Analog SFF, September 2010

by Dell Magazine Authors

  A flash of bright light and searing heat cut me off. I felt a sudden jolt.

  Then blackness.

  And nausea. After a few moments, I realized nausea probably meant I was still alive. “Juanita?"

  "I'm here,” she said.

  The darkness was complete. And I was weightless. Maybe I was dead—although this wasn't how I'd pictured the afterlife.

  "What happened?” I asked.

  "I'll tell you what didn't happen: The energy shield didn't fail. The ablative shell didn't fail. We didn't die."

  "So what did happen?"

  Juanita let out a long, slow breath. “Best guess: Electromagnetic pulse wiped out all our electronics. The engine's dead, artificial gravity's gone, life support's gone, comm system's gone, everything's gone."

  "Any chance—"

  "No,” she said.

  "You didn't even let me finish—"

  "No chance of anything. It's not fixable, and even if it was, I haven't a clue how to fix any of those things even if it weren't totally dark in here. Do you?"

  "No."

  "And no help is coming from Sol Central because not only do they not know we're in trouble, but also we're in another star that could be halfway across the galaxy. When the air in here runs out, we die. It's that simple."

  "Oh.” I realized she was right. “Do you think maybe we succeeded in freeing Neuter Kimball?"

  "Maybe. But it didn't exactly look like Kimball was trying all that hard to escape."

  "Well,” I said, “maybe it was thinking about how Abinidi's martyrdom led one of the evil king's priests to repent and become a great prophet. Perhaps Neuter Kimball believed something similar would happen to one of the great swales who—"

  "Whatever Neuter Kimball believed,” she said, her voice acidic, “it was because you and your church filled its mind with fairy tales of martyrs."

  I bit back an angry reply. Part of me felt she was right. At the end, Neuter Kimball had seemed to embrace the role of martyr. Would it have done so if not for the stories about martyrs in the scriptures?

  And I had been willing enough to risk my life, but now that I was going to die, I found myself afraid.

  Juanita didn't seem to need a reply from me. “And what's the point of martyrs anyway? A truly powerful god could save his followers rather than let them die. Where's God now that you really need him? What good is any of this?"

  "Look, I'm sorry,” I said. “If it weren't for me, you'd be safe at home, and Neuter Kimball would be alive. I've made a mess of things."

  "Yes."

  Hours passed—floating in darkness, it was hard to tell how many. I spent it in introspection and prayer, detailing all my faults that had led me here. Biggest of all was pride: the idea that I, Harry Malan, would—through sheer force of will and a good speech—change a culture that had existed for billions of years. I thought back to what I had been told while serving as a nineteen-year-old missionary on Mars: You don't convert people; the Spirit of the Lord does that, and even then only if they are willing to be converted.

  Juanita spoke. “You were just trying to do what you thought was right. And you were trying to protect the rights of smaller swales. So I forgive you."

  "Thank you,” I said.

  The shuttle jolted.

  "What was that?” I asked. My body sank down into my seat.

  "It sounded—"

  An ear-splitting squeal from the right side of the shuttle drowned out the rest of her reply. I twisted my head around and saw sparks flying from the wall.

  Then a chunk of the hull fell away and light streamed in, temporarily blinding me.

  "They're still alive,” said a man. “Tell Kimball they're still alive."

  * * * *

  All we got from the paramedics was that a large swale had dropped off our shuttle and Neuter Kimball just outside Sol Central Station's energy shield. Neuter Kimball had called the station, and the shuttle had been towed into a dock, where they cut through the hull to rescue us.

  It wasn't until Juanita and I were sitting in a hospital room, where an autodoc gave us injections to treat our radiation burns, that we were able to talk to Neuter Kimball.

  "It was Leviathan who brought us back here,” it said.

  I was stunned. “But why? And why didn't she kill you?"

  "When she saw that you were willing to die to save me, though I am not even of your own species, she was curious. She asked me why you would do such a thing, so I transmitted the Bible and the Book of Mormon to her. Then she brought us here in case you were still alive."

