Originally Alexander Alane, he was born at Edinburgh. He studied at St Andrews in the newly-founded college of St Leonard's, where he graduated in 1515. Some time afterwards he was appointed a canon of the collegiate church, where he contended vigorously for the scholastic theology as against the doctrines of the Reformers. His views entirely changed, however, on the execution of Patrick Hamilton, abbot of Fern, in 1528. He had been chosen to meet Hamilton in controversy, with a view to convincing him of his errors, but the arguments, of the Scottish proto-martyr, and above all the spectacle of his heroism at the stake, impressed Alesius so powerfully that he was won over to the cause of the Reformers.
A sermon which he preached before the Synod at St Andrews against the dissoluteness of the clergy offended the provost, who placed him in prison, and might have carried his resentment further if Alesius had not escaped to Germany in 1532. After travelling through northern Europe, he settled down at Wittenberg, where he made the acquaintance of Martin Luther and Philipp Melanchthon, and signed the Augsburg confession. Meanwhile he was tried in Scotland for heresy and condemned without a hearing. In 1533 a decree of the Scottish clergy, prohibiting the reading of the New Testament by the laity, drew from Alesius a defence of the right of the people, in the form of a letter to King James V of Scotland.
A reply to this by Johann Cochlaeus, also addressed to the Scottish king, occasioned a second letter from Alesius, in which he amplified his argument with great force and entered into more general questions. In August 1534 he and a few others were excommunicated at Holyrood by the deputy of the archbishop of St Andrews. When King Henry VIII of England broke with the church of Rome Alesius was persuaded to go to England, where he was cordially received (August 1535) by the king and his advisers, Thomas Cranmer and Thomas Cromwell.
After a short stay at Lambeth Palace he was appointed, through the influence of Cromwell, then chancellor of the university, to lecture on theology at the University of Cambridge; but when he had delivered a few expositions of the Hebrew psalms, he was prevented from continuing by the papal party. Returning to London he supported himself for some time by practising as a physician. In 1537 he attended a convocation of the clergy, and at the request of Cromwell conducted a controversy with John Stokesley, Bishop of London, on the nature of the sacraments. His argument was afterwards published under the title Of Me Auctorile of the Word of God concerning the number of the sacraments.
In 1539 Alesius was compelled to flee for a second time to Germany, as a result of the enactment of the statute of the Six Articles. He was appointed to a theological chair in the university of Frankfurt an der Oder, where he was the first professor to teach the reformed doctrines. In 1543 he left Frankfurt for a similar position at Leipzig, his contention that it was the duty of the civil magistrate to punish fornication, and his sudden departure, having given offence to the authorities of the former university. He was in England again for a short time during Edward VI's reign, and was commissioned by Cranmer to make a Latin version of the First Prayer-Book (1549) for the information of Martin Bucer, whose opinion was desired.
Alesius published a large number of exegetical, dogmatic and polemical works, of which over twenty are mentioned by Bale in his List of English Writers. In his controversial works he upholds the synergistic views of the Scottish theologian John Major. He displayed his interest in his native land by the publication of a Cohortatio ad Concordiam Pietatis, missa in Patriam suam (1544), which had the express approval of Luther, and a Cohortatio ad Pietatis Concordiam ineundam (1559).
The best early account of Alesius is the Oratio de Alexandra Alesio of Jacob Thomasius (April 1661), printed in the latter's Orationes (No. XIV., Leipzig, 1683.
Reference