About the Show: Neil deGrasse Tyson, Chuck Nice, and Walter Isaacson discuss CRISPR, the origin of life, and Jennifer Doudna’s groundbreaking work in gene editing. Jennifer Doudna: Jennifer Doudna is a biochemist and Nobel Laureate who co-invented CRISPR-Cas9, a gene-editing tool that allows scientists to precisely modify DNA. CRISPR-Cas9: CRISPR-Cas9 is a revolutionary gene-editing tool that allows scientists to make precise changes to DNA. It works by using a protein called Cas9 to cut DNA at a specific location, and then using another protein to insert or delete DNA at that location. Nobel Prize: In 2020, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for their work on CRISPR-Cas9. Walter Isaacson: Walter Isaacson is a biographer who has written books about Leonardo da Vinci, Einstein, Steve Jobs, Benjamin Franklin, and Jennifer Doudna. Origin of Life: The origin of life is a topic of great debate among scientists. Some scientists believe that RNA may have played a role in the origin of life, as it can both store genetic information and act as a catalyst for chemical reactions. CRISPR-Cas9 Applications: CRISPR-Cas9 has a wide range of potential applications, including developing new treatments for diseases, creating new crops, and producing biofuels. Ethical Concerns: CRISPR-Cas9 also raises a number of ethical concerns, such as the potential for unintended consequences and the possibility of creating designer babies.

RNA’s Potential Role in the Origin of Life:
RNA molecules were considered as potential clues to the origin of life on Earth. RNA’s ability to encode genetic information and perform chemical reactions, such as cutting and pasting other RNA molecules, may have allowed primitive forms of RNA to make copies of themselves. This could have formed the basis for a self-replicating RNA-based system or world in early life.

Recent Discoveries of RNA’s Functions:
Over the past few decades, scientists have uncovered various important functions of RNA in cells. RNA molecules aid cells in determining when and where to produce proteins. They regulate different parts of the chromosome. RNA is involved in CRISPR, a defense mechanism that helps cells protect themselves from viruses. There are likely many more undiscovered functions of RNA.

Mystery of RNA’s Origin:
While the synthesis of RNA in modern cells is understood, the origin of RNA itself remains a mystery. Scientists are exploring the possibility that RNA originated from outside Earth, potentially brought by cosmic events.

Ongoing Research and Future Prospects:
Jennifer Doudna is working on developing a “time machine” to go back and study the early years of Earth to gain insight into the origin of RNA. Understanding how RNA came into existence is a major scientific mystery that continues to be explored and investigated.

Where Did Life on Earth Come From?:
Scientists are exploring the panspermia hypothesis, which suggests that life on Earth may have originated from Mars. Even if life came from Mars, the question of how life began on Mars remains.

Jennifer Doudna’s Shift from DNA to RNA:
Doudna initially worked in the field of DNA research, but she later focused on RNA. RNA is a simpler molecule compared to DNA and can replicate itself. Doudna’s research on RNA led to the discovery of CRISPR, a gene-editing technology.

CRISPR’s Precision and Advancements:
CRISPR technology allows for precise gene editing, minimizing risks compared to previous methods. Off-target edits can still occur, but CRISPR technology is continuously advancing. Scientists like David Lu are developing more refined gene-editing techniques, such as base editing and prime editing.

CRISPR’s Impact and Potential Nobel Prize:
Jennifer Doudna and Emmanuel Charpentier’s discovery of CRISPR has revolutionized gene editing. David Lu’s work on base editing and prime editing may also lead to a Nobel Prize in medicine. CRISPR technology has made significant progress in the past 10 years and holds immense potential for the future.

CRISPR as a Natural Defense Mechanism in Bacteria:
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Originally evolved in bacteria as a defense against viral infections. Bacteria “steal” snippets of viral DNA and store them as a record. When a virus shows up again, the CRISPR system uses this molecular information to fight it off.

How CRISPR Works for Gene Editing:
CRISPR utilizes a protein called Cas9 to find and cut specific DNA sequences. In bacteria, Cas9 cuts viral DNA, leading to its destruction. In human cells, Cas9 can be programmed to make cuts that trigger DNA sequence changes during repair. This allows for precise editing of genes in a controlled manner.

Editing Complex Human Traits:
Human traits are typically influenced by multiple genes, not just a single one. Editing complex traits like musical ability or intellectual capabilities is challenging. However, CRISPR has the potential to manipulate individual genes that contribute to specific diseases or disorders.

Real-World Applications:
CRISPR is already being used in clinical trials to treat diseases like sickle cell anemia and muscular dystrophy. It offers the potential for cures by correcting genetic defects or reducing the propensity for certain diseases.

DARPA’s Interest in CRISPR:
DARPA (Defense Advanced Research Projects Agency) is investing in CRISPR technology. Concerns about potential misuse, such as creating gene drives or modifying soldiers’ genes, have led to the development of anti-CRISPR systems.

