An immigrant's tale: why we should welcome immigrants to the U.S.

1918 obituary for my grandfather.
This week I’m taking a break from science and choosing a more personal topic for my last column of the year. Many scientists wouldn’t be here if not for the opportunities offered by a new life in the U.S., and with so much anti-immigration talk in the news recently, I wanted to offer a counterpoint.

America is famously a land of immigrants. Some families came earlier than others, but most people in the U.S. today, including me, wouldn’t be here if some recent relative didn’t immigrate. Approximately 80 million people today are either immigrants or first-generation children of immigrants, and many more are 2nd or 3rd generation.

Despite the fearmongering of current Republican presidential candidate Donald Trump, immigrants are not and have never been the cause of America’s problems. On the contrary: immigrants have been the secret of our success. A true leader wouldn’t be afraid of them. (By the way, since when did candidates demonstrate their toughness by telling everyone to be afraid?)

The picture shown here is a newspaper obituary from the summer of 1918, showing my grandfather, Bernard Salzberg, after he was reported as killed in action in World War I. Bernard came to America as a 16-year-old boy, leaving his home in Lvov (part of modern-day Ukraine, though it was in Poland at the time) to find a better life here. He wasn’t yet a citizen when the U.S. declared war in 1917. As the obituary says,
“Salzberg could have avoided service, but instead … took out his first citizen papers before joining the American fighting forces in September 1917.”
Fortunately for me, the obituary was wrong in one critical detail: my grandfather was grievously injured by poison gas, but he didn't die. He survived and eventually came home, married, and had two children, one of whom was my father.

Both of my mother's parents were immigrants as well. They fled the pogroms in Poland in 1929 and 1930, barely in time to escape the Nazis. They arrived in the U.S. during the Great Depression, when jobs were scarce, and they never had much, but life in the U.S. was nonetheless far better than in their homeland. My immigrant grandparents could scarcely have imagined that their grandchildren would include doctors, scientists, lawyers, professors, and other productive members of society.

As a scientist, immigration affects me in another way. Our graduate education system attracts many of the best students from all over the world, especially in science and engineering. I first discovered this as a graduate student at Yale, when my fellow students came from Europe, Africa, China, and South America–and this in a graduate class with fewer than 20 students. In most U.S. science departments today, the majority of our graduate students are foreign-born, and we are delighted to get them. Many of these students remain here after graduation and become valuable members of society, creating much of the innovation that drives the U.S. economy. They stay because the U.S. offers opportunities that their own countries don’t. The U.S. is a far richer country today–not just economically but culturally, intellectually, and socially–than it would be if we closed our doors to immigrants.

I’m not saying we should open our doors to unrestricted immigration: we could be overwhelmed, as Germany and Sweden have been this year. But we should recognize that when immigrants come here to stay–when they want to join the U.S. and become part of our society, with all that entails–they contribute tremendously to the country.

We shouldn’t be afraid of immigrants: we should welcome them. Happy New Year, everyone.

Over-hyped claims that antidepressants cause autism and antidepressants

Over-hyped, overstated, and probably just wrong.

That's my summary of the latest high-profile study of autism, which reports that mothers who take antidepressants increase the risk of autism in their unborn children by up to 87%. The new study, which appeared this week in the journal JAMA Pediatrics, received widespread attention, both uncritical (Washington Post, Huffington Post) and more cautious (CBS News). But it was that 87% increase that caught most people's attention.

Many scientists, including me, read this news with skepticism. It seems particularly unlikely given that exactly two years ago, another large study reported exactly the opposite conclusion. The 2013 study, published in the New England Journal of Medicine, found that antidepressant use during pregnancy was NOT associated with an increased risk of autism. What's more, the 2013 study looked at exactly the same class of antidepressants, selective serotonin uptake inhibitors (SSRIs), as the new study.

