scientificamerican--2020-11-12--Do NASA's Lunar Exploration Rules Violate Space Law?

When they were first publicized by NASA earlier this year , the agency ’ s Artemis Accords seemed harmless and trivial , almost self-evident .
These tenets state , among other things , that emergency assistance will be rendered to foreign astronauts if they are endangered or in distress , that planning for space travel will take place transparently and that research findings will be published in a timely fashion—with these steps taken , of course , for the benefit of all humankind .
The Artemis Accords are NASA ’ s rules to which all international partners must adhere if @ @ @ @ @ @ @ agency ’ s Artemis program , which seeks to send new crews to Earth ’ s moon—and eventually beyond .
In addition to the U.S. , seven nations have already signed on .
According to NASA , those who do not agree to the accords can not participate .
In any case , signatures are merely a formality .
At least , that is the way the agency ’ s administrator Jim Bridenstine sees it .
“ Any responsible space-faring nation should be able to abide by these principles , ” he averred @ @ @ @ @ @ @ ( IAC ) , an annual meeting that was held virtually this year .
One Accord to Rule Them All ?
Anyone who examines the Artemis Accords carefully might come away with a different impression .
Its 13 sections seem to show that the rules are about the use and exploitation of the moon in order to maintain American dominance , possibly undermining international law .
“ The Artemis Accords are an attempt by the Americans to walk softly to legitimize their deviation from the Outer Space Treaty , ” says Stephan Hobe @ @ @ @ @ @ @ Law , Space Law and Cyber Law at the University of Cologne in Germany .
That treaty—which has been ratified by 110 countries via the United Nations and entered into force in 1967—has up to now provided the legal basis for the exploration and utilization of space .
Among other requirements , it specifies that member states must have “ free access to all areas of celestial bodies.
” In addition , “ the moon and other celestial bodies [ are ] not subject to national appropriation by claim of sovereignty , by @ @ @ @ @ @ @ by any other means.
” The Artemis Accords document seems to take a different approach , as evinced in Section 11 , which is by far the lengthiest section .
Under the innocuous-sounding title “ Deconfliction of Space Activities , ” it states that the countries subject to the agreements will support the development of safety zones , for example around a moon base or where mining activities occur .
This is meant to ensure that states do not come into conflict with one another .
At the IAC , Bridenstine maintained “ @ @ @ @ @ @ @ extract and utilize space resources .
Countries and companies should be able to enjoy the fruits of their labor.
” But this is where the problems begin .
“ Safety zones are specific areas , ” Hobe says , “ and it is precisely the acquisition of such areas that is , in fact , banned by the Outer Space Treaty.
” Speaking at the IAC , Frans von der Dunk , a professor of space law at the University of Nebraska–Lincoln , made it clear that although states may plant their flag @ @ @ @ @ @ @ Space Treaty , they may not annex regions nor reserve them for future settlement .
So are the accords a clear violation of international law ?
Not necessarily .
Their stated purpose “ is to establish a common vision via a practical set of principles , guidelines , and best practices.
” That is , they do not claim to form the basis for new law and thus , strictly speaking , can not violate existing international law .
“ We already have internationally binding law , ” Hobe says .
“ But @ @ @ @ @ @ @ not satisfied with the interpretation of this law .
So they create guidelines with the hope that eventually they will develop into customary law that will weaken the existing space law .
That ’ s a really clever maneuver.
” Von der Dunk also views the Artemis Accords as more of a political problem than a legal one .
The agreements ’ sizable list of signatory nations , he says , is meant to signal a broad international consensus that the U.S. is correct in its interpretation of the Outer Space Treaty with @ @ @ @ @ @ @ .
But Hobe , an expert in international law , notes that such consensus may be illusory , based on the way in which the agreements were developed .
There was no international committee and no broad discussion .
Instead the Artemis Accords were simply dictated by the U.S. “ The Americans always want to lay down the rules of the game .
Only then may many other countries be asked to cooperate , ” Hobe says .
“ And it is very important to them to quickly create facts on the ground.
@ @ @ @ @ @ @ strength in numbers : the more states that are a signatory to an agreement , the harder it is to turn back the wheel .
“ We are of the opinion that all of the countries that participate are complicit in hollowing out the Outer Space Treaty , ” he adds .
Although some European spacefaring nations have already agreed to the accords , several crucial holdouts remain—Germany among them .
That nation ’ s position on the accords is important , in part , because it is already an indirect participant in @ @ @ @ @ @ @ will be powered by a European service module largely built in Germany .
Queried about the status of the latter country ’ s involvement with the accords , a spokesperson for Germany ’ s Federal Ministry for Economic Affairs and Energy wrote , in carefully chosen words , that it was in “ close discussions ” with the Americans and that legal questions would “ play a role at the appropriate time.
” The spokesperson added that “ fundamentally , the [ German ] government is interested in the further elaboration of the @ @ @ @ @ @ @ a multilateral level.
” Russia is clearer on the matter .