Ethical Considerations:
Somatic editing (changes to body cells) is generally considered acceptable, as it affects only the individual undergoing the procedure. Germline editing (changes to reproductive cells) raises ethical concerns as it can alter the genetic makeup of future generations.

Germline Editing:
Germline editing involves making heritable changes to the DNA of eggs, sperm, or early-stage embryos. These changes can be passed on to future generations. Unlike somatic cell editing, germline editing can lead to permanent changes that can be inherited by future generations.

Ethical Considerations:
There is a debate about the ethics of germline editing, particularly when it comes to the potential to eliminate genetic diseases. Ethical issues include concerns about equitable use, affordability, and ensuring that such technology is not used to create designer babies or exacerbate social inequalities.

Potential Benefits:
Germline editing could potentially eliminate genetic diseases and improve the health of future generations. It could also enhance desirable traits and abilities, leading to a healthier and more resilient population.

Potential Risks:
Germline editing could lead to unintended consequences and unforeseen risks, as it is a relatively new technology and the long-term effects are not fully understood. There is a risk of creating designer babies, where parents select desirable traits for their offspring, leading to potential social and ethical issues.

Societal Readiness:
Society needs to have a broad discussion about the ethical implications of germline editing and come to a consensus on how and when it should be used. There is a need to ensure that germline editing is used responsibly and equitably, and that it does not exacerbate existing social inequalities.

Genetic Engineering and Societal Concerns:
Genetic engineering could exacerbate societal inequality by creating a permanent genetic divide between individuals. Reducing genetic diversity could limit the species’ creativity and resilience. Determining ethical boundaries for genetic engineering is crucial, involving public awareness and participation.

Regulation and Enforcement of Ethical Guidelines:
International conferences and collaborations aim to establish a consensus on ethical guidelines for genetic engineering. Regulation and enforcement of these guidelines can minimize unethical practices, such as off-target pharmaceuticals and illegal trafficking. Challenges exist in identifying individuals who circumvent ethical guidelines, particularly in cases involving genetic enhancements or modifications that are not easily detectable.

Societal Responsibility and Public Opinion:
Public awareness and social shaming can play a role in deterring unethical genetic engineering practices. Society’s willingness to accept a small percentage of cases slipping through regulatory cracks is a factor in determining the effectiveness of ethical guidelines.

Case Study: CRISPR-Edited Embryos in China:
In 2018, a scientist in China used CRISPR to edit the embryos of unborn human embryos to make them HIV resistant, raising ethical concerns. The incident highlights the need for international discussions and agreements on the responsible use of genetic engineering technologies.

The Irresponsible and Unethical Use of CRISPR in Human Embryos:
A scientist used CRISPR in human embryos not for research but to implant them and create a pregnancy, resulting in the birth of children. The stated purpose was to protect the children from future HIV infection by editing their cells. However, there are already well-known methods to prevent HIV infection in children born to parents with HIV. Using CRISPR in this manner was irresponsible and unethical due to the experimental and untested nature of the technology and the lack of parental understanding. The published data indicated that the technology was not ready for such use.

Regulating the Use of CRISPR:
Creating a culture that supports responsible use and strongly rejects unethical or uninformed uses is the most realistic strategy for regulation. After the 2018 announcement of the CRISPR embryo editing, there was international rejection of the work. The study was not published in any peer-reviewed journal, despite submissions.

Scientists’ Role in Policing Themselves:
Scientists have a responsibility to police themselves and ensure the ethical use of technology. Journals play a crucial role in upholding ethical standards by refusing to publish unethical research. Self-policing by scientists is essential for maintaining trust and integrity in the scientific community.

Government Regulation:
Government regulation of gene editing technology is challenging due to its complexity and the difficulty in enforcing global standards. Legislation is often outdated and unable to keep pace with rapidly evolving technology. Engaging scientists and technologists in discussions about ethics and appropriate use of the technology is more effective than government regulation.

Changing Morality and Eugenics:
Morality and societal norms evolve over time, leading to shifts in what is considered acceptable or desirable. Eugenics, once seen as a way to improve the human species, is now widely condemned. The possibility of free-market eugenics, where parents can make choices about their children’s genetic traits, raises ethical concerns.

Designer Babies and Societal Prejudices:
Designer babies, where parents can select specific traits for their children, raise ethical and societal questions. Distinguishing between true disabilities and societal prejudices is crucial. Societies must avoid labeling things as bad solely based on prejudices, as prejudices can change over time.

Government Interference in Fertility Decisions:
Governments have a history of interfering in fertility decisions, such as forced sterilization or selective breeding. Treaties should be established to prevent governments from using gene editing technology to interfere with individuals’ reproductive choices.

