Mitchel accepted Duffy's invitation to join the staff of The Nation, in the autumn of 1845. He discarded his profession, and brought his wife and children to live in Dublin, first, for a short time at, George's Place; then at 1 Heathfield, Upper Leeson Street, and finally at 8 Ontario Terrace, Rathmines, where he was arrested in 1848.
For the next two years Mitchel wrote both political and historical articles and reviews for The Nation. He covered a wide range of subjects, including the Famine, on which he contributed some influential articles which attracted significant attention. On 25 October 1845 he wrote on "The People's Food", pointing to the failure of the potato crop, and warning landlords that pursuing their tenants for rents would force them to sell their other crops and starve.
He reviewed Curran's Speeches, Carlyle's Life of Cromwell, a pamphlet by Isaac Butt on The Protection of Home Industry, The Age of Pitt and Fox, and later on The Poets and Dramatists of Ireland, edited by Denis Florence MacCarthy (4 April 1846); The Industrial History of Free Nations, by Torrens McCullagh, and Father Meehan's The Confederation of Kilkenny (8 August 1846).
But it was Mitchel's political writings in The Nation that would show how strongly he felt with regard to English rule in Ireland.
On 1 November 1845 his article was on "Foreign Relations", and was titled, "England's Difficulty is Ireland's Opportunity". In this edition also he raised the issue on "Potato Disease", he pointed out how powerful an agent hunger had been in certain revolutions.
On 8 November, in an article titled "The Detectives", he says, "The people are beginning to fear that the Irish Government is merely a, machinery for their destruction; that, for all the usual functions of Government, this Castle-nuisance is altogether powerless; that it is unable, or unwilling, to take a single step for the prevention of famine, for the encouragement of manufactures, or providing fields of industry, and is only active in promoting, by high premiums and bounties, the horrible manufacture of crimes!"
He followed this up on 22 November, with an article titled "Threats of Coercion", in which he advocated attacks on railways if they were used against the people by the Government, in response to an article in the London journal The Standard, which outlined how the railroads could be used for troops in Ireland. This led to a failed prosecution of the paper in the following year, Mitchel acting as solicitor for the editor, Gavan Duffy.
On 6 December 1845, Mitchel's article "Oregon—Ireland" referred to the dispute then pending between England and America about Oregon. He wrote, "If there is to be a war between England and the United States, tis impossible for us to pretend sympathy with the former. We shall have allies, not enemies, on the banks of the Columbia, and distant and desolate as are those tracts beyond the Rocky Mountains, even there may arise an opportunity for demanding and regaining our place among the nations."
On 20 December Mitchel made an appeal to the Protestants of Ireland to join their fellow countrymen. In the article "The Protestant Interest" he pointed to the efforts of the Whig leaders to win support in Ireland by the promise of gratuity and places. "But, Protestants of Ireland, shall it be so? Is it not time for all to rise above such vile influences as these? Does not our national interest, our national honour (for, after all, we are a nation), demand that we spurn the mean practice of both these foreign factions! that we shuffle off the coil of filthy place-hunting politics, that has kept us so long grovelling in the dust!... Ah! if you would hearken to us — and a hope dawns upon us that you will — if the Protestant magnates of the land would even now place themselves at the head of our national Confederacy, and, in this inter-regnum of foreign rule, would meet us as brothers."
In his article "The Administration of Justice", on 7 February 1846, Mitchel pointed out that the Englishman made his own laws, that they were not imported, that "no stranger," or "slave of a stranger, sat upon his judgment seats," that English men had grown "to love and honour their native land, and expected no premium upon its betrayal."
He wrote again on the Famine on 14 February, condemning the inadequate response, and asked whether the Government had even yet any conception that there might be soon "millions of human beings in Ireland having nothing to eat".
On 28 February, he observed on the Coercion Bill which was then going through the House of Lords, "This is the only kind of legislation for Ireland that is sure to meet with no obstruction in that House. However they may differ about feeding the Irish people, they agree most cordially in the policy of taxing, prosecuting and ruining them."
In an article on "English Rule" on 7 March, he wrote: "The Irish People are expecting famine day by day... and they ascribe it unanimously, not so much to the rule of heaven as to the greedy and cruel policy of England. Be that right or wrong, that is their feeling. They believe that the season as they roll are but ministers of England's rapacity; that their starving children cannot sit down to their scanty meal but they see the harpy claw of England in their dish. They behold their own wretched food melting in rottenness off the face of the earth, and they see heavy-laden ships, freighted with the yellow corn their own hands have sown and reaped, spreading all sail for England; they see it and with every grain of that corn goes a heavy curse. Again the people believe—no matter whether truly or falsely— that if they should escape the hunger and the fever their lives are not safe from judges and juries. They do not look upon the law of the land as a terror to evil-doers, and a praise to those who do well; they scowl on it as an engine of foreign rule, ill-omened harbinger of doom."
Mitchel made the acquaintance of Thomas Carlyle during his connection with The Nation. Carlyle described a dinner at Mitchel's house in 1846, saying that Mitchel was "a fine elastic-spirited young fellow, whom I grieved to see rushing to destruction palpable by attack of windmills, but upon whom all my persuasions were thrown away". Carlyle later said, when Mitchel was on trial, "Irish Mitchel, poor fellow… I told him he would most likely be hanged, but I told him, too, that they could not hang the immortal part of him."
In 1847 Mitchel resigned his position as leader writer on The Nation. He later explained that he had come to regard as "absolutely necessary a more vigorous policy against the English Government than that which William Smith O'Brien, Charles Gavan Duffy and other Young Ireland leaders were willing to pursue". He "had watched the progress of the famine policy of the Government, and could see nothing in it but a machinery, deliberately devised, and skillfully worked, for the entire subjugation of the island—the slaughter of portion of the people, and the pauperization of the rest," and he had therefore "come to the conclusion that the whole system ought to be met with resistance at every point, and the means for this would be extremely simple, namely, a combination among the people to obstruct and render impossible the transport and shipment of Irish provisions; to refuse all aid to its removal; to destroy the highways; to prevent everyone, by intimidation, from daring to bid for grain and cattle if brought to auction under 'distress' (a method of obstruction which put an end to Church tithes before); in short, to offer a passive resistance universally; but occasionally, when opportunity served, to try the steel." This revolutionary line conflicted with the stance of The Nation, so Mitchel started his own paper, The United Irishman.
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