Journal of the American Medical lnformatics Association Volume 3 Number 1 Jan / Feb 1996

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Review n

The : A Review of an Emerging -based for the Distribution of * Biomedical ::::~:::::::::::~::::::::::::9::::::::::::~::::::::::::::::::::::~::::::::::::::::::::~::::::~::::::::::::::::::::::::::::::::::::::::::::~::::::::::::::::::~:~::::~:::~,::::::::::::::~::~::~::::::::::

HENRY J. LOWE, MD, EDWARD C. LoM.~, MLS, STACEY E. POLONKEY

Abstract The Internetis rapidly evolving from a resource used primarily by the research community to a true global information network offering a wide range of and services. This evolution presents many opportunities for improved access to biomedical information, but Internet-based resources have often been difficult for the non-expert to develop and use. The World Wide Web (WWW) supports an inexpensive, easy-to-use, cross-platform, graphic to the Internet that may radically alter the way we retrieve and disseminate medical . This paper summarizes the Internet and origins of the WWW, reviews WWW-specific , and describes current and future applications of this technology in medicine and medical informatics. The paper also includes an appendix of useful biomedical WWW servers.

n JAMIA. 1996;3:1-14.

The Internet is rapidly evolving from a resource used (PCs), and the development of easy-to- primarily by the research community to a true global use . Media coverage of the information network offering, in many cases, unre- Internet has also resulted in more widespread aware- stricted access to a wide range of databases and ser- ness of how this global data network can enhance vices. This rapid growth in Internet use is being driven business, , and . In turn, this aware- by a number of factors, including- increasing “com- ness has produced a significant demand for afford- puter literacy,” availability of affordable personal able commercial services providing to those outside of the scientific and educational com- munities. Affiliation of the authors: Section of Medical Informatics, Univer- sity of , Pittsburgh, PA. One of the most significant developments driving this growth has been the of the World Dr. Lowe and Ms. Polonkey are supported by National of Medicine Biomedical Applications of High Performance Comput- Wide Web (WWW) as a technology for accessing the ing and (HPCC) Contract number NOI-LM4- vast array of resources available on the Internet. The ‘3507; Mr. Lomax is supported by National Library of Medicine WWW provides an easy-to-use, inexpensive, cross- Medical lnformatics Training Grant number 5-T15-LM070-59. platform, graphic interface that allows even a casual Correspondence and reprints: Henry J. Lowe, MD, Section of user to successfully navigate the complex web of linked Medical Informatics, University of Pittsburgh, B50A Lothrop Hall, systems that is the Internet. The impact of 190 Lothrop Street, Pittsburgh, PA 15261. e-: [email protected]. WWW technology on biomedicine may be significant. nih.gov The ease of creating and accessing Internet-based Received for publication: 3/28/95; accepted for publication: 9/12/95. WWW servers combined with the platform-indepen- LOWE ET AL., World Wide Web Review

