Danny Hillis (Applied Minds Co-founder) – TEDMED Conference (Dec 2010)


Chapters

00:00:24 Genomics and Proteomics: Beyond the Genome to Treat Cancer
00:07:46 Measuring Proteins for Medical Diagnosis
00:10:34 Automated Proteomics for Cancer Detection and Treatment
00:14:24 Cancering: A New Perspective on Understanding and Treating Cancer
00:18:42 Computer Models for Personalized Cancer Treatment

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.


Notes by: Hephaestus