Dmitry Rogozin , head of Russian spaceflight efforts , stated at the IAC that a key part of the Artemis program is “ too U.S.-centric.
” As a result , his country does not intend to fully participate in the American moon plans .
As early as July , Rogozin , who is known for his bluster , complained about Artemis in the Russian tabloid Komsomolskaya Pravda .
“ For the United States , this is now more of a political project @ @ @ @ @ @ @ else must help and pay , ” he told the newspaper .
“ To be honest , we are not interested in participating in such a project.
” At the IAC , Rogozin said that Russia intended to fly to the moon on its own , not with the U.S .
There , the country will establish a research base with China , another nation skeptical of the U.S. ’ s lunar intentions .
A spokesperson for China ’ s Ministry of Foreign Affairs noted that the rules of behavior for space should @ @ @ @ @ @ @ a single country .
China , however , would not be eligible to participate in Artemis in any case because of a long-standing prohibition from the U.S. Congress greatly restricting NASA ’ s cooperation with the nation in space .
Europe , by contrast , remains an attractive partner for the U.S. ’ s moon plans , as evidenced late last month when the European Space Agency ( ESA ) finalized an agreement with NASA to collaborate on the future lunar Gateway space station , including contributing two modules .
As envisioned by @ @ @ @ @ @ @ as the lunar-orbit-based successor to the International Space Station ( ISS ) .
The modules will probably be ready only by the end of the 2020s , however—long after the Trump administration ’ s aspirational announced moon-landing deadline of 2024 .
To date , only three European countries are involved in the Gateway—and their participation is indirect .
It is no coincidence that these same three countries—Luxembourg , Italy and the U.K.—are signatories to the Artemis Accords .
Luxembourg is a nation that has long advocated lunar mining of resources .
And it @ @ @ @ @ @ @ law , Hobe points out .
Then there is Italy , which , apart from its ESA membership , has continually entered into one-sided agreements with NASA for the inclusion of Italian astronauts on U.S. spaceflights .
The U.K. ’ s role has been less consistent .
In 2012 the nation saved Europe ’ s participation in the ISS with a one-time injection of funds .
NASA subsequently selected British astronaut Tim Peake to fly to the ISS on a half-year mission in 2015 .
Since then , however , neither Peake nor @ @ @ @ @ @ @ the ISS .
Do the Artemis Accords offer a second chance for the nation ’ s hopeful spacefarers ?
While far removed from issues of international law and space agreements , this is where the practical problems begin to make themselves felt .
What , exactly , does it mean when the U.S. states that only those who have signed the accords will be permitted to participate in Artemis ?
Does this relate to the mining of resources , the construction of moon bases or even the selection of astronauts ?
“ That @ @ @ @ @ @ @ it hasn ’ t come up yet in our discussions with NASA , ” ESA director general Johann-Dietrich Wörner told Spektrum der Wissenschaft .
Because of its role in making Orion ’ s main engine , Germany is clearly a vital partner in NASA ’ s Artemis program .
But the situation is roughly comparable to that of an engine manufacturer for Formula One racing : the driver and support crew get all the glory rather than the immensely important motor that lets them compete in the first place .
And whether in @ @ @ @ @ @ @ , if ever , does an engine manufacturer get to choose who sits in the cockpit .
That , however , is precisely the promise that Germany ’ s economics minister Peter Altmaier has made to German astronaut Alexander Gerst .
“ If there is any way we can get it done , we ’ ll shoot you to the moon , ” Altmaier told Gerst .
Matthias Maurer , another German astronaut , is also hoping for a moon flight .
But could such a mission take place without Germany signing on @ @ @ @ @ @ @ tersely worded response to an inquiry from Spektrum der Wissenschaft , a representative of that nation ’ s economics ministry stated that the ministry was working on “ concrete astronautical participation in Artemis.
” But for this to happen , a unified European position has to be agreed on first .
Because Italy , Luxembourg and the U.K. pressed ahead on their own , such a pan-European agreement looks less likely , however .
And it is not likely that ESA will be of any great help .
“ That is a matter @ @ @ @ @ @ @ “ Only countries can sign the Artemis Accords , and the ESA is not a country.
” For the Germans , ESA ’ s and NASA ’ s intermingled moon plans may provide late satisfaction .
For the past five years , Wörner has been advocating for a “ Moon Village , ” a lunar outpost that all spacefaring countries would contribute to and utilize .
But as he makes clear , it would be a village without a mayor .
Under the Artemis Accords , would such an outpost instead have the @ @ @ @ @ @ @ claims and ensure law and order ?
Wörner has a diplomatic response .
“ In the final analysis , the Artemis Accords only state that certain limits must be maintained—limits that I , too , would have to accept , ” he says .
It is critically important that the moon does not belong to the Americans alone .
But as Wörner concedes , NASA is proceeding skillfully “ in that it gets itself a couple of partners and hopes that others will be drawn in.
” Bridenstine , Wörner ’ s counterpart @ @ @ @ @ @ @ but he is more reserved in his characterization .
“ While a good number of countries [ have ] signed the Artemis Accords ... , there is room for more , ” he said at the IAC .
Even though it was not intended as such , that statement sounded a little like a threat .
This article originally appeared in Spektrum der Wissenschaft and was reproduced with permission .