dent capabilities of this technology will likely result Hypertext:A Brief Introduction in the widespread availability of clinical, research, and educational resources on the Internet. This paper The WWW is essentially a network-based, distributed provides an overview of the history and technology hypertext system. Initially envisioned by Bush,’ fur- of the WWW, describes a number of existing biomed- ther described by Engelbart,2 and defined by Nel- ical WWW servers, and discusses future medical ap- son,l the conceptual model underlying computer-me- plications of this important technology. In addition, diated hypertext in modern information systems is a we have included an appendix containing pointers simple one. Links to component objects or nodes to a variety of useful WWW resources and sites. (e.g., text, images, sound) are embedded in a given document or set of documents. These nodes may be linked to associated nodes to form a by way The Internet of a set of links. The logical extension of this model is that of a “meta-document” that would essentially The Internet, as we know it, was initially conceived be a hypermedia database of hypertext documents. by , an employee of the Rand Corporation. This model allows the user to easily navigate an ar- First published in a series of Rand reports in the early bitrary set of links between nodes in a document or 196Os, Baran’s ideas would become realized with the database based on the user’s information needs rather creation of the Advanced Research Projects Agency than the fixed data linkages defined in traditional Network (ARPANET) in 1968.is The introduction of systems. the Transmission Control Protocol/ In a definitive article on the subject, Conklin suggests (TCP/IP) in the early 1970s allowed for interopera- the following four broad applications for computer- bility between heterogeneous computer systems, end- based hypertext systems,‘O and potentially WWW, to-end communication across a multitude of diverse which are relevant to medical practice and medical networks, and robust, automatic handling of data informatics: link failures. The original aim of the ARPANET was to provide n macru literary stystems: systems and technology that remote access to distant computers, remote file shar- ” I ing, and the expansion of research support large on-line with computer me- through resource sharing. The ARPANET was dis- diated interdocument links (for example, network- solved in 1990, having evolved into the Internet, a oriented , reading, criticism, and collab- collection of interconnected networks that span the oration in document creation). globe. The Internet has become the fastest-growing problem exploration systems: tools to support early electronic network in the world. Current growth unstructured thinking on a given problem (for ex- rates are estimated at 10% per month, with network ample, early authoring, outlining, problem solv- traffic doubling annually.‘j7 TCP/IP, the principal ing, programming, and design). communications protocol of the Internet, has been widely accepted. Until recently, the U.S. portion of structured browsing systems: small-scale teaching, the Internet was funded, in part, by the federal gov- reference, and public information systems similar ernment. The National Information Infrastructure (NII) in design and function to macro literary systems. initiative sponsored by the federal government has In these systems, ease of use is a critical design redefined this funding model and replaced it with component. private-sector investment and network management. n general hypertext systems: general-purpose systems A significant recent development has been the wide- for reading, writing, , etc., designed spread adoption of the WWW,68 and, especially, a to allow experimentation with a range of hypertext number of easy-to-use browsers, which offers a graphic applications. to the Internet. This paper focuses on the WWW and its potential in clinical information Macro literary systems were among the first attempts dissemination and retrieval. For a more general treat- at computer-based hypertext systems. Bush’s vision- ment of the Internet and its application in medicine, ary concept of the “memex,“’ a /model for the reader may wish to consult a number of recent browsing and note creation in an environment of papers on the subject. 3~* WWW technology, based extensive on-line text and graphics, was the under- in part on the hypertext concept, may be a significant lying impetus for these systems. catalyst in the transformation of the Internet from a research tool to a true global information network. Among the major efforts in this include the work of Engelbart, the creator of the mouse, and his TheWorld Wide Web NLS/AUGMENT system’; Nelson and the Xanadu project”; and Trig,” credited with having written the In its mature form, Nelson saw the Xanadu project first PhD thesis on hypertext, and his TEXTNET sys- as a global literary system, with its vast “docuverse,” tem in which documents were organized as “primi- as the key to widely distributed access to and sharing tive pieces of text connected with typed links to form of information. In many respects, Nelson’s vision a network similar in many ways to a semantic net.” may be close to realization in the maturation of the hypertext model within the emerging WWW. Problem exploration systems are interactive systems de- signed to aid in the , filtering, and pre- The WWW project was initiated in 1989, as an in- sentation of ideas for . The Issue- personal hypertext , at the Based Information System developed by Rittel and European Particle Physics Laboratory (CERN) in Ge- Webber” and structured browsing systems such as ZOG” neva, Switzerland. According to Berners-Lee, the and Knowledge Systems’ principal architect, and colleagues, the “World Wide System (KMS)’ developed by McCraken and Akscyn Web was developed to be a pool of knowl- at Carnegie Mellon University were among the ear- edge, which would allow collaborators in remote sites liest and best-known hypertext of to their ideas and all aspects of a common this type. project.” I” Xerox PARC, with their NoteCards” product, is cred- Much of the present development of the WWW proj- ited with the earliest commercial of ect and related technology is actively supported by a general hypertext system. NoteCards was designed as the World Wide Web Consortium (W3C) and the an information analyst’s support tool. The aim of this Internet Task Force (IETF). The W3C, research effort was the development of a technology formed by CERN, the French National Institute for that would facilitate the formation and expression of Research in Computers and Automation (INRIA), and conceptual models and analyses. Many of the ideas the Massachusetts Institute of Technology (MIT), ex- behind the implementation of NoteCards have been ists to promote the development of common stan- used in later hypertext software packages. dards for the WWW and serve as a repository of related data, information, and software applica- Since Bush’s introduction of the conceptual foun- tions.“” The 1ETF is a forum for researchers, network dations of hypertext, technology and implementa- designers, and vendors to identify and propose so- tion, in his landmark 1945 article, “As We May lutions to operational or technical problems related Think,” I there has been increasing interest in both to the Internet.?’ the implementation and the practical application of hypertext. While the conceptual model supporting The WWW initiative was developed with a - hypertext has been extant for some time, Conklin - architecture as its de- suggests that the recent explosion of interest in hy- livery mechanism. The assumptions of the project pertext has been fueled by the general acceptance of were: the computer, especially the PC, as an idea-, word-, and -processing tool as well as an interper- sonal communication device. I” 1. The idea of a “boundless” information space in which all items have a referent that aids directly As an , hypertext is a curious in the item’s retrieval. hybrid that traverses a number of traditional com- puter science boundaries. First, hypertext is a data- 2. An addressing system, the Uniform Resource base methodology that offers a new and different Identifier (URl), created and implemented to make way of accessing data that is a radical departure from this space possible regardless of the underlying more traditional approaches. In addition, hypertext protocol necessary for transport or communica- is a representation scheme, similar in form to a se- tions. mantic network combining informally arranged tex- 3. A network communications protocol, the Hyper- tual material with formal, mechanized operations and text Transfer Protocol (HTTP), to provide network processes. Hypertext is also an interface modality performance and services for WWW servers. featuring linked objects (e.g., icons, images, and text) that are often embedded in a given document by the 4. The Hypertext (HTML), which user. The merging of these ideas with wide-area net- would be understood by every WWW client and working technology is the basis for development of used to transmit text, menus, and on-line help the WWW. information. 4 LOWE ET AL., World Wide Web Review

Table 1 n dicates that an electronic mail message is to be sent to a given electronic mail address. The mailto URL Some Common Default Values and Formats for is one of the URL schemes that does not use the CISS Each Uniform Resource Locator (URL) Scheme format. It is important to note, that, at present, a Protocol* URL Format number of WWW browsers (such as ) do not FTP ftp:(/user:password@host:port/path support the mailto URL. HTTP http://host:port/path?searchpart gopher://host:port.path telnet://user:password@host:port Hypertext Transfer Protocol Mailto user_name@host File file://host/path HTTP is the client-server unique to the WWW and was designed to be the *FTP = Protocol; HTTP = Hypertext Transfer Pro- toco1. communication for the transfer of information between the WWW client and the server.62 HTTP is a simple request-response protocol allowing for 5. A collection of documents and an associated body communication between the WWW client and a given of data, available on the Internet, that would em- HTTP server. One HTTP server can serve information ploy these elements. to a multitude of clients. HTTP provides the user with an efficient means to traverse the WWW and Uniform Resource Identifier retrieve data objects or items relatively quickly and from disparate servers. The idea of the WWW is predicated on the concept of a “boundless” information space populated by a HTTP 0.9 was initially implemented in 1991. HTTP/ collection of data objects linked via a communication 1.0 is in the draft stage as an Internet standard. All protocol. The URI, as defined in the IETF specifica- HTTP messages incorporate the Multipurpose Inter- tion document RFC-1630, is a convention that is used net Mail Extension (MIME) standard for the identi- to identify the “registered name spaces and ad- fication and transfer of data in a variety of formats dresses” of a given resource object (documents, im- as defined in the RFC 1341.37 Plain-text, hypertext, ages, etc.) on the Web. image, audio, and video data can be transferred using this protocol. At present, two forms of URIS exist: the Uniform Resource Locator (URL) and the Uniform Resource HTTP is a that limits a given client Name (URN). The more commonly used URL is a to one request per connection. In the stateless model, form of URI that, through the use of an addressing a client connects to the server, makes a request, re- protocol, provides an access method for retrieving a ceives a response, and disconnects. There is no re- given resource on the WWW. For example, one could cord of multiple transactions inherent in the protocol. use the (FTP) to retrieve a file An analogous view of this model would be the con- from a WWW server. The URN is an evolving schema trast between sending a and making a tele- for naming resources that may be used to map a phone call. In this instance, the call would specific name to one or more resources.62 be connection-oriented, requiring a physical “con- nection” (i.e., an open line) between the caller and have been in use on the WWW since 1990 and the called party. However, in the case of a letter, went on the Internet standards track (RFC 1738) in once it is mailed, the connection is complete. The 1994.40 The syntax of the URL follows the Common stateless protocol promotes efficient use of server re- Internet Scheme Syntax (CISS) and is as follows: sources. In this model, the server uses its resources :///. For example, for a limited time and only when requested. the URL for the home page of the University of Pitts- burgh Section of Medical Informatics WWW server is: http://www.smi.med.pitt.edul/welcome.html. In this case, Hypertext Markup Language http is the access protocol, www.smi.med.pitt.edu re- HTML is a simple markup language used to create fers to the host, and welcome. refers to the host hypertext documents that can be viewed on a variety directory path to the servers home page. of computing platforms. A markup language is de- In its present form, the URL provides the actual lo- signed to represent the data structures of a given cation of a given link. Every WWW resource page document (e.g., title, headings) for storage, pro- has a unique URL. As can be seen in Table 1, URLs cessing, and transmission. One of the increasing support protocols other than HTTP on the WWW numbers of Document Type Definitions (DTDs) of (e.g., FTP, Gopher, HTTP). The “mailto” URL in- the International ’s Standard Journal of the American Medical Informatics Association Volume 3 Number 1 Jan / Feb 1996 5

