The omicron variant evades vaccine immunity but boosters help

Scientists are very interested in the omicron variant and why it is so dangerous. Since vaccinated people are getting infected, it must mean that the omicron variant isn't effectively neutralized by vaccine-induced antibodies. Several preprints on this topic have been posted and they all reach the same conclusion. I'll discuss one of them.

Garcia-Beltran, W.F., St Denis, K.J., Hoelzemer, A., Lam, E.C., Nitido, A.D., Sheehan, M.L., Berrios, C., Ofoman, O., Chang, C.C. and Hauser, B.M. (2021) mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. medRxiv. doi: 10.1101/2021.12.14.21267755

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of vaccine-induced neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

On the effectiveness of vaccines

I've learned a bit of immunology from hanging out with immunologists so I'm going to try and explain how vaccines protect you from the worst consequences of an infection and why booster shots aren't as necessary as you think. This will be an illustration of how difficult it is for the media to keep you correctly informed about real science and why we should have more scientists explaining these things instead of doctors

Dozens of papers on this topic have been published over the past year or so and they all say the same thing. SARS-CoV-2 vaccinations induce an immediate production of antibodies in response to the spike protein antigen whether it's presented on the surface of a viral vector such as adenovirus or synthesized in your cells by mRNA. The antibodies are produced by a small number of B cells that just by chance happen to recognize the viral protein. These cells multiply rapidly so that within a few days you have enough antibodies being produced to fight off any infection.

Over time, the antibody production declines if there's no infection but some of the B cells become memory B cells that lie in wait for the next infection when they can be rapidly stimulated if you get infected months, or years, later. There's another type of cell called a T cell that also forms memory T cells that are very long-lasting and help fight off future infections.

Imagine that you encounter the virus several months after you've been vaccinated. As soon as the virus enters your body the memory cells are activated and the virus is attacked. You may have a mild case of COVID-19 for a few days but you are protected against the most severe forms of the disease. The point is that a reduction in antibody levels is perfectly normal. What's important is whether you have a robust level of memory B cells and memory T cells that can be activated. The hype in the media has convinced people that the vaccines are no longer effective after six months and you have to get a booster shot to protect you from COVID-19.

Here's a very recent paper that presents the data. It was published in Science on December 3, 2021.

Goel, R.R., Painter, M.M., Apostolidis, S.A., Mathew, D., Meng, W., Rosenfeld, A.M., Lundgreen, K.A., Reynaldi, A., Khoury, D.S. and Pattekar, A. et al. (2021) mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science 374:eabm0829. doi: 10.1126/science.abm0829

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven highly effective at preventing severe COVID-19. However, the evolution of viral variants, and waning antibody levels over time, raise questions regarding the longevity of vaccine-induced immune protection. Goel et al. examined B and T lymphocyte responses in individuals who received SARS-CoV-2 messenger RNA vaccines. They performed a 6-month longitudinal study of individuals who never had SARS-CoV-2 infection compared with people who had recovered from SARS-CoV-2. Humoral and cellular immune memory was observed in vaccinated individuals, as were functional immune responses against the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) viral variants. Analysis of T cell activity suggested that robust cellular immune memory may prevent hospitalization by limiting the development of severe disease.

The authors looked at the immune reaction in three different groups. The first was the naive group of people who have never had COVID-19 but got the vaccine (blue). The second group was people who had already survived COVID-19 and then got vaccinated (red). The third group was composed of people who had mild cases of COVID-19 and never got vaccinated (purple).

This is a long paper with lots of experiments but the data can be summarized in the figure below. The authors looked at antibodies to the spike protein and to its specific ACE2 binding site. They also looked at neutralizing antibodies or the abiity of circulating antibodies to neutralize whole virus particles. The results are summarized in the first graph and they show that the antibody levels rise to maximum levels about one week after receiving the second dose of vaccine (administered four weeks after the first dose).

The antibody levels fall to about 10% of the maximum value over the next six months. (The x-axis is a log scale.) This is exactly what you expect for a typical vaccine. Note that the levels for people who had already been infected were higher to begin with but the rate of decline was similar to the naive group. This suggests that booster shots will have a similar effect on antibody levels.

