Comparing Birth Control Trials Today to Those in the 60s Ignores a Sea Change in Research Ethics

Vox has a wonderful article on the recently published male birth control study that is a useful corrective to the narrative that falsely equates it to the original studies of The Pill. Though I say ignore their title, too, because it’s also not that helpful of a narrative either. But the content is useful in arguing against what seems like a terrible and callous framing of the study in most commentary. The key line: “And, yes, the rate of side effects in this study was higher than what women typically experience using hormonal birth control.” Also, can we point out if something like 10 women a year at a school like UVA were committing suicide and it might be linked to a medication they were taking, people would probably be concerned? There’s something disturbing about well-off American women mocking these effects that seemed to disproportionately affect men of color (the most side effects were reported from the Indonesian center, followed by the Chilean center).

My bigger concern here, though, is that most people seem to not understand (or are basically ignoring) how modern research ethics works. For instance, the notion of benefits being weighed in the evaluation of continuing the study aren’t merely the potential benefits of the treatment, but the added benefit of acquiring more data. This was an efficacy study (so I think Phase II, or maybe it was combined Phase I/II, although it might be a really small Phase III trial). It seems like the institutional review board felt enough data had been collected to reach conclusions on efficacy that more data didn’t justify the potential high rate of adverse effects. Which also DOES NOT mean that this treatment has been ruled out forever. The authors themselves recommend further development based on the 75% of participants claiming they would use this birth control method if it were available. I imagine they will tweak the formulation a bit before moving on to further trials. Also, it’s sort of amusing that complaints on this come from people who typically think moves toward regulatory approval are controlled by Big Pharma at the expense of patient health.

Yes, this is different than the initial birth control trials. Yes, the women of Puerto Rico were chosen as human guinea pigs. Though it’s worth pointing out another major factor in choosing Puerto Rico was that it actually had a pretty well organized family planning infrastructure in the 50s and 60s. Admittedly, there’s more racism almost certainly coming into play there, because the politics of family planning were super complicated through the early and mid 20th century and there were definitely overlaps between eugenics and family planning. It’s also worth pointing out the study was encouraged by Margaret Sanger (and earlier studies by Planned Parenthood). Also, the FDA didn’t even initially approve Enovid for contraception because the atmosphere was so repressive back then on reproductive health; it was for menstrual disorders but prescribed off-label for contraception, which is why we know so many women desperately wanted the pill. Heck, even the Puerto Rico study was nominally about seeing if the pill helped with breast cancer. It took another year of discussion by the researchers and companies to get the FDA to finally approve contraception as an on-label use. The company making the pill was actually so concerned about the dosage causing side effects they begged for FDA approval for a lower dose just for contraception (see page 27-28 there) but were rebuffed for another year or two and they refused to market the initial dose for solely for contraception. (Also, to clarify, no one is taking these medications anymore. These versions of the pill were phased out in the 80s.)

Was there sexism at play? Absolutely, and I totally get that. But that doesn’t mean the narrative from 2016 neatly maps onto the narrative of the 1950s and 1960s. Which brings me to my last point. If your view of research ethics is primarily colored by the 1960s, that’s terrifying. You know what else happened at the same time as the initial contraception pill studies? The US government was still letting black men die of syphilis in the name of research. The tissue of Henrietta Lacks was still being cultured without the knowledge or consent of anyone in her family. (And the way they were informed was heartbreaking.) People were unknowingly treated or injected with radioactive material (one of many instances is described here in the segment of testimony by Cliff Honicker). One study involved secretly injecting healthy people with cancer cells, and to prove a theme, those cells were descendants of the ones originally cultured from Henrietta Lacks. Heck, there’s the Milgram experiment and then the Stanford Prison Study was in the 70s. The ethics of human experimentation were a mess for most of the 20th century, and really, most of the history of science. Similarly, medical ethics were very different at the time. Which isn’t to justify those things. But don’t ignore that we’ve been working to make science and research more open, collaborative, and just over the last few decades, and people seem caught up in making humorous or spiteful points than continuing that work right now.

(Other aside, it’s worth pointing out that the comparison here probably does have to be to condoms, which you know, skip the side effects though their typical effectiveness rate is worse. Most of the methods don’t obviously change ejaculate, so unless measuring sperm concentration and motility is a couple’s idea of foreplay, sexual partners who don’t know each other well will still probably want a condom [or unfortunately another method, because yes, the system is sexist and women are expected to do more] as assurance. It’s worth pointing out the study design only worked with “stable” couples who were mutually monogamous and planned on staying together for at least a year during the duration of the study, so there presumably was a high degree of trust in these relationships.)