Generalized Markup Language“’ (SGML), HTML pendent (based on Postscript Level 2) al- conforms to SGML through the use of structural ele- lows one to compose complex page layouts of text ments such as headings, lists, buttons, and embed- and graphics and then capture them in a PDF file, ded images. In an HTML document, these elements which is then referenced in an HTML document. PDF are combined to present the document in a form that readers, such as Adobe Acrobat Reader, are freely can be read by any WWW client application. available for most major computer platforms and pro- vide PDF display capability to WWW clients. PDF HTML has been the principal language of the WWW applications such as Adobes’s Acrobat allow one to since 1990 and is primarily responsible for the ap- compose complex documents, using a variety of styles pearance of WWW data to the user. HTML has gone and formats, in a sophisticated graphic WYSIWYG through two revisions since 1990. HTML 2.0 was an (What You See Is What You Get) editing environment upgrade of the formal standard that added new fea- and then save that document as a WWW-publishable tures such as figures, tables, and forms in 1994. HTML PDF file. PDF documents support embedded hyper- 3.0 is expected to become an Internet standard in text and WWW URL links. The Centers for Disease 1996 and will support the use of style sheets and Control and Prevention (CDC) now makes its Mor- handle text flow around figures, math equations, cus- bidity and Mortality Weekly Report (MMWR) and other tom lists, and tables. As expressed by Dan-Connolly documents freely available in PDF format on its WWW of the W3C, “HTML 3.0 offers expressive capabilities server.” similar to those provided in word processing pro- grams.“28 The cross-platform capability of the WWW applies not only to text but also to still images, , HTML markup can represent hypertext , mail, and sound. This platform-independent documentation and hypermedia; menus of options; delivery is achieved by the use of standard multi- database query results; simple structured documents media data formats (such as GIF and JPEGIh for still with in-lined graphics; and hypertext views of exist- images, Quicktime and MPEG” for digital video, and ing bodies of information. As mentioned earlier, HTML AIFF for sound) referenced within HTML docu- is a MIME Content Type (RFC 1521) and has been ments. These multimedia data types are presented designed to be a simple format for providing linked “in-line” by the WWW client software or are for- information.“” warded to external “helper applications” on the user’s machine. For example, a WWW client such as the Augmenting the WWW National Center for Supercomputing Applications’ The early and enthusiastic acceptance of WWW tech- (NCSA’s) Mosaic7Y will download an MPEG digital nology is due to a number of factors. Perhaps the video file from a WWW server to the user’s computer most important is that the WWW provides an inex- and then automatically invoke an external “helper” pensive, widely available, and easy-to-implement application to display the MPEG-encoded video in universal client-server pardigm that supports the an external window. The use of “helper applications” widespread distribution of hypertext documents. In is likely to decrease as WWW clients begin to handle the past, building Internet-based information sys- standard multimedia formats internally. This may be tems was a complex in which developers had achieved by the integration of proprietary “media to create client applications for multiple platforms. viewers” into the WWW client software. This inte- The WWW provides an elegant solution to this prob- gration may also have the effect of standardizing the lem in that Web clients capable of interpreting stan- multimedia formats used on the WWW to a small set dard HTML documents are available on a wide range of core formats. The display of composed multimedia of platforms. In order to create a cross-platform, In- documents or complete multimedia presentations on ternet-based information system, the developer need the WWW will also be supported by the inclusion of only set up a WWW server on his or her platform of proprietary “player engines“ within WWW clients. choice and using standard HTML be assured that For example, in June 1995 the Corporation users on all major platforms will be able to access (Mountain View, CA) and Macromedia Inc. (San the server. Francisco, CA) agreed to integrate Macromedia’s Di- rector multimedia playback software into the Net- The success of the WWW has spawned a series of scape Navigator WWW browser, thus allowing WWW software-based enhancements to HTML and HTTP. access to sophisticated multimedia documents cre- While HTML offers a rich set of cross-platform text ated with Macromedia’s Director software. formatting features, many WWW publishers are be- ginning to use the Portable Document Format (PDF)“” An interesting extension to the idea of downloading developed by Adobe Software. This platform-inde- multimedia data from WWW server to client is the LOWE ET AL., World Wide Web Review

WWW Client WWW Server CGI Application External Database

F i 9 II r I? 1 Relationship of the World Wide Web (WWW) server to Macintosh National Center for Supercomputing Ap- plications (NCSA) Common Gateway Interface (CGI) application. HTML = Hypertext Markup Language.

