SynBioFromLeukipposInstitute

Dave Asprey plans to live until he is 180 and he insists he is not kidding.

The technology entrepreneur, businessman, author and top ranking health podcast host has made a career out of biohacking; the art of experimenting with diet, sleep, exercise and tech to improve your body, mind and life.

If you have heard of Bulletproof - the coffee, the diet, the books, the supplements - he is the brains behind the brand, which is all about reaching "a state of high performance".

His biohacking career began when he was fed up with being overweight and unhealthy as a technology entrepreneur hitting success in 1990s Silicon Valley.

"When I was 26 I made $6m (£4m). I lost it when I was 28. But when you're fat and tired nothing else matters," Dave said.

Since then, he believes he has spent close to $1m (£690,000) trying out different ways of eating, sleeping, meditating and exercising - as well as using various pieces of tech - to try and improve his health and wellbeing.

"I lost 100lbs of fat ... I can pay attention, I have more focus, my IQ is measurably higher than it used to be.

"I'm not special. I just started measuring and I started doing things that maybe weren't obvious."

His diet, which is high in specific fats and low in processed carbohydrates, challenges 1980s attitudes towards fatty foods. He started the US craze of adding grass-fed butter to coffee, which caught on with some high-profile celebrities.

Technology has also been key to Dave's biohacking.

When he met me in London, he said: "Technology absolutely makes biohacking more dangerous but it also gives us an amazing level of control over our own bodies that we've never had before."

Dave's top 'tech hacks' include: neurofeedback - wearing electrodes on your head to monitor and influence brain activity; reducing the brightness of your phone using a screen filter - reportedly helping you to sleep better at night; plus heart-rate variability training - the process of monitoring the spaces between your heartbeat to encourage relaxation.

A number of his biohacking techniques have come in for heavy criticism.

When questioned on whether he could be leading his masses of followers into dangerous experimentation, he insisted: "What I'm doing is showing people base principles so they can develop the things that work for them.

"When I talk about something that's dangerous, I really do my best to warn people and say: 'This can hurt you'."

But he insists biohacking methods are crucial for upgrading human performance.

"When we leave this up to doctors, nothing happens. They do not innovate at a rate that's acceptable.

"I'm planning on to live to 180 years old, and I'm not kidding about that.

"I'm not going to count on doctors, with their incredibly slow rate of fearful innovation."

 

Scientists and students have developed the DNA tools to modify bacteria normally found in fermented tea so they can customise cellulose production.

Cellulose is harvested in huge amounts from trees and plants to make materials like paper and cardboard. It’s also produced in a very strong and pure form by some harmless bacteria. This bacterial cellulose is currently used in a range of products including materials for headphones, ingredients in cosmetics and occasionally as a leather substitute in clothes.

The research, which was carried out by academics from the University of Glasgow and is published today in Nature Communications, describes how double-stranded DNA splits using delocalized sound waves that are the hallmark of quantum effects.

DNA contains the code to life and holds a blueprint for each and every living thing on earth. Dedicated enzymes responsible for making new proteins read the code by splitting the double strand in order to access the information. One of the big outstanding questions of biology has been how these enzymes find the initial hole or “bubble” in the double strand to start reading the code.

Dr Mario González Jiménez, researcher, explains, “It is believed that DNA has regions where a specific sequence of bases modifies the stiffness of the double helix favouring the formation of bubbles. This causes a break of the weak bonds between the strands showing the transcription and replication enzymes where to start their task.”

Dr Gopakumar Ramakrishnan adds: “It had been proposed by theoreticians that such DNA bubbles might behave like sound waves, bouncing around in DNA like echoes in a cathedral. However, the current paradigm in biology is that such sound-like dynamics are irrelevant to biological function, as interaction of a biomolecule with the surrounding water will almost certainly destroy any of these effects.”

Researchers in the Ultrafast Chemical Physics group at the University of Glasgow carried out experiments with a laser that produces femtosecond laser pulses about a trillion times shorter than a camera flash. This allowed them to succeed in the detection of sound-like bubbles in DNA. They could show that these bubbles whiz around like bullets in a shooting gallery even in an environment very similar to that which can be found in a living cell.

PhD student Dr Thomas Harwood, recently graduated from the University of Strathclyde, points out: “The sound waves in DNA are not your ordinary sounds waves. They have a frequency of a few terahertz or a billion times higher than a human or a dog can hear!”

