Danny Hillis (Applied Minds Co-founder) – TEDMED Conference (Dec 2010)
Chapters
00:00:24 Genomics and Proteomics: Beyond the Genome to Treat Cancer
Genomics vs. Proteomics: A Different Perspective Genomics is the study of genes and their role in an organism’s traits, while proteomics studies proteins and their interactions. While genomics provides insights into genetic predispositions, it has limitations in distinguishing healthy and sick individuals. Proteomics, on the other hand, examines the products of gene expression and cellular processes, offering a more comprehensive understanding of disease states.
The Analogy of a Restaurant Danny Hillis uses the analogy of a restaurant to illustrate the limitations of genomics. The genome, like a list of ingredients, can reveal certain abnormalities or missing components. However, just as tasting the food is crucial to assess a restaurant’s healthiness, examining protein expression and cellular processes is essential for diagnosing diseases.
The Importance of Proteomics Proteomics offers a more direct understanding of disease mechanisms and cellular processes. By studying proteins, researchers can identify disease-associated proteins, understand their interactions, and develop targeted therapies. Proteomics complements genomics by providing a dynamic view of cellular function and disease progression.
The Accessibility and Value of Proteomics Advances in technology have made proteomics more accessible and affordable. Proteomics can provide valuable insights into disease diagnosis, prognosis, and treatment response. By examining protein expression and interactions, proteomics can guide personalized medicine and improve patient outcomes.
Measuring Proteins: Proteins are critical for various functions in the human body, serving as messengers that communicate between cells. Understanding the protein network is crucial for identifying the root causes of diseases.
Challenges in Protein Measurement: Unlike DNA measurement, protein measurement is complex and time-consuming. The process requires numerous steps and specialized techniques, making it difficult to obtain accurate and consistent results. The amount of protein present is crucial, as even small changes can have significant implications.
Attempts to Measure Proteins: The speaker, Danny Hillis, has attempted to measure proteins in the past but encountered significant challenges. He highlights the difficulty in obtaining reliable measurements due to the complexity of the process.
The Importance of Accurate Protein Measurement: Oncologist David Agus emphasizes the urgent need for a better method to measure proteins. Agus stresses the importance of understanding the protein network to effectively treat diseases and save lives.
Conclusion: The speaker recognizes the significance of accurate protein measurement and the challenges associated with it. He acknowledges the potential impact of a reliable method and the need for further exploration and innovation in this field.
00:10:34 Automated Proteomics for Cancer Detection and Treatment
Introduction: Danny Hillis recognized the importance of automating the complex process of proteomics, which involves measuring proteins, to improve medical diagnosis and treatment.
Protein Measurement Technique: Applied Minds developed a robotic assembly line that measures proteins in a drop of blood. The technique involves sorting proteins based on weight and slipperiness, creating an image representing the protein profile. The protein profile can be compared over time or between patients to detect changes associated with health conditions.
Exquisite Sensitivity: The protein measurement technique is highly sensitive, allowing the detection of different isotopes of carbon, indicating the presence of extra neutrons.
Patterns and Markers: By comparing protein profiles of patients who respond differently to a drug, patterns can be identified that serve as markers for drug response. These markers can be used to predict patient response to a drug even if the specific protein is not yet known.
Cancer Treatment: The ability to measure and understand proteins in blood has significant implications for cancer treatment. By identifying patterns associated with cancer progression and response to therapy, personalized and targeted treatments can be developed.
00:14:24 Cancering: A New Perspective on Understanding and Treating Cancer
Cancer as a Systems Disease: Cancer is not an infectious disease caused by an external agent but rather a failure of the body’s internal systems.
Treating Cancer: Traditional approaches to cancer treatment view it as an infectious disease, aiming to kill the cancerous cells as if they were foreign invaders.
Diagnosis and Treatment Limitations: Diagnosing cancer often involves categorizing it based on the affected body part, leading to separate clinical trials and treatments for different types of cancer. This approach fails to recognize the systemic nature of cancer and the underlying biological processes that contribute to its development.
Cancer as a Verb: Danny Hillis argues that cancer should not be viewed as a noun (a thing) but rather as a verb (an action). Cancering is an ongoing process within the body, and tumors are symptoms of this process.
