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Marranos who escaped to Rome made bitter complaints to Pope Clement of the inhumanity with which the Inquisition persecuted them and their brethren, and urged that the king had obtained the bull by fraud, inasmuch as the facts of the case had not been set before the papal consistory in a proper light. They especially complained that emigration was prohibited, in direct opposition to the legal equality which had been granted. Clement VII, who regretted that he had issued the bull, to which he had been forced, sympathized with their grievances. He may have felt, too, that the fires of the Inquisition, employed against those who were neither Catholics nor willing converts, branded the Catholic Church, and gave the Lutherans more material to continue their hostile assaults, to depict it as bloodthirsty and a just object of hatred. Moreover, he was well aware that the Inquisition had been introduced into Portugal only because Spain and his arch-foe, Emperor Charles, desired it, with the object of placing Portugal in an unequivocally dependent condition. Hence Clement revolved a plan to revoke the bull. At this time Solomon Molcho and David Reubeni resumed their mystical activity, and conceived the daring scheme of going to the emperor at Ratisbon, where the Reichstag was then assembled. With a floating banner, embroidered with the letters "Machbi" (initials of the Hebrew words of the verse, "Who is like unto thee among the gods, O Lord"), they traveled from Bologna, by way of Ferrara and Mantua, to Ratisbon. Emperor Charles gave them audience, and they probably pleaded the cause of the Jews earnestly. An unwarranted and improbable report affirms that they attempted to convert the emperor to the Jewish faith. But they were not so heedless as to make this attempt. They simply petitioned the emperor to permit the Marranos to arm themselves, and, joining the Jewish tribes, attack the Turks. Joslin of Rosheim, who was also in Ratisbon, vainly warned them not to make this request. The end was that Charles put them both in chains (June-September, 1532), and carried them fettered to Mantua. The banner was left at Ratisbon. An inquisition, at the emperor's wish, was set on foot at Mantua, and Molcho was condemned to be burnt to death for relapse and heresy. While the emperor was diverting himself by triumphal processions, festivals, hunting, plays, and all imaginable merry-makings, the funeral pile of the Lisbon Marrano was built up, and set on fire. They led him to the place of execution with a gag in his mouth, for his eloquence was so powerful and persuasive that emperor and tribunal feared its effect on the crowd. He was, therefore, forced to keep silence. But when the executioners were ready to throw him into the blazing fire, a courier from the emperor arrived, removed the gag, and asked him in the emperor's name, whether he repented of his transgressions and was willing to return to the bosom of the church; if so, he should be pardoned. As might have been expected, Molcho replied that he had longed to die a martyr, "a burnt-sacrifice, of a sweet savour unto the Lord," that he repented him of only one thing – that he had been a Christian in his youth. Come life, come death, he commended his soul unto God. Then he was thrown into the midst of the flames, and died with unshaken constancy.

Molcho was the victim of a phantasmagoria, a delusion, into which, at feud with reality, he allowed himself to fall. The rich gifts bestowed on him by nature – a handsome person, glowing imagination, quick perception, ready enthusiasm – which would have been steps on the ladder of fortune for any character less fantastical, only served to ruin him, because, swept into the vortex of the Kabbala, he fondly hoped to accomplish the work of redemption. David Reubeni had not even the martyr's crown. Charles carried him to Spain, and cast him into a dungeon of the Inquisition, in which he was still living three years afterwards. It appears that he was at length put to death by poison. As a Jew, the Inquisition had no power over him. But many of the Spanish Marranos who had had intercourse with him, and whose names he probably betrayed on the rack, were burnt to death.

Enthusiasm for Molcho was so great that a mistaken faith was pinned to him, and various fictions respecting him were invented. In Italy and Turkey numbers believed that he had on this occasion, as once before, escaped death. Some said that they had seen him a week after his auto-da-fé; others gave out that he had visited his bride at Safet. Joseph Karo, whose name was soon to be widely known, longed for martyrdom like Molcho's. Even the circumspect Joseph Cohen of Genoa, a careful historian, averse to belief in miracles, was dazed, and knew not what to think of the affair. An Italian Kabbalist, Joseph of Arli, would not abandon the hope that the time of the Messiah, as announced and prepared by Molcho, would soon dawn on the Jewish world. Molcho's death, according to him, would soon find avengers. By a childish transposing of the letters of two verses in Isaiah (Notaricon), he predicted the downfall of the religion of Jesus from various causes: Luther's agitation, the many new sects springing up among Christians, the recent sack of Rome, and the mutually inimical attitude of the pope and the emperor.