When they were first publicized by NASA earlier this year, the agency’s Artemis Accords seemed harmless and trivial, almost self-evident. These tenets state, among other things, that emergency assistance will be rendered to foreign astronauts if they are endangered or in distress, that planning for space travel will take place transparently and that research findings will be published in a timely fashion—with these steps taken, of course, for the benefit of all humankind.
The Artemis Accords are NASA’s rules to which all international partners must adhere if they wish to participate in the space agency’s Artemis program, which seeks to send new crews to Earth’s moon—and eventually beyond. In addition to the U.S., seven nations have already signed on.
According to NASA, those who do not agree to the accords cannot participate. In any case, signatures are merely a formality. At least, that is the way the agency’s administrator Jim Bridenstine sees it. “Any responsible space-faring nation should be able to abide by these principles,” he averred in mid-October at the International Astronautical Congress (IAC), an annual meeting that was held virtually this year.
One Accord to Rule Them All?
Anyone who examines the Artemis Accords carefully might come away with a different impression. Its 13 sections seem to show that the rules are about the use and exploitation of the moon in order to maintain American dominance, possibly undermining international law.
“The Artemis Accords are an attempt by the Americans to walk softly to legitimize their deviation from the Outer Space Treaty,” says Stephan Hobe, director of the Institute of Air Law, Space Law and Cyber Law at the University of Cologne in Germany. That treaty—which has been ratified by 110 countries via the United Nations and entered into force in 1967—has up to now provided the legal basis for the exploration and utilization of space. Among other requirements, it specifies that member states must have “free access to all areas of celestial bodies.” In addition, “the moon and other celestial bodies [are] not subject to national appropriation by claim of sovereignty, by means of use or occupation, or by any other means.”
The Artemis Accords document seems to take a different approach, as evinced in Section 11, which is by far the lengthiest section. Under the innocuous-sounding title “Deconfliction of Space Activities,” it states that the countries subject to the agreements will support the development of safety zones, for example around a moon base or where mining activities occur. This is meant to ensure that states do not come into conflict with one another.
At the IAC, Bridenstine maintained “that we can, in fact, extract and utilize space resources. Countries and companies should be able to enjoy the fruits of their labor.” But this is where the problems begin. “Safety zones are specific areas,” Hobe says, “and it is precisely the acquisition of such areas that is, in fact, banned by the Outer Space Treaty.” Speaking at the IAC, Frans von der Dunk, a professor of space law at the University of Nebraska–Lincoln, made it clear that although states may plant their flag on the moon, per the Outer Space Treaty, they may not annex regions nor reserve them for future settlement.
A Space Law Loophole
So are the accords a clear violation of international law? Not necessarily. Their stated purpose “is to establish a common vision via a practical set of principles, guidelines, and best practices.” That is, they do not claim to form the basis for new law and thus, strictly speaking, cannot violate existing international law. “We already have internationally binding law,” Hobe says. “But there are a few countries that are not satisfied with the interpretation of this law. So they create guidelines with the hope that eventually they will develop into customary law that will weaken the existing space law. That’s a really clever maneuver.”
Von der Dunk also views the Artemis Accords as more of a political problem than a legal one. The agreements’ sizable list of signatory nations, he says, is meant to signal a broad international consensus that the U.S. is correct in its interpretation of the Outer Space Treaty with regard to the exploitation of the moon.
But Hobe, an expert in international law, notes that such consensus may be illusory, based on the way in which the agreements were developed. There was no international committee and no broad discussion. Instead the Artemis Accords were simply dictated by the U.S. “The Americans always want to lay down the rules of the game. Only then may many other countries be asked to cooperate,” Hobe says. “And it is very important to them to quickly create facts on the ground.” It is the old game of strength in numbers: the more states that are a signatory to an agreement, the harder it is to turn back the wheel. “We are of the opinion that all of the countries that participate are complicit in hollowing out the Outer Space Treaty,” he adds.
Although some European spacefaring nations have already agreed to the accords, several crucial holdouts remain—Germany among them. That nation’s position on the accords is important, in part, because it is already an indirect participant in Artemis: The U.S. moon capsule Orion will be powered by a European service module largely built in Germany. Queried about the status of the latter country’s involvement with the accords, a spokesperson for Germany’s Federal Ministry for Economic Affairs and Energy wrote, in carefully chosen words, that it was in “close discussions” with the Americans and that legal questions would “play a role at the appropriate time.” The spokesperson added that “fundamentally, the [German] government is interested in the further elaboration of the legal framework of existing international law at a multilateral level.”
Russia’s Rejection and China’s Chilly Reception
