What to read: "Harvard Necromancer" by Alexander Panchin - on the scientific approach to magic

2024 Author: Malcolm Clapton | [email protected]. Last modified: 2023-12-17 03:44

Science fiction about how an ambiguous mouse experiment can turn the whole picture of the world.

The publishing house "Peter" publishes a new book by Alexander Panchin, a biologist, popularizer of science and scientific journalist. "" - science fiction, in which the author skillfully shows how scientists would behave when faced with magic in reality. The story begins with a group of researchers jokingly performing a ritual of sacrifice of experimental mice, and the result is extremely unexpected.

- Can you explain who humanized mice are?

- Humanized animals are either chimeras, which have been transplanted with human cells or tissues, or genetically modified organisms, into whose genome one or more human genes have been transferred. At Alpha, we studied mice with a human variant of a gene called FOXO3A. It is very interesting for gerontologists because it activates other genes that slow down cellular aging. For example, genes that correct or prevent errors in DNA, or fight heat shock. Some carriers of one of the variants of this gene live surprisingly long. This option is much more common in centenarians than the population average.

So we created genetically modified humanized mice. One mice inherited the human variant of the FOXO3A gene, associated with a long lifespan. Others are a normal human variant of a gene. Still others have retained the mouse version. As part of Alpha, we needed to euthanize rodents in order to study the effect of human gene variants on various biomarkers of aging: telomere length - the ends of chromosomes, the activity of certain genes, modification of DNA and histones, and something else. For different organs.

- As I understand it, you disposed of the blood of these humanized animals in a rather non-standard way.

- Mary thought that the experiment would be very symbolic. It’s as if we are making a human sacrifice - even if in practice we only put humanized mice to sleep. For scientific purposes! All this is justified, because we were going to open them anyway. As a bonus, students will attend a strange magic show. Mary even got postdocs into her adventure. However, as a researcher and mentor, I wanted the students to learn at least some valuable lessons from the experiment.

“Excuse me, what valuable lessons can be learned from… um, spraying the blood of mice over a pentagram?”

- You very accurately described the surroundings of our experiments! True, the blood volumes were very small. I said that I would allow the ritual to be performed, provided that the students come up with a testable scientific hypothesis of what it might lead to, and plan a competent experiment to test it. So that later we can be convinced that the hypothesis has not been confirmed.

- And the students came up with a hypothesis and a test?

- Collective intelligence, yes. True, several clarifications had to be made. In addition to Alpha, we also had a Beta project. As part of Beta, we also studied normal and genetically modified mice. We tried to reproduce two well-known studies that claimed an increase in the lifespan of rodents. In one, mice lived about 20% longer than usual after gene therapy. The authors of the work, using a special viral carrier, delivered a gene that encodes the telomerase enzyme into the cells of an adult animal. When cells divide, their chromosomes are shortened. Each shortening is small, but over time, the changes accumulate and can significantly harm the chromosomes. To avoid this, there are special areas at the ends of the chromosomes called telomeres. Telomerase can increase the length of telomeres, allowing the cell to go through a large number of divisions. Theoretically, this can lead to an improvement in the regenerative potential of the body, since new cells are needed to replace old ones. In mammals, telomerase activity is high only in certain types of stem cells, but thanks to gene therapy, the enzyme can be made to work in any type of cells.

- Are you talking about the possibility of delivering genes using a virus that was first neutralized by disabling the ability to multiply and cause harm?

- Exactly! In addition, we wanted to replicate a study that found that molecular compounds made from pure carbon, fullerenes, diluted in olive oil, could practically double the lifespan of rats. The mechanism of action of fullerenes is unknown.

We assumed that the study was either complete nonsense that needs to be refuted, or a grossly underestimated discovery. We wanted to see which of the interventions works and, more interestingly, how they work with each other or with the presence of the human version of the FOXO3A gene in the body, which is found in over-longevity. So the Beta mice were part of an experiment already running. And the students suggested adding a fourth factor to the three that have already been studied.

- Blood ritual.

“Call it the Spooky Halloween Hypothesis. Can humanized sacrifice increase the lifespan of normal mice, humanized mice, or both? Will Project Alpha mice sacrifice affect Project Beta mice?

- And your dubious experiments could not spoil the main scientific experiment?

“In those days, no sane scientist would have believed in magic rituals. And if you don’t believe in magical rituals, then you don’t consider the possibility that they will affect the results of your experiments.

It just so happened that we were wrong. So in the end it really influenced our experiment. It was difficult for us to interpret the results obtained - and even more difficult to publish them.

- Who performed the ritual?

- Mary insisted that she should do it. She assured that "without a doubt, demonic entities will be delighted if a virgin from the human race brings humanized sacrifices." We then laughed heartily.