dynamic transfer of computer “bytecode” (computer cess. The CGI standard has contributed to the success code running on a ) to augment the of the WWW by providing developers with the ca- functionality of WWW clients. This approach is being pability to expand the functionality of HTTP and by pioneered by Sun Microsystems “Java”60 software, providing a mechanism for piping data between the which uses embedded systems technology to include WWW server and external applications. software modules (called “Applets”) in HTML pages. NCSA has also developed an experimental Common An applet is a program, written in the Java language, Client Interface (CCI) that allows external applica- that can be referenced in an HTML page, much like tions to communicate with the NCSA Mosaic client an image can be included. When one views a page via TCP/IP. Applications can use Mosaic to fetch URLs that contains an applet, the applet’s code is trans- or ask Mosaic to report the URLs selected by the ferred to the client computer and executed. This tech- user. Applications written to support CC1 can trans- nology has considerable potential for enhancing the fer data from the WWW to the local program space, functionality of WWW client applications to support essentially turning the client program into a potential features such as real-time animation image process- WWW browser itself. Currently (November 1995), ing, interactive simulation, and data analysis. The only NCSA Mosaic for X supports CCI. Netscape Corporation recently licensed Sun’s Java technology and will include it in Netscape WWW An alternative approach to augmenting WWW clients browsers by the end of 1995. uses component-based software architectures such as OpenDoc. 48 Apple Computer recently announced its A more widely used method of augmenting the WWW intention to release CyberDog,” an Internet-based client-server model is the use of applications sup- application that will use the OpenDoc standard to porting the NCSA Common Gateway Interface (CGI) provide a general-purpose .Internet access tool for standard.“3 CGI allows external programs to interface which third-party developers can provide external with information servers such as WWW servers, For “parts” to handle tasks such as image manipulation, example, a CGI application can be used to support database access, and electronic mail. a WWW interface to an external database by trans- lating queries received from a WWW client into quer- Currently, WWW clients are limited to the display ies appropriate for the database. The CGI would then of two-dimensional text and graphics, but the emer- send this query to the database and convert the re- gence of VRML53 ( Modeling Lan- trieved data to HTML for transmission to the WWW guage) will provide a method for interactive explo- client. How CGI applications communicate with ex- ration of three-dimensional (3D) data over the Internet. ternal applications is platform-specific. For example, VRML is an open, platform-independent, file format on the Apple Macintosh platform, many CGIs use for 3D graphics on the Internet. Similar in concept AppleEvents to effect this communication (Fig. 1). to the Web standard HTML, VRML encodes com- puter-generated graphics into a compact format for CGIs can be written in a wide range of languages transmission over a network. As with HTML, a user such as Applescript, C, C + + , and . Some com- can view the contents of a file (in this case an inter- mon WWW tasks implemented by CGIs include pass- active 3D graphics file) as well as navigate to other word-restricted access to WEB pages, HTML forms VRML “worlds” or HTML pages. OpenInventor, a processing, sending electronic mail from within WWW widely accepted, object-oriented 3D graphics toolkit clients, and displaying on WWW server ac- developed by Silicon Graphics (Mountain View, CA), Journal of the American Medical Informatics Association Volume 3 Number 1 Jan / Feb 1996 7

provides the framework for VRML. This exciting able cost. The popularity of the Internet and the phe- technology will make it possible for users to interact nomenal growth of the WWW are bringing increased with data in a virtual, 3D . VRML may interest in ISDN and a corresponding growth in its also allow users to manipulate 3D data sets such as availability nationwide.“* magnetic resonance imaging and computed tomog- Extensions to WWW technology are intended to ad- raphy reconstructions via the WWW. dress both the needs of users and the perceived WWW servers can be created using inexpensive mi- shortcomings in the underlying technology. How- crocomputers and freely available server software. ever, as a commercial competition between vendors While direct Internet connections are desirable, ac-- increases, it is important to note that there is a po- ceptable performance can often be obtained using tential conflict between proprietary extensions and high-speed and conventional telephone lines the open standards process that has made the WWW to connect to a server using the Serial Line Interface a success. ProtocoP (SLIP), the Point-to-Point ProtocoP9 (PPP), or similar communications methods. In addition, In- tegrated Services Digital Network (ISDN), where it Data Security and the WWW is available, also offers an alternative to direct Inter- WWW development is being increasingly driven by net connections. the commercial sector. As more and more companies SLIP allows desktop PCs to perform do business on the Internet, the problems of imple- essentially as terminals using “serial ” menting secure financial transactions and ensuring for data communications. SLIP is a “packet-framing data protection assume an increasing importance. protocol” that allows computers to easily exchange Health care applications on the WWW that involve Internet Protocol (II’) packets, the basic data unit of confidential patient information must also contend the Internet. With a standard voice grade telephone with similar security issues and will probably inherit line, a , and SLIP software, any SLIP-enabled many of the solutions currently being defined for use desktop PC can connect to the Internet. in the business sector. A detailed discussion of In- ternet security is beyond the scope of this paper, and PPP was developed by the IETF and designed to we will limit our discussion to issues specific to the provide temporary links between local area networks www. (LANs) over telephone lines. PPP differs from SLIP in that it provides a method for the establishment, There are two major approaches to securing WWW configuration, and evaluation of serial linkages as information systems. The first strategy involves pro- we11 as encapsulating the data that travel over these tecting individual servers and network sites. For ex- links. In addition, PPP supports the establishment ample, many commercial WWW servers allow the and configuration of different network-layer proto- administrator to restrict connections from clients at cols, e.g., II’, IPX (, Orem, UT). PPP is rapidly specific IP addresses or domains. If one is setting up replacing SLIP and is becoming the de facto standard a WWW-based information system for use within a for serial-based Internet connections.2h specific institution or by users at predefined sites, this feature can be very helpful in excluding potential With a SLIP/PPP connection, one can open multiple intruders. ‘However, for WWW services open to all network connections or sessions on his or her desk- comers, this strategy is of limited utility. In general, top PC and perform multiple tasks. For example, one administrators usually rely on network perimeter se- can open an FTP window, download a file, read curity schemes such as firewalls31 (gateways con- news, Telnet to a remote host, and connect the WWW trolling data communications between local networks using freely available WWW browsing software. and the Internet) and user . ISDN offers the user relatively inexpensive “dialed Even if the WWW server is secure, the data trans- digital access” to the network mitted between server and clients using HTTP is not and the Internet; eliminating the need for leasing encrypted or protected in any way. Using freely expensive dedicated high-speed telephone lines. In available network software, unscrupulous individ- tandem with data transmission protocols such as PPP, uals could acquire and alter or eavesdrop on data well suited for ISDN because of its initial design as transmissions containing sensitive medical or finan- a method of communicating via point-to-point links cial information. The second major approach to en- over telephone networks, 38 ISDN and its services are suring WWW security therefore focuses on securing gaining increasing popularity with Internet users client-server transactions to prevent “data snoop- looking for direct Internet connectivity at a reason- ing,” ensure data integrity, and authenticate users. LOWE ET AL., World Wide Web Review

