Part the First: How Not to Study a Disease – Update. We have covered the Amyloid Cascade Hypothesis of Alzheimer’s disease (AD) here previously. Sylvain Lesné, who altered images in a now retracted paper on AD, has resigned his tenured faculty position at the University of Minnesota. Charles Piller, who wrote the long article in Science that led to this inevitable final act, has now published Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. The former Professor Lesné engaged in scientific fraud and he will now find other things to occupy his time. That is a personal tragedy, entirely self-inflicted.
As amply demonstrated by Karl Herrup, it is true that the ACH has not been productive. And its champions have been arrogant. The opportunity costs have probably been large, and they may represent an unknown tragedy. But in my quick read of the book, I do think Piller overeggs the pudding a bit. There has been much good and important research on AD, even from the time of Dr. Alzheimer. The entire field is not corrupt. The situation can be recovered, but only if American biomedical research is resilient enough to weather the current storm that began on January 20th.
Part the Second: What’s New with the Pandemic? Contrary to current conventional unwisdom, vaccines are unlikely to be the answer to COVID-19. That leaves us with other approaches. One or more of them will work, but our biomedical science must get better, as in a current paper that describes a very promising “Antiviral covalent ACE2 vesicle spray.” This work is based on extracellular vesicles (EVs), which are relatively new to biology – we should always remember that as our sphere of knowledge grows, so does the boundary of what we do not know. Those who predict the end of science (with the inimitable Sabine Hossenfelder to the rescue) are no more prescient than those who predict the end of history. ACE2 is the binding protein that SARS-CoV-2 latches onto in its first step for entering its target cell. In this research, scientists developed nanovesicles that bind to the virus irreversibly and prevent it from infecting cells. There is a lot of work left to do, but this is clearly the right approach to a respiratory virus that cannot, by all previous research, be completely tamed by a vaccine. Very technical but paper is well done, summarized in Figure 1.
The FSY-ACE2-NV acts essentially as a circulating suicide sponge: Once the virus binds to the sponge it has reached its terminal destination. This sponge is not dependent on the SARS-CoV-2 variant. It is easy to imagine an effective nasal spray to prevent SARS-CoV-2 transmission and to treat the disease. Another Project Warp Speed, please! This time on an intervention that has legs. And no, it is not an accident this research was done in Beijing and Guangzhou. Young Americans who want to be scientists should skip French, Spanish, and German and learn Mandarin? See below.
And yes, masks still work! From the outstanding scientists who know, but have been scorned when not ignored. A guide for the perplexed:
Remember: Do not be bashful about keeping away from large indoor gatherings and wearing masks when necessary! Last month seven coworkers in my office of eighteen (39%) had COVID-19, most for the second or third time. Other respiratory viruses have not let up since October. A close colleague and friend died late last year of an apparent heart attack after a two-year battle with long Covid. She told me on more than one occasion that COVID would kill her. Alas, she was a veterinarian was right about everything.
Part the Third: What’s Up with American Science? This is really too depressing for me to ponder at the moment, but working staff and scientists at CDC, NIH, NSF, USDA, NFS, NPS, NOAA, and FDA are on the way out, apparently, whatever the courts may eventually decide. I do know from talking to friendly acquaintances that morale is shot, which is probably a main point of this episode of “Move Fast and Break Things” brought to you by The Oligarchy. Will morale return? Maybe. But trust is another matter. What the present Administration does not understand is that most of these people are pursuing a calling. But vocation has no place under the Neoliberal Dispensation, which is all about building your personal brand, faux gold-plated preferred in the current political climate , which is all about building your personal brand, faux gold-plated preferred in the current political climate.
Graduate programs are on hold across the country, and many are refusing to make formal offers after verbal assurances have been given to candidates in a very competitive market for the best applicants. This is potentially catastrophic. Once the pipeline is broken, it will be difficult to repair. These future graduate students have been working for years to get to this point. Preparation for graduate school in the sciences is not unlike preparation for medical school. No one gets into this kind of graduate program as an afterthought…“Hmm, college has been fun but what will I do now? I know, I’ll go to graduate school!”
There are prerequisites! For a biomedical sciences program at a leading research institution, these requirements include advanced courses in math, computer science, chemistry, physics, and biology. And just as important, experience! No leading graduate program accepts students who have not put in significant time in the lab, with results. Particular results do not matter). The test is whether the applicant can withstand the tedium while maintaining the attention to detail that scientific research requires. A biomedical scientist can work for months to complete one experiment. And every one of us has gotten to the moment of truth and been afraid to actually look at the result. If you can’t stand the disappointment, stay out of the lab! But when the result is positive, the high can last for the next six months. It is was a strange but rewarding life.
Which makes this particularly galling: Cancellation of NIH summer internships disrupts ‘vital’ training program for U.S. scientists. This is where thousands of American students have learned how to “do science” for as long as I can remember. And I got my first research job when Gerald Ford was President. Now, Satchel Bell of Colorado College says “the uncertainty is making him consider career options other than the M.D.-Ph.D. path he had been planning on. ‘With less money and less ways to get into the field, I’m thinking more industry, maybe pharmaceuticals…My priorities are shifting.’” This is exactly what we do not need, one of our future scientists tweaking the sixth generation of GLP-1 receptor agonists to extend the previous patent. Satchel Bell is the perfect applicant for this program. He attends an excellent liberal arts college, which means he will have research opportunities but probably not the kind that test one’s stamina and commitment for the long term.
In other news, according to a colleague who sits on an NIH study section (grant review panel) their meeting has not been rescheduled, and the knock-on effects will be devastating as grant applications and renewals are paused. Few academic institutions have the wherewithal and probably none of them has the desire to make up the difference. Graduate students and postdocs live from paycheck to the week before the next paycheck. This is why basic scientists feel so rich when they finally get a stable job: They can eat something other than ramen noodles on the 28th of the month if they want to. However, some do seem to get addicted to ramen just as polar explorers got to the point that they continued to eat pemmican even after returning to “civilization.”Part the Fourth: Ecologists Doing Science and Having Fun. Birds documenting the Anthropocene: Stratigraphy of plastic in urban bird nests:
The amount of plastics produced annually continues to grow. Of all the plastics ever produced, 79% is still with us, as they remain in landfills or in the natural environment (Geyer et al., 2017). The disruption driven by our collective human activities on Earth may result in a new geological epoch: the Anthropocene (Crutzen &Stoermer, 2021). This contemporary period in the geological history of planet Earth is defined by the impact humans have on our natural world and is already a firmly established term in environmental sciences. (Single use) plastic may be used as a global marker for the Anthropocene, which allows plastic items to be used as “index fossils” to date with accuracy sediment layers within the Anthropocene epoch (Corcoran et al., 2017)…
Indeed! The following figure is telling, about the breeding habits and ingenuity of the common coot and our capacity for defiling the Earth.
In the current political climate, this research undoubtedly will be considered frivolous, but urban ecology will become increasingly important in the coming Inconvenient Apocalypse. Maybe these avian architects can teach us something.