The levels of memory B cells and memory T cells rise to a maximum at four months, right at the time of the second dose. They remain high at the end of six months.

Taken together, these data demonstrate that mRNA vaccines induced a population of memory B cells that was durable for at least six months after vaccinaton, and these cells were capable of rapidly producing functional antibodies against SARS-CoV-2, including neutralizing antibodies against VOCs [variants of concern], upon stimulation....

Taken together, these data indicate that mRNA vaccination generates durable SARS-CoV-2-specific CD4⁺ T cell memory in individuals who were not previously infected with SARS-CoV-2 and only transiently boosts these responses in SARS-CoV-2-recovered individuals.

What this means is described by the authors in the concluding remarks,

These data may also provide context for understanding potential discrepancies in vaccine efficacy at preventing infection versus severe disease, hospitalization, and death. Declining antibody titers over time likely reduce the potential that vaccination will completely prevent infection or provide near-sterilizing immunity. However, the durability of cellular immunity, here demonstrated for at least 6 months, may contribute to rapid recall responses that can limit initial viral replication and dissemination in the host, thereby preventing severe disease.

In other words, if you are fully vaccinated (two doses of mRNA vaccine) then you are well-protected against severe disease although you may suffer mild symptoms for a few days. You may be able to avoid the mild symptoms if you have gotten a recent booster shot but that effect is likely to decline in a few months.

The hype about booster shots is extremely misleading. The media is making it sound like all of your vaccine protection declines after six months and you need the boosters to have any chance at all against the omicron variant. How many times have you heard that your vaccine protection drops to 33% after six months?

You could argue that boosters aren't even necessary but that ignores the possibility that even a mild infection may be harmful to some people. It also ignores the possibility that by preventing even a mild infection you could be blocking the spread of the virus. I don't know of any data on viral loads after vaccination but I suspect that a booster offers some protection against spread.

---

Image Credit: The coronavirus figure is from Alexy Solodovnikov and Wikmedia Commons.

"Has Science Killed Philosophy?"

This is a debate sponsored by the Royal Institute of Philosophy on the question "Has science killed philosophy?" It suffers from one of the main problems of the philosphy of science and that's an unreasonable focus on theoretical physics. What's interesting is that the question even arises because that suggests to me that there's some reason to suspect that philosophy might not be as important as most philosophers think.

Watch the debate and decide for yourselves whether philosophy is still useful. Frankly, I found it very boring. I didn't learn anything that I didn't know before and I didn't find the defense of philosophy compelling. The philosopher's best answer to the challenge is that their discipline has complete control over rational thinking so every time you are thinking seriously about something you are doing philosophy. Ergo, philosophy will never be killed by science.

What do you think of Eleanor Knox's description of the differences between your right hand and your left hand? Is she on to a deep metaphysical question that science can't address? Or is this an example of why scientists are skeptical of the value of philosophy?

All three panelists were asked to identify a modern philosopher who made a significant contribution to science. Alex Rosenberg immediately identified someone named Samir Okasha whom I've never heard of. Apparently, Okasha made a significant contribution to the levels of selection question in evolution. According to Alex Rosenberg, the philosophers that he listens to tell him that if anyone has settled these question it's Okasha. Perhaps he should listen to evolutionary biologists to get their view on the subject?

---

The first review of "Viral" is out and it ain't pretty

Michael Hiltzik is first off the mark writing for the Los Angeles Times: These authors wanted to push the COVID-19 lab-leak theory. Instead they exposed its weaknesses.

Hiltzik is one of the few science writers who know what they'r talking about.¹ You should read his entire review—here are some excerpts to tempt you.

... “Viral” is a laboratory-perfect example of how not to write about a scientific issue. The authors rely less on the scientists doing the painstaking work to unearth the virus’ origin than on self-described sleuths who broadcast their dubious claims, sometimes anonymously, on social media. In the end, Chan and Ridley spotlight all the shortcomings of the hypothesis they set out to defend....

