#394 — Bringing Back the Mammoth
In this episode of Making Sense with Sam Harris, Ben Lamm of Colossal Biosciences discusses his company's groundbreaking efforts to revive extinct species like the woolly mammoth through advanced genetic engineering tools. Lamm explains Colossal's rigorous approach, which involves analyzing ancient genomes and making precise edits to the DNA of living organisms like the Asian elephant, the mammoth's closest living relative.
Beyond the process and challenges of de-extinction, the conversation explores the broader implications of Colossal's work. Lamm highlights how innovations in genome editing and AI guidance could lead to breakthroughs in human health, anti-aging treatments, conservation efforts, and ecosystem restoration. While the science progresses, ethical debates around "playing God" and ecological impacts remain.
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De-Extinction Through Advanced Genetic Engineering
Colossal Biosciences, co-founded by Ben Lamm, is a pioneering company leveraging cutting-edge genetic tools like CRISPR and AI to revive extinct species like the woolly mammoth, Tasmanian tiger, and dodo.
Reversing Extinction Through Rigorous Genomic Analysis
Rather than the fictional "Jurassic Park" approach of combining incomplete DNA fragments from different species, Colossal takes a comprehensive approach:
- Analyzing over 65 mammoth genomes and achieving over 99% completion of the Tasmanian tiger genome to understand the key genetic differences from living relatives.
- Using the Asian elephant, which shares 99.6% of its DNA with the woolly mammoth, as a genetic starting point.
- Employing tools like CRISPR, gene knockouts, base editing, and multiplex editing to make precise genome changes in living elephant cells.
- Employing AI to guide efficient genome editing, with over 90% accuracy in recommending the optimal tools.
Practical and Ethical Considerations
Even as the science progresses, de-extinction efforts face significant challenges:
- Ensuring reliable cell culturing, gene editing, gestation and development to produce healthy, viable offspring.
- Understanding ecological impacts when reintroducing species like mammoths into modern environments.
- Considering ethical debates around "playing God" and resource allocation priorities for existing endangered species.
Potential for Broader Impact
Lamm highlights how Colossal's de-extinction work drives innovations applicable to human health and conservation:
- Insights into regulating genes like p53 could yield anti-aging and cancer treatments.
- Advanced genetic tools could enhance biodiversity and ecosystem restoration efforts.
- Colossal aims to make its conservation tech freely available to drive further innovation.
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Counterarguments
- The genetic similarity between Asian elephants and woolly mammoths may not be sufficient to ensure the viability and health of a de-extinct species.
- AI's 90% accuracy in genome editing recommendations may not account for unforeseen genetic complexities and interactions in a living organism.
- The challenges of cell culturing, gene editing, and gestation could be more significant than anticipated, leading to unforeseen ethical dilemmas and technical hurdles.
- Reintroducing extinct species could disrupt current ecosystems and potentially harm existing species and ecological balances.
- Ethical debates may not just revolve around "playing God," but also concern animal welfare, the rights of genetically engineered creatures, and the potential for unforeseen consequences.
- The focus on de-extinction might divert resources and attention from more pressing conservation efforts for species currently at risk of extinction.
- The promise of de-extinction technology contributing to anti-aging and cancer treatments is speculative and may not materialize.
- Making conservation tech freely available is commendable, but without proper regulation and oversight, it could lead to misuse or unintended negative consequences.
- The broader impact on biodiversity and ecosystem restoration is uncertain and may not be as positive as suggested, especially if de-extinction efforts do not integrate with holistic conservation strategies.
Actionables
- You can deepen your understanding of genetics by starting a DNA ancestry project to explore your own genetic heritage and see how traits are passed down in your family.
- By using a consumer DNA testing service, you can learn about the genetic markers that define your lineage. As you map out your family tree, pay attention to inherited traits and how they compare to broader population genetics, which can give you a personal perspective on the science behind de-extinction and genetic diversity.
- You can support biodiversity by creating a wildlife-friendly habitat in your own backyard or community garden.
