Visible Embryo Project

The VEP was created in 1992 as a collaboration between the UIC Biomedical Visualization Laboratory, directed by Michael Doyle, and the Human Developmental Anatomy Center at the National Museum of Health and Medicine (NMHM), directed by Adrianne Noe. Doyle had been appointed to the oversight committee of the Visible Human Project at the National Library of Medicine, but it would be several years before that data would become available. Looking for other sources of high-resolution volume data on the human anatomical structure, he came across the Carnegie Collection of Human Embryology, housed at the NMHM. During a sabbatical working on methods for magnetic resonance microscopy (MRM) in the laboratory of Paul Lauterbur, Doyle created a plan for the VEP and worked with Noe to recruit a large group of prominent researchers to join as initial collaborators. A primary goal of the project was to provide a testbed for the development of new technologies, and the refinement of existing ones, for the application of high-speed, high-performance computing and communications to current problems in biomedical science. ==Data==

Much of the early work involved creating serial section reconstructions from microscope slides and extracting volumetric data from the NMHM specimens, rather than just surface data. Sets of serial microscopic cross-sections through human embryos (prepared by Carnegie Collection contributors between the 1890s and 1970s) were used as sample image data around which to design and implement various components of the system. These images were digitized and processed to create 3D voxel datasets representing embryonic anatomy. Standard techniques for 3D volume visualization could then be applied to these data. and three-dimensional adult image data acquired via the Visible Human Project, in addition to embryo data. ==Collaborations==

The VEP became a far-reaching collaborative research program involving a large number of eminent scientists across the nation and around the world, including, among many others, Michael Doyle, of UIC, then UCSF, and project founder, Adrianne Noe, Director of the National Museum of Health and Medicine, George Washington University's Robert Ledley, inventor of the Full-body CT scanner, UIUC's Paul Lauterbur, MRI pioneer and Nobel laureate, LSU's Ray Gasser, eminent embryologist, Oregon Health & Science University's Kent Thornburg, internationally renown developmental biologist, Regan Moore, Director of the DICE group at the San Diego Supercomputer Center, William Lennon of Lawrence Livermore National Laboratory, Ingrid Carlbom of Digital Equipment Corporation's Cambridge Research Lab, and Demetri Terzopoulos of the University of Toronto. Some notable Visible Embryo Project collaborations include: Muritech In the mid-1990s, Michael Doyle collaborated with Harvard's Betsey Williams to create an internet atlas of mouse development, in a project named "Muritech." A prototype two- and three-dimensional color atlas of mouse development was developed, using two embryos, a 13.5 d normal mouse embryo and a PATCH mutant embryo of the same age. Serial sections of the embryos, with an external registration marker system, introduced into the paraffin embedding process, were prepared by standard histological methods. For the 2D atlas, color images were digitized from 100 consecutive sections of the normal embryo. For the 3D atlas, 300 gray-scale images digitized from the mutant embryo were conformally warped and reconstructed into a 3D volume dataset. The external fiducial system facilitated the three-dimensional reconstruction by providing accurate registration of consecutive images and also allowed for precise spatial calibration and the correction of warping artifacts. The atlases, with their associated anatomical knowledge base, were then integrated into a multimedia online information resource via the VEP's Web technology to provide research biologists with a set of advanced tools to analyze normal and abnormal murine embryonic development. Next-Generation Internet Contract The Human Embryology Digital Library and Collaboratory Support Tools project was begun in 1999 as a demonstration of the biomedical application potential of the Next Generation Internet (NGI). The collaborators included eight organizations at sites around the continental USA, a mix of medical and information technology organizations, including George Mason University, Eolas, the Armed Forces Institute of Pathology, Johns Hopkins University, Lawrence Livermore National Laboratory, the Oregon Health & Science University, the San Diego Supercomputer Center, and the University of Illinois at Chicago. The project undertook three major applications, based on the Carnegie Collection of Embryos at the AFIP's National Museum of Health and Medicine Human Development Anatomy Center (HDAC), a collection of cellular-level tissue slides that is one of the world's largest repositories of human embryos. These applications included: 1. Digitization, curation, and annotation of embryo data: The VEP team created a production digitization capability, using automated digital microscopy, with data automatically registered for tiling and transmitted to the repository at the San Diego Supercomputer Center, and annotated by teams of biomedical volunteers with expert-level quality control. 2. Distributed embryology education using materials derived from the Carnegie Collection to create animations of embryo development and recorded master classes that can be streamed over the Internet or downloaded to create a portable electronic classroom. 3. Clinical management planning where medical professionals and expectant parent patients can review normal and abnormal development patterns with collaborative consultation from distant experts. ==Technologies==