So what's going on? Was the 2013 study just wrong? It seemed the only way to answer this was to read the new study, written by Anick Bérard and colleagues. Looking over the new numbers, my conclusion is that Bérard simply tortured the data until she got the results–and the press headlines–that they wanted. Let's look a bit more closely.

Bérard and colleagues looked at 145,456 children born in Quebec between 1998 and 2009. From this total, 4,724 were born to mothers who took antidepressants (SSRIs) at some time during their pregnancy. The number of children diagnosed with autism was 1,054, about 0.7% of all babies. Only 46 of the 1,054 were born to mothers who had taken antidepressants. The study's main results concerns mothers who took antidepressants in the second or third trimester: these women accounted for 2,532 infants, of whom 31 were diagnosed with autism.

If these numbers seem confusing, try focusing on just one number: 31. The study's main conclusion–and all the headlines–are based on those 31 children diagnosed with autism whose mothers took antidepressants in their second or third trimesters.

The key results are found in Table 2 of the study. Out of 9207 infants whose mothers took antidepressants one year before getting pregnant, 82 were later diagnosed with autism. Bérard et al. found that, after adjusting for various confounders, this group of infants had no increased risk of autism. Another group was infants whose mothers took antidepressants, in the first trimester: of these 4200 infants, 40 were diagnosed with autism. Bérard et al. computed that the adjust risk for this group was 16% lower than average. This difference was not statistically significant, though.

Finally, there's the third group of 2,532 children whose mothers took antidepressants during the 2nd or 3rd trimesters. 31 of these children were later diagnosed with autism, which worked out to an increase in relative risk of 87%.

The first thing to note here is that the increase is relative, not absolute. The overall risk of autism in this study, which was consistent with other studies, was 0.7%. An 87% increase works out to a risk of 1.3% – that's an increase of 0.6% in the rate of autism. This doesn't sound nearly so dramatic as 87%.

But keep in mind that this supposed increased risk of autism is based on just 31 cases. Digging a bit deeper, we find that the way these 31 children were diagnosed was not so clear: the authors wrote that
"Autism spectrum disorder was defined as a medical service claim or hospitalization with a diagnosis of ASD."
Apparently this means only that the children were evaluated for autism, as Dr. Alison Stuebe at The Huffington Post pointed out. Bérard et al. admit this in their paper, where they report that when they restricted their analysis to children whose diagnoses were confirmed by a psychiatrist or neurologist, the number of children with autism was smaller and the increased risk was not statistically significant. In other words, if they looked only at children with confirmed autism, their main conclusion would fade away.

You also might have noticed that Bérard divided the data up in multiple ways to look for an increase in autism: they looked at mothers who took antidepressants before getting pregnant, during the first trimester, and during the 2nd and 3rd trimesters. They don't report any findings for the 2nd trimester alone, or for the 3rd trimester alone, which would have certainly involved smaller (and probably less significant) numbers.

This raises a potentially fatal problem with the study: multiple testing. Whenever a study considers more than one hypothesis, the statistics must be adjusted to account for that. If you look for an effect in ten different ways, you're more likely to find something by chance alone, so you have to find a much stronger effect in order for it to be valid. (The web comic xkcd has a great explanation of this.) Bérard doesn't explain how many hypotheses she tested, but she does write that:
"No adjustment was made for multiple comparisons; hence, we cannot rule out chance findings given the number of comparisons made."
No kidding! Upon reading this, my main question was how the journal editors let them get away with this. I guess JAMA's editors like headlines, perhaps a bit too much.

The senior author of the study, Anick Bérard, appears to have an agenda, as Slate's David Auerbach explained. Last year, she testified in a lawsuit against Pfizer, claiming that their antidepressant Zoloft caused birth defects. The judge in that case, Cynthia Rufe, threw out Bérard's testimony with the explanation that her methods were unscientific:
"Dr. Bérard’s opinions regarding Zoloft are only made possible by her departure from use of well-established epidemiological methods." 
Now, the fact that Bérard has previously testified in court cases doesn't prove that her current study is flawed, but it does indicate that she has a bias against antidepressants. This bias might explain why her study looked so hard to find an effect when the data don't seem to support it.

