The Iran nuclear deal upends the security of the Middle East region. Old alliances have been shoved aside. Massive new resources have been put at the disposal of the Iranian regime. The security implications of the agreement will take time to be felt. The U.S. political consequences will be immediate.

Here are five:

The Rand Paul Candidacy for the Republican Nomination Is Over

The Iran deal presents Republicans with a sharp binary choice. Line up with President Obama in support of a treaty achieved mostly by American concessions that puts Iran on the path to an internationally accepted nuclear weapon sometime in the 2020s? A treaty that bypasses Congress’ role and that is opposed by every U.S. ally in the region, including but not limited to Israel? No cash prize for predicting how the Republican primary electorate will align.

In the middle of Obama’s tenure, Rand Paul achieved for himself a standing within the GOP that eluded his father by focusing less on international security and much more on domestic surveillance. So long as as Congress was debating NSA and TSA, rather than Russia and Iran, Paul found a considerable constituency inside the party for his distinctive ideology. Now the spotlight shifts to Iran, Russia, and nuclear proliferation. Paul will either find himself isolated with the old Ron Paul constituency—or he’ll have to find some nimble way to jump to the “anti” side of the Iran deal. (Perhaps he will emphasize the slight to Congress it represents?) If he opts for the latter approach, however, he becomes just another Republican voice among many competing to voice their opposition, and one less powerful and credible than, for example, Ted Cruz will be.

Tough Is Back

The Republican candidates for president don’t disagree much on policy, but they diverge greatly in tone. Jeb Bush is conciliatory, Marco Rubio is inspirational, and Scott Walker is tough. “Tough" is about to become the most important quality for a Republican nominee.

Republicans won’t reject the Iran treaty because they want war with Iran. They will reject the treaty because they believe that a less feckless negotiating team—and a team more confident of American purposes and power—would have secured a less abject deal. Candidates will be judged according to how strong they seem. Candidates who have shown weakness in past negotiations—as many Republicans feel Rubio did when he negotiated with Chuck Schumer over the “Gang of Eight” immigration deal—will pay a penalty.

Hillary Clinton Will Discover That Incumbency Also Has Disadvantages

To date, Clinton has benefited hugely from running to succeed a president of her own party. She’s acceptable to almost all factions of a united party. She’s been permitted to avoid taking stands on divisive issues. She’s been buoyed by a rising economy. Now she’s about to experience a disadvantage: She’s about to be held politically responsible for somebody else’s decisions.

At first that disadvantage shouldn’t be too painful. Democrats will mostly support the Iran deal, if not for reasons of ideology (“negotiation is always better than confrontation”), then out of loyalty to Obama. Over the 16 months between now and the election, however, Iran will have many, many opportunities to remind even Democrats of the downsides of this deal—starting with the aid about to flow to every Iranian-backed terrorist and thug regime in the region and the world. The presumptive next leader of the party that sent those funds flowing will have to justify and defend an agreement that almost certainly will look even more one-sided in 2016 than it looks today. And she will have to defend it, or else risk dividing her party over the next consequence in the series:

Liberals Will Be Energized

The heyday of liberal activism and organization was the second Bush administration, when Democrats as conservative on domestic issues as Howard Dean and Wesley Clark could work with MoveOn.org in opposition to the Iraq war. As the Iraq issue faded, so did liberal activism. Groups like Occupy Wall Street tried to revive the old spirit, but they lacked a clear agenda—and anyway looked too radical and generally odd for the mainstream of their party.

Only last month, centrist Democrats handed liberal Democrats yet another indignity: defeat on the trans-Pacific trade deal. Aside from parking their votes with Bernie Sanders, liberals could do little but grumble. Now suddenly comes an issue that liberals will care about a lot more than they ever cared about trade. This issue even offers an individual to demonize: Israeli Prime Minister Benjamin Netanyahu. The Democratic base has turned increasingly hostile to Israel. Democratic elites have been more cautious. The debate over the Iran deal will unify both over an issue that promises peace while also conveniently rebuking Netanyahu and isolating Israel. Democratic elites can reassure themselves that the isolation of Israel is an unfortunate side effect of the deal; the Democratic base can straightforwardly enjoy it—and all can come together over an issue that probably won’t too badly alienate undecided voters, unlike such previous liberal causes as reducing incarceration or extending amnesty to undocumented immigrants.

Elites Will Matter

Over the past decade and a half, just about every bright idea recommended by one set or another of America’s financial, political, and national security elites has disappointed, if it has not failed outright. From the dot-com boom to the Iraq war to the stimulus, the people who claimed to know what they were talking about have been found wanting by voters and taxpayers. Trust in institutions, as measured by polls, has tumbled and then tumbled again. The Twilight of the Elites, to borrow the apt title of a book by Chris Hayes, an MSNBC host, made possible a new dawn for populists and demagogues.

But that was then. When we’re talking about nuclear proliferation and inspection, about centrifuges and enrichment levels, almost all of us must depend on the expertise of professionals in the field. Donald Trump may drown out George Borjas on immigration, but when the topic shifts to the weapons potential of uranium, it’s David Albright whom the TV cameras will seek.

Let’s hope that this time, the elites prove worthier of the public trust.