Tag Archives: bioengineering

Credit: University of Texas Medical Branch at Galveston.

Scientists transplant lab-grown lungs into pigs — they worked fine

Credit: University of Texas Medical Branch at Galveston.

Credit: University of Texas Medical Branch at Galveston.

In a landmark study of regenerative medicine, researchers at the University of Texas Medical Branch (UTMB) have transplanted bioengineered lungs into adult pigs, with no visible complications. This puts us one step closer to providing human patients in dire need of a transplant with the organs they need to survive.

According to the U.S. Department of Health & Human Services, 20 people die each day waiting for a transplant. Lung transplants are particularly problematic, with the number of people requiring one increasing worldwide, while the number of available transplantable organs has decreased. Lungs are harvested from only 15 percent of all cadaveric donors, whereas kidneys and livers are harvested from 88 percent and hearts from 30 percent of deceased donors

The first human lung transplant procedure was performed in 1963, and the recipient survived 18 days, ultimately succumbing to renal failure and malnutrition. Over time, the number of lung transplant procedures has increased, and the operation is now an accepted treatment for end-stage lung disease. In 2015, there were 4,122 adult lung transplants reported — and that’s not nearly enough. But what if it was possible to grow new, personalized organs for each patient in need of a transplant? Certainly, thousands of lives would be saved each year — and, today, we’re nearing such a goal.

“Our ultimate goal is to eventually provide new options for the many people awaiting a transplant,” said Nichols, professor of internal medicine and associate director of the Galveston National Laboratory at UTMB.

For years, Joan Nichols and Joaquin Cortiella from The University of Texas Medical Branch at Galveston have been working on bioengineering lungs. In 2014, they were the first to grow lung cells in a lab, and their method has been refined ever since to the point that the team is now able to bioengineer transplantable lungs.

The challenges were numerous, of course. For one, in terms of different cell types, the lung is probably the most complex of all organs. For instance, the cells near the entrance are very different from those deep in the lung,

The procedure first starts with a support scaffold, a protein structure of collagen and elastin onto which the new lung will grow. The scaffold is placed in a tank filled with a solution made of nutrients and the pig’s own lung cells, following a carefully designed protocol.

For 30 days, the bioengineered lungs grew in a bioreactor before being transplanted into adult pigs. The medical condition of the animals was assessed at ten hours, two weeks, one month, and two months following the operation, which allowed the team to construct a timeline of the lung tissue’s development. For instance, in just two weeks, the transplanted lungs had established a stable network of blood vessels, which it needs in order to survive.

All of the pigs that received the bioengineered lung remained healthy.

“We saw no signs of pulmonary edema, which is usually a sign of the vasculature not being mature enough,” the researchers wrote. “The bioengineered lungs continued to develop post-transplant without any infusions of growth factors, the body provided all of the building blocks that the new lungs needed.”

This study was only meant to evaluate how well a bioengineered lung could adapt to an adult host organism, with positive results so far. However, the team did not measure how much oxygenation the lungs had provided, which will be researched in the future. And, if all goes well, Nichols and Cortiella hope to grow and transplant bioengineered lungs into people within 5 to 10 years. Besides transplants, bioengineered lungs are a great testing medium for experimental drugs, another line of work that can save countless lives.

“It has taken a lot of heart and 15 years of research to get us this far, our team has done something incredible with a ridiculously small budget and an amazingly dedicated group of people,” they wrote.

The findings appeared in the journal Science Translational Medicine.


If stem cells don’t grow as you want them to, just add a dash of parsley-husk scaffolding

University of Wisconsin-Madison researchers are investigating de-cellularized plant husks as potential 3D scaffolds which, when seeded with human stem cells, could lead to a new class of biomedical implants and tailored tissues.


Image via Pixabay.

We may like to call ourselves the superior being or top of the food chain and all that, but as far as design elegance and functionality is concerned, the things nature comes up with make us look like amateurs. Luckily, we’re not above emulating/copying/appropriating these designs, meaning that structures created by plants and animals have long and liberally been used to advance science and technology.

Joining this noblest of scientific traditions, UWM scientists have turned to de-celled husks of plants such as parsley, vanilla, or orchids to create 3D scaffolds which can be seeded with human stem cells and optimized for growth in lab cultures. This approach would provide an inexpensive, easily scalable and green technology for creating tiny structures which can be used to repair bits of our bodies using stem cells.