and is widely used to encrypt transmitted data and authenticate communications sessions over the In- ternet. The private key is a secret key similar to that used in symmetric cryptosystems. The public key is freely available to all. The RSA (RSA Data Security Inc.) and ElGamal are the two most widely F i g II r #? 2 A symmetric cryptosystem. used schemes used to implement public key-private key cryptosystems.25 RSA technology is used by both SSL and SHTTP systems to encrypt WWW documents and authenticate clients. These issues can be addressed by creating a secure data channel over which client-server communica- As SSL and SHTTP technologies are being integrated tion occurs and by securing the actual data that are into a commercially available toolkit for WWW de- transmitted. velopers, some of the original architects of the WWW, such as Tim Bemers-Lee, are working to create Shen,& The Secure Sockets Layer (SSL)42 system developed an alternative security scheme for the WWW. When by the Netscape Corporation is the leading secure- implemented, Shen will provide mechanisms for both channel technology. The principal WWW document authentication and data encryption. security scheme is the Secure Hypertext Transport Protocol (SHTTP)49 developed by CommerceNet, a Security will be a major issue in determining the nonprofit consortium that includes leading computer feasibility of WWW-based clinical information sys- and banking companies. Both SSL and SHTTP have tems. The emerging standard for secure channels and been submitted to the IETF as Internet Drafts. In early document encryption on the WWW should help pro- 1995, Terisa Systems (Menlo Park, CA) announced vide adequate protection for sensitive clinical infor- SecureWeb6i-a WWW security system that com- mation. When combined with the standard strategies bines both SSL and SHTTP into a platform-indepen- for ensuring the integrity of clinical information sys- dent WWW security toolkit. SHTTP provides security tems, these technologies will make the WWW a se- services for transaction confidentiality, authenticity/ cure platform for developing innovative biomedical integrity, and non-repudiability of origin50 applications. Both SSL and SHTTP rely heavily on encryption tech- Biomedical Applications of the WWW nology. The process of encryption involves the trans- formation of a normal data item (plaintext) into an Currently, one finds a diverse selection of medical incomprehensible data item (ciphertext). Decryption WWW servers. The most common type of server reverses this process to enable an authenticated (au- represents the activities of a particular institution or thorized) user to view the original data item or plain- group. For example, the Section of Medical Infor- text. There are presently two families of cryptosys- matics at the University of Pittsburgh maintains a terns in widespread use: symmetric (or private-key) WWW server5’ that contains information on its re- systems and public-key (asymmetric) systems. A full search activities and fellowship program. Federal discussion of the mathematics behind encryption in agencies such as the National Institutes of Health general or specific cryptosystems is beyond the scope (NIH), the National Cancer Institute”’ (NCI), and the of this paper. National Library of Medicine% (NLM) were early adopters of this technology to distribute information Symmetric cyrptosystems are distinguished by the related to patient care, research, and education. NCI’s fact that the same key is used for both encryption CancerNet provides access to the Physicians Data and decryption (Fig. 2). If two individuals or systems Query (PDQ) databasei and fact sheets on various wish to communicate securely (in this case, A and cancer topics. NLM’s HyperDoc WWW server59 con- B), they can use the same key to encrypt/decrypt each tains pointers to important resources related to AIDS, other’s messages. A problem with this scheme is that cancer, medical informatics, molecular biology, and if a third party acquires this key, then security is NLM’s Visible Human project.5” In addition, NLM’s compromised. Health Services/Technology Assessment Text (HSTAT) Asymmetric cryptosystems employ two different and WWW server contains the Agency for Health Care separate keys, a public key and a private key, for Policy and Research (AHCPR) Clinical Guidelines and encryption and decryption (Fig. 3). This scheme is NIH’s Consensus Development Conference - more secure than the single key symmetric system ments. Journal of the American Medical Informatics Association Volume 3 Number 1 Jan / Feb 1996 9

A number of WWW servers provide access to im- B’s Public key B’s Private key portant health information resources previ- ously available only in paper format. The CDCJh now offers a server containing its MMWR, including back issues and supplements. WWW-based, peer-re- viewed, medical journals are beginning to emerge. Examples include The Journal of Medical Imagin and The journal of . ENCRYPTION MODE A number of groups have developed WWW servers to support clinical decision support and education. A’s Private kev A’s Public kev One notable example is The Virtual Hospital (VH) initiative based at the University of Iowa. The VH site is a continuously updated medical multimedia database available 24 hours a day. The goal of this project is to provide patient care support and distance learning opportunities to practicing clinicians. “VH information may be used to answer patient care ques- AUTHENTICATION MODE tions, thus putting the latest medical information at physicians’ fingertips. This same information may be F i g U r I? 3 A public-key cryptosystem. used for Continuing Medical Education (CME); de- livering CME to physicians’ offices and homes at a convenient time and location.“‘” The project uses NLM, uses the UMLS Metathesaurus to help a searcher WWW sotware to store, organize, and distribute mul- construct, execute, and refine MEDLINE queries. The timedia textbooks that incorporate features such as software includes an integrated Metathesaurus browser free-text searching, audio, video, and still images. that maps user terms through the UMLS Metathe- Many of the first biomedical WWW servers were es- saurus to MeSH headings. The current Internet sentially electronic document systems offering only Grateful Med prototype also supports direct links to basic navigational interactivity. However, HTTP/HTML the full text of the Clinical Practice Guidelines sup- now supports interactive documents containing fea- ported by the AHCPR-available from NLM on the tures such as sensitive image maps and standard Health Services/Technology Assessment Text (HSTAT) graphic user interface items such as buttons, scrolling World-Wide . Internet Grateful Med il- lists, tables, and pop-up menus. These features sup- lustrates how one can build powerful, easy-to-use, port an interactive, graphic, client-server paradigm cross-platform WWW interfaces to complex database in which a user can navigate through large biomed- systems. NLM is also developing a WWW interface ical multimedia databases using a familiar “point- to its UMLS Knowledge Source Server’# that provides and-click” metaphor. an easy-to-use interface for browsing the UMLS Metathesaurus. A more powerful feature of the current HTTP/HTML standard is the support of data entry “forms” that Using the “forms” capability of WWW servers, one allow the WWW server to accept user-entered data can take advantage of the WWW’s universal client- using standard GUI elements such as edit fields and server paradigm to offer widespread access to im- pop-up menus. Using CGI applications, these data portant biomedical databases without having to de- can then be recorded, by the WWW server, for later velop an Internet-based client-server system de novo. analysis, or more importantly, the data can be used For example, NLM’s On-line Images from the History to drive applications external to the WWW server of Medicine is a WWW-based system providing ac- such as databases or electronic mail programs. cess to nearly 60,000 images (reproducing photo- graphs, artwork, and printed texts) drawn from the A number of biomedical form-based applications are extensive (and much larger) collection of the History currently under development. NLM has developed of Medicine Division at NLM. a WWW-based system for assisted searching of MED- LINE and other MEDLARS databases. This software, As this CGI-based forms capability develops, one called Internet Grateful Med, is an evolution of the may anticipate that the WWW will become an im- Coach” system developed by NLM for use with portant mode of access to clinical information sys- Grateful Med.‘* The Internet Grateful Med Web server, tems. Currently, a number of WWW-based systems augmented by extensive additional code written at are under development. At Columbia-Presbyterian 10 LOWE ET AL., World Wide Web Review

