COMMENTARY

Stories of Science Gone Wrong: Paul Offit Discusses His New Book

Susan B. Yox; Paul A. Offit, MD

Disclosures

June 12, 2017

Health Professionals: Can We Learn From the Past?

Medscape: This takes me to the final chapter in the book, "Learning From the Past." The lessons learned have a lot of relevance to practice today. Maybe you can talk about a few of them for our readers.

Dr Offit: For Medscape readers, I think an important lesson is that if you read a paper that makes a particular claim, and it's a fantastic claim, you should be suspicious of it. Wait to see that it's reproduced by other investigators and reproduced in other populations before you jump on it. Sadly, not waiting for something to be reproduced happens all the time. It certainly happens in the world of vaccines, which is my world.

[I]f you read a paper that makes a particular claim, and it's a fantastic claim, you should be suspicious of it.

As you know, the claim by Andrew Wakefield in 1998 that the combination measles, mumps, rubella (MMR) vaccine caused autism was a fantastic one. We had the MMR vaccine, which everyone assumed was doing good but which was in fact, at least according to Andrew Wakefield, doing an enormous amount of harm.

His research was published in a very good medical journal. The Lancet is probably the oldest of the general medical journals and is certainly a well-respected journal. After that publication, many parents chose not to vaccinate their children. In the United Kingdom, hundreds were hospitalized. Children died of measles, and all because of that one paper.

We should be very careful about these papers—no matter how good the journal, no matter how good the researchers—that these findings are reproducible. Because that's what matters. And in the Wakefield case, 17 studies in seven countries on three different continents, involving hundreds of thousands of people and costing tens of millions of dollars, showed that his hypothesis was wrong. And so, the truth did emerge. But we shouldn't be so quick to jump on single studies.

Medscape: I think your second take-home point was that everything has a price—the issue being how big a price. And I assume that means weighing both before you make a move.

Dr Offit: Yes; anything that has a positive effect can have a negative effect. Anything. Vaccines are certainly no different. Vaccines may cause pain and redness at the injection site. Sometimes the costs are bigger. The squalene adjuvanted influenza vaccine that was given in Scandinavia and Europe in 2009 could cause narcolepsy, a disorder of wakefulness. And although it was rare—just 1 in 15,000, or 1 in 50,000, depending on the country—it was real. That was a painful lesson.

Antibiotics, which obviously have saved our lives so that we no longer routinely die of such diseases as pneumonia, meningitis, and bloodstream infections, are another example. We're now learning that there is an effect of antibiotics, especially early antibiotics, on the microbiome, and that that can affect our chances, when we get older, of having such diseases as asthma, diabetes, or obesity. I don't think anyone would have predicted this.

Medscape: Are there any other examples in medicine?

Dr Offit: General anesthesia is of course a lifesaver. I think it was Gore Vidal who, when asked the question, "Would you like to live in an age that you write about, such as the age of Lincoln?", answered that he would never want to live in an age that hadn't perfected anesthesia. However, there is some evidence that general anesthesia can affect long-term memory. One always must weigh the risks and benefits. There's nothing that's absolutely safe, and there's nothing generally that works 100% of the time. You have to weigh all of that.

Medscape: Do you have any more advice on critically looking at the literature, specifically for health professionals?

Dr Offit: Remember that there are about 4000 papers published in medical and scientific literature every day. So, not surprisingly, these papers follow a bell-shaped curve. Some are excellent, some are awful, and most are more or less mediocre. You can probably find a paper that claims almost anything.

For example, I think that if a scientific paper came out—where the science was no doubt poor—claiming that there was a genetic predisposition to rape or murder, and that people living in Mexico were more likely to have these genes, certain people in the population would believe it, because it fits with their biases.

Medscape: Another lesson learned was that "the dose makes the poison." Do you want to talk just a bit about what you mean by that?

Dr Offit: We see that in the thimerosal debate. Thimerosal is an ethyl mercury containing preservatives that used to be in vaccines. It's now included in some multidose vials of flu vaccine, but for the most part, it's no longer in vaccines. As you know, mercury is never going to sound good. It's not like the "National Association for the Appreciation of Heavy Metals" is standing up in defense of mercury.

