Even God’s first paper got rejected

All images and texts on this site copyright 2017 by Russ Hodge





Prof. God
Paradise Avenue
Heavenly Realm


Dear Prof. God,


Thank you for submitting your paper, “Genesis: A method of generating matter,
space, time, and living species from Nothingness,” for our consideration. We agree
that the creation of the universe might be of interest to our general readership.
However, after considering the reviewers’ comments, we regret that we are unable
to publish the manuscript in its current form. If you feel that you can satisfy their
concerns with further experiments, you are welcome to resubmit a revised version
of your manuscript at a later date.

The following represent only a small selection of the most significant issues,
in our view, but for a resubmission you should address all the reviewers’ comments,
which are in the 5000 GByte attachment appended to this file.


Reviewer #1:

Hasn’t this author ever heard of controls? The author should have started
with two samples of Nothingness, applied the method of creation to one
while observing the other to ensure that the various reactions did not occur
spontaneously over time. He provides no quantitative description of this
Nothingness, gives no account of the conditions under which it was produced,
and no proof that Nothing was actually there.   

There are no references to previous literature, so we have no way to judge
the author’s qualifications in the field or the extent to which this work is
innovative vis-a-vis that of other groups.

The indirect, third-person style of the text is old-fashioned and should be
updated. Phrases such as, “In the Beginning God created” should be modernized
to a form like, “In a first step, we produced…” Another example:
“And God found that it was good” should be replaced with,
“The results confirmed our initial hypothesis.”


Reviewer #2:

From what I can tell, the physical and biological systems described in the
paper seem to have gone from a very low state of order to high complexity
within a remarkably short period of time. This hints at the use of extremely
powerful catalysts, which are not described anywhere in the text. Are they
commercially available? If so, were the manufacturer’s protocols rigorously

In fact, the author has failed to offer any model or hypothesis that could
mechanistically explain the results, or justify the claim that His efforts
somehow caused them. The implication is that things happened just because
He willed them to. This is the reason we have double-blind experiments, people!


Reviewer #3:

The human cloning experiment was not described in nearly enough detail.
What types of cells were extracted from the male’s rib, and what method was
used to generate induced Pluripotent Stem Cells and then the female? More
significantly, since the cell was derived from a male, where did they get the
second X chromosome? Was it simply a clonal copy of the first? Theoretically
it is possible, I suppose, that the female was actually genetically male but
suffering from some sort of defect in her SRY gene. If that were the case, half
of her gametes would be chromosomally Y. This would lead a quarter of her
offspring to be entirely X-less, i.e., Y-Y, which might explain the violent behavior
of some of her children. Or perhaps radical genetic engineering technologies
were used to create the female, such as CRISPR/Cas9, although I hope not,
because the fight over the patent was already a mess, and getting God
involved certainly wouldn’t make things go any smoother.

In any case, the type of genetic modifications needed to make a female from
a male would have been in direct violation of every ethical standard and
numerous international laws. Not to mention the horrendous, ensuing inbreeding
effects that could be expected in a population descended entirely from a couple
who were not only closely related, but actual clones.

Please note that I did not receive any paperwork indicating that the project
had been submitted to ethical review. Apparently the Author considers
Himself superior to any sort of moral authority; either that, or he paid
someone off. If I am wrong, and an Ethics Commission did in fact approve
the project, please let me know the country. I would consider moving
my laboratory there.



An animal that runs on hybrid fuel

Research highlight from the MDC – a great story from Gary Lewin’s group in the current issue of Science


When oxygen gets scarce, the naked mole-rat throws a metabolic switch to draw energy from fructose rather than glucose

The naked mole-rat, a rodent native to Africa, can survive with little or no oxygen far longer than other mammals. The secret lies in its metabolism: in addition to the basic system by which animals generate energy from glucose, naked mole-rats have a backup system based on fructose. This discovery comes from Gary Lewin’s lab at the Max Delbrück Center (MDC), in a collaboration with the groups of Michael Gotthardt (MDC), Stefan Kempa (MDC and BIH), and Thomas Park (University of Illinois in Chicago), as well as scientists from several other countries. The work is published in the April 21 edition of the journal Science.

