Festival Overview:
The International Science Festival in Gothenburg, a prominent European popular science event and the sole one of its kind in Sweden, was made possible by Sten A. Olsson’s Foundation for Research and Culture. Over the past 25 years, the festival has successfully piqued the curiosity of adults, children, and teenagers alike, fostering a passion for scientific research.

Festival Theme and Objectives:
This year’s festival revolves around the theme “Level Up,” emphasizing the world’s ongoing development and our collective ambition to advance. The festival aims to address crucial questions about our trajectory, the subsequent levels we aspire to reach, and the responsible approach to achieving these goals while preserving the planet and its inhabitants.

CRISPR Technique and Its Revolutionary Impact:
Professor Jennifer Doudna, a Nobel Prize laureate in Chemistry 2020, is recognized for her pivotal role in revolutionizing modern science through her pioneering work on the CRISPR technique. CRISPR, a transformative genetic engineering tool, enables precise cutting, pasting, and editing of genetic material, specifically DNA. The technique has far-reaching applications in preventing genetic diseases and potentially treating various illnesses like cancer and HIV.

CRISPR Technology:
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary technology that allows scientists to edit DNA precisely. It was initially discovered as a defense mechanism in bacteria against viral infections. Scientists harnessed the DNA-cutting mechanism of CRISPR for various purposes, including modifying DNA in animal, plant, and human cells.

Potential Applications:
CRISPR enables scientists to study genetic functions and correct disease-causing mutations in specific cells. It has the potential to eradicate genetic diseases and revolutionize healthcare. CRISPR offers the possibility of altering DNA in human embryos, leading to heritable changes that can be passed on to future generations.

Ethical and Philosophical Challenges:
The ability to edit human genes raises significant ethical and philosophical concerns. The technology could be misused to create designer babies with specific traits or features. Modifying the human germline (sperm, eggs, or embryos) carries the risk of unintended consequences and raises questions about equality and social justice.

Technical Limitations:
Editing complex traits like intelligence or certain diseases involving multiple genes is challenging and may not be feasible in the near future. CRISPR technology is still in its early stages, and there are limitations to its precision and safety. Off-target effects and unintended consequences of gene editing need to be carefully considered and minimized.

International Dialogue:
The international scientific community has recognized the need for open discussion and careful consideration of ethical guidelines for using CRISPR technology. Criteria and regulations are being developed to ensure responsible and ethical applications of gene editing in humans.

CRISPR for Sickle Cell Disease:
CRISPR is used in clinical trials to cure sickle cell disease by activating fetal hemoglobin, overriding the disease-causing mutation. Future possibilities include correcting the mutation and restoring normal DNA sequence. This approach is limited to individuals and not embryos, aligning with standard therapies.

CRISPR for Complex Traits:
CRISPR’s potential for complex traits like schizophrenia is currently limited to research due to multiple genetic factors and difficulties in targeting many genes simultaneously. Altering traits like intelligence is challenging due to complexity and the difficulty in defining such traits.

Gene Editing in Human Embryos:
Gene editing in human embryos for assisted reproduction is banned in many countries due to ethical concerns and potential unintended consequences. In 2018, the first genome-edited babies were born in China, leading to the scientist’s imprisonment. The impact on research is significant, slowing down the application of CRISPR in human embryos for clinical use.

CRISPR in Human Embryos:
Jennifer Doudna believes responsible research into using CRISPR in human embryos is appropriate with proper regulation. A renewed international sense of responsibility exists among scientists and clinicians to ensure CRISPR is used responsibly in the future. Little is known about the health of the babies born from CRISPR-edited embryos due to privacy concerns.

Potential Misuses of CRISPR:
CRISPR raises concerns about biological warfare, engineered viruses, and ecological disruptions due to animal tinkering. The slippery slope between life-saving edits and pure enhancements raises ethical questions, including eugenics.

Jennifer Doudna’s Evolution on CRISPR Ethics:
Doudna organized a meeting in 2015 to discuss using CRISPR in human embryos before public attention arose. She highlights that technology doesn’t regress, emphasizing the benefits of CRISPR outweigh the risks with responsible scientific engagement. Doudna believes scientists share the responsibility for educating people about CRISPR’s capabilities and limitations.

