Lifeboat Foundation

In March of 2014, I knew my eight year old daughter was sick. Once borderline overweight, she was now skeletally thin and fading away from us. A pre-dawn ambulance ride to the hospital gave us the devastating news – our daughter had Type 1 diabetes, and would be dependent on insulin injections for the rest of her life.

This news hit me particularly hard. I’ve always been a preparedness-minded kind of guy, and I’ve worked to free myself and my family from as many of the systems of support as possible. As I sat in the dark of the Pediatric ICU watching my daughter slowly come back to us, I contemplated how tied to the medical system I had just become. She was going to need a constant supply of expensive insulin, doled out by a medical insurance system that doesn’t understand that a 90-day supply of life-saving medicine is a joke to a guy who stocks a year supply of toilet paper. Plus I had recently read an apocalyptic novel where a father watches his 12-year old diabetic daughter slip into a coma as the last of her now-unobtainable insulin went bad in an off-grid world. I swore to myself that I’d never let this happen, and set about trying to find ways to make my own insulin, just in case.

Researchers created an algorithm to identify similar cell types from species – including fish, mice, flatworms and sponges – that have diverged for hundreds of millions of years, which could help fill in gaps in our understanding of evolution.

Cells are the building blocks of life, present in every living organism. But how similar do you think your cells are to a mouse? A fish? A worm?

Comparing cell types in different species across the tree of life can help biologists understand how cell types arose and how they have adapted to the functional needs of different life forms. This has been of increasing interest to evolutionary biologists in recent years because new technology now allows sequencing and identifying all cells throughout whole organisms. “There’s essentially a wave in the scientific community to classify all types of cells in a wide variety of different organisms,” explained Bo Wang, an assistant professor of bioengineering at Stanford University.

To answer this question, an internal team of scientists, consisting of researchers affiliated with the Buck Institute for Research on Ageing, and researchers from Nanjing University decided to modify both the Insulin and the rapamycin pathways of a group of C.elegans worms, expecting to see a cumulative result of a 130% increase in lifespan. However, instead of seeing a cumulative effect in lifespan, the worms lived five times longer than they normally would.

“The synergistic extension is really wild. The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways.” – Jarad Rollins of Nanjing University.

What could this mean for human regenerative medicine? Humans are not worms, however on a cellular level they do possess very similar biology. Both the insulin pathway and the rapamycin pathway are what is known as ‘conserved’ between humans and C.elegans, meaning that these pathways have been maintained in both organisms. In the distant past, both humans and C.elegans had a common ancestor, in exactly the same way as humans and Chimpanzees have a common ancestor. Evolution has changed our bodies significantly over the millions of years that humans and C.elegans have diverged from one another, but a lot of our fundamental biological functions remain largely unchanged.

To begin with, why do we use mice in medical and biological research? The answer to this question is fairly straight forward. Mice are cheap, they grow quickly, and the public rarely object to experimentations involving mice. However, mice offer something that is far more important than simple pragmatism, as despite being significantly smaller and externally dissimilar to humans, our two species share an awful lot of similarities. Almost every gene found within mice share functions with genes found within humans, with many genes being essentially identical (with the obvious exception of genetic variation found within all species). This means that anatomically mice are remarkably similar to humans.

Now, this is where for the sake of clarity it would be best to break down biomedical research into two categories. Physiological research and pharmaceutical research, as the success of the mouse model should probably be judges separately depending upon the research that is being carried out. Separating the question of the usefulness of the mouse model down into these two categories also solves the function of more accurately focusing the ire of its critics.

The usefulness of the mouse model in the field of physiological research is largely unquestioned at this point. We have quite literally filled entire textbooks with the information we have gained from studying mice, especially in the field of genetics and pathology. The similarities between humans and mice are so prevalent that it is in fact possible to create functioning human/mouse hybrids, known as ‘genetically engineered mouse models’ or ‘GEMMs’. Essentially, GEMMs are mice that have had the mouse version of a particular gene replaced with its human equivalent. This is an exceptionally powerful tool for medical research, and has led to numerous medical breakthroughs, including most notably our current treatment of acute promyelocytic leukaemia (APL), which was created using GEMMs.

There’s some really interesting CRISPR news out today, and it’s likely to be a forerunner of much more news to come. A research team has demonstrated what looks like robust, long-lasting effects in a primate model after one injection of the CRISPR enzymatic machinery. There have been plenty of rodent reports on various forms of CRISPR, and there are some human trials underway, but these is the first primate numbers that I’m aware of.

