Another example of why basic research matters

Scientists have been working on techniques to treat mitochondrial diseases, and one strategy is to create “3 parent” babies, where the mother’s defective mitochondria are replaced or supplemented in her gametes with mitochondria from another woman, and the gamete is then fertilized with sperm from the father. It works!

In September, reproductive endocrinologist John Zhang and his team at the New Hope Fertility Center in New York City captured the world’s attention when they announced the birth of a child to a mother carrying a fatal genetic defect.

Using a technique called mitochondrial replacement therapy, the researchers combined DNA from two women and one man to bypass the defect and produce a healthy baby boy — one with, quite literally, three genetic parents.

There is, however, a significant possibility of failure.

Earlier this month, a study published in Nature by Shoukhrat Mitalipov, head of the Center for Embryonic Cell and Gene Therapy at the Oregon Health and Science University in Portland, suggested that in roughly 15 percent of cases, the mitochondrial replacement could fail and allow fatal defects to return, or even increase a child’s vulnerability to new ailments.

The findings confirmed the suspicions of many researchers, and the conclusions drawn by Mitalipov and his team were unequivocal: The potential for conflicts between transplanted and original mitochondrial genomes is real, and more sophisticated matching of donor and recipient eggs — pairing mothers whose mitochondria share genetic similarities, for example — is needed to avoid potential tragedies.

This is not at all surprising, and shouldn’t be used as a reason to stop the research. This was expected. Anyone who has studied mitochondrial genetics — and I’m sure this is the case for these researchers as well — knows about dominant negative effects. There are known alleles in mitochondria that are negative, that is they are deleterious to the organelle, and are also dominant, that is, one copy of the of the allele can suppress healthy mitochondria in the same cell. We also know that mitochondria replicate independently of the cell, and that in some cases the defective mitochondria can outcompete and replace the healthy mitochondria. This is the case in, for instance, poky mutants in Neurospora, and petite mutants in yeast.

So, old news. It seems to make the popular press only when it looks like it might affect human beings, though, which is too bad, because awareness of the problem arose from basic cell biology, and will be best solved by experimental work in non-human organisms. Let’s see more funding for yeast and Neurospora and fruit fly and zebrafish research!



That’s no insult, it’s a zebrafish craniofacial development website. It’s cool that it’s managed by my graduate advisor, Chuck Kimmel, but it’s also full of images of zebrafish skulls (fish skulls in general are amazingly beautiful, with all kinds of delicate detail). I’m pining for a confocal microscope of my very own now.

It’s also a subset of FaceBase, an even grander collection of data on craniofacial development in those lesser creatures, humans and mice. If you’re interested in the formation of the head and neck — and you should be, those are complex hotspots for all kinds of developmental disorders — check it out.

I don’t wanna make book recommendations

It’s that time of year when I think everyone got Amazon gift cards and then they go asking me to make book recommendations. It’s hard. Writing a science book is even harder. And there are a lot of bad science books out there.

One problem is that everyone wants the shortcut: there’s a hot new science topic, lots of people are curious about it, they want to know more, the publishers see an opportunity, so they commission a flashy pop sci book that will sate that curiosity. And it’s garbage, because it’s written by people who don’t know the basics, or because it’s written for people who want to hear that the answer is magic. Case in point: there are no good popular books about epigenetics right now, as far as I can see. If it’s got “epigenome” in the title, just scratch it right off your list. This may change, I hope it will change, but it’s an example of a topic where the situation is rather dire. That’s unfortunate, because it’s an important topic.

At the other extreme, there are the textbooks. There is a reason that textbooks exist, and it isn’t just the venality of publishers and the conservative nature of professors: they are dense repositories of basic knowledge. My genetics class uses Klug’s Concepts of Genetics, it’s not light reading, and to get the most out of it you should actually sit down and do the problems at the end of each chapter. Does that sound like fun? How does the $196 price tag sound to you?

There is a sweet spot in popular science writing where the author manages to simultaneously explain the basics and get them right, while also getting the big picture explained in an interesting way. Carl Zimmer consistently hits that target, Sean B. Carroll is good, Adam Rutherford’s Creation does a fine job of covering biotech and the origin of life, Nick Lane is always amazing. The microbiome was one of those buzzwords that spawned a lot of crap books, like the word “epigenetics” now, but Ed Yong rose above the dross and came out with a good general science book on the subject.

But it’s still really difficult to address requests for recommendations. Usually it’s because someone wants an answer that they can digest in a couple of days of light reading, and often, that can’t be done.

The correct answer is that what you need to do is register at the University of Minnesota and sign up for my classes. I’ll whip you into shape in 15 weeks of harsh discipline.