Doudna’s Shift Towards Accepting CRISPR’s Potential:
Doudna’s views have evolved over time, moving from initial concerns to a more open stance on CRISPR’s potential. She recognizes that CRISPR can prevent human suffering from known genetic diseases, potentially making it unethical not to use it for this purpose.

CRISPR Use in Individuals:
CRISPR use in individuals is ethically similar to other therapies, with risks and benefits. It affects the individual only.

CRISPR Use in the Human Germline:
Germline editing creates permanent changes that pass on. Most CRISPR applications are for individuals, not germline. Current germline work is primarily research.

Research Use of CRISPR in Embryos:
Limited information on early embryonic development. Potential value for learning fundamental biology. Appropriate guidelines and respect for embryos.

Clinical Use of CRISPR in Embryos:
Technology is not ready yet. Insufficient understanding of CRISPR in embryos. Open and transparent societal discussion needed.

Designer Babies:
Term “designer babies” may be unfair. Humans have manipulated genetics for centuries (plant breeding, etc.). Societal acceptance of IVF suggests similar acceptance of CRISPR in the future.

Historical Context:
Forced sterilization in Sweden and the US. Genetic design has happened and is happening. Irrational fear of technology may play a role in opposition to CRISPR.

CRISPR Revolutionizes Genetic Engineering in Plants:
CRISPR enables precise manipulation of genes in plants, allowing for targeted changes without introducing undesirable alterations. This precision eliminates the randomness and long duration associated with traditional plant breeding methods. CRISPR accelerates the process of genetic modification, enabling desirable changes to be made in a matter of weeks or months instead of years.

Human History of Organism Manipulation:
Humans have been manipulating organisms for millennia, demonstrating a long history of genetic engineering. CRISPR is a precise tool for genetic manipulation, comparable to traditional methods in terms of safety and effectiveness.

Growing Trend of Biohackers and the Need for Regulation:
Biohackers are experimenting with CRISPR in unregulated settings, raising concerns about the potential risks and ethical implications. Some argue for less regulation, advocating for the freedom to enhance oneself through genetic editing.

Science Accessibility and Education:
Jennifer Doudna expresses her concern about the growing mistrust of science and scientists. She emphasizes the importance of integrating science into everyday conversations and making technologies more accessible for educational purposes. CRISPR’s user-friendly nature enables high school students to perform editing experiments, making science more tangible and exciting.

Biohackers and Gene Editing:
Doudna believes that biohacking, or “science for all,” promotes the democratization of science, preventing its confinement to experts. She dismisses the notion of individuals hacking their genes in meaningful ways due to the current limitations of CRISPR technology.

Genetic Diversity and Evolution:
Miriam Frankl raises concerns about reducing genetic diversity through widespread gene editing, potentially increasing the risk of species extinction during ecological disasters. Doudna acknowledges the importance of genetic diversity, but deems the scenario of homogenous humans as unrealistic and fictional.

CRISPR for Organism Diversity:
Doudna highlights the potential benefits of CRISPR in introducing genetic diversity to certain organisms, such as bananas, to enhance their resistance to diseases. She emphasizes the role of CRISPR in assisting species adaptation to rapidly changing climates, potentially preventing extinction.

Social Implications of Homogeneous Traits:
Frankl questions the advantages of desirable traits if everyone possesses them, leading to potential challenges in assigning jobs and tasks. She also expresses concerns about the impact of conformity on human creativity and ingenuity, often attributed to individuals who feel like outsiders.

CRISPR and Human Diversity:
Doudna emphasizes the value of human diversity and individuality, viewing uniformity as undesirable. She acknowledges the potential of CRISPR to eliminate certain afflictions, such as genetic diseases, but stresses the need for careful consideration of ethical and societal implications.

Potential Uses of CRISPR:
CRISPR gene editing holds immense promise for treating monogenetic diseases, offering the possibility of restoring health by targeting and correcting specific genetic mutations. The technology has wide-ranging applications beyond medicine, including agriculture, addressing pandemics, and growing human organs and animal tissues.

Addressing Concerns:
Despite its transformative potential, CRISPR raises ethical concerns, particularly regarding environmental applications. The development of gene drives, designed to spread genetic changes across populations, poses risks, such as unforeseen ecological consequences.

The Importance of Accessibility:
Jennifer Doudna emphasizes the need for CRISPR-based treatments to be affordable and accessible to people worldwide. Ensuring equity in healthcare access remains a critical challenge, as high costs could limit the technology’s global impact.