The technology draws on the natural qualities of plant structures — strength, porosity, low weight, all coupled with large surface-to-volume ratios — to overcome several of the limitations current scaffolding methods, such as 3D printing or injection molding, face in creating efficient feedstock structures for biomedical applications.

“Nature provides us with a tremendous reservoir of structures in plants,” explains Gianluca Fontana, lead author of the new study and a UW-Madison postdoctoral fellow. “You can pick the structure you want.”

“Plants are really special materials as they have a very high surface area to volume ratio, and their pore structure is uniquely well-designed for fluid transport,” says William Murphy, professor of biomedical engineering and co-director of the UW-Madison Stem Cell and Regenerative Medicine Center, who coordinated the team’s efforts.

The team worked together with Madison’s Olbrich Botanical Gardens’ staff and curator John Wirth to identify which species of plants could be used for the tiny scaffolds. In addition to parsley and orchids, the garden’s staff also found that bamboo, elephant ear plants, and wasabi have structures that would be useful in bioengineering for their shape or other properties. Bulrush was also found to hold promise following examinations of plants in the UW Arboretum.

Human fibroblast cells growing on decellularized parsley.
Image credits Gianluca Fontana / UW-Madison.

Plants form such good scaffolds because their cellular walls are rich in cellulose — probably the most abundant polymer on Earth, as plants use it to form a rough equivalent of our skeleton. The UWM team found that if they strip away all the plant’s cells and chemically treat the left-over cellulose, human stem cells such as fibroblasts are very eager to take up residence in the husks.

Even better, the team observed that stem cells seeded into the scaffolds tended to align to the scaffold’s structure. So it should be possible to use these plant husks to control the structure and alignment of developing human tissues, Murphy says, a critical achievement for muscle or nerve tissues — which don’t work unless correctly aligned and patterned. Since there’s a huge variety of plants — with unique cellulose structures — in nature, we can simply find one that suits our need and use that to tailor the tissues we want.

“Stem cells are sensitive to topography. It influences how cells grow and how well they grow,” Fontana added.

“The vast diversity in the plant kingdom provides virtually any size and shape of interest,” notes Murphy. “It really seemed obvious. Plants are extraordinarily good at cultivating new tissues and organs, and there are thousands of different plant species readily available. They represent a tremendous feedstock of new materials for tissue engineering applications.”

Another big plus for the plantfolds is how easy they are to produce and work with, being “quite pliable […] easily cut, fashioned, rolled or stacked to form a range of different sizes and shapes,” according to Murphy. They’re also easy and cheap to mass produce as well as renewable on account of being, you know, plants.

So far, these scaffolds seem to hold a huge potential. They’ve yet to be tested in living organisms, but there are plans to do so in the future.

The scaffolds have yet to be tested in an animal model, but plans are underway to conduct such studies in the near future.

“Toxicity is unlikely, but there is potential for immune responses if these plant scaffolds are implanted into a mammal,” says Murphy.

“Significant immune responses are less likely in our approach because the plant cells are removed from the scaffolds.”

The full paper “Biomanufacturing Seamless Tubular and Hollow Collagen Scaffolds with Unique Design Features and Biomechanical Properties” has been published in the journal Advanced Healthcare Materials.

Artificial spleen cleans up blood

Magnetic nanobeads in the ‘biospleen’ device bind to Escherichia coli (left) and Staphylococcus aureus (right) and remove them from blood. Harvard’s Wyss Institute

Researchers have developed a device which can clean the blood in the body of virtually all infections – even those which they don’t know about. The device, which was heavily inspired from the human spleen can clean the blood of everything from E. coli to Ebola.

The spleen is an organ that appears in all vertebrates, acting basically as a blood filter. However, while the spleen is very effective at fighting off most blood infections, there are some which it cannot defeat. Those blood infections are extremely dangerous and can become septic; most cases are treated with large spectrum antibiotics – but that approach is not always effective.