Finally, I should note that even if the new study is correct (and I doubt it), it completely ignores the risk of stopping medication for pregnant women with severe depression, as Dr. Alison Stuebe discussed at length at the Huffington Post. (Recall that the 2013 study I mentioned above found that there was no increased risk of autism in women taking SSRIs.) No woman should go off her medication based on this study, although I fear that the headlines from last week will have exactly that effect.

The top 5 supplements you should not take

Ginkgo trees lining a path.
Dietary supplements are big business. They are promoted for all sorts of health benefits, including weight loss, memory enhancement, body building, and cancer prevention. Many of the claims featured on websites and product packaging are not true, but that doesn’t seem to stop supplement makers from promoting them.

Unlike drugs, supplements are not regulated by the FDA. With drugs, the FDA requires that they be both safe and effective, but with supplements, they can only take action when products are tainted in some way, or when supplement makers cross the line and make specific claims about curing disease. When they do cross that line, all the FDA can do (in most cases) is issue a stern warning and tell them to stop making false claims, which has little effect. In an effort to educate the public, the FDA regularly issues warnings such as this one, telling consumers to “beware of products promising miracle weight loss,” but supplements continue to sell briskly.

Many of the best-selling supplements have little or no evidence to back up their claims, and the vast majority of people will not benefit from taking them. So here are the top 5 dietary supplements that you should not take:

1. Ginkgo biloba. Ginkgo biloba extract is made from the leaves of a beautiful tree that is native to China. It is widely advertised as a supplement that can enhance memory, stave off dementia and Alzheimer’s, and treat other conditions. I found it available from many vendors, including Target, Whole Foods, CVS, Walgreens, and others.

Alas for any hopeful consumers, ginkgo biloba doesn’t work, as scientific studies have repeatedly shown. A recent meta-analysis of 28 different trials looked at its effect on memory, executive function, and attention, and found that it had zero effect on any of these functions.

Nonetheless, web vendors such as continue to promote ginkgo as a treatment for dementia and Alzheimer’s, despite having received a warning notice from the FDA stating that their advertising violates the Food, Drug, and Cosmetics Act. The FDA letter, dating from 2010, stated that ginkgo biloba is “not generally recognized as safe and effective” for dementia or Alzheimers, but the Zooscape website still claims otherwise..

2. Garcinia cambogia. “Garcinia cambogia is hot,” says Consumer Reports. Also known as the tamarind fruit, garcinia cambogia is promoted as a near-magical weight loss treatment. It does contain a substance that was once thought to have promise in treating obesity, but it’s been studied in multiple trials, all of them negative. The first trial, in 1998, concluded that
“Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.” 
According to Consumer Reports, multiple studies since then have all reached the same conclusion: it doesn’t work.

Garcinia cambogia’s popularity took off after Dr. Oz promoted it on his TV show in November 2012, where he called it a “revolutionary fat buster." This episode, which has now been removed from the Dr. Oz show website, was the subject of a U.S. Senate hearing led by Sen. Claire McCaskill, who sharply criticized Oz for promoting products that aren’t back by science. Said McCaskill, "I don't know why you need to say this stuff, because you know it's not true."

I had no trouble at all finding many sources for garcinia cambogia, all of them making strong weight loss claims. sells many brands, including Quality Encapsulations, which calls it a “powerful appetite suppressant” that will “block the formation of new fat cells” (there’s no evidence for this). A brand called Stay Healthy, also available from Amazon, claims you can “eat like a gorilla and lose belly fat fast!”

Sorry, but no: you can’t eat like a gorilla and lose weight. At least not like a healthy gorilla.

3. St. Johns wort is a flowering plant that some people use to treat depression. In this respect, it’s in a different category from the other supplements in this list, which are used for physical rather than psychological conditions.

