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Could both of us make it, do you suppose? They'd keep at least one man inside all the time. Even if we killed everybody outside, the ship would take off before we could get close enough to open the port with the outside controls. But I don't want you to work on that idea if you can think of a better one.

I've got passports and so on for you to be anything you want to be, from a tube-man up to an Ekoptian banker. Ditto for me, and for us both, as Mr. The sneak-boat isn't due for a week, and from what you've said it probably won't get here. But you might make it, at that. I'll drop you somewhere Tourists—newlyweds—from some town not too far away.

Pretty well fixed, to match what we're riding in. Can do? We'll have to dispose of the rest of these, and a lot of other stuff, too. And you had better get out of that leather and into a suit that matches this passport photo. Straight road for miles, and nothing in sight either way. Give me the suit and I'll change now. Keep on going or stop? While the man changed clothes, Kinnexa collected the contraband, wrapping it up in the discarded jacket. She looked up just as Phryges was adjusting his coat. She glanced at his armpits, then stared.

These aren't. They're air-guns. Poisoned needles. Not worth a damn beyond a hundred feet, but deadly close up. One touch anywhere and the guy dies right then. Two seconds max. Gimme, and show me how they work. Like so. The day wore on, nor was it uneventful. One incident, in fact—the detailing of which would serve no useful purpose here—was of such a nature that at its end:. Of course! Forgive me, Fry—it slipped my mind completely that you didn't know where it was. Area six; pin-point four seven three dash six oh five. But neither of the Atlanteans was "scragged", and at six P.

Their papers, tickets included, were in perfect order; they were as inconspicuous and as undemonstrative as newlyweds are wont to be. No more so, and no less. Strolling idly, gazing eagerly at each new thing, they made their circuitous way toward a certain small hangar.

As the girl had said, this field boasted hundreds of super-sonic fighters, so many that servicing was a round-the-clock routine. In that hangar was a sharp-nosed, stubby-V'd flyer, one of Norheim's fastest. It was serviced and ready. It was too much to hope, of course, that the visitors could actually get into the building unchallenged. Nor did they. Phryges' air-gun broke into soft but deadly coughing. Kinnexa whirled—hands flashing down, skirt flying up-and ran.

Guards tried to head her off; tried to bring their own weapons to bear. Phryges, too, ran; ran backward. His blaster was out now and flaming, for no living enemy remained within needle range. A rifle bullet w-h-i-n-g-e-d past his head, making him duck involuntarily and uselessly. Rifles were bad; but their hazard, too, had been considered and had been accepted. Kinnexa reached the fighter's port, opened it, sprang in. He jumped. She fell against him. He tossed her clear, slammed and dogged the door. He looked at her then, and swore bitterly.

A small, round hole marred the bridge of her nose: the back of her head was gone. He leaped to the controls and the fleet little ship screamed skyward. He cut in transmitter and receiver, keyed and twiddled briefly. No soap. He had been afraid of that. They were already blanketing every frequency he could employ; using power through which he could not drive even a tight beam a hundred miles.

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But he could still crash that missile in its tube. Or—could he? He was not afraid of other Norheiman fighters; he had a long lead and he rode one of their very fastest. But since they were already so suspicious, wouldn't they launch the bomb before seven o'clock? He tried vainly to coax another knot out of his wide-open engines. With all his speed, he neared the pin-point just in time to see a trail of super-heated vapor extending up into and disappearing beyond the stratosphere. He nosed his flyer upward, locked the missile into his sights, and leveled off.

Although his ship did not have the giant rocket's acceleration, he could catch it before it got to Atlantis, since he did not need its altitude and since most of its journey would be made without power. What he could do about it after he caught it he did not know, but he'd do something. He caught it; and, by a feat of piloting to be appreciated only by those who have handled planes at super-sonic speeds, he matched its course and velocity.

Then, from a distance of barely a hundred feet, he poured his heaviest shells into the missile's war-head. He couldn't be missing! It was worse than shooting sitting ducks—it was like dynamiting fish in a bucket! Nevertheless, nothing happened. The thing wasn't fuzed for impact, then, but for time; and the activating mechanism would be shell-and shock-proof. But there was still a way. He didn't need to call Artomenes now, even if he could get through the interference which the fast-approaching pursuers were still sending out.

Atlantean observers would have lined this stuff up long since; the Officer would know exactly what was going on. Driving ahead and downward, at maximum power, Phryges swung his ship slowly into a right-angle collision course. The fighter's needle nose struck the war-head within a foot of the Atlantean's point of aim, and as he died Phryges knew that he had accomplished his mission. Norheim's missile would not strike Atlantis, but would fall at least ten miles short, and the water there was very deep.

Very, very deep. Atlantis would not be harmed. It might have been better, however, if Phryges had died with Kinnexa on Norgrad Field; in which case the continent would probably have endured. As it was, while that one missile did not reach the city, its frightful atomic charge exploded under six hundred fathoms of water, ten scant miles from Atlantis' harbor, and very close to an ancient geological fault. Artomenes, as Phryges had surmised, had had time in which to act, and he knew much more than Phryges did about what was coming toward Atlantis.

Too late, he knew that not one missile, but seven, had been launched from Norheim, and at least five from Uighar. The retaliatory rockets which were to wipe out Norgrad, Uigharstoy, and thousands of square miles of environs were on their way long before either bomb or earthquake destroyed all of the Atlantean launching ramps.

But when equilibrium was at last restored, the ocean rolled serenely where a minor continent had been. Like two high executives of a Tellurian corporation discussing business affairs during a chance meeting at one of their clubs, Eddore's All Highest and Gharlane, his second in command, were having the Eddorian equivalent of an after-business-hours chat. When the Atlantean nations destroyed each other so thoroughly I thought that this thing called 'democracy' was done away with forever, but it seems to be mighty hard to kill.

However, I take it that you have this Rome situation entirely under control? Mithradates of Pontus was mine. So were both Sulla and Marius. Through them and others I killed practically all of the brains and ability of Rome, and reduced that so-called 'democracy' to a howling, aimless mob. My Nero will end it. Rome will go on by momentum—outwardly, will even appear to grow—for a few generations, but what Nero will do can never be undone. Since each creature lives only a minute or so, they change so fast that a man can't take his mind off of them for a second.

I've been wanting to take a little vacation trip back to our old time-space, but it doesn't look as though I'll be able to do it until after they get some age and settle down. But none of the others is having half the trouble that I am. Most of them, in fact, have things coming along just about the way they want them. My four planets are raising more hell than all the rest of both galaxies put together, and I know that it isn't me—next to you, I'm the most efficient operator we've got.

What I'm wondering about is why I happen to be the goat. Spores from an extinct life-form—suitable environments—operation of the laws of chance—Tommyrot! I am beginning to suspect that chance is being strained beyond its elastic limit, for my particular benefit, and as soon as I can find out who is doing that straining there will be one empty place in the Innermost Circle.

Whom do you accuse? The true angle never occurred to me until just now, while I have been discussing the thing with you. Nor shall I either suspect or accuse, ever. I shall determine, then I shall act. Of my orders? Assume that I am right, that these four planets of mine got the way they are because of monkey business inside the Circle.