Another (long term) problem with antibiotics is that they can kill most, but not all the bacteria – thus helping the remaining ones develop resistance to the drug. Specialized antibiotic would work much better, but the problem is that in over 50% of cases, physicians can’t accurately diagnose the cause of the infection. In search of an alternative, a team led by Donald Ingber, a bioengineer at the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts, developed an artificial ‘biospleen’ which can filter out blood, cleaning it of any potential infection – even if you don’t know what it is.


The ‘biospleen’ uses protein-equipped nanobeads and a magnet to cleanse blood of pathogens. Harvard’s Wyss Institute

The device uses a modified version of mannose-binding lectin (MBL) – a protein which occurs naturally in humans that binds to sugar molecules on the surfaces of more than 90 different bacteria, viruses and fungi. It also binds to the toxins which bacteria release when they are killed – it’s these toxins that trigger the immune overreaction in sepsis.

So far, they tested the device on rats; they infected the rats with E. coli or Staphylococcus aureus and filtered blood through the biospleen. After only 5 hours, 89% of the rats whose blood had been filtered were still alive, compared with only 14% of those that were infected but not treated. Researchers found that the device removed over 90% of the bacteria from the blood, also reducing inflammation in the internal organs.

They then tested the device to see if it could work on larger volumes of blood – like the 5 liters that humans have on average. They ran human blood through the biospleen at a rate of about 1 liter per hour and found that the device removed most of the pathogens within five hours. That rate is probably enough to cure most blood infections, even severe ones. Ingber is very confident in says that the biospleen could help treat even viral diseases such as HIV and Ebola. The group is now testing the device on pigs, and if that works out fine, then human trials will start soon.

This bacterium shoots wires out of its body to power itself

This bacterium has a lot in common with power companies. Power companies use copper wires to channel electricity (and therefore, electrons), and this bacterium developed a mechanism to do something similar: in the absence of oxygen, it grows nanowires from its own body through which it pushes electrons to nearby rocks.

nanowire bacteria

This is how it obtains energy, as opposed to almost all organisms, which use internal processes to produce their energy.

This being said though, researchers have long known that bacteria can swap electrons with minerals, but the details and specific cases were quite rare. Even visualizing bacteria ripping out material from itself to create nanowires to power itself up. But now, one team of physicists and biologists has imaged Shewanella oneidensis, a soil bacteria growing nanowires live – they actually caught them in the act.

Interestingly enough, the bacteria’s wires are actually formed from the bacteria’s outer membranes.

“What the cell is doing is actually morphing a little bit,” Mohamed El-Naggar, a physicist at the University of Southern California who led the new study, tells Popular Science. “It’s extending its outer membrane in the shape of a long tube.”

Previously, due to the lack of directly observed information, scientists believed that the nanowires were made out of cili – hair-like appendages that are common on single-celled organisms.

“This solves a long-standing mystery about how exactly does the charge move on these structures,” El-Naggar says. Bacterial cell membranes have proteins embedded in them called cytochromes, which—ta-da!—are known to pass electrons to one another. Pili don’t have cytochromes.

But studying this type of bacteria is not just about observing one of nature’s most curious behaviors; one day, the research could lead to the mixing of silicon components to biological ones, creating “cyborg” circuits. After all, if the bacteria can use their own biological matter to send electricity to rocks, they could certainly do the same thing with silicone circuits. Engineers are also trying to incorporate nanowire-making bacteria into fuel cells.

However, there’s still plenty of work to do on both fields – and there is no guarantee that the result would be more efficient than today’s options. But it is efficient for bacteria – and that gives researchers hopes; at the very least, they could learn from this interaction.

 “You kind of end up getting the best of both worlds,” El-Naggar says.

Indeed, at the very least, you could create components that fix themselves and replicate themselves (from the bacteria) but still have the precise characteristics of human components

A kidney in a bioreactor after seeding with cells. After transplantation it filtered blood and produced urine. Photograph: Ott Lab/Center for Regenerative Medicine

First bio-engineered kidney works after transplant in rats

A kidney in a bioreactor after seeding with cells. After transplantation it filtered blood and produced urine. Photograph: Ott Lab/Center for Regenerative Medicine

A kidney in a bioreactor after seeding with cells. After transplantation it filtered blood and produced urine. Photograph: Ott Lab/Center for Regenerative Medicine

In a milestone of modern medicine, medical researchers at the Harvard Medical School and Massachusetts General Hospital in Boston have produced the first bioengineered kidney and then successfully transplanted it in a host rat, where it become functional. Each year millions of people die of liver related diseases, and even those who go through the living hell of climbing up the waiting list and get a transplant don’t generally fair too well after the operation because of incompatibilities. Mass produced, bioengineered organs made from the patient’s own cells could save countless lives and the present research shows that we’re making huge strides towards achieving this monumental goal, albeit many more steps need to be taken.

