Avoiding, Treating & Curing Cancer With the Immune System | Dr. Alex Marson
Dr. Alex Marson, MD, PhD, discusses the immune system, cancer biology, and gene editing. He shares actionable insights on reducing cancer risk from factors like diet, smoking, and environmental toxins, and explains how CRISPR and CAR T-cell therapies are revolutionizing cancer treatment.
Deep Dive Analysis
22 Topic Outline
Current State of Biology and Medicine's Acceleration
Understanding the Innate and Adaptive Immune System
Thymus Function, T-Cell Education, and B-Cell Antibodies
General Health Factors Influencing Immune System Function
Childhood Exposures, Allergy Prevention, and Autoimmunity
Systemic Immune Responses, Cytokines, and Antibiotics
Cancer Biology: Mutations, Cell Regulation, and Risk Factors
Environmental Mutagens and Carcinogens
X-Rays, Airport Scanners, Carcinogens, and Charred Meat
Immune-Based Cancer Treatments: Checkpoint Inhibitors
CAR T-Cell Therapy: Engineering T-Cells to Fight Cancer
Age, Cancer Risk, and CAR T-Cell Targeting Challenges
CRISPR Gene Editing: Discovery and Mechanism
Precision, Risks, and Evolution of CRISPR Technology
Delivering CRISPR to Cells and Clinical Applications
Advanced Drug Delivery: Lipid Nanoparticles and Engineered Viruses
COVID-19 mRNA Vaccines and Public Trust in Science
Targeted Cancer Therapies: Immunotoxins and T-Cell Engagers
Ethical Considerations of CRISPR for Embryo Modification
Embryo Deep Sequencing and the Case Against Perfection
Future Therapeutics: Autoimmunity, CAR T-Cells, and Gene Function
Banking Immune Cells and the Future of Cell Programming
13 Key Concepts
Innate Immune System
The body's first alarm system, consisting of cells like dendritic cells and macrophages, that detect general signs of foreign invaders or damage and initiate an immune response.
Adaptive Immune System
A more specialized arm of the immune system, primarily involving B cells and T cells, which are finely tuned to recognize and eliminate specific foreign invaders.
T Cells
A type of white blood cell (lymphocyte) that develops in the thymus and has unique, randomly generated receptors on its surface. These receptors act as sensors to recognize and engage foreign targets, coordinating the immune response.
B Cells
Another type of lymphocyte that works with T cells to produce antibodies. B cells also generate diverse antibodies randomly, which are then released into the bloodstream to protect against infections.
Autoimmune Diseases
Conditions that arise when the immune system's delicate balance fails, causing T cells or B cells to inappropriately recognize and attack the body's own healthy cells and tissues. This leads to inflammation and damage in specific organs.
Cancer
A genetic disease where cells accumulate mutations, lose their normal regulatory signals, and begin to divide uncontrollably. These cells can disrupt local tissue function or spread to distant sites (metastasis), growing at the expense of the healthy body.
Mutagen
A substance or agent that causes changes or damage to the DNA sequence within a cell. Exposure to mutagens increases the likelihood of accumulating mutations, which can lead to cancer.
Carcinogen
A substance or agent that directly increases the rate of cancer development. While closely related to mutagens, carcinogens specifically refer to cancer-causing agents.
Checkpoint Inhibitors
A class of medicines that unleash the body's existing T cells against cancer by blocking natural 'brakes' on T cell activity. This allows the T cells to become more active and effectively target cancer cells.
CAR T-Cells
T cells that have been genetically engineered in a lab to express an artificial receptor (CAR) on their surface. This CAR is designed to specifically recognize and destroy cancer cells, offering a targeted immune-based treatment.
CRISPR
A gene editing technology originally discovered as a bacterial immune system against viruses. It functions as a protein 'scissor' guided by an RNA molecule to precisely cut and modify specific DNA sequences, enabling targeted genetic changes in cells.
Lipid Nanoparticles (LNPs)
Tiny fatty bubbles (formerly called liposomes) that can deliver genetic material, such as mRNA or CRISPR components, into cells. They are used in technologies like mRNA vaccines and are being engineered for targeted delivery to specific cell types.
Somatic Edits
Genetic modifications made to individual cells in the body, where the changes are passed on to daughter cells but not to subsequent generations of humans (i.e., not in sperm or egg cells).
13 Questions Answered
Biology and medicine are experiencing a 'step function' in progress, with a convergence of understanding and intervention at the root causes of disease, driven by tools like DNA sequencing, AI, and gene editing.
The immune system protects against foreign invaders and consists of the innate immune system (first alarm, generic recognition) and the adaptive immune system (specialized B and T cells for specific recognition and memory).
T cells are educated in the thymus, where they are 'selected' to remove any cells that accidentally generate receptors recognizing the body's own healthy targets, ensuring they only target foreign invaders.
No, Dr. Marson believes that antibiotics are a miracle for bacterial infections and that using them effectively does not inherently prevent the immune system from becoming robust.
Cancer is a genetic disease where cells accumulate mutations, lose their normal regulation, and divide uncontrollably, disrupting normal tissue function and potentially spreading throughout the body.
X-rays cause mutations, and while the dose from a single airport scanner is low, Dr. Marson personally tries to minimize exposure, suggesting that less radiation seems better, though not based on specific data.
Yes, charred meats are believed to contain carcinogens, although the exact level of risk compared to other factors is part of a complex balance of life decisions.