Russia is clearer on the matter. Dmitry Rogozin, head of Russian spaceflight efforts, stated at the IAC that a key part of the Artemis program is “too U.S.-centric.” As a result, his country does not intend to fully participate in the American moon plans. As early as July, Rogozin, who is known for his bluster, complained about Artemis in the Russian tabloid Komsomolskaya Pravda. “For the United States, this is now more of a political project.... There is America; everyone else must help and pay,” he told the newspaper. “To be honest, we are not interested in participating in such a project.”
At the IAC, Rogozin said that Russia intended to fly to the moon on its own, not with the U.S. There, the country will establish a research base with China, another nation skeptical of the U.S.’s lunar intentions. A spokesperson for China’s Ministry of Foreign Affairs noted that the rules of behavior for space should be established by U.N. committees, not a single country. China, however, would not be eligible to participate in Artemis in any case because of a long-standing prohibition from the U.S. Congress greatly restricting NASA’s cooperation with the nation in space.
Europe, by contrast, remains an attractive partner for the U.S.’s moon plans, as evidenced late last month when the European Space Agency (ESA) finalized an agreement with NASA to collaborate on the future lunar Gateway space station, including contributing two modules. As envisioned by NASA, the Gateway will supposedly serve as the lunar-orbit-based successor to the International Space Station (ISS). The modules will probably be ready only by the end of the 2020s, however—long after the Trump administration’s aspirational announced moon-landing deadline of 2024.
To date, only three European countries are involved in the Gateway—and their participation is indirect. It is no coincidence that these same three countries—Luxembourg, Italy and the U.K.—are signatories to the Artemis Accords. Luxembourg is a nation that has long advocated lunar mining of resources. And it has even awarded licenses—in contravention of international law, Hobe points out. Then there is Italy, which, apart from its ESA membership, has continually entered into one-sided agreements with NASA for the inclusion of Italian astronauts on U.S. spaceflights. The U.K.’s role has been less consistent. In 2012 the nation saved Europe’s participation in the ISS with a one-time injection of funds. NASA subsequently selected British astronaut Tim Peake to fly to the ISS on a half-year mission in 2015.
Since then, however, neither Peake nor any other U.K. astronaut has returned to the ISS. Do the Artemis Accords offer a second chance for the nation’s hopeful spacefarers? While far removed from issues of international law and space agreements, this is where the practical problems begin to make themselves felt. What, exactly, does it mean when the U.S. states that only those who have signed the accords will be permitted to participate in Artemis? Does this relate to the mining of resources, the construction of moon bases or even the selection of astronauts? “That’s an interesting question, but it hasn’t come up yet in our discussions with NASA,” ESA director general Johann-Dietrich Wörner told Spektrum der Wissenschaft.
Fly Germany to the Moon?
Because of its role in making Orion’s main engine, Germany is clearly a vital partner in NASA’s Artemis program. But the situation is roughly comparable to that of an engine manufacturer for Formula One racing: the driver and support crew get all the glory rather than the immensely important motor that lets them compete in the first place. And whether in such racing or human spaceflight, rarely, if ever, does an engine manufacturer get to choose who sits in the cockpit. That, however, is precisely the promise that Germany’s economics minister Peter Altmaier has made to German astronaut Alexander Gerst. “If there is any way we can get it done, we’ll shoot you to the moon,” Altmaier told Gerst.
Matthias Maurer, another German astronaut, is also hoping for a moon flight. But could such a mission take place without Germany signing on to the Artemis Accords? In a tersely worded response to an inquiry from Spektrum der Wissenschaft, a representative of that nation’s economics ministry stated that the ministry was working on “concrete astronautical participation in Artemis.” But for this to happen, a unified European position has to be agreed on first.
Because Italy, Luxembourg and the U.K. pressed ahead on their own, such a pan-European agreement looks less likely, however. And it is not likely that ESA will be of any great help. “That is a matter for governments,” Wörner says. “Only countries can sign the Artemis Accords, and the ESA is not a country.”
For the Germans, ESA’s and NASA’s intermingled moon plans may provide late satisfaction. For the past five years, Wörner has been advocating for a “Moon Village,” a lunar outpost that all spacefaring countries would contribute to and utilize. But as he makes clear, it would be a village without a mayor. Under the Artemis Accords, would such an outpost instead have the U.S. as a sheriff—some entity to regulate claims and ensure law and order? Wörner has a diplomatic response. “In the final analysis, the Artemis Accords only state that certain limits must be maintained—limits that I, too, would have to accept,” he says. It is critically important that the moon does not belong to the Americans alone. But as Wörner concedes, NASA is proceeding skillfully “in that it gets itself a couple of partners and hopes that others will be drawn in.”
Bridenstine, Wörner’s counterpart at NASA, views matters similarly, but he is more reserved in his characterization. “While a good number of countries [have] signed the Artemis Accords..., there is room for more,” he said at the IAC. Even though it was not intended as such, that statement sounded a little like a threat.
This article originally appeared in Spektrum der Wissenschaft and was reproduced with permission.