Surgeon Harald Ott Harvard Medical School and Massachusetts General Hospital in Boston along with colleagues  first collected cherry-sized kidneys from dead rats and then employed an ingenious method relying on a detergent solution to strip away the cells. After this operation was finished, what remained were the scaffolds of material the cells were normally embedded in that maintained the original architecture of the organs – a strategy which was previously shown to work for other organs as well, like hearts and lungs.

When bioengineering is concerned, one of the biggest challenges scientists face is growing the consisting cells such that they may work together to form an organ. Armed with this simple method, the basic structure they require is easily at hand now. Next, they carefully filled the scaffold with kidney and blood vessel cells from the recipient rats, and then placed the compound into a bioreactor where liquids filled with nutrients and other essential compounds fed the cells for them grow into a kidney within 12 days.

These bioengineered kidneys were then implanted in rats that had one of their kidneys removed, and since the implants kept the complex architecture of their scaffolds this meant they could be connected to the recipients’ blood and urinary systems. Amazingly, the transplanted kidneys performed their waste filtering functions, producing urine and showing no evidence of bleeding or clot formation. The only problem, one the researchers hope to solve or at least improve on, is that the transplanted kidneys are only 5 to 10 percent as efficient as healthy kidneys.

The researchers claim that this is because the cells they used were still immature, and with a bit of work they hope they can get to 20% which is still far away from healthy kidney functions, but still helpful to a lot of people. There are currently millions of people around the world who rely on blood dialysis machines to help them survive, machines that only provide 10 percent to 15 percent of the functioning of healthy kidneys, and come with an enormous hassle, making living a normal life extremely difficult.

Of course, we’re still talking about bioengineered rat kidneys. The human liver is roughly 100 times bigger and more complex, but the researchers are confident they can scale their work. So far, they have shown the cell-removal technique they applied on rat kidneys also works on pig and human kidneys, so they only need to find a way to refine their process to grow human liver cells on the scaffolds.

“We’ve shown an initial proof of concept that has some promise,” Ott says. “Now it’s time to start the nitty-gritty work, to solve all the technical problems.”

Not long ago, scientists used stem cells to grow the first human kidneys using such a procedure, and recently great strides are made in the attempt to 3-d print fully functional organs. No matter the method, we can only hope scientists come to a functioning transplant.

Findings were reported in the journal Nature Medicine.

An eye growing on the tail of a tadpole.

Tadpoles can see through eyes implanted in their tails

An eye growing on the tail of a tadpole.

An eye growing on the tail of a tadpole.

Most animals have eyes in the vicinity of their brains, typically inside the head, since these are very sensible organs that require a very sophisticated neural link. Recently, biologists at Tufts University have shown that they could implant working eyes in other locations as well, after they granted blind tadpoles vision after they implanted eyes in their tails. The findings might offer further insight into artificial visions and regenerative medicine.

The scientists experimented with 134 tadpoles of the African clawed frog Xenopus laevis, a popular lab pet for researchers worldwide. These had their eyes surgically removed, after which the scientists painstakingly implanted eyes in their torsos and tails.

An experimental set-up was devised with quadrants of water illuminated by either red or blue LED light. The arena, half illuminated in red, half illuminated in blue, would regularly switch between colors via software. The trick lied in the fact that whenever tadpoles when enter the red district, they would receive a mild electrical shock. A motion-tracking camera kept tabs on where the tadpoles were at all times.

Remarkably, it was observed that six of the tadpoles always kept away from the red half of the arena, hinting that they could see with the eyes implanted in their tails. These eyes came from other genetically engineered tadpoles that were instructed to grow a red florescent protein. This allowed the researchers to see whether the eyes sent red nerves outward in the body. Half the 134 recipient tadpoles had no such nerves grow, while about a quarter had nerves projecting toward the gut and the other quarter had nerves extending toward their spine. All of the six tadpoles that showed signs of vision had nerves plugged into their spine, meaning their new eyes were now linked to their nervous system.

