Bio Futures 1. The “DARPA Bio Futures” activity is focused on adding the “Bio Dimension” to DARPA Futures. DARPA already has some investments in the Bio area based on our general policy of being open to new ideas of potential application to the DARPA mission. Some of the existing programs, projects, and results are described in other parts of DARPATech. Beginning in January 1999, we decided to consider a much more comprehensive approach. This session is just an introduction to how we are beginning to think about “Adding the Bio Dimension to DARPA Futures”. We need your suggestions. There is a “Side Bar Session” scheduled to extend the process to this meeting. We are also open to visitors at DARPA or suggestions for site visits to have informal discussions. 2. The main topics presented in this briefing are identified on this slide. Some topics will be discussed in more depth than others. While we been doing a great deal of “homework” we are being very conservative about what we are saying at this time. We only want to describe our interests and possible intentions in the most general terms because we do not want people to try to “guess” what they should tell us based on over interpreting what specifics they might hear as an indication of decisions we may have already made. We are maintaining an open mind and aggressively listening. This is an important part of the process at this early phase. 3. We are considering potential Science and Technology Futures stimulated by interactions between Biological Sciences and Technology and more Conventional DoD Technologies (Information/ Electronics/ Photonics/ Chemical/ Mechanical Science and Technology). These general science and technology areas have been advancing at an accelerating rate for the past 50 years (since the end of WW II) with generally weak interactions among them. DARPA (ARPA) has made strategic investments in selected aspects of these individual areas throughout its history to enable fundamental advances. As part of a process of looking into the next 50 years, we have started to think about the challenges and opportunities of stimulating increased coupling between biological sciences and technology and the technical areas of DARPA historical expertise. The goal is to enable fundamental advances in science and technology with potential application to the DARPA mission in the future. 4. The information technology revolution was enabled by microelectronics while revolutions in biology in the same time period have had minimal coupling to information and microelectronics technologies. The increasingly pervasive use of information technology leads us to imagine the potential challenges and opportunities of focusing on coupling biology with the other science and technologies. We have started the process of identifying interested people within DARPA, existing projects, and suggestions for how to proceed in our internal exploration of this area. We would also like to identify potential new topics, additional people, projects, and places in other parts of the government, academic community, and industry; including professional societies and publications that represent the best people, activities, and results in individual areas and their combinations. Discussion “DARPA Bio Futures” at DARPATech 99 and a Side Bar Session is intended to open the process to more people and organizations. This is part of an overall bootstrapping process. 5. Imagine the potential of increased coupling among [Bio:Info:Micro]. Imagine applying and extending what we have learned in [Info:Micro] to include the Bio dimension … Identify major categories from using Bio for fundamental new devices of essentially the conventional kind, to new kinds of devices, to the use of new devices for new sensors and effectors, to new capabilities and new systems. IT can be used in the discovery of new devices, in their design, in the control of production processes, in the design of systems using them, in the integration of systems using them, and so on … Imagine their transformation to new scalable systems and applications that enable fundamentally new capabilities. 6. A simple way to see the major relationships among the Bio, Info, Micro dimensions is in a “Venn Diagram”. Examples in each of the regions provide “hints” about system structures. [Bio] “Wet Ware” Bio things in their environment. [Info] “Info Ware” Info things down to models in general … down to but not including particular “Hard Ware” or “Wet Ware” [Micro] “Hard Ware” Micro things in their environment. [Bio:Info] Information Systems applied to Bio Systems ... analyze, design, model, ... [Info:Micro] Computing and Networking Systems [Micro:Bio] [Micro] interacting with [Bio] like “Bio Chips” [Bio:Info:Micro] The areas working together as a system. 7. The broad characterizations can be refined by considering the scale involved within each of the area or dimensions involved. The scale can be the physical size of the objects, the number of objects involved, the number of operations on objects, or other relevant quantitative measure. 