- Plant native species to attract and support local wildlife, providing food, shelter, and breeding grounds. This hands-on approach to conservation can help you understand the importance of each species in an ecosystem, mirroring the larger-scale efforts of organizations like Colossal Biosciences.
- You can engage with ethical debates on de-extinction by starting a book club focused on science ethics.
- Choose books and articles that explore the ethical implications of genetic engineering and de-extinction. Discussing these topics with others can help you form well-rounded opinions on the subject and appreciate the complexity of the ethical considerations involved in such scientific endeavors.
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The science and technology behind de-extinction
Colossal Biosciences, co-founded by Ben Lamm, is at the forefront of leveraging advanced genetic engineering techniques like CRISPR and AI to reverse the extinction of species such as the woolly mammoth, Tasmanian tiger, and dodo.
Colossal Biosciences leverages advanced genetic engineering techniques like CRISPR and AI to pursue the resurrection of extinct species
Taking a comprehensive and scientific approach to de-extinction, Colossal Biosciences focuses on a deep understanding of the genomes of extinct species rather than the traditional fiction-cinema methods of filling genetic gaps with related-species DNA.
Colossal is using a reverse approach compared to the fictional "Jurassic Park", focusing on thoroughly understanding the complete genomes of target species like the woolly mammoth, Tasmanian tiger, and dodo rather than trying to fill in gaps with incomplete ancient DNA
Ben Lamm discusses how Colossal's goal is not to fill in genetic gaps with DNA from other species as depicted in "Jurassic Park." Instead, their real-life scientific approach is to fully understand the genomes of extinct species to accurately select and engineer key genes into a living species. He emphasizes the fundamental differences in approach, clarifying that contrary to the "Jurassic Park" method, where ancient DNA is sourced from amber—an unreliable storage medium—Colossal invests in robust genomic analysis using the closest living relatives as a starting point.
The company has collected over 65 mammoth genomes and is working to achieve over 99% completion of the Tasmanian tiger genome, allowing them to precisely identify and engineer the key genetic differences between these extinct species and their closest living relatives
The Asian elephant, sharing 99.6% of its genetics with the woolly mammoth, serves as the extant genetic proxy for the mammoth. With over 65 mammoth genomes collected from Siberian and Russian samples spanning approximately 700,000 years, including protein-coding regions from Colombian mammoths and step mammoths, Colossal has a comprehensive genetic catalog to work from. With regards to the Tasmanian tiger, Lamm highlights the near completion of its genome, a remarkable achievement that sets the stage for their de-extinction efforts.
Colossal employs a combination of techniques including individual nucleotide editing, gene knockouts, and large-scale DNA synthesis to make the necessary genetic changes, with a focus on developing efficient m ...
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The science and technology behind de-extinction
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Clarifications
- CRISPR is a genetic engineering tool that allows precise editing of DNA. It is based on a natural system found in bacteria and archaea. CRISPR-Cas9 is a commonly used form of this technology, enabling targeted modifications in the genetic code of living organisms. This tool has a wide range of applications in research, biotechnology, and medicine.
- Artificial Intelligence (AI) is the simulation of human intelligence processes by machines, typically computer systems. It involves tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies like CRISPR and AI are used in genetic engineering to analyze data, make predictions, and optimize processes. AI plays a crucial role in modern advancements, enabling more efficient and precise genetic editing techniques.
- A genome is the complete set of an organism's genetic material, including all its genes and non-coding sequences. It is like a blueprint that contains instructions for the development, functioning, and growth of an organism. Genomes can be studied through genomics, which involves analyzing and interpreting the genetic information to understand various aspects of an organism's biology. The genome sequencing of different organisms has provided valuable insights into genetics, evolution, and various biological processes.
- In the context of de-extinction, the "Jurassic Park" method refers to the fictional portrayal in the movie where ancient DNA is extracted from amber-preserved mosquitoes to fill in genetic gaps and recreate dinosaurs. This method, as depicted in the movie, involves using incomplete ancient DNA from fossils to reconstruct extinct species, which differs from the scientific approach of thoroughly understanding the complete genomes of extinct species before attempting de-extinction. The reference to "Jurassic Park" highlights the contrast between the cinematic approach of using incomplete ancient DNA and the real-life approach of genetic engineering based on a deep understanding of extinct species' genomes.