“Viral” is built on vague innuendo, dressed up with assertions that may strike laypeople as plausible but have long since been debunked by experienced virologists. An entire chapter, for example, is devoted to the “furin cleavage site,” a feature of the virus’ structure through which the enzyme furin makes the spikes on its surface — which it uses to penetrate and infect healthy cells — more effective.

The furin site was originally described by lab-leak advocates as so unusual that it could have been placed there only by humans. Virologists have since determined that the feature is not all that rare in viruses similar to SARS2, and in any case, it could have emerged through natural evolutionary processes well known to experts. Chan and Ridley place a heads-I-win-tails-you-lose gloss on these findings, writing that if the site “proves to have been inserted artificially, it confirms that the virus was in a laboratory and was altered. ... If, on the other hand, the furin cleavage site proves to be natural, it still says nothing about where the virus came from.” Why write about it at all, then?

Alina Chan's reputation is already about as low as it can get and now it looks like she's dragging Matt Ridely down with her. He was already part way there so he didn't have far to go.

The book is published by HarperCollins. Should American lawmakers look seriously at regulating the publishing industry for spreading misinformation since they're already investigating Facebook for the same crime?

---

1. See: Is the media finally realizing that they have been duped into promoting the lab leak conspiracy theory?.

Alina Chan teams up with Matt Ridley to promote the lab leak conspiracy theory

Harper is set to publish Viral: The Search for the Origin of COVID-19 in just a few days. The authors are Alina Chan, a postdoc at the Broad Institute of MIT and Harvard, and Matt Ridley, a science journalist who has written several respectable books.

The book promises to reignite discussion of the lab leak conspriracy theory with a focus on Alina Chan's role in promoting it. In preparation, you should read this article about her: They called it a conspiracy theory. But Alina Chan tweeted life into the idea that the virus came from a lab.

The origin of SARS-CoV-2 and gain-of-function research

I'm currently discussing the meaning of "function" with a small group of scientists and philosophers and it's not easy to come up with an acceptable definition. Imagine how much more difficult it is to identify research that results in a gain of function!

Gain-of-function research has been in the news recently because there are a group of conspiracy theorists who accuse the scientists at the Wuhan Institute of Virology of conducting gain-of-function research on bat caronaviruses leading to the creation of SARS-CoV-2 which then escaped from the lab to cause the pandemic. Some of these conspiracy theorists even accuse the American NIH of funding this gain-of-function research.

How do you define gain-of-function research in a meaningful manner? That's the question posed by Amber Dance in a recent Nature article. (Amber Dance is a freelance science journalist.) The first reference below is the title and subtitle of the article that was published in the magazine and the second reference is the online version.

Dance, A. (2021) The Truth About Gain-of-Function Research: Granting new abilities to pathogenic microbes sounds dangerous, but what has the research told us? Nature 598: 554-555. [doi: 10.1038/d41586-021-02903-x]

Dance, A. (2021) The shifting sands of ‘gain-of-function’ research: The mystery of COVID’s origins has reignited a contentious debate about potentially risky studies and the fuzzy terminology that describes them. Nature 598: 554-555. [Nature website]

The only relevant gain-of-function research is the type specified by NIH as "gain-of-function research of concern" (GOFROC). This is research that makes a potential pathogen more likely to cause disease in humans. This is the kind of research that would be carried out in a lab devoted to biological warfare but it could also apply to some research that was carried out in the past, as described in the article. There is no evidence to support the accusation that scientists in China, or anywhere else, were doing such research on coronaviruses.

There are other kinds of research that involve constructing chimeric viruses in order to test whether they have the potential to cause a pandemic. This is perfectly normal, even necessary, research but conspiracy theorists have claimed that this is forbidden gain-of-function research. The article does a good job of explaining this research and why it's not a problem.

---

Image Credits: The coronavirus figure is from Alexy Solodovnikov and Wikmedia Commons.

