New attack on cancer? (in mice)

Cancer cells delete the part of their own DNA that normally keeps them from reproducing out of control. Bad news (from the cancer’s viewpoint)? This deletion also removes some genes that any cell needs to survive. Good news (from the cancer’s viewpoint)? The cell has a backup version of the genes needed for survival.

So what happens if we turn off the backup genes? Normal cells don’t notice, their first set of genes is working just fine. But cancer cells are now screwed.

Again, this is in mice and may work differently in people. And it’s a very small study. But it might be very important…

Lots of articles on MTHFD2 inhibitors, but this one is clearer than most. 550 words: https://scitechdaily.com/cancer-weakness-discovered-new-method-pushes-cancer-cells-into-remission/.

The Atlantic’s top 10 breakthroughs of 2022

It’s been an amazing year in science, medicine, technology. The Atlantic has an article on what one writer thinks will be very important. Many of these have not really made the news (partly because many of these are the beginnings of breakthroughs and not yet available). Categories:

The Generative-AI Eruption
Large language models, such as ChatGPT, can answer complex questions, spit out bespoke Wikipedia articles in seconds, write song lyrics, and even conjure—admittedly mediocre—essays in the style of well-known writers. ((This has been getting a lot of attention in the past month.))
The Power to Reverse Death (Kind Of)
By pumping an experimental substance into the veins and arteries of animals that had been lying deceased for an hour, Yale researchers got their hearts to start beating again. … If we have the power to reanimate the heart or other organs of the recently deceased, at what point might we be able to reverse sudden deaths? Could we stock hospitals and nursing homes with buckets of the stuff to resuscitate patients? Should every future American household keep some on hand in the event of a terrible accident?
The Power to Synthesize Life (Kind Of)
This summer, scientists grew an embryo in a lab without the use of sperm, or eggs, or a womb. It happened to be that of a mouse. … Using only stem cells, a team at the Weizmann Institute of Science in Israel forged something in a lab that budded a tail on day six, grew a beating heart by day eight, and even evinced the beginnings of a brain.
The Vaccine Cavalry Is Coming
In September, a new malaria vaccine developed by Oxford University scientists was found to be extremely effective… In November, an experimental flu vaccine was found to induce a protective immune response against all known types of flu in animals. ((Italics mine.))
A Snapshot of the Beginning of Time
The exquisite photos could lead us to new discoveries in cosmology…. Behind those lush and dreamy images might lie evidence of what actually happened during, or just after, the Big Bang…. The James Webb Telescope is so much more than the solar system’s most sophisticated camera-zoom function. It is also history’s greatest time machine.
‘Unheard of’ Advances in Fighting Cancer
In a trial with 18 rectal-cancer patients who were prescribed a novel immunotherapy, researchers found that the cancer vanished in every single patient. No, not receded. Vanished. … Months later, a trial of a new metastatic-breast-cancer drug delivered similarly miraculous results.
The Obesity-Therapy Surge
In the 2010s, patients on the diabetes medication semaglutide noticed something interesting: They were losing a ton of weight. And that side effect wasn’t a fluke. Last year, the FDA approved injectable semaglutide for weight loss under a new name: Wegovy. And it’s not the only medication in the pipeline that helps people lose weight without suffering major side effects.
Cracking the Case of Multiple Sclerosis
This year, a team of scientists… reported strong evidence that the Epstein-Barr virus, best known for causing mononucleosis, is the leading cause of multiple sclerosis. Infection with EBV raised the odds of developing multiple sclerosis, or MS, by more than thirtyfold.
Legal Lab Meat
Some breakthroughs are about new rules, not just new technology. This year, the FDA cleared a California company, Upside Foods, to produce lab-grown chicken. It is the first-ever cultivated-meat product to pass this key regulatory hurdle.
New Toys for the Green-Energy Revolution
Fighting climate change will require the deployment of technologies already invented, such as solar panels and wind turbines. But it will also require new inventions in fields like nuclear and geothermal technology. This year, we edged closer to breakthroughs in both categories.