Oxygen is so essential to life that a very short deprivation is fatal to animals. Their cells need a constant supply to drive the chemical reactions that produce energy from food. In ancient times, cells evolved a form of metabolism that used the sugar glucose as a source of fuel and the high reactivity of oxygen atoms to extract its energy. This process was so efficient that glucose-based metabolism could fuel the bodies of humans and even larger animals, and it has been maintained over the course of evolution.

But life in a harsh environment can alter even very basic aspects of an animal’s biology. Long ago, something drove the ancestors of the naked mole-rat underground. There the rodent’s biology and behavior began an evolutionary dialogue with the extreme conditions it encountered. This led to some highly unusual adaptations. Naked mole-rats are insensitive to some forms of pain, and have lifespans that exceed 32 years – ten times the norm for most other rodents. Only one or two cases of cancer have ever been detected in the species. And now MDC scientists have discovered that the animal can go with little or no oxygen for extraordinary lengths of time.

Such characteristics have attracted the interest of scientists around the globe – including neurobiologist Gary Lewin. Over several years, his laboratory has gained deep insights into the biology of pain by comparing the nervous system of the naked mole-rat to that of mice and humans. Upon learning that the naked mole-rat could cope with little or no oxygen, he was immediately intrigued – and his lab was well prepared to pursue the biology behind this unique attribute.

Linking oxygen deprivation to a unique metabolic system

Oxygen deprivation was clearly connected to the animal’s biology, lifestyle and environment. “Naked mole-rats huddle in huge, underground colonies of up to 280 individuals,” Lewin says. “This means that they continually experience sharp declines in levels of oxygen and dramatic increases in carbon dioxide. Without adaptations, this would be just as deadly to the naked mole-rat as it is to other animals.”

Most organisms on Earth are suited to the surface atmosphere, composed of about 21% oxygen and only tiny amounts of carbon dioxide (about 0.04%). Reducing oxygen to about 5% is fatal for a mouse within about 15 minutes; total deprivation causes fatal damage within about a minute. The naked mole-rat, however, can cope with as little as 5% oxygen and high levels of carbon dioxide for hours on end with no apparent distress or ill effects. And amazingly, it can survive at least 18 minutes without any oxygen at all.

“Under these conditions the animal enters a sort of suspended animation,” says Jane Reznick, a postdoc in Lewin’s group and a lead author on the current paper. “It falls asleep and its heartbeat slows to about a quarter of the normal rate. When oxygen is restored the heart rate rises, and the animal quickly wakes up and goes about its normal behavior.”

This hinted that some backup system was protecting its heart and brain – two organs that are highly sensitive to oxygen in other species. Without it, their cells cannot produce energy and rapidly suffer fatal damage.

Hitting the stop button on an assembly line

There had to be some fundamental difference in the naked mole-rat’s metabolism. To find it, the scientists enlisted help from the MDC’s Metabolomics Unit, headed by Stefan Kempa. His team uses advanced technology to capture global and quantitative snapshots of cellular metabolism. Their methods reveal the presence of tiny metabolites: molecules that are created through the processing of fuels like glucose. Networks of enzymes break glucose down into small products that move through the metabolic pipeline, generating energy along the way.

“These experiments are a bit like hitting the ‘stop’ button on an assembly line,” Kempa says. “If you were to do that in a factory, then look at partially assembled pieces and the bits that were tossed out, you’d get an idea of what was being built, and how it was constructed.” Further experiments traced the remnants of the sugars as they flowed through an alternative metabolic route that generated energy without consuming oxygen.

Comparing mouse and naked mole-rat tissues under conditions with and without oxygen revealed some curious differences. In naked mole-rats, oxygen deprivation triggered a shutdown of cellular energy factories called mitochondria. In the mouse they continued to operate but quickly malfunctioned – mitochondria need oxygen to run.