What's in your genome?: 2021

This is an updated version of what's in your genome based on the latest data. The simple version is ...

about 90% of your genome is junk

On the importance of active learning

I'm on the editorial board of an education journal so I've been following the pedagogical literature for many years. The idea of active learning, or student-centered learning, has been around for decades and there's solid evidence showing that it's way more effective than traditional lecture-style learning. If you are a teacher and you haven't adopted some form of active learning in your class then you need to change as soon as possible. There's no scientific justification for sticking with the traditional ways of teaching.

Will Ontario parents vaccinate their children?

COVID-19 vaccinations are soon going to be available for children in Ontario, Canada. Will parents vaccinate their children?

The Toronto Star recently published a poll where parents of at least one child under 12 were asked this question and 69% said yes, they were going to get their children vaccinated [Nearly 70 per cent of Ontario parents of kids 5 to 11 planning to get them vaccinated, poll says]. Only 11% said they were not going to vaccinate their children. (19% were unsure.)

It's interesting to see the reasons parents gave for not vaccinating their children. 82% of these parents say that they don't trust the vaccine because it's too new and/or not enough research has been done. That's an illogical excuse because public health officials all over the world are recommending children's vaccinations and they wouldn't be doing it if there were any serious doubts about safety. The reluctance of these parents stems from the mistrust in public health officials and science that has been fostered by the media over the past eighteen months. The Toronto Star has been one of the worst offenders.

Some of the skepticism over decisions made by public heath officials is justified but the overall effect of constant criticism and nitpicking has been to undermine the authority of the very people we rely on to get us out of the pandemic. That's unfortunate.

The other problem for Canadians is that we are inundated with news from our neighbor to the South and that country really does have a bad track record. The somewhat more justified criticism of American public health officials spills over into Canada and taints our own physicians and scientists. That's also unfortunate.

Note that only 23% of these parents can be counted as vaccine deniers and since this group only represents 11% of the total surveyed, it means that the total number of those who don't believe in vaccines is less than 3% of the parents of children under 12. This is consistent with other surveys suggesting that the hard-core vaccine deniers represent less than 5% of the population.

A substantial percentage of those who say they aren't going to vaccinate their children think that vaccinations aren't really necessary for children under 12. Some of those people are probably going to change their minds when most of their children's friends get vaccinated. They will certainly change their minds if vaccinations are required for school.

I think the survey is very encouraging. It looks like most children will be vaccinated over the next few months. There will be holdouts but most of them will eventually give in to public pressure.

---

Science writing in the age of denial

Here's an interesting presentation by Sean B. Carroll, the evolutionary biologist and author of several books on evolution. He's also written a fascinating book on Jacques Monod and he gave a talk at the University of Toronto a few years ago on the role of chance in evolution—I have a signed copy of his book (see the photo and my blog post: Biologist Sean Carroll in Toronto).

Sean likes to emphasize the importance of storytelling in science communication and education. By this he sometimes means stories about individual scientists and sometimes stories about the history of a subject. As Vice President for Science Education at the Howard Hughes Medical Institute in Washington DC (USA) he has helped craft some short videos for high school students and the presentation contains an example of one on evolution. I'm not sure I fully agree with his emphasis on storytelling—as least not to the extent that he promotes it—but some version of it can be useful as long as it doesn't get in the way of understanding important concepts.

I leave it to you to decide whether the short HHMI video is the best way to teach high school students about evolution. I personally don't like the undue emphasis on natural selection and natural history.

The reason for drawing your attention to an old 2012 presentation is to remind you about the charactieristics of science denial. Sean explains the six rules of denialism.

1. Doubt the Science
2. Question Scientist's Motives and Integrity
3. Magnify Disagreements among Scientists and Cite Gadflies as Authorities
4. Exaggerate Potential Harm
5. Appeal to Personal Freedom
6. Acceptance Would Repudiate Key Philosophy

His examples are the denial of evolution by creationists and the rejection of vaccinations by chiropractors. Today, we see how the same rules apply to those who reject COVID-19 vaccinations and to the Lab Leak Conspiracy Theory.

---

Do scientists write books for the "casual reader"?

I just read a review in Science of Douglas Futuyma’s new book How Birds Evolve: What Science Reveals About Their Origin, Lives, and Diversity. [Contextualizing avian origins and evolution]. Many of you will be familiar with Futuyma because he’s the author of one of the best textbooks on evolution.

