New Video: Three Parent Babies: Mitochondrial Disease Treatment

In the video - Three Parent Babies: Mitochondrial Disease Treatment - I look at how mitochondrial disease can be treated using mitochondrial replacement therapy (MRT) and three-parent babies.

The mitochondria, often called the "powerhouses" of the cell, provide the energy that keeps our bodies functioning. Interestingly, mitochondria carry their own DNA, separate from the DNA in the cell’s nucleus. This mitochondrial DNA (mtDNA) is passed down almost entirely from our mothers, and it plays a key role in producing proteins essential for the mitochondria's function.

However, mutations in mitochondrial DNA can lead to serious and sometimes life-threatening conditions, referred to as mitochondrial diseases. These diseases primarily affect high-energy tissues such as the brain, muscles, and heart, resulting in a range of debilitating symptoms.

What is Mitochondrial Replacement Therapy?

Mitochondrial replacement therapy (MRT) has been developed to combat these inherited mitochondrial conditions. This procedure aims to replace faulty mitochondria and prevent transmitting mitochondrial diseases from mother to child.

Here’s how it works: 

• An egg is taken from a healthy donor, and its nucleus is removed, leaving behind healthy mitochondria.
• Then, the nucleus from the mother’s egg (who has mitochondrial disease) is transferred into the donor egg, essentially creating a new egg with the mother’s genetic material but the donor’s healthy mitochondria.
• This egg is fertilised with the father’s sperm and implanted into the mother’s womb.

The result is a baby who inherits the vast majority of their DNA from their biological parents but receives mitochondria from a third-party donor. This process prevents the faulty mitochondria from being passed on, giving the baby a chance at a healthy life without mitochondrial disease.

Ethical Considerations of MRT

While mitochondrial replacement therapy has successfully prevented mitochondrial diseases, it comes with significant ethical considerations. Since mitochondria contain their own DNA, this procedure changes the genetic makeup of the individual born through MRT and their future offspring. This raises important questions about the long-term impact on the human gene pool and whether we should alter human genetics this way.

Despite these concerns, mitochondrial replacement therapy has already been performed in some countries, offering families the chance to have healthy children free from mitochondrial disease.

New Video: Answering Your Questions on Genetic Engineering: Unintended Consequences, Science Models and Risks

On my video - Genetically Engineering Pigs to Reduce Environmental Pollution - I received a comment which included a series of important questions on genetic engineering. I was going to reply to the comment directly, but instead decided to do a video reply - Answering Your Questions on Genetic Engineering: Unintended Consequences, Science Models and Risks.

The questions raised in the comment can be broken down into four main areas of concern:

1. Understanding Unintended Consequences in Genetic Engineering

One of the central questions was about the potential unintended consequences of genetic engineering. While science has made remarkable progress, particularly with tools like CRISPR, it's essential to acknowledge that we still need to fully understand all biological systems. This incomplete picture means that, despite our best efforts, we can’t always predict every outcome of genetic modification.

For example, altering a gene in an organism may have unexpected downstream effects. In one case, when scientists genetically engineered babies to be resistant to HIV by removing the CCR5 receptor, they found off-target genetic changes that could have unintended consequences. I discuss these issues in my video - CRISPR Case Studies: Ethical Dilemmas and Revolutionary Applications.

Similarly, work in which I was involved on genetically modified potatoes showed that removing a harmful compound caused the plant to produce a different compound with potentially more harmful effects. You can get the full story in my video - Unexpected Challenges in Genetic Engineering: A Case Study on GM Crops.

The lesson? Genetic engineering requires caution. Scientists must always consider not only the intended outcomes but also the potential for unintended consequences.

2. The Incomplete Nature of Scientific Models

In the comment on the pooping pig video, I was asked whether I ever consider the incomplete nature of our understanding—whether scientific models are accurate or could fail in the long term. The simple answer is yes; I am well aware of this.

For example, at the start of my PhD studies, our understanding of insulin signalling was very basic. However, over the three years it took me to complete my PhD, scientists around the world significantly added to our knowledge and understanding. The model went from a simple black box to a complicated network involving many proteins. However, even this model is imperfect, and new discoveries are constantly reshaping our understanding.

This is true for all areas of biology, including genetic engineering. The more we experiment, the more we refine our models. However, the fact that our models are incomplete doesn’t mean we should stop pursuing genetic modification—it simply means we must proceed with caution and a sense of responsibility.

3. Ethical Concerns: Should We Be Playing God?

Another critical question raised was whether scientists are "playing God" by tinkering with nature. The concern here is that humanity might be overstepping its boundaries by altering the genetic makeup of living organisms.

Humans have indeed been manipulating nature for millennia, from selecting plants and animals for desirable traits to breeding dogs with specific characteristics. However, modern genetic engineering tools, such as CRISPR, allow us to make more precise and rapid changes, bypassing the slow process of natural selection and breeding.

While genetic engineering has the potential to solve significant problems—such as developing disease-resistant crops or addressing hereditary health issues—ethical considerations must remain at the forefront. Just because we can modify genes doesn't always mean we should.

