scientificamerican--2020-12-01--Viruses Can Help Us as Well as Harm Us

Viruses Can Help Us as Well as Harm Us

This year millions of people around the world have radically changed their way of life to avoid contact with other people and , thus , the novel coronavirus .
Despite social distancing , many have still gotten sick in part from other viral infections .
That is because , as scientists are increasingly learning , many viruses are lurking quietly in the human body , hidden away in cells in the lungs , blood and nerves and inside the multitudes of microbes that colonize our gut .
Biologists estimate that 380 trillion viruses are living on and inside your body @ @ @ @ @ @ @ .
Some can cause illness , but many simply coexist with you .
In late 2019 , for example , researchers at the University of Pennsylvania discovered 19 different strains of redondovirus in the respiratory tract ; a handful were associated with periodontal disease or lung disease , but others could possibly fight respiratory illnesses .
Scientists ' rapidly expanding knowledge makes it clear that we are not made up primarily of “ human ” cells that are occasionally invaded by microbes ; our body is really a superorganism of cohabitating cells , @ @ @ @ @ @ @ all : viruses .
The latest counts indicate that as much as half of all the biological matter in your body is not human .
A decade ago researchers were barely aware that the human virome existed .
Today we see the vast virome as an integral part of the larger human microbiome , a crazy quilt of passive and active microscopic organisms that occupy almost every corner of our being .
We have been mapping the virome for 10 years , and the deeper we investigate , the more the virome looks @ @ @ @ @ @ @ daily lives positively as well as negatively .
Recent research shows we could even harness the virome to promote our own health .
Investigators at the Rockefeller University , for example , have purified an enzyme from a virus that kills bacteria found in patients who are struggling against methicillin-resistant staphylococcal infection .
The results are so encouraging that the Food and Drug Administration has designated the enzyme as a “ breakthrough therapy , ” and it is now in phase 3 clinical trials .
Today we routinely speak about the “ good @ @ @ @ @ @ @ our lives .
Viruses fall into the same categories .
The challenge now is to figure out how to stop the bad ones and promote the good ones .
The human body is a rich environment for microbes , replete with proteins , fats and carbohydrates .
Many viruses have figured out how to peacefully thrive in it without making us sick .
Viruses need to invade host cells to reproduce , and they are adept at exploiting all the options in our body .
A dozen years ago inexpensive genome sequencing led @ @ @ @ @ @ @ mouth and gut .
By 2013 or so scientists located viruses on the skin and in the respiratory tract , blood and urine .
Most recently , we have found them in even more surprising places .
In September 2019 , for example , Chandrabali Ghose and our colleagues and I published details about viruses that we discovered in the cerebrospinal fluid of adults who were undergoing testing for various conditions .
The viruses belonged to several different families and were not associated with any known disease .
We also found the same @ @ @ @ @ @ @ and breast milk .
Scientists knew that a few rare , infectious viruses , notably herpes , could sneak into cerebrospinal fluid , but finding random viruses that seemed to be mere bystanders was a surprise .
The central nervous system , which is supposed to be a sterile environment , is colonized by a somewhat diverse viral community .
It appears that our viromes begin to accumulate when we are born .
Studies reveal a high diversity of viruses in the infant gut shortly after birth , suggesting that they probably come @ @ @ @ @ @ @ ingested from breast milk .
Some of these viruses decline in number as infants grow to weeks or months old ; others enter their bodies from the air , water , food and other people .
These viruses grow in number and diversity , infecting cells where they will persist for years .
Infant viromes are unstable , whereas adult viromes are relatively stable .
Anelloviruses , a family of 200 different species , are present in almost everyone as we get older .
This mirrors what we observe for bacteria as well @ @ @ @ @ @ @ us do not target our cells .
Instead they look for the bacteria in our microbiomes .
Known as bacteriophages , or phages , these viruses sneak inside bacterial cells , use the machinery there to make copies of themselves , then often burst out to infect more bacteria , killing their host cells in the process .
Bacteriophages are nearly ubiquitous in nature .
If you look hard enough , you will find them in soil , in any source of water from the ocean to your tap at home , and @ @ @ @ @ @ @ , the Arctic and hot springs .
You will even find them floating in the air .
They persist in all these places because they are hunting the bacteria that live in all these places .
We humans are just another hunting ground .
In 2017 Sophie Nguyen and Jeremy Barr , then at San Diego State University , demonstrated that many phages get to their final locations in the body by crossing through mucosal membranes .
In laboratory experiments , phages worked through membranes that line the intestine , lung , liver @ @ @ @ @ @ @ But when they randomly cross into a place such as the central nervous system , where there are few bacteria to be hosts , they may have no way to replicate and may ultimately perish .
The virome can vary greatly from one part of the body to another .
When Ghose and I looked for viruses in unexpected places , we also determined that viruses in the mouth are different from viruses in the gut , which are different from viruses in urine or in blood .
We knew this was the @ @ @ @ @ @ @ we did not have enough data for viruses .
Although it is not hard to find volunteers who will spit in a cup , it is hard to get them to provide stool or blood samples and to persuade universities to sign off on obtaining and processing these samples .
When we do have the goods , we must filter out the bacteria , leaving tiny bits of viral material we can examine under a microscope and insert into a machine that sequences the nucleic acids that encode the genes that are present @ @ @ @ @ @ @ of this work now to be able to tell what part of the body they are examining just by noting the viruses present .
My colleague Melissa Ly of the University of California , San Diego , and I have also shown that by comparing the viromes of unrelated people we can determine if any of them live together .
Although different people can have significantly different viromes , people who cohabitate appear to share about 25 percent of the viruses in their viromes .
Viruses can be transmitted from one household member @ @ @ @ @ @ @ contagious means such as coughing but also through casual contact and sharing sinks , toilets , desks and food .
Although we have only studied small numbers of people , the data show that nonromantic roommates share a similar percentage of viruses as romantic roommates do .
Intimate contact seems to make little difference ; just living in the same space is enough .
The puzzle is tricky , however .
Shira Abeles , also at U.C .
San Diego , has identified big differences in the oral viromes of men and women @ @ @ @ @ @ @ but no one has demonstrated such a connection .
We do know that viromes can vary considerably with geographic populations .
For example , there is less diversity in the viromes of individuals in Western countries than there is among individuals in non-Western countries .
These differences may be related to both diet and environment .
Many viruses in our virome infect bacteria , but a smaller proportion infect cells in our tissues directly .
These viruses may be in the minority because our immune system suppresses them .
Iwijn De Vlaminck , @ @ @ @ @ @ @ when a person 's immune system is strongly challenged—for example , when someone has received an organ transplant and must take immunosuppressing drugs to avoid rejecting the organ—the presence of certain viruses increases dramatically .
In these cases , we see a rise in both viruses known to cause disease and those that do not .
This observation suggests that under normal circumstances our immune system keeps the virome in check , but when immunity is hampered , viruses can multiply readily .
We may be seeing this kind of opportunism with COVID-19 @ @ @ @ @ @ @ SARS-CoV-2 virus , particularly those with severe illness , may develop coinfections .
The most common are a secondary bacterial pneumonia , or bacteremia ( a rise of bacteria in the bloodstream ) , involving organisms such as Staphylococcus aureus and Streptococcus pneumoniae .
Though less common , we have also seen viral coinfections such as influenza , respiratory syncytial virus and adenovirus .
Viruses lurking in the virome may also reactivate , such as Epstein-Barr virus and cytomegalovirus .
When the immune system is paying attention to COVID-19 , the patient may @ @ @ @ @ @ @ .
Many phages , despite being hunters , live in harmony with their prey for a long time and may never break out .
A virus is just a ball of protein enveloping a molecule of genetic instructions—the virus 's genetic code .
When some phages infect a bacterium , they integrate their genome into the bacterium 's genome .
Although certain viruses reproduce immediately , killing their host bacteria , other phages just persist inside their host , as if in quiet hibernation .
This is probably a survival strategy ; when @ @ @ @ @ @ @ copy of its genome , it copies the phage genome as well .
In this model , the survival of the host determines the survival of the phage , so the phage has a vested interest in maintaining its host .
It is clear why such a strategy benefits the phage but not so clear how it could benefit the bacteria .
For whatever reason , it seems that many bacteria in the body have grown accustomed to living with their phages .
When the opportunity arises , hibernating phages may awaken and @ @ @ @ @ @ @ cells .
Sometimes the exiting phages take bacterial genes along with them .
This payload can at times benefit the next bacteria the phages infect .
I have found phages in saliva , for example , carrying genes that help bacteria evade our immune system .
Some phages even carry genes that help bacteria resist antibiotics .
Phages have no need for such genes , because phages can not be killed by antibiotics , so when they provide the genes to bacteria they promote the hosts ' survival—synonymous with survival of the phages @ @ @ @ @ @ @ often .
Phages can take protection of their host further .
The bacterium Pseudomonas aeruginosa , best known for causing pneumonia , triggers a number of illnesses .