Medical Center in New York, the Medical lnformatics traversing several hypertext links, the user may be- group are prototyping a WWW-based interface to come confused as to where he or she is in the doc- their clinical data and vocabulary servers..3D The AR- ument hierarchy. In addition, because WWW client TEMIS project47 at the University of West Virginia applications usually maintain a list of previously ac- will make clinical information available electronically cessed pages, which the user can return to using to remote providers via a WWW server and their standard WWW navigational controls, it may be dif- Web* software. A research group based at the Boston ficult to ensure that the user views only the most up- Children’s Hospital and MIT is working on a proj- to-date version of a document. For example, if the ect,44,72 funded by NLM and AHCPR, to develop a user views WWW page X containing a patient prob- WWW-based, multimedia interface to the electronic lem list and then modifies that list, resulting in a new medical record that supports customization for spe- WWW page Y, both page X and page Y remain in cific clinical environments and needs. At the Uni- the navigational hierarchy. There are both human versity of Pittsburgh, the Image Engine project,74,75 interface and server logic solutions to this type of funded by NLM’s High Performance Computing and problem, but they need to be addressed by each Communications (HPCC) program, is exploring ways WWW development project rather than by built-in of providing access to clinical images and associated server features. reports via a WWW interface to an object-oriented, client-server database system. Other clinical WWW Lifelong Learning and the WWW servers are under development at Massachusetts CME via the WWW is a development that offers General Hospitalz9 and Stanford.71 much promise. Martindale’s Health Science Guide,77 an The growing acceptance of the WWW and its under- important and innovative “Health science multime- lying protocols by the medical community suggest dia education and specialized information resource an increasing use of this technology in the clinical center, ” is now available on the WWW. Coauthored environment. In addition to the security concerns by Jim Martindale,7h Frank Potter,X’) and the discussed previously, there are a number of potential of Physical Sciences at the University of California at problems that must be solved by developers when lrvine,x’ the guide features a variety of “virtual cen- creating WWW information systems. As mentioned ters“ of medicine, dentistry, veterinary medicine, earlier, HTTP is a stateless client-server protocol in , nursing, public health, nutrition, and al- which a client connects to a server, makes a request, lied health. An evolving entity, the guide contains and then disconnects. While this reduces the load on more than 3,100 multimedia health science teaching the server side, it makes it difficult for the server to materials, 3,900 multimedia medical cases, one mul- maintain state information for a client-server ses- timedia CME course (Category l), 47 multimedia sion, which may consist of many connections/re- medical school courses/textbooks, 33 multimedia health quests. Many WWW developers have created pro- sciences-related graduate/undergraduate courses, and prietary solutions to this problem. A number of a growing number of multimedia images and movies commercial WWW servers (such as that sold by the that are health sciences-related. Netscape Corporation) now support extensions, called The Department of Pathology of the Uniformed Ser- “Cookies,“41 to handle this issue. Using this tech- vices University of the Health Sciences in Bethesda, nology, a server, when returning an HTTP object to Maryland, now offers Category 1 CME credits to phy- a client, may also send a piece of state information, sicians who work with its WWW-based surgical pa- which the client will store. Included in that state thology cases.58 object is a description of the range of URLs for which that state is valid. Any future HTTP requests made The Loyola University Medical Education Network by the client that fall in that range will include a (LUMEN)27 is a WWW-based medical education proj- transmittal of the current value of the state object ect at Loyola University in , Illinois. LUMEN from the client back to the server. This simple mech- aims to provide access to medical education resources anism provides a powerful’too! that enables a host using hypertext and the WWW. Basic goals of the of new types of applications to be written for Web- project include: 1) the integration of basic and clinical based environments. science curricular content; 2) access to medical infor- mation worldwide; and 3) the development of edu- While the hypertext paradigm built into the WWW cation hypermedia. is one of its greatest assets, it also makes develop- ment of WWW-based clinical information systems The goal of University of Chicago’s Phoenix Project2” more difficult because of the limited navigational aids is to develop an integrated academic information sys- and restraints built into most WWW browsers. After tem that will provide full Internet connectivity and Journal of the American Medical lnformatics Association Volume 3 Number 1 Jan / Feb 1996 11

