The Michael Decon Program

[Dr. MD MD]

Live Saturday at 6:30 pm pst for you marks out there.

What happened to Mark?!

[Nyewalker]

https://www.youtube.com/watch?v=7nL-Sl4QDaU

[Jackstar]

I just heard genuine human emotion from Michael Decon. Someone check the timestamps.

[Silphion]

I just heard genuine human emotion from Michael Decon. Someone check the timestamps.

Apparently so.
Note the Master chortling in emojis on the sideline.
His best boy is showing a glint of promise.

Speak of the devil ...

[Ciardelo]

Gee, Myke has a caller. Oh, it's just Pubini.

again

[Ciardelo]

I get all my Covid information from Michael Horn.

He's been proven to be so trustworthy.

What is it with guys named Michael?

[Jackstar]

Note the Master

I would prefer not to.

[Silphion]

I would prefer not to.

He who shall not be named, but whose influence must be observed.

_____________________________________________________

Decon is actually a decent straight man with the Paula White sound bite.

[Ciardelo]

Gabcast is starting

[Silphion]

Chatty DVR simply can not resist pushing the shaggy Fake Earth dog show.

[Corona Kitty]

Thanks for listening in marks.

[Ciardelo]

I couldn't figure out why Myke was being a little rude to the guest, then I realized it was just Michael Horn.

[Jackstar]

Actual lol

Same experience

[Dr. MD MD]

I couldn't figure out why Myke was being a little rude to the guest, then I realized it was just Michael Horn.

Yeah and we know that Horn is really Amazon billionaire, Jeff Bezos so fuck that guy, right?

[Corona Kitty]

They don't call me the bad guy for nothing. Ladies.

[Dr. MD MD]

Scientific Papers
Scientific papers are for sharing your own original research work with other scientists or for reviewing the research conducted by others. As such, they are critical to the evolution of modern science, in which the work of one scientist builds upon that of others. To reach their goal, papers must aim to inform, not impress. They must be highly readable â€" that is, clear, accurate, and concise. They are more likely to be cited by other scientists if they are helpful rather than cryptic or self-centered.

Scientific papers typically have two audiences: first, the referees, who help the journal editor decide whether a paper is suitable for publication; and second, the journal readers themselves, who may be more or less knowledgeable about the topic addressed in the paper. To be accepted by referees and cited by readers, papers must do more than simply present a chronological account of the research work. Rather, they must convince their audience that the research presented is important, valid, and relevant to other scientists in the same field. To this end, they must emphasize both the motivation for the work and the outcome of it, and they must include just enough evidence to establish the validity of this outcome.

Papers that report experimental work are often structured chronologically in five sections: first, Introduction; then Materials and Methods, Results, and Discussion (together, these three sections make up the paper's body); and finally, Conclusion.

The Introduction section clarifies the motivation for the work presented and prepares readers for the structure of the paper.
The Materials and Methods section provides sufficient detail for other scientists to reproduce the experiments presented in the paper. In some journals, this information is placed in an appendix, because it is not what most readers want to know first.
The Results and Discussion sections present and discuss the research results, respectively. They are often usefully combined into one section, however, because readers can seldom make sense of results alone without accompanying interpretation â€" they need to be told what the results mean.
The Conclusion section presents the outcome of the work by interpreting the findings at a higher level of abstraction than the Discussion and by relating these findings to the motivation stated in the Introduction.
(Papers reporting something other than experiments, such as a new method or technology, typically have different sections in their body, but they include the same Introduction and Conclusion sections as described above.)

Although the above structure reflects the progression of most research projects, effective papers typically break the chronology in at least three ways to present their content in the order in which the audience will most likely want to read it. First and foremost, they summarize the motivation for, and the outcome of, the work in an abstract, located before the Introduction. In a sense, they reveal the beginning and end of the story â€" briefly â€" before providing the full story. Second, they move the more detailed, less important parts of the body to the end of the paper in one or more appendices so that these parts do not stand in the readers' way. Finally, they structure the content in the body in theorem-proof fashion, stating first what readers must remember (for example, as the first sentence of a paragraph) and then presenting evidence to support this statement.

The introduction
This is a chapter from Jean-luc Doumont's book, Trees, maps and theorems.
View Full-Size Image An effective introduction for a paper
The introduction reproduced here exhibits the four components that readers find useful as they begin to read a paper.
In the Introduction section, state the motivation for the work presented in your paper and prepare readers for the structure of the paper. Write four components, probably (but not necessarily) in four paragraphs: context, need, task, and object of the document.
First, provide some context to orient those readers who are less familiar with your topic and to establish the importance of your work.
Second, state the need for your work, as an opposition between what the scientific community currently has and what it wants.
Third, indicate what you have done in an effort to address the need (this is the task).
Finally, preview the remainder of the paper to mentally prepare readers for its structure, in the object of the document.
Context and need
At the beginning of the Introduction section, the context and need work together as a funnel: They start broad and progressively narrow down to the issue addressed in the paper. To spark interest among your audience â€" referees and journal readers alike â€" provide a compelling motivation for the work presented in your paper: The fact that a phenomenon has never been studied before is not, in and of itself, a reason to study that phenomenon.

Write the context in a way that appeals to a broad range of readers and leads into the need. Do not include context for the sake of including context: Rather, provide only what will help readers better understand the need and, especially, its importance. Consider anchoring the context in time, using phrases such as recently, in the past 10 years, or since the early 1990s. You may also want to anchor your context in space (either geographically or within a given research field).

Convey the need for the work as an opposition between actual and desired situations. Start by stating the actual situation (what we have) as a direct continuation of the context. If you feel you must explain recent achievements in much detail â€" say, in more than one or two paragraphs â€" consider moving the details to a section titled State of the art (or something similar) after the Introduction, but do provide a brief idea of the actual situation in the Introduction. Next, state the desired situation (what we want). Emphasize the contrast between the actual and desired situations with such words as but, however, or unfortunately.

One elegant way to express the desired part of the need is to combine it with the task in a single sentence. This sentence expresses first the objective, then the action undertaken to reach this objective, thus creating a strong and elegant connection between need and task. Here are three examples of such a combination:

To confirm this assumption, we studied the effects of a range of inhibitors of connexin channels . . . on . . .

To assess whether such multiple-coil sensors perform better than single-signal ones, we tested two of them â€" the DuoPXK and the GEMM3 â€" in a field where . . .

To form a better view of the global distribution and infectiousness of this pathogen, we examined 1645 postmetamorphic and adult amphibians collected from 27 countries between 1984 and 2006 for the presence of . . .

Task and object
An Introduction is usually clearer and more logical when it separates what the authors have done (the task) from what the paper itself attempts or covers (the object of the document). In other words, the task clarifies your contribution as a scientist, whereas the object of the document prepares readers for the structure of the paper, thus allowing focused or selective reading.

For the task,

use whoever did the work (normally, you and your colleagues) as the subject of the sentence: we or perhaps the authors;
use a verb expressing a research action: measured, calculated, etc.;
set that verb in the past tense.
The three examples below are well-formed tasks.

To confirm this assumption, we studied the effects of a range of inhibitors of connexin channels, such as the connexin mimetic peptides Gap26 and Gap27 and anti-peptide antibodies, on calcium signaling in cardiac cells and HeLa cells expressing connexins.

During controlled experiments, we investigated the influence of the HMP boundary conditions on liver flows.

To tackle this problem, we developed a new software verification technique called oblivious hashing, which calculates the hash values based on the actual execution of the program.

The list below provides examples of verbs that express research actions:

apply
We applied Laklöter's principle to . . .
assess   We assessed the effects of larger doses of . . .
calculate
We calculated the photoluminescence spectrum of . . .
compare   We compared the effects of . . . to those of . . .
compute   We computed the velocity predicted by . . .
derive   We derived a new set of rules for . . .
design   We designed a series of experiments to . . .
determine   We determined the complete nucleotide sequence of . . .
develop   We developed a new algorithm to . . .
evaluate   We evaluated the efficacy and biocompatibility of . . .
explore   We explored the relationship between . . .
implement   We implemented a genetic algorithm for . . .
investigate   We investigated the behavior of . . .
measure   We measured the concentration of cadmium in . . .
model   We modeled the diffraction behavior of . . .
For the object of the document,

use the document itself as the subject of the sentence: this paper, this letter, etc.;
use a verb expressing a communication action: presents, summarizes, etc.;
set the verb in the present tense.
The three examples below are suitable objects of the document for the three tasks shown above, respectively.

This paper clarifies the role of CxHc on calcium oscillations in neonatal cardiac myocytes and calcium transients induced by ATP in HL-cells originated from cardiac atrium and in HeLa cells expressing connexin 43 or 26.

This paper presents the flow effects induced by increasing the hepatic-artery pressure and by obstructing the vena cava inferior.

This paper discusses the theory behind oblivious hashing and shows how this approach can be applied for local software tamper resistance and remote code authentication.

The list below provides examples of verbs that express communication actions:

clarify
This paper clarifies the role of soils in . . .
describe   This paper describes the mechanism by which . . .
detail   This paper details the algorithm used for . . .
discuss   This paper discusses the influence of acidity on . . .
explain   This paper explains how the new encoding scheme . . .
offer   This paper offers four recommendations for . . .
present   This paper presents the results of . . .
proposes   This paper proposes a set of guidelines for . . .
provide   This paper provides the complete framework and . . .
report   This paper reports on our progress so far . . .
summarize   This paper summarizes our results for 27 patients with . . .
The body
Even the most logical structure is of little use if readers do not see and understand it as they progress through a paper. Thus, as you organize the body of your paper into sections and perhaps subsections, remember to prepare your readers for the structure ahead at all levels. You already do so for the overall structure of the body (the sections) in the object of the document at the end of the Introduction. You can similarly prepare your readers for an upcoming division into subsections by introducing a global paragraph between the heading of a section and the heading of its first subsection. This paragraph can contain any information relating to the section as a whole rather than particular subsections, but it should at least announce the subsections, whether explicitly or implicitly. An explicit preview would be phrased much like the object of the document: "This section first . . . , then . . . , and finally . . . "

Although papers can be organized into sections in many ways, those reporting experimental work typically include Materials and Methods, Results, and Discussion in their body. In any case, the paragraphs in these sections should begin with a topic sentence to prepare readers for their contents, allow selective reading, and â€" ideally â€" get a message across.

Materials and methods
This is a chapter from Jean-luc Doumont's book, Trees, maps and theorems.
View Full-Size Image A paragraph of materials and methods
This paragraph of materials and methods expresses the main idea first, in a topic sentence, so readers immediately know what it is about.
Most Materials and Methods sections are boring to read, yet they need not be. To make this section interesting, explain the choices you made in your experimental procedure: What justifies using a given compound, concentration, or dimension? What is special, unexpected, or different in your approach? Mention these things early in your paragraph, ideally in the first sentence. If you use a standard or usual procedure, mention that upfront, too. Do not make readers guess: Make sure the paragraph's first sentence gives them a clear idea of what the entire paragraph is about. If you feel you cannot or need not do more than list items, consider using a table or perhaps a schematic diagram rather than a paragraph of text.
Results and discussion
This is a chapter from Jean-luc Doumont's book, Trees, maps and theorems.
View Full-Size Image A paragraph of results and discussion
This paragraph of results and discussion (above) can easily be rewritten (below) to convey the message first, not last.
The traditional Results and Discussion sections are best combined because results make little sense to most readers without interpretation.
When reporting and discussing your results, do not force your readers to go through everything you went through in chronological order. Instead, state the message of each paragraph upfront: Convey in the first sentence what you want readers to remember from the paragraph as a whole. Focus on what happened, not on the fact that you observed it. Then develop your message in the remainder of the paragraph, including only that information you think you need to convince your audience.

The conclusion
This is a chapter from Jean-luc Doumont's book, Trees, maps and theorems.
View Full-Size Image An effective conclusion from a paper
This paragraph of results and discussion (above) can easily be rewritten (below) to convey the message first, not last.
In the Conclusion section, state the most important outcome of your work. Do not simply summarize the points already made in the body â€" instead, interpret your findings at a higher level of abstraction. Show whether, or to what extent, you have succeeded in addressing the need stated in the Introduction. At the same time, do not focus on yourself (for example, by restating everything you did). Rather, show what your findings mean to readers. Make the Conclusion interesting and memorable for them.
At the end of your Conclusion, consider including perspectives â€" that is, an idea of what could or should still be done in relation to the issue addressed in the paper. If you include perspectives, clarify whether you are referring to firm plans for yourself and your colleagues ("In the coming months, we will . . . ") or to an invitation to readers ("One remaining question is . . . ").

If your paper includes a well-structured Introduction and an effective abstract, you need not repeat any of the Introduction in the Conclusion. In particular, do not restate what you have done or what the paper does. Instead, focus on what you have found and, especially, on what your findings mean. Do not be afraid to write a short Conclusion section: If you can conclude in just a few sentences given the rich discussion in the body of the paper, then do so. (In other words, resist the temptation to repeat material from the Introduction just to make the Conclusion longer under the false belief that a longer Conclusion will seem more impressive.)

The abstract
This is a chapter from Jean-luc Doumont's book, Trees, maps and theorems.
View Full-Size Image An effective abstract
In just under 200 words, the abstract reproduced here conveys the motivation for and the outcome of the work with some accuracy but without intimidating readers by its length.
The readers of a scientific paper read the abstract for two purposes: to decide whether they want to (acquire and) read the full paper, and to prepare themselves for the details presented in that paper. An effective abstract helps readers achieve these two purposes. In particular, because it is typically read before the full paper, the abstract should present what the readers are primarily interested in; that is, what they want to know first of all and most of all.
Typically, readers are primarily interested in the information presented in a paper's Introduction and Conclusion sections. Primarily, they want to know the motivation for the work presented and the outcome of this work. Then (and only then) the most specialized among them might want to know the details of the work. Thus, an effective abstract focuses on motivation and outcome; in doing so, it parallels the paper's Introduction and Conclusion.

Accordingly, you can think of an abstract as having two distinct parts â€" motivation and outcome â€" even if it is typeset as a single paragraph. For the first part, follow the same structure as the Introduction section of the paper: State the context, the need, the task, and the object of the document. For the second part, mention your findings (the what) and, especially, your conclusion (the so what â€" that is, the interpretation of your findings); if appropriate, end with perspectives, as in the Conclusion section of your paper.

Although the structure of the abstract parallels the Introduction and Conclusion sections, it differs from these sections in the audience it addresses. The abstract is read by many different readers, from the most specialized to the least specialized among the target audience. In a sense, it should be the least specialized part of the paper. Any scientist reading it should be able to understand why the work was carried out and why it is important (context and need), what the authors did (task) and what the paper reports about this work (object of the document), what the authors found (findings), what these findings mean (the conclusion), and possibly what the next steps are (perspectives). In contrast, the full paper is typically read by specialists only; its Introduction and Conclusion are more detailed (that is, longer and more specialized) than the abstract.

An effective abstract stands on its own â€" it can be understood fully even when made available without the full paper. To this end, avoid referring to figures or the bibliography in the abstract. Also, introduce any acronyms the first time you use them in the abstract (if needed), and do so again in the full paper (see Mechanics: Using abbreviations).

[Dr. MD MD]

The Promise of mRNA Vaccines
Long before Moderna and Pfizer’s COVID-19 shots, scientists had been considering the use of genetically encoded vaccines in the fight against infectious diseases, cancer, and more.

Diana Kwon
Diana Kwon
Nov 25, 2020
ABOVE: © ISTOCK.COM, SERHEII YAKOVLIEV
Earlier this month, the world finally received some good news about COVID-19. Interim results from Phase 3 clinical trials revealed that two vaccine candidates â€"one from the Pfizer and BioNTech and another from Modernaâ€"were more than 90 percent effective. In addition to sharing what appears to be very high efficacy, the vaccines have something else in common: they are both made with messenger RNA (mRNA).

mRNA vaccines work by providing the genetic code for our cells to produce viral proteins. Once the proteins, which don’t cause disease, are produced, the body launches an immune response against the virus, enabling the person to develop immunity. mRNA can theoretically be used to produce any protein, with the upside that it much simpler to manufacture than the proteins themselves or the inactivated and attenuated versions of viruses typically used in vaccines, making it an appealing technique, says Norbert Pardi, an mRNA vaccine specialist at the University of Pennsylvania.

The concept of using mRNA to produce useful proteins to fight disease has been around for decades. But until now, no vaccines using this technology have made it this far in clinical trials. The success of the SARS-CoV-2 vaccines “is really good for the RNA field, because until very recently, there were just a handful of people who really believed in mRNA vaccines,” Pardi tells The Scientist. “We now have the chance to really prove [their usefulness] in an actual outbreak situation.”

Overcoming obstacles to mRNA vaccines

In an early proof-of-concept of using gene-based therapeutics to produce the proteins needed to fight disease, published in 1990, scientists reported that in mice, cells successfully produced proteins encoded in injected RNA or DNA. The method was potentially revolutionary: It could, in theory, be used to engineer any protein the body needed to boost immunity against pathogens and fight diseases such as cancer and rare genetic conditions.

I would predict, and others have too, that this will beckon a new era for the application of mRNA towards infectious diseases, particularly as rapid response platforms to help deal with outbreaks.
â€"Nick Jackson, Coalition for Epidemic Preparedness Innovations (CEPI)
Despite its promise, there are challenges associated with working with mRNA. Ordinary mRNA produces only low levels of proteins, and the molecule degrades too quickly inside the body to make it suitable as a therapeutic. On top of that, RNA can trigger an immune response that’s independent of the response to the protein it encodes. “If you just inject foreign RNA into people or animals, you can induce a very serious inflammatory response,” Pardi says. He adds that this is our bodies’ defense mechanism against viruses, which can use either DNA or RNA to store their genetic information.

Because of these problems, the uptake of this technology was slow, and many scientists chose to instead focus on developing vaccines with DNA, which is more stable and easier to work with, says Margaret Liu, the chairman of the board of the International Society for Vaccines and a pioneer of gene-based vaccines. (Liu is on scientific advisory board of the University of Oxford’s Jenner Institute, which developed AstraZeneca’s vaccine for COVID-19.)

A few key technological advances have contributed to the success of the SARS-CoV-2 vaccines from Moderna and Pfizer/BioNTech. In the early 2000s, mRNA vaccines got a boost when a pair of scientists at the University of Pennsylvania, Katalin Karikó and Drew Weissman, discovered that by altering the building blocks of RNAâ€"nucleosidesâ€"they could address some of key limitations of the technique. In a seminal 2005 paper, they reported that modified, synthetic nucleosides could both increase protein production from the mRNA and drastically suppress the immune system’s reaction to the mRNA molecules themselves. (Karikó is now a senior vice president at BioNTech.)

“I think pretty much everyone acknowledges this as the big breakthrough [for mRNA vaccines],” says Liu.

Scientists still needed a method to fortify the mRNA against rapid degradation after injection, however. Pardi, along with Karikó and Weissman, helped identify a solution: by encasing mRNA in small bubbles of fat known as lipid nanoparticles (LNPs), they were able to protect the molecule and enhance its delivery into cells.