  "And you're not hurt from what she did to you?” I asked.

  "I will recover,” said Neuter Kimball. “Before she left, Leviathan declared that from this time forward, Mormon swales are not to be forced into sexual activity."

  "That's great news.” I had won. No—I corrected myself—the victory was not mine. I thank thee, Lord, I prayed silently.

  "Leviathan also had a personal message for you, President Malan. She said to remind you of what King Agrippa said to Paul."

  I nodded. “I understand. Thanks for passing that along."

  After the call was over, Juanita said, “What was that message about? Another Book of Mormon story?"

  "No, it's from the Bible. Saint Paul preached before King Agrippa, and the king's response was, ‘Almost thou persuadest me to be a Christian.’ So, no, Leviathan hasn't become Mormon. But God softened her heart so she didn't kill Neuter Kimball. Or us, for that matter. Back on the shuttle, you were certain we were going to die. You asked where God was when I really needed him. Well, God came through."

  Juanita puffed out an exasperated breath. “Typical."

  "What do you mean by that?” I asked as the autodoc signaled that my treatment was complete.

  "In one story, the preacher converts the king. In another, the king kills the preacher. And in a third, neither happens. That's no evidence that God comes through.” She pointed at me. “As I see it, you came through. By mentioning that ‘greater love’ thing, you hit Leviathan where it counted: her pride at being the greatest."

  I shook my head. “I'm not taking credit for this."

  After we walked out of the hospital, she gave me a tight hug that reminded me how much I was attracted to her. But I knew it would never work out between us—our worldviews were just too different.

  So I was still a single Mormon man with no dating prospects within ninety million miles.

  And no, an attractive single Mormon woman did not arrive on the next solar shuttle. What would be the point of life if God solved all my problems?

  * * * *

  O Lord, how manifold are thy works! in wisdom hast thou made them all: the earth is full of thy riches. So is this great and wide sea, wherein are things creeping innumerable, both small and great beasts. There go the ships: there is that leviathan, whom thou hast made to play therein.

  —Psalm 104:24-26

  Copyright © 2010 Eric James Stone

  [Back to Table of Contents]

  Science Fact: BAD MEDICINE: WHEN MEDICAL RESEARCH GOES WRONG by H. G. Stratmann, M.D.

  Medical research has dramatically improved the care patients receive today. When I completed my cardiology training in 1982, most of the medicines and procedures cardiologists now use routinely weren't available yet or were in an early stage of development. Table 1 compares some of the tests and treatments for heart disease that were state-of-the-art fifty years ago to what we have now. Other medical and surgical fields have made similar advances.

  However, along with those successes there've also been stunning, even fatal failures. While medical science has traveled far along the path to improving our health, it's instructive to review some potholes along that road and see what went wrong.

  * * * *

  Of Mice and (Wo)Men

  Developing new medicines and medical devices is a complex process. New drugs undergo an extended period of evaluation regarding their safety and efficacy. The evaluation process may
begin with synthesis and initial laboratory evaluation of as many as 5,000 to 10,000 chemical compounds that, on theoretical grounds, might prove effective for a particular disease. On average, about 250 of these chemicals will show sufficient promise to proceed with further laboratory testing and studies involving mice and other test animals. Only about ten of these chemicals will typically qualify for human testing.

  There are four “classic” phases in evaluating new drugs in humans. Phase I trials usually involve a small number (often less than 100) of healthy volunteers. The primary goal is to assess an investigational medicine's safety and pharmacokinetics (how it is absorbed, distributed, metabolized, and excreted by the human body). This is often done by studying the effects of administering a range of dosages of the drug, with each dose being significantly less than that found to be harmful in laboratory animals.

  If the drug meets safety criteria in Phase I trials, its efficacy for treating a particular medical problem is evaluated in Phase II trials. These studies may involve as many as several hundred men and women. Assessment of the drug's safety continues in Phase II trials.