People who have lung diseases such as cystic fibrosis find it nearly impossible to clear this bacterium from their lungs , even when taking antibiotics designed to kill it .
Some P. aeruginosa have integrated what are called filamentous phages into their genomes .
In 2019 researchers led by a group at Stanford , including Elizabeth Burgener and Paul Bollyky , discovered that filamentous phages @ @ @ @ @ @ @ and proteins that help bacteria hide from antibiotics .
This allows the bacteria to shelter in place until the antibiotics go away , living to cause infection another day .
Viruses That Help Us It is not a big leap to wonder whether we can harness the viruses living within us to improve our health .
We have already found a few cases in which this happens naturally .
As phages move around the body looking for bacteria , some of them bind to cells on the surface of mucosal membranes , such @ @ @ @ @ @ @ throat , stomach and intestines .
The phages can not replicate there , but they can lie in wait for a vulnerable host to come by .
This process could theoretically protect us from some illnesses .
Say you eat food contaminated with Salmonella bacteria .
If the bacteria brush along the stomach 's membrane , phages there could ostensibly infect the bacteria and kill them before they can cause disease .
In this way , phages may serve as a de facto immune system that protects us against disease .
No one @ @ @ @ @ @ @ 2019 a research group in Finland showed that phages bound to mucus in pigs and rainbow trout persisted there for seven days and protected against one kind of bacterium that infects these animals .
One phage getting a lot of attention is crAssphage , discovered in 2014 by Bas Dutilh of the Radboud Institute in the Netherlands .
Studies since then have shown that it inhabits most people around the world—except , it seems , for traditional hunter-gatherer populations .
It is unusual to find the exact same virus spread so far and @ @ @ @ @ @ @ it to any disease .
Scientists think it controls the prevalence of a common gut bacterium called Bacteroides .
If so , we might be able to exploit it to improve gastrointestinal conditions .
It is so prevalent in human feces that researchers now test for it in drinking water to see if the water has been contaminated by sewage .
Physicians are especially interested in phages that might counteract the aggressive rise of antibiotic-resistant bacteria .
Development of new antibiotics has failed to keep pace .
The World Health Organization estimates that @ @ @ @ @ @ @ least 10 million deaths annually , so alternative therapies are vital .
Phages were discovered more than 100 years ago , and physicians tried to use them to treat bacteria that cause disease , though without great success .
In the 1940s antibiotics replaced phages in most of the world because the drugs were much more effective and much easier to use .
Now some medical researchers , such as the Rockefeller University investigators who used a phage enzyme to fight methicillin-resistant Staphylococcus infection , are taking a new look at phages .
@ @ @ @ @ @ @ to administer phages because they did not know whether the human immune system would overreact , causing dangerous levels of inflammation .
Phages for therapeutic use are grown in bacteria , and if the bacteria are not completely removed before the phages are administered , the bacteria can trigger an overly aggressive immune response .
Today we have more sophisticated methods of purifying phages , and worries about adverse reactions have largely subsided .
What really limits the use of phages to treat infectious disease is that effective viruses are hard to find @ @ @ @ @ @ @ through natural habitats for phages that might be active against bacteria that cause human disease .
Now that we know that viruses are plentiful in feces , saliva and sputum , researchers have realized that one of the richest sources of phages may be local sewage-processing plants .
A few such phages are already being used for experimental treatments .
In a landmark 2016 case overseen by Robert Schooley , also at U.C .
San Diego , doctors used phages from sewage , as well as those from environmental sources , to successfully @ @ @ @ @ @ @ the school who was in multiorgan failure because of Acinetobacter baumannii , a notoriously drug-resistant bacteria .
As we learn more about the roles of viruses in the human virome , we may uncover more therapeutic possibilities .
Alejandro Reyes of Washington University in St. Louis has shown that phages in mice can shape the rodents ' bacterial communities , although we are not sure what changes first : the viruses or the bacteria .
If the viral communities change first , they can sculpt the bacterial communities to serve them .
If @ @ @ @ @ @ @ viral communities are likely just adapting so they can infiltrate the reshaped bacteria .
Researchers have shown that viromes can change significantly in periodontal disease and in inflammatory bowel diseases .
Although it will take a long time for us to unravel the human virome , it is important to consider how far we have come in just 10 years .
A decade ago many scientists thought of the microbiome as a kind of passive layer of tiny organisms inside the body , mostly in the gut .
Now we know that although @ @ @ @ @ @ @ stable , some parts are active and changing .
And it is beginning to look like the most dynamic players are the viruses .
A 2018 study of brain tissue donated by people who had died of Alzheimer 's disease revealed high levels of herpesviruses .
Then , in May 2020 , investigators at Tufts University and the Massachusetts Institute of Technology , who have developed brainlike tissue in the lab , infected their tissue with herpes simplex 1 , and the tissue became full of amyloid plaquelike formations akin to those that @ @ @ @ @ @ @ Alzheimer 's .
It is startling to realize that we could discover remarkable roles for old viruses .
As we look deeper , we may find new categories of viruses that impact human health , as well as new ways to exploit viruses to manipulate our microbiome and protect us from disease .
If we humans can figure out how to manage the bad viruses and exploit the good ones , we could help ourselves become stronger superorganisms .

In the past few years millions of people around the world have radically changed their way of life to avoid contact with other people and, thus, the novel coronavirus. Despite social distancing, many have still gotten sick in part from other viral infections. That is because, as scientists are increasingly learning, many viruses are lurking quietly in the human body, hidden away in cells in the lungs, blood and nerves and inside the multitudes of microbes that colonize our guts.
Biologists estimate that 380 trillion viruses are living on and inside your body right now—10 times the number of bacteria. Some can cause illness, but many simply coexist with you. In late 2019, for example, researchers at the University of Pennsylvania discovered 19 different strains of redondovirus in the respiratory tract; a handful of them were associated with periodontal disease or lung disease, but others could possibly fight respiratory illnesses. Scientists’ rapidly expanding knowledge makes it clear that we are not made up primarily of “human” cells that are occasionally invaded by microbes; our bodies are really superorganisms of cohabitating cells, bacteria, fungi and, most numerous of all, viruses. The latest counts indicate that as much as half of all the biological matter in your body is not human.
A decade ago researchers were barely aware that the human virome existed. Today we see the vast virome as an integral part of the larger human microbiome, a crazy quilt of passive and active microscopic organisms that occupy almost every corner of our being. We have been mapping the virome for more than 10 years, and the deeper we investigate, the more the virome looks like a partnership that can influence our daily lives positively as well as negatively. Recent research shows we could even harness the virome to promote our own health. Investigators at the Rockefeller University, for example, purified an enzyme from a virus that kills bacteria found in patients who are struggling against methicillin-resistant staphylococcal infection. The results were so encouraging that the Food and Drug Administration designated the enzyme as a “breakthrough therapy.” Today we routinely speak about the “good” and “bad” bacteria in our lives. Viruses fall into the same categories. The challenge now is to figure out how to stop the bad ones and promote the good ones.
Infected at Birth
The human body is a rich environment for microbes, replete with proteins, fats and carbohydrates. Many viruses have figured out how to peacefully thrive in it without making us sick.
Viruses need to invade host cells to reproduce, and they are adept at exploiting all the options in our bodies. About a dozen years ago inexpensive genome sequencing led us to discover plentiful viruses in the mouth and gut. By 2013 or so scientists located viruses on the skin and in the respiratory tract, blood and urine. Most recently, we have found them in even more surprising places. In September 2019, for example, Chandrabali Ghose and our colleagues and I published details about viruses that we discovered in the cerebrospinal fluid of adults who were undergoing testing for various conditions. The viruses belonged to several different families and were not associated with any known disease. We also found the same viruses in blood plasma, joint fluid and breast milk. Scientists knew that a few rare, infectious viruses, notably herpes, could sneak into cerebrospinal fluid, but finding random viruses that seemed to be mere bystanders was a surprise. The central nervous system, which is supposed to be a sterile environment, is colonized by a somewhat diverse viral community.
It appears that our viromes begin to accumulate when we are born. Studies reveal a high diversity of viruses in the infant gut shortly after birth, suggesting that they probably come from the babies’ mothers, some ingested from breast milk. Some of these viruses decline in number as infants grow to weeks or months old; others enter their bodies from the air, water, food and other people. These viruses grow in number and diversity, infecting cells where they will persist for years. Infant viromes are unstable, whereas adult viromes are relatively stable. Anelloviruses, a family of 200 different species, are present in almost everyone as we get older. This mirrors what we observe for bacteria as well.
Many of the viruses living inside us do not target our cells. Instead they look for the bacteria in our microbiomes. Known as bacteriophages, or phages, these viruses sneak inside bacterial cells, use the machinery there to make copies of themselves, then often burst out to infect more bacteria, killing their host cells in the process. Bacteriophages are nearly ubiquitous in nature. If you look hard enough, you will find them in soil, in any source of water from the ocean to your tap at home, and in extreme environments such as acid mines, the Arctic and hot springs. You will even find them floating in the air. They persist in all these places because they are hunting the bacteria that live in all these places. We humans are just another hunting ground.