“The really difficult challenge for the field for the last at least four to five years has been the delivery [of the mRNA],” says Nick Jackson, the head of programs and technology at the Coalition for Epidemic Preparedness Innovations (CEPI), an organization providing funding for many SARS-CoV-2 vaccines, including Moderna’s. “It’s really been thanks to the incredible innovation around LNPs that has finally shown the validation of this platform and opens the floodgates to mRNA potential.”

“Exciting times for RNA vaccines”

Scientists have clinically tested mRNA vaccines for a wide range of infectious diseases, including rabies, influenza, and Zika. Until now, none have made it past small, early-phase clinical trials. The two SARS-CoV-2 vaccines are “by far the most advanced,” Liu tells The Scientist. “None [of the others] were as promising as what we’ve seen.”

In fact, the SARS-COV-2 vaccines from Pfizer/BioNtech and Moderna far exceeded expectations. The reported efficacy of more than 90 percent for both surpasses the US Food and Drug Administration’s 50 percent efficacy cutoff for considering a vaccine for emergency use authorization (EUA).

The results for Pfizer and BioNTech’s vaccine “are really quite good, I mean extraordinary,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID) told The Washington Post earlier this month. (NIAID collaborated with Moderna on the other SARS-CoV-2 mRNA vaccine.)

Why these vaccines seem so effective while previous attempts against other pathogens haven’t appeared as promising remains an open question. One simple reason, according to Liu, might be the sheer volume of resources that were poured into developing them. Liu also hypothesizes that one explanation for the high levels of efficacy is that the vaccines might be triggering a nonspecific inflammatory response to the mRNA that could be heightening its specific immune response, given that the modified nucleoside technique reduced inflammation but hasn’t eliminated it completely. On the flip side, she adds, this may also explain the intense reactions such as aches and fevers reported in some recipients of the mRNA SARS-CoV-2 vaccines. (Others have suggested that the lipid nanoparticle is responsible for these severe, but transient, side effects reported in some trial participants.)

Ultimately, it’s too early to say why these vaccines so far appear to work so well. “These do remain interim results. They do remain unpublished. And we still need to see the extensive safety databases associated with these products,” Jackson says. There are also issues to sort out, such as concerns about needing to store the vaccines in freezersâ€"especially in the case of the Pfizer/BioNTech vaccine, which needs to be kept at â€"70 °C. (Another mRNA vaccine against SARS-CoV-2, developed by the German company CureVac, can be stored at 5 °C. That vaccine, which is based on non-modified mRNA, is in a Phase I clinical trial.)

Still, the early success of the mRNA vaccines for COVID-19 have scientists optimistic about the future of this technology. “These are really exciting times for RNA vaccines,” Pardi tells The Scientist. In addition to applications in infectious diseases, researchers in both academia and industry have been pursuing the use of mRNA vaccines to harness the immune system to fight cancer. One of the biggest benefits of the mRNA platform is its flexibility, Pardi saysâ€"for example, he is currently investigating ways to encode multiple viral proteins into a single vaccine, which could help produce a more potent immune response against a virus.

Now that mRNA vaccines have revealed their potential, many more vaccine makers will likely develop an interest in the technique, according to Jackson. “I would predict, and others have too, that this will beckon a new era for the application of mRNA towards infectious diseases, particularly as rapid response platforms to help deal with outbreaks.”

[Dr. MD MD]

SARS-CoV-2 Genetic Variant May Be More Transmissible
The so-called 614G mutation in the viral spike protein does not appear to cause more severe cases of COVID-19, but multiple studies indicate that it could be more contagious.

Abby Olena
Abby Olena
Nov 25, 2020
ABOVE: © ISTOCK.COM,
FREEZELIGHT
Before March, most of the SARS-CoV-2 genomes that researchers worldwide isolated and sequenced encoded an aspartic acid (D) at residue 614 of the viral spike protein. By April, the majority of viral sequences harbored a single mutation in the genome converting the D to a glycine (G). Presently, the 614D variant has been all but replaced by the 614G variant globally.

These findings, described in a study published in Cell in August, and corroborating evidence from other groups have led scientists around the world to investigate whether the rapid shift in representation of circulating viral strains is based on random introduction by a group of mobile founders or if it indicates that 614G provides some sort of selective advantage to the virusâ€"making it more infective, for instance.

An answer to this question would have big importance to addressing the pandemic, according to Jessica Plante, a virologist at the World Reference Center for Emerging Viruses and Arboviruses at the University of Texas Medical Branch, because “a random event is unlikely to have massive epidemiological consequences.” On the other hand, she says, “if the virus is truly more infectious, or if the virus is causing more severe disease, that’s something that we need to be able to verify very quickly, so that the public health side can realize that a more contagious or a more severe form of the virus is now spreading.”

Several studies published this fall point to the latter, that 614G transmits more readily than 614D.

In a paper published in Cell November 18, researchers evaluated more than 25,000 whole genome SARS-CoV-2 sequences collected in the United Kingdom between January and June. As in other places, 614G became the dominant variant in late March in the UK, after multiple independent introductions, mostly from people who had traveled internationally. The authors also confirmed that 614G is not associated with infection severity and observed that younger patients were more likely to have 614G and have higher viral loads. Their results support the idea that 614G is under positive selection and likely affects virus transmissibility.

“Even with that massive data set, we were almost pushing the limit of the ability to identify that this effect was there,” coauthor Thomas Connor, a genetic epidemiologist at Cardiff University in Wales, tells The Scientist. Detecting such a subtle change in infectivity would be much more difficult with a smaller sample size.

What they suggest is that the patterns that we see are consistent with a selective advantage, and that this gene mutation arose and has now dominated because it is likely an adaptation [to] humans.
â€"Nathan Grubaugh, Yale School of Public Health
“A lot of groupsâ€"including [in] this study, which is by far the largest sample number in any of the studies published to dateâ€"were looking at the increase in this particular variant over time. But what makes this new study really exciting is that they had done it all within a small population, so all within the UK,” rather than amassing samples from around the world, which increases the possibility of additional confounders, says Judd Hultquist, an infectious disease researcher at Northwestern Memorial Hospital, who did not participate in the work.

“Their ability to sample this particular population with great depth allowed them to track multiple independent introductions of the same viral variant into the population,” he writes in an email to The Scientist. “Seeing the same trend emerge after multiple independent introductions allowed them to make conclusions about how these different viral variants spread.”

“What they suggest is that the patterns that we see are consistent with a selective advantage, and that this gene mutation arose and has now dominated because it is likely an adaptation [to] humans,” says Nathan Grubaugh, an epidemiologist at the Yale School of Public Health who did not participate in the work. “We’ve seen in the past where you have something from an animal population that spills over into humans, it’s going to slightly adapt to be better in the system.”

That apparent heightened contagiousness of 614G could be due to the production of more virus during infection. Hultquist’s group published a paper November 11 showing that patients infected with the 614G variant had higher viral loads in their upper airways than did patients with 614D.

The findings hold up in animal models, too. Plante and her colleagues showed in a study in October that hamsters infected with the 614G variant had higher viral loads in the upper respiratory tract, but not in the lungs, than did animals with 614D. They hypothesize that these higher viral loads could lead to increased transmission.

“It’s speculated that the more virus you have, the more contagious you might be to somebody else,” says Grubaugh. “And in principle that makes sense, but in reality that’s also a hard thing to prove or disprove.”

The next question is to determine in a transmission model whether the 614G variant really is more infectious, Hultquist says. “Multiple independent groups have now collected data that is consistent with the 614G variant of the virus being more transmissible, but it still hasn’t been proven that the virus is more transmissible.”

Martin Beer, a virologist at the Friedrich Loeffler Institute in Germany, and colleagues released a preprint on October 27 that includes a head-to-head comparison of 614G and 614D in ferret and hamster models of viral transmission. “In this competition experiment, with a 50/50 mixture, the 614G out-competed the 614D in most cases,” he says.

Taking all these various lines of evidence from the lab and epidemiological observations of the pandemic together, “there is an indication now . . . that this is most likely not a founder effect. This is probably a real advantage for the virus,” Beer says. But to which extent the 614G variant is more easily transmitted under real-world conditions is a difficult task, he adds. “614G is for sure not less efficient than the 614D. There is a good chance that it is more efficientâ€"for example, in a ‘super spreader’ event.”

Because multiple groups have shown that neither form has “an impact, at least that we know of, on disease severity, knowing what virus you’re infected with won’t impact your treatment regimen or whether or not you will be protected from a vaccine, or whether the drugs will work,” says Grubaugh.

“The things that [people] can do to protect themselves from one variant or another variant are all the same,” agrees Hultquist. “Wear a mask. Be cognizant of your social distancing. Wash your hands regularly, and follow local public health guidelines.”

[Dr. MD MD]

COVID-19 Research Biased Toward Only a Handful of Genes
Thomas Stoeger of Northwestern University has previously studied scientists’ limited focus on certain genes. In a new study, he shows how these same behaviors extend into the science of COVID-19.

Amanda Heidt
Amanda Heidt
Nov 24, 2020
ABOVE: © ISTOCK.COM, THEASIS
Scientists have identified more than 2,000 human genes linked to COVID-19, yet the bulk of the published literature is dominated by only a small subset of them, a fact that may be limiting progress in the fight against the pandemic.

A team at Northwestern University, led by data scientist Thomas Stoeger, had previously shown that scientists tend to focus on a handful of genesâ€"specifically, less than 20 percent of all genes in the human genome accounted for more than 90 percent of the publications they analyzed. Prior to the Human Genome Project, scientists had an incomplete view of the full suite of human genes and relied more heavily on those that had analogs in model organisms or were easier to study using knockout experiments. The advent of modern sequencing technologyâ€"including complementary tools such as CRISPR, mass spectrometry, and RNA-based approachesâ€"has broadened what researchers know, but it seems that scientists are still holding to old patterns.


Thomas Stoeger
HELIO TEJEDOR NAVARRO
In a study published today (November 24) in eLife, Stoeger and his Northwestern colleague Luís Amaral looked to COVID-19 research to see if scientists were similarly prioritizing certain genes during the pandemic in case reports and research on mechanisms of infection and transmission, diagnostic tools, and treatments. The pair analyzed 10,395 published papers and preprints and compared the genes studied in those publications against a list of genes linked to the virus through genome-wide association studies (GWAS).

As the pandemic has progressed, they found, scientists have become focused on a small subset of genes to the exclusion of others that may also be important. Of the roughly 2,000 genes identified by the GWAS reports, only 611 were included in the literature they scanned. In particular, three genes, which code [KG1] for angiotensin-converting enzyme 2 (ACE2), a receptor the virus uses to enter cells; C-reactive protein, an inflammation marker; and interleukin 6, a signaling molecule involved in inflammatory responses, accounted for 25 percent of the total research. When they compared these COVID-19 papers against a set of roughly 466,000 nonâ€"COVID-19 papers from before 2016, Stoeger and Nunes discovered that whether or not the research related to the pandemic, the same types of genesâ€"those advantageous to experimentationâ€"still command the most attention.

The Scientist spoke with Stoeger about how researchers choose which genes to study, what information they could be missing, and ways that research can open up to previously overlooked genes.

See “Scientists Play Favorites with Studying Human Genes. Here’s Why.”

The Scientist: In the paper, you mention this historical bias around the genes that scientists choose to focus on, and you talk about how these choices predate the Human Genome Project. Can you describe how people were selecting genes to study prior to the Human Genome Project?

Thomas Stoeger: Science is difficult, and so scientists start with the least difficult research problems. The research questions scientists worked on before the Human Genome Project tended to be on genes which are interesting and very useful to study, but also happened to be easier to study in a few different ways.

One way is that the human genes [they chose] also had related genes in model organisms, such as fruit flies or worms, and the related gene had already been studied. The shortest genes have also been studied much more than others . . . because they’re easier to work with. And there are also some other chemical properties, for instance, the proteins encoded by the genes. When proteins sit on the outside of the cell, for example, it’s easier to access them. All of these things together made experimentation less difficult.

TS:  How does this new paper build upon the previous work that you have done looking at this bias in gene choice for research?

Stoeger: It’s our wish to capture all aspects of biology and make them interlinked so that we can compare social questions to questions of chemistry [and] biology. Conceptually, this paper is a little bit different from the last one. The last one was mostly on things that were in the past. Now, we want to knowâ€"for something very current where many scientists are all working on the same thingâ€"to what extent [do] we stick to the same past bias or to what extent do we do something new? So maybe the better answer would be for me to say that we want to know if emerging global threats are subjected to the same biases that affect the rest of the medical literature.

See “Two Genetic Regions Linked with Severe COVID-19”

TS: Can you tell me a little bit more about LitCovid, the program that you used to identify the genes being studied in COVID-19 research?

Stoeger: I’m a data scientist who tries to integrate many different resources. I’m always particularly thankful when other institutions have already cleaned the data and brought it into a very nice shape.

LitCovid is a curated list of publications that relate to COVID-19 [managed by the National Institutes of Health], and they’ve already computationally tagged individual concepts within those articles. You can imagine it as having all of the abstracts and titles and results, and whenever there is a word linked to a gene there is something inserted into the text that says, “Here is a gene,” and each gene has a unique number. Computationally what they’re doing is using a type of natural language processing to make a model of how language works and making tags that relate to genes or diseases.

Sharing this data very openly allows people like myself to combine it with other data, such as data from the past or data from different experiments, to see how all of these different things relate together.

TS: What kinds of information might we be missing out on by focusing only on this small subset of genes?

Stoeger: The honest answer is that we really don’t know. We don’t know what all of these other genes that pop up in large experiments related to COVID-19 do. Many of the top studied genes in the COVID-19 literature are very important genes and should be studied, but they’re not the full story.

TS: How do scientists break out of this rut and bring some of these unexplored genes into scientists’ work?

Stoeger: This is something we try to answer in some upcoming work by looking historically at cases when people managed to make some genes more popular, [although] we realize that it is very rare that people succeed.

But there are a few strategies that might work better than others. One strategy is to basically . . . take these experiments that survey our genes and actually focus on the new ones. Another thing to encourage work in this sector [would be] initiatives that solicit individual research grants. Right now, these only include a couple of genes, but there’s maybe 10,000 or more genes that would be worthwhile to study. And then there’s one strategy that I personally follow, which is taking some really important biological context that has already been studied a lot, such as aging, and taking all of the evidence that’s out there and focusing on these genes that have been overlooked but have some mounting evidence that they’re important.

TS: You said that if you look in history, there are examples of genes becoming more popular. Do you have an example of that that comes to mind?

Stoeger: There is a gene called C9orf72 that is now one of the most popular genes of the last 10 years. A group [carried out] genome-wide association studies for the association between some neurological diseases and different mutations in the human genome. They found that mutations in this gene were associated with [dementia and amyotrophic lateral sclerosis (ALS)]. People didn’t expect this gene to be linked to these diseases, but all of a sudden people showed that this gene alone was actually better at explaining which patients would suffer from the diseases than any other gene that had already been studied.

T. Stoeger, L.A.N. Amaral, “COVID-19 research risks ignoring important host genes due to pre-established research patterns,” eLife, doi:10.7554/eLife.61981, 2020.

Editor’s note: The interview was edited for brevity.

[Dr. MD MD]

Immunity to SARS-CoV-2 Lasts at Least Six Months, Data Show
Half a year after infection, people who had recovered from COVID-19 had robust antibodies, along with traces of the virus in their gut, which may drive long-lasting immunity.

Ashley Yeager
Ashley Yeager
Nov 23, 2020
ABOVE: Recovered COVID-19 patients can harbor SARS-CoV-2 (green) in the lining of their intestines months after infection. The residual viral traces might shape the immune response to the virus.
C. GAEBLER ET AL, BIOARXIV, 2020
Immunity to the virus that causes COVID-19 lasts at least six months and might last much longer, according to a preprint posted November 5 on bioRxiv.

Among 87 individuals who had COVID-19, antibodies to SARS-CoV-2 dwindled after six months but were still detectable, the study’s authors found. A closer look at the samples of six of those patients revealed that the antibodies that remained six months after infection were, on average, more potent in neutralizing the virus than were antibodies generated only about a month after infection. And levels of the memory immune cells that make those more-potent antibodies did not drop off with time, the researchers report.

“This is fantastic news,” says immunologist Ziv Shulman of the Weizmann Institute of Science in Israel who wasn’t involved in the new work. “It was unclear if we make a long-lasting immunological memory against this new coronavirus. The study shows the memory cells are there [months after infection] and able to produce high-affinity, virus-neutralizing antibodies.”

The results, which have not yet been peer reviewed, suggest that individuals re-exposed to the virus have a good chance of mounting a quick and effective immune response against it, and they offer a bit of hope for making a long-lasting vaccine, experts say.

In the study, Christian Gaebler, a physician and immunologist at the Rockefeller University in New York City, and colleagues compared the levels and potency of SARS-CoV-2 antibodies in blood samples taken from 87 volunteers one month and then six roughly months after they’d been infected with the virus. The team specifically measured levels of antibodies called immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA), which are created to neutralize a pathogen. IgM is usually the first antibody to develop in response to an infection. IgG is the main type found in the blood, and IgA in the blood helps initiate an inflammatory reaction to infection.

The levels of IgM and IgG antibodies reactive to the SARS-CoV-2 spike protein’s receptor binding domain (RBD) dropped sharply between the two time points, the team found, while IgA levels didn’t decline as steeply. Levels of memory B cells, which generate all of these antibodies when there’s a sign of reinfection, remained steady over the course of the study. The results align with a preprint posted on medRxiv in August that also showed memory B cells to the virus persist after a mild COVID-19 infection.

Gaebler and colleagues next identified the antibodies present both one month and six months after infection, synthesized them in the lab, and tested their reactivity to the RBD. Antibodies from six months after infection bound more tightly to the docking component of the virus than did those from shortly after infection. Those antibodies were also better at neutralizing variants of the SARS-CoV-2 virus.

Those observations indicate that the patients’ bodies were activating a specific immune system program that generates long-lived memory B cells, which then produce potent antibodies against subsequent exposures to the virus, the researchers write. A lack of structures called germinal centers where this production of memory B cells takes place has been tied to severe COVID-19 infection and death.

See “Some COVID-19 Patients Lack Key Structures for Antibody Creation”

Curious if the B cells produced the same antibodies a month after infection as six months after infection, Gaebler and colleagues compared the memory B cell receptors’ genetic sequences and found significant shifts over time. This observation, combined with the improved potency of antibodies produced by these B cells, indicates the B cells and antibodies evolved in response to infection.

Gaebler says he was surprised to see the antibodies had evolved. That typically happens when a pathogen hides out somewhere in the body or specifically in cells’ DNA even after symptoms of infections ceaseâ€"for instance, with HIV. Saurabh Mehandru, a gastroenterologist at Mount Sinai Hospital, and colleagues had been looking for the SARS-CoV-2 virus in recovered COVID-19 patients’ intestines and had identified traces of it in the gut. His group and Gaebler’s decided to team up to see if those viral stowaways in the gut could be spurring memory B cells’ evolution.

Mehandru’s team took a close look at biopsies from 14 recovered patients infected roughly four months earlier, on average. At the time of the tissue collection, none of them had a positive PCR result for the virus, yet SARS-CoV-2 RNA was detected in the small intestine of three of the 14 patients, and biopsies from five of the patients contained SARS-CoV-2 N protein. Electron tomography on one patient’s biopsy also revealed SARS-CoV-2 viral particles.