It’s the same old racist genetics

Another domain the alt-right neo-Nazis want to claim for their own is genetics. Sarah Zang has a very good overview of how the deplorables are eyeballing modern genetics and genomics, and mangling it to support their racist theories, titled Will the Alt-Right Peddle a New Kind of Racist Genetics? My only objection would be that this isn’t a new kind of racist genetics at all — it’s the same old garbage, in which they misinterpret results to support their preconceptions. The interesting thing, though, is that geneticists are gearing up to fight back.

Jedidiah Carlson was googling a genetics research paper when he stumbled upon the white nationalist forum Stormfront. Carlson is a graduate student at the University of Michigan, and he is—to be clear—absolutely not a white nationalist. But one link led to another and he ended up reading page after page of Stormfront discussions on the reliability of 23andMe ancestry results and whether Neanderthal interbreeding is the reason for the genetic superiority of whites. Obsession with racial purity is easily channeled, apparently, into an obsession with genetics.

Stormfront has been around since the ’90s, which means it’s been around for the entirety of the genomic revolution. The major milestones in human genetics—sequencing of the first human genome, genetic confirmation that humans came out of Africa, the first mail-in DNA ancestry tests—they’re all there, refracted through the lens of white nationalism. Sure, the commentators sometimes disagreed with scientific findings or mischaracterized them, but they could also be serious about understanding genetics. “The threads would turn into an informal tutoring session and journal club,” observes Carlson. “Some of the posters have a really profound understanding of everyday concepts in population genetics.”

Carlson has been arguing with the bozos on Twitter, and I’ve been occasionally bouncing off them here and there — the “human biodiversity” gang, their intentionally neutral term for pseudo-scientific racism, kinda despises me. Even before I read this article, though, I was working up some new material for the genetics course I’ll be teaching in January specifically to address some of these problems at a fairly basic level.

One concern I’ve had for a while now is that often in undergraduate genetics we’re teaching a kind of simplified Mendelism as a starting point, and in the lab we do crosses that have been time-tested for clarity and consistency. Students start out with this kind of crude beanbag genetics in their heads, which actually is a good beginning point to get the concepts across, but then when we get into real genetics, that is considerably messier and more difficult, they may flounder. At least, that’s been my experience; but we also see it in the general public where they got a bit of Mendelian pea-crossing in high school, and then they hear something about epigenetics and just go off the rails.

This year I think my first class will involve throwing examples at them of unexpected genetics, stuff that doesn’t fit their high-school version, and start ’em out by preparing them to not trust simplistic interpretations, and to realize that Mendel’s results were a starting point for a model. It’ll also help to let them know that they don’t know everything right from the first day.

But then we’ll go right back to Mendel, and work our way up from that foundation to the hard, fun, bewildering stuff. And maybe I should try to include at least a little section on the genetics of race near the end. The garbage that Stormfront is peddling has been around for a long time, and maybe we need to start addressing it at the undergrad level now…and yes, at the high school level. I’ll have to leave that to the high school science teachers out there reading this.

There’s no such thing as male and female DNA

I’ve been away for a while — my beloved has been away for over a week (felt like longer), and I had to travel through the arctic wilderness and another icy storm to pick her up at the airport, and then we had to spend a night in a hotel because of said icy storm, and I just got home. It was aggravating because there was an extreme case of someone being wrong on the internet, and I’d left my laptop at home (it was supposed to be just a quick trip to Minneapolis and back!), so I was frustrated in my inability to reply. All I could see was Twitter, and that is not an appropriate place for a a sufficiently lengthy, ragey response.

It was Bryan Fischer. Savor the irony in this.

It’s a scientific, biological, genetic fact that DNA is either male or female. To reject that is to reject science. I’ll stick with science.

Yeah, the young earth creationist wants to stick with the science. Look, simple answer first: DNA is not gendered. There is no difference in sequence, structure, or conformation between males and females. Fischer has invented a false fact that only serves the sanctimoniousness of assholes.

[Read more…]

Science and race

The scientific conversation about race gets horribly warped in translation to the public — in general, a few right-wing crank sites are loud in their assertions that race is a biologically useful parameter, that it can be simplified into a few ‘obvious’ categories that somehow magically fall into perfect alignment with the assessment of bigots, and that culture is a relatively minor component that cannot overrule basic human nature…whatever that is. I highly recommend this article in which Agustín Fuentes and Carolyn Rouse talk about race — this is the biologically/anthropologically informed perspective.

One of the weird things I see over and over again is how recognizing the importance of human diversity is shoe-horned into simplistic categories. Rather than appreciating the complexity and ubiquity of genetic variation, it has to be mapped onto 18th and 19th century colonial perspectives, and it really doesn’t fit at all.

Agustín: There remains a strong desire to see that 0.1 percent as the “real” important part of the genome. In the United States, difference is always more important than similarity — the well-known “one-drop” racial classification categories. This is tied to the resilience of genetic determinism as an explanatory frame to make sense of social difference. There is an erroneous assumption that the variable genetic patterns in humans underlie relevant differences in health, behavior and even aptitude. This leads smack dab into the “race” issue.

