The debate about mandated vaccinations has the political world talking. A spike in measles cases nationwide has President Obama, lawmakers and even potential 2016 candidates weighing in on the vaccine controversy. (Pamela Kirkland/The Washington Post)

The latest tweet from Hillary Rodham Clinton sounded straightforward enough: “The science is clear: The earth is round, the sky is blue, and #vaccineswork.”

But the issue of vaccinations has long been politically and emotionally fraught — involving not just public health but also the proper role of government, the prerogatives of parents and medical riddles that have yet to be solved.

Probably no one in public life today has felt those crosscurrents more strongly than the presumed front-runner for the 2016 Democratic nomination. On the issue of vaccination over the past two decades, Clinton has repeatedly found herself on the front lines of advocacy and criticism.

Other politicians — including two potential GOP presidential hopefuls, New Jersey Gov. Chris Christie and Sen. Rand Paul (R-Ky.) — have been learning those political lessons the hard way in recent days. Both made statements questioning whether childhood vaccinations should be mandatory, bringing a torrent of criticism, including from medical professionals who are alarmed over a recent rise in measles cases.

As a new first lady in 1993, Clinton championed what became the Centers for Disease Control and Prevention’s Vaccines for Children program, designed to provide free inoculations against nine diseases to children who otherwise might not get them. It now covers 14 diseases.

How fast does measles spread?

Clinton’s role in that endeavor landed her in the crossfire. Conservatives blamed her when shortfalls of some vaccines developed in subsequent years, arguing that the private market was better at allocating resources. “One of her pet projects is a bust,” the conservative Wall Street Journal editorial board wrote in a 2003 piece headlined “Hillary’s Vaccine Shortage.”

Meanwhile, Clinton also found herself the target of a burgeoning movement that linked the rising rate of autism to thimerosal, a mercury-containing preservative that has since been removed from childhood vaccines. Some advocates of this theory went so far as to dub her “Thimerosal Hillary.”

For reasons that scientists cannot explain, the incidence of autism is up markedly. Last year, the CDC estimated that 1 in 68 children age 8 had been identified with the range of conditions known as autism spectrum disorder. That was about 30 percent higher than previous estimates, reported in 2012, of 1 in 88 children.

Clinton, as a presidential candidate in 2008, wrote in response to a candidate questionnaire: “I am committed to make investments to find the causes of autism, including possible environmental causes like vaccines. . . . We don’t know what, if any, kind of link there is between vaccines and autism — but we should find out.”

Her then-rival, Sen. Barack Obama (D-Ill.), also called for more research into whether there was some correlation. And 2008 GOP presidential contender John McCain (R-Ariz.) went so far as to say there was “strong evidence” of a connection between vaccines and autism. But even in 2008, the weight of medical evidence was against such a link and the candidates who indulged such speculation were accused of pandering.

In 2010, the argument against vaccination received a devastating blow from the Lancet, a medical journal that 12 years before had published a study alleging that inoculations for measles, mumps and rubella were a cause of autism. The journal retracted the study, saying the supposed research had been falsified.

Another iteration of the vaccination issue flared in the 2012 Republican primary campaign, when then-Gov. Rick ­Perry of Texas found himself under fire for a mandate requiring most girls in his state to get inoculated against the human papillomavirus, a sexual infection that can lead to cervical cancer. Some social conservatives argued that it would encourage girls to have sex.

Sen. Rand Paul (R-Ky.) is shown in this photo tweeted by his office being inoculated on Tuesday. (Senator Rand Paul's Office/Reuters)

Republican leaders have not welcomed the rekindling of the vaccine debate sparked by Christie’s comment Monday that parents should have “some measure of choice” in deciding whether to vaccinate their children. Paul — a physician with a libertarian philosophy — joined the argument with an unfounded claim that there are “many tragic cases of walking, talking, normal children who wound up with profound mental disorders after vaccines.”

Paul took to Twitter on Tuesday to defend himself, saying he supports vaccinations and posing for photographs as he received a booster shot.

“I did not say vaccines caused disorders, just that they were temporally related — I did not allege causation,” he wrote in one tweet.

House Speaker John A. Boehner (R-Ohio) sought to tamp the furor down by saying Tuesday, “I don’t know that we need another law, but I do believe that all children ought to be vaccinated.”

Meanwhile, several other potential 2016 contenders distanced themselves from Christie and Paul.

“Absolutely, all children in America should be vaccinated,” Sen. Marco Rubio (R-Fla.) said Tuesday. “Unless their immune [system is] suppressed, obviously, for medical exceptions, but I believe that all children, as is the law in most states in this country, before they can even attend school, have to be vaccinated for a certain panel.”

Louisiana Gov. Bobby Jindal (R) also released a statement criticizing “fear mongering” and added: “Personally, I would not send my kids to a school that did not require vaccinations.”

Alice Crites contributed to this report.