distributed hypermedia-authoring capability to the oncology, radiation oncology, medical oncology, sur- biologic sciences community at the university. One gical oncology, medical physics, and human services, program developed through this project is Case Stud- as well as their patients. Over time, patients and ies in Environmental Medicine, a self-instructional other users began to suggest a more disease-oriented unit on hazardous substances in the environment. approach. As a result, OncoLink now functions as a major WWW resource for oncology and patient-ori- The CliniWeb Project7 at Oregon Health Sciences ented cancer information. University is developing a WWW-based system for providing quick and easy access to biomedical infor- The WWW can potentially support consistent and mation on the WWW using NLM’s MeSH vocabulary effective health and diesease prevention (currently only the Disease Hierarchy is used) to clas- strategies to both the health care provider and the sify information. This approach may improve infor- patient. The existence of easily accessible clinical and mation retrieval by allowing the user to search for patient information resources on the WWW will likely WWW-based information using a controlled, bio- change the traditional clinician-patient relationship medical vocabulary. as both parties use these resources to educate and inform themselves and each other about diagnosis, The WWW and Decision Support therapy, and prognosis. Until recently, most clincians and other health professionals used computers primarily as a research Conclusion tool in the retrieval of bibliographic citations to ar- ticles published in the medical literature.= The WWW, The WWW is an important, evolving informatics by providing easy access to a wide variety of medical technology that may have a significant impact on information resources, may dramatically change the biomedicine by dramatically improving the ease with way health providers use computer and networking which we distribute and access information via the technology in patient care. Projects such as the VH, Internet. The success to date of the WWW may be Martindale’s Health Science Guide, and the LUMEN attributed in large part to its ease of use, its platform- project suggest the advent of the “ubiquitous orga- independent client-server software, the wide avail- nization.‘121 In this case, the ubiquitous organization ability of inexpensive WWW browser applications, would be a digital representation of much of the and its support of distributed hypertext and multi- information and services available in a physical or- media. Use of the WWW for financial transactions ganization. Essentially, the ubiquitous organization has resulted in the development of a number of tech- amplifies and extends the power and reach of the nologies designed to make Internet-based commu- physical organization through time and space. These nication secure. These encryption-based technologies projects represent an emerging electronic extension will facilitate the creation of secure wide-area access of the medical center with broad applications in areas to clinical information systems via the Internet. The such as telemedicine, rural health care delivery, and WWW represents a first, promising, step toward a community medicine. global information network that may radically alter the way we retrieve and use information in the prac- In the medical decision-making process, the clinician tice of medicine. must often assess information available in local and remote databases. In a health care environment that may be increasingly dominated by a reliance on pri- mary care, especially in rural and other medically Referencesn underserved areas, the WWW offers much promise (Sorted Chronologically by Year and in both the dissemination and the retrieval of medical Alphabetically by First Author information. “These solo practices are potentially a within Each Year) direct source of information concerning the profile of health and disease in the community as well as the 1945 variety of treatment and prevention activities being 1. Bush V. . Atlantic Monthly. 1945 Ju1;176(1): undertaken and the effectiveness of these activi- 101-8. ties.“2” 1963 One example of WWW-based clinical decision sup- 2. Engelbart DC. A conceptual framework for the augmentation port is the University of Pennsylvania’s OncoLink2” of man’s intellect. In: Howerton PD, Weeks DC, eds. Vistas WWW project. OncoLink was initially designed to in Information Handling, Volume 1. Washington, DC: Spartan service the information needs of clinicians in pediatric , 1963:1-29. 12 LOWE ET AL., World Wide Web Review

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49. http://www.commerce.net/cgi-bin/textit?/information/stan- American Medical Informatics Association Spring Congress, dards/drafts/shttp.txt 1995;87. 50. http://www.commerce.net/information/standards/drafts/shttp.b 72. Kohane 1, Greenspun I’, Fackler J, Cimino C, Szolovits I’. W3- 51. http://www.crawford.com/cdc/mmwr/mmwr.html EMRS: Access to Multi-Institutional Electronic Medical Rec- 52. http://www.nci.nih.gov/ ords via the World Wide Web [abstract]. Cambridge, MA: 53. http://www.ncsa.uiuc.edu/General/VRML/VRMLHome.html American Medical Informatics Association Spring Congress, 54. http://www.nlm.nih.gov/ 1995;86. 55. http://www.nlm.nih.gov/extramural_research.dir/visi- 73. @vh.radiology.uiowa.edu (About the Virtual Hospi- ble_human. html tal: http://indy.radiology.uiowa.edu/AboutVH.html) 56. http://www.nlm.nih.gov/hmd.dir/oli.dir/index.html 74. Lowe HJ, Buchanan B, Cooper GF, Vries J. Building a medical 57. http://www.ohsu.edu/cliniweb database system to integrate clinical information: an applica- 58. http://wwwpath.usuf2.usuhs.mil/ tion of high performance computing and communications 59. http://www.smi.med.pitt.edu/ technology. Bull Med Libr Assoc. 1995;83(1):57-63. 60. http://www.sun.com:80/sunworldonline/swol-07-1995/swol-07- 75. Lowe HJ, Walker WK, Vries JK. Using Agent-Based Technol- java. html ogy to Create a Cost-Effective, Integrated Multimedia View of 61. http://www.terisa.com/prod/prod.html the Electronic Medical Record Proceedings. Washington, DC: 62. http://www.w3.org/hypertext/WWW/Addressing/Address- Symposium on Computer Applications in Medical Care, 1995. ing html 76. Martindale J. Author’s Page. http://www-sci.lib.uci.edu/-mar- 63. http://www.w3.org/hypertext/WWWlConsortium/ tindale/Author.html 64. http://www.w3.org/hypertext/WWW/Protocols/HTTP/ 77. Martindale J. Martindale’s Health Sciences Guide. http://www- HTTP2. html sci.lib.uci.edu/-martindale/HSGuide.html 65. http://www.w3.org/hypertext/WWW/Shen/ref/secu- 78. McCray AT, Razi A. The UMLS Knowledge SourceServer. rity_spec.html MEDINFO 95 Proceedings. (Greenes RA, ed.):144-147. 66. http://www.ziff.com/-macuser/mu_0895/news2.html 79. McKinney WP, Wagner JM, Bunton G, Kirk LM. A guide to 67. The . Traffic on the NSFNet Backbone [slide]. Mosaic and the World Wide Web for physicians. MD Comput. Reston, VA: The Internet Society, March 1995. 1995;12:109-14, 141. 68. The Internet Society. WWW Server Growth. Reston, VA: The 80. Potter F. Author’s Page. http://www-sci.lib.uci.edu/SEP/-Ico- Internet Society, March 1995. sahedron.html 69. J Computat Biol. http://www 81. School of Physica! Sciences. http://www.cwis.uci.edu/ 70. J Med Imaging. http://www PhySci.html (Irvine, CA: University of California, 1995). 71. Kahn CE, Bell DS. Webstar: Platform-Independent Structured 82. Zelingher, J. Exploring the Internet. MD Comput. 1995;12:100- Reporting using Word Wide Web Technology [abstract]. 8.