Analogy of Plumbing: Hillis uses the analogy of plumbing to illustrate the limited understanding of cancer. Treating cancer by removing tumors is like mopping up water leaks without addressing the underlying plumbing issues.
Proteomics and Causative Modeling: Proteomics offers a deeper understanding of the biological processes involved in cancer. By studying proteomics, scientists can build causative models to identify the root causes of cancer and develop more targeted and effective treatments.
00:18:42 Computer Models for Personalized Cancer Treatment
Collaboration for Cancer Research: Danny Hillis and David Baltimore initiated a program at the National Cancer Institute to bring together experts from diverse fields to collaborate on cancer research. This consortium, established at USC, includes leading oncologists and biologists from various institutions worldwide.
Research Objectives: The five-year research project aims to develop a predictive model of cancer. This model will help understand the mechanisms of cancer development and identify effective treatments for specific patients.
Animal Model and Data Collection: The initial focus is on studying cancer in mice, involving the sacrifice of animals for scientific purposes. The research involves collecting proteomics data to gain insights into the molecular processes underlying cancer.
Personalized Treatment Approach: The ultimate goal is to create a personalized treatment plan for each patient, considering their unique cancer profile. This approach involves simulating different treatment sequences in a computer model to determine the most effective regimen.
Precision Medicine: The personalized treatment approach aligns with the concept of precision medicine, tailoring treatments to individual patients based on their specific genetic and molecular characteristics. This approach aims to minimize side effects and improve treatment outcomes.
Guiding the Body’s Natural Healing Mechanisms: Hillis believes that the body has the ability to heal itself if provided with the right support. The goal of cancer treatment should be to assist the body’s natural mechanisms in overcoming the disease. This involves providing targeted interventions, such as small doses of drugs, dietary modifications, or localized therapies, to stimulate the body’s healing processes.
Future of Cancer Treatment: Hillis envisions a future where cancer treatment is customized for each patient based on a comprehensive understanding of their disease. This approach will require extensive research and collaboration among multidisciplinary teams. The ultimate goal is to design personalized treatment plans that effectively guide the body back to health.
Abstract
Revolutionizing Cancer Treatment: Understanding the Interplay of Genomics, Proteomics, and Systems Biology
The battle against cancer is entering a new frontier, shifting from traditional gene and protein-focused treatments to a holistic systems approach. Genomics, though insightful, acts more as a parts list than a complete blueprint, failing to illuminate the intricate interconnections within biological systems. Proteomics, on the other hand, reveals the cellular workhorses, offering deeper insights into disease progression, particularly in cancer.
Genomics vs. Proteomics: A Different Perspective
Genomics is the study of genes and their role in an organism’s traits, while proteomics studies proteins and their interactions. While genomics provides insights into genetic predispositions, it has limitations in distinguishing healthy and sick individuals. Proteomics, on the other hand, examines the products of gene expression and cellular processes, offering a more comprehensive understanding of disease states.
1. Genomics and Proteomics: The Building Blocks of Life
Understanding cancer begins at the molecular level, with genomics and proteomics providing crucial insights. Genomics has revolutionized biology, yet its utility is limited as it offers a parts list without detailing interconnections. Proteomics, studying the plethora of proteins in organisms, brings us closer to understanding cellular functions and disease mechanisms, particularly in cancer’s progression.
The Analogy of a Restaurant
Danny Hillis uses the analogy of a restaurant to illustrate the limitations of genomics. The genome, like a list of ingredients, can reveal certain abnormalities or missing components. However, just as tasting the food is crucial to assess a restaurant’s healthiness, examining protein expression and cellular processes is essential for diagnosing diseases.
2. Rethinking Cancer Treatment: A Systems Approach
Current cancer therapies, often gene or protein-specific, show limited efficacy due to cancer’s complexity and adaptability. A new treatment paradigm is emerging, focusing on the system as a whole rather than individual components. This approach necessitates a comprehensive understanding of the interactions between genes, proteins, and environmental factors, along with the development of new multi-targeted drugs.
The Importance of Proteomics
Proteomics offers a more direct understanding of disease mechanisms and cellular processes. By studying proteins, researchers can identify disease-associated proteins, understand their interactions, and develop targeted therapies. Proteomics complements genomics by providing a dynamic view of cellular function and disease progression.