A double-blind, randomized, placebo-controlled trial of St. John’s wort as a treatment for major depression was published in 2002. This type of study is the gold standard for science-based medicine, and produces the most reliable results. The conclusion was clear: St. John’s wort performed worse than placebo, and the authors concluded that St. John’s work is not effective for major depression.

This might have settled things, but studies continued, and in 2008 a review article came to a different conclusion, finding that St. John’s wort was better than placebo for major depression. Even more recently, a 2011 study looking at minor (rather than major) depression found, just like the 2002 study, that St. John’s wort offers no benefit.

Thus the evidence for St. John’s wort is confusing and contradictory. One thing that is clear, though, is that St. John’s wort can have dangerous interactions with other drugs. The NIH warns that
“Combining St. John’s wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, a brain chemical targeted by antidepressants. St. John’s wort can also limit the effectiveness of many prescription medicines.” (emphasis in original)
Despite these dangers, you can buy St. John’s wort anywhere: it took me mere seconds to find dozens of choices. If you’re thinking about trying it, follow NIH’s advice and consult your physician first.

4. Glucosamin and chondroitin. These two supplements have been promoted for years as a treatment for joint pain. Scientists have run many experiments to see if they work, and some of the experiments have been mildly positive, encouraging people to give them a try. Joint pain, especially in the knees, is very common, and we don’t yet have a real cure (unless you count knee replacement). (I have chronic knee pain myself, and I would love to find a pill that would cure it.)

To finally resolve the question, NIH conducted a large $12.5 million study called GAIT, which compared glucosamin, chondroitin, celecoxib (an NSAID), and placebo. The conclusion: the only treatment that worked was celecoxib (Celebrex). In a small subset of patients with moderate to severe pain, there was a hint of a benefit for glucosamine-chondroitin, but it wasn’t significant. For patients with mild pain, only celecoxib worked better than a placebo.

So the door isn’t completely closed for this supplement: it clearly doesn't work for mild pain, but for moderate to severe pain, it might offer a small benefit, although an NSAID is better.

Of course, there’s no hint of this uncertainty in the advertising I found. For example, Puritan’s Pride says their pill “nourishes joints to improve flexibility, supports connective tissue in and around the joints," and "promotes healthy cartilege." Of course, the very bottom of their web page has a disclaimer stating that "these products are not intended to diagnose, treat, cure or prevent any disease." Oh, so why exactly should anyone purchase them?

5. Echinacea. Echinacea is a flower, similar to a daisy, that is widely used to treat the common cold. Apparently this got its start when a Swiss herbal supplement maker was erroneously told that Native American tribes used it as a cure. Regardless of the source, the use of echinacea grew, and it has now been subjected to multiple scientific studies.

What does the science say? In 2003, a randomized, placebo-controlled, double blind trial published in JAMA – again, these are the gold standard for scientific evidence – found that echinacea was not effective for treating colds in children aged 2-11, and that it appeared to causes rashes in some of them. Another study, also a randomized, placebo-controlled, double-blind trial, looked at college students, and found again that echinacea didn't work for them either: "echinacea provided no detectable benefit or harm in these college students who had the common cold." More recently, a 2014 review concluded "Echinacea products have not here been shown to provide benefits for treating colds."

Not surprisingly, though, everyone sells echinacea. The NatureMade brand just says "supports immune system health" (a vague claim that the FDA doesn't restrict). Puritan's Pride's label says the same thing. The Dr. Oz website doesn't sell echinacea, but an article there by Tod Cooperman claims that "echinacea can help you get over a cold faster and reduce symptoms." Zooscape is even bolder: it sells an echinacea tea that it advertises with the phrase "colds and flu be gone!"

Save your money. If you have a cold, echinacea won't help. I have it on very good authority, though, that chicken soup works wonders.

[For a list of the top vitamins you don't need, see my 2014 article on that topic.]