scientificamerican--2020-11-12--A Cosmic Video Miniseries to Ponder Gravity, the Universe and Everything

How did the big bang shape the structure of the universe ?
What would happen to reality if we tweaked the fundamental forces ?
Why is gravity just so strange ?
In our new three-part video miniseries , Scientific American contributors Jared Kaplan and Emily V. Driscoll ponder these weighty existential issues with you through the lens of beautifully rendered explanatory animations created by artist Lottie Kingslake .
Think of it as your cosmic therapy session for our on-edge times .
Part I : What if the laws of physics were different ?
In the video Did the Universe Have @ @ @ @ @ @ @ ?
we examine what our universe—and more specifically , our lives—might look like with some tweaks to the physics responsible for the world as we know it .
Part II : How did the universe get its texture ?
In this video , How the Big Bang Governs the Texture of Our Universe , we explore the concept of cosmic inhomogeneities—using zebras as an analogy for clumps of matter scattered throughout the universe .
Part III : Why is gravity different ?
In our video Why Is Gravity Different ?
we explore why @ @ @ @ @ @ @ it remains difficult to understand how Einstein ’ s general theory of relativity ( which covers gravity ) fits together with quantum mechanics .

How did the big bang shape the structure of the universe? What would happen to reality if we tweaked the fundamental forces? Why is gravity just so strange?
In our new three-part video miniseries, Scientific American contributors Jared Kaplan and Emily V. Driscoll ponder these weighty existential issues with you through the lens of beautifully rendered explanatory animations created by artist Lottie Kingslake.
Think of it as your cosmic therapy session for our on-edge times.
Part I: What if the laws of physics were different?
In the video Did the Universe Have to Be the Way That It Is? we examine what our universe—and more specifically, our lives—might look like with some tweaks to the physics responsible for the world as we know it.
Part II: How did the universe get its texture?
In this video, How the Big Bang Governs the Texture of Our Universe, we explore the concept of cosmic inhomogeneities—using zebras as an analogy for clumps of matter scattered throughout the universe.
Part III: Why is gravity different?
In our video Why Is Gravity Different? we explore why this force is so perplexing and why it remains difficult to understand how Einstein’s general theory of relativity (which covers gravity) fits together with quantum mechanics.


scientificamerican--2020-11-13--Whole-Genome Synthesis Will Transform Cell Engineering

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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ and explore ethical , legal and societal implications .