“If you have the virus persisting in the intestines, it has the potential to continue to inform the immune system,” Mehandru, a coauthor of the study, tells The Scientist.

Shiv Pillai, an immunologist at the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard who was not involved in the study, agrees, saying that the study makes a strong case for virus in the gut continuing to prime memory B cells for infection. The result also suggests that a latent gut infection may explain MIS-C, or multisystem inflammatory syndrome, a rare condition in which children who contracted SARS-CoV-2 suffer from symptoms, such vomiting, diarrhea, and severe abdominal pain, weeks after recovery. “This fits with that and says, look, there is a reservoir in the gut for the virus to stay,” Pillai says.

See “Kids’ Severe COVID-19 Reaction Bears Unique Immune Signature”

Mehandru says it is important to emphasize that even though the team found traces of the virus in the gut, there is no evidence that SARS-CoV-2 can be transmitted via stool.

Gaebler says the team is not yet entirely sure if it is the virus in the intestine that is causing the evolution in immunity, or if the virus also persists elsewhere in the body and continues to affect the immune system from there.

How long this memory B cell immune response will last past the six-month mark is not yet clear either. Individuals who were infected with the original SARS virus in 2003 still have memory B cells for that pathogen, so the pattern could be the same for SARS-CoV-2, Gaebler says. “Usually when you see such a memory response, it is quite long lasting.”

A next step, he says, is to screen the blood of individuals who receive a vaccine against the virus for the presence of memory B cells. “The immunity data that we see from those vaccines is very encouraging, and seems to resemble the natural infection very closely, which is good news,” Gaebler says. “That might suggest that [the vaccines] also lead to the same memory response. But this would obviously be very, very important to see.”

C. Gaebler et al. “Evolution 1 of Antibody Immunity to SARS-CoV-2,” bioRxiv, doi.org/10.1101/2020.11.03.367391, 2020.

[Dr. MD MD]

Alzheimer’s-Linked Mutation Causes Blockages in Neurons
The variant causes a buildup of BACE1 protein in axons in cultured neurons and mice. Researchers say it might be time to rethink failed trials that inhibit BACE1 to treat the neurodegenerative disease.

Ian Le Guillou
Ian Le Guillou
Nov 20, 2020

Pharmacological inhibition of BACE prevents the formation of Alzheimer’s disease-like axonal pathology in cultured neurons (top) and in the mouse brain (lower panels).
DR. SELENE LOMOIO, TESCO LABORATORY, TUFTS UNIVERSITY
The ongoing search for effective treatments for Alzheimer’s disease has focused on aggregates of amyloid-β peptides, which are the hallmark of the disease. However, efforts to inhibit one of the proteins responsible for producing amyloid-β, called BACE1, have led to several failed Phase 3 clinical trials.

But researchers aren’t giving up hope. A study published in Science Translational Medicine on November 18 reveals how variants in a gene called GGA3â€"which are a known risk factor for developing Alzheimer’sâ€"alter BACE1 movement through brain cells in culture and in mice. This causes the buildup of BACE1 protein and creates axonal damage similar to that seen in the pre-symptomatic stages of Alzheimer’s disease. This could mean BACE1 inhibitors still have promise as a treatment if used much earlier in the disease process.

“I think the core message from this paper is that this could be one additional primary pathogenic development that precedes amyloid plaques buildup,” says Henrik Zetterberg, a neuroscientist at the University of Gothenburg in Sweden who was not involved in the research. “What causes amyloid buildup? What are the primary pathogenic processes? That is pretty much unknown. We have the risk genes, of course, but this paper gives another very interesting piece of the puzzle of what might cause neurodysfunction in Alzheimer’s disease and could also cause amyloid buildup.”

Genetic studies have found that rare mutations in GGA3 increase the risk of Alzheimer’s disease. In previous research, the authors of the current study identified the role of the GGA3 protein in transporting BACE1 in non-neuronal cell lines. BACE1 is a protease responsible for cleaving the protein APP to produce the amyloid-β peptides that accumulate into plaques in Alzheimer’s. This new paper is the first demonstration of the consequences of GGA3 dysfunction on BACE1 in cultured neurons and mice.

“One of the big gaps that we have is taking the genetics, the biochemistry, the pathology, and putting it into a cell biological context. I think there’s a really critical need to understand where in the cell all of this biochemistry takes place,” says Shawn Ferguson, a cell biologist from Yale University who was not involved in the research. “That’s where this paper is interesting, because it’s focusing on where these proteins may encounter one another, what may regulate the movement of these proteins in the axon, and how all of this could influence the proteolytic processing of APP.”

The researchers found that deletion of the GGA3 gene or mutations found in people reduce the trafficking of BACE1 through the axons. BACE1 then builds up in the axons, causing them to swell. This swelling could explain the damage seen in patients’ brains.

“This axonal pathology can be detected in the human brain in the early stage of Alzheimer’s disease,” says lead author Giuseppina Tesco, a neuroscientist at Tufts University.

“If a patient doesn’t have the GGA3 mutation, it’s still possible that defects in axonal pathology are caused by other genes. It is still valuable to know that once you have axonal pathology early, BACE accumulation could be a factor. So these mechanisms can apply more generally.”

Phase 3 clinical trials of several drugs aiming to block the activity of BACE1 were abandoned, because they often caused side effects that made memory and thinking worse for people with Alzheimer’s disease. It is thought that side effects from BACE1 inhibition result from stopping its other functions in the brain.

In this new study, the researchers found that inhibiting the activity of BACE1 prevented the swelling seen in neurons without any functional GGA3 protein. Tesco suggests that using a lower dose of BACE1 inhibitors at an early stage of Alzheimer’s could be an effective approach for slowing the progression of the disease.

“The clinical trials that have been conducted, they had a pharmacological inhibition of BACE activity, up to ninety percent in some cases. So I think that what we learned is that probably we need to inhibit BACE to a lesser extent,” says Tesco.

The earliest damage to the neurons happens up to 20 years before the appearance of the clinical symptoms of Alzheimer’s disease, according to Tesco, so any treatment to prevent this would need to be given over a long period.

There is some evidence for the benefits of longer, weaker inhibition of BACE1 from studies of a genetic mutation found in the Icelandic population. The mutation reduces the ability of BACE1 to produce amyloid-β by about 20 percent and lowers the risk of developing Alzheimer’s disease.

“It looks like a small reduction over a very long time seems to be good enough,” Tesco says.

S. Lomoio et al., “Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer’s disease trigger BACE1 accumulation in axonal swellings,” Sci Transl Med, doi:10.1126/scitranslmed.aba1871, 2020.

[Corona Kitty]

Alzheimer’s-Linked Mutation Causes Blockages in Neurons
The variant causes a buildup of BACE1 protein in axons in cultured neurons and mice. Researchers say it might be time to rethink failed trials that inhibit BACE1 to treat the neurodegenerative disease.

Ian Le Guillou
Ian Le Guillou
Nov 20, 2020

Pharmacological inhibition of BACE prevents the formation of Alzheimer’s disease-like axonal pathology in cultured neurons (top) and in the mouse brain (lower panels).
DR. SELENE LOMOIO, TESCO LABORATORY, TUFTS UNIVERSITY
The ongoing search for effective treatments for Alzheimer’s disease has focused on aggregates of amyloid-β peptides, which are the hallmark of the disease. However, efforts to inhibit one of the proteins responsible for producing amyloid-β, called BACE1, have led to several failed Phase 3 clinical trials.

But researchers aren’t giving up hope. A study published in Science Translational Medicine on November 18 reveals how variants in a gene called GGA3â€"which are a known risk factor for developing Alzheimer’sâ€"alter BACE1 movement through brain cells in culture and in mice. This causes the buildup of BACE1 protein and creates axonal damage similar to that seen in the pre-symptomatic stages of Alzheimer’s disease. This could mean BACE1 inhibitors still have promise as a treatment if used much earlier in the disease process.

“I think the core message from this paper is that this could be one additional primary pathogenic development that precedes amyloid plaques buildup,” says Henrik Zetterberg, a neuroscientist at the University of Gothenburg in Sweden who was not involved in the research. “What causes amyloid buildup? What are the primary pathogenic processes? That is pretty much unknown. We have the risk genes, of course, but this paper gives another very interesting piece of the puzzle of what might cause neurodysfunction in Alzheimer’s disease and could also cause amyloid buildup.”

Genetic studies have found that rare mutations in GGA3 increase the risk of Alzheimer’s disease. In previous research, the authors of the current study identified the role of the GGA3 protein in transporting BACE1 in non-neuronal cell lines. BACE1 is a protease responsible for cleaving the protein APP to produce the amyloid-β peptides that accumulate into plaques in Alzheimer’s. This new paper is the first demonstration of the consequences of GGA3 dysfunction on BACE1 in cultured neurons and mice.

“One of the big gaps that we have is taking the genetics, the biochemistry, the pathology, and putting it into a cell biological context. I think there’s a really critical need to understand where in the cell all of this biochemistry takes place,” says Shawn Ferguson, a cell biologist from Yale University who was not involved in the research. “That’s where this paper is interesting, because it’s focusing on where these proteins may encounter one another, what may regulate the movement of these proteins in the axon, and how all of this could influence the proteolytic processing of APP.”

The researchers found that deletion of the GGA3 gene or mutations found in people reduce the trafficking of BACE1 through the axons. BACE1 then builds up in the axons, causing them to swell. This swelling could explain the damage seen in patients’ brains.

“This axonal pathology can be detected in the human brain in the early stage of Alzheimer’s disease,” says lead author Giuseppina Tesco, a neuroscientist at Tufts University.

“If a patient doesn’t have the GGA3 mutation, it’s still possible that defects in axonal pathology are caused by other genes. It is still valuable to know that once you have axonal pathology early, BACE accumulation could be a factor. So these mechanisms can apply more generally.”

Phase 3 clinical trials of several drugs aiming to block the activity of BACE1 were abandoned, because they often caused side effects that made memory and thinking worse for people with Alzheimer’s disease. It is thought that side effects from BACE1 inhibition result from stopping its other functions in the brain.

In this new study, the researchers found that inhibiting the activity of BACE1 prevented the swelling seen in neurons without any functional GGA3 protein. Tesco suggests that using a lower dose of BACE1 inhibitors at an early stage of Alzheimer’s could be an effective approach for slowing the progression of the disease.

“The clinical trials that have been conducted, they had a pharmacological inhibition of BACE activity, up to ninety percent in some cases. So I think that what we learned is that probably we need to inhibit BACE to a lesser extent,” says Tesco.

The earliest damage to the neurons happens up to 20 years before the appearance of the clinical symptoms of Alzheimer’s disease, according to Tesco, so any treatment to prevent this would need to be given over a long period.

There is some evidence for the benefits of longer, weaker inhibition of BACE1 from studies of a genetic mutation found in the Icelandic population. The mutation reduces the ability of BACE1 to produce amyloid-β by about 20 percent and lowers the risk of developing Alzheimer’s disease.

“It looks like a small reduction over a very long time seems to be good enough,” Tesco says.

S. Lomoio et al., “Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer’s disease trigger BACE1 accumulation in axonal swellings,” Sci Transl Med, doi:10.1126/scitranslmed.aba1871, 2020.

The fuck lol

[Dr. MD MD]

Q&A: COVID-19 Infectiousness Peaks Early in Sickness, Study Shows
Patients’ viral loads are highest within five days of their first symptoms, emphasizing the need to isolate early to prevent transmission.

Max Kozlov
Max Kozlov
Nov 23, 2020
ABOVE: © ISTOCK.COM,
JORDANSIMEONOV
Since early March, a number of studies have suggested that patients infected with SARS-CoV-2 generally have a long incubation period and are most infectious early on in their sickness, with viral loads dropping off after nine days. These results have informed guidelines put forth by public health bodies, such as the US Centers for Disease Control and Prevention, which recommend that people isolate for at least 10 days following a positive COVID-19 test.

A meta-analysis published November 19 in The Lancet Microbe reviewed 98 studies on coronavirusesâ€"79 of which focused on SARS-CoV-2 and the rest on SARS-CoV and MERS-CoVâ€"to determine when patients’ viral loads are highest and could therefore transmit the virus most effectively. Of the SARS-CoV-2 studies, 73 included hospitalized patients only.

Their report finds that patients with COVID-19 show the highest amount of live virus in the upper respiratory tract within the first five days of showing symptoms, while the highest amount of virus in SARS and MERS is seen during the second week after showing symptoms. Despite finding high viral RNA loads, no study in the review isolated live virus beyond day nine after the first symptoms of COVID-19.

The Scientist spoke with Muge Cevik, a virologist and a clinician at the University of St Andrews and the lead author of the analysis, about the findings.

The Scientist: What inspired you to do this research?


Muge Cevik, University of St Andrews
MUGE CEVIK
Muge Cevik: Around April, we were writing a review paper mainly for clinicians. In writing that paper, we realized that we don’t have a good understanding about viral load dynamics and infectiousness periods not only for [SARS-CoV-2] but also for [SARS-CoV] and MERS. With my colleague from Glasgow University, we set up this systematic review and recruited four doctors to work together because systematic reviews are quite a huge task. At the beginning of the pandemicâ€"I’m a clinician as wellâ€"we were not sure when to stop isolating patients, when we can safely discharge patients, and when patients stop being infectious. These have important implications for cases in the community but also cases in the hospital setting.

TS: How did you go about deciding which studies you were going to include in your analysis?

MC: In our analysis, we included papers mainly looking at viral load dynamics. We wanted to include large studiesâ€"that’s the reason we excluded case reports or case series with less than five patients because generally [they] report atypical, unusual cases, and that’s typically those who basically shed virus for a long time.

We didn’t want our subjective opinion to influence the results, so specifically we included studies that counted the viral shedding from the time of symptom onset, not from time of hospitalization, and some studies actually included patients after discharge from hospital, so we didn’t know when the symptoms started. We tried to make it really similar across all studies, and that’s the reason our inclusion criteria were really strict.

TS: The scientific community has had inklings in terms of COVID-19’s infectious window, so did the results surprise you at all?

MC: This study really emphasizes that people are highly infectious really early on, especially seeing peak viral loads around symptom onset to day five. I’m not that surprised, but I think it doesn’t align with our ‘test, trace, isolate’ practice because in order to prevent onward transmission, testing, on itself, is not enough. We need to ensure those people who are infectious isolate and their contacts isolate. In a way, that emphasizes that we need much more prompt testing and prompt results so we can prevent onward transmission. What happens at the moment is that people seek testing around two or three days after symptom onset, and by the time they get test results, they’re already past the most infectious time period. Many people struggle to take sick leave without having the test results, so that tells us that we need to change the way we look at ‘test, trace, and isolate’ nowâ€"maybe symptom onset needs to prompt isolation before testing.

There’s been a lot of emphasis on testing, but testing on its own is not an intervention. It needs to be connected to an intervention, especially when it’s a respiratory pathogen.
The other aspect is that the majority of studies agree that the infectious virus is not detectable after day nine, and when we put that result with the peak viral load, which happens around day five, it basically tells us that people are really infectious in the first week of symptom onset. At the moment, when patients come into the hospital, they’re already around day six or eight after symptom onset because people have pneumonia around day eight after symptom onset, so that tells us that, when people come to hospital with a possible diagnosis of COVID-19, they may not be as infectious as . . . a case in the community.

TS: Asymptomatic COVID-19 cases have also made it difficult to test, trace, and isolateâ€"what did you find among the asymptomatic cases you included in your analysis?

MC: There were very few studies looking into this, but what we found is that the majority of studies agreed that initial viral loads were similar between symptomatic and asymptomatic people. When I say asymptomatic, these were studies only recruiting those with no symptoms whatsoever throughout the disease course, not those presymptomatic patients, because we know that if you have peak viral load around symptom onset, that means people can be infectious before symptoms begin. What we found overall is that you know asymptomatic individuals have shorter viral shedding, which means they may be infectious but for a shorter period, and maybe that’s a reason that, in contact tracing studies, asymptomatic patients seem to be one-third as infectious as someone with symptoms. Another study we’ve done looks at transmission dynamics in asymptomatic people, and what we found is it generally happens among households. People have much more opportunity to transmit to each otherâ€"it may happen [over a] very short period of time, but they have [a greater] opportunity to transmit it to [each other].

TS: How does your analysis of SARS-CoV and MERS put the viral load dynamics of SARS-CoV-2 in perspective?

MC: It shows why SARS-CoV was a bit easier to control in the community because the viral load peak actually occurred in the second week after symptom onset. . . . It was probably the time when patients were already hospitalized, which is a bit different than COVID-19, where we’re seeing really high viral loads really early on, so people are really infectious in the community. Another major difference in SARS-CoV and MERS is that we saw a lot of hospital-based outbreaksâ€"almost sixty percent of all outbreaks were based in the hospital. We’re not seeing that much for SARS-CoV-2. These results put these three highly infectious pathogens into context and [explain] why we’re seeing different patterns and why we’re struggling to contain SARS-CoV-2 because it spreads really quickly in the community.

TS: Which of the ‘test, trace, and isolate’ protocol do you think we need to focus on more, based on your research?

Our results emphasize why it’s been very difficult over the last few months and how we move forwardâ€"maybe it could be shortening the isolation period but giving more support to people to isolate during that five-day period when everyone is so infectious.
MC: I think the isolation part is the weakest part of our programs. It’s not surprising that we’re having difficulty containing the virus because when we look atâ€"and I don’t know the numbers in the USâ€"but in the UK only one in five people isolate. That means even if we do more testing, if people don’t or are not able to isolateâ€"this may be [due to] their working or living conditionsâ€"we won’t be able to prevent onward transmission.

There’s been a lot of emphasis on testing but testing on its own is not an intervention. It needs to be connected to an intervention, especially when it’s a respiratory pathogen. If I’m someone that my family is dependent on and if I need to pay my rent, if I’m not getting sick leave from my employerâ€"people need to make difficult choices. I’m especially worried about people on zero-hour contract jobs where there’s no linkage to support. When we look at the global figures, countries who supported their citizensâ€"I’ve seen a couple of papers from Vermont and New Yorkâ€"have much better isolation numbers. That emphasizes that we need to do more to support more disadvantaged groups, especially working people, because even when we were in lockdown, we’ve seen that there there’s been a difference between those areas where [people are] still commuting to work versus people who are able to work from home.

We know that there are certain groups in the population that are at high risk of acquiring, being exposed to, and transmitting [the virus] to their household because of living conditions. And we know that crowded housing increases the risk of transmission, so I think we need to do more to support immediate isolation. Supported isolation needs to be a norm. In any public health intervention, if you support people, they will do what’s needed.

Our results emphasize why it’s been very difficult over the last few months and how we move forwardâ€"maybe it could be shortening the isolation period but giving more support to people to isolate during that five-day period when everyone is so infectious. There’s a need to balance risks and benefits but also listen to peopleâ€"what are their needs and how we can support them.

TS: How might your study help our readers decide what they should and shouldn’t be doing, particularly as the holiday season approaches?

MC: First of all, if you have symptoms, even mild symptomsâ€"COVID-19 does not only present with cough and fever, but people have other symptoms like severe muscle aches, fatigue, sore throat, [loss of taste and smell]. These are all early symptoms that tell us it could be COVID-19, so if you have those symptoms, isolation needs to start promptly. Especially within the first five days of symptoms, we need to be very, very careful not to interact with high risk and vulnerable contactsâ€"especially elderly people or those with comorbidities.