- Ancient DNA sourced from amber is a concept popularized by the movie "Jurassic Park." In the film, scientists extract dinosaur DNA from mosquitoes preserved in amber. However, in reality, DNA breaks down quickly after an organism dies, making it unlikely to survive for millions of years in amber. This method is not scientifically feasible due to the degradation of DNA over time.
- An extant genetic proxy is a living species that shares a significant amount of genetic similarity with an extinct species. In the context of de-extinction efforts, the extant genetic proxy serves as a reference point for understanding and recreating the genetic makeup of the extinct species. By studying the genetic similarities and differences between the extinct species and its extant genetic proxy, scientists can identify key genetic traits to engineer in order to bring the extinct species back to life. The extant genetic proxy provides valuable genetic information and a starting point for genetic resurrection projects.
- Protein-coding regions are specific segments of DNA or RNA that contain the instructions for building proteins. These regions are crucial for determining the characteristics and functions of living organisms. Studying protein-coding regions helps scientists understand gene organization, evolution, and can aid in various fields like genomics and gene therapy.
- Individual nucleotide editing involves making precise changes to single nucleotides, which are the building blocks of DNA. This process allows for targeted modifications at the level of individual genetic letters, enabling scientists to alter specific genetic sequences with high precision. By editing individual nucleotides, researchers can introduce or correct genetic variations, leading to tailored changes in an organism's traits or characteristics. This technique is crucial in genetic engineering for fine-tuning genetic information without affecting larger segments of DNA.
- Gene knockouts involve the targeted removal or inactivation of a specific gene within an organism's genome using techniques like CRISPR-Cas9. This technique allows researchers to study the function of a gene by observing the effects of its absence on the organism. Gene knockouts can be complete, permanently inactivating the gene, or conditional, allowing for control over when and where the gene is turned off and on. This method is widely used across various organisms to understand gene function in development, physiology, and disease research.
- Large-scale DNA synthesis involves creating long stretches of DNA molecules in significant quantities, typically in the laboratory setting. This process is crucial for various applications in genetic engineering, such as creating synthetic genes or genomes for research or biotechnological purposes. It enables scientists to design and produce custom DNA sequences for a wide range of scientific and industrial uses. Large-scale DNA synthesis plays a vital role in advancing fields like synthetic biology, genetic engineering, and biotechnology.
- Multiplex editing is a technique that allows for making multiple edits to the genome simultaneously with high efficiency. It involves targeting and modifying multiple locations in the DNA at the same time. This approach streamlines the genetic engineering process by enabling several changes to be made in a single step. Multiplex editing is a key tool used by Colossal Biosciences in their efforts to bring back extinct species through genetic engineering.
- David Liu's PRIME is a tool used in genetic engineering for precise editing of individual nucleotides. It is a technology that allows for targeted changes at the level of single DNA building blocks. This tool is part of the arsenal of techniques employed by researchers like Ben Lamm at Colossal Biosciences to make specific genetic modifications in their de-extinction efforts.
- Base editing is a genome editing technique that allows for precise changes to individual nucleotides in the DNA without cutting the DNA strands. It involves modifying specific bases (A, T, C, or G) directly, enabling targeted corrections of genetic mutations. Base editing is distinct from traditional met ...
Counterarguments
- Ethical considerations: There are ethical questions surrounding de-extinction, such as the welfare of the animals created, their impact on current ecosystems, and the prioritization of resources that could be used for conserving existing endangered species.
- Ecological concerns: Reintroducing species that have been extinct for centuries could disrupt current ecosystems and potentially harm existing species, as these ecosystems have evolved in the absence of the extinct species.
- Genetic purity and authenticity: Even with advanced genetic engineering, the animals created may not be true replicas of the extinct species due to potential gaps in the genetic information and the necessity of using a closely related species as a surrogate.
- Technological limitations: While CRISPR and AI are powerful tools, they may not yet be capable of fully recreating complex traits that involve multiple genes and environmental interactions.