Who would be next? And how sure are you that there isn't something similar, but not so far advanced, already aimed at you? It seems to me that serious thought is in order. You may be right There have been a few nonconformable items. Taken separately, they did not seem to be of any importance; but together, and considered in this new light Thus was borne out the conclusion of the Arisian Elders that the Eddorians would not at that time deduce Arisia; and thus Eddore lost its chance to begin in time the forging of a weapon with which to oppose effectively Arisia's—Civilization's—Galactic Patrol, so soon to come into being.

If either of the two had been less suspicious, less jealous, less arrogant and domineering—in other words, had not been Eddorians—this History of Civilization might never have been written; or written very differently and by another hand. In the brief interval between the fall of Atlantis and the rise of Rome to the summit of her power, Eukonidor of Arisia had aged scarcely at all. He was still a youth.

He was, and would be for many centuries to come, a Watchman. Although his mind was powerful enough to understand the Elders' visualization of the course of Civilization—in fact, he had already made significant progress in his own visualization of the Cosmic All—he was not sufficiently mature to contemplate unmoved the events which, according to all Arisian visualizations, were bound to occur. It is, however, necessary. In no other way can the ultimate triumph of Civilization be assured. We can do little enough. Our forms of flesh—Petronius, Acte, and the others—will do whatever they can; but their powers will be exactly the same as those of other human beings of their time.

They must be and will be constrained, since any show of unusual powers, either mental or physical, would be detected instantly and would be far too revealing. On the other hand, Nero—that is, Gharlane of Eddore—will be operating much more freely. Practically unhampered, except in purely physical matters. But, if nothing can be done to stop it If Nero must be allowed to sow his seeds of ruin But, like horses, we are lower than slaves. Slaves have some freedom of action; most of us have none.

We fight—fight whoever or whatever our cursed owners send us against. Those of us who live fight again; but the end is certain and comes soon. I had a wife and children once. So did you. Is there any chance, however slight, that either of us will ever know them again; or learn even whether they live or die? At this price, is your life worth living? Mine is not. Livius the Bithynian, who had been staring out past the bars of the cubicle and over the smooth sand of the arena toward Nero's garlanded and purple-bannered throne, turned and studied his fellow gladiator from toe to crown.

The heavily-muscled legs, the narrow waist, the sharply-tapering torso, the enormous shoulders. The leonine head, surmounted by an unkempt shock of red-bronze-auburn hair. And, lastly, the eyes—gold-flecked, tawny eyes—hard and cold now with a ferocity and a purpose not to be concealed. I take it that someone swore his life for me and that I should not ask who that friend might be.

To my unknown sponsor, then, and to the gods, I give thanks, for I am wholly with you. Not that I have any hope. Although your tribe breeds men—from your build and hair and eyes you descend from Spartacus himself—you know that even he did not succeed. Things now are worse, infinitely worse, than they were in his day.

No one who has ever plotted against Nero has had any measure of success; not even his scheming slut of a mother. All have died, in what fashions you know. Nero is vile, the basest of the base. Nevertheless, his spies are the most efficient that the world has ever known. In spite of that, I feel as you do. If I can take with me two or three of the Praetorians, I die content. But by your look, your plan is not what I thought, to storm vainly Nero's podium yonder.

Have you, by any chance, some trace of hope of success? But, this time, so are we. Just as hard and just as ruthless. Many of his spies among us have died; most, if not all, of the rest are known. They, too, shall die. Glatius, for instance. Once in a while, by the luck of the gods, a man kills a better man than he is; but Glatius has done it six times in a row, without getting a scratch. But the next time he fights, in spite of Nero's protection, Glatius dies. Word has gone out, and there are gladiators' tricks that Nero never heard of. One question, and I too may begin to hope.

This is not the first time that gladiators have plotted against Ahenobarbus. Before the plotters could accomplish anything, however, they found themselves matched against each other and the signal was always for death, never for mercy. Has this? It is that which gives me the hope I have. Nor are we gladiators alone in this. We have powerful friends at court; one of whom has for days been carrying a knife sharpened especially to slip between Nero's ribs. That he still carries that knife and that we still live are proofs enough for me that Ahenobarbus, the matricide and incendiary, has no suspicion whatever of what is going on.

At this point Nero on his throne burst into a roar of laughter, his gross body shaking with a merriment which Petronius and Tigellinus ascribed to the death-throes of a Christian woman in the arena. The prisons and the pits are so crowded with Christians that they die and stink, and a pestilence threatens. To mend matters, some scores of hundreds of them are to be crucified here tomorrow.

Everyone knows that they are poisoners of wells and murderers of children, and practitioners of magic. Wizards and witches. A gorgeous spectacle, truly, almost as thrilling as to feel a man die on your sword. Men and women, wrapped in oil-soaked garments smeared with pitch and chained to posts, make splendid torches indeed. You mean, then, that? In Caesar's own garden. When the light is brightest Nero will ride in parade. When his chariot passes the tenth torch our ally swings his knife.

The Praetorians will rush around, but there will be a few moments of confusion during which we will go into action and the guards will die. At the same time others of our party will take the palace and kill every man, woman, and child adherent to Nero. A few gladiators—such champions as Patroclus of Thrace—are at times allowed to do pretty much as they please in their free time, and hence could possibly be on hand to take part in such a brawl, but most of us will be under lock and guard. Our allies near the throne and certain other nobles and citizens of Rome, who have been winning large sums by our victories, have prevailed upon our masters to give a grand banquet to all gladiators tomorrow night, immediately following the mass crucifixion.

It is going to be held in the Claudian Grove, just across from Caesar's Gardens. By the round, high breasts of Isis! For the first time in years I begin to live! Our masters die first, then and there Bystanders will have them, and armor and shields, under their cloaks. Our owners first, yes; and then the Praetorians. But note, Livius, that Tigellinus, the Commander of the Guard, is mine—mine alone.

I, personally, am going to cut his heart out. I heard that he had your wife for a time. But you seem quite confident that you will still be alive tomorrow night. By Baal and Ishtar, I wish I could feel so! With something to live for at last, I can feel my guts turning to water—I can hear Charon's oars. Like as not, now, some toe-dancing stripling of a retiarius will entangle me in his net this very afternoon, and no mercy signal has been or will be given this day. Such is the crowd's temper, from Caesar down, that even you will get 'Pollice verso' if you fall.

But you had better get over that feeling, if you want to live. As for me, I'm safe enough. I have made a vow to Jupiter, and he who has protected me so long will not desert me now. Any man or any thing who faces me during these games, dies. The door behind them swung open. A lanista, or master of gladiators, laden with arms and armor, entered. The door swung to and was locked from the outside. The visitor was obviously excited, but stared wordlessly at Patroclus for seconds. Something special? The sensation of the year. Fermius himself. Free choice of weapons and armor.

But listen, Bronze-head. If you get the best of Fermius, I'll give you a full third of my winnings. You'll collect. A good man, Fermius, and smart. I've heard a lot about him, but never saw him work. He has seen me, which isn't so good. Both heavy and fast—somewhat lighter than I am, and a bit faster. He knows that I always fight Thracian, and that I'd be a fool to try anything else against him. He fights either Thracian or Samnite depending upon the opposition. Against me his best bet would be to go Samnite.

Do you know? He'll have to. These unlimiteds are tough, but it gives me a chance to use a new trick I've been working on. I'll take that sword there—no scabbard—and two daggers, besides my gladius. Get me a mace; the lightest real mace they've got in their armory. The mace was brought and Patroclus banged it, with a two-handed roundhouse swing, against a stone of the wall. The head remained solid upon the shaft. They waited. Any weapons that either chooses to use, used in any way possible. No rest, no intermission. Two armored figures strode toward the center of the arena.