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News Publications without Science Sections

Inspired by Dr. Danielle Lee’s recent Twitter musings that STEM coverage directed towards minority communities is rare, which is compounded by the lower recognition that black scientists, engineers, and technologists get in their professional communities and the lack of STEM-focused coverage in African American media, I was curious to see how other major “thought leader” publications fared.

No Science or Science-Related Sections

JET – Though the website seems more lifestyle-focused than I expected, so maybe this is unfair

The National Review – Okay, their website is confusing, because I see a “Space” tag that doesn’t actually lead anywhere and they evidently have a “Planet Gore” section that is devoted to what they view as climate change hypocrisy. “Human Exceptionalism” is probably notable as the only column that routinely talks about bioethics in mainstream political publications.

No Science Sections, but Tech(nology), Health, or Other Science-Related Sections

The New Republic – Has a Technology section, which mainly seems to exist chronicle technical developments as they relate to politics or the economy

The Atlantic – Has Health and Tech sections, with science stories kind of split between them

EBONY – Has health (subsection of Wellness) and tech (subsection of Life); tech seems more consumer focused

The Daily Beast – has a combined “Tech + Health” section

ABC News – Has Tech and Health sections, and strangely, in that order

CNN – Has Tech and Health sections

MSNBC – Has Health and a “Green” section

NewsOne – Has a Health section

Some surprises

In contrast to ABC, CBS News has a joint Science and Technology section and a separate Health section and NBC News has separate Health, Tech, and Science sections.

Similarly, Fox News has separate TechScience, and Health sections, and I would have expected them to parallel CNN in structure. Also, I’m really surprised that they list Health as the last of those sections since if the stereotype of Fox News watchers/readers as being older holds true, I would expect them to be more interested in health and wellness articles.

There Are Probably No Nanoparticles in Your Food… At Least, Not Intentionally

Recently, Mother Jones posted an article about “Big Dairy” putting microscopic pieces of metal in food. Their main source is the Project on Emerging Nanotechnologies and its Consumer Products Inventory, a collaboration between the Wilson Center and Virginia Tech. Unfortunately, the Mother Jones piece seems to misunderstand how the CPI is meant to be used. But another problem is that the CPI itself seems poorly designed as a tool for journalists.

So what’s the issue? The Mother Jones piece mainly focuses on the alleged use of nanoparticles of titanium dioxide (TiO2) in certain foods to enhance colors, making whites whiter or brightening other colors. First, the piece makes an error in its description of TiO2 as a “microscopic piece of metal”. Titanium is a metal, but metal oxides are not, unless you consider rust a metal (which would also be wrong). But another issue is “microscopic”. Just because something is microscopic, which generally means smaller than your eye can see, doesn’t mean it’s a nanomaterial. The smallest thing you can see at a normal reading distance is about a tenth of a millimeter, which is 1000 times bigger than the 100 nanometer cut-off we typically use to talk about nanoparticles.

A clear glass dish holds a bright white powder.

Titanium dioxide is a vivid white pigment, even as macroscopic particles.

And that’s what confuses me most here. As you can see above, titanium dioxide is white as a powder, but in that form it’s several hundred nanometers wide at minimum, if not on the scale of microns (1000 nanometers). In fact, nanoparticles of TiO2 are too small to scatter visible light and so they can’t appear white. A friend reminded me how sunscreens have switched from large TiO2 particles to actual nanoparticles precisely because it helps the sunscreen go on clearer. I’m not naive enough to think food companies wouldn’t try to cut a buck to help improve and standardize appearances, but I also don’t think food scientists are dumb enough to pay for a version of a material they can’t fulfill the purpose they’re adding it for. So TiO2 is probably used in some foods, but not on a nanoscale that radically changes it’s health properties.

But I don’t entirely blame Mother Jones. The thing is, the main reason I had a hunch the article seemed wrong is because one of my labmates at UVA has been working with TiO2 nanotubes for the last three years, and I’ve seen his samples. If I didn’t know that, and I just saw PEN include TiO2 on its list of nano additives, I would be inclined to believe it. PEN saw the Mother Jones piece and another similar article and responded by pointing out that the inventory categorized their inclusion of TiO2 in the products as having low confidence it was actually used. But their source is an environmental science paper including actual chemical analyses of food grade TiO2, so why do they give that low confidence? Also, PEN claims the CPI is something the public can use to monitor nanotechnology in products, so maybe they should rethink how confident they are in their analysis if they want to keep selling it that way.

