Monday 9 September 2024

New Video: Unexpected Challenges in Genetic Engineering: A Case Study on GM Crops

This video - Unexpected Challenges in Genetic Engineering: A Case Study on GM Crops - is a true story from my research career.

In 2004, I was involved in a €3 million research project that brought together labs from Europe and China. The research team included sociologists, psychologists, biochemists, botanists, and chemists, and we were looking at food safety in genetically modified (GM) crops and people's attitudes to 'functional foods'.  ('Functional foods' are foods that have been produced using genetic modifications or have added vitamins and minerals.)

The project focused on two staple foods—rice and potatoes—and our aim was to reduce harmful compounds in these crops that could pose risks to human health. Specifically, we were trying to develop a strain of rice with low levels of phytic acid and a variety of potatoes with reduced glycoalkaloid content.

Phytic acid, though naturally occurring in many plants, can bind essential nutrients like zinc, calcium, and iron, making them unavailable to the body. This is a particular problem in regions where diets heavily rely on rice, leading to widespread iron deficiency and anaemia, affecting one in four people globally. Rice produces phytic acid to store phosphate in the seed to help it grow.

Some of the different glycoalkaloids found in potatoes have been linked to health risks such as cancer. While potatoes are generally safe to eat, reducing the levels of certain glycoalkaloids could further enhance their safety. The potato produces glycoalkaloids to prevent it from rotting.

Our collaborators in China irradiated rice to introduce mutations, grew the plants and screened them for low phytic acid levels. Meanwhile, our colleagues in Aberdeen developed a potato with a gene knocked out that was responsible for producing a specific glycoalkaloid.

As with many scientific endeavours, our project encountered unexpected results. 

In the case of low phytic acid rice, the mutation that blocked phytic acid production also disrupted a key component of the glycolytic pathway. This meant that the rice could only complete one turn of the TCA cycle per glucose molecule, severely stunting its growth. The rice, though low in phytic acid, grew poorly.

The potato project presented its own surprises. While the gene responsible for producing one of the glycoalkaloids was successfully knocked out, the potato plant compensated by activating another gene that produced a different glycoalkaloid. The total glycoalkaloid content remained unchanged.

For me, this project was a powerful reminder that science, particularly genetic engineering, is often unpredictable. Despite our best efforts and the involvement of many bright minds in the field, the natural complexity of these plants outsmarted us. The results we achieved were not what we had hoped for, but they were incredibly valuable in their own right. They highlighted the intricate balance of biological systems and the challenges of modifying them without unintended consequences.

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Friday 6 September 2024

New Video: Genetically Engineering Pigs to Reduce Environmental Pollution

In this very short video - Genetically Engineering Pigs to Reduce Environmental Pollution - I look at how genetically engineering a pig has produced an animal that is less harmful to the environment.

The problem of phosphate pollution in the runoff from farms, particularly in pig farming, is a significant environmental concern. Animals' diets are often rich in grains, which contain phytic acid, a compound that pigs cannot digest due to the absence of a specific enzyme. The undigested phosphate-rich phytic acid is then excreted as waste, contributing to environmental issues like algal blooms and water contamination.

Phytic acid, found abundantly in grains, is a form of phosphorus that pigs—and many other animals—cannot utilise because they lack the phytase enzyme to break it down. Without this enzyme, the phosphorus passes through the pigs' digestive system and is excreted, leading to the concentration of phosphate in the environment.

To combat this issue, pigs have been engineered to contain the E. coli appA gene, which enables them to produce phytase, the enzyme needed to digest phytic acid. This modification allows the pigs to break down the phytic acid in their diet, effectively reducing the amount of phosphate in their waste.

What makes this solution particularly innovative is the way the gene is expressed. The E. coli appA gene is under a promoter from a mouse, which regulates the expression of proteins in the mouse salivary gland. This means that the pig only produces the phytase enzyme in its saliva. This targeted expression ensures that the enzyme is active exactly where it needs to be—in the pig's mouth. As the pig chews and swallows, the phytase is mixed with the grain, breaking down the phytic acid before it can pass through the digestive system.

This genetic modification significantly lowers the levels of phosphate pollution associated with pig farming by reducing the amount of undigested phytic acid excreted by pigs. 

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Thursday 5 September 2024

New Video: How Plants Are Fighting Climate Change and Pollution?

 In this video - How Plants Are Fighting Climate Change and Pollution? - I look at how plants are being used to help fight climate change and polution.

Genetically engineered plants are being explored to combat climate change and environmental pollution. 

Slowing Climate Change with Carbon-Capturing Plants

One area of research focuses on using plants to slow climate change by enhancing their ability to capture and store carbon. Plants have been engineered to produce suberin, a cork-like substance that resists degradation and effectively traps carbon. These plants are also being developed to grow deeper root systems, ensuring that the suberin (and the carbon it contains) is buried deep within the soil, where it can remain sequestered for long periods.