Patroclus' armor, from towering helmet down, and including the shield, was of dully-gleaming steel, completely bare of ornament. Each piece was marred and scarred; very plainly that armor was for use and had been used. On the other hand, the Samnite half-armor of the Gaul was resplendent with the decorations affected by his race. Fermius' helmet sported three brilliantly-colored plumes, his shield and cuirass, enameled in half the colors of the spectrum, looked as though they were being worn for the first time.

Five yards apart, the gladiators stopped and wheeled to face the podium upon which Nero lolled. The buzz of conversation—the mace had excited no little comment and speculation—ceased. Patroclus heaved his ponderous weapon into the air; the Gaul whirled up his long, sharp sword. They chanted in unison:. The starting-flag flashed downward; and at its first sight, long before it struck the ground, both men moved.

Fermius whirled and leaped; but, fast as he was, he was not quite fast enough. That mace, which had seemed so heavy in the Thracian's hands a moment before, had become miraculously maneuverable—it was hurtling through the air directly toward the middle of his body! It did not strike its goal—Patroclus hoped that he was the only one there who suspected that he had not expected it to touch his opponent—but in order to dodge the missile Fermius had to break his stride; lost momentarily the fine co-ordination of his attack.

And in that moment Patroclus struck. Struck, and struck again. But, as has been said, Fermius was both strong and fast. The first blow, aimed backhand at his bare right leg, struck his shield instead. The left-handed stab, shield-encumbered as the left arm was, ditto. So did the next trial, a vicious forehand cut. The third of the mad flurry of swordcuts, only partially deflected by the sword which Fermius could only then get into play, sheared down and a red, a green, and a white plume floated toward the ground. The two fighters sprang apart and studied each other briefly.

From the gladiators' standpoint, this had been the veriest preliminary skirmishing. That the Gaul had lost his plumes and that his armor showed great streaks of missing enamel meant no more to either than that the Thracian's supposedly surprise attack had failed. Each knew that he faced the deadliest fighter of his world; but if that knowledge affected either man, the other could not perceive it. But the crowd went wild. Nothing like that first terrific passage-at-arms had ever before been seen. Death, sudden and violent, had been in the air. The arena was saturated with it.

Hearts had been ecstatically in throats. Each person there, man or woman, had felt the indescribable thrill of death—vicariously, safely—and every fiber of their lusts demanded more. Each spectator knew that one of those men would die that afternoon. None wanted, or would permit them both to live. This was to the death, and death there would be. Women, their faces blotched and purple with emotion, shrieked and screamed.

Men, stamping their feet and waving their arms, yelled and swore. And many, men and women alike, laid wagers. The fighters closed—swung—stabbed. Shields clanged vibrantly under the impact of fended strokes, swords whined and snarled. Back and forth—circling—giving and taking ground—for minute after endless minute that desperately furious exhibition of skill, of speed and of power and of endurance went on. And as it went on, longer and longer past the time expected by even the most optimistic, tension mounted higher and higher.

Blood flowed crimson down the Gaul's bare leg and the crowd screamed its approval. Blood trickled out of the joints of the Thracian's armor and it became a frenzied mob. No human body could stand that pace for long. Both men were tiring fast, and slowing.

With the drive of his weight and armor, Patroclus forced the Gaul to go where he wanted him to go. Then, apparently gathering his every resource for a final effort, the Thracian took one short, choppy step forward and swung straight down, with all his strength. The blood-smeared hilt turned in his hands; the blade struck flat and broke, its length whining viciously away.

Fermius, although staggered by the sheer brute force of the abortive stroke, recovered almost instantly; dropping his sword and snatching at his gladius to take advantage of the wonderful opportunity thus given him. But that breaking had not been accidental; Patroclus made no attempt to recover his balance. Instead, he ducked past the surprised and shaken Gaul. Still stooping, he seized the mace, which everyone except he had forgotten, and swung; swung with all the totalized and synchronized power of hands, wrists, arms, shoulders, and magnificent body. The iron head of the ponderous weapon struck the center of the Gaul's cuirass, which crunched inward like so much cardboard.

Fermius seemed to leave the ground and, folded around the mace, to fly briefly through the air. As he struck the ground, Patroclus was upon him. The Gaul was probably already dead—that blow would have killed an elephant—but that made no difference. If that mob knew that Fermius was dead, they might start yelling for his life, too. Hence, by lifting his head and poising his dirk high in air, he asked of Caesar his Imperial will.

The crowd, already frantic, had gone stark mad at the blow. No thought of mercy could or did exist in that insanely bloodthirsty throng; no thought of clemency for the man who had fought such a magnificent fight. In cooler moments they would have wanted him to live, to thrill them again and yet again; but now, for almost half an hour, they had been loving the hot, the suffocating thrill of death in their throats.

Now they wanted, and would have, the ultimate thrill. Nero's right thumb pressed horizontally against his chest. Every vestal was making the same sign. Pollice verso. The strained and strident yelling of the mob grew even louder. Patroclus had never seen the Bithynian so buoyant. But by the red beak of Thoth and the sacred Zaimph of Tanit, it gave me the horrors when you made that throw so quick and missed it, and I went as crazy as the rest of them when you pulled the real coup.

But now, curse it, I suppose that we'll all have to be on the lookout for it—or no, unlimiteds aren't common, thank Ninib the Smiter and his scarlet spears! He's a high-rater—one of the best of the locals—and I was afraid he might snare you, but from the looks of you, you got only a couple of stabs. Nice work. Prayer is the stuff. I prayed to 'em in order, and hit the jackpot with Shamash.

My guts curled up again, like they belong, and I knew that the portents were all in my favor. Besides, when you were walking out to meet Fermius, did you notice that red-headed Greek posturer making passes at you? So did she, probably, because after a while she came around behind with a lanista and made eyes at me. I must have the next best shape to you here, I guess.

What a wench! Anyway, I felt better and better, and before she left I knew that no damn retiarius that ever waved a trident could put a net past my guard. And they couldn't either. A couple more like that and I'll be a Grand Champion myself. But they're digging holes for the crosses and there's the horn that the feast is ready. This show is going to be really good. They ate, hugely and with unmarred appetite, of the heaped food which Nero had provided.

They returned to their assigned places to see crosses, standing as close together as they could be placed and each bearing a suffering Christian, filling the whole vast expanse of the arena. And, if the truth must be told, those two men enjoyed thoroughly every moment of that long and sickeningly horrible afternoon. They were the hardest products of the hardest school the world has ever known: trained rigorously to deal out death mercilessly at command; to accept death unflinchingly at need.

They should not and can not be judged by the higher, finer standards of a softer, gentler day. The afternoon passed; evening approached. All the gladiators then in Rome assembled in the Claudian Grove, around tables creaking under their loads of food and wine. Women, too, were there in profusion; women for the taking and yearning to be taken; and the tide of revelry ran open, wide, and high.

Although all ate and apparently drank with abandon, most of the wine was in fact wasted. And as the sky darkened, most of the gladiators, one by one, began to get rid of their female companions upon one pretext or another and to drift toward the road which separated the festivities from the cloaked and curious throng of lookers-on. At full dark, a red glare flared into the sky from Caesar's garden and the gladiators, deployed now along the highway, dashed across it and seemed to wrestle briefly with cloaked figures.