“One of the things that this study showed us is that connecting a sense organ as complex as the eye to the spinal cord is sufficient to confer vision,” Dr. Michael Levin said. “So you don’t have to plug in to the actual brain.”

Does this mean that the tadpoles can see just as well as they used to with their original eyes? In reply to this vexing questions, the scientists’ answer is straightforward – they don’t know. “We have no idea what a tadpole is experiencing. This is a philosophical question that is not immediately tractable,” the researchers write in their paper published in the Journal of Experimental Biology.

It’s well worth noting that applications for this kind of research aren’t limited to regenerative medicine only, augmented technology for instance would have a lot to benefit.

“You may want to increase your sensory capacity with sensors that normal people usually don’t have,” he said. “This opens the possibility for attaching all sorts of peripherals to your body.”

Robot designers could also learn a thing or two from the findings, in terms of adaptive flexibility.

“You can imagine that information that comes from any sensory structure – any part of the body – is tagged in some way that uses a unique identifier,” said Dr. Douglas Blackiston, a post-doctoral associate. “So, the source of that information is not nearly as important as what the brain is sensing.”


Synthetic jellyfish made from rat heart cells can swim like the real deal

A team led by researchers at the California Institute of Technology (Caltech) and Harvard University have built this remarkable display of modern bioengineering – a completely engineered jellyfish that blends both living and non-living parts, masterfully fitted together. Called the medusoid, this cyborg jellyfish was created using silicone and muscle cells from a rat’s heart, and surprisingly, it can move and behave exactly like its living, biological counterpart, as seen in the video above.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work.

MedusoidJellyfish are believed to be the oldest multi-organ animals in the world, possibly existing on Earth for the past 500 million years. They can swim with rhythmical contractions of the bell (muscles) that propel it with the force of the water pushed from inside the bell, sort of like jet propelling does with air jets, the action creates an equal and opposite reaction. This is very similar to how the human heart functions at a principle level, making it a viable candidate to model and analyze for tissue engineering purposes.

And Parker along with colleagues from the lab, where they work on creating artificial models of human heart tissues for regenerating organs and testing drugs, didn’t waste one moment after recognizing the jellyfish’s potential.

“It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps,” says Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at Harvard and a coauthor of the study. “I started looking at marine organisms that pump to survive. Then I saw a jellyfish at the New England Aquarium, and I immediately noted both similarities and differences between how the jellyfish pumps and the human heart. The similarities help reveal what you need to do to design a bio-inspired pump.”

The scientists enlisted Caltech biotechnology researcher Janna Nawroth  for their jellyfish-emulating cause.  Nawroth performed most of the experiments, including the mapping of every cell in the bodies of juvenile moon jellies (Aurelia aurita), indispensable to understanding the animal’s propulsion system.

The team looked at an array of possible materials they could use to fashion their synthetic jellyfish; eventually they settled for a silicone polymer that makes up the body of the Medusoid into a thin membrane that resembles a small jellyfish, with eight arm-like appendage. The scientists then grew and applied  a single layer of rat heart muscle on the patterned sheet of silicone.

The swimming behaviour of the Medusoid closely mimics that of the real thing

The swimming behaviour of the Medusoid closely mimics that of the real thing

The medusoid was inserted in an electrically conducting container of fluid and  placed between two electrodes. The current was oscillated  from zero volts to five volts, and the medusoid began to swim with synchronized contractions that mimic those of real jellyfish.

“I was surprised that with relatively few components—a silicone base and cells that we arranged—we were able to reproduce some pretty complex swimming and feeding behaviors that you see in biological jellyfish,” says John Dabiri, a bioengineer who studies biological propulsion at the California Institute of Technology (Caltech) in Pasadena. “I’m pleasantly surprised at how close we are getting to matching the natural biological performance, but also that we’re seeing ways in which we can probably improve on that natural performance. The process of evolution missed a lot of good solutions.”

Parker says his team is taking synthetic biology to a new level. “Usually when we talk about synthetic life forms, somebody will take a living cell and put new genes in. We built an animal. It’s not just about genes, but about morphology and function.”