  * * * *

  Table 1. A Partial Comparison of Evaluation and Treatment of Cardiovascular Diseases—1960 versus 2010

  —

  DIAGNOSTIC TESTS, TECHNIQUES, AND TOOLS

  1960

  History and physical

  Stethoscope

  Sphygmomanometer (used to check blood pressure)

  Limited laboratory tests

  Electrocardiogram (EKG)

  Chest x-ray and fluoroscopy

  Master's two-step test

  Cardiac catheterization and initial use of coronary angiography

  —

  2010

  Markedly expanded use of laboratory tests, including new tests such as cardiac enzymes

  Exercise (treadmill and bicycle) and pharmacological stress testing

  Echocardiography and other ultrasound tests

  Nuclear cardiac imaging

  Computed tomography (CT)

  Magnetic resonance imaging (MRI)

  Routine coronary angiography

  Coronary angioscopy and ultrasound

  Electrophysiological studies

  Routine use of cardiac monitoring

  Holter and event monitors

  * * * *

  MEDICATIONS

  1960

  Nitroglycerin

  Amyl nitrite

  Atropine

  Limited medications used to treat high blood pressure, such as reserpine, guanethidine, and hydralazine

  Limited antiarrhythmics, such as quinidine and procainamide

  Anticoagulants, such as heparin and warfarin

  Limited diuretics, such as chlorothiazide

  Digitalis

  Morphine

  Aspirin was available but not routinely used for cardiovascular disease

  Antibiotics to prevent rheumatic and syphilitic heart disease and treat endocarditis

  —

  2010

  Beta-blockers

  Calcium channel blockers

  Oral, topical, and intravenous nitrates

  Angiotensin-converting enzyme (ACE) inhibitors

  Angiotensin receptor blockers (ARBs)

  Statins, fibrates, and other cholesterol-lowering medications

  Expanded use and variety of diuretics

  Markedly expanded range of antiarrhythmic medications

  Dopamine, dobutamine, nitroprusside

  Antiplatelet agents such as clopidogrel

  Glycoprotein IIb/IIIa inhibitors

  Thrombolytic agents

  Low-molecular-weight heparins

  Additional antibiotics

  * * * *

  DEVICES

  1960

  Initial use of temporary and permanent pacemakers

  Initial use of defibrillators

  Initial use of cardiopulmonary bypass ("heart-lung machines")

  —

  2010

  Routine use of implantable pacemakers

  Implantable cardioverter-defibrillator (ICD)

  Ventricular assist device

  Intra-aortic balloon pump

  Routine use of defibrillators, including automated external defibrillators (AED)

  * * * *

  SURGERY AND THERAPEUTIC PROCEDURES

  1960

  Operations available for a variety of congenital heart defects

  Commissurotomy for mitral and aortic stenosis

  Initial use of mechanical heart valves

  Initial techniques for cardiopulmonary resuscitation (CPR)

  —

  2010

  Coronary angioplasty and coronary stents

  Coronary atherectomy

  Percutaneous (catheter-based) techniques for procedures that previously could only be done by surgery, such as mitral valve repair

  Coronary artery bypass surgery

  Routine use of a wide variety of mechanical and bioprosthetic heart valves

  Expanded techniques for heart valve repair

  Heart transplantation and the artificial heart

  Radio frequency (RF) ablation treatments for arrhythmias

  Transmyocardial laser revascularization

  External enhanced counterpulsation

  Refinement of techniques for CPR

  * * * *

  * Tests and treatments available in 1960 are also still available in 2010. However, some (such as the Masters two-step test or use of amyl nitrite) have been supplanted by newer and better ones.

  * * * *

  Drugs demonstrating acceptable safety and efficacy graduate to Phase III trials. These often involve thousands of patients and are performed at a large number of medical centers and clinics. They typically evaluate how well the new drug works and its safety compared to placebo, as well as to the best currently available ("gold standard") treatment for a disease. Statistical analyses of how effective the study medication is and its adverse effects are performed during and at the end of the trial.