But the most startling finding had to do with the sugar molecules found in the animals’ blood and tissues. Overall, naked mole-rats had a lot less glucose than mice, which hinted that other sugars might be providing an alternative source of energy. During oxygen deprivation, there was a significant rise in levels of other sugars. Naked mole-rats had more sucrose – and truly stunning was the amount of fructose, which had skyrocketed.

Can tissues run solely on fructose fuel?

Could the naked mole-rat be using fructose rather than glucose as a source of energy? The two sugars weren’t that different – even our own bodies make use of fructose-based metabolism, although this only happens in the kidney and liver. These organs have an enzyme called ketohexokinase, or KHK, which can trim fructose into a form that can be plugged into the energy production line. From that point on the modified fructose, called F1P, is handled like glucose. Since the subsequent stages of processing don’t require oxygen, it wouldn’t be absolutely necessary in a metabolic system based on fructose.

“In humans, fructose metabolism occurs only in the kidney and liver because they’re the only tissues that contain KHK,” Lewin says. “We found that brain tissue from the naked mole-rat contained high levels of F1P – suggesting that KHK was at work – but only under oxygen deprivation. This told us two things: that their brains might really be using fructose as a source of energy, and that the switch only happened when oxygen grew scarce.”

The evidence for fructose metabolism was accumulating, but so far it was all indirect; the next step would be to determine whether the animals were actually using the alternative source of fuel. First the scientists performed experiments using brain tissue to test whether neurons could function if they were deprived of glucose and fed exclusively on fructose. While an hour of this treatment severely damaged the cells of mice, naked mole-rat neurons continued to show activity. Experiments carried out in Michael Gotthardt’s group showed even more dramatic results for the naked mole-rat heart, which could beat just as well when supplied with fructose as it could using glucose.

“This was proof that fructose can replace glucose as an energy source in the naked mole-rat brain and heart,” Reznick says. “It helps explain how these organs – and the animal as a whole – can recover from long periods of oxygen deprivation.”

A two-part system for switching to alternative fuel

Cells can only use fructose as an energy source if they can absorb it from their surroundings. This requires a protein called GLUT5, which snatches fructose and draws it into the cell. In mice and humans, GLUT5 appears in kidney and liver cells, but other tissues have almost none. It’s another factor that restricts fructose metabolism to the kidney and liver in humans and prevents it from serving vital organs such as the brain and heart. In the naked mole-rat those tissues – and most other cells – have at least ten times as much GLUT5.

“This gives the naked mole-rat a two-part system that allows it to survive long periods of oxygen deprivation,” Lewin says. “Throughout its body you find both the GLUT5 transporter and the KHK enzyme that converts fructose into a usable energy source.”

Fructose metabolism has been encountered in human diseases including malignant cancer, metabolic syndrome, and heart failure. This hints that there might be some link between the naked mole-rat’s metabolism, its resistance to cancer, and possibly even its extraordinary lifespan.  Only further research will tell – but the current study provides an interesting new handle on such questions.

“It’s important to understand how these unusual animals make the metabolic switch without any obvious long-term damage to their tissues,” Lewin says. “We might learn something about how our own cells attempt to cope with situations in which they are deprived of oxygen, such as strokes or heart attacks. Our work raises questions about the biology of fructose metabolism that will ‘fuel’ research for years to come.”


Russ Hodge

Thanks to Jana Schlütter and Martin Ballaschk for comments on an earlier draft.


