Abbott Laboratories Fights a Winning Battle Against Deadly Disease Using StereoGraphics CrystalEyes
Since the first documented case of AIDS and HIV, the world has been looking to the scientific community to provide aggressive treatments for the deadly disease. This effort has been a major global concern for over a decade and a half. Today, new aggressive treatments developed by Abbott Laboratories have turned the tide on HIV, allowing those with this affliction to treat it more effectively. Though not a cure, treatments developed by Abbott, such as the HIV protease inhibitor Ritonovir (Norvir™), have given many patients new hope.
Abbott research scientists’ race against time to develop these treatments was aided significantly by the ability to design drugs in a digital environment using StereoGraphics’ CrystalEyes or Projector Z-Screen stereoscopic visualization.
Abbott Labs uses CrystalEyes at each workstation and Projector Z-Screen in their conference room to visualize the complex, multidimensional nature of drug and protein interaction. This allows Abbott to quickly evaluate the potential of a given substance for use as a drug treatment, eliminate ineffective treatments, and concentrate on those with the most promise.
The company’s efforts in pharmaceutical research focus on infectious and immunologic disease, neurological disease, metabolic disease, urological disease and cancer. It’s cadre of drug treatments, including those for HIV, have been heralded by medical professionals worldwide. Today, Abbott Labs is working on its next-generation HIV treatment and the follow-up to Norvir, known simply by its code name ABT378.
Seeing is Believing
Abbott Labs is a pioneer in the use of stereovision technology in the pursuit of more powerful treatments. The company began using stereoscopic visualization products nearly a dozen years ago and currently employs approximately 20 CrystalEyes-equipped workstations. Nearly 30 researchers work with stereo imaging on a regular basis using Silicon Graphics Indigo2 Impact and Extreme workstations running X-PLOR and QUANTA™ molecular modeling software from Molecular Simulations Inc. In addition, Abbott scientists have a conference room outfitted with a high-powered Electrohome CRT projector outfitted with a StereoGraphics Projector Z-Screen for collaborating on the development of drug molecules.
The Abbott researchers use stereo imaging to look for ligands. Ligands are molecules being tested as potential drug treatments. The interaction between ligands and a wide variety of compounds is modeled on-screen to determine the ligand’s potential. The very nature of these interactions is highly dynamic and complex—so complex that they are nearly impossible to understand and interpret using a flat 2D view. This is the main reason Abbott labs uses stereo viewing as a standard element of their research efforts.
Stereoscopic Viewing - How CrystalEyes and Z-Screen products work
Stereoscopic viewing has long been a useful technique for many professionals dealing with complex, multidimensional data sets. By seeing images in a realistic 3D environment, these professionals can visualize problems and analyze information more quickly and effectively. Common applications for stereoscopic viewing include molecular modeling, mechanical design, mapping, medical imaging and simulation.
The effect of three-dimensionality is a combination of what the human eye sees and the brain process. The distance between human eyes results in each eye seeing an image from a slightly different perspective. The brain interprets information from these two perspectives to create the perception of three dimensions—an effect known as stereopsis.
CrystalEyes relies on the same stereoscopic principle. The product works with the user’s computer display and software to separate left-eye and right-eye-specific images using liquid crystal shutters. These shutters operate in sequence with the independent left/right-eye views to create the illusion that on-screen objects have depth and presence in three dimensional space.
An emitter transmits synchronized pulses of infrared signals that are received by CrystalEyes eyewear, which employ liquid crystal shuttering lenses. The lenses continuously transmit separate images to the left and right eyes, creating the illusion that computer- or video-based objects have depth, perspective, and presence in three-dimensional space.
Projector Z-Screen works in a similar fashion. However, instead of employing active shuttering eyewear, the Z-Screen is a CRT projector overlay that alternately polarizes left and right images. The user wears polarized glasses that transmit the correct image to each eye while filtering out the incorrect one. The effect is the same as CrystalEyes and the user sees a crisp, high-definition stereoscopic image.
Alternately displaying left- and right-eye perspectives on a standard workstation monitor solves a major problem of the past—true control of the Z-axis necessary for displaying realistic 3D images. For remote manipulation and viewing of objects, stereo 3D gives the user control, along all axes including the z-axis, or depth, of changes made to a structure on the screen.
The Drug Discovery Cycle
Abbott describes their process as interactive structure-based drug design. The process is carried out as follows:
Abbott researchers begin with a molecule that they believe will bind to a protein they are trying to affect. Crystals are grown from the protein and x-ray crystallography is used to determine the molecular structure of the protein. This structure is captured using highly sensitive CCD detectors and are converted to digital format using Molecular Simulation Inc.’s X-PLOR and QUANTA™ software.
Once protein and drug molecules are modeled, Abbott scientists can observe these molecules, see how they interact and determine how to make drug molecules more effective. What the scientists are looking for is a pocket in the protein molecule that isn’t already occupied. They will use this pocket to dock a drug compound and a protein together and test the reaction.
However, the drug design process isn’t quite that simple. These pockets are complex, and drug compounds must fit exactly for them to work. The size of the pocket, which atoms make up the pocket, whether the pocket is negatively or positively charged and myriad other factors must be taken into account. Abbott scientists describe this process as finding an odd-size glove and then designing the perfect hand to fit inside.
The interactive element of drug design occurs once a drug compound is tested in a digital environment. The tests are evaluated and the compound is modified and tested again several times before a ligand is chosen for the next step.
The new ligand is then produced in a lab and tested for effectiveness. Then, more crystals are grown, X-ray crystallography is again conducted and new digital models are created for testing. With each step, increasingly effective compounds are created until a final ligand is produced—one which ultimately will go through FDA testing and be released on the market.
Norvir is a key example of how using stereoscopic visualization as part of the interactive drug design process has major impact. Norvir is a protease inhibitor, which is a new class of drug with different behavior than previously available antiretroviral treatments for HIV. Protease inhibitors like Norvir block the action of the HIV protease, an enzyme involved in the final development of the virus. By blocking protease activity, Norvir prevents the production of infectious particles, thereby slowing HIV production.
Yet the development of protease inhibitor compounds has not stopped simply because Norvir has been so successful worldwide. By using the interactive, structure-based drug design process and stereoscopic visualization, Abbott has developed the next-generation HIV treatment. Known simply as ABT378, this new compound has tremendous potential. Without the ability to accurately visualize the complex interactions between these compounds and HIV, ABT378 would never have been developed.
Showing The World
At any given time, Abbott researchers may collaborate on molecular analysis during the design process. In addition, these scientists must periodically demonstrate their progress to others in the Abbott organization. Chemists, biologists, marketing professionals and senior management are all frequent guests of the research team’s visualization room to observe the latest findings.
Equipped with an Electrohome Marquis 8000 CRT projector and a StereoGraphics Projector Z-Screen, the Abbott visualization room can accommodate 20 guests wearing passive polarized glasses. Stereoscopic images shown on a 6’ x 8’ screen can be presented, discussed, evaluated and modified in real-time with input from anyone in the room.
The end result is a process for designing the most advanced drug treatments possible through the use of advanced science and visualization technology. Though nothing can replace the exceptional capabilities of Abbott scientists, the ability to see their work in stereoscopic 3D advances their skills immeasurably.