Smallpox, or variola, is estimated to have killed hundreds of millions of people over thousands of years before a global vaccination campaign eradicated the virus by 1980.
The World Health Organization (WHO) has pushed for the numbers of laboratories holding samples of the virus to be reduced, and in 1984 it was agreed that smallpox be kept in two WHO-authorized laboratories in Russia and the United States.
Whether to destroy the remaining strains has since sparked fierce debates in global public health.
The 34-member WHO executive board meeting in Geneva this week is expected to include the issue in the agenda of the agency's larger decision-making body, the World Health Assembly, meeting in Geneva in May.
"This is an issue that has been very controversial for the past 20 years or so within the World Health Organization," says Dr. Jonathan Tucker, professor at the Technische Universitat in Germany.
"And a group of developing countries -- particularly in Africa but also other parts of the world -- have become increasingly impatient, and they want the research to stop and for a firm deadline to be set for destruction of the authorized stocks of the virus."
In the 20th century alone, an estimated 300 million people died from variola, an infectious disease that affects only humans.
One of the last major European outbreaks occurred in the former Yugoslavia in 1972, claiming 35 lives.
The last natural case of smallpox was contained in Somalia in 1977.
The following year, smallpox made one last attempt to stage a comeback when a medical photographer at the University of Birmingham was accidentally infected with the virus and later died; her mother also developed the disease, but survived.
This accident showed the risks of continued research with live variola virus and was a reminder that humans remain vulnerable to the virus, particularly because people are no longer vaccinated against it.
Fear In Developing World
Today, Russia keeps 120 different strains of the variola virus at the State Research Center of Virology and Biotechnology (Vector) in Koltsovo, near Novosibirsk, while the Atlanta-based U.S. Centers for Disease Control and Prevention holds 451 samples.
Tucker says the two Cold War-era foes, supported by a few dozen predominantly Western states, favor continued medical-countermeasure research with the live virus.
There are concerns that other states have kept secret caches of the variola virus and that terrorists might gain access to the agent and use it to stage mass-casualty attacks.
"Unfortunately, the opportunities for creating biological weapons are now much greater than they used to be during the Cold War," says Aleksandr Goltz, a leading independent defense expert based in Moscow. "Smallpox cultures are necessary to develop an efficient vaccine to counter this potential future weapon."
Tucker of the Technische Universitat says the G77 group of developing countries, however, is suspicious of Russian and U.S. intentions, and view research with live variola virus as a potential threat.
They fear an accidental release would take a heavy toll within their populations, which have already suffered from the disease.
Health officials also question the need to invest resources to combat an eradicated disease when they face serious challenges from AIDS, malaria, tuberculosis, and other infections.
A consensus approach on a firm deadline for destroying authorized caches of the virus appears unlikely. So in order to avoid an international confrontation at the upcoming World Health Assembly meeting, Tucker proposes partial destruction of the virus stocks to about 10 strains at each authorized depository as part of "a great bargain."
If differences are not bridged before the assembly convenes, Tucker insists, the meeting could result in a diplomatic train wreck that harms U.S. and Russian interests.
Tucker says that if there is not a "negotiated understanding" before the assembly, "there could be a serious confrontation, and some of the developing countries could demand a vote. And that vote could leave the U.S. and Russia with some very unpalatable options.
"So, I think the political cost and risk outweigh the medical benefits at this point of retaining the live virus, given that we now have a very good set of defenses against the disease."
In general, the World Health Assembly prefers to act by consensus, but on a few occasions it has made decisions by a majority vote.
For example, the 1966 decision to go ahead with an intensified smallpox Global Eradication Program was approved by a margin of two votes.
If no consensus or compromise is reached on the destruction of smallpox virus stocks, Tucker says, there is a strong possibility for a vote this year "because the issue has become so controversial and feelings are so strong on both sides."
RFE/RL correspondent Claire Bigg contributed to this report