Thomas J. Park1, Jane Reznick2, Bethany L. Peterson1 , Gregory Blass1 , Damir Omerbašić2, Nigel C. Bennett3, P. Henning J.L. Kuich4, Christin Zasada4, Brigitte M. Browe1, Wiebke Hamann5, Daniel T. Applegate1, Michael H Radke5,10, Tetiana Kosten2, Heike Lutermann3, Victoria Gavaghan1, Ole Eigenbrod2,  Valérie Bégay2, Vince G. Amoroso1, Vidya Govind1, Richard D. Minshall7, Ewan St. J. Smith8, John Larson9, Michael Gotthardt5,10, Stefan Kempa4, Gary R. Lewin2,11 (2017): „Fructose driven glycolysis supports anoxia resistance in the naked mole-rat.“ Sciencedoi:10.1126/science.aab3896

1Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America; 2 Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 3Department of Zoology and Entomology, University of Pretoria, Pretoria, Republic of South Africa; 4Integrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 5Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany; 7Departments of Anesthesiology and Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America; 8Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom; 9Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, United States of America; 10DZHK partner site Berlin, Germany; 11Excellence cluster Neurocure, Charité Universitätsmedizin Berlin, Germany

Note: finally some science articles again!

Dear followers of this blog,

Over the next few days I’ll be returning a bit to the original intent of this blog with some recent articles about SCIENCE – extremely interesting stories that are appearing in press over the next few days… Most of these will also appear on the website of my institute, the Max Delbrück Centre for Molecular Medicine. I’ll also be posting more articles about my teaching activities soon. And not to worry – there are plenty of cartoons, updates to the Devil’s Dictionary, and maybe even a revival of the “Best of PubMed series” coming soon.



Breaking the temperature barrier

With an advanced ERC grant, Thoralf Niendorf’s group will aim ultrahigh-field MRI at a critical, yet largely unexplored dimension of life


Temperature is one of the most rigidly controlled aspects of life, as seen by the very narrow range maintained in the tissues of warm-blooded animals. The heat briefly rises through fevers and inflammations as a part of immune responses to infections. But there has been a major obstacle to exploring this crucial dimension of life: scientists have not had a method to alter temperatures within living tissues.

Soon that may change thanks to an advanced ERC grant just awarded to Thoralf Niendorf’s group and his team, who work at the high end of magnetic resonance imaging (MRI) technology. “Every time a doctor takes an image using MRI, there’s a generation of heat,” Niendorf says. “The unknown impact of this has led to strict regulations governing the amount that can reach patient tissues. We’re hoping to take this side effect and turn it into a tool for research, new forms of diagnosis, and hopefully even therapies.”

That will require an instrument which can focus exact amounts of energy on precise, microscopic targets inside animal bodies. The group has found a way to build it: start with a new ultrahigh-field MRI instrument, then add a custom-designed array of radiofrequency transmitters to shape and focus its powerful magnetic field. The scientists have already worked out the theory and tested designs; now, with the new grant, they can build the machine.

At that point they will enter uncharted scientific territory. The first projects will involve thermal phenotyping studies – a term coined by the group – carried out in collaborations with scientists working on a range of systems. The goal is to determine whether various tissues have unique thermal properties that can be detected by MRI and might have diagnostic value. The next step will be to observe how tissues respond to highly focused increases in temperature. Disease-related processes may be susceptible in ways that could usher in new MRI-based therapies. A unique feature of this strategy would be the ability to deliver a treatment and monitor its effects simultaneously, using the same instrument.

Another part of the project will involve an ongoing collaboration with scientists in Sydney, Australia and Berlin who are building temperature-responsive polymers to deliver drugs or other molecules. These “nano-vehicles” can be introduced into the body, where they remain inactive until heated. They can be loaded with several substances which are released at different temperatures upon activation through MRI. The interest for research is that scientists could alter tissues in a step-wise manner, to control complex processes over time. And the same strategy could be used to strike a disease with successive blows, targeting different weaknesses.

“Planning this project has already drawn together a group of people with diverse expertise,” Niendorf says. “We’re excited about exploring this dimension of life in a truly interdisciplinary way. We can’t predict what we’ll find. But the fact that organisms keep temperature under such tight control hints at vitally important functions across the body.”


The original version of this article was published on the MDC website and can be seen here.