This carbon sequestration will help reduce the amount of carbon dioxide in the atmosphere and slow global warming. 

Building Resilient Crops for a Changing Climate

As climate change continues to impact agricultural productivity, crops must be developed that can withstand extreme conditions such as heat, drought, disease, and high salinity. Researchers are working to make plants more resilient, ensuring that food supplies remain stable even as the environment becomes increasingly unpredictable.

By enhancing plants' natural defences, it is hoped that crops can be produced that can thrive in adverse conditions, reducing the risk of crop failures and food shortages.

Plants as Pollution Fighters

Plants are also being engineered to tackle pollution. 

A particularly interesting approach involves cloning the rabbit gene P4502E1 into Devil's Ivy, a popular houseplant. This gene encodes an enzyme that breaks down harmful chemicals, including potential carcinogens, into less toxic compounds. By introducing this gene into plants, researchers are creating a natural air purification system that can absorb and detoxify pollutants in urban environments and indoor spaces.

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Wednesday 4 September 2024

New Video: The genetically engineered mouse and COVID-19

 In this video - How Genetically Engineered Mice Help Us Study COVID-19 - I look at how a mouse that was genetically engineered for studying one virus, helped us understand COVID-19.

To develop effective treatments and vaccines for COVID-19, we needed to understand how the virus interacted with living organisms. For this, scientists typically use model organisms like mice. However, using mice for COVID-19 research presented a significant problem.

COVID-19, caused by a coronavirus, gains entry into human cells by binding to a specific receptor on the cell surface known as ACE2 (angiotensin-converting enzyme 2). However, the ACE2 receptor in mice differs from the human version, making it impossible for the virus to bind to mouse cells. This meant that mice could not be used to study the virus in a living organism to better understand how it works and to test potential treatments.

Fortunately, genetic engineering provided a solution. 

Back in 2007, during the outbreak of another coronavirus, SARS, scientists developed a line of genetically engineered mice that express the human version of the ACE2 receptor. These “humanised” mice could be infected with SARS-CoV-2, the virus responsible for COVID-19, making them an invaluable tool in the fight against the pandemic.

Using these genetically modified mice, researchers could study how COVID-19 interacted with cells, how it causes disease, and how different treatments might work in a living organism.

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Tuesday 3 September 2024

New Video: Gene Drives: A Powerful and Controversial Genetic Technology

In this video - Gene Drives: A Powerful and Controversial Genetic Technology - I look at gene drives. A genetic engineering technique that I find equally fascinating and scary.

Gene drives are a revolutionary and controversial advancement in genetic engineering. The process allows scientists to introduce self-propagating changes into an organism's genome, bypassing traditional Mendelian inheritance. By ensuring that specific mutations become homozygous in offspring, gene drives have the potential to rapidly spread these changes throughout populations.

The applications of gene drives are both promising and far-reaching. They could play a crucial role in eradicating mosquito-borne diseases such as malaria and Zika, which continue to claim millions of lives globally. Additionally, gene drives could help tackle drug-resistant fungal pathogens that pose a significant threat to human health and be employed to control or eliminate invasive species that disrupt ecosystems.

But how does this technology work? 

Gene drives use CRISPR, a gene-editing tool. In a gene drive, the CRISPR machinery is introduced along with the desired mutation. This machinery then actively copies itself onto the corresponding chromosome, ensuring the organism becomes homozygous for the mutation. This process allows the mutation to "drive" through the population, even if it does not provide a traditional selective advantage.

However, the power of gene drives comes with significant ethical concerns. The ability to alter ecosystems and species at such a fundamental level raises the question: Just because we can, should we? That is, once you introduce a change in a system using gene drive, how could you change or reverse it, or stop it spreading to other organisms?

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Monday 2 September 2024

CRISPR Case Studies: HIV resistant babies, cancer and blindness

In the video - CRISPR Case Studies: Ethical Dilemmas and Revolutionary Applications - I look at the illegal use of CRISPR on babies and its legal use to treat some conditions.

CRISPR has emerged as a powerful genetic engineering tool. However, it does come with the ethical implications.

CRISPR

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing tool that allows scientists to alter DNA sequences within organisms. Using this technology, researchers can add, remove, or modify genetic material, leading to potential cures for genetic diseases, improved agricultural practices, and innovative solutions to environmental issues.

However, using CRISPR, especially in humans, raises significant ethical issues.