But again, we can be infectious before having symptoms so that tells us that we need to be careful and behave as if we have the infection and could transmit it to someone else.

M. Cevik et al., “SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis,” The Lancet Microbe, doi:10.1016/S2666-5247(20)30172-5, 2020.

Editor’s note: The interview was edited for brevity.

[Dr. MD MD]

Black in X Addresses Long-Standing Inequity in STEM
In a year of racial tumult, Black scientists are uniting for visibility and action.

Lisa Winter
Lisa Winter
Nov 16, 2020
ABOVE: © ISTOCK.COM, CASTIGATIO
On May 25, Christian Cooper was bird-watching in New York City’s Central Park when he asked a woman to put her dog on a leash, as was mandated for the area. The woman responded to the request by saying she was going to call the cops and she was “going to tell them there is an African-American man threatening [her] life.” As evidenced by the video taken by Cooper during the exchange, she did just that and urged the police to come immediately.

While the incident was unique in making national news, in its aftermath, scores of Black birders, naturalists, and ecologists recounted experiencing white onlookers calling the police on them while in outdoor spaces. One birder, for instance, tweeted that after having dealt with many police calls, he now displays a sign to explain what he’s doing while in natural areas. In June, a geoscientist shared a 10-minute-long video describing how survey work yields daily stares and sometimes tense encounters with people displaying neo-Nazi or other white supremacy symbols.

“Unfortunately, the safety of Black naturalists continues to be an issue,” Angelica Patterson, a PhD candidate at Columbia University, tells The Scientist in an email.

Cooper’s encounterâ€"combined with uproar over the deaths of George Floyd, Breonna Taylor, and other Black Americans at the hands of law enforcementâ€"have propelled a number of initiatives to raise the profile of Black people in STEM and awareness of the continuing effects of racism.

Black in X

In the immediate aftermath of the incident in Central Park, economist Anna Gifty Opoku-Agyeman had the idea of celebrating Cooper and other Black birders. Black Birders Day was born, with a goal of providing a space for Black naturalists to get to know one another and show that interest in birding and other outdoor activities is not exclusive to white people.

Opoku-Agyeman, a cofounder of The Sadie Collective, an organization dedicated to helping Black women break into the world of finance and economics, shared her idea on Twitter and had conversations with others in @BlackAFInSTEM, an organization for Black scientists. She realized that Cooper’s experience wasn’t a one-off incident, but that racist encounters were common while out in the field, she tells The Scientist.

Enthusiasm for Black Birders Day spread on social media, and what was meant to be a day stretched into the first-ever Black Birders Week, which ran from May 31 through June 5. Each day featured a theme and encouraged Black birders to share pictures of themselves in nature or of their favorite bird species. Thousands of tweets went out with the hashtag #BlackBirdersWeek, and the event attracted attention from some high-profile organizations, including the National Audubon Society.

The success of the event led to the creation of #BlackInNature, a social media space where Black ecologists and naturalists of all kinds, not just birders, can connect.

From there, Twitter exploded with Black scientists celebrating their disciplines. Soon, #BlackInAstro, #BlackInNeuro, #BlackInCardio, #BlackInMicro, and others had their own awareness weeks and were garnering international participation. As momentum grew, the awareness weeks progressed beyond hashtags and began integrating live events with expert speakers and sessions focused on career development. Researchers who are members of other underrepresented minority groups also created their own accounts and hashtags, such as @LatinxinSTEM and #LGBTQinSTEM.

“If you had asked me a month ago, ‘Who are the other Black microbiologists?’ . . . I would have had one, maybe two people that I would have known offhand,” Black in Micro co-organizer Ariangela Kozik, a postdoc at the University of Michigan, tells The Scientist. Now, because of Black in Micro Week, “I know at least 30 very well, and about 100 more.”


Ariangela Kozik, co-organizer of Black in Micro
COURTESY OF CALVIN UNIVERSITY
“We’re all one cohesive group that needs each other in order to move forward. We’re not an island or a silo,” Kozik explains. All of the different groups, collectively known as “Black in X,” connect via Slack, where they discuss the logistical challenges of pulling off an awareness week and share advice. “It kind of solidifies the fact that we are not out here on our own,” Kozik says. “Now that we can finally see each other, we can now support each other.”

The topics of the events, which are still ongoing, vary from week to week, and increasingly include career development sessions. Black in Chem, for instance, held a live “elevator pitch” contest, encouraging participants to present their research and interests succinctly. The microbiologists discussed the science around the COVID-19 pandemic, and the neurologists addressed the need for mentorship.

Moving forward, each group is taking a slightly different approach so that their organizations become lasting entities, not ephemeral Twitter trends. Some groups have already planned their awareness weeks for next year and have ongoing digital meetups to stay in touch with one another. Black in Neuro held a digital mini-conference for October 31 through November 4.

Because of how interdisciplinary modern science is, some scientists are able to participate in multiple weeks, growing their networks and learning about other areas they might not be well-versed in. This isn’t good just for Black scientists, it’s good for science, says Ayanna Jones, a leader within Black in Chem and a PhD student at Emory University.

It hasn’t been long enough to say what the lasting effects of this movement will be, but several of the organizers who spoke to The Scientist shared that as a result of growing awareness of the issues faced by academics who are members of underrepresented groups, their institutions have been undertaking conversations about acknowledging racism and assessing what needs to be done to create lasting change.

This isn’t a simple fix, as most of the problems are thought to be rooted in implicit bias and have been reinforced over generations. Black students are less likely to begin STEM degrees and drop out of them far more often than their white peers are. Entrance into graduate school creates another barrier due to factors such as the cost of the GRE and the fact that Black students are less likely to have attended prestigious undergraduate institutions or worked at unpaid internships. In their careers, Black scientists are less likely to receive funding or get their research published. Even with equal resumes, people with African -Americanâ€"sounding names are less likely to be called to interview for a job.

“Systemic bias in the workplace, unwelcoming spaces and cultures in science departments, and outright harassment of people of color venturing outdoors have prevented opportunities for all of these spaces and visible roles to be diversified,” says Patterson. “When doing science work or recreating in the outdoors alone,  individuals will have to be more cognizant of their surroundings, be mindful of what time of day they are going outside, and be prepared with a way to communicate with friends, family members, or authorized person of a park or forest if one finds themselves in a hostile situation.”

Several organizers also pointed to the prevalence of microaggressions, acts that don’t constitute outright discrimination, but lead to feelings of discomfort and exclusion. This can include giving compliments with a racial caveat, such as, “You’re so articulate for a Black woman,” negating lived experiences by saying “I don’t see color,” or questioning a person’s qualifications.

“Especially with Black women, people don’t believe us when we say things,” explains Devin Swiner, a graduate student at the Ohio State University and one of the organizers of Black in Chem. “People are always trying to check my credentials. If I say something in a group meeting, then people might not take me seriously. But if my advisor or another man in my lab is like, ‘Oh, no, Devin had a really great point,’ then it’s like, ‘Oh, maybe Devin knows what she’s talking about.’ That happens pretty often.”

By themselves, these behaviors are irritating, says Jones, but they can snowball into an unwelcoming, unhealthy culture. “So it’s all these microaggressions building up and the next thing you know, you have a macroaggression,” Jones explains. “There’s all these statistics about the lack of Black people in STEM, but let’s break that down. Where did that begin? And what is the root cause?”

How to be an effective ally

While the focus of these groups is on Black scientists, their organizers emphasized to The Scientist the need for strong, effective allyship. “Show up when it counts. I feel like it’s that simple,” economist Anna Gifty Opoku-Agyeman says. “Because I think what ends up happening is that people are very performative around their allyship . . . where it’s kind of like, ‘I’ll retweet #BlackInMicro, but I won’t hire any Black microbiologists in my lab.’”

Support Black colleagues as scientists

“Yes, I’m a chemist. But I’m also seen as a Black woman first,” says Ayanna Jones, a leader within Black in Chem and a PhD student at Emory University. “It’s just so sad that it’s been this long and it’s not made progression, and not to be recognized as contributing scientists in our field, and that was what about Black in Chem that I loved.”

Invite Black scientists to be on panels and in leadership roles pertaining to the actual science, not just for diversity events. Place value on their wisdom and insight so they are seen more readily as scientists, not novelties.

Share resources

“There are a lot of spaces that our allies have access to, that we don’t even know about,” Swiner explains. “If [there are] fellowship opportunities that you hear about from someone in your network, pass that along to Black people in STEM. If there are awards, nominate people for work, that’s something very easy to do. Invite Black scientists to come give seminars.”

Empathize

“Realize that there are people right next to you having a completely different experience who may not be talking about it,” Kozik explains. “We shouldn’t have to kind of broadcast the negativity or the trauma, and a lot of times people won’t, because it would be risky for us to do so in those environments.”

Use your power for others

“We also need department chairs, we need divisional chiefs, we need university leadership, we need CEOs, we need people all the way up the ladder to be committed to allyship at their level, so that we can all move things together in unison,” Kozik says. “Because I feel like what usually happens at the different tiers [is that] down at the very bottom, the people with the least privilege usually have to make a lot of noise to even break through the barrier for the level above them.”

[chefist]

Myke still strung out on meth..posting on BG..bwahahha


LOSER!

[Dr. MD MD]

Myke still strung out on meth..posting on BG..bwahahha


LOSER!

This is going to be the new format of his thread here. Enjoy!

[Dr. MD MD]

Covid’s Cassandra: The Swift, Complicated Rise of Eric Feigl-Ding
REPUBLISH
The scientist has gained popularity as Covid’s excitable play-by-play announcer. But some experts want to pull his plug.
Visual: Undark

BY JANE C. HU
11.25.2020
3 COMMENTS
ERIC FEIGL-DING picked up his phone on the first ring. “Busy,” he said, when asked how things were going. He had just finished up an “epic, long” social media thread, he added â€" one of hundreds he’s posted about society’s ongoing battle with the coronavirus. “There’s so many different debates in the world of masking and herd immunity and reinfection,” he explained, among other dimensions of the pandemic. “We at FAS, we’ve been kind of monitoring all the debates and how we’re seeing signals in which the data goes one way, the debate goes the other,” he said, referring to his work with the Federation of American Scientists, a nonprofit policy think tank. He rattled off a rapid-fire sampler of hot-button Covid-19 topics: the growing anti-vaxxer movement, SARS-CoV-2 reinfection and antibodies, the body of research suggesting masks could decrease viral load, along with a quick mention of the debate among experts about what “airborne” means.

This whirlwind tour through viral Covid-19 themes felt like the conversational equivalent of Feigl-Ding’s Twitter account, which has grown by orders of magnitude since the dawn of the pandemic. The Harvard-trained scientist and 2018 Congressional aspirant posts dozens of times daily, often in the form of long, numbered threads. He’s fond of emojis, caps lock, and bombastic phrases. The first words of his very first viral tweet were “HOLY MOTHER OF GOD.”


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Made in January, weeks before the massive shutdowns that brought U.S. society to a halt, that exclamation preceded his observation that the “R0” (pronounced “R-naught”) of the novel coronavirus â€" a mathematical measure of a disease’s reproduction rate â€" was 3.8. That figure had been proposed in a scientific paper, posted online ahead of peer review, that Feigl-Ding called “thermonuclear pandemic level bad.” Further in that same Twitter thread, he claimed that the novel coronavirus could spread nearly eight times faster than SARS.

The thread was widely criticized by infectious disease experts and science journalists as needlessly fear-mongering and misleading, and the researchers behind the pre-print had already tweeted that they’d lowered their estimate to an R0 of 2.5, meaning that Feigl-Ding’s SARS figure was incorrect. (Because R0 is an average measure of a virus’s transmissibility, estimates vary widely based on factors like local policy and population density; as a result, researchers have suggested that other variables may be of more use.) He soon deleted the tweet â€" but his influence has only grown.

At the beginning of the pandemic, before he began sounding the alarm on Covid-19’s seriousness, Feigl-Ding had around 2,000 followers. That number has since swelled to over a quarter million, as Twitter users and the mainstream media turn to Feigl-Ding as an expert source, often pointing to his pedigree as a Harvard-trained epidemiologist. And he has earned the attention of some influential people. These include Ali Nouri, the president of FAS, who brought Feigl-Ding into his organization as a senior fellow; the journalist David Wallace-Wells, who meditated on Feigl-Ding’s “holy mother of God” tweet in his March essay arguing that alarmism can be a useful tool; and former acting administrator of the Centers for Medicare and Medicaid Services Andy Slavitt. (“We all learn so much from you,” he tweeted at Feigl-Ding in July.) Ronald Gunzburger, senior adviser to Maryland Gov. Larry Hogan, even wrote a letter to Feigl-Ding attesting to how his “intentionally provocative tweet” in January “elevated the SARS-CoV-2 virus to the top of our priorities list.”

But as Feigl-Ding’s influence has grown, so have the voices of his critics, many of them fellow scientists who have expressed ongoing concern over his tweets, which they say are often unnecessarily alarmist, misleading, or sometimes just plain wrong. “Science misinformation is a huge problem right now â€" I think we can all appreciate it â€" [and] he’s a constant source of it,” said Saskia Popescu, an infectious disease epidemiologist at George Mason University and the University of Arizona who serves on FAS’ Covid-19 Rapid Response Taskforce, a separate arm of the organization from Feigl-Ding’s work. Tara Smith, an infectious disease epidemiologist at Kent State University, suggested that Feigl-Ding’s reach means his tweets have the power to be hugely influential. “With as large of a following as he has, when he says something that’s really wrong or misleading, it reverberates throughout the Twittersphere,” she said.

Critics point to numerous problems. Not too long after his “holy mother of God” tweet, for example, Feigl-Ding took to Twitter to discuss a titillating but non-peer-reviewed paper that some readers interpreted as evidence that SARS-CoV-2 was engineered in a lab; once the authors retracted the pre-print, he deleted a series of tweets from the middle of the thread. In March, Feigl-Ding tweeted a CDC graph as evidence that young people were “just as likely to be hospitalized as older generations,” but failed to mention an important detail about the age ranges represented in the graph’s bars, which didn’t actually support that claim. In August, he tweeted his support for a proposition to allow people early access to a vaccine. After criticism from epidemiologists, bioethicists, doctors, and health policy experts, Feigl-Ding deleted a few tweets at the beginning of his thread, saying they were “confusing” and “murky.” (He also argued that his critics were “spreading misinformation about what they think I said.”)

More recently, Feigl-Ding wrote a thread about coronavirus particles in flatulence, which drew criticism from researchers.

“With as large of a following as he has, when he says something that’s really wrong or misleading, it reverberates throughout the Twittersphere,” Smith said.

Even when his public exclamations are technically accurate, Feigl-Ding’s critics suggest that they too often invite misinterpretations. In a thread about the first study of a Covid-19 outbreak on an airplane, for example, Feigl-Ding failed to mention the important caveat that researchers suspected all but one case occurred before people got on the airplane. In another, Feigl-Ding appeared to summarize a Washington Post piece on a coronavirus mutation, but omitted crucial phrases â€" including the fact that just one of the five mentioned studies was peer-reviewed. It wasn’t until the sixth tweet in the thread that Feigl-Ding mentioned the important detail that the “worrisome” mutation doesn’t appear to make people sicker, though it could make the virus more contagious.

To Angela Rasmussen, a Columbia University virologist, this represents a pattern. “[T]his is his MO,” she wrote in an email. “He tweets something sensational and out of context, buries any caveats further down-thread, and watches the clicks and [retweets] roll in.”

Such critiques of Feigl-Ding’s particular brand of Covid-19 commentary are by no means new, and previous articles â€" in The Atlantic as far back as January, for example, New York Magazine’s Intelligencer in March, the Chronicle of Higher Education in April, and in The Daily Beast in May â€" have explored questions about his expertise in epidemiology (his focus prior to Covid-19 was on nutrition) and whether his approach to public health communication is appropriate or alarmist. But as his influence has grown, and as the pandemic enters a much more worrying phase, critics have continued to debate whether Feigl-Ding, for all his enthusiasms, is doing more harm than good. Some complain that Feigl-Ding’s army of followers can be hateful when other scientists publicly disagree with his tweets. Others say that Feigl-Ding himself has been known to privately message his critics â€" a tack that some found unwelcome.

For his part, though, Feigl-Ding says many of his critics’ disagreements with him have come down to a difference in style. “Sometimes it’s a matter of a philosophical approach about tone: Should I say ‘whoa’ or ‘wow?’” he said â€" adding that he thinks of those words as a type of “subject line” for a tweet. “Some people don’t like the all-caps initial thing, but it’s more of a stylistic thing. And of course, some people think: ‘This tweet is sensational.’ I’ve heard that,” he said â€" adding that, indeed, he has contacted critics, but always in a professional capacity. “I [direct-message] a lot of people,’ he said, “sometimes email them when I have a question.

“We have spirited debates,” he added.

“[T]his is his MO,” Rasmussen wrote. “He tweets something sensational and out of context, buries any caveats further down-thread, and watches the clicks and [retweets] roll in.”

But Feigl-Ding makes no apologies for trying to amplify and draw attention to the seriousness of Covid-19. Sounding the alarm â€" even if sometimes imperfectly â€" Feigl-Ding insists, is a moral obligation. “The whole New York Magazine article by David Wallace-Wells, the whole article was that alarmism is needed,” he said. “It was arguing for the case of alarmism. How do we listen to the early alarms? We could have reacted faster. It’s getting people to sit up from the chair and pay attention.”

He also argues that in some cases, his Twitter influence has helped to shape policy. Specifically, he mentions a thread â€" which began with the words “BLOODY HELL” â€" criticizing broadcast company Sinclair for their decision to air a segment featuring Judy Mikovits, the star of a popular, discredited video that surfaced various conspiracy theories about the pandemic. (The media watchdog group Media Matters for America first reported on Sinclair’s plans a couple days before Feigl-Ding’s tweet.)

That tweet got “more impressions than CNN,” Feigl-Ding said, adding that hours after making it, Sinclair announced they would postpone airing the segment. Two days later Sinclair decided not to air the interview at all. “Clearly, it had an impact. That’s what I’m going for,” he said.

“The alarmism got action,” he added.

Whether or not his critics agree with that assessment, there’s little doubt that Feigl-Ding â€" who, depending on the context, might best be described as a scientist, a politician, an advocate, and a self-styled public health Cassandra â€" continues to opine, with great emotion and inflection, on myriad Covid-19-related topics, using phrases like “I’m crying”; “whoa”; “buckle up,” and “worrisome.” And on any given day, it’s easy to find other experts picking apart a Feigl-Ding tweet, explaining what he’s gotten wrong, or what nuance he’s left out.

Sometimes, Feigl-Ding is driven to clarify his position, or even delete tweets. And where his detractors suggest that his missteps are more than mere nuisances, Feigl-Ding characterizes his critics as staid scientists who want him to “stay in his lane.” Indeed, when asked about their concerns, he often steers the conversation away quickly, saying their interpersonal issues are a distraction from what this moment needs: more people like him.

THE HIGH POINTS of Feigl-Ding’s career have been repeatedly recounted in the news media â€" a point he seemed keen to emphasize in recent phone calls. “Everything I’ve ever said, there’s articles for it,” he said.