In 2017 Sophie Nguyen and Jeremy Barr, then at San Diego State University, demonstrated that many phages get to their final locations in the body by crossing through mucosal membranes. In laboratory experiments, phages worked through membranes that line the intestine, lung, liver, kidney and even the brain. But when they randomly cross into a place such as the central nervous system, where there are few bacteria to be hosts, they may have no way to replicate and may ultimately perish.
Your Personal Virus Profile
The virome can vary greatly from one part of the body to another. When Ghose and I looked for viruses in unexpected places, we also determined that viruses in the mouth are different from viruses in the gut, which are different from viruses in urine or in blood. We knew this was the case for bacteria, but early on we did not have enough data for viruses. Although it is not difficult to find volunteers who will spit in a cup, it is hard to get them to provide stool or blood samples and to persuade universities to sign off on obtaining and processing these samples. When we do have the goods, we must filter out the bacteria, leaving tiny bits of viral material we can examine under a microscope and insert into a machine that sequences the nucleic acids that encode the genes that are present. Still, researchers have done enough of this work now to be able to tell what part of the body they are examining just by noting the viruses present.
Credit: AXS Biomedical Animation Studio
My colleague Melissa Ly of the Duke Human Vaccine Institute and I have also shown that by comparing the viromes of unrelated people, we can determine if any of them live together. Although different people can have significantly different viromes, people who cohabitate appear to share about 25 percent of the viruses in their viromes. Viruses can be transmitted from one household member to another not just through typical contagious means such as coughing but also through casual contact and sharing sinks, toilets, desks and food. Although we have studied only small numbers of people, the data show that nonromantic roommates share a similar percentage of viruses as romantic roommates do. Intimate contact seems to make little difference; just living in the same space is enough.
The puzzle is tricky, however. Shira Abeles of the University of California, San Diego, has identified big differences in the oral viromes of men and women; hormones could be the reason, but no one has demonstrated such a connection. We do know that viromes can vary considerably with geographic populations. For example, there is less diversity in the viromes of individuals in Western countries than there is among individuals in non-Western countries. These differences may be related to both diet and environment.
Credit: AXS Biomedical Animation Studio
Vagabonds or Freeloaders?
Many viruses in our virome infect bacteria, but a smaller proportion infect cells in our tissues directly. These viruses may be in the minority because our immune system suppresses them. Iwijn De Vlaminck, then at Stanford University, demonstrated that when a person’s immune system is strongly challenged—for example, when someone has received an organ transplant and must take immunosuppressing drugs to avoid rejecting the organ—the presence of certain viruses increases dramatically. In these cases, we see a rise in both viruses known to cause disease and those that do not. This observation suggests that under normal circumstances our immune system keeps the virome in check, but when immunity is hampered, viruses can multiply readily.
We may be seeing this kind of opportunism with COVID-19. People who get sick from the SARS-CoV-2 virus, particularly those with severe illness, may develop coinfections. The most common are a secondary bacterial pneumonia, or bacteremia (a rise of bacteria in the bloodstream), involving organisms such as Staphylococcus aureus and Streptococcus pneumoniae. Though less common, we have also seen viral coinfections such as influenza, respiratory syncytial virus and adenovirus. Viruses lurking in the virome may also reactivate, such as Epstein-Barr virus and cytomegalovirus. When the immune system is paying attention to COVID, the patient may be more susceptible to other viral outbreaks.
Many phages, despite being hunters, live in harmony with their prey for a long time and may never break out. A virus is just a ball of protein enveloping a molecule of genetic instructions—the virus’s genetic code. When some phages infect a bacterium, they integrate their genome into the bacterium’s genome. Although certain viruses reproduce immediately, killing their host bacteria, other phages just persist inside their host, as if in quiet hibernation. This is probably a survival strategy; when the host bacterium divides, creating a copy of its genome, it copies the phage genome as well. In this model, the survival of the host determines the survival of the phage, so the phage has a vested interest in maintaining its host. It is clear why such a strategy benefits the phage but not so clear how it could benefit the bacteria. For whatever reason, it seems that many bacteria in the body have grown accustomed to living with their phages.
When the opportunity arises, hibernating phages may awaken and produce many progeny, killing their host cells. Sometimes the exiting phages take bacterial genes along with them. This payload can at times benefit the next bacteria the phages infect. I have found phages in saliva, for example, carrying genes that help bacteria evade our immune system. Some phages even carry genes that help bacteria resist antibiotics. Phages have no need for such genes, because phages cannot be killed by antibiotics, so when they provide the genes to bacteria they promote the hosts’ survival—synonymous with survival of the phages. We see these kinds of transfers often.
Phages can take protection of their host further. The bacterium Pseudomonas aeruginosa, best known for causing pneumonia, triggers a number of illnesses. People who have lung diseases such as cystic fibrosis find it nearly impossible to clear this bacterium from their lungs, even when taking antibiotics designed to kill it. Some P. aeruginosa have integrated what are called filamentous phages into their genomes. In 2019 researchers led by a group at Stanford, including Elizabeth Burgener and Paul Bollyky, discovered that filamentous phages can form a protective cloak—layers of carbohydrates and proteins that help bacteria hide from antibiotics. This allows the bacteria to shelter in place until the antibiotics go away, living to cause infection another day.
Viruses That Help Us
It is not a big leap to wonder whether we can harness the viruses living within us to improve our health. We have already found a few cases in which this happens naturally. As phages move around the body looking for bacteria, some of them bind to cells on the surface of mucosal membranes, such as those that line the nose, throat, stomach and intestines. The phages cannot replicate there, but they can lie in wait for a vulnerable host to come by.
This process could theoretically protect us from some illnesses. Say you eat food contaminated with Salmonella bacteria. If the bacteria brush along the stomach’s membrane, phages there could ostensibly infect the bacteria and kill them before they can cause disease. In this way, phages may serve as a de facto immune system that protects us against disease. No one has proved this yet, but in 2019 a research group in Finland showed that phages bound to mucus in pigs and rainbow trout persisted there for seven days and protected against one kind of bacterium that infects these animals.
One phage getting a lot of attention is crAssphage, discovered in 2014 by Bas Dutilh of the Radboud Institute in the Netherlands. Studies since then have shown that it inhabits most people around the world—except, it seems, for traditional hunter-gatherer populations. It is unusual to find the exact same virus spread so far and wide, and no one has linked it to any disease. Scientists think it controls the prevalence of a common gut bacterium called Bacteroides. If so, we might be able to exploit it to improve gastrointestinal conditions. It is so prevalent in human feces that researchers now test for it in drinking water to see if the water has been contaminated by sewage.
Physicians are especially interested in phages that might counteract the aggressive rise of antibiotic-resistant bacteria. Development of new antibiotics has failed to keep pace. The World Health Organization has estimated that by 2050 these pathogens will cause at least 10 million deaths annually, so alternative therapies are vital. Phages were discovered more than 100 years ago, and physicians tried to use them to treat bacteria that cause disease, though without great success. In the 1940s antibiotics replaced phages in most of the world because the drugs were much more effective and much easier to use. Now some medical researchers, such as the Rockefeller University investigators who used a phage enzyme to fight methicillin-resistant Staphylococcus infection, are taking a new look at phages.
For years most physicians have been afraid to administer phages because they did not know whether the human immune system would overreact, causing dangerous levels of inflammation. Phages for therapeutic use are grown in bacteria, and if the bacteria are not completely removed before the phages are administered, the bacteria can trigger an overly aggressive immune response. Today we have more sophisticated methods of purifying phages, and worries about adverse reactions have largely subsided.
What really limits the use of phages to treat infectious disease is that effective viruses are hard to find. For many years researchers have combed through natural habitats for phages that might be active against bacteria that cause human disease. Now that we know viruses are plentiful in feces, saliva and sputum, researchers have realized that one of the richest sources of phages may be local sewage-processing plants.
A few such phages are already being used for experimental treatments. In a landmark 2016 case overseen by Robert Schooley, also at U.C. San Diego, doctors used phages from sewage, as well as those from environmental sources, to successfully treat Tom Patterson, a professor at the school who was in multiorgan failure because of Acinetobacter baumannii, a notoriously drug-resistant bacteria.
Improved Health
As we learn more about the roles of viruses in the human virome, we may uncover more therapeutic possibilities. Alejandro Reyes of Washington University in St. Louis has shown that phages in mice can shape the rodents’ bacterial communities, although we are not sure what changes first: the viruses or the bacteria. If the viral communities change first, they can sculpt the bacterial communities to serve them. If the bacterial communities change first, the viral communities are probably just adapting so they can infiltrate the reshaped bacteria. Researchers have shown that viromes can change significantly in periodontal disease and in inflammatory bowel diseases.
