When scientific hypotheses don’t come true
The team’s first study was not wrong; viruses cooperate in the cells of the laboratory. But the second question is usually the most difficult, the researchers said.
“There are obviously a lot of differences between viruses that grow in a controlled environment in a petri dish and an actual human,” Xue said.
She and Bloom aren’t too brooding about their disproved hypothesis, however. This line of inquiry has opened new doors in the lab, Bloom said.
Before Xue’s study, he and his colleagues exclusively studied viruses in Petri dishes. Now more and more of his lab team are also using clinical samples – an approach made possible by the closer collaborations between basic and clinical research at Hutch, Bloom said.
Some of their findings in Petri dishes are not true in clinical samples. But they’re already making some interesting discoveries about how influenza evolves in the human body – including the discovery that the evolution of influenza in single people with unusually long infections may indicate how the virus will evolve around the world, years later. They would never have done this study if they had not already tried to follow their original hypothesis of cooperation.
“It opened up this whole new way of trying to think about this,” Bloom said. “Our state of mind has changed a lot.”
The prevention hypothesis reversed
Fred Hutch and Swedish cancer prevention researcher Goodman and his fellow epidemiologists had good reason to believe that the vitamins they were testing in clinical trials could prevent lung cancer.
All of the data indicated an association between the vitamins and a reduced risk of lung cancer. But the studies hadn’t shown a causal link – just a correlation. The researchers therefore set out to do large clinical trials comparing high doses of vitamins to placebos.
In the CARET trial, led by Goodman and launched in 1985, 18,000 people at high risk of lung cancer (mainly smokers) received either a placebo, vitamin A, beta-carotene (a precursor of vitamin A). A) or a combination of both supplements. Two other similar trials started in other parts of the world around the same time, also testing the effect of beta-carotene on lung cancer risk.
Likewise, at the same time, a small trial suggested that supplementing with selenium reduced the incidence of prostate cancer. Thus, in 2001, the SELECT test thrown through SWOG, a national cancer clinical trial consortium, testing whether high-dose selenium or vitamin E or the combination could prevent prostate cancer. SELECT enlisted 35,000 men; Goodman was the study leader for the Seattle area.
Designing and conducting cancer prevention trials where participants take a drug or other intervention is a delicate business, Goodman said.
“In prevention, most of the people you treat are healthy and will never get cancer,” he said. “So you have to make sure the agent is very safe.”
Previous studies had all shown that vitamins were safe, even beneficial. And the vitamins tested in the trials are all naturally present in our diets. No one thought they could possibly hurt.
But that’s exactly what happened. In the CARET study, participants taking the combination of vitamin A and beta-carotene had higher rates of lung cancer than those taking the placebo; other trials testing these vitamins have given similar results. And in the SELECT trial, people taking vitamin E had higher rates of prostate cancer.
All of the trials had close monitoring, and all were stopped early when the researchers found that cancer rates were moving in the opposite direction to what they expected.
“It was just devastating when we learned of the results,” Goodman said. “Everybody [who worked on the trial] was so optimistic. After all, we’re here to prevent cancer.
When the CARET study ended, Goodman and his team hired additional people to answer questions from study participants and angry phone calls they thought they were getting. But very few phone calls arrived.
“They said they were involved in the study for altruistic reasons, and we got a response,” he said. “One of the advantages of our study is that we have shown that high doses of vitamins can be very harmful.”
It was an important discovery, Goodman said, because the prevailing dogma at the time was that high doses of vitamins were good for you. Although these studies have disproved this widespread belief, even today not everyone in the general public buys this message.
Another benefit of this difficult experiment: The bar for giving healthy people a supplement or medication to prevent cancer or other illnesses is much higher now, Goodman said.
” Prevention, [these studies] really changed people’s perceptions of what kind of evidence you need before you can invest the time, money, effort, human resources, people’s lives in an intervention study, ”he said. -he declares. “You really have to have good data to suggest that an intervention will be beneficial. “