Genomics vs. Proteomics:
Genomics: Studies the genome, a list of ingredients or parts used in a restaurant. Proteomics: Studies the proteins, the actual food prepared in the kitchen.

The Blueprint Analogy:
The genome is often compared to a blueprint, but this analogy is flawed. The genome is more like a parts list than a blueprint.

Proteins: The Dynamic Conversation:
Proteins are the active components of cells, the conversation between cells. Genomics provides the vocabulary, but proteomics reveals the actual dialogue.

Challenges of Proteomics:
Measuring proteins is technically difficult. Protein levels are dynamic and sensitive to changes. Traditional methods were unreliable and highly variable.

Reliable Proteomics:
Automation, process control, and semiconductor-like approaches improved reliability. Robotics and nanoliter quantities enhance precision.

Complexity of Proteins:
Proteins are more complex than DNA. Understanding protein interactions and modifications is challenging.

Cancer and Proteomics:
Cancer is a complex disease influenced by multiple factors. Proteomics can provide insights into cancer development and progression. Identifying protein signatures can aid in diagnosis and treatment.

Conclusion:
Proteomics is a rapidly developing field with the potential to revolutionize our understanding of biology and disease. By studying proteins, we can gain insights into the complex processes that occur within cells and organisms.

Protein Measurement Breakthrough:
Developed a machine that measures 100,000 protein markers from a drop of blood with consistent and precise results.

Sorting Proteins:
Proteins are sorted by mass and slipperiness through a controlled chromatography process.

Isotopes and Protein Precision:
Different isotopes of carbon in proteins create distinct lines, demonstrating the precise measurement of proteins.

Dynamic Range and Protein Concentration:
Proteins differ in concentration by six orders of magnitude, making it challenging to display the full dynamic range in images.

Consistency and Comparison:
Consistent protein measurements allow for overlaying data from different samples, enabling comparisons between healthy and diseased individuals.

Body State and Protein Expression:
Proteins reflect various aspects of body state, including diet, mood, and sleep, requiring numerous measurements for meaningful analysis.

Consistency as a Foundation for Treatment:
Achieving consistency in protein measurements paved the way for using this technology in treatment.

Colon Cancer Prevention:
Colon cancer, a preventable disease, kills approximately 50,000 people annually in the United States.

Colon Cancer Prevention:
Colon cancer is preventable by removing colon polyps through endoscopic surgery. Colonoscopies are the only current method to detect colon polyps, but they are invasive, expensive, and carry risks. As a result, many people do not get colonoscopies, leading to unnecessary deaths from colon cancer.

The Need for a Better Screening Method:
A blood test that could accurately identify individuals with colon polyps would be a valuable tool for preventing colon cancer. Such a test could be taken annually during routine physicals, leading to earlier detection and treatment of colon polyps.

Promising Research:
Hillis and his team conducted a study to determine if protein patterns in blood samples could indicate the presence of colon polyps. Their preliminary results suggest that specific protein patterns may indeed be associated with colon polyps.

Potential Benefits:
A blood test for colon polyps would save lives by enabling early detection and removal of polyps before they progress to cancer. This would reduce healthcare costs associated with treating advanced colon cancer. Insurance companies would be incentivized to cover the cost of such a test due to the potential savings.

Diagnosis-Treatment Paradigm:
The traditional paradigm in medicine is scientific medicine, which involves diagnosing patients based on objective criteria and then treating them with specific treatments based on clinical trials.

Effectiveness for Infectious Diseases:
This approach has been very effective for infectious diseases, which naturally divide into species and can be treated differently depending on the specific species.

Limitations for Cancer:
However, this paradigm may not be as effective for cancer, as cancer is not a single disease but a complex group of diseases with many different causes and manifestations.

Complexity of Cancer:
Cancer is not like malaria or polio, which are distinct diseases with a specific parasite or cause. Cancer is a highly variable disease with different types and stages, making it difficult to categorize and treat effectively.

Cancer: A Verb, Not a Thing:
Traditional cancer classification divides patients based on the body part where the tumor appears, e.g., breast cancer, prostate cancer, brain cancer. This approach is flawed because cancer is not an infection coming from outside but a process (cancering) that the body does.

Cancering: A Constant Process:
Cancering, the abnormal division of cells, is an ongoing process in the body. The body’s immune system usually controls cancering, preventing the development of tumors.

Tumors as Symptoms:
Tumors are not the cancer itself but symptoms of the underlying cancering process. The type of cancering, not the tumor location, determines the appropriate treatment.

Body Part Hierarchy: A Misguided Approach:
Approving cancer drugs based on body part hierarchy is illogical. The same drug may be effective for different types of cancer, regardless of tumor location. Dividing cancer into subtypes (e.g., breast cancer type A, B, C) is a step in the right direction but still inadequate.