Although it will take a long time for us to unravel the human virome, it is important to consider how much progress we made in just 10 years. A decade ago many scientists thought of the microbiome as a kind of passive layer of tiny organisms inside the body, mostly in the gut. Now we know that although some parts of the microbiome are indeed stable, some parts are active and changing. And it is beginning to look like the most dynamic players are the viruses. A 2018 study of brain tissue donated by people who had died of Alzheimer’s disease revealed high levels of herpesviruses. Then, in May 2020, investigators at Tufts University and the Massachusetts Institute of Technology, who have developed brainlike tissue in the lab, infected their tissue with herpes simplex 1, and the tissue became full of amyloid plaquelike formations akin to those that riddle the brains of people who have Alzheimer’s. It is startling to realize that we could discover remarkable roles for old viruses.
As we look deeper, we may find new categories of viruses that impact human health, as well as new ways to exploit viruses to manipulate our microbiome and protect us from disease. If we humans can figure out how to manage the bad viruses and exploit the good ones, we could help ourselves become stronger superorganisms.
Watch This Next


scientificamerican--2020-12-01--Are We Real? And Other Questions of Physics

What if this life is just a computer simulation running on some intellectually superior alien ’ s console ?
Something about this idea is tantalizing to people ( evidenced by the success of The Matrix films ) and has special appeal for our readers .
It ’ s hooked physicists , philosophers , computer scientists and engineers , too , as author Anil Ananthaswamy writes in this edition ’ s cover feature [ “ Do We Live in a Simulation ?
Chances Are about 50–50 ” ] .
What is it , exactly , that is so enticing about this @ @ @ @ @ @ @ mere puppets of a more advanced species ?
Or perhaps it ’ s the calm that comes from the idea that none of this is real anyway .
Examining the nature of our own reality , indeed whether we have a reality , is the most “ meta ” branch of physics .
In more satisfying endeavors , journalist Daniel Garisto reviews the long history of the search for black holes , whose champions were awarded this year ’ s Nobel Prize in Physics [ “ Nobel Prize Work Took Black Holes from @ @ @ @ @ @ @ recipient , physicist Andrea Ghez , pushed her fellow astronomers and technicians tirelessly , despite doubt from the field , as her colleague Hilton Lewis describes in this issue ’ s opinion section [ “ How Andrea Ghez Won the Nobel for an Experiment Nobody Thought Would Work ” ] .
Sometimes we have to fight for the realities we believe in .

What if this life is just a computer simulation running on some intellectually superior alien’s console? Something about this idea is tantalizing to people (evidenced by the success of The Matrix films) and has special appeal for our readers. It’s hooked physicists, philosophers, computer scientists and engineers, too, as author Anil Ananthaswamy writes in this edition’s cover feature [“Do We Live in a Simulation? Chances Are about 50–50”]. What is it, exactly, that is so enticing about this possibility? The fear that we are mere puppets of a more advanced species? Or perhaps it’s the calm that comes from the idea that none of this is real anyway. Examining the nature of our own reality, indeed whether we have a reality, is the most “meta” branch of physics.
In more satisfying endeavors, journalist Daniel Garisto reviews the long history of the search for black holes, whose champions were awarded this year’s Nobel Prize in Physics [“Nobel Prize Work Took Black Holes from Fantasy to Fact”]. One recipient, physicist Andrea Ghez, pushed her fellow astronomers and technicians tirelessly, despite doubt from the field, as her colleague Hilton Lewis describes in this issue’s opinion section [“How Andrea Ghez Won the Nobel for an Experiment Nobody Thought Would Work”]. Sometimes we have to fight for the realities we believe in.


scientificamerican--2020-12-01--Our Immigration Policy Has Done Terrible Damage to Kids

Over the past four years of the Trump administration , thousands of migrant children were separated from their parents , stuck in squalid tent camps on our southern border , and made victims of violence , trafficking and exploitation during their journey and in U.S. custody .
These traumatic experiences inflicted grievous psychological damage that can have lifelong consequences .
The children also lost opportunities to learn , explore and play—things we value for our own children .
Our punitive immigration policies have harmed a generation of children , and we must act immediately to change this .
The Biden-Harris @ @ @ @ @ @ @ and humane immigration system and is prioritizing important changes to immigration policy .
Given the harm to children ’ s development that has been done by our current immigration system and the urgency of addressing this , the new administration should adopt a set of science-based policies that best support children ’ s needs in its first weeks in office .
For optimal development , children need stability , love and nurturing care .
Substantial evidence from neuroscience to economics indicates that the early years of a child ’ s life are critical @ @ @ @ @ @ @ .
What happens during these important years can have long-term and irreversible consequences on children ’ s ability to grow , learn and thrive—and on future generations as well .
In the context of immigration , children ’ s needs are accentuated .
To address their unique and urgent needs , the Biden-Harris administration should start immigration reform with four child-centered policies in its first weeks .
First , prioritize family reunification .
The Trump administration ’ s “ zero tolerance ” policy led to the separation of more than 2,500 migrant children @ @ @ @ @ @ @ .
Stories of children in cages sparked public outcry , and a subsequent court order compelled the government to reunite families .
While many families have been reconnected , as of November 2020 , the parents of 666 separated children had not yet been reached .
A strong base of evidence demonstrates the destructive impacts of family separation .
According to Jack Shonkoff , director of the Harvard University Center on the Developing Child , separation from a parent removes the connection children need with a primary caregiver and subjects them to an @ @ @ @ @ @ @ can cause short-term physical health problems like high blood pressure , headaches and stomachaches , as well as mental health problems like anxiety and depression .
The trauma of separation , especially for children under five , can cause long-term impacts on health and well-being , including post-traumatic stress disorder , heart disease and diabetes .
In his congressional testimony about family separation , Shonkoff explained : “ Forcibly separating children from their parents is like setting a house on fire .
Prolonging that separation is like preventing the first responders from doing @ @ @ @ @ @ @ a top priority , the Biden-Harris administration has committed to creating a federal task force to spearhead this .
This task force should launch immediately and include members with expertise in child development , Central American cultures , and Spanish and indigenous languages .
Second , ensure that children ’ s development is a priority at the U.S.-Mexico border .
Children arriving at our southern border have made harrowing journeys , faced violence and suffered severe physical distress .
Currently , border policies disregard the specific needs and vulnerabilities of children and put @ @ @ @ @ @ @ , the Migrant Protection Protocols ( MPP ) force asylum seekers to wait in Mexico for the duration of their legal proceedings , placing children and families in squalid and dangerous makeshift camps or shelters where they are easy targets of violent cartels .
A recent study by the University of Virginia and Texas A & M in the largest tent encampment in Matamoros , Mexico , found that parents and children suffered from sustained fear and trauma , and children had deteriorating behavioral , emotional and cognitive functioning .
A new paper @ @ @ @ @ @ @ 's handling of migrant children at the border constitutes “ cruel , inhuman , or degrading treatment that rises to the level of torture.
” The first clear policy priority , about which Biden is outspoken , is to end MPP .
However , this must be done in coordination with humanitarian actors to ensure support for children during the rollback process , including fundamental health , nutrition , sanitation , education and protection services .
Furthermore , as outlined in the Kids in Need of Defense ( KIND ) blueprint to protect @ @ @ @ @ @ @ is essential to improve treatment of children arriving at the border .
This means enlisting trained and licensed child welfare professionals with expertise in children ’ s psychological , emotional and physical needs and ensuring hygienic , child-friendly spaces for screening and processing children ’ s cases .
Third , upon entry to the U.S. , improve care and appropriate custody of children .
Detention center conditions—cold , unceasingly lit and lacking proper food and health care—are hostile environments for children .
A recent study of unaccompanied minors in detention found high levels @ @ @ @ @ @ @ say that being trapped in such conditions can have a lasting impact on development and mental health .
According to another , broader study of children in U.S. detention centers , one third had elevated emotional problems , with younger children suffering more .
There are custody models more suitable for children .
Placing children with family or in familylike or small-group settings with case management will benefit their well-being and development .
Indeed , a review of 250 alternatives to detention from 60 countries by the International Detention Coalition found such community-based @ @ @ @ @ @ @ more effective , and cheaper—by 80 percent !
—than detention .
And fourth , it ’ s essential to ensure access to social safety nets for immigrant children and families .
Under the Trump administration , immigrant families ’ enrollment in the Supplemental Nutrition Assistance Program declined , with the trend accentuated when particular policies were announced , such as the “ public charge ” rule restricting legal immigrants ’ access to the federal safety net .
Repealing the public charge rule , restricting detention to those who have committed serious crimes , @ @ @ @ @ @ @ Childhood Arrivals program , which protects undocumented individuals who came to the United States as children from deportation , rather than terminating it would go far in easing the current climate of fear that afflicts immigrant communities and assuring the health and development of America ’ s immigrant-origin children .
The harm to our nation ’ s refugees , asylees , legal immigrants and mixed-status families has been extreme in the current administration , but not irreversible .
The Biden-Harris administration can take immediate science-based action to improve the lifelong health , economic @ @ @ @ @ @ @ youth and their families nationwide .

