Washington CNN  — 

The long trail of civilian death left by President Barack Obama’s drone war finally has an innocent American face.

In an extraordinary moment, Obama appeared Thursday in the White House briefing room to apologize for the accidental killings of an American and an Italian hostage in an attack on an al Qaeda compound on the Afghanistan-Pakistan border.

The deaths of U.S. hostage Warren Weinstein and Italian Giovanni Lo Porto were an agonizing personal blow to Obama and White House and CIA counterterrorism officials, who were forced to confront the horrifying reality that as a result of their actions, the United States killed two innocent captives.

“It is a cruel and bitter truth that in the fog of war generally, and our fight (against) terrorists specifically, mistakes, sometimes deadly mistakes, can occur,” Obama said.

But the killings also have political and policy implications. It was a serious jolt for the drone war program, which is a bedrock of his counterterror legacy. They raised questions of whether U.S. covert agencies had done absolutely everything they could to ensure that no civilians were in the path of the drone strikes or whether the CIA was guilty of another intelligence failure.

READ: Will the drone debate come back?

The methodology of Obama’s campaign against Islamic extremism – including strikes to kill unidentified suspected militants – and the risks inherent in basing military targeting decisions on the imperfect science of intelligence will also face new scrutiny.

The death of Weinstein also will supercharge a controversy about whether the United States, which refuses to negotiate with al Qaeda and ISIS for the release of most detained Americans, does enough to find and bring home U.S. hostages.

In a political sense, the tragedy handed the administration a new national security crisis at a time when Obama’s foreign policy is already under assault from Capitol Hill critics and public alarm is rising over the threat from groups like ISIS.

Four years after the stunning special forces raid that killed Osama bin Laden, Obama’s national security legacy is being called into question on multiple fronts. The latest episode comes after a failed raid to free U.S. hostages in Syria, a controversy over a Taliban prisoner swap to free a U.S. soldier and the collapse of the Yemeni government, a vital U.S. partner in the fight against al Qaeda in the Arabian Peninsula.

graphic drone casualties pakistan

Obama, in his determination to end U.S. land wars in the Middle East and South Asia, significantly escalated the drone program put in place by the Bush administration and has carried out hundreds of strikes in the lawless border regions of Afghanistan and Pakistan in a classified program that top officials rarely discuss publicly.

Indirectly, the deaths of the two hostages in January, which were only made public Thursday, can be traced back to that fateful presidential decision.

Grief was etched into Obama’s face as he made the dramatic announcement, one of the lowest points of a presidency scarred by perpetual crises and marked by his effort to put the war on terror on a sustainable footing.

‘No words’ to express loss

“I realize that there are no words that can ever equal their loss,” Obama said in a somber appearance that recalled his grief-stricken comments from the same podium after the Newtown school massacre in December 2012.

“As President and as commander-in-chief, I take full responsibility for all our counterterrorism operations, including the one that inadvertently took the lives of Warren and Giovanni,” Obama said in a grave tone. “I profoundly regret what happened.”

The President did not specifically sign off on the operation that killed Weinstein, but the White House said it was conducted in line with procedures he has put in place to regulate counterterrorism operations.

U.S. intelligence agencies had been spying for months from the air on the al Qaeda hideout at an undisclosed location, but they had seen no sign that Weinstein and Lo Porto were being hidden in the building.

READ: U.S. drone strike accidentally killed 2 hostages

One key question that Obama will face – and one that may emerge from reviews the White House and members of Congress say they will mount – is whether the deaths of civilian hostages were an unavoidable accident or whether the intelligence community committed serious errors.

“My own instinctive reaction, without having a huge number of facts in front of me, is that if you are striking terrorists using military force for many years in a row, then something like this unfortunately becomes almost a statistical inevitability,” said Daniel Benjamin, formerly the top counterterrorism adviser to then-Secretary of State Hillary Clinton, who is now at Dartmouth College. “It is very hard to avoid.”

The fact that it has been deemed too dangerous to put American operatives on the ground in the lawless tribal regions of Pakistan and the reality that U.S. anti-terror operations are conducted from the air introduces a high degree of risk. Intelligence agencies can never know for sure who is being targeted, and civil liberties groups have long complained about the randomness of the attacks that have killed significant numbers of Pakistani civilians.

Officials refuse to give figures for the number of attacks. But the Bureau for Investigative Journalism estimates there have been more than 400 U.S. strikes in Pakistan, which have killed between 423 and 962 bystanders along with hundreds of suspected al Qaeda operatives.