The Wrong Doctor:
The current approach often leads patients to seek care from specialists based on tumor location, e.g., urologists for prostate cancer. This practice is misguided because the type of cancering, not the tumor location, should determine the specialist.

Arbitrary Criteria in Treating Diseases:
Current medical approaches to diseases like cancer are often based on arbitrary criteria, such as the location of a tumor or the type of tissue affected. This approach leads to fragmented treatment strategies that address symptoms rather than underlying causes.

Plumbing Analogy:
Hillis uses the analogy of a plumber to illustrate the absurdity of treating diseases based on arbitrary criteria. Just as a plumber would not fix a leak based solely on the location of the puddle, doctors should not treat diseases based solely on the symptoms or affected body part.

Systemic Diseases and Measurement of Body States:
Complex diseases like cancer, neurodegenerative diseases, and autoimmune diseases are often systemic, involving imbalances in the body’s functions. To effectively treat such diseases, it is crucial to measure and understand the body’s state, including protein production and other molecular information.

Modeling Disease Progression and Treatment Effects:
With a comprehensive understanding of the body’s state, it is possible to develop models that simulate disease progression and the effects of various treatments. These models can help predict the most effective treatment strategies for individual patients, considering both conventional and unconventional approaches.

Personalized Treatment Plans:
This new paradigm of treating complex diseases would lead to personalized treatment plans tailored to each patient’s specific condition and state. Such plans may involve a combination of conventional therapies, lifestyle interventions, and innovative treatments aimed at restoring the body’s balance and promoting healing.

Paradigm Shift in Medicine:
Historically, doctors intuitively viewed the body as a system with balanced forces, but lacked empirical measurement. Scientific medicine abandoned this paradigm, leading to a need for integrating science and systems thinking in medicine.

Complexity of Systems Biology:
Measuring proteins and other variables provides insights into the body’s systems. The systems view of the body involves complex models encompassing gene expression, cell growth, tissue formation, blood supply, and endocrine system responses.

Research Initiative:
Danny Hillis received a grant from the National Cancer Institute to explore systems biology in cancer treatment. The grant attracted 200 proposals, leading to the expansion of the program and the issuance of a dozen grants.

Collaboration and Integration:
Consortia of researchers from various institutions are working together to develop comprehensive models of the body’s systems. Integration of models for gene expression, cell growth, tissue formation, blood supply, and endocrine system responses is essential for a holistic understanding.

Practical Application and Challenges:
Initial experiments are conducted on mice due to the ethical and practical considerations of repeatedly performing experiments. The goal is to develop a functional model for treating cancer in mice, with the ultimate aim of applying it to humans.

Conclusion:
Danny Hillis emphasizes the importance of adopting a systems biology approach in medicine, which involves integrating diverse models to understand the complex interactions within the body. While the research is challenging, he believes that it holds the potential to revolutionize cancer treatment and improve overall healthcare outcomes.

Key Points:
The future of medicine involves personalized healthcare through data analysis of blood samples. This enables proactive treatment before symptoms arise. Treating signals of the body as noise allows for mathematical analysis to distinguish between good and bad signals, aiding predictive analysis. Information theory and extracting signals from noise are crucial in analyzing vast amounts of data obtained from blood measurements. Applied Minds specializes in interdisciplinary work, hiring individuals with diverse backgrounds. Project selection at Applied Minds is based on passion, financial sustainability, and the potential to impact the world positively.

Danny Hillis’ Journey:
Hillis’ background in computer science and interdisciplinary collaboration led him to establish Applied Minds, a company focused on tackling diverse projects. His experiences at the Artificial Intelligence Laboratory and Disney emphasized the importance of interdisciplinary approaches beyond science. At Applied Minds, Hillis seeks projects that align with the company’s values, have financial viability, and have the potential to make a meaningful impact.

Applied Minds’ Approach:
Applied Minds embraces interdisciplinary teams to address complex problems that require diverse expertise. The company’s project selection criteria prioritize passion, financial sustainability, and the potential for positive impact. Projects range from medical advancements to climate modeling, reflecting the company’s commitment to exploring diverse fields.

Criteria for Project Selection:
Exciting: Projects that have the potential to make a significant impact and positively affect people’s lives. Financially Viable: Projects that have a clear business model and potential for financial success. Interdisciplinary: Projects that require expertise from multiple disciplines and cannot be solved by a single field.

Example Projects:
Satellite Launch: Launching a satellite for various purposes, such as communication or scientific research. Self-Driving Vehicles: Developing and building autonomous vehicles for transportation. Toys: Creating innovative and educational toys. Aircraft: Designing and constructing unique aircraft. Online Learning: Developing new and effective methods for online education.

Project Funding:
Collaboration with Large Companies: Working with large companies on specific problems, often with a designated budget for research and development. Gates Foundation Support: Receiving funding from the Gates Foundation for projects with significant social impact, even if they lack a clear business model. Reinvestment of Profits: Using profits from successful projects to invest in new research and development initiatives. Spin-Off Companies: Occasionally forming new companies based on successful research projects.