- Unintended consequences: Genetic engineering can have unforeseen effects, and the introduction of de-extinct species might lead to new diseases or other unintended ecological impacts.
- Conservation priorities: Some argue that the resources and attention dedicated to de-extinction ...
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The practical and ethical considerations of resurrecting extinct species
Resurrecting extinct species, such as the work being done by Colossal, introduces various practical and ethical challenges that require careful consideration.
Practical Challenges of De-Extinction
One of the significant technical hurdles in de-extinction efforts involves reliably culturing and editing the cells of the target species. Techniques such as CRISPR gene editing have revolutionized the field, but ensuring that these cells can develop properly is a complex task. For instance, Colossal has had to learn how to regulate the overexpression of a protein called p53, which is crucial to allowing cell editing without causing either senescence, which is cellular aging, or cancer in animals related to the extinct ones, such as elephants.
Ensuring that the edited cells lead to viable and healthy offspring is another significant challenge. There needs to be a capability to gestate and deliver these offspring, which may require surrogate animals from related species or even artificial wombs. Furthermore, genetic modifications must be done with precision to reduce off-target effects or unintended consequences that could harm the animal or alter its behavior and functionality in unpredictable ways.
Ecological and Evolutionary Considerations
Beyond the technical aspects, there are open questions surrounding the ecological and evolutionary impacts of reintroducing extinct megafauna like the woolly mammoth. The reinsertion of such species into modern ecosystems can have wide-reaching effects, including altering plant communities, influencing the behavior of other animals, and potentially disrupting current habitats.
Understanding these potential ecological impacts and risks is critical before moving forward. This includes considering how the reintroduced species would interact with existing wildlife and their habitats and the possible unintended consequences that may arise as a result of their presence in today's ecosystems.
Ethical Debates and Conservation Priorities
The ethical debates around de-extinction are as robust as the scientific ones. There a ...
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The practical and ethical considerations of resurrecting extinct species
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Clarifications
- CRISPR gene editing is a powerful tool that allows scientists to make precise changes to an organism's DNA. It is based on a natural defense system found in bacteria and involves using a protein called Cas9 to target specific genes for editing. This technology has revolutionized genetic research and has applications in various fields, from medicine to agriculture. The CRISPR-Cas9 system has the potential to treat genetic diseases, create genetically modified organisms, and address other important challenges in biotechnology.
- The overexpression of the protein p53 is a deliberate increase in the production of this specific protein within cells. p53 is known as a tumor suppressor protein that plays a crucial role in regulating cell growth and preventing cancer development. In the context of de-extinction efforts, controlling the overexpression of p53 is important to ensure proper cell editing without causing issues like cellular aging or cancer in the resulting animals. This regulation is necessary to balance the benefits of gene editing with potential risks to the health and development of the resurrected species.
- Senescence is the gradual deterioration of functional characteristics in living organisms as they age. It involves an increase in death rates or a decrease in fecundity in the later stages of an organism's life cycle. This process can be influenced by genetic factors, environmental conditions, and lifestyle choices. Senescence is a natural part of the life cycle of organisms and is distinct from chronological aging.
- Off-target effects in genetic modifications refer to unintended changes or impacts caused by gene editing that are not the desired outcome. These effects can lead to unpredictable alterations in an organism's characteristics or behaviors, potentially causing harm or disrupting normal functions. Scientists strive to minimize off-target effects through precise editing techniques to ensure the safety and integrity of the modified organisms. Understanding and addressing off-target effects are crucial in genetic engineering to achieve the desired outcomes without unintended consequences.
- Unintended consequences are outcomes that result from an action but were not intended or anticipated. They can manifest as unexpected benefits, drawbacks, or perverse results contrary to the original intention. Understanding unintended consequences is crucial in decision-making to mitigate risks and ensure that actions have the desired effects. These consequences can have significant impacts on various aspects of a situation, including social, economic, and environmental factors.
- Megafauna are large animals that have significant impacts on their ecosystems. They often have slower reproductive rates and play a role in regulating the abundance of smaller animals. During the Pleistocene epoch, megafauna were diverse globally, but many large mammal species became extinct, with human activity and climatic changes being major factors. The term "megafauna" was first used in Alfred Russel Wallace's 1876 work.
