Background of the Convergence Science Network:
The Convergence Science Network is a platform for research scientists to share their knowledge and advancements in biomedical science with the public. Established in 2008, the network has hosted over 100 events, including an annual showcase event, the Graham Clark Oration, reaching over 32,000 people. The network aims to encourage conversation, inspire the next generation of scientists, and maintain public trust in biomedical researchers.

CRISPR Gene Editing Technique:
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene editing technique that has revolutionized genetic research and holds promise for gene therapies. CRISPR allows scientists to delete, edit, and replace genes, enabling the investigation of gene roles in diseases and human development. Its simplicity, speed, and affordability have accelerated research agendas and fueled hopes for potential therapies.

Current State of Personalized Medicine:
Despite initial hopes, the age of personalized medicine has not yet fully materialized due to the slow pace of discovery and translation of research into clinical practice.

Increased Hype and Urgency:
Recent advances in gene editing techniques, particularly CRISPR, have generated renewed hype and urgency in the field of personalized medicine. Scientists worldwide are enthusiastic about the potential of CRISPR to transform research and lead to innovative treatments.

Benefits and Applications of CRISPR:
CRISPR offers several advantages, including its ability to delete, edit, and replace genes, as well as its affordability, speed, and relative ease of use. It facilitates the study of gene roles in diseases and human development, opening up avenues for potential therapies.

Introduction:
The development of CRISPR technology has raised ethical questions and concerns. Hundreds of questions were submitted by the audience, including topics such as limiting science, regulation, clinical trials, germline editing, IVF clinics, and access to technology.

Speakers:
Jennifer Doudna, co-inventor of CRISPR, and Kevin Esfeld, trailblazer in CRISPR for eliminating diseases, will discuss the ethics of gene editing. Both speakers emphasize the importance of public dialogue and transparency in scientific research.

CRISPR-Cas9 Discovery:
Jennifer Doudna describes the discovery of the CRISPR-Cas9 mechanism, which has revolutionized the field of gene editing. The ability to read, write, and rewrite DNA has opened up extraordinary opportunities and challenges for humanity.

Understanding DNA:
The double helical structure of DNA discovery in the 1950s led to a deeper understanding of life’s underlying chemistry. Scientists can now read the DNA code of various organisms and comprehend how it controls development and properties. Researchers aim to go beyond understanding DNA to modifying and changing it, which has been a long-standing question in the scientific community.

Gene Editing as Text Editing:
The concept of gene editing resembles editing a document, where scientists can erase, replace, or correct specific sequences in the DNA code. This idea has been explored since the discovery of the DNA structure, and initial research in the 1980s aimed to cut DNA at precise locations. Mapping genes, such as the one causing Huntington’s disease, became possible using early gene editing techniques.

Introduction to CRISPR-Cas9 Technology:
CRISPR-Cas9 is a revolutionary technology derived from a natural bacterial immune system that allows precise editing of DNA. Scientists harnessed this capability for altering DNA in cells, enabling targeted gene editing for various purposes.

CRISPR-Cas9 Mechanism:
CRISPR-Cas9 targets viral DNA in bacteria, protecting them from infection. Cas9 is a protein that holds an RNA molecule (guide RNA) that matches the sequence of the viral DNA. When a match occurs, Cas9 holds the DNA, unwinds it, and cuts it, creating a double-stranded break.

DNA Repair and Gene Editing:
Animal and plant cells have a sophisticated mechanism to repair double-stranded breaks in DNA. This repair process can be harnessed for gene editing by introducing a break at a specific location. Scientists can control the repair process to either disrupt a gene, insert new genetic material, or integrate a new piece of DNA.

CRISPR-Cas9 Applications:
CRISPR-Cas9 can be programmed to cut DNA at a desired sequence, allowing precise gene editing. This technology has been applied to various organisms, including animals, insects, plants, and human cells. CRISPR-Cas9 has accelerated the pace of scientific research and has potential applications in biomedicine and commercial sectors.

Conclusion:
CRISPR-Cas9 technology represents a powerful tool for precise gene editing, enabling groundbreaking research and potential applications in biomedicine and various industries.