The Kabbalist of Arli was ill-disposed towards the pope, though unreasonably so, for he was certainly not guilty of Molcho's death; on the contrary, the pope had to look on while the emperor, to gain his own ends, executed one, and imprisoned the other, of his favorites. However, Clement seems to have made a countermove. He strove to bring about the revocation of the fatal bull authorizing the institution of the Inquisition in Portugal, or at least to make it less drastic in its effects. The Marranos knew this, and made every effort to win the papal curia to their side. As soon as they understood that Solomon Molcho, their most successful advocate, was no longer to be reckoned upon, they sent another envoy to Rome, to bring their grievances before the pope and defend their cause. This new advocate of the Marranos, Duarte de Paz, was the very opposite in character to Molcho: cool-headed, far removed from any extravagance, cunning, calculating, bold, and eloquent, initiated into all the trickery of diplomacy, possessing profound knowledge of human nature, and able to make use of men's foibles for his own ends. Duarte de Paz for nearly eight years looked after the interests of Portuguese new-Christians. He was himself of Marrano descent, and as a reward for his services to the Portuguese court in Africa had obtained an important post and the confidence of King João III. Chosen by the king to perform a secret mission, and made a knight of the order of Christ (styled also Commendatore) on the day of his departure, he set out, not for the appointed place, but for Rome, to work for the Marranos. Duarte de Paz entwined the threads of his intrigues so intricately that to this day it is impossible to ascertain exactly whom he deceived, whether the king or the Marranos. His clients, the Marranos, kept him well supplied with money, which, for good or evil, was almighty at the pope's court. Duarte de Paz obtained substantial successes in return for his pains and his presents. Clement was convinced anew that most atrocious injustice was done the new-Christians in demanding Catholic orthodoxy from those who had been dragged with brutal force to be baptized, and in denying them liberty to journey beyond the confines of Portugal. The pope issued an apostolical brief (October 17th, 1532) stopping the proceedings of the Inquisition until further notice. Duarte de Paz continued his efforts in order to procure a general pardon for all Marranos denounced or imprisoned. It appears that intrigues were set on foot in favor of the Marranos even at the court of João III. The party in favor of the Inquisition worked for Spanish interests, and, in view of the probability of the king's remaining without issue, was eagerly bent on making the Portuguese crown one with the Spanish. On the other side, the national party, which sought to preserve the independence of Portugal, seems to have been against the Inquisition. Hence plotting and counter-plotting continued for several years to such an extent, that the inquisitor general, Diogo de Silva (appointed by the pope himself), declared that he would not undertake so great a responsibility, and resigned his office. Duarte de Paz obtained a second extraordinarily important brief from Pope Clement. The pope recognized as fair and legitimate the reasons urged by new-Christians to justify their lack of attachment to the church.

"Since they were dragged by force to be baptized, they cannot be considered members of the church, and to punish them for heresy and relapse were to violate the principles of justice and equity. With sons and daughters of the first Marranos the case is different, they belong to the church as voluntary members. But, as they have been brought up by their relatives in the midst of Judaism, and have had their example continually before their eyes, it would be cruel to punish them according to the canonical law for falling into Jewish ways and beliefs; they must be kept in the bosom of the church through gentle treatment."