Two al Qaeda operatives killed

Supporters of the program say it has been a hugely effective tool in eradicating the core leadership of al Qaeda. And although the deaths of Weinstein and Lo Porto are dominating the aftermath of Obama’s announcement, the White House did note that strikes also killed two key al Qaeda operatives, also Americans.

“I think the story of the drones has been one of success; it broke the backbone of al Qaeda. But at the end of the day it is not a totally accurate way to fight terrorism,” said CNN intelligence analyst Robert Baer, a former CIA operative.

“There are a lot of civilian casualties. They always knew it was never 100% certain. There is no way to see whether somebody is in that building, simply because you cannot see through walls.”

Republican Rep. Devin Nunes of California also pointed to the difficult task that U.S. spies have in getting reliable intelligence in difficult-to-reach parts of the world.

“Although our intelligence is outstanding, it is not perfect,” Nunes, chairman of the House Permanent Select Committee on Intelligence, said in a statement.

Obama put in place protocols designed to eliminate civilian deaths in drone strikes, which have caused a significant anti-U.S. backlash in Pakistan, and explained them in a speech at the National Defense University in 2013.

Democratic Rep. Adam Schiff of California pledged to investigate the operation to ensure that those steps were properly followed in this case.

“We have to take everything with a certain degree of skepticism,” Schiff said. “We owe it to the families and to the American public not to take anything as an article of faith.”

The White House argued Thursday that intelligence assessments were correct in identifying al Qaeda operatives at the site of the operation but, tragically, a separate assessment that no civilians were there turned out to be incorrect.

White House spokesman Josh Earnest said that Obama’s protocols were followed fully in the case. But he suggested the tragedy could still lead to changes.

Questions about drone policy

“What’s also clear, and what I would also readily admit to you, is that in the aftermath of a situation like this, it raises legitimate questions about whether additional changes need to be made to those protocols,” Earnest told reporters.

It also raises questions about efforts to recover hostages. Weinstein’s death followed the beheadings of U.S. hostages Steven Sotloff and James Foley and the swap of Taliban prisoners for U.S. soldier Bowe Bergdahl, who has since been charged with desertion.

In light of the Bergdahl swap, families of slain hostages have accused the administration of doing too little to save their loved ones, despite a failed rescue operation to free Foley and other U.S. hostages held by ISIS in Syria.

READ: Could Warren Weinstein have been saved?

Weinstein was not the only American bystander killed in a drone strike by accident. Abdulrahman al-Awlaki , the teenaged son of a US born al Qaeda operative was killed in a drone strike in 2011 in Yemen. He was said to have been killed by a U.S. strike against another suspected terror suspect, but his family connections and the secrecy surrounding his case meant his fate never garnered the publicity the killing of Weinstein is getting.

Political blowback quickly erupted over Weinstein’s death, and there are accusations that the administration erred in not finding the U.S. hostage before now.

“I think it was a very significant failure. Our country let Warren down,” said Democratic Rep. John Delaney, who serves the Maryland congressional district where the Weinstein family lives and is calling for a “czar” to coordinate government efforts to trace hostages.

“We have let him down by not being able to find him. We don’t have someone who wakes up every morning and can cut across all bureaucracy and can grab any resource at any agency and bring it to bear to help find these hostages.”

Delaney’s concerns were mirrored by those of Weinstein’s family.

‘Disappointing’ assistance to family

“Unfortunately, the assistance we received from other elements of the U.S. government was inconsistent and disappointing over the course of 3½ years,” said Weinstein’s wife, Elaine, in a statement.

Republican Rep. Duncan Hunter of California, a Marine veteran of the Iraq and Afghan wars, said the U.S. government was failing detained Americans abroad.

“Warren Weinstein did not have to die,” Hunter said. “His death is further evidence of the failures in communication and coordination between government agencies tasked with recovering Americans in captivity – and the fact that he’s dead, as a result, is absolutely tragic.”

But Obama’s statement also drew plenty of support on Capitol Hill, even from those who are usually deeply critical of his foreign policy.

“You can’t stop the drone program because of this,” said Republican Sen. Lindsey Graham of South Carolina, who is mulling a run for president. “The hostages are innocent victims. I feel terrible for them, but we’re at war and we’ve got to keep prosecuting this war.”

So far, none of the other candidates vying for the Republican presidential nomination has weighed in, despite making Obama’s perceived failings on national security a centerpiece of the young campaign.

That may reflect an appreciation of the gravity of the choices faced by the person who holds the job they are fighting to get.