In those articles, Feigl-Ding shared versions of the same anecdotes he relayed in interviews with Undark. A Science article detailed his 2018 run for Congress, as well as the highlights of his childhood: that he spent his earliest years in Shanghai, before immigrating to the U.S. at age five; that he didn’t have a lot of friends growing up (“Imagine a chubby kid with a double chin,” he said, recounting how cruel classmates had called him “ching chong” and “pan face”); that instead of cartoons, he watched documentary series on psychology and statistics. And the media coverage goes much further back: A 2006 New York Times article described a JAMA study Feigl-Ding co-authored that provided further evidence that the drug rofecoxib, known to consumers as Vioxx, was associated with heart and kidney issues, after which “my phone did not stop ringing for a week, or two weeks,” he said. A 2007 Newsweek article featured the Facebook campaign Feigl-Ding started in support of breast cancer research. A 2011 New York Times article details the tumor doctors found in his chest at age 17, which turned out to be a benign teratoma, but launched Feigl-Ding’s interest in public health.

While Feigl-Ding is eager to discuss his successful public ventures, he doesn’t bring up his less vetted projects, like Happy Vitals, a now-defunct startup he and his wife created, which sold at-home breast milk nutrition tests. He said he’d rather not talk about Health Justice For All, a “grassroots movement” and political action committee, which received few contributions from anyone other than himself. (Feigl-Ding’s documented contributions to the PAC come in the form of unpaid Facebook posts, valued at $0.011 per impression.) He’s also not eager to talk about his failed 2018 political run to represent Pennsylvania’s 10th district in Congress. “If I run again, I don’t want a completely blunt exposé of how difficult it was,” he said. When asked if running again is something he’s considering, her responded: “Someday. Someday. I don’t want to â€" someday, maybe. Let’s just say maybe.”

Feigl-Ding also glosses over his decision to leave medical school, which he enrolled in briefly after completing his Harvard degree. “I realized life’s about what you do, not the number of letters behind your name,” Feigl-Ding said, “and at that point, I already had dual doctorates in two other things, and you know, pursuing a medical degree would’ve been a little bit overkill.” He is fond of talking about the “letters behind your name”; he used the phrase in a 2017 lecture at the University of Connecticut, as well as in a 2018 interview with the Harvard Crimson. Yet he also frequently refers to the impressive credentials of people he knows, even when they’re irrelevant to the conversation. These can include a double-inductee to the National Academies, or a Rhodes scholar who wrote a book with a former president’s child.

   
For all of Undark’s coverage of the global Covid-19 pandemic, please visit our extensive coronavirus archive.

Perhaps more than anything, though, Feigl-Ding â€" who says he earns most of his income as a consultant on federal projects and is unpaid for his communication and research work at FAS â€" frequently steers conversation towards metrics of influence, importance, or virality. In discussing how his Facebook campaign began, for example, he says he originally created two pages through the site’s now defunct Causes application; one focusing on heart disease and stroke research and another focusing on breast cancer. Unfortunately, the former “never went anywhere,” so he pivoted to concentrating on his cancer page. Eventually, the page gave him “one-click access to millions of people on Facebook,” his first foray into social media virality. “You learn to master social networks when you have your pulse on millions of people,” he said. The word “millions” is big with Feigl-Ding â€" he talks about the 6 million members of that Facebook campaign, the half-million dollars he says the campaign raised for cancer research, the 14 million views on a viral conspiracy video he’s publicly decried, and the millions of impressions one needs on social media to make an impact. One night, after a lengthy telephone interview, he texted a blog’s analysis that characterized him as more influential than CNN, along with a screenshot of a one of his recent tweets â€" one debunking hydroxychloroquine as a Covid-19 treatment. It showed that the tweet had garnered more than 2 million “impressions.”

Feigl-Ding’s descriptions of his work evoke images of him as a protagonist in a quest to fix the world’s problems. He often invokes war metaphors: He’s a “tank” against online detractors, and he refers to disagreements about Covid-19 policy as an “information war” or a “battle of the minds.” When talking about the role of viral tweet threads, Feigl-Ding recounts a Chinese parable about whistleblowers. The story, as he tells it, starts with a wizard offering a man the ability to talk to animals, but only if he agrees to never talk to humans ever again. The man accepts, but then the animals tell him an earthquake and flood will devastate his village. The man wants to warn the villagers, but if he does, the wizard will turn him to stone. He decides to do it anyway. “He made a choice and he sacrificed,” Feigl-Ding said, sighing. “I don’t want to be a martyr, but I felt like it was more important to tweet this and raise the alarm,” he says, referencing his “holy mother of God” tweet. Though the research he was citing had not yet been peer reviewed, he felt it could have important insights.

He also acknowledged the blowback he received as a result, but added: “I think it was still worth it.”

Indeed, Feigl-Ding expresses frustration about the times he wished he could have sounded the alarm sooner. “I’ve had so many of these Cassandra moments, and so many of these ‘Ah, what could have been,’ moments,” he says, mentioning his Vioxx study, the issue of toxins in the drinking water of rusting urban centers like Flint, Michigan, and even the general topic of cancer prevention. He wonders what would have happened, for example, if Toxin Alert, the website he developed with engineer Pius Lee, had launched earlier, rather than more than a year after news of Flint’s water crisis broke.

This desire to warn, to be heard, is the thread Feigl-Ding uses to connect the various facets of his career â€" and according to him, it’s what drove him to begin tweeting about the Covid-19 pandemic. “The world needs more whistleblowers, and those [who] whistleblow early, not just after the fact or whimper at the time,” he said, pointing to what he considers one of his own triumphs in having nudged the Maryland governor’s office into action: “Gov. Larry Hogan’s office, his chief policy adviser, credits me â€" that my January tweet made them stand up, sit up in their seats and start preparing.”

FEIGL-DING â€" often referred to as a Covid-19 expert in the media â€" clearly has the ear of some influential people. In addition to advising Hogan’s office, claims he’s made in tweets have been addressed by Mexican officials in government press conferences, and his tweets or commentary have recently appeared in publications like The Washington Post, Vox, and Salon. After all, who could speak to the science of the pandemic better than a Harvard-trained epidemiologist?

But epidemiology is a big field, and Feigl-Ding’s previous research focuses mostly on nutrition and cancer, different sub-areas of the field than infectious disease. Popescu, the infectious disease epidemiologist, likens this distinction to different specialties in medicine. “I’m not going to go to a cardiologist to have brain surgery,” she said. “Many of us have called attention to his lack of experience or training” in infectious disease epidemiology, she said of Feigl-Ding.

“It’s really challenging to communicate when someone really can sell themselves, like, ‘I’m a Harvard scientist, I’m an epidemiologist,’” she added.

But Feigl-Ding is, indeed, a Harvard-trained scientist and a degreed epidemiologist â€" though his critics argue that most of his training has focused on nutrition, not infectious disease, making him prone to mistakes. An example: In one of his most popular tweets â€" known widely within Twitter’s science community as the “holy moly” tweet â€" Feigl-Ding said he was “crying for Mexico” because the country’s testing positivity percentage was 50 percent. A full half of people being tested in Mexico were proving to be infected with Covid-19, a figure even New York, Lombardy, and Madrid didn’t approach at their “worst periods,” he wrote. “Mexico may be undergoing unprecedented #Covid19.”

The message clearly struck a nerve with Twitter users, as it received tens of thousands of retweets and more than 1,500 responses. But while all of the information in the tweet was technically true, what Feigl-Ding had actually done, according to his critics, was paint an incomplete â€" and alarming â€" picture of an out-of-control outbreak without providing upfront context about what that positivity percentage actually represented: the fact that Mexico still was not testing very many people, and that most of its testing was being done on people who were already ill. Under such circumstances, a 50 percent positivity rate would not be considered unusual. Indeed, as Boston University epidemiologist Ellie Murray wrote in a tweet, positivity percentages are “used for evaluating whether you’re doing ENOUGH tests, not estimating how much disease you have.” Along with her explanation was a screenshot of Feigl-Ding’s tweet, which she called “bad and misleading.” Feigl-Ding clarified the meaning of positivity percentages in a continuation of that thread hours later â€" in fact, before Murray tweeted her criticism â€" but those tweets received only a fraction of the attention as Feigl-Ding’s original “holy moly” tweet.

“The world needs more whistleblowers, and those [who] whistleblow early, not just after the fact or whimper at the time,” Feigl-Ding said.

Finding experts publicly correcting or critiquing Feigl-Ding’s tweets is not hard. More recently, infectious disease experts refuted his claims that the suggestion of White House coronavirus adviser Dr. Anthony Fauci that eyewear could improve Covid-19 protection meant that things were “getting serious,” and a slew of scientists â€" including Popescu, University of Florida biostatistician Natalie Dean, and University of California, San Francisco physician Vinay Prasad, among others â€" expressed concern about Feigl-Ding’s take on releasing vaccines early to certain populations.

But others suggested that the blowback from Feigl-Ding’s Twitter supporters has deterred them from raising more concerns about his missteps. “He has a couple hundred thousand followers,” said Michael Bazaco, an epidemiologist at the U.S. Food and Drug Administration and an adjunct professor at the University of Maryland. “They’re very assertive and aggressive, and I don’t want to deal with that.”

Rasmussen, the Columbia virologist, said she was initially reluctant to comment for this piece because she similarly feared online criticism from his fans. Feigl-Ding’s followers “have ganged up on anyone who criticizes him publicly,” she said, adding that her own Twitter feed has been “clogged with Feigl-Ding’s fans calling me stupid, petty, inept, gatekeeping, etc., along with the usual gendered slurs and insults.” (A search for specific instances of these terms being directed at Rasmussen on Twitter turned up few results, though evidence of Feigl-Ding defenders offering sometimes arch disagreement â€" and even some vulgar commentary â€" is easy to find.)

Dueling with strangers, Popescu said, is “emotionally draining.”

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Ahead of publication of this article, Feigl-Ding pointed to complaints from other scientists on Twitter about the online argumentation style of some of his fiercest critics, including Popescu, though he declined to elaborate. “Trying to stay above it,” he wrote in an email to Undark on Tuesday, “since we need science to be respectful and publicly trusted.” Asked earlier about his own followers’ behavior, Feigl-Ding acknowledged some early issues. “Some of my early followers, those who were harassing, I actually removed them,” he said, while others eventually stopped following him. But he also said he has experienced rough treatment online himself, including by Twitter users of even greater influence. And on Twitter, too, he has responded to criticism from colleagues by pointing to his own dealings with what he called “anti-science trolls.”

Feigl-Ding may not bear any responsibility for â€" or even have any control over â€" the actions of his followers, of course, but he has also been known to privately contact his critics himself. After Murray tweeted her criticism, for example, she said Feigl-Ding messaged her privately to discuss the issue. Six other infectious disease experts that Undark spoke to say they’ve received private messages from him, often after publicly remarking on his tweets. Some, like Bazaco, say they simply ignore such forays. Popescu says that in talking with other scientists who have accepted Feigl-Ding’s messages, she discerns a pattern. “It’s always the same: ‘I want to learn, I want to be better’ â€" but he spends the entire time saying why he was right, giving you articles that were written about him, and how he called this and how he’s been misunderstood.”

In addition to infectious disease experts, Mexican journalist Maria Fernanda Mora said she also received messages from Feigl-Ding after she tweeted a thread questioning his reliability as a source, based on information she’d read in several articles published about him. But Feigl-Ding’s message â€" which included two articles about himself â€" arrived via Instagram, not Twitter, where Mora blocks strangers from directly messaging her. “I was truly surprised,” she wrote to Undark in a Twitter message.

When asked about these various interactions, Feigl-Ding expressed frustration, suggesting that such complaints were a “distraction” from the issues. “I don’t understand,” he said. “I’ve never said anything rude. I’ve never asked anyone to send anything rude,” arguing that his stated goal was always a polite and professional dialogue. “I’ve never kind of sent any harass[ing] messages whatsoever,” he said. “I don’t understand.”

“He has a couple hundred thousand followers,” said Bazaco. “They’re very assertive and aggressive, and I don’t want to deal with that.”

Indeed, from his perspective, Feigl-Ding said, professional disagreements ought to be considered healthy and par for the course. And science communicators are, after all, trying to accomplish the same thing. But he also said he believed that disagreements should be handled privately, to avoid conflicting information. If people see disagreement among scientists online, he reasoned, there’s a risk that they’ll ignore scientists’ messages entirely.

When this reasoning was shared with Popescu, she challenged its logic â€" in part because she said it seems to suggest that while Feigl-Ding can speak publicly, his critics ought not. “You’re saying we can’t disagree with you,” she added, “because we’re ‘on the same side.’”

Popescu also said she felt Feigl-Ding’s positioning himself alongside infectious disease epidemiologists toiling in the Covid-19 trenches was misleading to the public. The latter are “living it, working in it, and will continue to after this,” she said. “He’s just tweeting about it.”

FEIGL-DING SAYS that he believes his ability to grab people’s attention is an asset, and his unique contribution to an inherent and ongoing conflict â€" he called it a “battle” â€" between science and misinformation. “Tweeting is an art form,” he said.

“If your initial tweet does not draw them in,” he added, “you’ll get maybe a respectable four or five hundred retweets. I just call that respectable, but that’s not impactful. Anything impactful, you need a thousand retweets, at least.” Once you’ve got an audience’s attention, he said â€" that’s when you can get “into the weeds” or use a thread to “give information that goes beyond the headlines.”

Some experts consider that a savvy formula. Nouri, the president of the Federation of American Scientists, first reached out to Feigl-Ding in February, when the organization was thinking about how to debunk disinformation around Covid-19. “Eric is one example of somebody who has managed to break through the noise,” he said. (Feigl-Ding’s Harvard affiliation has ended.) Feigl-Ding, Nouri added, not only has a large following, but his tweets weigh in on the latest news quickly. “Speed is very important when it comes to countering disinformation,” he said, noting that Feigl-Ding is also prolific, “constantly pushing material out on social media.”


RELATED

Interview: Ioannidis Responds to Critics
When asked about critics’ concerns that Feigl-Ding’s tweets are often misleading or lack nuance, he suggests there’s a trade-off. “Whenever you want to get information out in a rapid way, in a succinct way, and in a way that really resonates with people â€" and you really want to grab their attention,” Nouri said, “you can’t do that effectively and at the same time have a caveat and an explanation for everything that you’re trying to convey.” Getting information out there is “a bigger value to public health,” he added, “than the fact that some aspect of the tweet may have been misrepresented.”

Devi Sridhar, the chair of Global Public Health at the University of Edinburgh, agrees that Feigl-Ding’s tweets have value. While she doesn’t agree with everything he tweets, she said, she believes he’s acting in good faith. With so much misinformation out there, it’s “all hands on deck,” said Sridhar, and at the end of the day, Feigl-Ding is on the same side as many of his critics. “Whoever wants to counter that misinformation â€" I’m not going to criticize them on style or their tone,” she said. “We’re all trying to get a handle on this and spread good information.”

And to be sure, there is some evidence that Feigl-Ding’s tweets have contributed to positive outcomes, and he pointed to some potential successes: He says, for example, that the day after one of his tweets about Arizona’s rising cases went viral, the state’s governor permitted local governments to create and enforce local mask orders.

Just how direct the line is between a Feigl-Ding tweet and an action in the world, of course, is difficult to discern â€" and not all the impacts have necessarily been in the direction Feigl-Ding would hope. Nicholas Evans, a bioethicist at the University of Massachusetts in Lowell, for example, said that within 24 hours of seeing Feigl-Ding’s tweet about the results of the since-retracted pre-print which many touted as evidence that SARS-CoV-2 was engineered, he saw Feigl-Ding referenced in support of the conspiracy theory that the virus was intentionally released by China. And Mora, the Mexican journalist, says that Feigl-Ding’s tweets about Mexico’s positivity percentage have been used by President Andrés Manuel López Obrador’s political opponents to criticize his administration’s handling of the pandemic.

Getting information out there is “a bigger value to public health,” Nouri said, “than the fact that some aspect of the tweet may have been misrepresented.”

But the central and long-running critique of Feigl-Ding â€" that the high profile he’s cultivated through arguably sensational, often imprecise, and above all, relentless Covid-19 messaging is problematic â€" suggests that many scientists simply don’t buy the notion that the urgency of the moment necessarily outweighs the need for scientific precision in public messaging during a crisis. Scientists need to be especially careful when explaining new research, said Jason Kindrachuk, a virologist at the University of Manitoba. Studies might be interesting without actually telling the public anything new about the state of Covid-19, for example. “That’s where we science communicators really have to do our diligence in providing that context back to the public,” he said. Kindrachuk is concerned that, among other things, “sounding the alarm bell too much” could needlessly concern people over trivial findings.

It also, some experts said, could lead the public to become desensitized to scientists’ concerns entirely. Paige Jarreau, a science communication scholar and vice president of science communication at the software company LifeOmic, suggested that there’s an important balance to be struck between speed and accuracy. Communicating complex ideas and nuanced arguments around the latest Covid-19 findings is indeed difficult, she said â€" but that makes it all the more important to think carefully about how to communicate it.

“If you’re trying to be really fast and sexy, and you put out something that breaks someone’s trust in you, maybe you ended up having to take it down because it was wrong or you were too quick to jump to sharing something and it wasn’t actually correct,” Jarreau said. “Then you’ve broken the audience’s trust.”

Feigl-Ding concedes he’s made mistakes â€" just as many public health experts have, he says â€" pointing by way of example to Anthony Fauci, who in the earliest days of the pandemic suggested that Americans needn’t be immediately alarmed about Covid-19 (though he added the situation was serious and could quickly change â€" as it did). Still, sometimes scientists just don’t have definitive answers to questions the public is asking, Feigl-Ding added: “We’re always trying,” he said, “to push the best available information.”

Jane C. Hu is a science journalist living in Seattle. Her work can be found at Slate, Nautilus, Wired, the Atlantic, and Smithsonian, among other publications.

UPDATE: An earlier version of this piece imprecisely described Eric Feigl-Ding as a lobbyist. While he is the founder of a political action committee, or PAC, he has never been a registered lobbyist. The story has been updated.

[Dr. MD MD]

Milk
For a few days in 1995, many Indians believed a religious idol had developed a lifelike ability to drink milk.
fiftytwo

TABLE OF CONTENTS

Chapter 1
21 September 1995: The day of
Chapter 2
Ebb and flow
Chapter 3
Enter elephant
Chapter 4
Disbelief
Chapter 5
A question of faith
Chapter 6
The age of miracles
06
sukhada tatke
05 nov 20
52 detail
25 min
21 September 1995: The day of
Loud and persistent knocks at the entrance of a small temple in Delhi sliced through the calm of deep night. The clatter stirred Radha Krishna Bharadwaj awake. A pious devotee was at the gate.

“Wake up, Panditji,” he said to Bharadwaj, the temple priest. “Lord Ganesh is drinking milk. Please open the gates.”[1]

The men approached the sanctum sanctorum. The priest spooned out some milk from a bowl and raised it to the idol’s mouth at an angle. Within seconds, it was sucked clean.

Arrow Up
As day broke, the news spread rapidly across the country. By night, it had circumnavigated the world. Bharadwaj’s experience was among the first reported cases of the story. But from Delhi to West Bengal and Maharashtra to Tamil Nadu, millions of people, in possession of varying amounts of milk, faith and curiosity swarmed the streets and queued up at temples and shrines to see if it was true: if god was really drinking milk.