By this brief Clement VII abrogated the power of the Portuguese Inquisition, ordered that denunciation of Marranos should be carried before his own tribunal, and granted to all a thorough absolution or amnesty for past defection from the church. Those languishing in the dungeons of the Inquisition were to be set free, the banished allowed to return, and those robbed of their goods to have them restored. Clement declared, with the peculiar untruthfulness of the papacy, from which even the best popes were unable to free themselves, that he had issued this brief of his own accord, without the suggestion of the Marranos, although the whole world knew the contrary, and counted up how many scudi the see had received for the letter. Clement also declared all who should resist this brief, clergy as well as laity, to be under the ban, and urgently pressed his envoy, Marco della Ruvere, to make it known throughout Portugal. To do Pope Clement VII justice, it must be said that he steadfastly defended the cause of humanity towards the unhappy Marranos against the bloodthirsty spirit of the Christianity of his time, though it must be admitted that other and not quite pure motives may have conduced to his action – viz., hatred of Charles V, who upheld the proposal for a Portuguese Inquisition, and greed for the sums of money paid him and his retainers. The thought of delivering the Marranos to the tender mercies of those bloody-minded wretches in Portugal was not to be lightly endured. Although the question had been thoroughly discussed, Clement appointed a commission, consisting of the two neutral cardinals, De Cesis and Campeggio, to consider the matter once more. The grand penitentiary, Antonio Pucci, Cardinal de Santiquatro, could not be excluded, although a partisan of the Portuguese court. Nevertheless, this commission officially attested the perpetration of devilish atrocities by the Inquisition against pseudo-Christians. In consequence of their report, Clement VII (July 26th, 1534), feeling that his end was near, issued a brief to the nuncio at the Portuguese court to press the release and absolution of imprisoned Marranos. There were about twelve hundred of them, and it may be doubted whether this brief effected their deliverance. Clement's death (September 25th, 1534) brought to naught his good intentions and the Marranos' hopes.

Intrigues concerning the Inquisition were woven anew under his successor, Paul III Farnese (1534–1549), at first to the prejudice of the Marranos, though this pope belonged to the old school of worldly-minded, diplomatic, by no means bigoted princes of the church. He was a subtle schemer, and paid more attention to earthly than to heavenly powers. Paul III was specially well-disposed to Jews. If a description by a narrow-minded bishop (Sadolet of Carpentras) is true only to a small extent, it still proves that this friendliness must have been remarkable. "No pope has ever bestowed on Christians so many honors, such privileges and concessions as Paul III has given to the Jews. They are not only assisted, but positively armed with benefits and prerogatives." Paul III had a Jewish physician in ordinary, Jacob Mantin, who dedicated some of his works to him.

As soon as Paul III had ascended the papal chair, the king of Portugal deemed it most important to procure a revocation of Clement's bulls and briefs in favor of the Marranos, and opposed to the Inquisition. But Duarte de Paz, the Marranos' advocate, who had been given an aid in Diogo Rodrigues Pinto, spared no effort to oppose the contemplated change of policy. Gold also was not wanting. Duarte de Paz, although apparently engaged in a traitorous correspondence with the king, Don João, offered Cardinal Santiquatro, the partisan of Portugal, a yearly pension of 800 crusados, if he would give his support to the Marranos. The pope, diplomatically cautious as he was, and disinclined to bind himself, decided at first (November 3d, 1534), that Clement's brief should not be promulgated. But when he learned that it had already taken effect, he ordered the case to be again considered, and for that purpose named two cardinals, Ghinucci and Simoneta, of whom the first decidedly favored the Marranos, having published a work in their defense. The result of their investigation was that Paul III emphatically admonished the Portuguese court to obey Clement VII's bull of absolution. He was decidedly opposed to the imprisonment of Marranos in inaccessible dungeons and against the confiscation of their property. But the Catholic kings of that day showed obedience to the papal see only as long as it suited them and their interest; so João III paid but small heed to the pope's admonition. His envoy even advised him, in order to carry on the Inquisition, to cut himself adrift from the Romish Church as England had done. A complete web of intrigues was spun over this affair in Rome and Portugal. In Portugal the court was on the one side, and the Marrano leaders, Thomé Sarrão and Manuel Mendes, with the papal legate on the other – at Rome, Duarte de Paz and Pinto, against or with the Portuguese ambassador and against Cardinal Santiquatro.

Disgusted and wearied, Paul III, who did not readily give up an intention once formed, issued a new, decisive bull (October 2d, 1535), giving absolution to the Marranos, and protecting them against all clerical and civil penalties for relapse and heresy, provided that they would not be guilty of similar offenses in future. The Inquisition in Portugal, which for the sake of appearance could not proceed without the authorization of the pope, was once again arrested. The nuncio set to work energetically, made the bull known throughout Portugal, and carried matters so far, that even the inimically disposed Infante Don Alfonso opened the prison doors to free those whose release was so pressingly recommended by Rome. Altogether there were eighteen hundred Marranos liberated (December, 1535).