The CRISPR Babies

One of the most shocking uses of CRISPR on humans occurred when the genomes of human embryos were edited, leading to the birth of two genetically modified babies. The primary goal was to disable the CCR5 gene to produce babies that were HIV-resistant. That is, remove the receptor that HIV uses to enter human cells.

The CCR5 gene was selected because a naturally occurring mutation in this gene provides resistance to HIV and the Black Death in about 1% of Northern Europeans.

Researchers attempted to mimic this natural 32-base pair deletion using CRISPR, disrupting the CCR5 receptor's function and preventing HIV infection.

Outcomes and Concerns

The resulting edits did not replicate the exact natural mutation. One baby had a 15-base pair deletion in one copy of the gene, while the other had different insertions and deletions across both gene copies.

These unintended mutations raise serious health concerns as studies suggest that individuals with CCR5 mutations may have a 20% lower likelihood of reaching age 76 and could be more susceptible to other infections and diseases.

There is also the risk of off-target edits, where CRISPR inadvertently alters other parts of the genome, potentially leading to unforeseen health issues.

The scientific community widely condemned this work for its ethical breaches, lack of transparency, and disregard for established guidelines. The researchers involved faced legal consequences, including fines and imprisonment.

This case highlights the ethical dilemmas associated with germline editing:

  • Consent: The edited changes are heritable, affecting future generations who cannot consent.
  • Risk vs. Benefit: The potential health risks may outweigh the intended benefits, especially given existing alternatives to prevent HIV transmission.
  • Regulatory Oversight: The need for strict guidelines and oversight in genetic editing research is evident to prevent misuse and ensure ethical compliance.

Promising and Legal Applications of CRISPR

CRISPR has the potential for legitimate and beneficial medical applications. Here are two examples:

1. Cancer Treatment

Treatment of testicular cancer resistant to conventional therapies.

Patient-derived T cells are collected and genetically modified using CRISPR to disrupt three specific genes that regulate T cell targeting. 

A lentivirus is then used to introduce a new targeting mechanism, directing the T cells to recognise and attack proteins unique to the patient's cancer cells.

The modified T cells are then reintroduced into the patient, aiming to boost the immune system's ability to fight cancer effectively.

This represents a personalised and targeted approach to cancer therapy and demonstrates CRISPR's potential to improve immunotherapy treatments.

2. Treating Childhood Blindness

CRISPR is also being used to address Leber Congenital Amaurosis 10 (LCA10), a cause of blindness in children.

The procedure targets the CEP290 gene, where specific mutations disrupt normal retinal development.

The CRISPR components are packaged into adeno-associated viruses (AAVs), and the system precisely removes the mutation in the CEP290 gene, aiming to restore proper protein function and improve vision.

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Friday 30 August 2024

Exploring Genetic Engineering: How It's Protecting Crops and Enhancing Food

In this video - Exploring Genetic Engineering: Protecting Crops and Enhancing Food - I look at three examples of how genetic engineering has been used to protect crops from insects and enhance the nutritional value of food.

1. BT Cotton: A Solution with Unintended Consequences

BT cotton is a prime example of how genetic engineering can provide a targeted solution to agricultural problems. This cotton variety has been engineered to produce a toxin derived from a specific type of bacteria. The toxin crystallises within the plant, and when an insect eats the leaves, the toxin dissolves the insect’s gut, eliminating the pest without the need for widespread insecticide use. This approach has the added benefit of protecting beneficial insects, as the crop itself becomes a selective defence mechanism.

However, this crop has had some unintended consequences. For example, in India, the high cost of BT cotton seeds has created a debt cycle for many farmers. Additionally, the market has seen a rise in counterfeit seeds, complicating the situation further. 

2. Venomous Cabbage: A Controversial Defense

I do like this one.... what made the researchers think of it?

The venomous cabbage - these cabbages have been modified to express scorpion venom in their leaves. The Diamondback moth larvae, notorious for damaging cabbage crops, eat the leaves of cabbages producing the venom and dying. Luckily, this venom is not toxic to humans, making the cabbage safe to eat.

Would you be comfortable eating such a cabbage?

3. Golden Rice: Tackling Vitamin A Deficiency

I was involved in a similar project - more about that in a later video.

Golden Rice represents a more human-centric approach to genetic engineering. This rice has been enriched with beta-carotene, a compound the human body can convert into vitamin A - making it a potent tool in the fight against vitamin A deficiency, which is prevalent in many parts of the world.

The rice owes its yellow colour to the addition of genes from daffodils and bacteria.

While Golden Rice has the potential to significantly improve public health, it also raises important questions. How do we feel about consuming a staple food that contains genes from other species? This case exemplifies the broader debate surrounding genetically modified organisms (GMOs) and their role in our food supply.

What are your thoughts on these genetically engineered crops? Would you eat them? Let me know in the comments or comment on the video.

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