The Path Forward:
Doudna advocates for active engagement with technology development, similar to the ongoing dialogue surrounding artificial intelligence. She stresses the importance of creating an inclusive and supportive culture in science, particularly for women, to address the “leaky pipeline” phenomenon.

Personal Experience as a Woman in Science:
Doudna acknowledges the challenges faced by women in science, particularly the intersection of career advancement with childbearing years and caregiving responsibilities. She highlights the importance of flexible work environments and supportive partners to facilitate women’s success in scientific careers.

Winning the Nobel Prize:
Doudna describes her surprise and disbelief upon receiving the news that she and Emmanuel Charpentier had won the Nobel Prize in Chemistry. She credits her collaborator, Martin Jinek, for confirming the news, leading to the realization that it was indeed a reality.

Addressing Off-Target Effects:
Doudna acknowledges the need to minimize off-target effects, unintended DNA cleavage or genome edits caused by CRISPR. Ongoing research focuses on improving the precision of CRISPR technology to reduce such off-target effects.

CRISPR Accuracy Improvements:
Extensive research has shed light on factors affecting CRISPR accuracy. Careful selection of guide RNAs to avoid off-target matches improves accuracy. Engineering new forms of CRISPR enzymes with higher accuracy and lower overall activity reduces off-target events.

Challenges of Gene Insertion and Cell Targeting:
While gene disruption with CRISPR is relatively straightforward, gene insertion remains challenging. Achieving efficient targeting of specific cell types and ensuring all cells receive the desired genetic correction is difficult.

Current Approach for Genetic Disorders:
Cells are extracted from patients, edited in the laboratory, and transplanted back. This method is used in blood disorders like sickle cell disease due to the accessibility of blood cells.

Future Prospects for Gene Editing:
Development of delivery vehicles for CRISPR genome editors holds promise for correcting genetic mutations in various tissues. Muscular dystrophy research has made significant progress, leading to potential human trials using virus-based CRISPR delivery.

Advice for Early Career Researchers in Less Developed Countries:
Seek out opportunities to collaborate with researchers in better-resourced institutions. Take advantage of online resources and open-source platforms for research and collaboration. Consider pursuing further education or training in countries with more research opportunities.

Background and Motivation:
Jennifer Doudna grew up in Hawaii, where she had to actively seek out opportunities to pursue her passion for science due to a lack of scientists in her family. She emphasizes that passion and self-driven exploration can lead to progress, regardless of one’s circumstances. Doudna believes that successful scientists share a common trait: genuine passion for their work.

CRISPR and Evolution:
CRISPR will likely affect evolution and natural selection in certain organisms, such as plants and animals, but its impact on human evolution is unlikely to occur anytime soon. The engineering of humans through CRISPR is a complex and lengthy process that would take generations to have a noticeable impact. Despite the long timeline, Doudna urges responsible and thoughtful consideration of CRISPR’s use in heritable human genome editing.

Ethical and Societal Implications:
The potential use of CRISPR in heritable human genome editing raises concerns about equity, access, and the potential divide between those who can afford the technology and those who cannot. Doudna highlights the need for discussions and considerations regarding the ethical and societal implications of CRISPR’s applications.

Ongoing Research:
Doudna’s lab continues to explore the fundamentals of CRISPR biology, particularly in microbes and bacteriophage. They aim to understand how these systems operate naturally and discover new insights. The lab is also actively working on developing efficient and targeted delivery methods for CRISPR genome editing molecules into various cell types.

CRISPR Applications in Tissue Types:
Jennifer Doudna emphasizes the need for more efficient methods of delivering CRISPR technology to specific tissue types, such as animal cells, human tissues, and various cell lines.

CRISPR for Climate Change:
The Innovative Genomics Institute explores the potential of CRISPR to mitigate the effects of climate change, aiming to harness its capabilities for beneficial purposes.

Accessible and Affordable CRISPR:
The institute prioritizes affordable and accessible uses of CRISPR for clinical applications, seeking to make the technology available to individuals worldwide.

Public Discussion and Engagement:
Jennifer Doudna stresses the importance of public discourse and engagement regarding CRISPR technology. She encourages people to discuss, form opinions, and continue learning about its implications.

Cocktail Conversation Encouraged:
Miriam Frankl hopes that the discussion about CRISPR will continue beyond the presentation, urging listeners to carry the conversation forward during social gatherings.