CRISPR-Cas9 in Medicine:
CRISPR-Cas9 technology holds promise in correcting genetic mutations causing diseases like Huntington’s disease. Researchers have developed modified CRISPR-Cas9 proteins that can enter neurons and edit DNA in the brain. Experiments in mice show precise editing of brain cells, leading to the potential cure of previously intractable diseases.

CRISPR-Cas9 in Agriculture:
CRISPR-Cas9 technology has potential applications in agriculture to improve crop yield and resistance to pests and diseases. Researchers are using CRISPR-Cas9 to develop drought-resistant crops and crops resistant to specific pests and diseases. CRISPR-Cas9 technology could help address global food security challenges by increasing crop productivity.

Conclusion:
CRISPR-Cas9 technology has the potential to revolutionize medicine and agriculture, offering new avenues to address diseases and global food security challenges.

Agricultural Impact:
* CRISPR-Cas9 has demonstrated remarkable potential in revolutionizing agriculture.
* Scientists have successfully applied gene editing to tomato plants, resulting in plants capable of bearing three times more fruit.
* Applications of gene editing in agriculture include creating plants tolerant to drought, resistant to disease, and with enhanced nutritional value.
* Precise genetic modifications can be achieved, avoiding the introduction of random mutations.

Animal Applications:
* Gene editing holds promise for beneficial applications in animals, particularly in agriculturally important species.
* Researchers are exploring the use of CRISPR-Cas9 to create pigs with organs that are more compatible for human organ transplantation.
* By removing viruses and making organs more human-like, the risk of rejection can be reduced.

Types of Gene Editing:
* Gene editing can be performed in somatic cells, which are fully differentiated cells.
* Somatic cell gene editing is used for therapeutic purposes, targeting specific cells within an organism.
* Germline gene editing, which involves modifying genes in reproductive cells, is a more controversial area of research due to its potential to create heritable changes.

Precision of Germline Editing:
Editing germ cells can lead to changes that are transmitted to future generations, unlike somatic cell editing.

Experiment in Frog Embryos:
A student injected CRISPR-Cas9 with a guide RNA and a gene for green fluorescent protein into one of two cells in a frog embryo. The editing removed a gene for brown color and replaced it with the green fluorescent protein gene.

Results in Tadpoles:
Edited embryos developed into tadpoles with a distinct split down the center. The top half of the tadpoles had brown cells, while the bottom half lacked pigment. Under fluorescent light, all of the edited cells were green.

Significance:
This experiment demonstrates the precision of germline editing, with the edited cells passing along the edit to their progeny.

Background:
In early 2014, a phone call from a reporter alerted Jennifer Doudna to a groundbreaking research article on using CRISPR-Cas9 to modify DNA in monkeys, raising the possibility of human embryo gene editing. This realization prompted Doudna to discuss the implications of this technology and the need for public discourse.

Scientific Developments:
The CRISPR-Cas9 technology enables precise editing of DNA, offering potential for treating genetic diseases and altering the human germline. Scientists have conducted research using CRISPR-Cas9 in viable human embryos to remove genes causing genetic disorders, sparking discussions on the technical and ethical aspects of this approach.

Ethical Considerations:
The report from the National Academy of Sciences in the U.S. recommends against clinical applications of germline editing until thorough public discussions and transparent conversations are held. Ethical concerns center around the responsible use of gene editing, ensuring public understanding, and addressing the potential unintended consequences of altering the human genome.

Public Engagement and Education:
Doudna and her graduate student, Sam Sternberg, co-authored the book “A Crack in Creation” to share their personal experiences and insights on the development of CRISPR-Cas9 and its implications for the future. The Innovative Genomics Institute, co-founded by Doudna, conducts research on gene editing while also emphasizing ethics and outreach. They aim to educate non-scientists and provide resources for teaching about gene editing in schools.

Conclusion:
The CRISPR-Cas9 technology holds tremendous potential for revolutionizing medicine and addressing genetic diseases, but ethical considerations and responsible use are paramount. Ongoing discussions and public engagement are essential to shape the future of gene editing and ensure that it is used in a responsible and beneficial manner.