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.


scientificamerican--2020-11-13--Green Hydrogen Could Fill Big Gaps In Renewable Energy

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 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ why , earlier this year , Goldman Sachs predicted that green hydrogen will become a $ 12-trillion market by 2050 .

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.


scientificamerican--2020-11-13--A New Cell Map of the Human Heart

A New Cell Map of the Human Heart

The human heart is an amazing organ .
Its muscle cells must contract in exquisite synchrony to pump oxygenated blood @ @ @ @ @ scientists have created a detailed map of cells in six regions of the heart .
@ @ @ @ @ , we have a zip code for each cell to know what population it belongs @ @ @ @ @ Seidman , a cardiovascular geneticist at Harvard University and director of the Cardiovascular Genetics Center @ @ @ @ @ s Hospital , in a recent statement .
Seidman , who is also an investigator @ @ @ @ @ , and her colleagues described the heart atlas in September in Nature .
Understanding these @ @ @ @ @ a healthy heart could help them determine what goes wrong in heart disease , the @ @ @ @ @ of death .
This video shows a beating heart with a protein involved in muscle @ @ @ @ @ Science in Images is a new category of articles featuring photographs and videos from all @ @ @ @ @ Click on the button below to see the full collection .

The human heart is an amazing organ. Its muscle cells must contract in exquisite synchrony to pump oxygenated blood throughout the body. Now scientists have created a detailed map of cells in six regions of the heart. “For the first time, we have a zip code for each cell to know what population it belongs to,” said Christine Seidman, a cardiovascular geneticist at Harvard University and director of the Cardiovascular Genetics Center at Brigham and Women’s Hospital, in a recent statement. Seidman, who is also an investigator at Howard Hughes Medical Institute, and her colleagues described the heart atlas in September in Nature.
Understanding these cells and their functions in a healthy heart could help them determine what goes wrong in heart disease, the world’s leading cause of death. This video shows a beating heart with a protein involved in muscle contraction labeled in green.
Science in Images is a new category of articles featuring photographs and videos from all the disciplines of science. Click on the button below to see the full collection.
Science in Images