Cancer as a Systems Disease
Cancer is not an infectious disease caused by an external agent but rather a failure of the body’s internal systems. Treating cancer requires understanding and fixing the underlying system, not just treating symptoms.
3. Challenges and Opportunities in Cancer Treatment Innovation
Developing a systems-based cancer treatment is daunting but ripe with opportunity. Advances in genomics and proteomics are bringing us closer to grasping cancer’s complexities, paving the way for more effective treatments. Proteins, as cellular communicators, play a crucial role in this endeavor. However, measuring proteins is complex and fraught with inconsistencies, highlighting a significant challenge in the field.
Measuring Proteins: Challenges and Attempts
Unlike DNA measurement, protein measurement is complex and time-consuming. The process requires numerous steps and specialized techniques, making it difficult to obtain accurate and consistent results. The amount of protein present is crucial, as even small changes can have significant implications. The speaker, Danny Hillis, has attempted to measure proteins in the past but encountered significant challenges. He highlights the difficulty in obtaining reliable measurements due to the complexity of the process.
4. A Leap in Proteomics: Measuring Proteins with Precision
In response to the intricate challenge of measuring proteins, Danny Hillis’s team at Applied Minds innovated a robotic system to automate this process. This advancement allows for the consistent measurement of proteins, providing detailed insights into the intricate protein patterns that vary with health conditions.
Protein Measurement Technique
Applied Minds developed a robotic assembly line that measures proteins in a drop of blood. The technique involves sorting proteins based on weight and slipperiness, creating an image representing the protein profile. The protein profile can be compared over time or between patients to detect changes associated with health conditions.
5. The Multifaceted Nature of Cancer
Cancer’s complexity is further evidenced by its diverse manifestations and the heterogeneity of cancer cells within the same tumor. This diversity poses significant challenges to treatment, as resistance to therapy often leads to treatment failure.
Patterns and Markers
By comparing protein profiles of patients who respond differently to a drug, patterns can be identified that serve as markers for drug response. These markers can be used to predict patient response to a drug even if the specific protein is not yet known.
6. Precision Medicine: Tailoring Treatment to the Individual
Precision medicine emerges as a beacon of hope, proposing treatments tailored to individual molecular profiles. By identifying specific genetic mutations and protein alterations, this approach seeks to develop targeted therapies that inhibit cancer’s molecular drivers, potentially improving treatment outcomes and patient survival.
7. Rethinking Cancer: From Disease to System Failure
Danny Hillis offers a novel perspective, critiquing the current infectious disease-like approach to treating cancer. He argues that cancer is not an external invader but a systemic failure, suggesting a shift in focus from treating symptoms to understanding and fixing the underlying system.
Exquisite Sensitivity
The protein measurement technique is highly sensitive, allowing the detection of different isotopes of carbon, indicating the presence of extra neutrons.
8. Cancering: A Dynamic Process
Hillis advocates for a paradigm shift in viewing cancer, proposing “cancering” as a verb, emphasizing the dynamic, processual nature of the disease. This view aligns with the need for a new paradigm in cancer research and treatment, one that concentrates on the root causes and systemic nature of the disease.
Cancer Treatment: Implications for Cancer Treatment
The ability to measure and understand proteins in blood has significant implications for cancer treatment. By identifying patterns associated with cancer progression and response to therapy, personalized and targeted treatments can be developed.
A New Era in Cancer Research and Treatment
The journey towards effective cancer treatment is steering away from traditional methods towards a comprehensive systems biology approach. By integrating the insights from genomics and proteomics, and embracing the complexity of cancer as a systemic issue, we stand on the cusp of a revolution in cancer therapy. This new paradigm, emphasizing precision medicine and a deeper understanding of the disease process, holds the promise of more effective, personalized treatments, marking a significant stride in our fight against cancer.
Genomics and proteomics are transforming medicine by improving disease diagnosis and treatment through a deeper understanding of cellular interactions and personalized medicine. Measuring and understanding body states through proteomics, combined with systems biology and interdisciplinary collaboration, is leading to more effective and personalized treatments for complex diseases like cancer....
Hillis' work in proteomics, extracting data from blood, could revolutionize healthcare by shifting focus from treatment to early detection of diseases like colon cancer....
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