8. The [Bio, Info, Micro] Space shown this way with [Info, Micro] at its base emphasizes where DARPA has been operating and the opportunity and challenge of adding the Bio dimension. The Bio dimension covers biology science and technology from fundamental devices to integrated components to systems of devices and components. The Info dimension covers information science and technology from fundamental concepts to compositions of concepts to systems that embody the concepts and their compositions. May be used to describe and support the Info aspects and activities of the Bio and Micro dimension but does not include them. The more specific issues are part of the other dimensions. The Micro dimension covers micro science and technology from fundamental devices to integrated components to systems of devices and components. Each of the dimensions is expressed in terms of the “log” of some measure of interest to provide a way to indicate the scale involved. Appropriate units are used in each dimension depending on the issue. 9. One way to describe the emerging vision is in terms of fundamental devices ... Just as a small number of fundamental devices provided the physical foundation for the [Info:Micro] revolution when combined with an elaborate bootstrapping process … There is an opportunity to apply and extend the lessons learned in identifying potential new fundamental devices [Bio:Info:Micro] revolutions. Bio can enable new approaches to developing Micro devices. Info can be used to design, analyze, and control production processes. The devices are used for functional units of replication that can be used individually or in integrated systems. Scalable designs can be developed to provide a range of capabilities based on system design parameters. The new devices can be integrated into systems. 10. “Solid State” technologies are the foundation for the modern information technology revolution. These technologies include the major categories of transistors, lasers, displays, and “magnetics” of mass storage devices including their storage surfaces, heads, and control systems of other solid state components. Once the fundamental devices were discovered it became a matter of engineering to apply and further develop them into more advanced forms. Since much of the early discovery process happened so long ago and the continuing improvement process is so technical and often proprietary it is not well known to most of the existing user community. The foundations of the Micro Dimension are in Quantum Mechanics. Each of these builds on many years of fundamental science including physics and chemistry with increasing application of engineering and information technology. This has gone through many generations of increasingly intricate bootstrapping processes. While this dimension may seem very different than the “Bio Dimension” there are aspects of Bio that could be applied and are expected to be essential to enable the continued improvement of these devices. 11. Consider the [Micro:Info] plane. Some easily recognized points on the Micro Dimension are shown with some of their direct relationships. These include “a transistor” at micron scale, the use of millions of transistors in a chip such as a microprocessor, and the use of many chips in a computer system. In addition to the hardware level of the Micro Dimension there are additional relationships (not shown) with the Info Dimension. These relationships involve the analysis, design, production, and application of the technologies to develop new capabilities. The largest scale example is the Internet, a global scale computing and networking systems. There are 4 major categories of devices that enable modern [Info:Micro] 1. Solid State Switches (Transistors) 2. Magnetic Storage Systems 3. Solid State Lasers 4. Solid State Displays Each has a similar story. 12. The first transistor. Brattain and Bardeen's pnp point-contact germanium transistor operated as a speech amplifier with a power gain of 18 on December 23, 1947. 13. The progression from a transistor in a “can”, through the first “integrated circuit held by tweezers” to a photomicrograph of the first microprocessor, shows the extraordinary progress in just the first 20 years of modern IT. The discovery of the fundamentals that enable the development of these devices is a form of “reverse engineering” of the physical world in a process that is normally called basic science. 1953: Transistor in a “can” … 1958: Kilby (his hand) Holding (with tweezers) the First Integrated Circuit 1971: 4004 Microprocessor The 4004 was Intel's first microprocessor. This breakthrough invention powered the Busicom calculator and paved the way for embedding intelligence in inanimate objects as well as the personal computer. 14. The progress in just microprocessor terms in the 30 years since the first microprocessor has been extraordinary. Microprocessors have replaced the more discrete technologies used in the highest performance computing systems (previous Supercomputers). There are similar curves for solid state memory, magnetic mass storage, photonic devices, and solid state display technologies. 15. Progress in optical fiber transmission capacity. The growth in commercial capacity is due to the increasing bit rate of electronic-time- division multiplexing (ETDM) and the introduction of multi-channel wavelength-division multiplexing (WDM). Experimental systems used ETDM, WDM, and optical-time- division multiplexing (OTDM) to achieve record-setting results. 