Introduction:
The future of civilization is largely determined by the technologies we invent and deploy. Scientists should consider the potential consequences of their research, especially when it involves altering organisms or ecosystems.

XKCD’s Risk Assessment:
A webcomic plot illustrates the risk of research being used for world domination or unintended consequences. Genetic engineering, including CRISPR-edited organisms, may pose a significant risk due to their potential impact on wild populations.

Gene Drive Systems:
Gene drive systems are naturally occurring genetic elements that can spread through populations, even if they don’t benefit the organisms’ reproduction. With CRISPR, scientists can harness gene drive to make changes in organisms that will spread through wild populations, potentially affecting entire ecosystems.

Function of Gene Drive:
CRISPR components and guide RNAs are delivered into an organism’s reproductive cells, along with the desired DNA change. The CRISPR system cuts the target site on the genome and inserts the new sequence, resulting in self-propagating gene drive. This process continues in offspring, leading to the inheritance of the edited copies and further spread of the change.

Potential Applications:
Malaria eradication: Gene drive could alter mosquitoes to prevent malaria transmission or suppress their population, potentially eradicating the disease. Schistosomiasis control: Gene drive could suppress schistosome populations, combined with treatments, to eradicate the disease. Controlling harmful organisms: Gene drive could be used to target invasive species or organisms with negative impacts on the environment or human health.

Conclusion:
Gene drive systems, harnessed with CRISPR, have the potential to address global health challenges and environmental issues. However, careful consideration and ethical discussions are necessary to ensure responsible and beneficial applications of this technology.

Gene Drive Technology:
Gene drive technology utilizes gene editing tools like CRISPR to insert genetic changes that propagate through populations, potentially solving ecological problems and improving public health.

Ethical Considerations:
Concerns arise due to the potential for unintended consequences and lack of complete understanding of complex ecosystems.

Operational Rules:
Minimizing changes and starting small are crucial, emphasizing the need for caution and incremental implementation.

Daisy Drive System:
A proposed solution to address scalability concerns is the Daisy Drive system, which involves separating and linking gene drive components across different chromosomes. This approach enables controlled propagation and geographic limitation of the gene drive, allowing for targeted and localized interventions.

Potential Applications:
Daisy Drive could address various issues such as invasive species, animal suffering, and agricultural pest control, offering a sustainable alternative to chemical interventions.

Moral Responsibility:
Developing gene editing technologies carries moral obligations to intervene and prevent suffering, comparable to saving a drowning child. Inaction and standing still are not viable options, as problems will worsen without intervention.

Loss Aversion Bias:
Humans tend to prioritize avoiding losses over pursuing gains, leading to reluctance in intervening and taking action.

Conclusion:
Gene drive technology presents both opportunities and ethical challenges, requiring careful consideration and responsible implementation to minimize unintended consequences and maximize benefits.

Gene Drive Development and Traditional Science:
Gene drive technology development typically follows a closed approach, where researchers keep their work confidential to prevent others from gaining credit for their ideas. This approach can hinder collaboration and transparent progress in the field.

Pre-Registering Gene Drive Experiments:
Pre-registering gene drive experiments involves disclosing research plans and protocols before conducting the experiments. This ensures transparency and allows for community input and feedback on the potential ecological and societal implications of the research.

Reasons for Pre-Registering Gene Drive Experiments:
1. Shared Environment: Gene drive systems are intended to alter the shared environment, affecting everyone in the affected area.
This eliminates the option for individuals to opt out, making it crucial to involve communities in decision-making processes.
2. Ecological Engineering: Pre-registration is important for ecological engineering projects, such as engineering mice to break the transmission cycle of diseases.
This allows for discussions and input from affected communities.
3. Building Trust: Pre-registration builds trust between scientists and the public.
It demonstrates transparency and willingness to listen to concerns and feedback.
4. Accidental Releases: Pre-registration helps address concerns about accidental releases of gene drives from laboratories.
It allows for contingency plans and risk mitigation strategies to be developed in advance.

Skepticism Towards Ecological Consequences:
The speaker expresses skepticism about the potential ecological consequences of accidental gene drive releases. They believe that most gene drives are designed to make minor changes, such as changing the organism’s color, and pose minimal ecological risks.