Prof Klaas Wynne, leader of the research team and Chair in Chemical Physics at the University of Glasgow, explains: “The terahertz sound-like bubbles we have seen alter our fundamental understanding of biochemical reactions. There were earlier suggestions for a role of delocalized quantum phenomena in light harvesting, magneto reception, and olfaction. The new results now imply a much more general role for sound-like delocalized phenomena in biomolecular processes.”

Last year, researchers working to synthesize the genome of a strain of yeast began to eye a much bigger prize: assembling from scratch the 3 billion base pairs of DNA that drive a human cell. The idea caught the attention of other prominent scientists, and inspired a proposal published online in Science today. The so-called Human Genome Project–Write (HGP-write) aims to synthesize entire genomes—of humans and other species—from their chemical components, and get them to function in living cells.

The initiative generated buzz last month after an invitation-only meeting to discuss the prospect at Harvard Medical School in Boston. Its organizers aimed to keep the details under wraps until this more formal proposal was published—a move that rankled those hoping for a broader public discussion about its ethical, legal, and social implications. Some speculated that scientists would use these engineered cells to create designer humans with no genetic parents.

The new proposal makes clear that HGP-write has no such aim, the authors say. The main goal instead is to drive down the cost of engineering large stretches of DNA and testing their activity in cells. “HGP-write would push current conceptual and technical limits by orders of magnitude,” the authors write.

That “learning by building” approach would put scientists’ understanding of the genome to the test, says chromosome biologist Torsten Waldminghaus of Philipp University of Marburg in Germany, who is not involved in the project. “You know all the parts needed [to make a chromosome], so you take these parts and rebuilt it,” he says. “If it’s functional, you see that you were right.”

Researchers have already constructed functioning viral and bacterial genomes, and the yeast genome project, known as Sc2.0, aims to have all 16 chromosomes—roughly 10 million base pairs—assembled by the end of next year. But a mammalian genome is a different prospect, says synthetic biologist Tom Ellis of Imperial College London, an Sc2.0 collaborator who attended the Harvard meeting. Researchers would need to choose an appropriate cell line to act as a host and then gradually swap out large chunks of its genome with the synthetic DNA. It’s not yet clear how best to physically shuttle this DNA into a mammalian cell, or how to design synthetic sequences that keep their host cell functioning normally. “How do you debug it if you’re throwing in a million bases at a time?” Ellis says. “That’s a lot of hunting.”

Those challenges were enough to give pause to a veteran of the field. “I’m kind of a conservative guy, and at first my reaction [to HGP-write] was not very enthusiastic,” says geneticist Jef Boeke of New York University’s Langone Medical Center in New York City, another Sc2.0 collaborator who eventually helped organize the Harvard meeting and is the lead author on the new paper. When Boeke met with Sc2.0 colleagues last summer to discuss their next target organism, San Francisco, California–based futurist Andrew Hessel of the software company Autodesk “sort of made this impassioned speech” for a new human genome project that would capture the public’s imagination and inspire the field around a single goal, Boeke says. As more potential collaborators got onboard, including Harvard geneticist George Church, Boeke says he “became more and more convinced that this really was a good focus.”

Compared with gene editing with tools such as CRISPR/Cas9, constructing a full genome could allow more widespread manipulation, Church explains. CRISPR is already being refined to make large numbers of genetic changes to cells with increasing precision, but to recode various points throughout the genome, “it might actually be lower-cost to just synthesize the whole thing,” he says.

Pilot projects

The new publication describes pilot projects that might harness large-scale synthesis for human health applications. One set of examples involves “ultrasafe” human cell lines: Cells used to secrete proteins used in drug treatments could be engineered to be resistant to viruses that might contaminate the product. Or stem cells injected into a patient as therapy might be designed so that their tumor suppressor genes are less likely to mutate and cause cancer. One possible pilot project would create human cells that can tolerate a simpler and less costly culture medium by surviving without the typical amino acids and vitamins. Another would engineer a pig genome—eliminating embedded viral genes and genes encoding molecules that are immunogenic, for example—so that researchers could grow pig organs suitable for human transplant.

The paper’s 25 authors hope to launch their project this year with $100 million in funding—a figure Boeke calls “a somewhat arbitrary milestone.” At least for now, the collaborators aren’t expecting a big infusion of new federal funding. The initial sum could be pooled from existing grant funding for labs already working in genome synthesis, he says.