Then armed, more-or-less-armored men ran back to the scene of their reveling. Swords, daggers, and gladii thrust, stabbed, and cut. Tables and benches ran red; ground and grass grew slippery with blood. The conspirators turned then and rushed toward the Emperor's brilliantly torch-lit garden. Patroclus, however, was not in the van. He had had trouble in finding a cuirass big enough for him to get into. He had been delayed further by the fact that he had had to kill three strange lanistae before he could get at his owner, the man he really wanted to slay.

He was therefore some little distance behind the other gladiators when Petronius rushed up to him and seized him by the arm. White and trembling, the noble was not now the exquisite Arbiter Elegantiae; nor the imperturbable Augustian. In the name of Bacchus, Patroclus, why do the men go there now? No signal was given—I could not get to Nero! It was given—I heard it myself! What went wrong?

No one else was near enough to interfere. It was—should have been—easy. But after I got my knife out I couldn't move. It was his eyes , Patroclus—I swear it, by the white breasts of Venus! He has the evil eye—I couldn't move a muscle, I tell you!

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Then, although I didn't want to, I turned and ran! But what are we—you—going to do? Patroclus' mind raced. He believed implicitly that Jupiter guarded him personally. He believed in the other gods and goddesses of Rome. He more than half believed in the multitudinous deities of Greece, of Egypt, and even of Babylon. The other world was real and close; the evil eye only one of the many inexplicable facts of every-day life. Nevertheless, in spite of his credulity—or perhaps in part because of it—he also believed firmly in himself; in his own powers. Wherefore he soon came to a decision.

And then to give Tigellinus what I have owed him so long. At full run, he soon overtook his fellows, and waded resistlessly into the fray. He was Grand Champion Patroclus, working at his trade; the hard-learned trade which he knew so well. No Praetorian or ordinary soldier could stand before him save momentarily. He did not have all of his Thracian armor, but he had enough. Man after man faced him, and man after man died. And Nero, sitting at ease with a beautiful boy at his right and a beautiful harlot at his left, gazed appreciatively through his emerald lens at the flaming torches; the while, with a very small fraction of his Eddorian mind, he mused upon the matter of Patroclus and Tigellinus.

Should he let the Thracian kill the Commander of his Guard? Or not? It didn't really matter, one way or the other. In fact, nothing about this whole foul planet—this ultra-microscopic, if offensive, speck of cosmic dust in the Eddorian Scheme of Things—really mattered at all. It would be mildly amusing to watch the gladiator consummate his vengeance by carving the Roman to bits. But, on the other hand, there was such a thing as pride of workmanship. Viewed in that light, the Thracian could not kill Tigellinus, because that bit of corruption had a few more jobs to do. He must descend lower and lower into unspeakable depravity, finally to cut his own throat with a razor.

Although Patroclus would not know it—it was better technique not to let him know it—the Thracian's proposed vengeance would have been futility itself compared with that which the luckless Roman was to wreak on himself. Wherefore a shrewdly-placed blow knocked the helmet from Patroclus' head and a mace crashed down, spattering his brains abroad. Thus ended the last significant attempt to save the civilization of Rome; in a fiasco so complete that even such meticulous historians as Tacitus and Suetonius mention it merely as a minor disturbance of Nero's garden party.

The planet Tellus circled its sun some twenty hundred times. Sixty-odd generations of men were born and died, but that was not enough. The Arisian program of genetics required more. Therefore the Elders, after due deliberation, agreed that that Civilization, too, must be allowed to fall. And Gharlane of Eddore, recalled to duty from the middle of a much-too-short vacation, found things in very bad shape indeed and went busily to work setting them to rights. He had slain one fellow-member of the Innermost Circle, but there might very well have been more than one Master involved.

Sobbing furiously, Captain Ralph Kinnison wrenched at his stick—with half of his control surfaces shot away the crate was hellishly logy. He could step out, of course, the while saluting the victorious Jerries, but he wasn't on fire—yet—and hadn't been hit—yet. He ducked and flinched sidewise as another burst of bullets stitched another seam along his riddled fuselage and whanged against his dead engine. Not yet—good! Maybe he could land the heap, after all! Slowly—oh, so sluggishly—the Spad began to level off, toward the edge of the wheatfield and that friendly, inviting ditch.

If the krauts didn't get him with their next pass He heard a chattering beneath him—Brownings, by God! He knew that he had been just about over the front when they conked his engine; it was a toss-up whether he would come down in enemy territory or not. But now, for the first time in ages, it seemed, there were machine-guns going that were not aimed at him! His landing-gear swished against stubble and he fought with all his strength of body and of will to keep the Spad's tail down.

He almost succeeded; his speed was almost spent when he began to nose over. He leaped, then, and as he struck ground he curled up and rolled—he had been a motorcycle racer for years—feeling as he did so a wash of heat: a tracer had found his gas-tank at last! Bullets were thudding into the ground; one shrieked past his head as, stooping over, folded into the smallest possible target, he galloped awkwardly toward the ditch.

The Brownings still yammered, filling the sky with cupro-nickeled lead; and while Kinnison was flinging himself full length into the protecting water and mud, he heard a tremendous crash. One of those Huns had been too intent on murder; had stayed a few seconds too long; had come a few meters too close.

Keep low, you boneheads! Take down them guns; we gotta get to hell out of here. Hey, you flyer! Are you O. Kinnison spat out mud until he could talk. He stopped, however, as whistling metal, sheeting in from the north, told him that such action would be decidedly unsafe. It's hotter than the hinges of hell, from behind that ridge over there.

But ooze down that ditch a piece, around the first bend. It's pretty well in the clear there, and besides, you'll find a ledge of rocks running straight across the flat. Cross over there and climb the hill—join us by that dead snag up there. We got to get out of here. That sausage over there must have seen this shindig and they'll blow this whole damn area off the map. Snap it up! And you, you goldbricks, get the lead out of your pants! Kinnison followed directions. He found the ledge and emerged, scraping thick and sticky mud from his uniform.

He crawled across the little plain. An occasional bullet whined through the air, far above him; but, as the sergeant had said, this bit of terrain was "in the clear. He heard men moving, and cautiously announced himself. What outfit is this, and where are we? Below and to the north, almost exactly where the machine-guns had been, an awe-inspiring cloud billowed majestically into the air; a cloud composed of smoke, vapor, pulverized earth, chunks of rock, and debris of what had been trees. Nor was it alone.

The landscape disappeared. The little company of Americans, in complete silence and with one mind, devoted themselves to accumulating distance. Finally, when they had to stop for breath:. We got hell knocked out of us yesterday, and have been running around lost ever since.

They shot off a rally signal on top of this here hill, though, and we was just going to shove off when we seen the krauts chasing you. I'd better rally with you, I guess—find out where we are, and what's the chance of getting back to my own outfit. They approached the summit, were challenged, were accepted. They saw a gray-haired man—an old man, for such a location—seated calmly upon a rock, smoking a cigarette. His smartly-tailored uniform, which fitted perfectly his not-so-slender figure, was muddy and tattered. One leg of his breeches was torn half away, revealing a blood-soaked bandage.

Although he was very evidently an officer, no insignia were visible. As Kinnison and the gunners approached, a first lieutenant—practically spic-and-span—spoke to the man on the rock. Slayton, Major-General. Slayton—give me Weatherby This is Slayton No, but I want Hellanddamnation, Weatherby, shut up and let me talk—don't you know that this wire's apt to be cut any second?