“It felt like Holi or Diwali,” Bhardwaj later told the BBC. “It was even more festive. Everyone was happy and telling each other about it. For Hindus it was so significant, I can’t explain it.” Bharadwaj later told the BBC. Stores ran out of milk, and prices soared. In Punjab, a rumour spread that Vishnu’s final avatar had arrived, signalling the end of Kalyug or the age of strife. A priest at a Hanuman temple in Delhi said that the gods had come down to earth to solve our problems. Everybody seemed to have a story.

Newspaper headlines in the days that followed screamed: Milk Drinking Frenzy Spills Over the Globe, Shiv Shakti Dazzles India, Milk-Drinking Idol Creates Countrywide Frenzy. International publications latched on to one of the biggest stories to come out of South Asia that year. Reports emerged of Ganesh idols quaffing spoonfuls of milk in the USA, the UK, Thailand, Indonesia, Argentina.

“The milk sipping mania has once again placed India back in its place as far as world opinion is concerned,” the journalist Dilip Cherian[2] wrote in The Daily. “Once again, we are left with the long lingering image of a nation of Godmen, snake-charmers and miracles.” The French anthropologist Denis Vidal, who was working in India at the time, called it the first “globalised” miracle. Earlier miracles were sanctified in stories and folklore. This one was consecrated by television.

The Bombay police went to investigate matters at the city’s famous Siddhivinayak temple at the behest of Gopinath Munde, Maharashtra’s deputy chief minister. They reported that a silver idol next to the main one had refused their overtures. Dagdusheth Maharaj in Pune also proved lactose-intolerant. Pre-empting chaos, the temple closed its doors and put up a board that read: Our Ganapati does not drink milk.

These cases of non-cooperation notwithstanding, the milk miracle was a key episode in modern India’s protracted tangling of faith and reason. Long before some of India’s best-known rationalists began to be murdered, it portended how religion and superstition would be instrumentalised in the new millennium.

Twenty-five years later, as virologists and scientists raced against time to decode Covid-19, quack remedies did the rounds on WhatsApp. Early in the pandemic, lamps were lit in balconies after Prime Minister Narendra Modi suggested that the “superpower of light” would aid the fight against the coronavirus. Over this monsoon, a dead actor’s girlfriend was repeatedly accused on national television of practising black magic. In the face of widespread panic and alienation, India’s constitutional ideal of developing “scientific temper, humanism and the spirit of inquiry and reform” seemed to be forgotten.[3]

“Maine pol khol di. I have unmasked it.”

Dulichand Arya, cobbler, Delhi.
I
n Delhi, Gauhar Raza threaded his way through an unusual hubbub at the National Institute of Science, Technology and Development Studies, where he headed the department of science communication. The institute was founded in 1980 to promote a “scientific temper,” a term popularised by India’s first prime minister Jawaharlal Nehru[4] to underscore the spirit of logical and rational thought in newly independent India. Within minutes of settling in to work, Raza was summoned by the director of the institute. Journalists had been calling all morning about a supposed miracle: could Raza handle them?

He was still coming to grips with what was going on when he heard that a cobbler outside the institute was demonstrating something interesting. Raza dashed out and saw him feeding water to the top arm of his three-pronged anvil with a spoon. When the water vanished, Dulichand Arya looked around at those who had gathered and said: Maine pol khol di. I have unmasked it.

Raza crossed the road to a temple and watched devotees streaming in. He returned to his office and gathered his thoughts on a blackboard. He was now ready to face journalists.

In Bombay, the rainy morning had melted the roads into monsoon slush. Smruti Koppikar, a reporter with India Today, left her home in Borivali and headed to the train station to ride the north-south needle of the city. At her Nariman Point office, a strange piece of news had just begun to flash on the wires. “We did a double take. Ganesh drinking milk? Where? How?” Koppikar, who was assigned to go temple-hopping in South Bombay, said.

Riding pillion on her photographer colleague’s motorbike, Koppikar noticed that the air quivered with the frisson of something rare, something larger than life. “It was like India had won the World Cup,” she remembered.

At the small Ganesh mandir in the Mahalakshmi temple complex, Koppikar asked the priest: why milk? Unlike the deity Krishna, Ganesh isn’t popularly believed to be fond of dairy. The priest had no answer, but they watched as one old woman hobbled towards the idol. This miracle was why she had been kept alive for so long, she declared, teary-eyed.

Back at the office, Koppikar and her colleagues phoned scientists for rational explanations. “That day showed us how important it was for journalists to have not two, but multiple versions of the same story,” said Koppikar.

Ebb and flow
T
he ebb and flow of religious faith is shaped by socio-economic environments. “When people grow up in conditions where their survival is not secure, they tend to be more religious,” Meera Nanda wrote in her 2009 book The God Market: How Globalization is Making India More Hindu.

India in the early 1990s was in the sort of churn it would not experience again for two decades. The Mandal Commission Report, which recommended caste-based reservations in public employment, provoked reactionary outrage from dominant caste groups. Economic liberalization meant that the income gap was widening. It seemed that, almost overnight, the world had been invited to India.

When the milk miracle occurred, memories of the Babri Masjid demolition and the ensuing communal riots were still fresh. When then-BJP president LK Advani embarked on his nationwide roadshow in 1990 to inflame the Ramjanmabhoomi agitation, a kind of social and political mobilization was already underway, aided indirectly by a televised adaptation of the Ramayana which had captivated the nation in the late 1980s.[5] When a mob finally brought down the mosque on 6 December 1992, many Indians started to believe that the right-wing project to remake India from a constitutionally pluralist state to a Hindu one had triumphed.[6]

For most Indians, the fruits of internationalization appeared as if behind a glass-caseâ€"you could look but not touch. But now there were new ways to display pride in civilisational legacy.[7] Religiosity, defined by dominant caste and class groups and often rooted in idol worship for Hindus, became key to that revivalism.

India’s tradition of spiritual teachers and guides found an offshoot in a new crop of miracle-working men and women in the 1980s and 1990s. They spoke the language of faith and devotion and enjoyed wide public appeal. Sathya Sai Baba, for instance, was revered as the reincarnation of the Sai Baba of Shirdi. Devotees flocked to watch the new Baba produce ash, sarees, and gold chains out of thin air: miracles, they insisted, and not sleight of hand. The tantric godman Chandraswami, favoured by a number of political leaders, built himself an ashram soon after PV Narasimha Rao of the Congress became prime minister in 1991.

California’s technology majors were making their way to still-idyllic Bangalore and a nascent Gurgaon to set up cost-efficient back offices. Meanwhile, India’s brightest started to work their way up to critical technical and management roles in Silicon Valley headquarters. In the early days of the World Wide Web, non-resident Indians became emissaries of Hindu identity and glory on discussion fora and mass e-mail chains.

“A key characteristic in their construction of Hinduism was to give the legitimacy of science to unrealistic, fantastic claims,” the academic Rohit Chopra explained.[8] “So, on the one hand, Hinduism was praised as the source of all kinds of scientific and technological achievements, from satellite television to nuclear weapons, cures for diseases and the internet itself. On the other hand, events like Ganesh drinking milk, the claims of astrology, or some baba reincarnating himself at will were given a scientific veneer.” Many of the sites and email chains from which falsehoods emerged were maintained and populated by NRIs working in technologyâ€"â€"“both in relatively privileged professional positions,” Chopra said, “as well as contract coders working for tech body shops or on deputation to IBM.”

Enter elephant
G
anesh iconography has changed over centuries, the cultural theorist Ranjit Hoskote, former religion and philosophy editor at The Times of India, explained. He was not always elephant-headed. One origin story of the cult of Ganesh dates back to when speakers of Indo-European languages started clearing forests along the Ganga valley for agriculture. They met with resistance from the original inhabitants, worshippers of an intractable deity who prevented the advance of the cultivators. Naturally, this divinity became identified with obstacle-making.

“As the indigenous population became absorbed into the communities established by the incoming Indo-European language speakers, their gods and forms of worship became part of an emerging pantheon of convergence,” Hoskote told me. “By stages, the fierce forest deity became first a yaksha or unpredictable guardian spirit of nature. And later, through rituals of propitiation, the vighnakarta became the vighnaharta”: the maker of obstacles became their destroyer.

Pre-Vedic representations of Ganesh were aniconic, represented by vermillion smears or a pair of eyes fashioned with silver leaf on tree trunks. The tradition persists, even as the elephant-headed god acquired the iconography he is known for today.[9] “It can be read as an allegory of how the memory of the first aboriginal inhabitants of South Asia has been absorbed and forgotten,” Hoskote said.[10]

Over time, Ganesh, like other tertiary deities such as Hanuman and some local forms of the devi or mother goddess, found a place in the Hindu pantheon. These deities were easier to pray to and have an intimate and emotional connection with, not high and mighty like the abstract trinity and the great gods.[11]

But one day, Ganesh, seemingly, had a demand.

O
n that September day in 1995, scientists and rationalists grew alarmed as the hours wore on. Public fervour was unprecedented, and the threat of some kind of mob reaction was on everyone’s mind.

In Satara, Narendra Dabholkar, founder of the rationalist group Maharashtra Andhashraddha Nirmulan Samiti (MANS),[12] offered ₹5 lakh to anyone who could prove that the gods were actually drinking milk. Dabholkar and other well-known rationalists and scientists,[13] appeared on television and radio to parry the wonder of the miracle with the rapier of reason. They reconstructed the ‘miracle’ with props like tea pots (the spout being similar to Ganesh’s trunk), breaking down abstruse concepts of physics to convince the layperson that there had been no miracle.

These were the facts, they said. Idols made of porous substances such as clay or mud could have absorbed some milk.  What made it “vanish” in most cases, though, was a combination of capillary action and surface tension.

Capillary action: The ability of a liquid to move up through the narrow spaces of porous substances, against gravity. Think of a blotting paper that sucks up ink, or a colour spreading across the paintbrush through its fine tip.
Surface tension: The property of the surface of a liquid that allows it to resist an external force, due to the cohesive nature of its molecules.
When part of an object (in this case, an idol’s mouth, trunk or tusk) punctures the surface of a liquid, some fluid flows out. To the untrained eye, it appears that the liquid is vanishing from the spoon. What we don’t see is the thin film clinging to the object and flowing downwards. Think of the times you’ve lifted a cup of tea only to realise that some of it has flowed down and gathered in the saucer. Something similar happened, scientists explained, to the Ganesh idols.

Disbelief
T
he psychiatrist and MANS activist Pradip Patkar watched events unfold in disbelief.  The TV coverage looked similar to what he was used to seeing in his clinicâ€"patients blocking rational thinking in extraordinary emotional settings. The term that came to his mind was mass hysteria.[14]

Patkar and his fellow activists fanned out across Panvel, just outside Bombay city, visiting schools and temples. He urged people to feed a small Ganesh idol he carried with him. Add turmeric, he said, proffering some, it’s good for his throat. The milk ‘disappeared,’ but within moments, yellow liquid flowed down the idol’s portly body.

In Delhi, the scientist Gauhar Raza went on news channels with Arya the cobbler. Together, they demystified the occurrence using Arya’s anvil, and other objects such as teacups and teapots.

[Dr. MD MD]

In early april, Paul Hiley was kicking back in the executive suite at Desert King International LLC, gazing out the window at the San Diego sunshine and daydreaming about his golf game. California had issued its initial stay-at-home order for COVID-19, but apart from the hand sanitizer around the office, life was more or less normal. Retirement was on the horizon for Hiley. Maybe he’d sell the business. Maybe his son, Damian, would take over.

For more than 42 years, Hiley has been a leading purveyor of certain plant-based food additives such as saponins, foaming agents used in root beer and Slurpees. Most of us never think about these compounds, and Hiley has always liked it that way. “My theory of business is the only two people who need to know my name are my wife and my banker,” he told me recently.

Then, one dayâ€"April 14th, to be exactâ€"his son told him that they had a call with Stanley Erck. Erck is the CEO of Novavax, a Maryland-based maker of vaccines. Not a seller of vaccines, mind you: The company had yet to bring one of its candidates to market. But like other companies around the world, Novavax had thrown its hat into the coronavirus-vaccine race. And its success, Erck believed, depended on that odd ingredient in Slurpees.

The inner bark of the Chilean soapbark tree, Quillaja saponaria, is the source material for some of these saponins. Pulverized and soaked in water at the Desert King factory in Chile, the bark is transformed into a brown, bitter, bubbly fluid. This precious goo does many things well, and it happens to be the raw material for one of the world’s most coveted vaccine adjuvants: QS-21. Adjuvants are compounds that boost the body’s immune reaction to a vaccine. Owing to their potential risks to human health, however, only a handful of adjuvants have been approved by the U.S. Food and Drug Administration, and QS-21 is one of the newest.

A single gram of powdered QS-21 costs more than $100,000, though only about $5 worth is needed for each shot. Nine years ago, researchers estimated that the global supply of pharmaceutical-grade Quillaja extract was sufficient for just 6 million doses of vaccine. Everyone in the business knew the story of the Pacific yew tree, whose bark was the original source of the chemotherapy drug paclitaxel, and which was threatened by large-scale harvesting in the 1980s. “If you take out all the trees in one shot and deplete the source of saponin, you are in deep shit in the future,” says Garo Armen, whose company, Agenus, helped bring QS-21 to market. Novavax has its own saponin-based adjuvant, called Matrix-M, and warned investors last year that their vaccines could be delayed if they failed to “secure sufficient supplies” of high-quality extract. And the Hileys practically had a monopoly on it.

During his call with the Hileys, Erck asked if Desert King could increase their production for Novavax a hundredfold. Paul Hiley’s jaw dropped to the table. Novavax was on the cusp of receiving $384 million in international funding to help it produce 100 million doses of its COVID-19 vaccine for the world by the end of the year, and a billion doses by the end of 2021. It would also soon be on the short list of vaccine candidates funded by the Trump administration’s Operation Warp Speed. Novavax needed guarantees of 1,500 pounds of saponin now, and up to three times as much next year.

Hiley’s immediate concern was that his Chilean operation had already missed the bark-harvesting windowâ€"typically during the trees’ spring growth, between September and December. And last year he had made the ill-timed decision to postpone expanding their pharmaceutical operations in favor of investing in Desert King’s booming animal-feed business.

In the end, Hiley knew there was only one way to answer Erck: “Of course, we can deliver it,” he said. Three months later, inside the Desert King conference room in early July, sitting across from a shelf displaying Slurpee cups and bottles of Stewart’s Root Beer, Hiley let out a chuckle through his surgical mask. “I had no idea if we could.”

For all the talk about the cutting-edge vaccines that may just get us out of the COVID-19 mess, little has been written about adjuvants. Perhaps that shouldn’t be surprising: The late Yale professor Charles Janeway famously called adjuvants the “immunologist’s dirty little secret.”

These unheralded helpers can turn a half-baked vaccine into an effective one, or stretch a scarce vaccine supply during a pandemic. Not every vaccine requires an adjuvant, but many do: Of the more than 200 vaccines listed in the Milken Institute’s COVID-19 vaccine tracker, approximately 40 percent are protein-based vaccines, which rarely work without an adjuvant. Yet adjuvants have never attracted much funding from industry and government. “Adjuvants have been the weak link in vaccines for the last hundred years,” says Nikolai Petrovsky, a vaccine researcher at Flinders University in Adelaide, Australia.

The discovery of adjuvants is credited to a bearded veterinarian named Gaston Ramon, who worked at the Pasteur Institute in Paris in the 1920s. At the time, horses were routinely injected with toxins from tetanus and diphtheria so their bodies would produce antibodies that could be used in human therapies. Ramon, who was trying to develop the first human vaccines for these life-threatening diseases, observed that the horses’ circulating antibodies generally declined over timeâ€"even if the animals were re-injected with bacterial toxins every few weeks. Every so often, however, a new injection would cause waning antibody levels to rebound.

When he examined the horses whose antibody levels rebounded, Ramon discovered abscesses at their injection sites. Those pus-filled lumps, he thought, could be temporarily trapping the toxins, giving the horses’ immune systems more time to ramp up their responses. Ramon experimented with ways of artificially slowing the absorption of the injected toxins, mixing them with bread crumbs, powdered infant formula, and tapioca starchâ€"which happens to contain high levels of saponinsâ€"to produce local swelling without a full-blown abscess. One horse in his study, injected with a mix of toxins and tapioca, produced five times the normal levels of antibodies.

Meanwhile, a British researcher found that aluminum salts, injected into guinea pigs, had similar but more predictable effects on antibody production. For the next 70 years, they would be the only adjuvants used in vaccines. (While aluminum adjuvants can produce swelling and pain that lasts for a few days, abscesses and other side effects are uncommon.)

The earliest viral vaccines actually did fine without adjuvants. The polio and measles vaccines were initially made from weakened or inactivated whole viruses, which were more than 90 percent effective after several doses. Both vaccine types generate an antibody response, and the live ones also activated another part of the immune system, the T-cell response, which is important for fighting more complex pathogens and can even kill the body’s own cells if they become infected.

The risk of live-virus vaccines is that they can possibly revert to their more dangerous selves or replicate uncontrollably in people with weakened immune systems. Inactivated-whole-virus vaccines have also raised alarm after episodes where they altered the immune system in unpredictable ways. During a clinical trial in the 1960s, 31 infants received a vaccine made with inactivated respiratory syncytial virus (RSV). Those who later caught the virus ended up with a more severe form of the disease; two of the 23 who were infected died. By the early 1980s, the quest for ever-safer vaccines against ever-trickier viruses, such as RSV, hepatitis B, and HIV, led researchers to develop vaccines that contained just a fragment of the virus, typically a protein.

But the immune system seemed blind to these new vaccinesâ€"until researchers added just the right adjuvant. Aluminum didn’t stimulate an appropriate T-cell response, which scientists noticed could be induced with other substances, such as heat-killed tuberculosis bacteria. “Why do we need to use adjuvants?” Janeway asked in 1989. “To be quite honest, the answer is not known.”

Adjuvants posed their own dangers. During a pilot study of an adjuvanted flu vaccine in the 1990s, some subjects got triple-digit fevers and egg-shaped lumps on their arms. “That scared people,” says Tyler Martin, who once worked at the Chiron Corporation, which developed that vaccine. Adjuvants became a frequent target for the anti-vaccination community, which contributed to the FDA’s conservative approach to them. “At advisory-committee meetings, people come out to rail against adjuvants,” Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, says. “We want to make sure they are safe.”

In any event, the side effects were proof that adjuvants weren’t simply slowing down the spread of the antigen through the body. Perhaps, as Janeway himself theorized, they were flipping on some ancient danger switch to alert our immune system of an invader. In 1997, scientists located that switch: Our dendritic cellsâ€"the tentacled sentries lurking in our tissuesâ€"have at least 10 receptors attuned to pathogens. Some adjuvants act on those receptors. Martin, now the CEO of Adjuvance Technologies in Lincoln, Nebraska, told me, “Once we understand what’s the nature of the immune response we really want to create to COVID, then we can pick the right adjuvants to sculpt that response.”

Acouple of weeks after meeting the Hileys, I stood across the street from a Starbucks on the wooded edge of the University of California at Berkeley. It was 10 o’clock on a Wednesday morning in mid-July, but the place was uncannily quietâ€"all summer classes had moved online. During the previous week, the county had reported more than 1,000 new cases of COVID-19, the highest totals since the outbreak began.