16. “Bio State” technologies have emerged from a different direction than the solid state technologies. At the fundamental level of “Bio Systems” important relationships to Chemistry and other physical sciences become important. There have been increasing interactions among these disciplines. The health care system has been and will continue to be a major driver of the Bio Science and Technology areas. While there are major opportunities for other applications, effective coupling for these other purposes will be a continuing challenge in both technical and policy terms. For example, NIH has been investing for 50 years in its internal and external labs with additional investments by the private sector. In addition, Bio deals (usually) with living systems in an environment of other living systems. Therefore, there are fundamental challenges associated with protecting such systems by avoiding doing them harm. While this dimension seems very different from the “Micro Dimension” there are also may similarities at the fundamental level. Lessons learned in the [Info:Micro] bootstrapping process can be applied to advance of the combined dimensions. 17. Now consider the [Info:Bio] plane. This is somewhat analogous to the [Info:Micro] plane. Some easily recognized points on the Bio Dimension are shown with some of their direct relationships. The “devices” and processes are fundamentally different. In addition, there is an increasing role emerging for the Info Dimension. At this time, the Info Dimension is used as mainly a tool in the process of discovering, developing, and applying Bio devices and systems. In the future, the relationships could be much richer, particularly when the three dimensions [Bio: Info:Micro] are progressively coupled. The Bio Dimension involves concepts and structures that have emerged from many decades of basic science and benefit from many of the fundamental science discoveries at the foundation for the Micro Dimension. 18. Scientific discovery is a form of reverse engineering … … from an X-ray crystallography image ... The DNA discovery was enabled by physical measurements using X-ray crystallography that enabled the insight to suggest the structure expressed in a paper and later used to construct a 3-D model at the atomic level. … to a published description ... James D. Watson and Francis H. C. Crick describe the structure in the article titled "Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid” in Nature, London, 1953. … to a 3-D model at atomic level ... In Feb. of 1953,Francis Crick & James Watson of Cavendish Laboratory at Cambridge University of London, assembled a 3-D model of the helical polypeptide chains with double strands facing opposite directions using this knowledge. 19. “Bio Objects” from the foundations of bio systems … (Scale in Meters) (10-9 meters = 10 angstroms = 1 nanometer) The molecules of DNA: The central molecule in this image represents the carbon tetrahedral bond. Since the carbon atom has four electrons in its outer shell, it can form bonds with four other atoms or molecules, including other carbon atoms. The ability of carbon to form long chains and rings provides the molecular complexity required for life. The carbon bond is so important to life that chemistry is divided into two branches: organic and inorganic. Organic chemistry is the branch of chemistry devoted to carbon- hydrogen molecules -- the chemistry of life. (10-8 meters = 100 angstroms) The structure of DNA: In 1953, James Watson and Francis Crick worked out the structure of DNA. The DNA molecule is composed of two complementary strands in the form of a double helix, like a long spiral ladder. Each strand is made up of a sequence of nucleotides -- a substance consisting of a phosphate, a sugar, and a nitrogen-containing base. In all of life, there are but four bases forming the rungs of the ladder of DNA. It is the particular sequence of bases that determines the function of a segment of DNA. (10-7 meters = 0.1 microns = 1000 angstroms) Strands of DNA: The double helix of DNA is further coiled around particles of protein called nucleosomes to form a beaded structure. The structure is then further folded so that the beads associate in regular coils. The coiled coils of DNA constitute the genes and chromosomes within the nucleus of living cells. It is DNA that directs the formation of proteins and enzymes which in turn control the chemical reactions of life. Viruses are forms of life made up almost exclusively of DNA. Once inside living cells, viruses are able to use the host cell's material to make more copies of the virus, which can then infect other cells. 