About 2,900 words: https://www.theatlantic.com/newsletters/archive/2022/12/technology-medicine-law-ai-10-breakthroughs-2022/672390/.

CRISPR versus AIDS

AIDS is a particularly difficult infection to treat because it actually infiltrates, and becomes part of, the patient’s own DNA. It’s not easy to edit our own genetic blueprint. But we have new techniques…

In 2019, researchers at Temple University and the University of Nebraska found that using Crispr to delete those regions eliminated HIV from the genomes of rats and mice. A year later, the Temple group also showed that the approach safely removed viral DNA from macaques with SIV, the monkey version of HIV…

The Excision trial will eventually enroll nine participants and test three dosage amounts to determine which is most effective.

Layperson-friendly article: https://arstechnica.com/science/2022/10/a-bold-effort-to-cure-hiv-using-crispr/.

Detailed report: https://www.nature.com/articles/s41467-020-19821-7.

By the way, CRISPR techniques (CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats) are something we learned by studying bacteria, which can be attacked by viruses. They evolved a way to recognize and destroy viral genetic codes, a crude immune system. Researchers first discovered the repeats in 1987 (see Wikipedia), and studied these for years, eventually resulting in a Nobel Chemistry Prize in 2020 for Emmanuelle Charpentier and Jennifer Doudna.

Detecting Parkinson’s by smell

When Les Milne was 31, his wife Joy detected that his odor had changed. And some ten years later, his personality began changing. He was diagnosed with Parkinson’s, and at a Parkinson’s support group, Joy realized that all the sufferers there had that odor. But she had detected it years before other symptoms were noticeable:

Parkinson’s begins slowly, taking years or maybe even decades before symptoms such as tremors appear, Kunath says. “Imagine a society where you could detect such a devastating condition before it’s causing problems and then prevent the problems from even occurring,”

And it’s not just Parkinson’s:

Joy’s superpower is so unusual that researchers all over the world have started working with her and have discovered that she can identify several kinds of illnesses — tuberculosis, Alzheimer’s disease, cancer and diabetes.

NPR article for laypeople: https://www.npr.org/sections/health-shots/2020/03/23/820274501/her-incredible-sense-of-smell-is-helping-scientists-find-new-ways-to-diagnose-di. Scientific paper: https://pubs.acs.org/doi/10.1021/acscentsci.8b00879.

Cure for leukemia?

From February 2022:

Two people with leukemia achieved remission over a decade after being infused with CAR-T cells, immune cells that had been modified in a lab, according to a new study. The findings suggest that this approach could be a long-term therapy for leukemia — and some researchers describe it as a possible cure.
Chimeric antigen receptor or CAR-T cell therapy may be a “curative regimen” for chronic lymphocytic leukemia, according to the researchers, who announced their findings in a news briefing this week. Chronic lymphocytic leukemia accounts for about a quarter of new cases of leukemia.

https://www.cnn.com/2022/02/02/health/cancer-t-cell-therapy-remission-study/index.html

and discussion at https://news.ycombinator.com/item?id=30192209.

Precision cancer treatments

We (with the help of artificial intelligence) are more and more able to find exactly the right chemical to attack an individual’s cancer. This article looks like an excellent overview of the state of the art, the possible future of precision treatments, and the obstacles.

Doctors are taking a far more nuanced view of what drugs and treatments will work on which patients and on what different kinds of cancers. The idea of this so-called precision medicine, or personalized medicine, is that ultimately doctors will use genetic tests—of both the patient and the cancer tumor—to determine the exact drugs or treatments that have the best chance of working.
(…)

To wring useful insights out of the data from 170,000 cancer patients that Caris has access to, the company enlists hundreds of different deep-learning algorithms. The programs essentially compete with one another to find patterns in the data that indicate which drugs will work best with which patients. “Different algorithms will miss different patients, but together they can do a better job,” says Spetzler.