Over the decades since it was begun, the work done in the Visible Embryo Project has led to the development of several important technological breakthroughs that have had a worldwide impact: Spatial transcriptomics Even though spatial mapping of Omics data had been described as an initial goal of the VEP, it wasn't until 1999 that four VEP collaborators, Michael Doyle, George Michaels, Maurice Pescitelli, and Betsey Williams worked together to create a system for what they called "spatial genomics." The cloud In 1993, Doyle became the Director of the UCSF Center for Knowledge Management (CKM). To create the underlying software and hardware that would provide the needed computational power for the VEP, Doyle's CKM group designed a new paradigm for performing remote client-server volume visualization over the Internet. To hide the complexity of the system from the user, they modified one of the earliest versions of the NCSA Mosaic Web browser to allow their interactive cloud-computing applications to be automatically launched and run embedded within Web pages, so any user would need only to load a Web document from the VEP and would be able to immediately interactively explore the project's multidimensional datasets, rather than static representations of those datasets. In November 1993, the CKM's VEP research group demonstrated this system, the first Web-based Cloud application platform, on-stage to a meeting of approximately 300 Bay Area SIGWEB members at Xerox PARC. Today, this capability is called "the Cloud." The VEP team's work opened the door to the potential of the Web to provide rich information resources to users, regardless of where they were located and spawned a multi-trillion-dollar industry as a result. zMap Doyle then began to focus more directly on the problem of how to navigate within these complex biomedical volume datasets and developed a system for mapping the semantic identity of morphological structures within the datasets and integrating those mappings with the hypermedia linking mechanism of the Web. This led to the creation of the first three-dimensional Web image map system and was used to create a variety of online interactive reference systems for biomedical education and research throughout the 90s and beyond. Blockchain One of the challenges for large collaborative knowledge bases is how to assure the integrity of data over a long period of time. Standard cryptographic methods that depend upon trusting a central validation authority are vulnerable to a variety of factors that can lead to data corruption, including hacking, data breaches, insider fraud, and the possible disappearance of the validating authority itself. To solve this problem for the VEP data collections, Doyle created a novel type of cryptographic system, called Transient-key cryptography. This system allows the validation of data integrity without requiring users of the system to trust any central authority, and also represented the first decentralized blockchain system, enabling the later creation of the Bitcoin system. In the mid-2000s, this technology was adopted as a national standard in the ANSI ASC X9.95 Standard for trusted timestamps. Virtual assistants Since the mid-2000s, the VEP team has made great use of digital voice and text communications systems, to facilitate communications among geographically-distributed team members. To increase the efficiency of these communications, Michael Doyle and Steve Landers collaborated to create the Skybot system, the first AI-based mobile virtual assistant system. Skybot used the power and flexibility of AI to dramatically expand the use of messaging systems. Using Skybot, one could create a variety of programmable responses to incoming calls and chat messages. The system incorporated a state machine that could be configured to automatically trigger automated responses to various communication and user-context events. This provided the user with a surprisingly broad and powerful set of capabilities for automating mobile communication operations and pioneered the mobile intelligent-assistant product category that is now ubiquitous worldwide. ==Current status==

Plans are underway to secure the funding necessary to expand the Visible Embryo Project to create a national resource that combines large-scale knowledgebase with advanced analytical tools in an innovative online collaborative environment to support and continue to advance the art and science of Spatial Omics. == See also ==