Over the past four years of the Trump administration, thousands of migrant children were separated from their parents, stuck in squalid tent camps on our southern border, and made victims of violence, trafficking and exploitation during their journey and in U.S. custody. These traumatic experiences inflicted grievous psychological damage that can have lifelong consequences. The children also lost opportunities to learn, explore and play—things we value for our own children. Our punitive immigration policies have harmed a generation of children, and we must act immediately to change this.
The Biden-Harris administration recognizes the need for a just and humane immigration system and is prioritizing important changes to immigration policy. Given the harm to children’s development that has been done by our current immigration system and the urgency of addressing this, the new administration should adopt a set of science-based policies that best support children’s needs in its first weeks in office.
For optimal development, children need stability, love and nurturing care. Substantial evidence from neuroscience to economics indicates that the early years of a child’s life are critical for building a foundation for healthy development. What happens during these important years can have long-term and irreversible consequences on children’s ability to grow, learn and thrive—and on future generations as well. In the context of immigration, children’s needs are accentuated. To address their unique and urgent needs, the Biden-Harris administration should start immigration reform with four child-centered policies in its first weeks.
First, prioritize family reunification. The Trump administration’s “zero tolerance” policy led to the separation of more than 2,500 migrant children from their families in 2017 and 2018. Stories of children in cages sparked public outcry, and a subsequent court order compelled the government to reunite families. While many families have been reconnected, as of November 2020, the parents of 666 separated children had not yet been reached.
A strong base of evidence demonstrates the destructive impacts of family separation. According to Jack Shonkoff, director of the Harvard University Center on the Developing Child, separation from a parent removes the connection children need with a primary caregiver and subjects them to an onslaught of elevated stress. This stress can cause short-term physical health problems like high blood pressure, headaches and stomachaches, as well as mental health problems like anxiety and depression. The trauma of separation, especially for children under five, can cause long-term impacts on health and well-being, including post-traumatic stress disorder, heart disease and diabetes. In his congressional testimony about family separation, Shonkoff explained: “Forcibly separating children from their parents is like setting a house on fire. Prolonging that separation is like preventing the first responders from doing their job.”
Embracing family reunification as a top priority, the Biden-Harris administration has committed to creating a federal task force to spearhead this. This task force should launch immediately and include members with expertise in child development, Central American cultures, and Spanish and indigenous languages.
Second, ensure that children’s development is a priority at the U.S.-Mexico border. Children arriving at our southern border have made harrowing journeys, faced violence and suffered severe physical distress. Currently, border policies disregard the specific needs and vulnerabilities of children and put their safety at risk. For example, the Migrant Protection Protocols (MPP) force asylum seekers to wait in Mexico for the duration of their legal proceedings, placing children and families in squalid and dangerous makeshift camps or shelters where they are easy targets of violent cartels. A recent study by the University of Virginia and Texas A&M in the largest tent encampment in Matamoros, Mexico, found that parents and children suffered from sustained fear and trauma, and children had deteriorating behavioral, emotional and cognitive functioning. A new paper from Pediatrics argues that the federal government's handling of migrant children at the border constitutes “cruel, inhuman, or degrading treatment that rises to the level of torture.”
The first clear policy priority, about which Biden is outspoken, is to end MPP. However, this must be done in coordination with humanitarian actors to ensure support for children during the rollback process, including fundamental health, nutrition, sanitation, education and protection services. Furthermore, as outlined in the Kids in Need of Defense (KIND) blueprint to protect unaccompanied children on the move, it is essential to improve treatment of children arriving at the border. This means enlisting trained and licensed child welfare professionals with expertise in children’s psychological, emotional and physical needs and ensuring hygienic, child-friendly spaces for screening and processing children’s cases.
Third, upon entry to the U.S., improve care and appropriate custody of children. Detention center conditions—cold, unceasingly lit and lacking proper food and health care—are hostile environments for children. A recent study of unaccompanied minors in detention found high levels of violence and physical abuse. Psychologists say that being trapped in such conditions can have a lasting impact on development and mental health. According to another, broader study of children in U.S. detention centers, one third had elevated emotional problems, with younger children suffering more.
There are custody models more suitable for children. Placing children with family or in familylike or small-group settings with case management will benefit their well-being and development. Indeed, a review of 250 alternatives to detention from 60 countries by the International Detention Coalition found such community-based case management programs to be safer, more effective, and cheaper—by 80 percent!—than detention.
And fourth, it’s essential to ensure access to social safety nets for immigrant children and families. Under the Trump administration, immigrant families’ enrollment in the Supplemental Nutrition Assistance Program declined, with the trend accentuated when particular policies were announced, such as the “public charge” rule restricting legal immigrants’ access to the federal safety net. Repealing the public charge rule, restricting detention to those who have committed serious crimes, and building on the Deferred Action for Childhood Arrivals program, which protects undocumented individuals who came to the United States as children from deportation, rather than terminating it would go far in easing the current climate of fear that afflicts immigrant communities and assuring the health and development of America’s immigrant-origin children.
The harm to our nation’s refugees, asylees, legal immigrants and mixed-status families has been extreme in the current administration, but not irreversible. The Biden-Harris administration can take immediate science-based action to improve the lifelong health, economic and educational outcomes of immigrant-origin children, youth and their families nationwide.


scientificamerican--2020-12-01--Top 10 Emerging Technologies of 2020

Top 10 Emerging Technologies of 2020

If some of the many thousands of human volunteers needed to test coronavirus vaccines could have been replaced by digital @ @ @ @ @ Top 10 Emerging Technologies—COVID-19 vaccines might have been developed even faster , saving untold lives @ @ @ @ @ could be a reality for testing new vaccines and therapies .
Other technologies on the @ @ @ @ @ emissions by electrifying air travel and enabling sunlight to directly power the production of industrial @ @ @ @ @ ” computing , the digital and physical worlds will be integrated in ways that go @ @ @ @ @ reality .
And ultrasensitive sensors that exploit quantum processes will set the stage for such @ @ @ @ @ and vehicles that can see around corners .

If some of the many thousands of human volunteers needed to test coronavirus vaccines could have been replaced by digital replicas—one of this year's Top 10 Emerging Technologies—COVID-19 vaccines might have been developed even faster, saving untold lives. Soon virtual clinical trials could be a reality for testing new vaccines and therapies. Other technologies on the list could reduce greenhouse gas emissions by electrifying air travel and enabling sunlight to directly power the production of industrial chemicals. With “spatial” computing, the digital and physical worlds will be integrated in ways that go beyond the feats of virtual reality. And ultrasensitive sensors that exploit quantum processes will set the stage for such applications as wearable brain scanners and vehicles that can see around corners.
These and the other emerging technologies have been singled out by an international steering group of experts. The group, convened by Scientific American and the World Economic Forum, sifted through more than 75 nominations. To win the nod, the technologies must have the potential to spur progress in societies and economies by outperforming established ways of doing things. They also need to be novel (that is, not currently in wide use) yet likely to have a major impact within the next three to five years. The steering group met (virtually) to whittle down the candidates and then closely evaluate the front-runners before making the final decisions. We hope you are as inspired by the reports that follow as we are.
MEDICINE: Microneedles for Painless Injections and Tests
Fewer trips to medical labs make care more accessible
By Elizabeth O'Day
Credit: Vanessa Branchi
Barely visible needles, or “microneedles,” are poised to usher in an era of pain-free injections and blood testing. Whether attached to a syringe or a patch, microneedles prevent pain by avoiding contact with nerve endings. Typically 50 to 2,000 microns in length (about the depth of a sheet of paper) and one to 100 microns wide (about the width of human hair), they penetrate the dead, top layer of skin to reach into the second layer—the epidermis—consisting of viable cells and a liquid known as interstitial fluid. But most do not reach or only barely touch the underlying dermis, where the nerve endings lie, along with blood and lymph vessels and connective tissue.
Many microneedle syringe and patch applications are already available for administering vaccines, and many more are in clinical trials for use in treating diabetes, cancer and neuropathic pain. Because these devices insert drugs directly into the epidermis or dermis, they deliver medicines much more efficiently than familiar transdermal patches, which rely on diffusion through the skin. This year researchers debuted a novel technique for treating skin disorders such as psoriasis, warts and certain types of cancer: mixing star-shaped microneedles into a therapeutic cream or gel. The needles' temporary, gentle perforation of the skin enhances passage of the therapeutic agent.
Many microneedle products are moving toward commercialization for rapid, painless draws of blood or interstitial fluid and for use in diagnostic testing or health monitoring. Tiny holes made by the needles induce a local change in pressure in the epidermis or dermis that forces interstitial fluid or blood into a collection device. If the needles are coupled to biosensors, the devices can, within minutes, directly measure biological markers indicative of health or disease status, such as glucose, cholesterol, alcohol, drug by-products or immune cells.
