President Obama on Monday hailed international efforts to reduce the threat of loose weapons left over from the Cold War and said he is “optimistic” that Russia will renew its cooperation after backing out of the program this fall.

But Obama also used a speech at the National Defense University in Washington to warn of a new threat looming in Syria, where intelligence reports suggest that President Bashar al-Assad’s regime may be preparing chemical weapons for use against rebels.

“The world is watching,” Obama said. “The use of chemical weapons is and would be totally unacceptable. And if you make the tragic mistake of using these weapons, there will be consequences and you will be held accountable.”

The president added: “We simply cannot allow the 21st century to be darkened by the worst weapons of the 20th century.”

Obama’s main purpose Monday was to mark the 20th anniversary of the Nunn-Lugar Cooperative Threat Reduction Program, the outgrowth of a 1992 law championed by Sens. Sam Nunn (D-Ga.) and Richard G. Lugar (R-Ind.) focused on securing and dismantling nuclear, chemical and biological weapons and materials in former Soviet states.

Still uncertain is how the effort will continue without Russia’s help. The country’s decision to withdraw from Nunn-Lugar in October came at a time when U.S.-Russian relations were already deteriorating after Russian President Vladi­mir Putin decided to expel the U.S. Agency for International Development from his country.

The withdrawal stemmed in part from disagreements over the terms of cooperation spelled out in the program. Obama signaled Monday that he is willing to change those terms to bring Russia back in.

“Let’s update it,” he said. “Let’s work with Russia.”

That sentiment did not come as a surprise to U.S. supporters of Nunn-Lugar, who said the program has survived darker moments and has enduring support among key members of the Russian defense establishment.

“The program and activity up to now has survived the cycles of relations,” said Joseph Cirincione, president of the nonproliferation group Ploughshares. “Of course it’s mutually beneficial. It’s in everyone’s interests to secure these weapons.”

Obama has made nonproliferation a priority as president and as a U.S. senator before that. In 2006, he joined with Lugar to co-sponsor legislation that expanded Nunn-Lugar to efforts aimed at containing conventional weapons.

On Monday, Obama called Nunn-Lugar “one of the country’s smartest and most successful national security programs.” He thanked Lugar and Nunn, who attended the 15-minute speech at Fort McNair.

“They challenged us to think anew, after decades of confrontation, how our nations might engage in cooperation,” the president said. “Early in the Cold War, Einstein warned of our wisdom not keeping pace with technology. With Nunn-Lugar, our wisdom began to catch up.”

Obama took extra time to pay tribute to Lugar, who was defeated in a primary this year and will leave the Senate in January. He reminisced about taking his first overseas trip as a senator with Lugar, during which he observed weapons of mass destruction being destroyed.

“The first thing I learned is that when Dick Lugar travels overseas, it’s not a junket,” Obama said, prompting laughter from the audience. “You know, we didn’t stop and look at a lot of beautiful sites and sort of lounge around on a lot of shopping excursions. He wore out every 25-year-old staffer that was part of this delegation. “