Public Understanding and Engagement:
Public understanding of gene editing technology is essential for informed decision-making and preventing authoritarian regimes from abusing the technology. Individuals need to develop a sense of morality and ethics regarding gene editing to influence leaders’ actions.

Fear Factor and Designer Babies:
The fear of designer babies is justified to some extent, as the technology has the potential to allow parents to make genetic modifications to their children. However, it is important to be realistic about the current capabilities and limitations of the technology. Conversations about the ethical implications of gene editing should happen now, while the technology is still developing, to avoid potential future problems.

CRISPR’s Role in the COVID-19 Vaccine Race:
CRISPR technology has played a significant role in the rapid development of vaccines for COVID-19. CRISPR allows scientists to quickly and precisely target and modify specific parts of the virus’s genetic material. This technology has accelerated the vaccine development process, potentially saving lives and ending the pandemic sooner.

Competition in Science:
Competition can be beneficial in science, driving scientists to work hard and make discoveries quickly. Doudna’s competitive spirit pushed her to work tirelessly on CRISPR when she heard of other scientists working on it.

CRISPR and Nobel Prize:
Doudna won the Nobel Prize in Chemistry in 2020 for her discovery of CRISPR, a gene-editing tool. The discovery was recognized as a basic chemistry discovery rather than a human physiology discovery, hence the Chemistry Prize. Isaacson believes that scientists who apply CRISPR to humans for medical purposes may win the Nobel Prize in Medicine in the future.

Collaboration during COVID:
During the COVID-19 pandemic, scientists around the world put aside competition and shared information openly. This collaboration led to faster discoveries and the development of vaccines and treatments.

Competition and Personal Glory:
Isaacson highlights that competition in science is not necessarily a negative aspect. Just like in sports, competition can drive scientists to achieve great things, leading to valuable discoveries.

CRISPR’s Contribution to COVID-19:
The discussion shifts to the question of how CRISPR helped in addressing COVID-19, leaving this topic to be explored in the next part of the presentation.

Detection and Testing:
CRISPR technology can be used as a detection tool to identify the genetic material of coronavirus. This application has the potential to enable rapid and at-home testing for COVID-19.

Targeted Treatment:
CRISPR can be used to fight coronavirus through targeted treatment by detecting and cutting up the virus in the body, leading to its elimination.

RNA as a Messenger:
RNA can be coded to carry messages that instruct cells to produce specific proteins. The Pfizer and Moderna vaccines use this principle to deliver RNA that encodes the instructions for producing immunity-inducing proteins against the coronavirus.

Importance of RNA:
RNA is a versatile molecule that can be coded to act as a guide or a messenger. Its coding abilities enable the development of vaccines and gene editing tools.

Inspiration from COVID-19:
The COVID-19 pandemic motivated the exploration of CRISPR’s potential in fighting viruses. This led to the acceleration of research and development in CRISPR technology.

Future Applications:
CRISPR technology has the potential to address climate change through its application in agriculture. Ongoing research aims to make CRISPR affordable and widely accessible for solving real-world problems.

Inequality Concerns:
Concerns were raised about the potential for inequality if CRISPR technology remains expensive and accessible only to the wealthy. The goal is to make CRISPR technology as widely available as possible to avoid widening the inequality gap.

Augmentation vs. Manipulation:
The focus is shifting from manipulating genes to augmenting individuals’ existing abilities and improving their well-being. CRISPR technology has the potential to enhance desirable traits and address disabilities.

Society’s Role in Defining Disability:
Walter Isaacson suggests that society’s definition of disability is often subjective and influenced by societal norms. The hearing-enabled community may consider congenital deafness a disability, while the deaf community may view it as a cultural identity that enriches society.

Fuzzy Boundary Between Disabilities and Traits:
Isaacson acknowledges that the line between true disabilities and traits that are considered disabilities due to societal factors is unclear. He emphasizes the need to question conventional notions of disability and consider the diverse perspectives of different communities.

Ethical Dilemmas in Gene Editing:
Isaacson presents various examples that highlight the ethical dilemmas in gene editing for disability correction. Curing sickle cell anemia, for instance, could eliminate the genetic predisposition that led to Miles Davis’s extraordinary jazz talent.

Respecting Individuality and Diversity:
Chuck Nice emphasizes the importance of preserving individual diversity and respecting people’s unique abilities and desires. Gene editing should aim to remove true disabilities while allowing individuals to flourish according to their own capabilities and aspirations.

Balancing Benefits and Risks:
Isaacson advocates for a thoughtful approach to gene editing, considering both the potential benefits and risks. He highlights the need to engage in open-minded discussions with various communities, including those with disabilities, to navigate the ethical challenges.

Addressing Societal Biases:
Isaacson encourages us to question societal biases and assumptions about what constitutes a disability. He suggests that we should strive to create a society that accommodates and celebrates differences rather than viewing them as deficits.