerance (HT) and the second insect resistance (Bt). In other cases nutritional changes have been made, but the major cash crops are based around the following approaches.

Herbicide-tolerant (HT) crops are developed to survive application of specific herbicides that previously would have destroyed the crop along with the targeted weeds. So you can plant your seeds and spray a herbicide that kills everything apart from your desired crop.

Herbicides target key enzymes in the plant metabolic pathway, which disrupt plant food production and eventually kill it. Genetic modification creates a degree of tolerance to the broad-spectrum herbicides – in particular glyphosate and glufosinate – which will control most other green plants.

Industrial Herbicide Techniques

Industrial Herbicide spreading Techniques

1. Glyphosate-tolerant crops
Glyphosate herbicide kills plants by blocking the EPSPS enzyme, an enzyme involved in the biosynthesis of aromatic amino acids, vitamins and many secondary plant metabolites.  There are several ways by which crops can be modified to be glyphosate-tolerant. One strategy is to incorporate a soil bacterium gene that produces a glyphosate-tolerant form of EPSPS. Another way is to incorporate a different soil bacterium gene that produces a glyphosate degrading enzyme.

2. Glufosinate-tolerant crops
Glufosinate herbicides contain the active ingredient phosphinothricin, which kills plants by blocking the enzyme responsible for nitrogen metabolism and for detoxifying ammonia, a by-product of plant metabolism. Crops modified to tolerate glufosinate contain a bacterial gene that produces an enzyme that detoxifies phosphonothricin and prevents it from doing damage.

The developers argue that use of this type of seeds cuts fuel usage and tilling as there are fewer weeds, (tilling leads to top soil loss as it is blown in the wind). They also argue that GM production has led to less herbicide use, and this seems to currently be the case.

Unfortunately one effect of this mass usage seems to be the development of ‘superweeds’, that are becoming resistant to theses herbicides. Farmers have had to address this problem by using more and different types of herbicide, with the journal Nature recently reporting a Pennsylvania State University research article that claims that pesticide use will increase dramatically in the very near future as a result, questioning the sustainability of the process. Something similar to the present antibiotics resistance problem that we are seeing in the human population. It should also be noted that the use of broad spectrum herbicides has grown as GM usage has grown, as its ease of application using the new seeds has made it more widespread, even though it only needs to be applied once.

Insect-resistant crops containing the gene from the soil bacterium Bt (Bacillus thuringiensis) have been available for corn and cotton since 1996. These bacteria produce a protein that is toxic to specific insects. Instead of the insecticide being sprayed, the plants produce the bacteria so the insects eat the plant and die.

There are risks associated with this approach as well as the advantage that farm workers are not exposed to spraying insecticides.

Invasiveness – Genetic modifications, through traditional breeding or by genetic engineering can potentially change the organism to become invasive. Few introduced organisms become invasive, yet it’s a concern for the users.

Resistance to Bt – The biggest potential risk to using Bt-crops is resistance. Farmers have taken many steps to help prevent resistance but as in the previous case it is a potentially serious problem.

Cross-contamination of genes, genes from GM crops can potentially introduce the new genes to native species.

Now I am no scientist as we all know but I presume that the human must consume the bacteria too, although scientists assure me that the bacteria is not harmful to humans or other mammals.

Much of the recent dramatic growth in GM usage can be attributed to the development of plants that offer both of these systems.

Next week I will take a look at the regulation of GM foods.