At first dazed as by a sudden blow, the Portuguese court later on set every lever in motion once more to obtain sovereign power over the Marranos and their property. It did not shrink from assassination to gain its ends. One day Duarte de Paz was attacked on the high road by assassins, and left lying there for dead, covered with fourteen wounds (January, 1536). All Rome believed the murderers to be hirelings of the Portuguese court. The pope was greatly provoked at this crime, and sent physicians to pay every attention to the procurator, who eventually recovered. Nevertheless, with respect to the Inquisition, the pope had to comply with the wishes of the Portuguese court, which had at last found out the right way to reach its goal. It had recourse to the victorious Charles V, urgently requesting him to manage the affair. Just at that time the emperor had fought a hard battle near Tunis with the Mahometan Barbarossa, who, supported by Turkey, had disquieted all Christendom. After many struggles, the numerous host of Christians, led by Charles himself, gained the day, and Barbarossa was defeated.

When Charles arrived in Rome after a triumphal progress through Italy, he asked the pope, as a reward of his victory for Christianity, to authorize the Inquisition in Portugal. Paul III did not yield without a struggle. He always returned to the contention that the Portuguese Marranos were originally dragged by force to be baptized, and that, therefore, the sacrament had no hold upon them.

Unfortunately for the Marranos, their means for satisfying the greed of the papal court for gold were exhausted. Their advocate, Duarte de Paz, had promised exorbitant sums for the frustration of the Inquisition, and had misappropriated to his own use part of the money intrusted to him. The pseudo-Christians thus found themselves obliged, when pressed for payment by the papal nuncio, to declare that they were not in a position to redeem the exaggerated promises of Duarte de Paz. Moreover, this commerce between the nuncio and Marranos was betrayed, and the latter had to exercise yet greater caution. Hence interest in the Marranos gradually cooled down at the pope's court. As the emperor put increasing pressure on Paul III to authorize the Inquisition in Portugal, the pope at last sanctioned the tribunal for the Portuguese dominions (May 23d, 1536). The pope, friend of the Jews as he was, granted his sanction with a heavy heart, forced thereto by pressure from the emperor. He added all sorts of restrictions, that for the first three years the method of procedure in current civil courts must be adhered to, i. e., open confrontment with witnesses – at least as regarded that class of Marranos which was not greatly esteemed – and that the confiscation of condemned Marranos' goods should take place only after the expiration of ten years. Personally, the pope recommended gentle measures in dealing with pseudo-Christians. Don João's joy at the ultimate fulfillment of his heart's desire was so great that he accepted the conditions. But the concession was only a pretense; in reality, the same rigor was employed against the Portuguese Marranos as against the Spanish. The admonition published by the Inquisition, that it was everyone's duty, under penalty of excommunication or a yet more severe punishment, to denounce any Jewish observances or expressions of the new-Christians, differed in no respect from that published by the first bloodthirsty Spanish inquisitor, Torquemada. In November of the same year, after the expiration of the thirty so-called days of grace, the bloody tribunal began its revolting and abominable activity, once again outraging and dishonoring human nature. The Portuguese Inquisition was conducted with almost more cruelty than the Spanish, because, on the one hand, its introduction had cost so much trouble, and the public mind was thereby embittered; on the other, because the Portuguese Marranos were more steadfast than their Spanish brethren, and finally, because the common people supported the Inquisition, and took part against the new-Christians. João III even made them wear a distinguishing mark to separate them visibly from other Christians.

They did not, however, accept their defeat inactively, but rather set to work with all imaginable energy to bring about a revocation of the bull. The most subtle intrigues were again commenced at the papal court. Duarte de Paz once more displayed his diplomatic skill. The Marranos raised complaints of the cruel dealings of the judges, who neglected to obey the pope's instructions. More especially they complained that liberty to emigrate and dispose of their real estate was still denied them.