The paper CPI references in the TiO2 claim is interesting too. That paper actually shows that most of the TiO2 is around 100 nm (figure below). But like I said, that’s kind of pushing the limit on how small the particles can be and still look white. It might be that the authors stumbled across a weird batch, as they note that in liquid products containing TiO2, less than 5% of the TiO2 could go through filters with pores that were 450 nanometers wide. Does the current process used to make food grade TiO2 end up making a lot of particles that are actually smaller than needed? Or maybe larger particles are breaking down into the smaller particles that Weir sees while in storage. This probably does need more research if other groups can replicate these results.

A histogram showing the distribution of particle sizes of TiO2. Categories go from 40 nanometers to 220 nanometers in intervals of 10. The greatest number of particles have diameters of 90-100 or 100-110 nanometers.

Distribution of TiO2 particle sizes in food grade TiO2. From Weir et al, http://pubs.acs.org/doi/abs/10.1021/es204168d?journalCode=esthag

What do Einstein and Elvis Have In Common?

  Aside from fantastic hair and piercing eyes?

They can both help diagnose dementia.

Recognizing famous pop culture figures can be used as a measure of several mental tasks, like the ability to recognize faces (which can be a really complicated process, resulting in the common phenomenon of seeing faces in random objects called pareidolia) and how easily a person can name things. One problem that the researchers came across when evaluating people was how old the original face test was. A person in their 70s or 60s may know what Emperor Hirohito looked like, but could you expect that of a 40-year-old coming in to see if they had early-onset dementia? So the team at Northwestern decided to modernize the sample. Einstein made the cut to stay, since his mug can still be found everywhere in our culture. But now we have Oprah instead of Martha Mitchell (the wife of Nixon’s attorney general, evidently).

Wine Tasting 101

NPR’s blog about food and science, The Salt, has an amusing story on wine tasting this week. Part of it is pointing out the actual science in wine tasting, which has recently been a victim of fights on the Internet*. Basically, The Salt’s post focuses on the actual chemicals present in wines and wants to help wine newbies detect by saying where we can find them in other foods. So here’s the quick lowdown

  • Whites aren’t aged in oak as often as reds.
  • Wine aged in American oak picks up more vanillin from the word than wines aged in French oak. Evidently American oaks have a higher concentration of the lactones than the French oaks. (I can’t find an explanation why, but that’s interesting) Vanillin, of course, is the primary chemical responsible for the flavor of vanilla.
  • Cabernet sauvignon and green peppers have the same chemical responsible for their smell. In cabernet, it’s strongest when the grapes aren’t ripe, so smelling green pepper would suggest a low quality wine. Aside: I definitely did not know that. I actually thought it wasn’t bad to have the green pepper scent. I also almost never drink cabernet, so maybe nothing should surprise me.
  • Diacetyl, a chemical commonly used in artificial butter flavorings (but also present in actual butter, potential chemophobes), develops in wines that have undergone a further fermentation process that converts the more sour malic acid (found in green apples) to lactic acid (found in milk).

NPR talks about sniffing all the foods with the same chemicals so you can “follow your nose”, if you will.

We went there.

They even suggest putting the good things in a cheap wine and comparing it’s smell to a more expensive one so you can find the similarities. But maybe I’m just taking the wrong lesson from this article, because I want to spray Pam into a wine glass and add some vanilla flavoring after pouring some Two Buck Chuck in and seeing if that tastes good.

*Just a quick thought on the “wine science wars”. I don’t think wine critics view themselves as scientific arbiters of wine, but I do think they present themselves as having far more precision than the studies suggest they do. Wine blogger Heimoff asks why we never see a headline saying that restaurant reviews are all junk science. Because they don’t claim to be picking up 12 distinct flavors from a single component, unlike a wine reviewer who honestly said a single wine had flavors of “red roses, lavender, geranium, dried hibiscus flowers, cranberry raisins, currant jelly, mango with skins, red plums, cobbler, cinnamon, star anise, blackberry bramble, whole black peppercorn” (perhaps take that review with a grain of salt, since the story sounds like it is coming from an ad almost).

I also think they do have a harder job than the restaurant critics. At a restaurant, you get to examine multiple things: the food, the service, the atmosphere, etc. Heck, even if you only focus on the food, that still leads to several different things to examine, whether that’s multiple courses at a Michelin-rated restaurant or just the multiple ingredients in a sandwich. A wine critic has one thing to look at, and they try to go into intense detail. But humans aren’t meant for analytical chemistry. I think things like this Salt article are perfect. It does show what people can appreciate in a wine and what the industry tries to create.