Social Impact of Invisible Gene Drives:
Invisible gene drives may not have ecological effects, but the social reaction could be negative, potentially delaying research efforts. The fear of secret gene drive research could delay progress and lead to significant loss of life.

Importance of Open Science:
Scientists should share their research openly to prevent unintended consequences. Closed research can lead to accidental gene drive creation, highlighting the need for awareness and communication.

Unpredictability of Technological Advancements:
Scientists cannot reliably anticipate the consequences of their work due to the complexity and diversity of the world. Rapid technological advancements, like gene editing, can lead to unexpected outcomes.

Benefits of Open Science:
Open science fosters collaboration and competition, leading to faster and more efficient research. Informed decision-making allows scientists to choose collaboration or competition based on shared knowledge.

Radical Transparency in Science:
Open science, sharing research openly, is a safer approach as it allows others to identify potential risks and provide valuable insights. Collective action is needed to change incentives for scientists working with gene drives. Intellectual property could play a role in promoting open development of gene drives.

Public Engagement and Governance:
Radical transparency can alleviate anxiety among scientists by fostering trust and inviting input. Disagreements and public debate are essential in gene drive research, given its shared impact nature. Civic governance and public decision-making are necessary when deploying gene drives.

Respect for Indigenous Knowledge:
Indigenous knowledge and traditional wisdom should be valued and incorporated into decision-making. Researchers should be willing to walk away if indigenous communities express concerns, even if those concerns are not scientifically explainable.

Public Dialogue Beyond Science:
Engaging the public in discussions about gene drives helps cultivate public interest and understanding. It is important to consider the full range of ethical and societal implications, including potential applications in genetic disease.

Addressing Genetic Disorders:
Gene editing has potential applications in addressing genetic disorders with a well-defined single genetic cause. Multigenic disorders will take longer to address with gene editing technology.

Considerations for Genetic Editing:
Determining the feasibility of genetic corrections for diseases in adults versus children. Debating the potential alteration of the germline (heritable genetic material) for certain therapies. Defining disorders within the disability activist community.

Equity and Access Concerns:
Gene editing may initially be applied in agriculture, potentially promoting equitable access to improved crops. The technology’s accessibility allows scientists worldwide to adapt it for various purposes, leading to potential benefits and risks. Access to healthcare, particularly expensive gene editing treatments, remains a significant challenge, requiring active discussion and solutions.

Gene Drives and Climate Change:
Gene drives have the potential to empower organisms and ecosystems to adapt or overcome climate change consequences.

Prioritizing Healthcare:
A discussion ensued on whether healthcare should take precedence over other applications of gene editing technology, such as eugenics or enhancing traits. Ethical and societal considerations around the use of gene editing were brought up, with a focus on prioritizing uses that address severe and commonly agreed-upon problems.

Impacts on Agriculture:
Gene editing in plants has the potential to significantly impact human health by addressing food challenges. The Green Revolution’s promise of feeding the world with genetic engineering techniques has not been fully realized, but gene editing offers new opportunities. Challenges such as a growing population and climate change require innovative solutions, and gene editing can potentially improve plant resilience and productivity.

Clinical Applications and Ethical Considerations:
Prioritizing gene editing applications for diseases that are widely recognized as desirable to fix was discussed. Specific examples of treatable or curable diseases, such as degenerative neurological disorders, cystic fibrosis, and muscular dystrophy, were mentioned. The reality of potential non-therapeutic uses, such as enhancements, was acknowledged, emphasizing the need for ongoing discussions and ethical considerations.

Public Support and Early Applications:
Concern was raised regarding the potential impact on public support if gene editing applications were to face setbacks or negative outcomes. The importance of carefully selecting early applications that demonstrate clear benefits and address severe problems was highlighted. The example of GMO foods and their limited impact on consumers was mentioned as a cautionary tale.

Treatment Options:
A distinction was made between treating adult patients with gene-edited cells versus editing embryos at the genetic level. The question of whether to start gene editing at the embryo stage or focus on treating adults was raised, emphasizing the need for ethical and societal discussions.