After a few minutes, a man rolled up on his bicycle, a buff cinched around his nose and mouth. Intense dark eyes peeked out from under his fluorescent-green helmet. This was Ricardo San Martin, a scientist who had helped develop the Chilean soapbark industry. He had moved on to other projects, but he still consulted for Desert King. In April, he said, he got a WhatsApp message from Damian Hiley that said simply: “Google Novavax.”

When San Martin heard that Novavax was going to need several thousand pounds of Quillaja extract each year, he started doing the calculations in his head. Since 2000, Chile has cleared 11 percent of its native forests, and mature, accessible Quillaja saponaria trees have become rare. Under Chilean law, landowners need a special permit to cut down Quillaja trees, but they are allowed to prune up to 35 percent of their biomass every five years. Over the next few years, the industry was on course to exceed one published estimate of the maximum sustainable harvest of 27,000 tons, or about 67,500 trees. The Hileys say that number is a significant underestimate of what the forests can bear. Regardless, just one major vaccine rollout would require bark from the equivalent of 5,000 to 7,000 trees per yearâ€"or more if you’re only relying on prunings. San Martin realized that while most of the world was thinking about the pandemic’s risk to the human species, someone needed to be thinking about its antidote’s risk to Quillaja. “I feel like if I don’t do it,” he told me, “then who’s going to do it?”

Keeping a safe distance from each other, San Martin and I walked around the perimeter of a small grove of trees just within the campus boundary, mostly eucalyptus and redwoods. We came to a tree about 60 feet tall with gray, sandpapery bark and waxy, oval-shaped leaves with rippled margins. This was it: a Chilean soapbark, one of a handful planted on the Berkeley campus starting in the late 1800s. San Martinâ€"a chemical engineer, not a botanistâ€"doesn’t know how they all ended up here, just that he’s lucky to live near them. (The soapbark is uncommon in the United States and tends to grow well only in California, which has a climate similar to Chile’s.)

Pulling a pair of garden clippers out of a pannier on the side of his bike, he snipped off a few leafy branches to tuck inside a paper bag. Later, back in his garage laboratory a few blocks from campus, San Martin ground up the dried leaves and soaked them in warm water to produce an extract. As he shook the liquid up in a large graduated cylinder that looked like a theater prop, counting to 30, it produced a dense foam like the head of a beer. The amount of that foam, he explained, was roughly equivalent to the extract’s saponin content.


Melanie Lambrick
Leaves aren’t currently used by industry because they represent just 5 percent of a mature tree’s weight. In a sapling, however, they may account for 30 to 50 percent of the tree’s biomass and are the only material that can be harvested sustainably. In the face of the current public-health emergency and the potentially life-saving role of saponin adjuvants, San Martin believes we should be establishing new soapbark-tree plantations inside and outside of Chile, and preparing to harvest leaves from the young trees. He’s now testing local soapbark stock inside Berkeley’s greenhouses, hunting for the plants best suited to found plantations on American soil. “What I want now, urgently, is to provide a second source of this natural raw material,” he said.

He hopes to finish a mission he began long ago.

Flash back to the early 1990s: Picture, if you will, San Martin sitting on the toilet. He was a newly minted Ph.D., working at the Catholic University in the Chilean capital of Santiago. He was looking for a project with commercial potential, something that might contribute to the Chilean economy as the country recovered from the cruelty and corruption of the Pinochet dictatorship. He had brought a copy of a United Nations newsletter into the bathroom, and one article caught his eye. It said that a “South American tree” was being tested in a vaccine against HIV.

Only later did he realize that one of those very trees was growing in his own backyard. Chilean soapbarks were once abundant in the sun-soaked hills around the capital, climbing up the flanks of the Andes to about 6,000 feet. For hundreds, if not thousands, of years, the tree bark, ground up and mixed with water, was used as soap by the indigenous Mapuche people. In his 1782 treatise on the natural history of Chile, the Jesuit priest Juan Ignacio Molina wrote of its use by locals: “There is never to be seen on their clothes the least spot or dirt.”

Over the next century, soapbark became an international commodity. American magazines offered up recipes for hair-curling liquids and wool detergents made with the soap-like saponins. Sozodont toothpaste advertised itself as “the only dentifrice” that contained “this salubrious botanical product.” (“When rosy lips part, pearls should glitter behind them.”) In the early 1900s, makers of carbonated beverages discovered that adding soapbark extract to their drinks created a coating of bubbles on the surface that kept the carbonation from escaping. From there, the applications of saponin expanded rapidly: During World War II, it was used in surveillance efforts as both a lens cleaner and an ingredient in photographic reagents.

In 1949, a U.S. government report noted that careless bark-stripping methods were destroying “thousands of trees each year” and regulations were poorly enforced. Some harvesters simply peeled off the vital bark from around the main trunk, girdling the trees and leaving behind a slowly dying forest. Felling 25-year-old trees for about 35 pounds of bark was also wasteful: Up to 95 percent of their weight was being left to rot in the field. Landowners were paid just $30 for a tree’s worth of bark, which was then sent overseas for processing. Chile was destroying its natural heritage for a pittance, and when San Martin met with forestry experts, they asked if there was anything he could do to help.

Back in his lab, San Martin began to study the chemical makeup of the tree’s fibers. Although saponins are most abundant in, and easiest to extract from, the bark, he found he could also obtain them from the trunk and the branches. Using this method, a single tree could replace five or six destroyed in the past. He also found that through judicious pruning, one could improve the condition of the scraggly stump-sprout trees left behind from previous clearcutting.

San Martin hoped to develop a soapbark-processing industry in Chile, and he set out to find international buyers for saponin. With the help of a university loan, he started a company called Natural Response and spent several years hunting for customersâ€"with little luck. With three kids to support, his bank account was shrinking, and interest on the loan was piling up. “I had one car from 1970-something with no brakes,” San Martin said. “I was bankrupted, honestly.”

In 1995, one of San Martin’s employees sent a fax to Paul Hiley, whose business at that time revolved around saponins from Mexican yucca. Within days, Hiley was stepping off a plane in Chile. San Martin took him to the university to show him a small barrel of highly purified, powdered white saponin. “He was proud of his little production facility,” Hiley told me.

But Hiley wasn’t interested in the high-grade stuff back then. He pointed at the cola-colored syrup that San Martin had yet to process. The crude extract was exactly what Hiley needed for his clients in the soft-drink business. “I’ll buy 10 tons,” Hiley said. He purchased that first shipment and then wired San Martin an extra $300,000 to partner with him and expand the business.

San Martin was still in a hole: He needed his extract to be a pure liquid, but it came out cloudy, filled with microscopic particles. Every attempt to refine it in the factory negated the cost-saving efficiencies he’d achieved in the field, and he wasn’t hitting the price targets he had promised Hiley. “I couldn’t say, ‘Paul, pay me 12, and you sell it at 11.’”

In the late 1990s, while visiting his children in Montpellier, France, he stopped in a bookstore. He plucked a two-volume treatise on wine making off the shelf. “Why did I pull that out? I don’t know,” San Martin said. As he started reading, he realized that the food-safe processes that vintners used to remove clumps of tannin from their fermented grape juice could be applied to soapbark extract: “I rushed to Chile with that thing.” It was his Eureka moment.

It was also his introduction to the Jevons paradox, the frustrating phenomenon by which technological increases in efficiency fuel increased demand. With San Martin’s innovations, the annual harvest of Quillaja declined from a high of 20,000 tons per year to around 5,000 tons. Then it started creeping up, exceeding 11,000 tons in 2012. The annual harvest is now approaching 20,000 tons again, according to Hiley.

To some degree, this was San Martin’s own fault. He couldn’t stop inventing new applications for the soapy substance. He discovered that it could be used as a bio-pesticide for nematodes on grapes. (Saponins likely evolved as a defense against pests.) Then he found that it reduced the toxic mist of sulphuric acid that rises out of copper-extraction tanks.

San Martin sold his remaining stake in the business to Hiley in 2005, and moved to Berkeley in 2013. Over the past 15 years, the fastest-growing part of Desert King’s business has been their saponin-based animal supplements, which can improve growth rates and reduce Salmonella infections in chickens. Desert King says its saponins, manufactured and sold by major feed companies, are now fed to more than 50 percent of antibiotic-free poultry in the U.S. The supplements are also showing promise in preventing infections of viruses and parasites in fish, including farmed salmon, a big business in Chile.

Everyone at Desert King was enough of a believer in Quillaja’s juju that they began putting a few drops of extract into their coffee or orange juice each day to ward off disease. “It tastes like soap,” Damian Hiley told me. Whether this did anything for their health was doubtful, but the profits were undeniable: By the late 2000s, the company was bringing in tens of millions of dollars per year. Then, three years ago, the Food and Drug Administration gave QS-21 the nod of approval. “Everyone was knocking on our door,” Damian said.

It is often said that vaccines are one of the most successful public-health interventions in human history. They are also bad business propositions. Two-thirds of vaccines fail in clinical trials. Once approved, they are often less profitable than drugs for cancer or rare diseases. In 2004, just five companies were manufacturing vaccines for Americans, down from 26 in 1967.

Since then, vaccine makers have lost money trying to develop vaccines for Zika and Ebola, because the outbreaks subsided and government funding dried up. When the new coronavirus landed on U.S. shores, the major vaccine makers sat on the sidelines for weeksâ€"a situation that Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, characterized as “very frustrating” during a February event at the Aspen Institute.

Novavax, however, was the eager kid waving a hand in the back of the room. Founded in 1987, the company had so far failed to bring a vaccine to market, and stayed afloat through private investment, research contracts, and licensing deals. Last year, its clinical trial for an RSV vaccine was a bust. Tens of millions of dollars went down the drain, employees were laid off, and two development and manufacturing facilities were sold. Soul searching ensued. “If you get bad data, everybody thinks you’re a failure,” Gregory Glenn, the company’s president of R&D, says. “I have PTSD from that.”

They got a gold star for attendance, though. Over the past decade, Glenn’s scientists have repeatedly pursued vaccines for emerging diseases including swine flu, Ebola, and Middle East respiratory syndrome, another coronavirus. Their laboratories maintained a stock of cells originally plucked from the ovaries of caterpillars in the 1970s. These cells were little factories that could be induced to pump out just about any kind of virus protein, including the coronavirus spike.

Before Glenn joined Novavax in 2010, the company wasn’t a believer in adjuvants, arguing that an unadjuvanted flu vaccine would be faster to win FDA approval. But Glenn, a pediatrician who had worked in the laboratory of an adjuvant expert at the Walter Reed Army Institute of Research, thought it was time to embrace them.

Adjuvants had undergone a renaissance, and QS-21 was its poster child. A crude saponin extract had been used in veterinary vaccines since the 1950s, but it was too toxic for humans, causing red blood cells to burst. In the 1990s, a researcher named Charlotte Kensil separated some of the 50 or so saponins in Quillaja saponaria extract, then tested them individually in mice. QS-7 was a potent adjuvant, but there wasn’t a lot of it. QS-18 proved to be the most toxic. QS-21 was relatively mild and generated both an antibody and a T-cell response.

GlaxoSmithKline licensed QS-21 from the maker. In order to tune the immune response, it combined QS-21 with a second adjuvant, a fat-like substance derived from Salmonella bacteria. Three years ago, this potent combo came onto the market in their shingles vaccine, called Shingrix. “That vaccine hit the ball out of the park,” says Janet McElhaney, an expert on aging and immunity at Health Sciences North in Ontario.

Shingrix conferred immunity on 91 percent of people over 70 years old, more than double that of a previous shingles vaccine. Last year, the same adjuvant combo was rolled out in parts of the world in GSK’s malaria vaccine, Mosquirix, and it is also a component of a late-stage-tuberculosis vaccine candidate.

Novavax, meanwhile, obtained the rights to a different saponin-based adjuvant, now called Matrix-M, which was developed by a Swedish researcher who had worked on that HIV vaccine San Martin first read about. Recently, Novavax has tested Matrix-M as part of its NanoFlu vaccine, which not only provided a stronger antibody response than existing flu vaccines but also offered cross-protection against multiple strains of influenza.

By the time COVID-19 arrived, the company was finishing up Phase 3 clinical trials of NanoFlu, which would demonstrate Matrix-M’s safety in 2,650 human subjects. In February, it began testing its COVID-19 vaccine with Matrix-M in animals, and the results coming out in the spring were promising. “We all need to be humble in front of trying to make a billion doses,” Glenn told me a couple of months ago. “But, so far, things have gone exceptionally well for us.”

No matter how effective a COVID-19 vaccine is, it won’t put a dent in the pandemic unless it can be produced on a massive scale. The downside of an adjuvant is that it adds one more link to the global supply chain, one more crucial connection that can be broken. And by the time Novavax was preparing for its first human tests, the Hileys were struggling to keep their doors open.

As COVID-19 started to circulate in the U.S., Desert King had to provide van transportation for its 220 Chilean workers to replace the public buses forced out of service due to pandemic restrictions. The company pulled strings with local officials for lockdown waivers, and solicited letters of support from Coca-Cola and GSK. By the middle of May, however, they no longer had enough employees coming to work to run their boilers, and they had to shut down. “Every company had the same sob story,” Damian Hiley said. “Maybe our messaging was falling on deaf ears.”

The impending closure triggered a red alert at Novavax’s headquarters, some 5,000 miles away. The company sent an official letter to Chilean President Sebastián Piñera, requesting his assistance to help them put a halt to the pandemic. A couple of days later, Desert King got the exemption it needed and was cranking out Quillaja extract around the clock. It also resolved to break ground on a new pharmaceutical manufacturing suite. In July, Novavax made headlines with a $1.6 billion commitment from Operation Warp Speed, the largest award at the time.

The Hileys knew that their harvesting practices in Chile were now under the global microscope. During my visit to Desert King’s headquarters, Damian showed a brand-new company video that included drone photos of vast stands of Quillaja, an upbeat soundtrack, and the soothing voice of a female narrator describing the company’s “sustainable objectives” and “responsible management.”

“We hadn’t had to do this before,” he said of the public-relations campaign. “We really want to make sure that people understand, especially in Chile, that we are doing this in a responsible, sustainable, renewable, kosher, dotting-every-i-and-crossing-every-t way.”

“I’m not an environmentalist by any stretch,” his father added. “As a capitalist, which I am, if I can make a buck, honestly, legally, and help people and not damage Mother Earth, well, check, check, check.”

Desert King doesn’t own much land in Chile. Instead, they make agreements with local landowners. Their harvesters prune trees at intervals ranging from seven years to 20, using San Martin’s low-impact methods. They peel off all the bark they need for vaccines and use the rest of the tree biomass they harvest for their other businesses. They have mapped and tested thousands of trees to track their saponin makeup, which varies greatly by location. “Any fool can go to Chile and harvest a few trees,” Damian said. “The problem with QS-21 is that out of 100 trees, maybe five of them have the right profile.”

As part of its long-term growth plan, Desert King gives out seedlings to Chilean landowners and encourages them to plant native Quillaja instead of exotic eucalyptus and pine. The country’s forestry managers have also distributed Quillaja seedlings around the countryâ€"139,000 last year, more than any other species. Five years ago, Desert King invested in a plantation specifically for their pharmaceutical contracts, using cloned trees high in QS-21. Those trees are now large enough for harvesting, but the company still has to ensure that the adjuvant produced from their extract will be equivalent in makeup and quality to what they were using before.

Desert King plans to establish additional plantations in Chile, and possibly elsewhere, to match the needs of Novavax’s adjuvant, but any seedlings planted now will take years to produce harvestable barkâ€"which is why San Martin’s work on Quillaja leaves is so critical. “Who knows what’s going to happen in Chile?” Damian said. “What if they say it’s illegal to harvest Quillaja?” The current supply is vulnerable in other ways: In January 2017, the country had the worst fires in its history, which burned more than a million acres of central-south Chileâ€"a region home to Quillaja trees.

Such concerns have provided an opening for Desert King’s competitors. Tyler Martin of Adjuvance Technologies told me that they can increase the adjuvant yield from a tree by a factor of a hundred, using its semisynthetic version of QS-21. Meanwhile, Agenus is now working with another company to grow QS-21 inside vats filled with cultured plant cells. Its partner, Phyton Biotech, used this method to wean the world off the Pacific yew, and is now the world’s largest supplier of paclitaxel.

The other drugmakers partnering on a protein-subunit vaccine in Operation Warp Speed aren’t taking any chances with the saponin supply chain. GSK and Sanofi are using GSK’s less-potent oil-in-water adjuvant. It, too, contains a natural productâ€"an oily compound from shark liversâ€"but it is unlikely to face a supply constraint and has already been stockpiled. “That’s the way I would have gone,” Carl Alving, a retired Army adjuvant expert, says. “It’s much less expensive and much less difficult to formulate and put together in a very rapid period of time.”

Damian Hiley brushes off the suggestion that the world shouldn’t rely on Quillaja for a COVID-19 vaccine. “That’s complete bullshit,” he said. “There’s plenty of material.” What his naysayers don’t realize, he said, is that San Martin recently revamped their process of extracting saponin from bark, allowing the company to double its efficiency. The company also believes Chile’s forests can sustain four times the current annual harvest. If supplies become tight and saponins are needed for multiple vaccines, they’d just shift production away from, say, chicken feed. “Maybe one day,” he said, “we’ll have to say to those customers, ‘Sorry, guys, we’re no longer supplying this.’”

On august 4th, Novavax released the first data from its initial safety trials, which had tested the vaccine on 131 human subjects. The immune response was stellar, activating both antibody and T-cell production. “This is the first time I’m looking at something and saying, ‘Yeah, I’d take that,’” the Cornell virologist John Moore told The New York Times. As with other COVID-19 vaccines, some patients had experienced headaches, fatigue, and swelling at the injection site, but there were no serious side effects.

Novavax’s protein-based vaccine will likely only arrive on the U.S. market after the faster-to-develop RNA vaccines from Moderna Therapeutics and Pfizer have received emergency approval. But unlike those gene-based vaccines, which require ultra-low-temperature freezers, protein-based vaccines can be stored in refrigerators, simplifying global distribution. Novavax has entered Phase 3 trials in the United Kingdom, while interim data from their Phase 2 trial in the U.S. is expected by the end of the year. Japan, Canada, South Korea, and the United Kingdom have now secured purchase agreements with Novavax, and the company expects to be able to produce 2 billion doses of vaccine annually in 2021.

San Martin wants a safe, effective vaccine as much as anyone on Earth. While I was in Berkeley, he told me that two of his old friends from Chile had recently died from COVID-19. He and his wife had decided to temporarily increase their social-distancing measures. Six feet wasn’t far enough; he wanted 10.

He is looking forward to being able to have a beer with friends, listen to live music, and talk about old times with Paul Hiley without wearing a mask. At times, the thought crosses his mind that he’s the only person who can save the trees in Chile. He brushes such anxious thoughts aside, though, because they prevent him from focusing on the science.

As San Martin and I stood next to Berkeley’s soapbark trees, a groundskeeper rolled up behind us in a maintenance vehicle, a weed whacker and trash can in its bed. “What are we doing?” she hollered.