In a memorial to the pope they ventured on almost threatening language:

"If your Holiness despises the prayers and tears of the Hebrew race, or despite our hopes, refuses to redress our grievances, as would beseem the vicar of Christ, then we protest before God, and with tears and cries that shall be heard afar off will we protest in the face of the universe, that our lives, our honor, our children, who are our blood, our very salvation made the butt of persecution, we will nevertheless try to hold ourselves aloof from the Jewish faith; but if tyranny ceases not, we will do what no one of us would else think of, i. e., return to the religion of Moses, and abjure Christianity, which we are made to accept by main force. We solemnly cry aloud that we are victims, by the right which that fact gives us – a right which your Holiness recognizes. Leaving our native land, we will seek protection among less cruel peoples."

The nuncio who had returned from Portugal, knowing by long years of experience the position of men and affairs, managed to convince the pope that his sanction of the Inquisition was a mistake, and as Paul III had only given way to momentary pressure, a change of sentiment soon followed, and he repented the step he had taken. He went so far as again to submit his bull to a committee which was to examine its legality. To this commission the Marranos' friend, Cardinal Ghinucci, was elected along with another of like mind, Jacobacio. They contrived to prejudice the third member, the honest but narrow-minded Cardinal Simoneta, against the Inquisition, so that he begged the pope to right matters by the revocation of his former bull. Another nuncio was sent to Portugal, with authority within certain limits to nullify the proceedings of the Inquisition against the Marranos, to protect the latter, and particularly to render easier their emigration from Portugal. The pope sent a brief (dated August, 1537) after the nuncio, empowering and, to some extent, encouraging all to give protection and assistance to the accused Marranos – in fact, to do exactly what in Portugal was held to be conniving at and participating in heresy. The king must have been considerably puzzled. Here he was at length in possession of a bull, a tribunal, a grand inquisitor and his colleagues – the whole apparatus of a slaughter-house for the glory of God – and he might just as well have had nothing at all.

An incident again turned the chances of the game in favor of the king and the fanatics. One day (February, 1539) a placard was discovered fastened on the door of the Lisbon Cathedral: "The Messiah has not yet appeared – Jesus was not the Messiah, and Christianity is a lie." All Portugal was indignant at such blasphemy, and a strict investigation was set on foot to find out the offender. The king offered a reward of 10,000 crusados (ducats). The nuncio also offered 5,000 crusados, as he, with many others, was of opinion that this was a blow from some enemy of the Marranos, designed to excite the king's fanaticism to a higher degree, and to get the nuncio into trouble. To turn aside suspicion the new-Christians posted a notice on the same place – "I, the author, am neither a Spaniard nor a Portuguese, but an Englishman, and though you raise your reward to 20,000 crusados, you will not find me out." After all, the writer turned out to be a Marrano, one Emanuel da Costa. He confessed everything when cited before the Inquisition. The civil court then took him in hand, and put him on the rack to make him name his accomplices. Finally, after both hands had been cut off, he was burnt to death. The Marranos foresaw evil consequences for themselves, and took to flight. The king made the best of this opportunity to enforce the rules of the Inquisition with increased severity and bloodthirstiness, and to thwart the nuncio's efforts. The maddest fanatics were at once elected inquisitors, to the great anger of the pope and his nuncio. João Soares, whom the pope himself once described as "not a learned, but a most daring and ambitious, monk, with opinions and ideas of the very worst kind, who takes pride in his enmity to the apostolic see," was now given unbounded power over the lives of the new-Christians, and his colleague was Mallo, an arch-foe of the new-Christians. For the Marranos the state of affairs grew worse every day. On three points the pope showed immovable firmness: the Infante Don Henrique must not remain grand inquisitor; Marranos accused of heresy should have the witnesses' (that is, their accusers') names announced to them; finally, after sentence is passed they should be allowed recourse to the papal court of appeals. Indeed, Paul III caused a new bull to be drawn up (October 12th, 1539) – a supplement of that issued three years before – which throughout was of a favorable tenor to new-Christians, and would completely have crippled the Inquisition. But this likewise remained a dead letter. After this, fires for the obstinate heretics were kindled more frequently than ever, and more victims were sacrificed (from ten to forty a year) without permitting them to appeal to the pope. The denounced and suspected Marranos filled the prisons.