We're on top of Hill Fo-wer, Ni-yun, Sev-en—that's right—about two hundred men; maybe three. Composite—somebody, apparently, from half the outfits in France. Too fast and too far—both flanks wide open—cut off Want to try to get through? Tell him Slayton says that we're cut off, but the Germans aren't in much force nor in good position, and for God's sake to get some air and tanks in here to keep them from consolidating. Just a minute. Sergeant, what's your name? Then set up to enfilade if they try to come up over there. Then, if I could find any more guns, I'd Second Lieutenant Wells, from now.

GHQ will confirm. Take charge of all the guns we have. Report when you have made disposition. Now, Kinnison, listen. I can probably hold out until tonight. The enemy doesn't know yet that we're here, but we are due for some action pretty quick now, and when they locate us—if there aren't too many of their own units here, too—they'll flatten this hill like a table. So tell Weatherby to throw a column in here as soon as it gets dark, and to advance Eight and Sixty, so as to consolidate this whole area.

Got it? A hair north of due west, about a kilometer and a half. Keep cover, because the going will be tough. Then you'll come to a road. It's a mess, but it's ours—or was, at last accounts—so the worst of it will be over. On that road, which goes south-west, about two kilometers further, you'll find a Post—you'll know it by the motorcycles and such. Phone from there.

Bullets began to whine and the general dropped to the ground and crawled toward a coppice, bellowing orders as he went. Kinnison crawled, too, straight west, availing himself of all possible cover, until he encountered a sergeant-major reclining against the south side of a great tree. Take the pack.

I've got another that'll last me—maybe more. But what the hell goes on here? Who ever heard of a major general getting far enough up front to get shot in the leg, and he talks as though he were figuring on licking the whole German army. Is the old bird nuts, or what? Didn'cha ever hear of 'Hellandamnation' Slayton? You will, buddy, you will. If Pershing doesn't give him three stars after this, he's crazier than hell.

Out here on a look-see trip and couldn't get back. But you got to hand it to him—he's getting things organized in great shape. I came in with him—I'm about all that's left of them that did—just waiting for this breeze to die down, but its getting worse.

We'd better duck—over there! Bullets whistled and stormed, breaking more twigs and branches from the already shattered, practically denuded trees. The two slid precipitately into the indicated shell-hole, into stinking mud. Wells' guns burst into action. They made objective, but it turns out the outfits on their right and left couldn't, leaving their flanks right out in the open air.

Orders come in by blinker to rectify the line by falling back, but by then it couldn't be done. Under observation.

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Kinnison nodded. He knew what a barrage would have done to a force trying to cross such open ground in daylight. You saw them boots without any hobnails in 'em, sticking out from under some blankets? I get you. Conniving, my guess is, behind old Slayton's back. Anyway, a kraut aviator spots 'em and dives. Our machine-guns got him, but not until after he heaved a bomb. Dead center. Christ, what a mess! But there's six-seven good glasses in there. I'd grab one myself, but the general would see it—he can see right through the lid of a mess-kit.

Well, the boys have shut those krauts up, so I'll hunt the old man up and tell him what I found out. Damn this mud! Kinnison emerged sinuously and snaked his way to a row of blanket covered forms. He lifted a blanket and gasped: then vomited up everything, it seemed, that he had eaten for days. But he had to have the binoculars. Then, still retching, white and shaken, he crept westward; availing himself of every possible item of cover. For some time, from a point somewhere north of his route, a machine-gun had been intermittently at work.

It was close; but the very loudness of its noise, confused as it was by resounding echoes, made it impossible to locate at all exactly the weapon's position. Kinnison crept forward inchwise; scanning every foot of visible terrain through his powerful glass. He knew by the sound that it was German. More, since what he did not know about machine-guns could have been printed in bill-poster type upon the back of his hand, he knew that it was a Maxim, Model —a mean, mean gun. For example, the Australia Group adopts consensus national export controls to impede the transfer of biological agents and technology where possible.

Nevertheless, the biological nonproliferation regime faces intrinsically greater challenges than does its nuclear or even chemical counterpart, because many of the relevant materials, technologies, and knowledge are far more widespread in the biological case. As this report documents, these technologies. Deterrence through the threat of retaliation was a central nuclear weapons strategy during the Cold War.

Deterring any form of terrorism may prove difficult, since some terrorist groups may be unconcerned about retaliation or may hope to remain unidentified. This conclusion may hold regardless of the type of weapon being used. However, biological weapons pose a unique challenge, as some infections may incubate without symptoms for days or even weeks, making it especially difficult to trace an attack back to its perpetrators.

Biological attacks may also be dissuaded through means other than the threat of retaliation dissuasion by deterrence , such as the force of law. In the initiatives now being pressed forward nationally and internationally to criminalize the activities of individuals i. So far, biological weapons have been based on agents that also cause naturally occurring disease outbreaks. This aspect of these weapons has no good analog in the realm of nuclear weapons and only partial ones in the realm of chemical weapons. Many of the same tools that address natural disease threats will be needed to respond to an attack using biological weapons, or to prevent such an attack from succeeding, and this is likely to remain true even in a future case involving a genetically engineered pathogen.

In the biological case, therefore, there is the opportunity to ensure that many of the steps required to improve biodefense will benefit public health even if major acts of bioterrorism never occur. The recent evolution of biomedical defense programs has largely focused on detection and vaccine development. They may have minor modifications such as induction of antibiotic resistance, but generally most countermeasures will be expected to be active, and the list of candidate agents is only debated in a small group of organisms.

In this situation, production of vaccines and countermeasures is not inherently destabilizing provided transparency and interchange are maintained. It is worth noting that we are far from solving defenses against these agents at this time. The primary driver of offensive capabilities in that biological arms race is not mainly a particular adversary but rather the ongoing global advance of biotechnology and microbiological and biomedical research. That is, protective measures are in a race with the malevolent application of potentially beneficial basic research, rather than primarily against technologies being developed in weapons programs of other countries.

For example, would it be legal and wise to have classified biodefense research activities produce modified pathogens that no adversaries are believed to have yet created in order to ostensibly understand and more robustly defend against them?

Strategic decisions must be made about what, if any, biological weapons research will be conducted in the name of biodefense, how much of this research will be classified, and how that program will be publicly described or even per-. This too is very different from the nuclear weapons case and the NPT, under which it is legally permissible, at least for the time being, for the United States and certain other NPT states to stockpile and conduct research in nuclear weapons.

Under the BWC, no nation may develop or stockpile biological weapons. However, the situation is complicated by the reality that a vast reservoir of technical information that could be used to develop bioweapons capabilities is freely available in the public domain, unlike the smaller number of closely held secrets associated with nuclear weapons technology. Moreover, much of biotechnology, unlike nuclear technology, is increasingly accessible even to minimally trained individuals. The risks associated with open versus closed biodefense research activities highlight the difficult questions surrounding the issue of secrecy and whether there is certain biological information that should be kept secret and, if so, where the boundary that defines this information lies and what circumstances dictate a need for secrecy.

Much of this report focuses on the potential misuse of technology. Indeed, the rationale for conducting this study was based on the growing threat of misuse posed by dual-use advances in science and technology. Importantly, there are also tremendous benefits to be gained from the very same scientific and technological advances. The purpose of this section is to enumerate some of these benefits.