San Martin spun around, a bouquet of leaves in his hand. “I’m taking a sample,” he said. “This tree has some compounds that are now being used in the best candidates for the COVID vaccine.”

“Wow! That’s amazing,” the woman replied. “We’ll have to plant a lot of those, huh?”

We took a moment to laugh, and to appreciate a brief social connection in dark times. The woman zoomed away. San Martin turned back to the tree with a serious look in his eyes. He craned his neck up toward the drooping branches overhead, then back at the promising leaves in his hand. “Okay,” he said. “So, here we go.”

BRENDAN BORRELL is a Los Angelesâ€"based writer. He is currently working on a book about the coronavirus-vaccine race.

[Dr. MD MD]

The Last Giraffes on Earth
The planet’s tallest animal is in far greater danger than people might think.

Story by Ed Yong

The giraffe is nearly down. Two men have stretched a thick black rope in front of the animal, to trip her up. The giraffe hits the rope, and the plan seems to be working until she gains a second wind and breaks into a fresh run. Her body sways backward and forward like a rocking horse being pulled along on a dolly. Six more people grab onto the ends of the rope, and the group runs behind her, holding tight, pitting their meager strength against her weight. It would be no contest, were her veins not coursing with tranquilizer. She loses her footing and careens forward, her legs splaying out behind her. But her seven-foot-long neck still stretches resolutely skyward. A woman leaps from behind her back, collides with her neck midair, and rugby-tackles it to the ground. People run over, carrying a hood and a drill. The giraffeâ€"an emblem of verticalityâ€"is now fully horizontal.

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The team of people who have drugged, tripped, and tackled the giraffe is a mix of scientists, veterinarians, and rangers who study giraffes in the few parts of the world where the animals still live. Giraffes are so beloved and familiar that it’s tempting to think their numbers are solid and their future secure. Neither is true. Giraffe populations have decreased by 30 percent over the past three decades. Only 111,000 individuals remain. There are at least four African elephants for every giraffe. To safeguard a future for giraffes, researchers need basic information about how far they roam. GPS trackers can offer answers, but to get a tracker on a giraffe, one must first take it down.

This is harder than it sounds, and it sounds hard. Etorphineâ€"an opioid about 1,000 times more potent than morphineâ€"is the preferred anesthetizing agent, but some giraffes resist doses that would knock out an elephant. And unlike elephants, many of them respond by breaking into a run. Also, etorphine depresses a giraffe’s breathing, reduces its heart rate, and increases its blood pressure. The drug is tolerable in the short term, but after only 15 minutes, it can cause problems for an animal whose heart must pump blood up a seven-foot neck. A darted giraffe must be tripped as quickly as possible. Once it’s horizontal and restrained, the team can immediately reverse the etorphine with a second drug, while attaching a tracker.

“You want it to stand up as soon as possible,” says Sara Ferguson, a vet for the Giraffe Conservation Foundation, and the woman who body-slammed the giraffe’s neck. Though they look slender, giraffes are massive, sturdy animals. The head and neck alone can weigh 600 poundsâ€"more than a large black bear. When males fight over mates, they swing their necks in long arcs to bludgeon each other with their reinforced heads. Their necks can take the impact of one airborne vet.

Until recently, giraffes have suffered from surprising scientific neglect. Few researchers have studied them in the wild, so even basic aspects of their lives remain mysterious. Perhaps that’s because giraffes live in what researchers suspect are protean societies lacking the cohesiveness of elephant herds or lion prides. Whatever the reason, one of the world’s most conspicuous creatures has somehow been overlooked. The same goes for its impending extinction. And without fanfare, many other major animal groupsâ€"insects, birds, and amphibiansâ€"have also declined precipitously. Quite a few of the public’s favorite wild animals, including lions, cheetahs, and gorillas, are in greater peril than is widely realized. But, according to a 2018 study, this gap between rose-tinted perceptions and dire reality is greatest for giraffes. Their prevalence in the zeitgeist has masked their disappearance from the planet. In 2010, eight times as many Sophie the Giraffe teething toys were sold in France alone as there are actual remaining giraffes. In 2016, the number of Britons who watched a giraffe kick a lion in Planet Earth II exceeded the giraffe population by more than a hundredfold. That same year, the International Union for Conservation of Nature reclassified the giraffe as “vulnerable” to extinction. Even this grave assessment might be too optimistic: New genetic evidence suggests that the giraffe may actually be four separate species that have been evolving on their own for 1 million to 2 million years. The iconic animal faces several falls instead of one.

Ferguson and her colleagues are trying to find out how the giraffe became so endangered, and how to save it while they still have time. They’re traveling across the few parts of Africa where giraffes still exist, to affix trackers to several hundred individuals. The process is exhilarating, but also dangerousâ€"for both humans and giraffes. Julian Fennessy, the foundation’s founder and director, only recently recovered from three broken ribs and a dislocated shoulder, sustained when the neck of a stumbling giraffe fell across his torso. He sometimes has to reassure tourists on safari that he is not a poacher. On occasion, his team has had to free tranquilized giraffes that got stuck in trees, or steer them away from rivers.

Imagine you are one of these giraffes. You are the tallest thing for miles. Everything about you defies gravity. Your hips and shoulders are level with the tops of many acacia trees, which to shorter mammals are the world’s ceiling. Your head rises 19 feet into the air. As your sharp gaze sweeps over vast swaths of savannah, you see five jeeps driving toward you.

Read: Giraffes edge closer to extinction

Riding in the jeeps, we head toward a group of giraffes. I’m in one of the back jeeps, standing next to two men from the Kenya Wildlife Service. We watch the animals graze quietly, using their long, prehensile, bizarrely bluish tongues to rip foliage from the trees’ thorny branches. Giraffes evolved from short-necked ancestors, and whether they stretched to feed on leaves that are beyond the reach of competitors, or to swing their head with greater force during ritual combat, or to keep an eye on approaching predators, they ended up with a neck that’s more than twice as long as that of any other living animal. They’re tall in a way that the planet hasn’t otherwise seen since the dinosaurs’ reign. On Kenya’s Laikipia Plateau, where the landscape is all flat-bottomed clouds and flat-topped acacia trees, they tend to stick out.

From the lead jeep, Dominic Mijele, an experienced vet from the Kenya Wildlife Service, selects a femaleâ€"the one that Ferguson will later tackleâ€"and uses a tranquilizer gun to shoot a pink-tufted dart at her. His aim is perfect. The dart embeds in the giraffe’s right shoulder and delivers its etorphine payload. The female twitches nonchalantly, as if bitten by a horsefly, and returns to eating. For a few minutes, nothing happens. Then, she starts running.

Unexpectedly, a calf runs behind her. It can’t be more than two weeks old, but it was born taller than most of the people pursuing it. Its presence complicates matters, but it quickly takes itself out of the equation by crouching and hiding, flattening its neck in a most un-giraffelike way. Its mother, meanwhile, leads the jeeps on a chase.

We tear after her, swerving between the trees and occasionally bulldozing them. When the terrain allows, we leap out and sprint after her, ducking branches covered in inch-long thorns. If the giraffe falls backwards, she risks serious injury to her head and neck. Taking a page from The Empire Strikes Back’s playbook, the team tries to wrap ropes around her legs and guide her into a safer forward stumble.

After Ferguson brings her down, four rangers sit astride her neck like bobsledders. Someone slips a hood over the giraffe’s head so she can’t see. Another threads a device into a nostril to collect data on the animal’s breathing. More than a dozen people surround the giraffe to measure her, collect samples of her skin and DNA, and pick off ticks, while sloshing water on her side to keep her cool. With the effects of the etorphine reversed, the animal is fully conscious, but calm. Nonetheless, everyone stays back from her long and powerful legs, which can deliver a lion-disemboweling kick.

2 photos: scientists, veterinarians, and giraffes
A whole crew of scientists and veterinarians is required for the giraffe-collaring process, during which the 1,500-pound animal is kept awake and stabilized. (Tyler Schiffman)
At the giraffe’s head, Fennessy kneels down and begins to attach the tracking deviceâ€"a black box, no bigger than a pack of cards. Some people call it a collar, but it’s not meant for the animal’s neck. Nearly two decades ago, when Fennessy’s team first tried tracking giraffes with GPS, it used gigantic collars adapted from those used on elephants, but the giraffes just bent their heads and slipped the devices off. It also tried fixing the collars in place with elastic straps, but feared this might restrict the animal’s esophagus. Head harnesses weren’t quite universal enough to fit the unique head shapes of each giraffe species, and creating one for each species was too expensive. Eventually, the team hit upon the perfect solution: Fix the tracker to a giraffe’s ossicones, the pair of hornlike structures on top of the animal’s head.

Giraffes hit each other with their ossicones, so these structures are thick, bony, and insensitive, with only one nerve at their base. When Fennessy drills a hole in one of them, his subject barely reacts. He threads a steel bolt through the hole, and fastens the unit in place. Once it’s secure, the hood is removed, the men on the neck get off, and the giraffe lifts her head. The seven vertebrae in her neckâ€"the same number as in a human’sâ€"are connected by ball-and-socket joints like those in our shoulders, so instead of lifting up like a rigid beam, her neck snakes upward in an almost reptilian way. She staggers up, and Fennessy slaps her on the rump to get her moving. After a few unsteady steps, she walks off. Somehow, whether through her reportedly excellent (but seldom tested) eyesight, or through low, infrasonic calls (that have long been suspected but never documented), the mother detects her hidden calf, and makes a beeline toward it.

Video: The World Without Giraffes

When i’d arrived in kenya, I’d assumed that the primary threat to giraffes was poaching. And people do kill giraffes, with guns, bows, and spears. They snag their legs using circular traps lined with thorns or metal shards. They strip the wires from vehicle tires to make snares that they dangle from trees or scatter on the ground. In Uganda, Ferguson desnared dozens of giraffes just last summer.

“We’ve swept an area and come back literally the next day to find new snares,” she says. Four of the 11 giraffes the team collared in Kenya in 2017 were likely poached, “a much higher rate than anyone suspected,” says Jared Stabach of the Smithsonian Conservation Biology Institute. Unlike elephants, rhinos, and pangolins, giraffes aren’t poached to supply a big, illegal, international market in body parts. Instead, in countries like Kenya, people mostly kill giraffes for their meatâ€"to feed themselves, their families, their villages. “They’re a shitload of food,” Fennessy says.

Poaching is only one threat among many to giraffes. It’s a significant threat, it’s easy to visualize, and it offers an antagonist to focus onâ€"but there are less direct and dramatic ways of killing a giraffe.

From July 2019: Ed Yong on caring for the last of a species

Since the 1970s, Kenya’s human population has more than quadrupled, and it is projected to double again by 2050. Livestock populations have also ballooned, and now collectively outnumber wildlife biomass by a factor of eight. Not coincidentally, wildlife numbers have declined by about 70 percent. As the human world expands, the world for wildlife contracts. Giraffes are left with few resources as more land is dedicated to agriculture and livestock. Humans’ and other animals’ very presence can make life harder for giraffes. They flood the landscape with loud noises, divert water for irrigation, and overgraze the land. “They chop down trees for charcoal, so there’s nothing to eat,” says Symon Masiaine, who leads a team called Twiga Walinzi, or “Giraffe Guards.” “The livestock disturb [giraffes] from grazing. The dogs chase them.” People block giraffe migration routes with fences and roads.

The story of the giraffe’s decline is not one of villainous poachers and murdered animals. It is a story of two species dealing with the same crowded, rapidly changing world.
Growing human populations and the fragmentation of the landscape are the biggest culprits behind the decline of giraffes. David O’Connor, who researches population sustainability at San Diego Zoo Global, points out the problem on three maps. The first shows where giraffes lived in the 18th centuryâ€"a broad, continuous brushstroke sweeping over much of Africa. The second shows their current whereaboutsâ€"a few pathetic splotches totaling just 10 percent of their former range. The third superimposes all of Kenya’s ongoing and planned development projects onto that shrunken range, which becomes further fragmented. The pattern reminds me of the one I’ve been staring at for days: the islands of tawny brown on a giraffe’s hide, separated by unbroken white lines. It’s as if the giraffe’s woes have been etched onto its skin.

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“When the land is not open, it reduces the animals’ ability to be flexible to change,” Fennessy says. And change is certainly upon them. Kenya’s temperatures are set to rise by an estimated 2 degrees Celsius by 2060. Giraffes, already confined to the driest regions that are untouched by agriculture, must now contend with shorter rainy seasons, more erratic rainfall, and more severe and prolonged droughts. Pastoralists, who once had free rein of Kenya’s lands, must deal with the same challenges. Decades of decisions by British colonialists and the postcolonial government have severely restricted their lifestyle. Constrained and marginalized, they now compete with giraffes for the same dwindling resources, through the same climatic upheavals. Conflict is inevitable, and the giraffes almost always lose.

“All of these things make the animals immune-compromised and more susceptible to disease,” says Maureen Kamau, a veterinary fellow with the Smithsonian Conservation Biology Institute. Giraffes across East Africa have been known to carry a mysterious skin disease that causes oozing, crusty lesions on their limbs and necks. Other species are experiencing similar problems: In Laikipia, a previously healthy population of wild dogs was all but wiped out in 2017 by a virus that spread from domestic canines.

Read: The quiet disappearance of birds in North America

These combined stresses are especially costly for giraffes, which reproduce only a few times in their lives, and gestate for 15 months. “Anything happens during that period and it’ll lose the young one, and when it’s got all these other threats, it won’t breed,” Fennessy says.

photo of giraffes and their shadows from overhead
Giraffe herds may have a mix of males and females or be segregated by sex. We still know strikingly little about the animals’ range and behavior. (Davis Huber)
If animals cannot move through a fragmented world, humans may have to move them. In August 2018, people living along a particular road in northern Uganda were treated to a peculiar sight: a large green truck with shrubbery strapped to its sides, five Nubian giraffes peering out through its open roof. The driver went slowly so as not to hit any bumps. The giraffes, for their part, were remarkably calm during the 10-hour drive. “We drove past schools, and kids would flood out,” Ferguson says. “It was the first time many of them had seen a giraffe, let alone five driving through their town.”

Nubian giraffes are a subspecies of northern giraffe, and just 2,645 are left in the wild. More than half of those live in Murchison Falls National Park. The Uganda Wildlife Authority has relocated small groups to other protected areas, and all the populations are now growing. But this strategy has limits, because the new and growing populations are still isolated islands in a changing world. And in some countries, the giraffes have nowhere to go. Kenya’s national parks and reserves cover just 8 percent of the country, and most big mammalsâ€"including almost all reticulated giraffesâ€"live outside them. If the giraffes are to survive, they will have to do so in the presence of people.

The trick is to make the presence of giraffes more valuable to local communities than either their flesh or their absence. Consider Niger. In the mid-1990s, it was home to the last 49 West African giraffes, all of which lived outside national parks and on community-owned lands. Conservation groups supported those communities by offering loans, building wells, and providing ecotourism opportunities. Such measures, together with a strict government-enforced ban on killing, brought the West African giraffe back from the brink. Today, 600 of them graze the croplands.

Read: Climate change put animals on an escalator to extinction

In Kenya, many communities have turned their lands into conservanciesâ€"areas where livestock grazing is more carefully managed. In exchange for giving wildlife refuge, some communities receive revenue from ecotourism operators or development programs run by conservation organizations; the state-operated Kenya Wildlife Service offers veterinary support and ranger training. This model, first developed decades ago, has bloomed exponentially in the past two decades, such that community conservancies now cover more land than Kenya’s national parks.

photo: scientists and plane
Davis Huber
Most conservancies aren’t fenced, though, and animals can easily move beyond them. “They come back with injuries,” says Mijele, the vetâ€"if they come back at all. Each conservancy is still a fragment, but some are starting to connect, creating large, continuous refuges. The famous Maasai Mara National Reserve is now surrounded by community conservancies in the northern areas that cover almost as much ground as the reserve itself. The Northern Rangelands Trust is an especially successful umbrella group of 39 conservancies that cover more than 10 million acres. Slowly, the land is being defragmented.

The collaring team hopes that its data can help. By showing where giraffes go, the team can help conservation groups prioritize areas that need the most protection. Jenna Stacy-Dawes, a research coordinator from San Diego Zoo Global, shows me a map of the privately owned area where the team has tagged giraffes. Squiggly colored lines snake across its borders, each representing a tracked giraffe. Most eventually roam outward, into community-owned lands. One yellow line heads north and abruptly ends. The giraffe’s tracker stopped transmitting in June 2017, just a few weeks after it was attached.

The giraffe guards went up to investigate, and discovered that the giraffe had been poached for food near a primary school in Morijo. The team responded by organizing education days focused on giraffe conservation, starting wildlife clubs, and donating desks and textbooksâ€"the school’s first educational materials. “People there are now some of the biggest supporters of giraffes,” Stacy-Dawes says. “And they’re seeing that giraffes are providing for their families in other ways.” The story of the giraffe’s decline is not one of villainous poachers and murdered animals. It is a story of two species dealing with the same crowded, rapidly changing world. Only through coexistence will the tale have a happy ending.

photo of two giraffes
Davis Huber
Toward the end of the collaring expedition, I ride with Steve Lenguro, a vet from the Kenya Wildlife Service. He points out a giraffe, but all I see is a tree. Then the tree turns to look at us.

Over three days, the team fixes tracking units to seven giraffes. Every collaring is challenging in its own way. On one occasion, the tranquilizer dart doesn’t fully penetrate its target, and Mijele is forced to pick a second. The darts fall off both animals, and they run into a grove of trees that are tall enough to obscure even their lofty profiles. The jeeps lose track of them, and the convoy is forced to drive through thick bush. Finally, one of the animals breaks into the distinctive etorphine-induced run, and vaults a ditch that the trucks can’t pass. We get out and run again, in sweltering mid-morning heat and through thick grass. David O’Connor twists his ankle. The rangers get the giraffe down, and Fennessy yells for someone to inject the reversal drug, but it’s in a jeep that became separated from the main group.

Fennessy is visibly and audibly annoyed about how long it takes for the drug to arrive. He’s not pleased that some of the rangers are kneeling on the animal’s neck instead of sitting on itâ€"a position that he says places less pressure on joints and blood vessels. The Kenyan team, meanwhile, finds Fennessy’s attitude patronizing. “We’ve done this hundreds of times before,” Lenguro tells me. After some tense debriefings, egos deflate, and the team settles into a groove. It doesn’t lose a single animal.

The seventh and final giraffeâ€"a young maleâ€"doesn’t even run. It takes the dart, walks 100 yards, and slumps against a tree. It looks preposterous, its body slack but supported, its neck stuck in the branches. The long thorns can’t pierce its thick skin, but they probably aren’t pleasant either. The etorphine is still coursing through his body, and clearly having a stronger effect than anyone anticipated. Working urgently, the team wraps a rope around the body and, with at least six people pulling, drags the giraffe to the ground. The drug is reversed, the hood goes on, and everything proceeds as planned.

Imagine what a shock it would be to be that giraffe, to come to in a posture that you haven’t experienced since you dropped out of your mother and first got to your feet. Whatever was fogging your senses has cleared, but your eyes are still covered. You lash out with a hoof, connecting with nothing but air. A loud drilling noise rumbles through your skull, and you lash out again. Your vision returns. You lift your head, snake your neck upward, and rise to your proper placeâ€"upright, aloft, above all things.