Paging Mike Pence … Vice President Mike Pence, please pick up the emergency Senate red phone … After Harry Reid’s 2013 nuclear-option deployment and the GOP’s surprisingly strong Senate performance in 2016, Republicans believed that they could get any of Donald Trump’s Cabinet nominees across the confirmation line without any help — from Democrats or Pence. Susan Collins may have dashed hopes of easy confirmations earlier today by telling the media that she’s “leaning against” confirming Betsy DeVos, Trump’s pick for Secretary of Education.

Did I say “may have”? Later, Collins made her opposition explicit:

#BREAKING – @SenatorCollins announces on Senate floor she will NOT support the nomination of Secretary of Education nominee Betsy Devos.

— NEWS CENTER Maine (@newscentermaine) February 1, 2017

And shortly after that, Collins was joined by Lisa Murkowski (R-AK):

BREAKING: Second Republican senator, Lisa Murkowski of Alaska, says she cannot support Education nominee Betsy DeVos.

— The Associated Press (@AP) February 1, 2017

Did Collins and Murkowski go “RINO,” as charges on social media allege? It’s … complicated. Collins not only defended the most controversial of the Cabinet nominees, Jeff Sessions, she introduced him at his Judiciary Committee confirmation hearing in glowing terms. Sessions is as conservative as Collins is moderate, so the issue doesn’t appear to be ideological, but more based on policy and experience. As the Washington Post reports, Collins balked because she’d prefer to see someone with more focus on public schools in this position:

Nevertheless her concentration on charter schools and vouchers raises the question of whether or not she fully appreciates that the secretary of education’s primary focus must be on helping states and communities, parents, teachers, school board members and administrators strengthen our public schools.

That is why I wrote to Mrs. DeVos seeking her assurances in writing that she would not support any federal legislation mandating that states adopt vouchers nor will she condition federal funding on the presence of voucher programs in the states. She has provided that commitment…

There remain other questions about Mrs. DeVos’s knowledge of certain education laws. While it is unrealistic and unfair to expect a nominee to know all of the details of such programs, I was surprised and concerned about Mrs. DeVos’ apparent lack of familiarity with the landmark 1975 law, IDEA, that guarantees a free and appropriate education for children with special needs. Therefore, I will continue to evaluate this nomination before it comes to the floor, even as I vote today to advance it so that all of our colleagues have the opportunity to assess this nominee.

Murkowski had the same reservations, according to the Post.

That brings up a very tough position for Mitch McConnell — especially depending on when he schedules the vote for Sessions, as my friend Christine Rousselle points out:

With Collins and Murkowski out, it is increasingly unlikely that DeVos will be confirmed by the Senate if Alabama Sen. Jeff Sessions is confirmed as Attorney General.

That all depends on McConnell. Clearly, after all of the chaos the last few days regarding Sally Yates and the Department of Justice, expediting Sessions’ confirmation is a high priority. However, McConnell can schedule DeVos’ confirmation vote first and ensure Sessions is still eligible to cast his vote in her favor. If that works out, and assuming that the Republican caucus has no other defections, DeVos could still get confirmed on a 50-50 vote, as long as Pence dropped by to cast the deciding vote. That, however, won’t work if another Republican bails on DeVos and no other Democrats sign up in support. The most likely of the latter, Joe Manchin, has already declared his opposition to DeVos, so that escape route has likely been cut off.

That leaves McConnell and Senate majority whip John Cornyn with some heavy lifting to do. They either need to convince Collins and/or Murkowski to get back on board with DeVos, or make sure no one else disembarks before Pence can cast the 101st vote and keep Sessions in the Senate long enough to pull off this high-wire act. Stay tuned.

Update: More from the AP:

Sens. Susan Collins of Maine and Lisa Murkowski of Alaska both say they cannot support DeVos, a wealthy Republican donor and school choice activist. Both said in Senate floor speeches Wednesday that DeVos’ commitment to the nation’s public schools is in question in light of her long-held support for vouchers and charter schools.

Update: Per a source close to the situation, they have Sessions’ replacement ready to go if they need one for the DeVos vote after Sessions gets confirmed, but at least as of earlier this week, no one has been publicly named. It’ll almost certainly be Luther Strange, though.