A more detailed discussion of these benefits, particularly for the developing world, may be found in an earlier workshop summary report from this committee, An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks: A Workshop Report. There is no question that many populations have benefited greatly from advances in biotechnology and applications of related technologies e.

Health biotechnology holds out promises for improved nutrition, a cleaner environment, a longer and healthier lifespan, and cures for many once-formidable diseases. Even older technologies, such as classic vaccine technology, have enabled the eradication or reduction of many once-dreaded diseases, such as smallpox, polio, diphtheria, tetanus, and whooping cough. Newer reverse genetic technologies for RNA viruses may make possible rapid, rational development of vaccines against newly recognized pathogens, such as SARS, avian influenza, Nipah, and many others for.

In the developing world, broader application of biotechnology may make it economically feasible for resource-limited countries to produce inexpensive vaccines to protect their own populations against emerging infections that most afflict them. However, the potential applications of life sciences technologies extend far beyond more affordable vaccines. A technology foresight study conducted by the University of Toronto Joint Centre for Bioethics JCB identified the ten biotechnology-related developments that are likely to improve human health in developing countries within the next five to ten years: molecular diagnostics, recombinant vaccines, drug and vaccine delivery systems, bioremediation, sequencing pathogen genomes, female-controlled STI protection, bioinformatics, enriched genetically modified crops, recombinant drugs, and combinatorial chemistry.

In addition to improved health, world agriculture stands to benefit greatly from new discoveries in the life sciences and growing technological capabilities. Many staple crop plants represent virtual monocultures—that is, specific strains that were selected and propagated to give high yield under certain specific conditions. Such modified agricultural stock could be both an assurance for the future—against the possibility of a disease wiping out a major part of the food supply, as happened in the Irish potato famine of the midth century—and a boon to resource-poor farmers in developing countries.

Importantly, while posing risks, U. Efforts to expand disease surveillance, improve detection and diagnostic capabilities, and develop new vaccines and therapeutics—all of which are crucial for a rapid, effective response in the event of either a deliberately introduced or a naturally occurring biological attack—will continue to rely on excellent scientific research and technological growth. Much of the latter in particular relies, in turn, on international collaboration, a theme explored in depth in Chapter 2. Of the six category A biological threats on the U.

Department of Health. Global cooperation, including the training of foreign nationals in the United States, also provides opportunities to introduce foreign scientists to the concept of dual-use risk and the need to pursue a culture of awareness and responsibility in the global scientific community. It can be expected that tension between the potential beneficial and malevolent uses of technology will increase in the future, as science and technology increasingly empower users to manipulate the materials and processes of life itself.

The same reverse genetic technologies that can be used to develop new vaccines against RNA viruses could also be used to construct modified viruses, including possibly viruses that express heterologous virulence factors that result in more lethal disease. The following serve as additional illustrative examples of scientific publications that pose dual-use dilemmas see also Figure :. Publication of the complete DNA sequences of human pathogens. This information, which is widely available on public databases, could potentially facilitate the development and production of novel biological weapons agents.

Development of a genetically engineered strain of Bacillus anthracis containing an inserted gene for a foreign toxin, potentially rendering the agent resistant to the existing anthrax vaccine. Publication of molecular details of two highly virulent strains of influenza, the Hong Kong flu and the Spanish flu. Genetic engineering of the tobacco plant to produce subunits of cholera toxin, making it theoretically possible to produce large quantities of this toxin cheaply and relatively easily, for good or bad. Efforts to do away with insulin injections for diabetes by developing new technologies for delivering drugs by aerosol spray.

The deliberate release of botulinum toxin into the U. Researchers have explored the effects of a deliberate release of botulinum bacteria at various points in the milk supply chain, including raw milk silos and tanker delivery trucks, with varied assumptions for key variables. In the past, dual-use concerns have focused on pathogens and on the challenges associated with controlling dangerous pathogens.

For example, advances in neurobiology may make it possible to manipulate behavior and thought processes, while gene therapy and gene expression technologies just now coming to fruition will make it possible to activate endogenous molecules in the body—with possibly wide-ranging and devasting effects. Advances in synthetic biology and nanotechnology will offer similar rich opportunities for dual use. Nanodevices that may be used to unplug blocked arteries could instead be employed to interfere with circulatory function.

Advanced drug delivery technologies and pharmacogenomics knowledge could be used to develop and deliver. In considering the rapid and unpredictable advance of life sciences technologies, it became apparent to the committee that the possibility of inappropriate or malevolent use could never be completely eliminated without fundamentally undermining the vitality of the scientific enterprise and endangering the tremendous benefits this enterprise brings.

However, we can also learn from past experiences. For example, recombinant DNA was a new enabling technology some 30 years ago, and the possibilities of this powerful new technology led to widespread concern in both the scientific and the political communities. The issue was discussed at the now-famous Asilomar Conference of , when scientists gathered to discuss the safety of manipulating DNA from different species and when many of the safeguards now in place were originally developed.

Similarly, this committee has considered how possibilities for inappropriate and malicious use could be greatly reduced or mitigated, as discussed in greater detail in Chapter 4. In creating the ad hoc Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats, the National Research Council the operating arm of The National Academies and the Institute of Medicine selected committee members representing a broad spectrum of backgrounds, expertise, and interests.

Areas of expertise included public health, molecular and cellular biology, biophysics, clinical medicine, drug and vaccine discovery, national security and law enforcement, bioethics, and sociology see Appendix C for biographical information of committee members. In addition, the committee relied on the expertise and advice of representatives of the executive branch of the U. Chapter 2 of this report reviews the current global dispersion of tools and technologies used in the life sciences enterprise both domestically.

This global dispersion is being driven by a multitude of economic, social, and political forces. Chapter 3 provides an overview and perspective on the breadth and types of technologies that will—directly or indirectly—have an impact on how the life sciences enterprise will evolve in the near-term future. Cracraft, J. BioScience November. Meselson, M. The problem of biological weapons. National Intelligence Council. National Research Council.

Biotechnology Research in an Age of Terrorism. Couzin, J. Breakthrough of the year: small RNAs make big splash. Cancer Bulletin, National Cancer Institute. Technology Review February Scherr, M. Oligonucleotides ; Song, E. RNA Interference targeting Fas protects mice from fulminant hepatitis. Nature Medicine 9 3 ; Soutschek, J. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature February Ball, P. Synthetic biology: Starting from scratch. Nature : Morton, O. Life, reinvented.

Wired Craig Venter, Ph. Synthetic Genomics, Inc. The company is applying recent scientific advances, including newly discovered genetic sequences of novel photosynthetic and metabolic pathways, to execute various life functions within a synthetically devised organism. These breakthroughs present unprecedented opportunities that could restructure and revolutionize industries including energy, industrial organic compounds, pharmaceuticals, CO 2 sequestration, fine chemicals, and environmental remediation. After leveraging enormous archives of genomic sequence data, the company will integrate novel processes to design, build, and test desired outputs from synthetic organisms.

Service, R. Nanotechnology grows up. Science : Chang, K. New York Times February 22 ; N. How fast can nanotechnology go? National Journal 37 8. Moradi, M. Six opportunities in nano-enabled drug delivery systems.

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NanoMarkets, LC February Rapamune, which was developed to reduce organ rejection in patients who receive kidney transplants, had previously been available only as an oral solution which required refrigeration and mixing with water or orange juice prior to administration. The NanoCrystal-based tablet allows for more convenient storage and administration.

