Musings from Jay (blog site permanently frozen 11/05/2024 morning)

  Xenobots , named after the African clawed frog,  are synthetic lifeforms that are designed by computers to perform some desired function and built by combining together different biological tissues.   Whether Xenobots are robots, machines, organisms, or something else entirely remains a subject of debate among scientists. Xenobots built to date have been less than 1 millimeter (0.04 inches) wide and composed of just two things: skin cells and heart muscle cells,  both of which are derived from stem cells  harvested from early (blastula stage)  frog embryos.  The skin cells provide rigid support, and the heart cells act as small motors, contracting and expanding in volume to propel the Xenobot forward.  The shape of a Xenobot's body, and its distribution of skin and heart cells, are automatically designed in simulation to perform a specific task.  Xenobots have been designed to walk, swim, push pellets, carry payloads, and work together in a...

  SynBio has given us some very interesting new materials. This essay explores some of those. Synthetic biology materials (SBMs) are macromolecules whose molecular structure are encoded by DNA and produced by genetically engineered organisms using synthetic biology. In materials synthetic biology, engineering principles from both synthetic biology and materials science are integrated to redesign living systems as dynamic and responsive materials with emerging and programmable functionalities. Materials can be pivotal for an industry. For example, we would have no commercial jet airline industry without aluminum. New materials can solve problems that have not been solved before and spawn a new industry.  One material is spider silk. It has strength (stronger than steel) and toughness (tougher than Kevlar) and yet has flexibility (as flexible as a guitar string) and is light weight. It is not really feasible to farm spiders for commercial production at scale. This material has n...

It is estimated that we will have to increase our food production by 70% by 2050 to meet demand. Over 40% of land surface has already been converted to agriculture production. Moreover, the global agriculture industry as it stands already emits more greenhouse gases than the global transportation industry.  Nitrogen fixing bacteria in the soil transforms atmospheric nitrogen into fixed nitrogen that plants use. Since the early 20th century, we have had processes that mimic this process mechanically by pulling nitrogen from the air as a step in making chemical fertilizers. Today, we’ve nearly doubled the natural rate of nitrogen available in soils.  An estimated 1/3 of global food production is made possible by its use, with 100 million tons applied to Earth’s surface annually. But its use has come at a price. When nitrogen fertilizer is applied faster than plants can use it, soil bacteria convert it to nitrate.  Water-soluble nitrate is flushed out of soils in r...

In an essay on Geology, I had talked about mankind possibly having launched a whole new geological era with his impact on the environment. In the essay on paleontology, I had talked about a new sixth mass extinction event potentially being in progress triggered mostly by mankind's activities. The science of climate change is clear and there is little doubt that the climate is changing due to mankind's activities with potentially devastating consequences.  In the essay on materials, I talked about conserving the lives of animals like deer that produce musk by manufacturing synthetic musk with SynBio. In the essay on de-extinction, I talked about using SynBio to stave off extinction for an ecologically important species or resurrect an important extinct species. But this technique can practically be only used for a few species. In the essay on food/agriculture,  I talked about gene editing coupled with a gene drive to target very harmful species in the ecology, but this tool has...

Xenobiology is a new subfield of synthetic biology that may make some people uncomfortable. I will briefly talk about it here. DNA is common to all life on earth. But Xenobiology is biology not based on DNA. It goes beyond the DNA-RNA-20 amino acids life forms. Xeno means alien or foreign.  Xenobiology has the potential to shed light on our basic understanding of life and why it works. The most fundamental question in biology is how did life really start? Why does life have only one language (DNA) we know of? If life could evolve so soon after the formation of the earth, and was so successful, why did it not emerge multiple times using multiple codes? Is our current code optimal? Could a parallel biology be possible? A biology that exists in parallel with but not compatible with existing creatures? Viruses that exist but do not infect our cells? A biology not even compatible with known lineages?  Let us take an XNA with an expanded set of letters. XNA is thought to be safer to...

Given our growing ability to build organisms using genetic blueprints, is true extinction a thing of the past? Probably not. On the other hand, Synthetic Biology is being used in research to create hybrid versions of the wooly mammoth, passenger pigeon, American chestnut and other extinct species.  No one really knows how many species really exist or existed, but it is estimated that up to 90% of all species are yet to be discovered. Many species that are quietly going extinct are plants, insects, marine life and microorganisms, often tied to humanities activities. These species play a large role in supporting the larger animal species we more focus on. Many believe we are in the middle of a sixth mass extinction wave in earth's history. Synthetic Biology ushers in new tools to help with de-extinction although some people do have reservations about such attempts. The new tools are available but synthetic biology is NOT the solution to the bigger extinction problem.  Scientists...

Synthetic virology  is a branch of virology engaged in the study and engineering of synthetic man-made viruses. It is a multidisciplinary research field at the intersection of virology, synthetic biology, computational biology, and DNA nanotechnology, from which it borrows and integrates its concepts and methodologies. There is a wide range of applications for synthetic viral technology such as medical treatments, investigative tools, and reviving organisms. Both RNA and DNA viruses can be made using existing methods. The first man-made infectious viruses generated without any natural template were of the polio virus and the φX174 bacteriophage. With synthetic live viruses, it is not whole viruses that are synthesized but rather their genome at first, both in the case of DNA and RNA viruses. Read the paleontology essay on viruses for more info on viruses.  This technology is now being used to investigate novel vaccine strategies.   The abilit...