scientificamerican--2020-11-13--Why Polls Were Mostly Wrong

Why Polls Were Mostly Wrong

In the weeks leading up to the November 2016 election , polls across the country predicted an easy sweep for Democratic nominee Hillary Clinton .
From Vanuatu to Timbuktu , everyone knows what happened .
Media outlets and pollsters took the heat for failing to project a victory for Donald Trump .
The polls were ultimately right about the popular vote .
But they missed the mark in key swing states that tilted the Electoral College toward Trump .
This time , prognosticators made assurances that such mistakes were so 2016 .
But as votes were tabulated on November 3 @ @ @ @ @ @ @ experience a sense of déjà vu .
Once again , more ballots were ticking toward President Trump than the polls had projected .
Though the voter surveys ultimately pointed in the wrong direction for only two states—North Carolina and Florida , both of which had signaled a win for Joe Biden—they incorrectly gauged just how much of the overall vote would go to Trump in both red and blue states .
In states where polls had favored Biden , the vote margin went to Trump by a median of 2.6 additional percentage points @ @ @ @ @ @ @ did even better than the polls had indicated—by a whopping 6.4 points .
Four years ago , Sam Wang , a neuroscience professor at Princeton University and co-founder of the blog Princeton Election Consortium , which analyzes election polling , called the race for Clinton .
He was so confident that he made a bet to eat an insect if Trump won more than 240 electoral votes—and ended up downing a cricket live on CNN .
Wang is coy about any plans for arthropod consumption in 2020 , but his predictions were again @ @ @ @ @ @ @ electoral votes and projected that the Democrats would have 53 Senate seats and a 4.6 percent gain in the House of Representatives .
Scientific American recently spoke with Wang about what may have gone wrong with the polls this time around—and what bugs remain to be sorted out .
[ An edited transcript of the interview follows . ]
How did the polling errors for the 2020 election compare with those we saw in the 2016 contest ?
Broadly , there was a polling error of about 2.5 percentage points across the board @ @ @ @ @ @ @ the presidential race .
This was similar in size to the polling error in 2016 , but it mattered less this time because the race wasn ’ t as close .
The main thing that has changed since 2016 is not the polling but the political situation .
I would say that worrying about polling is , in some sense , worrying about the 2016 problem .
And the 2020 problem is ensuring there is a full and fair count and ensuring a smooth transition .
Still , there were significant errors .
@ @ @ @ @ @ @ discrepancies ?
The big polling errors in red states are the easiest to explain because there ’ s a precedent : in states that are historically not very close for the presidency , the winning candidate usually overperforms .
It ’ s long been known turnout is lower in states that aren ’ t competitive for the presidency because of our weird Electoral College mechanism .
That effect—the winner ’ s bonus—might be enhanced in very red states by the pandemic .
If you ’ re in a very red state , and @ @ @ @ @ @ @ knows your vote doesn ’ t affect the outcome of the presidential race , you might be slightly less motivated to turn out during a pandemic .
That ’ s one kind of polling error that I don ’ t think we need to be concerned about .
But the error we probably should be concerned about is this 2.5-percentage-point error in close states .
That error happened in swing states but also in Democratic-trending states .
For people who watch politics closely , the expectation was that we had a couple of @ @ @ @ @ @ @ on election night ] .
Some states count and report votes on election night , and other states take days to report .
The polls beforehand pointed toward the possibility of North Carolina and Florida coming out for Biden .
That would have effectively ended the presidential race right there .
But the races were close enough that there was also the possibility that things would continue .
In the end , that ’ s what happened : we were watching more counting happen in Pennsylvania , Michigan , Wisconsin , Arizona and @ @ @ @ @ @ @ presidential race compare with the errors we saw with Senate races this year ?
The Senate errors were a bigger deal .
There were seven Senate races where the polling showed the races within three points in either direction .
Roughly speaking , that meant a range of outcomes for between 49 and 56 Democratic seats .
A small polling miss had a pretty consequential outcome because every percentage point missed would lead to , on average , another Senate seat going one way or the other .
Missing a few points in @ @ @ @ @ @ @ deal this year , but missing by a few points in Senate races mattered .
What would more accurate polling have meant for the Senate races ?
The real reason polling matters is to help people determine where to put their energy .
If we had a more accurate view of where the races were going to end up , it would have suggested political activists put more energy into the Georgia and North Carolina Senate races .
And it ’ s a weird error that the Senate polls were off by more @ @ @ @ @ @ @ explanation would be that voters were paying less attention to Senate races than presidential races and therefore were unaware of their own preference .
Very few Americans lack awareness of whether they prefer Trump or Biden .
But maybe more people would be unaware of their own mental processes for say , [ Republican incumbent ] Thom Tillis versus [ Democratic challenger ] Cal Cunningham [ in North Carolina ’ s Senate race ] .
Because American politics have been extremely polarized for the past 25 years , people tend to [ end @ @ @ @ @ @ @ ticket for their own party .
Considering that most of the polls overestimated Biden ’ s lead , is it possible pollsters were simply not adequately reaching Trump supporters by phone ?
David Shor , a data analyst [ who was formerly head of political data science at the company Civis Analytics ] , recently pointed out the possibility that people who respond to polls are not a representative sample .
They 're pretty weird in the sense that they ’ re willing to pick up the phone and stay on the phone @ @ @ @ @ @ @ that people are more likely to pick up the phone if they ’ re Democrats , more likely to pick up under the conditions of a pandemic and more likely to pick up the phone if they score high in the domain of social trust .
It ’ s fascinating .
The idea is that poll respondents score higher on social trust than the general population , and because of that , they ’ re not a representative sample of the population .
That could be skewing the results .
This is also @ @ @ @ @ @ @ more QAnon followers experienced more inaccurate polling .
The QAnon belief system is certainly correlated with lower social trust .
And those might be people who are simply not going to pick up the phone .
If you believe in a monstrous conspiracy of sex abuse involving one of the major political parties of the U.S. , then you might be paranoid .
One could not rule out the possibility that paranoid people would also be disinclined to answer opinion polls .
In Florida ’ s Miami-Dade County , we saw a surprising @ @ @ @ @ @ @ Trump .
How might the polls have failed to take into account members of that demographic backing Trump ?
Pollsters know Hispanic voters to be a difficult-to-reach demographic .
In addition , Hispanics are also not a monolithic population .
If you look at some of the exit polling , it looks like Hispanics were more favorable to Trump than they were to Clinton four years ago .
It ’ s certainly possible Hispanic support was missed by pollsters this time around .
Given that the presidential polls have been off for the @ @ @ @ @ @ @ should people pay to polls ?
I think polling is critically important because it is a way by which we can measure public sentiment more rigorously than any other method .
Polling plays a critical role in our society .
One thing we shouldn ’ t do is convert polling data into probabilities .
That obscures the fact that polls can be a few points off .
And it ’ s better to leave the reported data in units of opinion [ as a percentage favoring a candidate ] rather than try to @ @ @ @ @ @ @ ’ s best not to force too much meaning out of a poll .
If a race looks like it ’ s within three or four points in either direction , we should simply say it 's a close race and not force the data to say something they can ’ t .
I think pollsters will take this inaccuracy and try to do better .
But at some level , we should stop expecting too much out of the polling data .