Some products would allow the draws to be done at home and mailed to a lab or analyzed on the spot. At least one product has already cleared regulatory hurdles for such use: the U.S. and Europe recently approved the TAP blood collection device from Seventh Sense Biosystems, which enables laypeople to collect a small sample of blood on their own, whether for sending to a lab or for self-monitoring. In research settings, microneedles are also being integrated with wireless communication devices to measure a biological molecule, use the measurement to determine a proper drug dose, and then deliver that dose—an approach that could help realize the promise of personalized medicine.
Microneedle devices could enable testing and treatment to be delivered in underserved areas because they do not require costly equipment or a lot of training to administer. Micron Biomedical has developed one such easy-to-use device: a bandage-sized patch that anyone can apply. Another company called Vaxxas is developing a microneedle vaccine patch that in animal and early human testing elicited enhanced immune responses using a mere fraction of the usual dose. Microneedles can also reduce the risk of transmitting blood-borne viruses and decrease hazardous waste from the disposal of conventional needles.
Tiny needles are not always an advantage; they will not suffice when large doses are needed. Not all drugs can pass through microneedles, nor can all biomarkers be sampled through them. More research is needed to understand how factors such as the age and weight of the patient, the site of injection and the delivery technique influence the effectiveness of microneedle-based technologies. Still, these painless prickers can be expected to significantly expand drug delivery and diagnostics, and new uses will arise as investigators devise ways to use them in organs beyond the skin.
CHEMICAL ENGINEERING: Sun-Powered Chemistry
Visible light can drive processes that convert carbon dioxide into common materials
By Javier Garcia Martinez
Credit: Vanessa Branchi
The manufacture of many chemicals important to human health and comfort consumes fossil fuels, thereby contributing to extractive processes, carbon dioxide emissions and climate change. A new approach employs sunlight to convert waste carbon dioxide into these needed chemicals, potentially reducing emissions in two ways: by using the unwanted gas as a raw material and sunlight, not fossil fuels, as the source of energy needed for production.
This process is becoming increasingly feasible thanks to advances in sunlight-activated catalysts, or photocatalysts. In recent years investigators have developed photocatalysts that break the resistant double bond between carbon and oxygen in carbon dioxide. This is a critical first step in creating “solar” refineries that produce useful compounds from the waste gas—including “platform” molecules that can serve as raw materials for the synthesis of such varied products as medicines, detergents, fertilizers and textiles.
Photocatalysts are typically semiconductors, which require high-energy ultraviolet light to generate the electrons involved in the transformation of carbon dioxide. Yet ultraviolet light is both scarce (representing just 5 percent of sunlight) and harmful. The development of new catalysts that work under more abundant and benign visible light has therefore been a major objective. That demand is being addressed by careful engineering of the composition, structure and morphology of existing catalysts, such as titanium dioxide. Although it efficiently converts carbon dioxide into other molecules solely in response to ultraviolet light, doping it with nitrogen greatly lowers the energy required to do so. The altered catalyst now needs only visible light to yield widely used chemicals such as methanol, formaldehyde and formic acid—collectively important in the manufacture of adhesives, foams, plywood, cabinetry, flooring and disinfectants.
At the moment, solar chemical research is occurring mainly in academic laboratories, including at the Joint Center for Artificial Photosynthesis, run by the California Institute of Technology in partnership with Lawrence Berkeley National Laboratory; a Netherlands-based collaboration of universities, industry and research and technology organizations called the Sunrise consortium; and the department of heterogeneous reactions at the Max Planck Institute for Chemical Energy Conversion in Mülheim, Germany. Some start-ups are working on a different approach to transforming carbon dioxide into useful substances—namely, applying electricity to drive the chemical reactions. Using electricity to power the reactions would obviously be less environmentally friendly than using sunlight if the electricity were derived from fossil-fuel combustion, but reliance on photovoltaics could overcome that drawback.
The advances occurring in the sunlight-driven conversion of carbon dioxide into chemicals are sure to be commercialized and further developed by start-ups or other companies in the coming years. Then the chemical industry—by transforming what today is waste carbon dioxide into valuable products—will move a step closer to becoming part of a true, waste-free, circular economy, as well as helping to make the goal of generating negative emissions a reality.
HEALTH CARE: Virtual Patients
Replacing humans with simulations could make clinical trials faster and safer
By Daniel E. Hurtado and Sophia M. Velastegui
Credit: Vanessa Branchi
Every day, it seems, some new algorithm enables computers to diagnose a disease with unprecedented accuracy, renewing predictions that computers will soon replace doctors. What if computers could replace patients as well? If virtual humans could have replaced real people in some stages of a coronavirus vaccine trial, for instance, it could have sped development of a preventive tool and slowed down the pandemic. Similarly, potential vaccines that weren't likely to work could have been identified early, slashing trial costs and avoiding testing poor vaccine candidates on living volunteers. These are some of the benefits of “in silico medicine,” or the testing of drugs and treatments on virtual organs or body systems to predict how a real person will respond to the therapies. For the foreseeable future, real patients will be needed in late-stage studies, but in silico trials will make it possible to conduct quick and inexpensive first assessments of safety and efficacy, drastically reducing the number of live human subjects required for experimentation.
With virtual organs, the modeling begins by feeding anatomical data drawn from noninvasive high-resolution imaging of an individual's actual organ into a complex mathematical model of the mechanisms that govern that organ's function. Algorithms running on powerful computers resolve the resulting equations and unknowns, generating a virtual organ that looks and behaves like the real thing.
In silico clinical trials are already underway to an extent. The U.S. Food and Drug Administration, for instance, is using computer simulations in place of human trials for evaluating new mammography systems. The agency has also published guidance for designing trials of drugs and devices that include virtual patients.
Beyond speeding results and mitigating the risks of clinical trials, in silico medicine can be used in place of risky interventions that are required for diagnosing or planning treatment of certain medical conditions. For example, HeartFlow Analysis, a cloud-based service approved by the FDA, enables clinicians to identify coronary artery disease based on CT images of a patient's heart. The HeartFlow system uses these images to construct a fluid dynamic model of the blood running through the coronary blood vessels, thereby identifying abnormal conditions and their severity. Without this technology, doctors would need to perform an invasive angiogram to decide whether and how to intervene. Experimenting on digital models of individual patients can also help personalize therapy for any number of conditions and is already used in diabetes care.
The philosophy behind in silico medicine is not new. The ability to create and simulate the performance of an object under hundreds of operating conditions has been a cornerstone of engineering for decades, such as for designing electronic circuits, airplanes and buildings. Various hurdles remain to its widespread implementation in medical research and treatment.
First, the predictive power and reliability of this technology must be confirmed, and that will require several advances. Those include the generation of high-quality medical databases from a large, ethnically diverse patient base that has women as well as men; refinement of mathematical models to account for the many interacting processes in the body; and further modification of artificial-intelligence methods that were developed primarily for computer-based speech and image recognition and need to be extended to provide biological insights. The scientific community and industry partners are addressing these issues through initiatives such as the Living Heart Project by Dassault Systèmes, the Virtual Physiological Human Institute for Integrative Biomedical Research and Microsoft's Healthcare NExT.
In recent years the FDA and European regulators have approved some commercial uses of computer-based diagnostics, but meeting regulatory demands requires considerable time and money. Creating demand for these tools is challenging given the complexity of the health care ecosystem. In silico medicine must be able to deliver cost-effective value for patients, clinicians and health care organizations to accelerate their adoption of the technology.
COMPUTING: Spatial Computing
The next big thing beyond virtual and augmented reality
By Corinna E. Lathan and Geoffrey Ling
Credit: Vanessa Branchi
Imagine Martha, an octogenarian who lives independently and uses a wheelchair. All objects in her home are digitally catalogued; all sensors and the devices that control objects have been Internet-enabled; and a digital map of her home has been merged with the object map. As Martha moves from her bedroom to the kitchen, the lights switch on, and the ambient temperature adjusts. The chair will slow if her cat crosses her path. When she reaches the kitchen, the table moves to improve her access to the refrigerator and stove, then moves back when she is ready to eat. Later, if she begins to fall when getting into bed, her furniture shifts to protect her, and an alert goes to her son and the local monitoring station.
The “spatial computing” at the heart of this scene is the next step in the ongoing convergence of the physical and digital worlds. It does everything virtual-reality and augmented-reality apps do: digitize objects that connect via the cloud; allow sensors and motors to react to one another; and digitally represent the real world. Then it combines these capabilities with high-fidelity spatial mapping to enable a computer “coordinator” to track and control the movements and interactions of objects as a person navigates through the digital or physical world. Spatial computing will soon bring human-machine and machine-machine interactions to new levels of efficiency in many walks of life, among them industry, health care, transportation and the home. Major companies, including Microsoft and Amazon, are heavily invested in the technology.