Interdisciplinary Approach:
Emphasis on Interdisciplinary Teams: Seeking individuals with diverse backgrounds and expertise to tackle complex problems. Need for Interdisciplinary Collaboration: Recognizing that many problems cannot be solved by a single field and require collaboration across disciplines.

Ethical Considerations:
Animal Studies: Using mice for interventionist studies to develop models and test treatments, while ensuring ethical considerations are followed. Human Clinical Trials: Conducting human clinical trials with caution and careful consideration, ensuring the safety and well-being of participants.

Patents:
Danny Hillis believes that the patent system is generally harmful, particularly in software. He argues for a weakening of the patent system, selectively using it only where it provides societal benefits.

Proteomics Technology:
The current state of proteomics technology is slow and expensive. The turnaround time for a blood test can take days, and the cost is in the thousands of dollars. Most of the cost is associated with PhDs working on the signal-to-noise problem and similar issues.

Identifying Patterns and Producing Antibodies:
Once a pattern, like the colon polyp pattern, is identified, an antibody can be produced for it. Producing antibodies is a capital expense but a fairly well-known process. The technology is similar to the “pee on a stick” test, making it very affordable. The challenge lies in broad tests where the target is unknown, which is slow and expensive at present.

Genomics and Proteomics Comparison:
Just like genomics, proteomics will initially focus on specific tasks for specific proteins. Eventually, analyzing the entire star field of proteins will become affordable, similar to sequencing everyone’s genome.

Working with Disney:
Working for Disney was Danny Hillis’ only paid job, unlike his other ventures. The experience of receiving a paycheck with benefits was surprising to him, as he was used to paying for benefits in his previous companies. He eventually realized he did not enjoy working in a large organization with a traditional job structure.

Innovation and Resistance to Change:
Danny Hillis shares his experiences at Disney R&D, where he witnessed firsthand how companies can become resistant to change and innovation that pushes beyond their core competencies. Disney was hesitant to adopt new technologies, such as DVRs, due to concerns about disrupting their existing business model and advertising revenue.

Disney’s Focus on Core Competencies:
Hillis acknowledges that Disney’s focus on its core competencies in storytelling, theme parks, and movie-making has contributed to its success and profitability. However, he also recognizes that this approach may limit the company’s ability to innovate and adapt to changing market trends.

The Challenge of Technology Adoption in Developing Countries:
Andreas, a team member working on a project to address the lack of road infrastructure in developing countries, highlights the challenges of applying cutting-edge technology in regions with limited resources. The team is exploring the potential of using small air vehicles to transport goods and leapfrog the need for extensive road infrastructure, similar to the impact of cell phones on telecommunications.

Hillis’ Experience in the Developing World:
Hillis reveals that he spent a significant portion of his childhood in the developing world, where his father worked as an epidemiologist. These experiences gave him a firsthand understanding of the challenges and opportunities present in these regions.

Applying Cutting-Edge Thinking to Developing Countries:
Hillis provides an example of his online learning initiative, which aims to apply cutting-edge technology to address the educational needs of developing countries. This approach involves leveraging technology to provide affordable and accessible education to underserved communities.

Challenges Faced by People in Developing Countries:
Danny Hillis grew up in various parts of Africa and Asia, witnessing firsthand the struggles and lack of opportunities faced by people in those regions. He recognized that people in developing countries possess the same intelligence and potential as those in developed countries but lack the means to exercise their abilities.

Internet and Cell Phones as Potential Equalizers:
Hillis believes that the increasing ubiquity of the internet and cell phones can potentially provide universal access to information and education. This accessibility can break down barriers and allow individuals in developing countries to tap into a global network of knowledge and resources.

Bridging the Educational Divide:
Hillis envisions a future where every child in the world has access to the best teachers and educational materials, regardless of their geographic location. He emphasizes that this access to knowledge is the only factor preventing children in developing countries from having the same opportunities as those in developed regions.

Mapping Ignorance and Providing Tailored Learning:
Hillis’s work focuses on creating a system that maps all the available knowledge and educational materials. This system aims to guide individuals through their learning journey, showing them the areas they need to focus on and providing them with resources in their own language and based on their existing knowledge.

Personalized Education and Global Problem-Solving:
Hillis believes that this personalized approach to education can empower individuals worldwide to solve global problems more effectively and sustainably. He envisions a world where people can access the knowledge and resources they need to make significant contributions, regardless of their background or location.

Improving Healthcare and Addressing Global Challenges:
Hillis criticizes the current approach to disease management, highlighting the excessive suffering and resource consumption it entails. He emphasizes the need for better solutions and calls for the creative capacity of the world to engage in addressing global challenges more effectively. He believes that improved access to education is essential for this endeavor.