A contemporary poet, Samuel Usque, gives a dreadful picture of the tortures of the Portuguese Inquisition, which he himself had experienced in his youth:

"Its institution deprived the Jews of peace of mind, filled their souls with pain and grief, and drew them forth from the comforts of home into gloomy dungeons, where they dwelt amid torment and sighs of anguish. It (the Inquisition) flings the halter round their necks, and drags them to the flames; through its decrees they must see their sons murdered, husbands burnt to death, and brothers robbed of life; must see their children made orphans, the number of widows increased, the rich made poor, the mighty brought low, the nobly born transformed into highway robbers, chaste, modest women housed in lewd, ignominious dwellings, through the poverty and desertion in its wake. It has burnt numbers to death, not one by one, but by thirties, by fifties at a time. Not content with mere burning and destroying, it leads Christians to boast of such deeds, to rejoice when their eyes behold the members of my body (the sons of Jacob) burning to death in the flames, kindled with fagots dragged from afar on men's shoulders. Those baptized against their will, steal about overpowered with fear of this savage monster (the Inquisition); they turn their eyes on every side lest it seize them. With ill-assured hearts they pass to and fro, trembling like a leaf, terror strikes them suddenly, and they stay their steps lest it take them captive. When they sit down together to eat, every morsel is lifted to their mouths in anguish. The hour that brings repose to all other beings only increases their anxiety and exhaustion. At times of marriage and the birth of children, joy and feasting are turned into mourning and disquietude of soul. In fine, there is no moment not paid for by a thousand deadly fears. For it suffices not that they make themselves known as Christians by outward signs. Fire rages in their hearts, their tortures are innumerable."

Is this an exaggerated description? Did the poet's imagination transform petty sufferings into the pains of martyrdom? Every word of it is corroborated by an assembly of cardinals, officially gathered to investigate the proceedings of the Portuguese Inquisition against the Marranos.

"When a pseudo-Christian is denounced – often by false witnesses – the inquisitors drag him away to a dismal retreat where he is allowed no sight of heaven or earth, and least of all to speak with his friends, who might succor him. They accuse him on obscure testimony, and inform him neither of the time nor the place where he committed the offense for which he is denounced. Later on he is allowed an advocate, who often, instead of defending his cause, helps him on the road to the stake. Let an unfortunate creature acknowledge himself a true believing Christian, and firmly deny the transgressions laid to his charge, they condemn him to the flames, and confiscate his goods. Let him plead guilty to such and such a deed, though unintentionally committed, they treat him in a similar manner under the pretense that he obstinately denies his wicked intentions. Let him freely and fully admit what he is accused of, he is reduced to extremest necessity, and condemned to the dungeon's never-lifting gloom. And this they call treating the accused with mercy and compassion and Christian charity! Even he who succeeds in clearly proving his innocence is condemned to pay a fine, so that it may not be said that he was arrested without cause. The accused who are held prisoners are racked by every instrument of torture to admit the accusations against them. Many die in prison, and those who are set free, with all their relatives bear a brand of eternal infamy."

As the Inquisition grew more and more severe and bloodthirsty, the Portuguese new-Christians clung with increasing tenacity to the last anchor of hope left – to the pope and their other protectors. They had found a new advocate and mediator, who gave promise of being more honest and energetically active on their behalf. The battle between the Portuguese court and the papal see blazed up afresh. It was war to the death, not for those immediately concerned, but for the miserable beings who, in spite of self-repression, could not become reconciled to Christianity, yet were not courageous enough to suffer for Judaism – who would give up neither convictions, wealth, nor position. To influence the pope, or at least those about his person against the Marranos, the Infante and grand inquisitor Henrique had a list of the delinquencies of the new-Christians made out and sent to Rome (February, 1542). The Marranos, also, to wrest the weapons from their opponents' hands, in Rome and elsewhere, and for all times to refute the lying reports and statements of the Portuguese court, drew up a bulky memorial (1544), detailing their troubled lot, from the time of King João II and Manoel, who forced them to accept Christianity, until the most recent times, and verifying their statements by documentary evidence – a monument of everlasting disgrace to that age.