20. “Bio Objects” from the foundations of bio systems … (Scale in Meters) (10-6 meters = 1 micron) The nucleus of the cell: We are inside the ruffly lymphocyte, only to face another surface, a protective membrane within the cell that encloses its nucleus. The minute pores allow materials from within to enter the larger volume of the cell. Every complete cell has such a nucleus, whose molecular products inform the entire life of the cell. In one human body are a hundred times more cells than there are stars in the Galaxy. (10-5 meters = 10 microns) A lymphocyte: This is a white blood cell, called a lymphocyte. It is an important part of the immune system. Lymphocytes identify and destroy invading organisms, or antigens. Lymphocytes can make billions of different antibodies by creating antigen-specific receptors. But each lymphocyte can make only one specific receptor. When an antigen enters the body, it activates only those lymphocytes whose receptors match up with it. White blood cells are one component of the extremely intricate and complex immune system. (10-4 meters = 0.1 mm = 100 microns) Micro-organisms: This microscopic view of human skin displays a single pore. In one human body are a hundred times more cells than there are stars in the Galaxy. (Milky Way) 21. We are in the process of developing a strategic vision to stimulate research focused on the fundamentals of the interactions in [Bio:Info:Micro]. We need to learn how to do this. It will build on fundamental research analogous to some of the most fundamental work at the device and theoretical areas that were the foundation of [Info:Micro]. There is an excellent collection of Bio projects at DARPA. A review of these suggests that we could do even better if there was a greater understanding of the fundamentals in DARPA terms. These issues are not a significant part of activities outside the DARPA area. We believe this new dimension has strategic potential for a kind of “Strategic Biology Program” that in some ways is analogous to the “Strategic Computing Program” of the early 1980s. We need to enable real people to do real experiments at the frontier to learn how to accelerate the discovery of new concepts in [Bio, Info, Micro] and transition them into technologies that can be applied in realistic system contexts. The best of the small projects with the best people in the best places with access to the best resources able to collaborate over the net to the greatest extent that is useful. 22. Stimulating strategic processes to achieve the strategic vision ... There are major Bio research activities that can be leveraged. These need to be coupled to advanced Info and Micro research. To provide access to Info resources: Visual, Persistent, Computational. To provide access to Micro resources: Design, Prototyping, Instrumentation. Transition to IT-based processes including: users access to local and remote systems, user activities coordinated by the system, research models represented in the system, interface to measurement instruments, interface to experiments, data and analysis tracking, access controls. The new “devices” for both “solid state” and “bio state” environment and their combinations provide a foundation for new integrated components. We expect that these will enable us to imagine new capabilities to focus our attention on particular issues toward particular directions. Transitioning the imaginations simulated toward technologies will lead to fundamentally new capabilities that will be important for the DARPA Mission. Some might choose to wait for the opportunities to develop, since we can see the potential opportunity. We believe it is more effective for DARPA to engage this process at this very early stage so that we can learn how to operate in this new dimension and be better prepared. The accelerating rate of advance, combined with the new aspects of the Bio Dimension requires that we engage in more fundamental activities. 23. An important part of this process is to enable IT-based approaches to the full range of activities associated with these processes including: measurement, analysis, design, prototyping, integration, collaboration. This will enable everything to be accessible over the Net as needed. We envision a new infrastructure for the overall process of basic research through technology development and applications. We believe that we can get the best of small teams operating in a system to give the benefits of larger projects without the usual burdens of such projects. We expect that this will lead to a much more flexible and agile innovation enterprise. 24. We are preparing for the future through these activities. This could lead to a “Strategic Biology Program” that is somewhat analogous to the DARPA “Strategic Computing Program”… Recall that Strategic Computing provided a foundation for what became the Federal HPCC Program, its extension to include the NII, and its more recent programs. There are also similarities to the time when DARPA initiated the Materials Science Research Program. Going back even further to the mid 1960s, ARPA initiated the development of the field of experimental computer science that enabled the formation of the major computer science research groups in US universities that produced the foundation for most of the information technology available in the US and around the globe. Imagine adding the Bio Dimension to the system in the context of all of the advances made since the early 1980s. We see many potential opportunities. The challenge is to translate the emerging vision into action to begin Adding the “Bio Dimension” to DARPA Futures to accelerate the process of discovery and enabling revolutions.