Fortina, P. Nanobiotechnology: The promise and reality of new approaches to molecular recognition. Trends in Biotechnology 23 4 ; C. Niemeyer and C. Mirkin, eds. Nanobiotechnology: Concepts, Applications and Perspectives , Wiley. Paull, R. Investing in nanotechnology. Nature Biotechnology 21 10 Choi, B. Artificial allosteric control of maltose binding protein. Physical Review Letters 94 3 Georganopoulou, D. Proceedings of the National Academy of Sciences 7 First described in the mids, PCR has become the workhorse of biological laboratories worldwide.

Researchers and clinicians use the technology to multiply, or copy, specific regions of genomes for use in various types of downstream analyses e. Mullis, K. The unusual origin of the polymerase chain reaction. Scientific American 4 and Saiki R. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.

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Science ; Saiki R. Castilla, J. In vitro generation of infectious scrapie prions. Cell 2 Carlson, R. The pace and proliferation of biological techniques. Eldredge, N. Punctuated equilibria: An alternative to phyletic gradualism. Models in Paleobiology.

Throughout most of the last century, researchers developing the synthetic theory of evolution primarily focused on microevolution, which is slight genetic change over a few generations in a population. Beginning in the early s, this model was challenged by Stephen J. Gould, Niles Eldredge, and other leading paleontologists. They asserted that there is sufficient fossil evidence to show that some species remained essentially the same for millions of years and then underwent short periods of very rapid, major change.

Gould suggested that a more accurate model in such species lines would be punctuated equilibrium. This is technologically feasible at Blue Heron today, which means that the year may be far too conservative. Tian, J. Accurate multiplex gene synthesis from programmable DNA microchips. Lohmann, V. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Chen, Y. Putting a brake on an autonomous DNA nanomotor. Normile, D. Vogel, and C. Stem cells: Cloning researcher says work is flawed but claims results stand.

Berg, C. The evolution of biotech. Nature Reviews. Drug Discovery 1 1 Wheelis, M. Biotechnology and biochemical weapons. The Nonproliferation Review 9 1 Available online at cns. Of course, there might be an equivalent concern raised by companies holding this information. Carlson, S. Scientific American July. The definition of a bioweapon, while meant to be inclusive, does not extend to nuclear weapons or devices. The Information Technology community is working to develop an ethic that this is not acceptable, even if there is no malice involved.

Some such activity may be playful, or pranks, or done without malice; other hacking causes massive damage without any real intent to do so, and still other such activity is intended to, and succeeds at, causing real damage. But all are illegitimate. Human Security—Now. Available at www. One of the earliest recorded instances of biological warfare occurred in BC, when the Athenian leader Solon used the noxious roots of the Helleborus plant to poison the water supply in the city of Kirrha.

Later, the Greeks and Romans may have used human and animal corpses to poison drinking water wells. And Alexander the Great is thought to have catapulted dead bodies over the walls of besieged cities, possibly as a means of spreading disease and inciting terror among the urban inhabitants. A related technique, used in the Middle Ages, was to deliberately leave dead human or animal corpses behind, in areas that would be occupied shortly by invading troops; catapults were used as well.

For further details about these and other later examples of germ-based warfare, including allegations that U. The Rise of CB Weapons. Vol 1. New York: Humanities Press. Biological sabotage in World War I. Van Courtland Moon, eds. Redmond, C. Deadly relic of the great war. Geissler, E. Bernstein, B. Journal of Strategic Studies 11 September : , especially and In addition to Bacillus anthracis and Clostridium botulinum , pathogens studied at Camp Detrick included the causative agents of: glanders; brucellosis; tularemia; melioidosis; plague; smallpox; psittacosis; coccidiomycosis; a variety of plant pathogens including the causative agents for rice blast; rice brown spot disease; late blight of potato; and cereal stem rust.

Animal and avian pathogens studied included rinderpest virus, Newcastle disease virus, and fowl plague virus. See also Cochrane, R. Biological Warfare Research in the United States. II declassified. Department of the Army. Army Activity in the U. Biological Warfare Programs I. See Williams, P. London: Hodder and Stoughton: ; and Harris, S. London: Routledge. At least 3, people, including Chinese civilians, Russians, Mongolians and Koreans, died in the experiments between and , Chinese state media have said. Outside the site, more than , Chinese were killed by biological weapons produced by Unit , they said.

Reuters, July 18, Guilleman, J. Anthrax: The Investigation of a Deadly Outbreak. The Sverdlovsk anthrax outbreak of Science ; Meselson, M. Note regarding source strength. The ASA Newsletter , See portal. Kelly, D. The trilateral agreement: Lessons for biological weapons verification. In Finlay, T. Meier, eds. Verification Yearbook Amherst, NY: Prometheus Books. Alibek, K. New York: Random House. For personnel numbers, see Leitenberg, M. For the environmental impacts associated with biological weapons field testing, see Choffnes, E.

Germs on the Loose. The Soviet military had tested smallpox. Although Moscow has denied that it ever conducted open-air testing of smallpox, a detailed report prepared by the Monterey Institute of International Studies Center for Nonproliferation Studies asserts that the former Soviet Union did conduct such tests on Vozrozhdeniye Island. For more on this program, see Bozheyeva, G. Kunakbayev, and D. Gould, D. See also Burgess S.

Institute of Medicine. Specter, M. The New Yorker February 28 For detailed discussions of antigenic drift and shift in influenza A virus, see Krug, R. The potential use of influenza virus as an agent for bioterrorism. Antiviral Research 57 ; and Wright, P. In: D. Knipe and P. Influenza viruses are defined by two protein components on the virus surface: haemagglutinin H and neuraminidase N.

See www. Chen, H. The evolution of H5N1 influenza viruses in ducks in southern China. Avian influenza H5N1 in tigers and leopards. Emerging Infectious Diseases 10 12 Finlay, B. Common themes in microbial pathogenicity revisited. Microbiology and Molecular Biology Reviews 61 2 — Casadevall, A. Host-pathogen interactions: redefining the basic concepts virulence and pathogenicity.

Infection and Immunity 67 8 Infection and Immunity. What is a pathogen? ASM News —; Finlay,. Savage, D. Microbial ecology of the gastrointestinal tract. Annual Reviews of Microbiology , as cited in Hooper, L. Host-microbial symbiosis in the mammalian intestine: exploring an internal ecosystem. Host-bacterial mutualism in the human intestine. Science ; Buchanan, M. A billion bacteria brains are better than one.

New Scientist Also, Rakoff-Nahoum, S. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. The protective advantage of Lactobacillus spp. Commensal host-bacterial relationships in the gut. Science ; Gionchetti, P. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2 : ; Cunningham-Rundles, S. Bacterial infections in the immunocompromised host. In Nataro, J. Persistent Bacterial Infections. See also, Rao et al. Proceedings of the National Academy of Sciences 34 Blaser, M.

Ecology of Helicobacter pylori in the human stomach. Frontal and stealth attack strategies in microbial pathogenesis. Host-pathogen interactions: Basic concepts of microbial commensalism, colonization, infection, and disease.

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Infection and Immunity 68 12 —; Pirofski, L-A. The meaning of microbial exposure, infection, colonisation, and disease in clinical practice. Lancet Infectious Diseases 2 10 —35; Casadevall, A. The damage-response framework of microbial pathogenesis. Nature Reviews Microbiology 1 1 Journal of Clinical Investigation 4 — It may also be possible to produce more dangerous pathogens by intentionally or inadvertently disrupting this dynamic equilibrium.