But the mere principle of a fully synthetic human cell is problematic to some. The list of potential benefits is “not an adequate reason to take such an enormous moral step,” says Laurie Zoloth, a bioethicist at Northwestern University, Chicago, in Illinois. “I think developing the tools to make large genetic sequences is an important human goal. Creating an entirely new [human] genomes—that’s a different kind of a project.” Zoloth and synthetic biologist Drew Endy of Stanford University in Palo Alto, California, first drew attention to the May meeting when they published a critical response, arguing that these initial discussions should have been open to the broader public.

The authors had hoped that this paper would coincide with last month’s event, Church explains, but “we didn’t really have a completed message,” when the meeting date arrived. The new proposal promises an “open and ongoing dialogue” about the ethical, legal, and social implications of the work, and suggests that a percentage of the project’s funding should go to supporting such discussions. How genetic engineering might be applied to humans is “one of these things where people keep talking about it,” Church says. “That’s good. It’s not going to happen accidentally.”

Every two hours in Matthew Bennett’s Rice University lab, cyan and yellow lights flashed in synchronization. Bennett and his team had engineered 12 components to generate the coordinated oscillations. This circuit wasn’t electronic, however; it was biological. Two populations of E. coli, each carrying a synthetic gene circuit, cycled in synchronous pulses every 14 hours.
Bennett’s work, published last year in Science,1 is a key application of modern synthetic biology: taking biological components and linking them together to form novel functional circuits. Instead of a program coded in Java and executed by a computer’s working memory, commands were written in DNA and carried out by the microbes’ cellular machinery. LEDs were replaced with fluorescent proteins, and molecular signaling cascades served as the system’s wires.

Stripped back to its most basic components, a synthetic or natural biological network consists of a gene that either switches another gene on (activation) or turns it off (repression). By assembling networks from components found in nature, and harnessing these simple activation and repression interactions, synthetic biologists can engineer oscillators, sensors, counters, and computations of Boolean logic that can be expressed in bacteria, yeast, or mammalian cells, with applications ranging from biological computation to medical diagnostics and biofuel production.

The first synthetic networks were created in 2000, when researchers built an oscillator and others constructed a bistable switch in E. coli. In an oscillator circuit, three genes form a cascade, in which each gene triggers the inactivation of the next gene. In the case of the landmark oscillator constructed by Rockefeller University’s Stanislas Leibler, then at Princeton, and his graduate student Michael Elowitz, one of the three repressor genes was also linked to green fluorescent protein (GFP), resulting in visible pulses of light.2 A bistable switch, on the other hand, consists of just two genes that inactivate each other. When one gene is on, the other is off. Due to variation in the expression of the active gene, the inactive gene occasionally gets the chance to switch on and suppress the expression of the first gene. Like Leibler and Elowitz, MIT bioengineer James Collins and his grad student Tim Gardner, then at Boston University, linked one of the genes with a sequence encoding GFP, and they were able to see the cells switch between states.3 (See “Tinkering With Life,” The Scientist, October 2011.)

Since these early studies, engineers, computer scientists, mathematicians, and physicists have been applying their expertise to engineer synthetic gene networks. In addition to supporting the creation of novel functions, synthetic networks can also give insight into how naturally occurring ones work. As physicist Richard Feynman once wrote on his office blackboard, “What I cannot create, I do not understand.” Studying gene circuits in their natural context is complicated by the complex cellular environment in which they function; reconstructing and tuning gene interactions in vitro can provide a simplified model for how equivalent networks behave in nature. (See illustration below.)

“Naturally occurring gene oscillators, especially the circadian oscillator that regulates our daily rhythms, are hard to study,” says Bennett. “We can easily make changes and fine-tune synthetic gene circuits in ways that are difficult in natural systems. Though our synthetic circuits are inherently different from their natural counterparts, we can use them to study some of the basic principles of how genes dynamically regulate each other.”

A naturally occurring gene network consists of many interacting genes that can activate or repress each other (top). But embedded within a larger network, their function can be hard to study. Synthetic biology can simplify the study of such gene interactions by engineering analogous circuits separate from the larger network (bottom).

A new biosensor can isolate a single molecule in a diffuse solution, boosting the resolving power of such devices one million times and pointing the way toward an effective early detection system for cancer and other illnesses.