There were about 10 million deaths worldwide due to cancer in 2020 making it one in six deaths. Cancer is a particularly potent cause of death in richer countries where other causes like infectious diseases and maternal mortality have been significantly reduced. The rise in global cancer deaths is driven by two demographic changes: population growth and population ageing. There are many types of cancer.  The key conventional treatments have been Chemotherapy, Radiation therapy and Bone Marrow transplants.  SynBio has started to offer clues and new potential answers to the scrouge of cancer. Immunotherapies are emerging.  SynBio can be used to reprogram a patient's own T-cells to target cancer cells. FDA approved two such therapies for blood cancer in 2017. In CAR T-cell therapy (chimeric antigen receptor T-cell therapy), T-cells are obtained from the patient's blood. CAR T-cells are then made in the lab. Millions of them are then grown. CAR T-cells are then infused into t...

Regenerative medicine  deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function".  This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.  The US regenerative medicine market is poised for significant expansion. primarily fueled by increased government funding (like NIH and BARDA) and favorable regulatory policies. Moreover, private investments and partnerships between biotech companies and research institutions have also played a vital role. As a leading global player in this field, the US is at the forefront of R&D with numerous groundbreaking therapies and treatments being developed and commercialized.  Although great strides have been made to prolong life, we have not yet mastered ways to improve it. We often spend the last decade of our life wit...

In 1991 James Bailey defined metabolic engineering as "the improvement of cellular activities by manipulation of enzymatic, transport, and regulatory functions in the cell with the use of Recombinant DNA technology". Recombinant DNA (DNA derived by combining DNA from more than one source) was a precursor to SynBio in the 1990's. Metabolic engineering had been in practice for several decades. SynBio supercharges Metabolic engineering by vastly decreasing both cost and time. It turns cells into cell factories.  Let us take a great showcase example of SynBio and metabolic engineering. In Chinese medicine, a plant named sweet wormwood has been used to treat malaria fever for almost 2000 years. Chinese researcher Tu Youyou isolated its active ingredient Artemisinin for which she got a Nobel prize in 2015. Sweet wormwood is still used as a traditional cure for malaria. The demand though far exceeded the supply. Using metabolic engineering, SynBio came to the rescue. Scientist J...

Synthetic Biology holds great potential and ushers in a world of promise, but also introduces a world of new risks, both deliberate and accidental. These risks need to be managed.  When discoveries are made, it is easy to forget that allowing organisms to be much more easily engineered and altered can often also be applied to humans who are made up of the same set of 4 molecules in their DNA and share many other biological processes. So, every time you hear of better tomatoes being engineered, that same technology also applies to alter humans. In germline gene editing, making any genetic change to an organism can result in unintended consequences, including disease and deformities. These alterations are hereditable bringing up a host of social and ethical issues. There is also a major concern that genetically engineered humans (example super soldiers) may further divide our society. There are also ethical concerns by not acting - For example having the power to eliminate a horrible...

Synthetic biology and artificial intelligence revolutions are proceeding in parallel and are overlapping in major ways.  In the mid 90's a field called bioinformatics came into existence to manage the growing databases of information on genes, proteins and other data intensive aspects of biology. It  is an interdisciplinary  field of science  that develops methods and software tools  for understanding biological  data, especially when the data sets are large and complex. There was an increased use of mathematics and computation to understand this data.  Computational approaches to biology are now being integrated with AI.  More lately, AI is being used to process and make sense of the complexity of our biological experiments, make suggestions to fine tune our biological designs, controlling biological robots, and attempt to predict the outcome of biological experiments. These capabilities will only be enhanced in the future with more powerful com...

Computer users face frequent upgrades that make older models obsolete and eventually unusable. The same goes for data storage which degrades over time. By contrast, computers using synthesized DNA for storage and processing could in theory offer a stable super-compact system that would last for millions of years. Intriguing idea?  Famed physicist Richard Feynman is known as the father of DNA computing. In his lecture in 1959 "There is plenty of room at the bottom", he said "This fact - that an enormous amount of information can be carried in an exceedingly small space - is of course well known to the biologists, and resolves the mystery which existed before we understood all this clearly, of how it could be that, in the tiniest cell, all of the information for the organization of a complex creature such as ourselves can be stored.". These thoughts were ignored for decades but now lays the cornerstone of both DNA computing and nano technology.  In 1994 Prof Leonard M...

Before dwelling more deeply into SynBio, we need to examine more broadly the four key tools that are used. To read DNA. To write DNA. To Edit DNA. I will also touch on a key tool used called directed evolution.  Directed evolution is an important tool for SynBio. It mimics the Darwinian evolution process in the test tube. In a typical directed evolution experiment, the gene encoding a macromolecule of interest is randomized and expressed in a suitable host. Appropriate screening or selection methods are then used to identify mutants that have particular properties of interest, such as binding to a specific small molecule or catalyzing a desired chemical reaction. Through iterative cycles of mutagenesis and amplification of selected mutants, beneficial desired mutations accumulate as in genuine Darwinian evolution but on a vastly shorter time scale. In this way, populations of macromolecules may be deliberately evolved toward useful synthetic and therapeutic properties.  The ab...