The team’s next goal is to design a completely self-contained system that is able to sense and actuate on its own using internal signals, as human hearts do. “You’ve got a heart drug?” says Parker. “You let me put it on my jellyfish, and I’ll tell you if it can improve the pumping.”

The findings were reported in the journal Nature Biotechnology.

In this 2007 file photo, a farmer laments over his destroyed crop in Tamin Nadu. (c) M. Srinath

The flood-tolerant crops of the future

In this 2007 file photo, a farmer laments over his destroyed crop in Tamin Nadu. (c) M. Srinath

In this 2007 file photo, a farmer laments over his destroyed crop in Tamin Nadu. (c) M. Srinath

Floods are a major hazard to crops worldwide. This year alone, billions of dollars worth of crops came to waste after catastrophic floods raided Pakistan, Bangladesh, Vietnam, Australia, Thailand, the UK and America, and famines have hit millions of people worldwide as a result of ruined agriculture. What if you could, however, engineer crops that could resist floods and steadily return to their usual cycle after waters retreat? Scientists at University of Nottingham and the University of California, Riverside have made a break through in this sense, as they may have stumbled across the key to engineering flood-resistant crops.

“We have identified the mechanism through which reduced oxygen levels are sensed. The mechanism controls key regulatory proteins called transcription factors that can turn other genes on and off. It is the unusual structure of these proteins that destines them for destruction under normal oxygen levels, but when oxygen levels decline, they become stable. Their stability results in changes in gene expression and metabolism that enhance survival in the low oxygen conditions brought on by flooding. When the plants return to normal oxygen levels, the proteins are again degraded, providing a feedback control mechanism,” explained Nottingham University crop scientist Michael Holdsworth.

Basically, the engineered plants in the researchers’ lab can sense low oxygen levels and change their metabolism accordingly to survive in the new conditions, a brilliant feat which came more or less via an adjacent research, which involved investigating the regulation of gene expression during seed germination. Holdsworth now hopes that the crops of the future will be safer against folds, as years from now the protein turnover mechanism will be fully understood and prone to manipulation.

“At this time, we do not know for sure the level of conservation across plants of the turnover mechanism in response to flooding. We have quite a bit of assurance from our preliminary studies, however, that there is cross-species conservation. Our experiments on Arabidopsisshow that manipulation of the pathway affects low oxygen stress tolerance. There is no reason why these results cannot be extrapolated to other plants and crops. What we plan to do next is to nail down this mechanism more clearly,” said Bailey-Serres, a geneticist at the University of California.

University of Nottingham

Transistor gates created out of E. Coli bacteria – huge biocomputing leap forward!

Scientists at London’s Imperial College have successfully managed to create biological logic gates, indispensible for the production of electronical devices, simply our of bacteria and DNA. Though the research detailed in a recently published study in the journal Nature Communications was anything but simple, it provides an incredible advancement in the field of biotechnology.

“Logic gates are the fundamental building blocks in silicon circuitry that our entire digital age is based on,” said Richard Kitney co-author of the research project recently published in the journal nature Communications. “Without them, we could not process digital information. Now that we have demonstrated that we can replicate these parts using bacteria and DNA, we hope that our work could lead to a new generation of biological processors, whose applications in information processing could be as important as their electronic equivalents.”

Scientists have expermentally proven that their that their biological gates can replicate the process that is equivalent to an electronic transistor gate that can be switched on and off. In one experimental instance, the team made an AND gate from E Coli bacteria, a keyword most of us link with an impending pandemic (there are numerous variants of the strain, few are indeed dangerous), which had its DNA altered to perform a switch on/off action when interacting with a certain chemical.

While these are the most advanced biological gates created so far, Kitney and his team aknowledge that they’re still very far away from presenting to the world a reliable product. The future, however, seems to shine for bio technology. Such bio processing units could be streamed through one’s arteries and monitor various parameters through biosensors. In case of misbalanced parameters, the biodevice might then trigger medication to relieve the affected area. Cancer cells could be pounded imediately before they have the chance to spread. The potential applications are too many to ennounce here, albeit still very far away from reality.

The next step in the development are multiple gates in “more complex circuitry”, which could one day lead to building blocks for “microscopic biological computers,” like the ones listed in the potential applications above. One step at a time.