Origen's immediate successor at the Didascalia was Heraclas, (185-248). When Origen was obliged by his father's martyrdom and the consequent confiscation of his goods to commence teaching grammar and philosophy, Heraclas and his brother Plutarch were his first pupils, and thus it was Origen who converted them both to Christianity. (St. Plutarch soon suffered for the faith, being the first of Origen's pupils to gain the crown of martyrdom) At the Catechetical School Heraclas became known for his knowledge of philosophy and Greek learning. He had admirers who travelled from afar such as Julius Africanus. Origen made him his assistant as he himself had so many students. When Demetrius exiled Origen from the diocese, he appointed Heraclas as Head of the School in c.230. This was short lived however as he followed the aged Demetrius as bishop in c.230. It is said that when he increased the number of local bishops to 20, the presbyters decided to distinguish him from the rest of the bishops by calling him "Papa." Thus, he was the first to bear the title of Pope, long before its use in Rome. He died in c.246.
The next head of the School, another famous pupil of Origen, was Dionysius of Alexandria (c.190- c.264), later surnamed the Great. He occupied that post from c. 232 and probably even after he became the patriarch in 246. Dionysius as did prelates after him issued from Alexandria the time of Easter for each year at Epiphany. During the persecution under Decius c.250, Dionysius was rescued by friends and taken away to the desert in Libya until it ended. Because of his own experience throughout the persecution he sided with Cornelius against Novatian in Africa over the issue of apostasy. He took a somewhat milder view than Cyprian, for he gave greater weight to the "indulgences" granted by the martyrs, and refused forgiveness in the hour of death to none. However the validity of baptism by those who apostasied spread from Africa to the East. Dionysius disagreed with those who held that a baptism conducted by a "schismatic" or "heretic" soiled rather than cleansed the catchumem. In other words such baptisms were valid. It was partly Dioynsius's attitude that enabled the baptism issue to heal much quicker in the East than it did in the West.
When the Valerian persecutions began in 257 Dionysius after being tried with a priest and two deacons before the prefect of Egypt was banished to Kephro in the Mareotis. Unlike Cyprian, Dionysius was spared and returned to Alexandria when the persecutions ended. Peace had returned to the Church, but not to Alexandria which was in a state of tumult. Even the bishop had to communicate by letter to his flock as walking through Alexandria was dangerous.
During his time as Head of the School and also as bishop Dionysius upheld the Orthodox teaching of the Faith and he thus opposed heresies vehemently. One such heresy was propounded by an Egyptian bishop, Nepos, whose parousia's doctrine taught that there would be a reign of one thousand years of Christ upon earth in his Refutation of the Allegorizers. After Nepos' death, Dionysius refuted his argument in On the Promises. Another heresy was Sabellianism, which denied the distinctness of the Persons of the Blessed Trinity. Dionysius wrote four letters against this heresy and sent copies to Sixtus II. But it would seem in responding to this heresy that Dionysius went so far in the opposite direction that he spoke of the Son as poíema (i.e. something made) and distinct in substance, xénos kat' oùsian, from the Father, even as is the husbandman from the vine, or a shipbuilder from a ship. When he was accused of heresy, Dionysius wrote two books Refutation of this dogma and Apology. In these two works he certainly declared that there was never a time when God was not the Father and that Christ was and is the Word and Wisdom and Power and co-eternal with the Father. The "Trinity in Unity and the Unity in Trinity" he clearly expressed.
After Dionysius the history of the Alexandrian School is not too clear. It would seem that he was followed by Theognostus, Pierius, Pomphilus and Peter. Theognostus upheld Origen's teaching as expressed in his Hypotyposes. Pierius shared the Head position with Achillas, whilst Theonas was bishop of Alexandria. He died in Rome, c. 309, and it seems that although he underwent sufferings during the Diocletian persecution he was not martyred. Pierius' skill as an exegetical writer and as a preacher gained for him the name, "Origen the Younger". He wrote a work (biblion) comprising twelve treatises or sermons (logoi), some of which reflect Origen's teaching, even some of his "erroneous" ones such as the Holy Spirit being subordinated to the Father and the Son, and the pre-existence of human souls. His known sermons are: one on the Gospel of St. Luke; Easter sermons; a sermon on the Theotokos; and a eulogy on St. Pamphilus, who had been one of his disciples but only some fragments of these writings are extant. The next name associated as Head is Pomphilus, but practically nothing is known of him.
The next Head was Peter. Unlike his predecessors he was anti-Origen in his theology, and perhaps he began the hard feeling against the brilliant Origen. Peter held this position when the Diocletian persecution broke out and it would seem that he concealed himself and fled from Alexandria. He also had to deal with the lapsi before his own martyrdom in 311. There is extant a collection of fourteen canons issued by Peter in the third year of the persecution dealing chiefly with the lapsi, excerpted probably from an Easter Festal Epistle. The fact that they were ratified by the Council of Trullo, and thus became part of the canon law of the Eastern Church, probably accounts for their preservation.
When Athanasius (296 373) was bishop of Alexandria he appointed the blind Didymus, a layman (c.310-c.395) as Head of the School over which he presided for about half a century. Like Origen when at the School, he was highly respected and amongst his pupils were Rufinus and Gregory Nanzianen. The historian Palladius visited him four times over a period of ten years. Another visitor was Jerome who sought advice on difficult passages of the Scriptures. Didymus was a loyal follower of Origen and when Jerome declared war on the Origenists he ceased to boast of being one of Didymus' disciple. When Origenists were condemned by Justinian in sixth century Didymus and his writings fell into disfavour, despite the high praise many had heaped upon them including the orator Libanius. Writing to an official in Egypt, he stated, "You cannot surely be ignorant of Didymus, unless you are ignorant of the great city wherein he has been night and day pouring out his learning for the good of others."
Being blind himself from the age of four, he cared for the welfare of the blind by promoting a system of writing for them. In this method, he anticipated Braille by fifteen centuries.
Like Athanasius and Anthony, Didymus was a great opponent of the Arian heresy, which was taught in Alexander by Arius, a presbyter and his followers. One of Didymus' important works was De Trinitate, written in 379 in which he taught the doctrine of the Trinity and the Incarnation. A treatise against the Manichæans surives almost complete. There are also exegetical fragments, of which the Psalms are the most important. A commentary on the Catholic Epistles is known to us through the Latin translation made by a certain Epiphanius for Cassiodorus.
After Didymus, an obscure period in the history of the school followed. Its great days were over as it gave way to more pagan than Christian traditions. After the first split of the Church which happened as a result of the Council of Chalcedon in 451, the emperors of Constantinople closed the School in their persecution against the Copts. Nothing however can be taken away from the wealth of teaching and scholarship that the Didascalia gave to the early Church.