Checkpoint inhibitors are drugs that remove natural 'brakes' on T cells, allowing the body's own T cells to become more active and effectively attack cancer cells, as seen in cases like melanoma.
CAR T-cells are engineered with artificial receptors (CARs) that target specific proteins found on cancer cells. For some cancers, like B-cell leukemias, the targeted protein (CD19) is also on healthy B cells, but the body can largely tolerate the loss of these healthy B cells.
Cancer risk increases with age because it's an evolutionary process where cells accumulate mutations over time. The longer cells divide and persist, the more likely they are to acquire the specific combination of mutations that transform them into cancer cells.
CRISPR is a gene-editing tool derived from a bacterial immune system that uses a protein 'scissor' (Cas9) guided by an an RNA molecule to precisely locate and cut specific DNA sequences. This allows for targeted removal or insertion of genetic material.
The primary ethical concern is the introduction of heritable genetic edits that would be passed on to future generations. Dr. Marson advocates for a 'hard line' against such edits due to worries about unintended consequences, fads, and the potential loss of human diversity.
While there might be edge cases, Dr. Marson does not currently advise banking T cells, as future technologies are expected to be able to re-engineer existing T cells. Similarly, for iPSCs, while the technology is powerful, it's not yet clear that individual banking is necessary for everyone, with efforts underway for broader immune-compatible IPSC banks.
11 Actionable Insights
1. Avoid Heritable Gene Editing
Do not introduce genetic edits that will be passed on to future generations (germline edits), as this crosses a critical ethical line and carries unknown long-term societal and biological risks, according to Dr. Marson’s firm stance.
2. Embrace Human Diversity
Embrace the beauty of chance and human diversity rather than pursuing genetic engineering of offspring for perceived ‘perfection,’ as this could lead to a loss of diversity and an overemphasis on superficial traits, potentially limiting human depth and resilience.
3. Quit Smoking Entirely
Avoid smoking to significantly reduce exposure to chemicals that cause DNA damage and mutations, thereby lowering your risk of developing cancer, as smoking is a major cause of DNA damage.
4. Limit Excessive UV Exposure
Avoid excessive UV light exposure and sunburns, as too much UV is a clear risk factor for DNA damage in skin cells and increases the risk of melanoma.
5. Minimize Environmental Toxin Exposure
Minimize exposure to known mutagens and carcinogenic chemicals, including those found in certain workplaces, paints, thinners, and pesticides, as they can cause DNA damage and increase cancer risk.
6. Prioritize Sleep & Healthy Diet
Prioritize great sleep and maintain a healthy diet, specifically avoiding high-fat diets, to support overall immune system function and prevent qualitative differences in inflammatory responses.
7. Consider BRCA Gene Testing
Consider getting tested for BRCA mutations, especially if there is a family history of cancer, as these tests are readily available and can identify a high individual risk for certain cancers.
8. Early Life Exposure for Allergies
Ensure critical early life exposure to various environmental factors and foods (e.g., peanuts, if not already allergic) to develop tolerance and prevent hypersensitivity, which can manifest as allergies.
9. Use Antibiotics When Needed
Do not purposefully avoid antibiotics for susceptible bacterial infections with the aim of ‘strengthening’ your immune system, as antibiotics are a miracle for such infections and do not inherently impair immune robustness.
10. Limit Charred Meats
Limit consumption of charred meats, as the char is implicated as a potential carcinogen due to the formation of DNA-damaging compounds.
11. Minimize Radiation Exposure
Minimize exposure to unnecessary X-rays and airport scanners, as they involve radiation which can cause mutations; while the risk is low per exposure, frequent exposure may accumulate.
10 Key Quotes
Something is materially different right now. And there is a convergence of so many different ways of understanding biology, but then not having that stop at understanding, but to actually intervene at the root causes of disease.
Dr. Alex Marson
Our immune system permeates almost every aspect of our health and disease. It is a system really in the sense of it's involved in every part of our body that has evolved to protect us, largely to protect us against infections, viruses, bacteria, fungus, all sorts of foreign invasions.
Dr. Alex Marson
Cancer is a genetic disease where cells lose the normal regulation and are dividing out of control in various tissues.
Dr. Alex Marson
The dogma was don't waste time thinking about cancer immunology. Cancer immunology is a field that's going nowhere... It was just, we were just wrong.
Dr. Alex Marson
We can put a gene that encodes something on the surface of T-cells that will make them programmed to search and destroy for cancer cells.
Dr. Alex Marson
CRISPR fundamentally is a tool to rewrite DNA sequences.
Dr. Alex Marson
You're going into the source code of DNA inside of a cell and you can when you make that change you can say what happens to the cell?
Dr. Alex Marson
I think that we should have a line in the sand where we do not introduce genetic edits that will be passed on to the next generation.
Dr. Alex Marson
I worry deeply about losing human diversity if we see fads in what genes are popular for our offspring.
Dr. Alex Marson
Things that we think are hardships or disabilities often end up being the things that make us who we are and, you know, make us more sympathetic, give us at a depth as humans.
Dr. Alex Marson
1 Protocols
CAR T-Cell Therapy for Cancer
Dr. Alex Marson- Patient undergoes a blood donation to extract their own T cells.
- The T cells are genetically modified in a lab to express an artificial receptor (CAR) that targets cancer cells (e.g., using lentiviruses or CRISPR).
- The engineered T cells are grown up for a few days and tested in a centralized facility.
- The cells are frozen down for storage and transport.
- The frozen cells are sent back to the patient's treatment center.
- The cells are thawed and re-infused into the patient, similar to a blood transfusion.