APPENDIX

A Review of Medical Applications and the World Wide Web-An Emerging Health Care lnformafion Management Model: Selecfed WWW Servers Active as of 9/l/95

I. WWW Servers to Begin Internet Exploration 4. A Beginner’s Guide to HTML 1. CMC Information Resources http://www.ncsa.uiuc.edu/demoweb/html-primer.html http://www.rpi.edu/Internet/Guides/decemj/icmc/ 5. HTML Editors toc3.html http://akebono.stanford.edu/yahoo/Computers/ 2. WWW Search Engines World_Wide_Web/HTML_Editors http://web66.coled.umn.edu/WWWinfo/ meta-index. html III. URLs for Locating WWW Client Software 3. WWW FAQ 1. Netscape-A multiplatform WWW Browser http://sunsite.unc.edu/boutell/faq/www_faq.htmI http://home.mcom.com/home/welcome.html 4. WWW Project History ftp://ftp.mcom.com/netscape/ http://monge.univ-mlv.fr/History.html 2. Mosaic-The Best-known WWW Browser 5. The Whole Internet Catalog http://www. ncsa.uiuc.edu/SDG/Software/Mosaic/Docs/ http://gnn.com/wic/index.html help-about. html n MAC: ftp://ftp.ncsa.uiuc.edu/MAc/Mosaic/ II. URLs for WWW Development n PC Windows: ftp://ftp.ncsa.uiuc.edu/Mosaic/ 1. WWW Development Windows http://www.charm.net/-web/Vlib.html n X Windows: ftp://ftp.ncsa.uiuc.edul/Mosaic/Unix/ 2. A Beginner’s Guide to URLs 3. MacWeb-A full-featured Macintosh WWW Browser http://www.ncsa.uiuc.edu/demoweb/url-primer.html http://galaxy.einet.net/EINet/MacWeb/ 3. WWW Names and Addresses, URIS, URLs, URNS MacWebHome. html http://www.w3.org/hypertext/WWW/Addressing/ ftp://ftp.einet.net/einet/mac/macweb Addressing. html 4. -An ASCII Terminal WWW Browser 14 LOWE ET AL., World Wide Web Review

tp://ftp2.cc.ukans.edu/pub/lynx/ 11. Medical Illustrators’ Home Page 5. Emacs-An Emacs Subsystem Providing a Means to http://siesta.packet.net/med_illustrator/ Browse the WWW That Runs under UNIX Welcome.html http://www.sinica.edu. tw/simtel/ 12. ANCPR Clinical Guidelines simtel_index_freemacs.html http://text.nlm.nih.gov/ahcpr/ahcprc.html ftp://ftp.uu.net/systems/gnu/xemacs/ 13. CancerNet http://biomed.nus.sg/Cancer/welcome.html IV. URLs for Locating WWW Server Software 14. Clinical Preventive Services Guidelines 1. CERN-The Original WWW Server http://text.nlm.nih.gov/cps/www/cps.html http://www.w3.org/hypertext/WWW/Daemon/ 15. HIV/AIDS Database Status.html http://text.nlm.nih.gov/atis/list.html 2. MacHttp-A WWW Server for the Macintosh 16. Medical Sciences Bulletin http://mijuno.larc.nasa.gov/MHI/MacHTTPinfo.html http://pharminfo.com/pubs/msb/ 3. Http for Windows/NT-A WWW Server for Windows/ msbmnu.html#msb_contents NT 17. Virtual Library: Biosciences-Medicine http://info.cern.ch/hypertext/WWWIHTTPS/ http://golgi.harvard.edu/biopages/medicine.html Status.html 18. MSDS Healthcare Standards Home Page 4. NCSA-A WWW Server for Files That Runs under http://dumccss.mc.duke.edu:/ftp/standards.html UNIX 19. National Cancer Institute Home Page http://info.cern.ch/hypertext/WWW/NCSA-httpd/ http://www.NCI.NIH.gov// Overview. html 20. Yahoo: Health: Medicine 5. SerWeb-A WWW Server That Runs under Windows http://akebono.stanford.edu/yahoo/HeaIth/Medicine/ 3.1 21. Pharmaceutical Information Network Home Page http://riskweb.bus.utexas.edu/www.htm http://pharminfo.com/pin_hp.html 6. Netscape-A Multiplatform WWW Browser 22. U.S. Department of Health and Human Services http://home.mcom.com/ http://www.os.,dhhs.gov/ ftp://ftp.mcom.com/netscape/

V. Medical WWW Servers 1. Martindale’s Health Science Guide-‘95 VI. Medical Informatics Selected WWW Servers http://www-sci.lib.uci.edu/-martindale/HSGuide. html 1. American Medical Informatics Association 2. The Department of Pathology of the Uniformed Ser- http://amia2.amia.org/ vices of the Health Sciences 2. CAMIS (Stanford) http://wwwpath.usuf2.usuhs.mil/default.html http://camis.stanford.edu/ 3. The Virtual Hospital 3. Columbia Medical Informatics http://vh.radiology.uiowa.edu/ http://www.cpmc.columbia.edu/“ADD_DATE 4. Morbidity & Mortality Weekly Report 4. Decision Systems Group (Harvard) http://www.crawford.com/cdc/mmwr/mmwr.html http://dsg.harvard.edu/ 5. Hospital Web 5. Duke Medical Informatics http://demOnmac.mgh.harvard.edu/hospital http://dmi-www.mc.duke.edu/default.htm web. html 6. MGH Laboratory of Computer Science (Harvard) 6. PDQ NC1 Gopher http://lcs-guide.mgh.harvard.edu/ gopher://gopher.nih.gov:70/11/clin/cancernet/pdqinfo 7. National Library of Medicine 7. The Virtual Medical Center http://www.nlm.nih.gov/ http://www-sci.lib.uci.edu/-martindale/ 8. OHSU Medical Informatics Medical.html http://www.ohsu.edu/ 8. OncoLink (Penn) 9. University of Pittsburgh Section of Medical Informatics http://cancer.med.upenn.edu:80/ http://kappa.smi.med.pitt.edu/welcome.html 9. LUMEN Home Page: Loyola University Medical Edu- 10. Department of Medical Informatics cation Center http://www.medlib.med.utah.edu/medinfo/main.html http://scuba.meddean.luc.edu:80/lumen/ 11. Vanderbilt Division of Biomedical Informatics 10. Image Engine WWW Server http://vumclib.mc.vanderbilt.edu/dbmi/ http://dublin.smi.med.pitt.edu/ImageEngine/ 12. Yale Center for Medical Informatics ImageEngine.html http://paella.med.yale.edu/