I

n just the last few years, new medications have turned hepatitis C into a widely and quickly curable disease — for those who can afford it.

But the lesser-known origins of the story trace back to a 1990s laboratory invention that made it all possible. Now, two virologists who pioneered that pivotal development, and a drug researcher who created the first revolutionary drug, are being honored with one of the most prestigious awards in medical science.

Ralf Bartenschlager, a German at the University of Heidelberg, and Charles Rice, an American at Rockefeller University, will receive one of the Lasker Awards for developing a technique to replicate hepatitis C in the lab, the Albert and Mary Lasker Foundation announced on Tuesday. They’ll share the foundation’s award for clinical medical research with Michael Sofia, an industry scientist who invented the hepatitis C drug sold as Sovaldi with the help of Bartenschlager and Rice’s advancement.

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Collectively, their efforts laid the groundwork for a host of subsequent innovations in basic and clinical research that have transformed patients’ lives while making billions for drug companies and putting enormous strain on health care systems.

Twists and turns

For the first decade after the hepatitis C virus was discovered in 1989, scientists had no way of efficiently replicating it in lab-grown cells. Bartenschlager’s and Rice’s labs devised a method to make “replicons,” fragments of the virus’s RNA carried within human cells. That made it possible for scientists to rapidly screen thousands of potential drug candidates to see whether they could stop the replicons from replicating.

Bartenschlager’s and Rice’s triumphs, published in journal articles in 1999 and 2000, came after many failed attempts and halting steps. “With each advance on the basic science side, we were met with an advance but then also a roadblock,” Rice recalled in a telephone conference with reporters on Tuesday.

The reason: Unlike, say, influenza, hepatitis C is among the viruses that are notoriously difficult to reproduce in the lab, for reasons that are still not fully understood.

Researchers had first unsuccessfully tried to replicate hepatitis C RNA by standard recombinant DNA techniques.

Rice, then at Washington University in St. Louis, made progress in 1997 when he reported a technique that weeded out genetic errors in the RNA, allowing for a clone of the virus that could be used to infect chimpanzees.

Bartenschlager, then at the University of Mainz, inserted a gene that helped keep host cells alive, but still very few of them were surviving. What was the survivors’ secret?

The key, Rice and Bartenschlager demonstrated, was that the survivors had picked up mutations that enhanced their ability to replicate. Engineering those sequence changes back into the original RNA dramatically sped up the production of lab-grown cells infected with hepatitis C.

“That was the novelty: They took what we know about the virus, but then they had made it in such a way that it could be expressed,” said Stephen Polyak, a virologist and cell biologist at the University of Washington. Polyak has called Rice’s and Bartenschlager’s inventions, along with the subsequent development in 2005 that allowed researchers to study the virus’s entire life cycle, the most important achievements in his field in the past 20 in the United States.

Bartenschlager and Rice last year shared the Robert Koch award, handed out by a German foundation, for the same work.

New cures and high prices

In the 2000s, drug makers targeting hepatitis C were able to make use of the replicon system devised by Rice and Bartenschlager to rapidly test their own libraries of potential drugs. Among them: Pharmasset, a small biotech company where Sofia led a team that designed a chemical that could block hepatitis C replication.

The drug they refined, known to scientists as sofosbuvir, was named after Sofia. (He’s now at Arbutus Biopharma.)

The rest of the story is well-known. Clinical trials looked promising, prompting Gilead to acquire Pharmasset in 2012. Sofosbuvir was approved by the Food and Drug Administration in 2013 to treat some forms of hepatitis C, which collectively affects about 3.5 million Americans. Sold as Sovaldi, it rapidly became a best-selling drug, curing patients in a matter of weeks without the harsh side effects of existing treatments. Other drugs from Gilead and other drug makers have since followed.

But the new wave of hepatitis C drugs have also generated ongoing outrage for their high prices — between $54,000 and $94,000 for a full course of treatment, before discounts. That’s made a massive dent in the budgets of many state health plans. So some populations, such as prisoners with hepatitis C, aren’t getting the drugs because they’re not deemed sick enough, and nationalized health care systems such as the United Kingdom are rationing access.

Did the drugs’ eyewatering price tags give the Lasker Foundation pause in its award choice? Asked that question by a reporter during Tuesday’s telephone conference, foundation president Dr. Claire Pomeroy deferred. “It’s the beauty of the science that we really celebrate,” she said.

The Lasker Foundation also awarded two other prizes on Tuesday. The award for basic medical research went to three scientists — William Kaelin of Harvard, Peter Ratcliffe of the University of Oxford, and Gregg Semenza of Johns Hopkins — for identifying the molecular pathway by which cells detect and adapt to changing oxygen levels. A third award, for special achievement in medical science, went to Bruce Alberts, an American biochemist and former editor of Science magazine.

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