But we're exposed to mercury all the time. Mercury is in the earth's crust. We ingest mercury when we drink anything made from water on this planet. And the quantity of thimerosal that was in vaccines was logarithmically less than anything we were exposed to anyway. But, again, it didn't sound good. And so we rushed to try to take it out of vaccines, as if that made vaccines safer, when it didn't make them safer at all.

The dose makes the poison.

Medscape: A key lesson learned was to "be cautious about being cautious." I liked your explanation of this lesson as it relates to current screening controversies.

Dr Offit: There are certain things that clearly do prevent cancer. Sunblock prevents skin cancer. Hepatitis B vaccine prevents a common cause of liver cancer. Human papillomavirus vaccine prevents cervical cancer and other cancers. Colonoscopies are an excellent way of preventing colon cancers. Pap smears prevent cervical cancer. Those things are of value.

But it gets a little murkier with prostate-specific antigen tests, digital rectal exams, and prostate biopsies. We've done a lot of radiation therapy and surgical therapy for men, without clearly prolonging their lives. So, obviously, that's not perfect.

It is similar with thyroid scanning. We could screen for thyroid cancers and then do thyroidectomies, but there's no evidence that has in any way increased our lifespan.

The analogy I love, actually, is Gilbert Welch's barnyard analogy. It includes turtles, birds, and rabbits. If you open up a barn door, the bird's going to fly out before you can close the door, no matter how fast you try to close it. The bird is just too fast. And so, that's the aggressive cancer—no matter whether you diagnose it early or not, you're still going to die of that disease.

And then there's the turtle, which, if you open the door, you have plenty of time to close it. That's analogous to the cancer that you die with, and not of. For example, for men older than 85 years, if you examine their prostates at autopsy, you find that most had prostate cancer. So, most people die with prostate cancer, not of it. That's the turtle.

Then there are the rabbits, where it is possible to close the door. That's the kind of cancer that, if you pick it up early, you can save someone's life.

So that's the issue for these cancers. What's the ratio of turtles, birds, and rabbits? Regarding prostate, thyroid, and breast cancer, which are mostly turtles and birds, screening programs haven't offered much.

Medscape: If we could identify the rabbits beforehand and screen for them, we could truly make a difference, but it's very hard to do.

Dr Offit: That's exactly it.

Medscape: And then track those people specifically.

Dr Offit: Yes; we need to have either biochemical or genetic markers in cancers to tell us which are the innocuous cancers and which are the cancers that are likely to kill us.

Medscape: Your last take-home point was, "Pay attention to the little man behind the curtain." And your chapter on Linus Pauling was very interesting in illustrating this point.

Dr Offit: Linus Pauling won two Nobel prizes—the only person ever to win two unshared Nobel prizes. He was brilliant. His work on secondary structure of proteins, such as the alpha helix, was brilliant. A hard-earned, hard-won, Nobel Prize.

But he then came to believe that megavitamins could not only prevent colds but also treat them, and then he took it a step further, suggesting that megavitamins, in doses vastly in excess of the recommended daily amounts, could treat cancers, as well as a variety of other diseases.

He was wrong, and he was shown to be wrong. But he still simply believed that he was right, and he stood on a platform that was built by two Nobel Prizes. So, people believed him.

David Gorski, who writes the blog Respectful Insolence, calls it "Nobel disease." I think that's just right. Just because you win a Nobel Prize doesn't mean you're right about everything.

Medscape: After reading your book, I certainly agree. Is there anything else about the book that we should tell readers? I will certainly tell them that I think they should read the book. Not only are key topics really interesting, but the side stories are fascinating as well. Are there any other thoughts or messages you might have for our Medscape readers?

Although science has allowed us to move out of the Age of Enlightenment, we shouldn't be so quick to go back to the Dark Ages.

Dr Offit: I might summarize by saying that I think science, at some level, is under siege. We're in this postmodern era, when people believe that any attitude and belief, independent of whether it's backed by expertise or experiences, is valid. People believe that one person's opinion is as valid as the next.

Although science has allowed us to move out of the Age of Enlightenment, we shouldn't be so quick to go back to the Dark Ages. I think that science is enormously valuable, but one needs to be fair to science. You need to understand what it is and what it isn't. Hopefully, this book can help define that.

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