How to build a virtual embryo

Drashti Shah
Bioinformatics with Rust
8 min readDec 28, 2023

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This work is a simplified version of an article published in Nature called how to build a virtual embryo. I suggest reading this simplified version before reading the article in Nature. Through posts like these, I am trying to reduce barriers to learning that come with technical jargon that accomplished biologists can understand, but amateur biologists (like me) cannot.

This article discusses a new and exciting area in biology: the creation of virtual embryos using computers. Just like virtual worlds, scientists are now trying to simulate how real embryos develop in the early stages of life. This is a complex task because it involves understanding and mimicking the intricate processes that occur in early development. But if successful, these virtual embryos could help us understand human development better, without the ethical concerns of using real human embryos.

Scientists are making these virtual embryos by using a lot of data from actual biological experiments. They especially focus on a stage of development called ‘gastrulation’, which is crucial because this is when a simple group of cells starts transforming into a structured body plan with different types of cells. Imagine it like a lump of clay starting to take the shape of a sculpture. This stage is very important to understand, as errors during gastrulation can lead to serious problems or diseases.

One of the challenges in creating these virtual embryos is ensuring that the models are as realistic as possible. This means they need to accurately reflect the complex interactions and processes that occur in real embryos. It’s not just about creating a visual model; it’s about simulating the dynamic, living processes that occur during development. It’s similar to creating a highly detailed and functional virtual reality simulation, not just a static 3D model.

And to build a realistic virtual embryo, scientists need to understand not just how cells change into different types, but also how they move and arrange themselves in the embryo. This process is like a complex puzzle where each cell has to find its right place and shape to form different body parts. Researchers are using 3D models and time-lapse imaging to see how cells move and interact with each other over time in the developing embryo. This approach helps them to visualize and better understand the dynamic nature of embryo development.

Scientists often deal with huge datasets where they collect thousands of different pieces of information from each cell. This is a common challenge across many scientific fields. Even something like the shape of a cell is complex and requires many different measurements to fully describe. To manage and understand these large, high-dimensional datasets, scientists use tools from machine learning.

One specific method they use is called principal component analysis. This technique helps to simplify the data by reducing it to its most important elements. For example, it can take hundreds of measurements and condense them down to the two most important ones. This not only makes the data easier to visualise (like plotting it on a two-dimensional graph) but also helps highlight the most crucial aspects of the data.

The scientists are particularly interested stem cells. Stem cells are unique because they have the potential to become any type of cell in the body, like a heart cell or a brain cell. This flexibility is crucial in the early stages of an embryo’s development. To create their virtual embryos, researchers are using advanced techniques to study these stem cells in detail. They’re examining how stem cells transform into different types of cells and what factors influence this process. It’s like unraveling a mystery of how a general-purpose cell decides its specific role in the body.

The complexity of embryonic development becomes even more apparent when we consider the timing and location of these cellular communications. Not only do cells need the right signals, but they also need them at the right time and place. A signal that is beneficial at one stage or location might be harmful in another. This precise coordination is like a choreographed dance, where timing and positioning are crucial for the overall performance.

Moreover, researchers are interested in the mechanical forces at play in embryo development. Just like buildings need to be structurally sound, the developing embryo needs the right balance of forces to shape its tissues and organs correctly. Scientists study how cells push, pull, and organize themselves, contributing to the physical structure of the embryo. This aspect of development is like the architectural and engineering principles that govern the construction of a complex structure.

Another focus is on the environment surrounding the cells in an embryo, known as the extracellular matrix. This matrix provides support and signals to the cells, influencing their behavior. It’s like the scaffolding and signals around a construction site that guide the builders or cells in their work. Understanding this environment is crucial because it plays a big role in how cells arrange themselves and how tissues and organs are formed.

In addition to cell movement and changes, genes play a crucial role in embryo development. Genes are like instructions that tell cells what to do. By studying which genes are active at different stages of development, scientists can gain insights into how an embryo grows and develops. This involves analysing the patterns of gene expression — basically, which genes are switched on or off at specific times. Understanding these patterns is key to figuring out the biological processes that guide the formation of the embryo.

This research is leading to some fascinating discoveries. For instance, scientists are finding that the same sets of genes can be used in different ways at various stages of development or in different types of cells. This versatility of genes is like a toolkit that can be adapted for different purposes. Understanding this flexibility is key to understanding how a relatively small number of genes can create such a diverse range of organisms.