- The reintroduction o ...
Counterarguments
- The potential benefits of de-extinction, such as restoring lost ecosystems and advancing scientific knowledge, are not highlighted.
- The role of human activity in causing extinctions may justify human efforts in reversing the damage through de-extinction.
- The argument that resources might be better spent on preserving existing species does not consider that de-extinction technologies could also benefit conservation efforts for endangered species.
- The concern about "playing God" may be seen as anthropocentric, as humans constantly alter ecosystems through agriculture, urban development, and climate change.
- The idea that resurrecting species is reversing natural extinction events does not account for the fact that many extinctions are the result of human actions, not natural processes.
- The discussion on the extent of human intervention might overlook the potential for de-extinction to be part of a broader strategy to repair and mitigate human impacts on the environment.
- The focus on the risks of disrupting curren ...
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The potential real-world applications and impacts of this work
Colossal, a company leading the de-extinction initiative, sees its work not just as a means to bring back extinct species but as a catalyst for innovation with far-reaching implications for both human healthcare and environmental conservation.
Colossal views the de-extinction initiative as a way to drive innovation and breakthroughs with broader applications in human healthcare and environmental conservation
Ben Lamm, a key figure in Colossal, articulates that the technologies being honed for the de-extinction of lost species could lead to significant advancements in human health. He suggests that the tools employed in de-extinction will find direct applications in healthcare, affirming the potential to create substantial value.
The company's work on regulating cell senescence and cancer resistance in elephants could yield insights and treatments applicable to human aging and oncology
Colossal's research into elephant genetics, specifically the regulation of p53—a gene tied to cancer resistance—may unlock new insights into combating human aging and cancer. By manipulating this gene, Colossal may foster breakthroughs that can be extrapolated to human oncology, providing potential new avenues for treatment.
The advanced genetic engineering capabilities being developed for de-extinction have the potential to be repurposed for enhancing biodiversity and ecosystem restoration efforts
Though no specific details are provided, Lamm alludes to the possibility of using the company's genetic engineering technology for biodiversity and ecosystem restoration. The tools designed for de-extinction could be repurposed to support broader conservation efforts, thus enhancing global biodiversity.
Colossal aims to make its de-extinction technol ...
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Clarifications
- De-extinction initiatives involve efforts to bring back extinct species through methods like cloning, genome editing, and selective breeding. These projects aim to recreate organisms that resemble or are genetically similar to extinct species. The process can contribute to biodiversity conservation and scientific advancements but also raises ethical considerations.
- Cell senescence is a biological process where cells stop dividing. It can be triggered by factors like DNA damage or stress. Senescent cells play roles in preventing cancer and are linked to aging-related conditions.
- The p53 gene, also known as TP53, is a crucial gene that helps prevent cancer formation by regulating gene expression to maintain genome stability. Mutations in the p53 gene are common in human cancers, highlighting its significance in tumor suppression. The gene encodes various protein isoforms that play roles in DNA binding and gene regulation. In humans, the TP53 gene is located on chromosome 17 and consists of coding and non-coding regions essential for its function.
- The commercial viability of de-extinction endeavors refers to the potential profitability and economic sustainability of projects aimed at bringing back extinct species. Companies like Colossal aim to demonstrate that these initiatives can generate revenue and attract investment interest, showcasing that there are financial opportunities in leveraging advanced technologies for conservation purposes. This focus on commercial viability helps drive innovation and funding in the field of de-extinction, ensuring that efforts to revive extinct species are not on ...
Counterarguments
- The effectiveness and safety of technologies developed for de-extinction in human healthcare are not yet proven and may not translate as expected.
- The ethical implications of manipulating genes such as p53 in humans could be complex and controversial.
- The impact of de-extinction on existing ecosystems and biodiversity is uncertain, and it may not contribute positively to ecosystem restoration.
- Releasing de-extinction technologies for free could undermine the potential for recovering research and development costs, possibly affecting the sustainability of such initiatives.
- The commercial viability of de-extinction as a f ...
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