3,500 words. https://www.newsweek.com/2019/07/26/targeting-each-patients-unique-tumor-precision-medicine-crushing-once-untreatable-cancers-1449287.html

How a new pill could spell the end of ageing

Not immediately, of course. But one cause of ageing (British spelling) is cells that have aged until they can’t do their job any more:

Senolytics (is) a branch of medicine that targets senescent cells; the various faulty cells that have been identified as instrumental in our eventual demise. These so-called “zombie” cells linger and proliferate as we age, emitting substances that cause inflammation and turn other healthy cells senescent, ultimately leading to tissue damage throughout the body.

Works in mice!:

A team at the Mayo Clinic (…) showed in 2011 that “using a genetic trick to get rid of these senescent cells can significantly improve health and lifespan” in prematurely aged mice. In 2016, the same group achieved similar results in naturally aged mice, releasing an arresting image of two elderly rodents born of the same litter. The one cleared of its senolytic cells seems spry and glossy, while its sibling is shrunken, greying and looks its age.

https://www.theguardian.com/science/2019/sep/02/the-science-of-senolytics-how-a-new-pill-could-spell-the-end-of-ageing

Fighting bullshit

The Washington Post calls it “BS” in this informative article, but I’m willing to call it bullshit:

BS “involves language, statistical figures, data graphics and other forms of presentation intended to persuade by impressing and overwhelming a reader or listener, with a blatant disregard for truth and logical coherence.”…
A right-wing media site, for example, blared in a headline that several thousand DACA beneficiaries (undocumented children shielded from deportation by an Obama-era policy) have committed crimes against U.S. citizens, Bergstrom said. “But it’s an extremely low percentage of DACA recipients,” he pointed out. “Which means they’re being accused of crimes at substantially lower rates — massively lower rates — than American citizens. Of course the article doesn’t say that.”

Another example: there is an excellent (but probably spurious) correlation between pool drownings per year and the number of films that Nicolas Cage appeared in during that year:

https://www.washingtonpost.com/science/2019/06/24/misinformation-is-everywhere-these-scientists-can-teach-you-fight-bs/

and the course:

https://www.callingbullshit.org/index.html

“Source code” of Pfizer COVID vaccine

Non-trivial, as we programmers say, but this is a very clear description of how one COVID vaccine works. If you want to know the details, it’s complicated but fascinating. I was particularly intrigued by how much we understand and can manipulate at a very basic level of our own biology:

An mRNA vaccine achieves the same thing (‘educate our immune system’) but in a laser like way. And I mean this in both senses – very narrow but also very powerful.
So here is how it works. The injection contains volatile genetic material that describes the famous SARS-CoV-2 ‘Spike’ protein. Through clever chemical means, the vaccine manages to get this genetic material into some of our cells.
These then dutifully start producing SARS-CoV-2 Spike proteins in large enough quantities that our immune system springs into action. Confronted with Spike proteins, and (importantly) tell-tale signs that cells have been taken over, our immune system develops a powerful response against multiple aspects of the Spike protein AND the production process.
And this is what gets us to the 95% efficient vaccine.

https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/

Using Pokémon to Detect Scientific Misinformation

There are legitimate scientific journals, and then there are legitimate-sounding ripoff “predatory journals” that will print almost anything for a fee. Matan Shelomi submitted an article to one:

On March 18, 2020, the American Journal of Biomedical Science & Research published my paper claiming that eating a bat-like Pokémon sparked the spread of COVID-19. This paper, “Cyllage City COVID-19 outbreak linked to Zubat consumption,” blames a fictional creature for an outbreak in a fictional city, cites fictional references (including one from author Bruce Wayne in Gotham Forensics Quarterly on using bats to fight crime)…
Some would argue that editors cannot recognize Pokémon names, but lines in the text such as “a journal publishing this paper does not practice peer review and must therefore be predatory” or “this invited article is in a predatory journal that likely does not practice peer review” would have tipped off anyone who bothered to read the articles. These papers did not slip in under the radar; they were welcomed in blindly.

https://www.the-scientist.com/critic-at-large/opinion-using-pokmon-to-detect-scientific-misinformation-68098