The march in Washington, timed to coincide with the Earth Day environmental event, will put Trump's questioning of climate change and proposed cuts to federal science programs at center stage.
Demonstrations are also scheduled in U.S. cities including San Francisco, along with smaller towns like Dillingham, Alaska. Overseas, people are due to rally in support of science from Australia to Brazil.
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Participants say the Washington march will be nonpartisan and marks a new frontier for scientists more accustomed to laboratories and classrooms than activism in the streets.
"It has dawned on some of them it is time to speak up," Rush Holt, chief executive of the American Association for the Advancement of Science, told reporters on a conference call this week. "I wouldn't say that it is fundamentally because of Donald Trump, but there's no question that there's been concern in recent months about all sorts of things."
The White House did not respond to a request for comment.
Trump has called climate change a hoax. His administration is mulling withdrawing from the so-called Paris Agreement aimed at reducing global emissions of carbon dioxide and other greenhouse gases.
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Trump's proposed 2018 budget calls for deep spending cuts by government science agencies, including a 31 percent reduction for the Environmental Protection Agency.
Rally organizers are also worried by what they see as growing skepticism from politicians and others on topics such as vaccinations, genetically modified organisms and evolution.
"It's really the age-old debate of the rational view of the universe against the irrational view of the universe," Elias Zerhouni, former director of the National Institutes of Health, said on the conference call.
Guests at the Washington event will include television personality Bill Nye "the Science Guy," former White House technology aide Megan Smith and Dr. Mona Hanna-Attisha, a pediatrician who helped expose the lead water crisis in Flint, Michigan.
But some questioned whether scientists should play a political role, and whether the march would change the minds of Trump, his top aides, or skeptical voters.
"We need to go to county fairs, and we need to personalize the scientific issues we care about," said geologist Rob Young, a professor at North Carolina's Western Carolina University.
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