4. Safeguards and the Role of Scientific Scrutiny

A significant factor that should be considered is the safeguards scientists put in place to prevent unintended consequences from spiralling out of control. For instance, if we genetically modify an organism, we can sequence its entire genome to ensure no other changes were made. This type of oversight is crucial when dealing with changes that could have long-term effects on ecosystems or human health.

The issue of gene drives—where genetic changes are engineered to spread through a population—is of particular concern as once released, there’s no way to reverse such changes. This makes it all the more important to thoroughly study and assess the implications before moving forward.

A Balanced Approach to Genetic Engineering

Genetic engineering holds immense promise but also carries significant risks. It is the duty of scientists to consider both the benefits and the possible dangers. By continuing to question the work, refine the models, and engaging with ethical concerns, science can harness the potential of genetic engineering in a way that’s safe and beneficial for society.

At the heart of this debate lies a critical question: how do we balance innovation with responsibility? And we should always consider the question — just because we can, should we?

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.

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. 

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.

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.

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?

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.

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.

The Cavendish Banana Crisis: How CRISPR Could Save Our FavoUrite Fruit

I like bananas — there, I have said it. They are one of my go-to fruits. But did you know they are in danger of being wiped out and no longer available?

In this video - How CRISPR Could Save Bananas from Extinction | The Cavendish Crisis Explained -  I look at why bananas are in trouble and how genetic engineering may come to the rescue.

About 99% of bananas we eat come from a single strain known as the Cavendish. Unfortunately, this strain faces a threat that could wipe it out.

The Cavendish Banana: A Monoculture at Risk

As popular as it is, the Cavendish banana has a significant vulnerability. It's sterile, meaning it can’t reproduce through seeds like many other plants. Instead, it’s propagated through cuttings. While this has allowed us to produce vast quantities of genetically identical bananas, it also means that if a disease affects one plant, it can quickly spread to all Cavendish bananas worldwide.

Fusarium wilt tropical race 4, or TR4, is a fungus threatening to wipe out the Cavendish banana. TR4 attacks the plant's roots, eventually killing it. Because the Cavendish is sterile, traditional breeding methods can’t be used to introduce resistance to this fungus, making the banana especially vulnerable.

Worryingly, this isn’t the first time a banana strain has faced extinction due to a fungal disease. Before the Cavendish, the Gros Michel banana was the world's favourite. However, attacked by a different strain of Fusarium wilt, leading to its near-total disappearance from the market. The Cavendish was introduced as a replacement, but now it’s facing a similar fate.

How Can We Save the Cavendish Banana?

Traditional breeding can't be used as the Cavendish is sterile. Hence, scientists are using genetic engineering to save the banana. One of the most promising approaches involves tweaking the banana’s genome to make it resistant to TR4. 

One explored method is inserting a resistance gene from wild bananas into the Cavendish. The wild bananas have naturally evolved to resist the fungus, and by transferring their genes, we could give the Cavendish the same level of resistance.

However, an even more interesting approach would be to use CRISPR to make precise changes to the banana’s DNA. In the case of the Cavendish banana, CRISPR could be used to activate a gene that has been silenced but could provide resistance to TR4. Additionally, CRISPR could deactivate genes that make the Cavendish susceptible to the fungus.

Why CRISPR is a Game-Changer

The advantage of using CRISPR is that it doesn’t involve inserting foreign DNA into the banana. This means the resulting banana wouldn’t be considered transgenic, which could ease regulatory hurdles and public concerns about genetically modified organisms (GMOs). 

New Video Posted: Introduction to Genetic Engineering: Ethics, Science, and Innovation

I have posted a video - Introduction to Genetic Engineering: Ethics, Science, and Innovation.

Genetic engineering often evokes strong emotions and heated debates. When people hear the term, they might immediately think of genetically modified organisms (GMOs), "Frankenstein foods," or the ethical dilemmas surrounding altering life at its most fundamental level. But what exactly is genetic engineering, and what are the implications of this technology?

In its simplest form, genetic engineering directly manipulates an organism's DNA to achieve desired traits. Humans have used genetic engineering through selective breeding to cultivate crops and livestock that yield better produce and more reliable outcomes for centuries. But today’s technology allows scientists to bypass traditional breeding processes and make precise changes to DNA in a laboratory setting. This raises a profound question: just because we can modify life in this way, should we?

In the video, I look at the ethical and scientific complexities of genetic engineering and wonder where society should draw the line. Is it acceptable to engineer a potato or a chicken for better production? What about a cow? How about a human? These questions are not just theoretical but have real-world implications as technology continues to advance.

I also discuss how genetic engineering can be further divided into two broad categories of genetic engineering: research and applications. Research involves using genetic engineering to understand biological systems and diseases, while applications focus on improving crops, livestock, and human health. The ethical dilemmas become particularly acute when considering human health. Should genetic modifications be limited to somatic cells (which don’t get passed on to offspring), or is it ethical to alter germ cells, thereby affecting future generations?

Finally, I wrap up the video by explaining the difference between transgenic and non-transgenic organisms. Transgenic organisms have DNA from a different species introduced into their genome, while non-transgenic organisms involve changes made to the organism’s own DNA. But this distinction leads to another intriguing question: Is DNA truly species-specific?