But Mary also had a scientific argument in favor of her candidacy. The girl was on the team that worked on "Alpha", and had nothing to do with the more complicated and prolonged "Beta". The design of the "magic" experiment assumed that the rodents from "Beta" were randomly divided into two groups. Only one group will be present during the Alpha mouse sacrifices.

We numbered the mice in advance. Using a random number generator, Mary compiled a list of which mice would be present during the ritual and which would be kept in a remote location. The list was sealed in an envelope - I kept it in a drawer until the end of the experiment. The members of the team that worked on "Beta" had no idea which group the animals were from. Even with all the desire, they could not influence the results of the experiment. This is called blinding. Randomization and blinding are two important tools that we use in the vast majority of research.

- I see you are very serious about performing all kinds of experimental procedures. But it was meant as a joke, wasn't it?

- Of course! Like one big joke! We had fun in our own way. Just imagine the picture: twilight, dim candlelight … And our Mary with false horns, lenses for eyes the color of flame and phosphorescent make-up stands in the middle of a pentagram sprayed with rodent blood. It was something! I even took a photo as a souvenir.

- And it didn't seem to you that it was too much: to spray blood over the pentagram?

“As one British proverb says,“done for a penny, you have to do it for a pound”. So yeah, there was real blood there. Mary sacrificed humanized mice and repeated the incantation: "With vampiric power, I drain your life." She took this verbal component of the life drain spell on the Internet from the Southern Live Action Reconstruction Organization's rulebook. Personally, I suggested that she take something from the role-playing games Dungeons & Dragons, Pathfinder or the Warcraft universe. Mary replied that it would be better to take a simple spell and in English. She wasn't sure if she had the correct draconic pronunciation or something.

Then Mary and other students measured organs, took blood samples and did everything that was supposed to be done in the framework of "Alpha". Only with the unusual condition that all this time they were surrounded by numerous cages with mice from Beta. We covered the cages with a black cloth so as not to expose the animals to unnecessary stress during the ritual. Then the mice were placed back in the vivarium, and we continued the party.

- Good. What happened next?

- Then we had a boring Halloween the next year and the next year. I had already forgotten about all these rituals, until the first results on Beta appeared.

- You went to look for an envelope in your drawer?

- Yes, but not right away. My students found that a significant proportion of the Beta mice did not age at all. We thought this indicated that something worked. Fullerenes, telomerase, or the human FOXO3A gene … Or maybe a combination of these factors? But the research protocol involved blinding. The students who took care of the mice didn’t know which of them were exposed to one or another factor, so we didn’t know what was going on there, and we were looking forward to the end of the project.

- Have you waited for the mice to expire?

- That was the long-term plan, yes. But some mice simply refused to die. Even after four years, some of the mice were still alive! By this time, we planned to cancel the blinding protocol. I remember we opened champagne on this occasion. You see, four years is a very long time for mice. They usually live for two to three years.

- And at that moment you decided to check which mice were subjected to the ritual?

- As I said, I managed to forget about our sacrifices. The attentive Mary reminded me of them. I laughed, but I opened the envelope and gave the list to her and another student. Soon they returned, and I immediately noticed that something shocked them. It turned out that most of the long-lived mice were present during the ritual. Humanized sacrifices explained the anomaly in our data.

- And nothing else strange happened to the mice?

- For example?

- Well, if it was a horror movie, the rodents would become aggressive and attack scientists.

- Sounds funny, but no. Our mice did not make angry sounds and did not turn into blood-sucking vampires. And in general they behaved like the most ordinary boring laboratory rodents.

- It's a pity, of course … Have you already thought about the possible publication of the research results?

- You see, we found ourselves in a difficult position. The fact that some mice lived for more than four years looked incredible. Any researcher who had such a cohort in the laboratory would jump with happiness and, of course, would continue to work with her. In addition, we could not publish our biological results without mentioning the rituals performed. Without this additional information, the results made little sense, although they made even less sense with them. I was also absolutely sure that there was some mistake. It was obvious that any sane reviewer would think we were screwed if we tried to publish the entire story. Of course, I'm not very dependent on the opinions of others, but being branded as a psycho among colleagues is not a big idea.

We were also lucky: by this point, our previous research had been published in top-rated journals. It turns out that we still had the results to report to the national institutions of health, which funded us. In general, there was no need to write a new article. And yet the Beta executive discussed the long-lived mice work with the department head at the annual meeting. He did not mention the sacrifices, but presented all the data and admitted that the results were anomalous. According to the leader, we made a mistake somewhere, and he promised that we would double-check everything. Meanwhile, I decided to repeat the experiment …

Alexander Panchin, author of Defense Against the Dark Arts and Apophenia, reflects on applying the scientific method to some of the most startling discoveries. The main character of "Harvard Necromancer" is faced with the inexplicable, and his further experiments change fundamental ideas about our world. Not to be missed by fans of "Harry Potter and Rational Thinking", as well as anyone interested in the inner kitchen of scientific work.