  Phase III trials are customarily “randomized” and “double-blinded” to make this evaluation as objective as possible. “Randomized” means that whether an individual patient receives the investigational medication, placebo, or a standard medication is determined by chance. This helps avoid “selection bias"—the possibility that physicians supervising the study would, however inadvertently, give the study drug to patients more likely to respond to it or assign placebo to those less likely to respond, thus making the study drug seem better than it really is.

  "Double-blinded” means that neither the patients in the study nor the physicians caring for them know what kind of medication (e.g. study drug or placebo) an individual patient is getting. This reduces the influence of any purely subjective feelings of well-being or harm that patients or physicians might feel if they knew what type of medication was being taken. This information is, however, kept in a central database for analysis by third-party monitors.

  In the United States, drugs that meet appropriate safety and efficacy criteria following Phase III trials can be submitted to the Food and Drug Administration (FDA). This federal agency decides whether the drug can be approved for marketing and sale. If the drug is approved, it may be evaluated further via Phase IV trials. These are typically surveillance studies that monitor the safety of the drug in a much larger number of patients than were evaluated in Phase I, II, and III trials. Data are also obtained to assess the drug's interactions with other commonly used medications as well as its safety and efficacy in particular types of patients, including those usually excluded from pre-approval trials, such as pregnant women or the very elderly.

  Medical devices and biologics (agents that include vaccines and biological substances produced using recombinant DNA) undergo similar stages of testing.

  Overall, it may take twelve to fifteen years from the time a new drug is discovered to when it is approved for use. The average cost of developing an entirely new medicine has been est
imated at around eight hundred million to two billion dollars.[1]

  And yet, despite all the time and effort that go into developing new medications, things can go wrong. Only about one out of five drugs that reach the stage of human trials is ultimately approved. And even a few that are approved can turn out to be more hazardous than helpful.

  * * * *

  The Terrible Swift SWORD

  Over my career as a cardiologist, I've been an investigator for over two dozen clinical research trials involving new medications. It's sometimes been challenging for me to find patients who were suitable and willing to participate in these studies. But in one case, I'm grateful I didn't enroll a patient before the study was stopped.

  The Survival With ORal D-sotalol (SWORD) study was a large Phase III multicenter trial conducted in the mid 1990s. Its goal was to see if d-sotalol, a medication used to treat arrhythmias (abnormal heart rhythms), could reduce the risk of death in certain patients following a myocardial infarction (a “heart attack,” usually caused by a blood clot completely or nearly completely blocking off one of the heart's arteries). The study included patients with at least moderately decreased systolic function of the left ventricle (the main pumping chamber of the heart, which contracts during “systole") and who'd either had a myocardial infarction within six to 42 days or who had symptoms of heart failure (such as shortness of breath) more than 42 days after a myocardial infarction.

  People who survive a myocardial infarction and have at least moderately decreased left ventricular systolic function have an increased long-term risk of death. This greater mortality can be due to the occurrence of life-threatening arrhythmias such as ventricular tachycardia or ventricular fibrillation. With both arrhythmias, either the right ventricle or left ventricle produces electrical impulses at an abnormally fast rate. With ventricular tachycardia, this may be as fast as 300 times per minute. Ventricular fibrillation is even faster, generating impulses at 400 to 600 times per minute. These heart rates are too rapid for the heart to effectively pump blood and can cause irreversible brain injury and death within minutes.

  The scientific rationale behind SWORD was to see if d-sotalol could reduce the risk of death by preventing these life-threatening arrhythmias. The sotalol molecule has two “isomers” with antiarrhythmic properties, d-sotalol and l-sotalol. (Isomers are molecules with the same numbers and types of atoms but in different arrangements.) D-sotalol differs from l-sotalol in that it essentially lacks “beta-blocking” properties. The heart contains a type of “beta receptor” (SS1) that, when stimulated by epinephrine (adrenaline) or similar chemicals, increases heart rate and how forcefully the left and right ventricles contract. Conversely, a beta-blocker reduces heart rate and contractility.