Yes, different populations vary in some of the 0.1 percent of the genome that makes up much of human genetic diversity, but this variation does not represent biological races no matter how one manipulates/packages/represents it. Wade and others love to use standard data sets and compare the 0.1 percent variants in clusters of people from Nigeria, Western Europe, Beijing and Tokyo, and so on. Doing this does yield some patterned differences, but these populations do not reflect the entire continental areas of Africa, Europe and Asia, the classic “races.” A comparison of geographically separated populations within the continental areas also yields easily measurable variation of similar magnitude. Comparing 60 Nigerians to 60 European-descendant Americans to 60 people from Beijing and Tokyo gives the same level of differences in genetic variation as does comparing such clusters of people from Siberia, Tibet and Java (Asia) or from Finland, Wales and Yemen (“Europe”) or even Somalia, Liberia and South Africa (Africa). None of these comparisons give us races. Identifying a few genetic variants that are more common in some populations in some parts of some continents than they are in other populations in other parts of other continents does not come close to any biologically valid demonstration of race.

Then there are the academics that misrepresent the broader view that environment and genetics interact in complex ways that can’t be reduced to simple biological determinism. For decades, that’s been touted as the “blank slate” model, which is a total strawman, but it’s really easy to write popular essays and books that mock other academics for essentially recognizing the complexity of human behavior.

Carolyn: Some of these beliefs have been promoted for years by well-funded racist organizations such as the Pioneer Fund; this group had among its members the late Philippe Rushton, who believed that there is an inverse relationship between penis size and IQ. But there is also the more mainstream Heterodox Academy, an online forum dedicated to pushing the academy to the political right because, the group’s members believe, liberal scholars teach orthodox ideas “without any real evidence.” Listed among the entrenched, unsubstantiated orthodoxies held up for critique by the Academy is this one: “All differences between human groups are caused by differential treatment of those groups, or by differential media portrayals of group members” [11] They don’t like the idea that scholars question what actually constitutes human behavior. Notables listed on the Heterodox Academy’s advisory board in 2016 include Steven Pinker of Harvard, John McGinnis of Northwestern and John McWhorter of Columbia. It is fascinating that some scholars think evolutionary biologists who challenge the idea that humans can be neatly sorted into racial groups are doing so for political reasons.

It’s actually a pretty good recipe for getting well-known — conform to human biases, claim scientific justification, and write lots of reductionist tracts that pander to “common sense” attitudes about race. It’s especially successful in the US, I think, and then the people who know better have to write more complex dissections of reality that get ignored.

And then the lies simmer in the public consciousness and ooze up into academia. This is shocking:

While the compassion driving attempts to find genetic causes for racial health disparities can be celebrated, the insidiousness of the discourse must be noted. This can be seen in a 2016 Proceedings of the National Academy of Sciences (PNAS) article that indicates many medical students think blacks and whites have significant physical differences based on their genes [14]. The authors interviewed first-, second- and third-year med students as well as residents about biological difference. The research showed, for ex- ample, that 63 percent of first-year students believed black skin is thicker than white skin. 46 percent of first-year students believed black people’s blood coagulates more quickly than whites’. The authors conclude, “A substantial number of white laypeople and medical students and residents hold false beliefs about biological differences between blacks and whites and demonstrate that these beliefs predict racial bias in pain perception and treatment recommendation accuracy.” Science historian Keith Wailoo wrote a response to the article in The Daily Beast, where he noted, “The UVA study turns our gaze to one important place where race problems are manifest — medical training and physician perceptions” [15].

While I agree that the findings are horrifying, I would like to highlight two things. First, the statistics seem to point not to medical school per se, but to undergraduate preparation and to public health discourses about race and biological difference. Notably, the data show that first-year and third-year students have vastly different beliefs about race. For example, 33 percent of first-year medical students said “Blacks have stronger immune systems than whites,” whereas only 5 percent of third-year students held this belief. Similarly, 42 percent of first-year students believed “Black people’s blood coagulates more quickly than whites,” whereas 5 percent of third-year students agreed. Again, about 13 percent of first-year students believed “Blacks’ nerve endings are less sensitive than whites,” whereas 0 percent of third- year students held this belief [16].

I’ve encountered a few students who enter undergraduate studies with the idea that men have one fewer rib than women, which is a horrifying level of ignorance. That can get corrected quickly the first time they’re shown a display skeleton, though.

But medical students — they’ve already completed 4 years of undergraduate work, usually with a biology major, and they come out of it with those gross misconceptions? I’ve been trying to readjust religiously warped brains in the introductory biology class I teach with two whole lectures on creationism and misunderstandings of basic evolutionary biology, but I think I’ve been missing an entire vast category of bad folk biology assembled around misunderstandings about race. I’m going to have to drop one of my creationism sessions and replace it with a biology of race session, instead. A discussion about that PNAS article might be a good place to start.

Or we could just require every college student to take an anthropology course.