As is true of virtual and augmented reality, spatial computing builds on the “digital twin” concept familiar from computer-aided design (CAD). In CAD, engineers create a digital representation of an object. This twin can be used variously to 3-D-print the object, design new versions of it, provide virtual training on it or join it with other digital objects to create virtual worlds. Spatial computing makes digital twins not just of objects but of people and locations—using GPS, lidar (light detection and ranging), video and other geolocation technologies to create a digital map of a room, a building or a city. Software algorithms integrate this digital map with sensor data and digital representations of objects and people to create a digital world that can be observed, quantified and manipulated and that can also manipulate the real world.
In the medical realm, consider this futuristic scenario: A paramedic team is dispatched to an apartment in a city to handle a patient who might need emergency surgery. As the system sends the patient's medical records and real-time updates to the technicians' mobile devices and to the emergency department, it also determines the fastest driving route to reach the person. Red lights hold crossing traffic, and as the ambulance pulls up, the building's entry doors open, revealing an elevator already in position. Objects move out of the way as the medics hurry in with their stretcher. As the system guides them to the ER via the quickest route, a surgical team uses spatial computing and augmented reality to map out the choreography of the entire operating room or plan a surgical path through this patient's body.
Industry has already embraced the integration of dedicated sensors, digital twins and the Internet of Things to optimize productivity and will likely be an early adopter of spatial computing. The technology can add location-based tracking to a piece of equipment or an entire factory. By donning augmented-reality headsets or viewing a projected holographic image that displays not only repair instructions but also a spatial map of the machine components, workers can be guided through and around the machine to fix it as efficiently as possible—shrinking down time and its costs. Or if a technician were engaging with a virtual-reality version of a true remote site to direct several robots as they built a factory, spatial-computing algorithms could help optimize the safety, efficiency and quality of the work by improving, for example, the coordination of the robots and the selection of tasks assigned to them. In a more common scenario, fast-food and retail companies could combine spatial computing with standard industrial engineering techniques (such as time-motion analyses) to enhance the efficient flow of work.
MEDICINE: Digital Medicine
Apps that diagnose and even treat what ails us
By P. Murali Doraiswamy
Credit: Vanessa Branchi
Could the next prescription from your doctor be for an app? A raft of apps in use or under development can now detect or monitor mental and physical disorders autonomously or directly administer therapies. Collectively known as digital medicines, the software can both enhance traditional medical care and support patients when access to health care is limited—a need that the COVID-19 crisis has exacerbated.
Many detection aids rely on mobile devices to record such features as users' voices, locations, facial expressions, exercise, sleep and texting activity; then they apply artificial intelligence to flag the possible onset or exacerbation of a condition. Some smart watches, for instance, contain a sensor that automatically detects and alerts people to atrial fibrillation, a dangerous heart rhythm. Similar tools are in the works to screen for breathing disorders, depression, Parkinson's, Alzheimer's, autism and other conditions. These detection, or “digital phenotyping,” aids will not replace a doctor any time soon but can be helpful partners in highlighting concerns that need follow-up. Detection aids can also take the form of ingestible, sensor-bearing pills, called microbioelectronic devices. Some are being developed to detect things such as cancerous DNA, gases emitted by gut microbes, stomach bleeds, body temperature and oxygen levels. The sensors relay the data to apps for recording.
The therapeutic apps are likewise designed for a variety of disorders. The first prescription digital therapeutic to gain FDA approval was Pear Therapeutics's reSET technology for substance use disorder. Okayed in 2018 as an adjunct to care from a health professional, reSET provides 24/7 cognitive-behavioral therapy (CBT) and gives clinicians real-time data on their patients' cravings and triggers. Somryst, an insomnia therapy app, and EndeavorRX, the first therapy delivered as a video game for children with attention deficit hyperactivity disorder, received FDA clearance earlier this year.
Looking ahead, Luminopia, a children's health start-up, has designed a virtual- reality app to treat amblyopia (lazy eye)—an alternative to an eye patch. One day college students might receive alerts from a smart watch suggesting they seek help for mild depression after the watch detects changes in speech and socializing patterns; then they might turn to the Woebot chat bot for CBT counseling.
Not all wellness apps qualify as digital medicines. For the most part, those intended to diagnose or treat disorders must be proved safe and effective in clinical trials and earn regulatory approval; some may need a doctor's prescription. (In April, to help with the COVID-19 pandemic, the FDA made temporary exceptions for low-risk mental health devices.)
COVID-19 highlighted the importance of digital medicine. As the outbreak unfolded, dozens of apps for detecting depression and providing counseling became available. Additionally, hospitals and government agencies across the globe deployed variations of Microsoft's Healthcare Bot service. Instead of waiting on hold with a call center or risking a trip to the emergency room, people concerned about experiencing, say, coughing and fever could chat with a bot, which used natural-language processing to ask about symptoms and, based on AI analyses, could describe possible causes or begin a telemedicine session for assessment by a physician. By late April the bots had already fielded more than 200 million inquiries about COVID symptoms and treatments. Such interventions greatly reduced the strain on health systems.
Clearly, society must move into the future of digital medicine with care—ensuring that the tools undergo rigorous testing, protect privacy and integrate smoothly into doctors' workflows. With such protections in place, digital phenotyping and therapeutics could save health care costs by flagging unhealthy behaviors and helping people to make changes before diseases set in. Moreover, applying AI to the big data sets that will be generated by digital phenotyping and therapeutic apps should help to personalize patient care. The patterns that emerge will also provide researchers with novel ideas for how best to build healthier habits and prevent disease.
TRANSPORTATION: Electric Aviation
Enabling air travel to decarbonize
By Katherine Hamilton and Tammy Ma
In 2019 air travel accounted for 2.5 percent of global carbon emissions, a number that could triple by 2050. While some airlines have started offsetting their contributions to atmospheric carbon, significant cutbacks are still needed. Electric airplanes could provide the scale of transformation required, and many companies are racing to develop them. Not only would electric propulsion motors eliminate direct carbon emissions, they could reduce fuel costs by up to 90 percent, maintenance by up to 50 percent and noise by nearly 70 percent.
Among the companies working on electric flight are Airbus, Ampaire, MagniX and Eviation. All are flight-testing aircraft meant for private, corporate or commuter trips and are seeking certification from the U.S. Federal Aviation Administration. Cape Air, one of the largest regional airlines, expects to be among the first customers, with plans to buy the Alice nine-passenger electric aircraft from Eviation. Cape Air's CEO Dan Wolf has said he is interested not only in the environmental benefits but also in potential savings on operation costs. Electric motors generally have longer life spans than the hydrocarbon-fueled engines in his current aircraft; they need an overhaul at 20,000 hours versus 2,000.
Forward-propulsion engines are not the only ones going electric. NASA's X-57 Maxwell electric plane, under development, replaces conventional wings with shorter ones that feature a set of distributed electric propellers. On conventional jets, wings must be large enough to provide lift when a craft is traveling at a low speed, but the large surface area adds drag at higher speeds. Electric propellers increase lift during takeoff, allowing for smaller wings and overall higher efficiency.
For the foreseeable future, electric planes will be limited in how far they can travel. Today's best batteries put out far less power by weight than traditional fuels: an energy density of 250 watt-hours per kilogram versus 12,000 watt-hours per kilogram for jet fuel. The batteries required for a given flight are therefore far heavier than standard fuel and take up more space. Approximately half of all flights globally are fewer than 800 kilometers, which is expected to be within the range of battery-powered electric aircraft by 2025.
Electric aviation faces cost and regulatory hurdles, but investors, incubators, corporations and governments excited by the progress of this technology are investing significantly in its development: some $250 million flowed to electric aviation start-ups between 2017 and 2019. Currently roughly 170 electric airplane projects are underway. Most electric airplanes are designed for private, corporate and commuter travel, but Airbus says it plans to have 100-passenger versions ready to fly by 2030.
INFRASTRUCTURE: Lower-Carbon Cement
Construction material that combats climate change
By Mariette DiChristina
Credit: Vanessa Branchi
Concrete, the most widely used human-made material, shapes much of our built world. The manufacture of one of its key components, cement, creates a substantial yet underappreciated amount of human-produced carbon dioxide: up to 8 percent of the global total, according to London-based think tank Chatham House. It has been said that if cement production were a country, it would be the third-largest emitter after China and the U.S. Currently four billion tons of cement are produced every year, but because of increasing urbanization, that figure is expected to rise to five billion tons in the next 30 years, Chatham House reports. The emissions from cement production result from the fossil fuels used to generate heat for cement formation, as well as from the chemical process in a kiln that transforms limestone into clinker, which is then ground and combined with other materials to make cement.
Although the construction industry is typically resistant to change for a variety of reasons—safety and reliability among them—the pressure to decrease its contributions to climate change may well accelerate disruption. In 2018 the Global Cement and Concrete Association, which represents about 30 percent of worldwide production, announced the industry's first Sustainability Guidelines, a set of key measurements such as emissions and water usage intended to track performance improvements and make them transparent.