Right after reading the review, I signed on to Amazon intending to buy the book but when I saw the price ($95 Cdn) I had second thoughts. Much as I’d like to see how Futuyma handles a complex topic like bird evolution, I don’t think I want to spend that much money.

But there are parts of the review that I find intriguing enough to address because they relate to my concern about science writing. Here’s the first thing that caught my eye. The reviewer, Alan Feduccia, writes,

Although casual readers might find the text somewhat advanced and laborious, the chapters are composed in well-written conversational prose, with expositions on multifarious evolutionary phenomena that are infused with scientific explanations.

This highlights an issue that I’ve been writing about recently. "Casual readers" are not going to buy this book and I’m confident that Futuyma is not writing for casual readers. What’s the point of saying that such readers might find the book "advanced and laborious"? What I want to know is whether the actual intended audience would find the book laborious.

The reviewer goes on to describe some of things that are in the book.

Futuyma’s discussion begins with a section that explains Charles Darwin’s transformative ideas—from natural selection and fitness to brood parasitism to gene flow and genetic drift—and thematic chapters elaborate on the relationship between these ideas and bird lineages. The book describes complex evolutionary issues in understandable terms, ...

That sounds like the kind of science writing that I admire. We should aim for explaining complex issues in terms that are understandable to an audience that is prepared to buy the book. This may mean that the casual readers - who will never buy the book - are left out but that’s okay. It may mean that Futuyuma’s book is not going to win a Pulitzer Price for general nonfiction but that’s okay too since good science books are not high on the list of previous award winners.¹ I’m pretty sure that scientific accuracy isn’t a prominent criterion in selecting award winners (in any category).

The reviewer is somewhat critical of the science in the book and takes Futuyma to task for promoting “just-so” stories and for not fully explaining the speculative nature of some of his conclusions. The reviewer notes that “controversy, not consensus, is grist to the mill of good science” and that strikes me as insightful. The problem is that writing about controversy and attempting to explain both sides of an issue are very hard to do and often in conflict with the emphasis on style that is promoted by science writers and editors.

---

1. Previous Pulitzer Prize winning books that might be counted as science books are: The Emperor of All Maladies by Siddhartha Mukherjee (2011); Guns, Germs and Steel: The Fates of Human Societies, by Jared Diamond (1998); The Beak Of The Finch: A Story Of Evolution In Our Time, by Jonathan Weiner (1995); The Ants, by Bert Holldobler and Edward O. Wilson (1990); and On Human Nature, by Edward O. Wilson (1979).

Science reviews a creationist book

You can't get much more anti-science than a book about Adam and Eve. Nevertheless, Stephen Schaffner—a computational biologist at the Broad Institute of MIT in Boston—decided that such a book was worthy of a mostly favorable review in one of the most prestigious science journals in the world [Adam. Eve, and the evolution of humankind].

Schaffner is reviewing a book by William Lane Craig whom he describes as "a widely published philosopher, theologian, and Christian apologist." There are others who would dispute that laudatory description including Richard Dawkins in a ten-year-old essay published in The Guardian [Why I refuse to debate with William Lane Craig].

I won't bother to mention all of the issues with the review since Jerry Coyne has covered them on his website but I would like to quote part of the second-last paragraph of the review.

Craig’s goal in writing this book, of course, is not a scientific one, and it cannot be judged on scientific grounds. I suspect that for many scientists, including religious ones, the exercise will be seen as misguided or simply incomprehensible.

Having followed Craig's anti-science crusade for several years, I have no difficulty in understanding why he would write such a book. What I find truly misguided and incomprehensible is why Science would publish such a review. Perhaps it's because AAAS, the publisher of Science, has a history of accommodating religion?

---

They can smell dead people

Dogs can be trained to detect fresh cadavers but can they detect bodies that have been buried for months or years? Can they detect places where a dead body has rested for a short period of time, such as the trunk of a car, during commission of a crime? Can the odor linger for months or years?