Introduction of Human Germline Editing:
Human germline editing, involving the alteration of genes passed down to future generations, has sparked ethical debates due to its potential to impact human biology and society.

Past Controversies and Acceptance of Assisted Reproductive Technologies:
The use of assisted reproductive technologies, such as in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD), initially faced resistance due to ethical concerns. Over time, as technologies evolved and their benefits became evident, they gained wider acceptance.

Evolving Perspectives on Human Germline Editing:
The ethical implications of human germline editing are complex and will likely evolve as the technology advances. Ongoing research aims to improve the precision and safety of gene editing techniques.

Potential Future of Germline Editing in Sperm or Eggs:
Future advancements may allow for gene editing in sperm or eggs, potentially avoiding the ethical concerns associated with modifying embryos. This approach would involve selecting cells with desired edits for fertilization, potentially making the process more ethically appealing.

Non-Viable Embryos in Research:
Much of the current research on embryos involves non-viable embryos that will not be implanted or develop into babies. This research helps scientists understand human development and biology.

Engaging the Wider Community in Scientific Understanding:
Open science initiatives, such as the Convergent Science Network, aim to engage the wider community in scientific discussions and encourage participation. Inviting people to share their concerns and suggestions can foster a sense of inclusion and responsibility.

Addressing Skepticism and Concerns:
Engaging with skeptics and addressing their concerns can help build trust and promote informed decision-making. Open dialogue and transparency can encourage participation and collaboration.

Real-World Applications and Societal Impact:
Early applications of gene editing technologies should focus on solving real-world problems and benefiting society. Positive outcomes can engender goodwill and willingness to engage with scientists.

Balancing Commercial Imperatives with Open Science:
Striking a balance between commercial interests and open science is crucial for ensuring ethical and responsible development.

Anecdotes of Public Perception:
Public perceptions of gene editing technologies can vary widely, with some embracing the potential benefits while others express concerns. Understanding these diverse perspectives is essential for effective engagement and responsible decision-making.

Evolutionary Stability and Reversing Gene Drives:
Scientists are researching ways to make gene drives evolutionarily stable to address concerns about potential environmental harm.

Kill Switches:
Including inducible toxins or kill switches in gene drives raises questions about triggers, environmental chemicals, and the effectiveness of such methods compared to insecticides.

CRISPR’s Versatility:
CRISPR’s ability to target various sequences enables the development of gene drives that can overwrite and undo previous modifications.

DAISY Threshold Drives:
DAISY threshold drives are being developed to tightly control gene drives by linking them to genetic changes that cause natural selection to act against them when in the minority.

Suppression Drives:
Suppression drives can be released to reduce the population of modified organisms if undesirable changes occur. Natural selection would then eliminate the engineered genes.

Skepticism about Environmental Damage:
The speaker expresses skepticism about the potential environmental damage caused by gene drives in most cases.

Moral Concerns about Engineered Genes:
Many people consider nature sacred and are deeply troubled by the idea of introducing engineered genes, viewing it as morally wrong. Respecting these concerns is essential, even if they differ from personal beliefs.

Obligation to Develop Gene Removal Tools:
The speaker feels compelled to create tools that can remove engineered genes and restore populations to their original state.

The Uncertainty of Evolving Engineered Genes:
Engineered genes are unprecedented in terms of their potential for self-evolution. The speaker’s experience with microbial evolution raises skepticism about kill switches, as even one escape can have significant consequences.

Testing Stability and Escape Rates:
Thorough testing is crucial to assess the stability and escape rates of engineered genes. Organisms like worms are useful for such testing due to their ability to grow in large numbers.

Sponsors of the Event:
The event was made possible by various sponsors, including the Club Melbourne Ambassador Program, Victorian Department of Education and Training, Monash Biomedicine Discovery Institute, and others.

Acknowledgment of Support:
Additional support came from the Lawn Genome Conference and the School of Biosciences at the University of Melbourne, which enabled the participation of Jennifer Doudna and Kevin Espel.

Appreciation for Attendees and Organizers:
The organizers expressed gratitude to the 2,000 attendees and the Convergence Science Network, particularly Luan and his team, for their contributions to the event.