The gene they chose to inactivate is PCSK9, which has been a hot topic in drug discovery for some years now. It’s a target validated by several converging lines of evidence from the human population (see the “History” section of that first link). People with overactive PCSK9 have high LDL lipoproteins and cholesterol, and people with mutations that make it inactive have extremely low LDL and seem to be protected from a lot of cardiovascular disease. There are several drugs and drug candidates out there targeting the protein, as well there might be.

It’s a good proof-of-concept, then, because we know exactly what the effects of turning down the expression of active PCSK9 should look like. It’s also got the major advantage of being mostly a liver target – as I’ve mentioned several times on the blog already, many therapies aimed at gene editing or RNA manipulation have a pharmacokinetic complication. The formulations used to get such agents intact into the body (and in a form that they can penetrate cells) tend to get combed out pretty thoroughly by the liver – which after all, is (among other things) in the business of policing the bloodstream for weird, unrecognized stuff that is then targeted for demolition by hepatocytes. Your entire bloodstream goes sluicing through the liver constantly; you’re not going to able to dodge it if your therapy is out there in the circulation. It happens to our small-molecule drugs all the time: hepatic “first pass” metabolism is almost always a factor to reckon with.

“Gene editing offers unique opportunities to make food production more sustainable and to further improve the quality, but also the safety, of food. With the help of these new molecular tools, more robust plants can be developed that deliver high yields for high-quality nutrition, even with less fertiliser,” says co-author Stephan Clemens, Professor of Plant Physiology at the University of Bayreuth and founding Dean of the new Faculty of Life Sciences: Food, Nutrition & Health on the Kulmbach campus.

For more sustainability on a global level, EU legislation should be changed to allow the use of gene editing in organic farming. This is what an international research team involving the Universities of Bayreuth and Göttingen demands in a paper published in the journal “Trends in Plant Science”.

In May 2020, the EU Commission presented its “Farm-to-Fork” strategy, which is part of the “European Green Deal”. The aim is to make European agriculture and its food system more sustainable. In particular, the proportion of organic farming in the EU’s total agricultural land is to be increased to 25 percent by 2030. However, if current EU legislation remains in place, this increase will by no means guarantee more sustainability, as the current study by scientists from Bayreuth, Göttingen, Düsseldorf, Heidelberg, Wageningen, Alnarp, and Berkeley shows.

Great new episode with renowned geneticist Christopher Mason who talks about his book on how we will need to bioengineer our own species in order to expand beyond our solar system.

Geneticist Christopher Mason chats about his new book, “The Next 500 Years: Engineering Life to Reach New Worlds” from MIT Press. We discuss both the nuts and bolts and the philosophy driving our expansion offworld. Mason’s goal is to preserve our species by expanding to an Earth 2.0 in order to avoid our star’s own Red Giant endgame.

Continue reading “Episode 50 --- Bioengineering Our Human Species To Reach The Stars” »

Can We Immunize The World Against Future Pandemics? Dr Jonna Mazet, DVM, MPVM, PhD, UC Davis School of Veterinary Medicine — Global Virome Project.

Dr. Jonna Mazet, DVM, MPVM, PhD, is a Professor of Epidemiology and Disease Ecology at the UC Davis School of Veterinary Medicine, Founding Executive Director of the UC Davis One Health Institute, and Vice Provost For Grand Challenges At UC Davis.

Continue reading “Dr. Jonna Mazet, DVM, MPVM, PhD — One Health — Can We Immunize The World Against Future Pandemics?” »

First discovered in 1984, retrons are floating ribbons of DNA in some bacteria cells that can be converted into a specific type of DNA—a single chain of DNA bases dubbed ssDNAs (yup, it’s weird). But that’s fantastic news for gene editing, because our cells’ double-stranded DNA sequences become impressionable single chains when they divide. Perfect timing for a retron bait-and-switch.

Normally, our DNA exists in double helices that are tightly wrapped into 23 bundles, called chromosomes. Each chromosome bundle comes in two copies, and when a cell divides, the copies separate to duplicate themselves. During this time, the two copies sometimes swap genes in a process called recombination. This is when retrons can sneak in, inserting their ssDNA progeny into the dividing cell instead. If they carry new tricks—say, allowing a bacteria cell to become resistant against drugs—and successfully insert themselves, then the cell’s progeny will inherit that trait.

Because of the cell’s natural machinery, retrons can infiltrate a genome without cutting it. And they can do it in millions of dividing cells at the same time.