Embryos explore possibilities. Think of embryos as exploring different possibilities or configurations in their development. Scientists call this exploring “phase space”. It’s like trying out different ways to grow and form. As embryos develop, they naturally take on certain shapes that are stable and efficient. This is similar to how bubbles are round because that shape uses the least amount of energy to maintain. In the same way, embryos grow into shapes that are mechanically stable.

Researchers are not just looking at human embryos; they are also studying animal embryos. This is because many fundamental processes in embryonic development are similar across different species. By comparing human and animal embryos, scientists can learn about general principles of development. For example, they study zebrafish and fruit flies, as these species have simpler and more accessible embryos. This cross-species study helps in understanding basic developmental processes that are common to many organisms, including humans.

However, there are limitations to using animal models. While they provide valuable insights, not all processes and structures in animal embryos are the same as in humans. This means that scientists must be careful when trying to apply their findings from animals to human development. They need to identify which aspects of animal development are relevant to humans and which are not. This requires a careful comparison and understanding of the differences and similarities between species.

To overcome these limitations, researchers are also using human stem cells to create structures that resemble early embryos. These structures are not actual embryos, but they mimic key aspects of embryonic development. By studying these models, scientists can observe processes that are difficult or impossible to study in real human embryos. This approach provides a more direct way to understand human development, complementing the insights gained from animal models.

They are also using a technique called ‘organoids’ to gain even more insights into human development. Organoids are tiny, 3D structures grown from stem cells that mimic real organs. By growing these organoids, researchers can study how different types of cells come together to form complex organs. It’s like having a miniature version of an organ in a lab dish, which allows scientists to observe how cells behave and interact in a more realistic environment.

One of the challenges in this research is that many of the processes in embryo development happen at incredibly small scales and are difficult to observe directly. To overcome this, scientists use advanced imaging techniques. These techniques allow them to see the tiny details of how cells behave and interact during development. It’s like having a super-powerful microscope that can reveal the hidden world inside the developing embryo.

Another challenge is understanding the variability and flexibility in embryonic development. Not every embryo develops in exactly the same way; there are variations. Scientists need to figure out which variations are normal and which might lead to developmental problems. This is similar to understanding the range of normality in human behaviors and characteristics.

Moreover, just looking at the embryo isn’t enough. Scientists also use mathematical models and computer simulations to understand the complex interactions and processes. These models help them predict how changes in one part of the embryo can affect the whole development. It’s like using a computer program to simulate a complex system, allowing researchers to experiment and see what might happen under different conditions.

The ultimate goal of this research is to create a complete and accurate virtual model of the embryo. This model would not only show how the embryo looks at each stage but also how each part of it functions and interacts with the rest. Achieving this would be a major breakthrough, providing a deep understanding of embryonic development and helping to address issues like birth defects and infertility.

Even with the best models, there are always uncertainties and unknowns. Since embryonic development is so complex, it’s difficult to capture every detail perfectly. Researchers continually update and improve their models as they learn more and as technology advances. This process is like refining a map of a newly discovered territory; as more is explored, the map becomes more detailed and accurate.

Ethical considerations are also very important in this research. Since it involves simulating human development, there are questions about how far these simulations should go and what they should be used for. It’s essential to have guidelines and regulations to ensure that the research is conducted responsibly.

Finally, this research has significant implications for medicine and biology. Understanding embryonic development in detail could lead to breakthroughs in treating diseases and addressing fertility issues. It could also provide insights into how to prevent developmental disorders. This potential makes the research not just a scientific endeavour, but also a quest with profound impacts on health and well-being.

In the future, these models could be personalised based on individual genetic information. This would allow for simulations of embryonic development that are specific to a particular person. Such personalised models could have significant implications for personalised medicine and understanding individual development patterns. It’s like having a custom-made blueprint of how a person’s development might have occurred, based on their unique genetic makeup.

In conclusion, the study of embryonic development through computational models is a fascinating and complex field with enormous potential. It combines biology, technology, ethics, and society, presenting both opportunities and challenges. As this field continues to grow, it promises to unveil deeper insights into the mysteries of life and have a profound impact on medicine and biology.

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Drashti Shah
Bioinformatics with Rust

ESG & climate data scientist by day. Aspiring computational biologist by night.