Merrell, D. It should, however, be noted that severe disease or mortality enhances the transmissibility of some pathogens—eg. Nature ; Mascie-Taylor, C. The burden of chronic disease. Staskawicz, B. Common and contrasting themes of plant and animal diseases. Science 22 Plotnikova, J. Pathogenesis of the human opportunistic pathogen Pseudomonas aeruginosa PA14 in arabidopsis.

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Plant Physiology 4 ; Woolhouse, M. Population biology of multihost pathogens. Reeve, J. Archaebacteria then…Archaes now are there really no archaeal pathogens? Journal of Bacteriology 12 ; Eckburg, P. Archaea and their potential role in human disease. Infection and Immunity 71 2 — Lepp, P. Methanogenic Archaea and human periodontal disease. Proceedings of the National Academy of Sciences 16 Worobey, M.

Extensive homologous recombination among widely divergent TT viruses. Journal of Virology 74 16 Shimono, N. Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon. Hypervirulence and pathogen fitness. Trends in Microbiology 11 3 Mouslim, C. Conflicting needs for a Salmonella hypervirulence gene in host and non-host environments. Molecular Microbiology 45 4 Lorange, E. Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis. Journal of Infectious Diseases 11 The Committee recognizes that virulence can evolve to increase or decrease in a pathogen, in response to specific circumstances, such as how the pathogen is transmitted from person to person.

Kagan, E. Bioregulators as instruments of terror. Clinics in Laboratory Medicine 21 3 See also, Wheelis, M. Will the new biology lead to new weapons? Arms Control Today 34 6 Pirofski, Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity. Infection and Immunity 67 8 : ; Ingham, H.

Pathogenic synergism. Goodnow and R. Immunological tolerance: danger—pathogen on the premises! Current Biology Kagnoff, M. Epithelial cells as sensors for microbial infection. Journal of Clinical Investigation 1 Science ; Rakoff-Nahoum, S. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Kobayashi, K. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.

Science ; Maeda, S. Science ; Girardin, S. Trends in Immunology 24 12 ; Girardin, S. Nod1 detects a unique muroopeptide from gram-negative bacterial peptidoglycan. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide MDP detection. Journal of Biological Chemistry 11 : ; Fiocchi, C. Inflammatory Bowel Disease: Etiology and Pathogenesis. Gastroenterology 1 Nixdorff, K. Ethics of university research, biotechnology and potential military spin-off. Minerva 40 1 Proliferation: Threat and Response.

Block, S. Living nightmares: Biological threats enabled by molecular biology. In Drell, S. Sofaer, and G. Krug, R. Antiviral Research 57 Kobasa, D. Enhanced virulence of influenza A viruses with the haemagglutinin of the pandemic virus. Tumpey, T. Characterization of the reconstructed Spanish influenza pandemic virus. Science ; Taubenberger, J.

Characterization of the influenza virus polymerase genes. An evaluation of bioregulators as terrorism and warfare agents. ASA Newsletter 90 The list was initiated in , when the Antiterrorism and Effective Death Penalty Act of required the Secretary of HHS to establish and enforce safety procedures for the transfer of listed biological agents select agents , including measures to ensure proper training and appropriate skills to handle such agents, and proper laboratory facilities to contain and dispose of such agents. An expanded list of pathogens and toxins went into effect on February 11, Agricultural plant and animal pathogens are now also included; other changes reflect taxonomic changes and a few reassessments of what constitutes the most dangerous biothreat agents.

See Table in National Research Council. Our current biosafety system and select agents lists are mostly concerned with full systems or whole organisms. But as we start to construct new things via the combination of many functions in novel ways, the current scheme will not scale. Averting the hostile exploitation of biotechnology. Information about current biological weapons capabilities summarized in Squassoni, S. Nuclear, biological, and chemical weapons and missiles: Status and trends.

Theodore Kaczynski, the Unabomber, was charged in with making and delivering four bombs that killed two men and maimed two scientists. In all, Mr. Kaczynski was alleged to have killed three people and injured 29, in 16 attacks between and Hacking the genome. They also worry about innocent mistakes: organisms that could potentially create havoc if allowed to reproduce outside the lab. Associated Press, November Much of this discussion draws from Chyba, C. Toward biological security. Foreign Affairs 81 3 ; and Chyba, C. Biotechnology and bioterrorism: An unprecedented world. Survival 46 2 Weapons of Mass Effect i.

Weiss, L. Atoms for peace. And because these nuclear materials advertise their presence by emitting various distinctive signatures as radioactive emissions from the source. Chyba, C. For a more in-depth discussion of this point see, National Research Council. The Draft Convention and a discussion about the need for such a convention may be found at www. The protective technologies that are developed in such a competition are very unlikely to be classified for all the reasons described and hence may enable malicious applications of that same technology.

This means that it is difficult for defensive applications to win, and bears on the question which should be discussed to a greater extent of whether defense can win an offense-defense competition. Center for Strategic and International Studies. Controlling biological warfare threats: Resolving potential tensions among the research community, industry, and the national security community. Critical Reviews in Microbiology, 27 4 , especially pp.

Daar, A. Top 10 biotechnologies for improving health in developing countries. Nature Genetics As an exercise in practical GM crops, consider the lessons of Lansing, J. Hoyt, K. A double-edged sword. International Security 28 Winter Jackson, R. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. Journal of Virology 75 3 Cello, J.

Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Rosengard, A. Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement. Proceedings of the National Academy of Sciences 99 13 Fraser, C. Genomics and future biological weapons: The need for preventive action by the biomedical community. Nature Genetics 29 3 See, also, National Research Council. Arora, N. Fusions of anthrax toxin lethal factor with shiga toxin and diptheria toxin enzymatic domains are toxic to mammalian cells.

Infection and Immunity 62 11 Broad, W. Gene-engineered anthrax: Is it a weapon? Tests with anthrax raise fears that American vaccine can be defeated. New York Times March Aldous, P. Biologists urged to address risk of data aiding bioweapon design. Nature : as cited in Zilinskas, R. Limiting the contribution of the open scientific literature to the biological weapons threat. Journal of Homeland Security. Hatta, M. Gibbs et al. Boyce, N. US News and World Report 6 Wang, X. Biotechnology and Bioengineering 72 4 US News and World Report 22 : Wein, L.

Analyzing a bioterror attack on the food supply: The case of botulinum toxin in milk. Proceedings of the National Academy of Sciences 28 Berg, P. Proceedings of the National Academy of Sciences 72 6 : Biomedical advances have made it possible to identify and manipulate features of living organisms in useful ways--leading to improvements in public health, agriculture, and other areas. The globalization of scientific and technical expertise also means that many scientists and other individuals around the world are generating breakthroughs in the life sciences and related technologies.

The risks posed by bioterrorism and the proliferation of biological weapons capabilities have increased concern about how the rapid advances in genetic engineering and biotechnology could enable the production of biological weapons with unique and unpredictable characteristics. Globalization, Biosecurity, and the Future of Life Sciences examines current trends and future objectives of research in public health, life sciences, and biomedical science that contain applications relevant to developments in biological weapons 5 to 10 years into the future and ways to anticipate, identify, and mitigate these dangers.