Meanwhile a variety of lower-carbon approaches are being pursued, with some already in practice. Start-up Solidia in Piscataway, N.J., is employing a chemical process licensed from Rutgers University that has cut 30 percent of the carbon dioxide usually released in making cement. The recipe uses more clay, less limestone and less heat than typical processes. CarbonCure in Dartmouth, Nova Scotia, stores carbon dioxide captured from other industrial processes in concrete through mineralization rather than releasing it into the atmosphere as a by-product. Montreal-based CarbiCrete ditches the cement in concrete altogether, replacing it with a by-product of steelmaking called steel slag. And Norcem, a major producer of cement in Norway, is aiming to turn one of its factories into the world's first zero-emissions cement-making plant. The facility already uses alternative fuels from wastes and intends to add carbon capture and storage technologies to remove emissions entirely by 2030.
Additionally, researchers have been incorporating bacteria into concrete formulations to absorb carbon dioxide from the air and to improve its properties. Start-ups pursuing “living” building materials include BioMason in Raleigh, N.C., which “grows” cementlike bricks using bacteria and particles called aggregate. And in an innovation funded by DARPA and published in February in the journal Matter, researchers at the University of Colorado Boulder employed photosynthetic microbes called cyanobacteria to build a lower-carbon concrete. They inoculated a sand-hydrogel scaffold with bacteria to create bricks with an ability to self-heal cracks.
These bricks could not replace cement and concrete in all of today's applications. They could, however, someday take the place of light-duty load-bearing materials, such as those used for pavers, facades and temporary structures.
COMPUTING: Quantum Sensing
High-precision metrology based on the peculiarities of the subatomic realm
By Carlo Ratti
Quantum computers get all the hype, but quantum sensors could be equally transformative, enabling autonomous vehicles that can “see” around corners, underwater navigation systems, early-warning systems for volcanic activity and earthquakes, and portable scanners that monitor a person's brain activity during daily life.
Quantum sensors reach extreme levels of precision by exploiting the quantum nature of matter—using the difference between, for example, electrons in different energy states as a base unit. Atomic clocks illustrate this principle. The world time standard is based on the fact that electrons in cesium 133 atoms complete a specific transition 9,192,631,770 times a second; this is the oscillation that other clocks are tuned against. Other quantum sensors use atomic transitions to detect minuscule changes in motion and tiny differences in gravitational, electric and magnetic fields.
There are other ways to build a quantum sensor, however. For example, researchers at the University of Birmingham in England are working to develop free-falling, supercooled atoms to detect tiny changes in local gravity. This kind of quantum gravimeter would be capable of detecting buried pipes, cables and other objects that today can be reliably found only by digging. Seafaring ships could use similar technology to detect underwater objects.
Most quantum-sensing systems remain expensive, oversized and complex, but a new generation of smaller, more affordable sensors should open up new applications. Last year researchers at the Massachusetts Institute of Technology used conventional fabrication methods to put a diamond-based quantum sensor on a silicon chip, squeezing multiple, traditionally bulky components onto a square a few tenths of a millimeter wide. The prototype is a step toward low-cost, mass-produced quantum sensors that work at room temperature and that could be used for any application that involves taking fine measurements of weak magnetic fields.
Quantum systems remain extremely susceptible to disturbances, which could limit their application to controlled environments. But governments and private investors are throwing money at this and other challenges, including those of cost, scale and complexity; the U.K., for example, has put £315 million into the second phase of its National Quantum Computing Program (2019–2024). Industry analysts expect quantum sensors to reach the market in the next three to five years, with an initial emphasis on medical and defense applications.
ENERGY: Green Hydrogen
Zero-carbon energy to supplement wind and solar
By Jeff Carbeck
Credit: Vanessa Branchi
When hydrogen burns, the only by-product is water—which is why hydrogen has been an alluring zero-carbon energy source for decades. Yet the traditional process for producing hydrogen, in which fossil fuels are exposed to steam, is not even remotely zero-carbon. Hydrogen produced this way is called gray hydrogen; if the CO 2 is captured and sequestered, it is called blue hydrogen.
Green hydrogen is different. It is produced through electrolysis, in which machines split water into hydrogen and oxygen, with no other by-products. Historically, electrolysis required so much electricity that it made little sense to produce hydrogen that way. The situation is changing for two reasons. First, significant amounts of excess renewable electricity have become available at grid scale; rather than storing excess electricity in arrays of batteries, the extra electricity can be used to drive the electrolysis of water, “storing” the electricity in the form of hydrogen. Second, electrolyzers are getting more efficient.
Companies are working to develop electrolyzers that can produce green hydrogen as cheaply as gray or blue hydrogen, and analysts expect them to reach that goal in the next decade. Meanwhile energy companies are starting to integrate electrolyzers directly into renewable power projects. For example, a consortium of companies behind a project called Gigastack plan to equip Ørsted's Hornsea Two offshore wind farm with 100 megawatts of electrolyzers to generate green hydrogen at an industrial scale.
Current renewable technologies such as solar and wind can decarbonize the energy sector by as much as 85 percent by replacing gas and coal with clean electricity. Other parts of the economy, such as shipping and manufacturing, are harder to electrify because they often require fuel that is high in energy density or heat at high temperatures. Green hydrogen has potential in these sectors. The Energy Transitions Commission, an industry group, says green hydrogen is one of four technologies necessary for meeting the Paris Agreement goal of abating more than 10 gigatons of carbon dioxide a year from the most challenging industrial sectors, among them mining, construction and chemicals.
Although green hydrogen is still in its infancy, countries—especially those with cheap renewable energy—are investing in the technology. Australia wants to export hydrogen that it would produce using its plentiful solar and wind power. Chile has plans for hydrogen in the country's arid north, where solar electricity is abundant. China aims to put one million hydrogen fuel–cell vehicles on the road by 2030.
Similar projects are underway in South Korea, Malaysia, Norway and the U.S., where the state of California is working to phase out fossil-fuel buses by 2040. And the European Commission's recently published 2030 hydrogen strategy calls for increasing hydrogen capacity from 0.1 gigawatt today to 500 gigawatts by 2050. All of which is why, earlier this year, Goldman Sachs predicted that green hydrogen will become a $12-trillion market by 2050.
SYNTHETIC BIOLOGY: Whole-Genome Synthesis
Next-level cell engineering
By Andrew Hessel and Sang Yup Lee
Credit: Vanessa Branchi
Early in the COVID-19 pandemic, scientists in China uploaded the virus's genetic sequence (the blueprint for its production) to genetic databases. A Swiss group then synthesized the entire genome and produced the virus from it—essentially teleporting the virus into their laboratory for study without having to wait for physical samples. Such speed is one example of how whole-genome printing is advancing medicine and other endeavors.
Whole-genome synthesis is an extension of the booming field of synthetic biology. Researchers use software to design genetic sequences that they produce and introduce into a microbe, thereby reprogramming the microbe to do desired work—such as making a new medicine. So far genomes mainly get light edits. But improvements in synthesis technology and software are making it possible to print ever larger swaths of genetic material and to alter genomes more extensively.
Viral genomes, which are tiny, were produced first, starting in 2002 with the poliovirus's roughly 7,500 nucleotides, or code letters. As with the coronavirus, these synthesized viral genomes have helped investigators gain insight into how the associated viruses spread and cause disease. Some are being designed to serve in the production of vaccines and immunotherapies.
Writing genomes that contain millions of nucleotides, as in bacteria and yeast, has become tractable as well. In 2019 a team printed a version of the Escherichia coli genome that made room for codes that could force the bacterium to do scientists' bidding. Another team has produced an initial version of the brewer's yeast genome, which consists of almost 11 million code letters. Genome design and synthesis at this scale will allow microbes to serve as factories for producing not only drugs but any number of substances. They could be engineered to sustainably produce chemicals, fuels and novel construction materials from nonfood biomass or even waste gases such as carbon dioxide.
Many scientists want the ability to write larger genomes, such as those from plants, animals and humans. Getting there requires greater investment in design software (most likely incorporating artificial intelligence) and in faster, cheaper methods for synthesizing and assembling DNA sequences at least millions of nucleotides long. With sufficient funding, the writing of genomes on the billion-nucleotide scale could be a reality before the end of this decade. Investigators have many applications in mind, including the design of plants that resist pathogens and an ultrasafe human cell line—impervious, say, to virus infections, cancer and radiation—that could be the basis for cell-based therapies or for biomanufacturing. The ability to write our own genome will inevitably emerge, enabling doctors to cure many, if not all, genetic diseases.
Of course, whole-genome engineering could be misused, with the chief fear being weaponized pathogens or their toxin-generating components. Scientists and engineers will need to devise a comprehensive biological security filter: a set of existing and novel technologies able to detect and monitor the spread of new threats in real time. Investigators will need to invent testing strategies that can scale rapidly. Critically, governments around the world must cooperate much more than they do now.
The Genome Project-write, a consortium formed in 2016, is positioned to facilitate this safety net. The project includes hundreds of scientists, engineers and ethicists from more than a dozen countries who develop technologies, share best practices, carry out pilot projects, and explore ethical, legal and societal implications.
Click here to view the emerging technologies steering group.