These are the questions addressed by Peter Andrey Smith in a recent article in a special issue of Science devoted to criminal injustice [The Sniff Test]. The article asks whether juries can understand science, You will not be surprised to find out that the answer is "no."

---

The case for a natural origin of SARS-CoV-2

Lots of people seem to be confused about the origin of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The investigating committee ot the World Health Organization (WHO) concluded last winter that a natural origin is the most likely scenario but there still seems to be a substantial percentage of the population who think that the virus was being studied at the Wuhan Institute of Virology (WIV) and leaked from there to start the pandemic. This belief in a lab leak scenario persists in spite ot the fact that 21 expert scientists have discounted it and concluded that a natural origin is the best hypothesis. The lab leak speculation persists even when the United States intelligence agencies reached the same conclusion as the scientific experts and said that a natural origin was more likely.

I've published several posts on this topic over the past year trying to emphasize four points: (1) the evidence strongly favors a natural origin, (2) there is no scientific evidence to support the claim that the WIV scientists were working on SARS-CoV-2 before the pandemic started, (3) the most knowledgeable science experts agree that a natural origin is the most likely scenario, and (4) the media is misrepresenting the science and treating the two competing explanations as equivalent.

In this post I want to describe the case for a natural origin in as simple a manner as possible so that people can refer to the main lines of evidence and so that opponents of a natural origin can explain why they dismiss that evidence. I also want to briefly explain why we need to listen to the experts instead of arbitrarily dismissing their views as a argument from authority and assuming that our own research trumps the experts.

Electron transport supercomplexes in the mitochondria

The generation of ATP in mitochodrial membranes is driven by the energy from a protonmotive force caused by the movement of protons from a high concentration in the space between the inner and outer membranes and a low concentration on the inside of the mitochondria. The discovery of this mechanism, called the chemiosmotic theory, is due to Peter Mitchell, who won a Nobel Prize in 1978. It's one of the classic examples of a real paradigm shift because the mechanism completely changed the way biochemists looked at chemical reactions [Ode to Peter Mitchell].

The creation of the proton gradient is due to a series of oxidation-reduction reactions that involve the transfer of electrons from one molecule to another. The electrons pass down a chain of reactions from a relatively high energy molecule such as NADH to successively lower energy molecules and end up in water. As the electrons lose energy, the excess energy is coupled to the pumping of protons from the inside of the mitochondrion to the inner membrane space, creating a proton gradient. This gradient is what drives ATP production.

The chemical reactions are catalyzed by three large enzyme complexes: Complex I (NADH-ubiquinone oxidoreductase); Complex III (Ubiquinol-cytochrome oxidoreductase; and Complex IV (Cytochrome C oxidase). The electrons are transported between the complexes by ubiquinone (Q) and cytochrome C.

The structure and function of each of these complexes are usually described in separate sections of a biochemistry textbook because they are so complex but we've always known that they function together as an electron transport chain. When I first started writing this section of my textbook it was obvious that the three complexes would cluster together in the inner mitochondrial membrane and there was even some evidence to suggest that they were in close contact. The idea that they would form a well-defined supercomplex was hypothesized in the 1990s but the evidence was weak so it didn't make it into most textbooks.

The structures of Complexes I, II and III were eventually solved by X-ray diffraction studies of the isolated complexes but isolating any supercomplexes was difficult. With the advent of high resolution three dimensional electron microscopy one could finally see the predicted supercomplexes. The latest result, just published in Nature, characterizes the CI-CIII-CIV supercomplex from mammalian mitochondria (Vercellino and Sazanov, 2021).

The nice thing about this result, and the earlier studies on supercomplexes in yeast and plants, is that it confirms earlier speculations that such complexes must exist even though the evidence was weak. It shows you that a deep understanding of biochemistry structure and function can lead to reasonable hypotheses than can be tested when the technology improves.

---

Image credit: The first image is a modified version of Figure 14.6 from Moran et al. Principles of Biochemistry, 5th edition. The second image is from Vercellino and Sazanov (2021).

Vercellino, I. and Sazanov, L.A. (2021) Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV. Nature 598:364-367. [doi: 10.1038/s41586-021-03927-z]