In the weeks leading up to the November 2016 election, polls across the country predicted an easy sweep for Democratic nominee Hillary Clinton. From Vanuatu to Timbuktu, everyone knows what happened. Media outlets and pollsters took the heat for failing to project a victory for Donald Trump. The polls were ultimately right about the popular vote. But they missed the mark in key swing states that tilted the Electoral College toward Trump.
This time, prognosticators made assurances that such mistakes were so 2016. But as votes were tabulated on November 3, nervous viewers and pollsters began to experience a sense of déjà vu. Once again, more ballots were ticking toward President Trump than the polls had projected. Though the voter surveys ultimately pointed in the wrong direction for only two states—North Carolina and Florida, both of which had signaled a win for Joe Biden—they incorrectly gauged just how much of the overall vote would go to Trump in both red and blue states. In states where polls had favored Biden, the vote margin went to Trump by a median of 2.6 additional percentage points. And in Republican states, Trump did even better than the polls had indicated—by a whopping 6.4 points.
Four years ago, Sam Wang, a neuroscience professor at Princeton University and co-founder of the blog Princeton Election Consortium, which analyzes election polling, called the race for Clinton. He was so confident that he made a bet to eat an insect if Trump won more than 240 electoral votes—and ended up downing a cricket live on CNN. Wang is coy about any plans for arthropod consumption in 2020, but his predictions were again optimistic: he pegged Biden at 342 electoral votes and projected that the Democrats would have 53 Senate seats and a 4.6 percent gain in the House of Representatives.
Scientific American recently spoke with Wang about what may have gone wrong with the polls this time around—and what bugs remain to be sorted out.
[An edited transcript of the interview follows.]
How did the polling errors for the 2020 election compare with those we saw in the 2016 contest?
Broadly, there was a polling error of about 2.5 percentage points across the board in close states and blue states for the presidential race. This was similar in size to the polling error in 2016, but it mattered less this time because the race wasn’t as close.
The main thing that has changed since 2016 is not the polling but the political situation. I would say that worrying about polling is, in some sense, worrying about the 2016 problem. And the 2020 problem is ensuring there is a full and fair count and ensuring a smooth transition.
Still, there were significant errors. What may have driven some of those discrepancies?
The big polling errors in red states are the easiest to explain because there’s a precedent: in states that are historically not very close for the presidency, the winning candidate usually overperforms. It’s long been known turnout is lower in states that aren’t competitive for the presidency because of our weird Electoral College mechanism. That effect—the winner’s bonus—might be enhanced in very red states by the pandemic. If you’re in a very red state, and you’re a Democratic voter who knows your vote doesn’t affect the outcome of the presidential race, you might be slightly less motivated to turn out during a pandemic.
That’s one kind of polling error that I don’t think we need to be concerned about. But the error we probably should be concerned about is this 2.5-percentage-point error in close states. That error happened in swing states but also in Democratic-trending states. For people who watch politics closely, the expectation was that we had a couple of roads we could have gone down [on election night]. Some states count and report votes on election night, and other states take days to report. The polls beforehand pointed toward the possibility of North Carolina and Florida coming out for Biden. That would have effectively ended the presidential race right there. But the races were close enough that there was also the possibility that things would continue. In the end, that’s what happened: we were watching more counting happen in Pennsylvania, Michigan, Wisconsin, Arizona and Nevada.
How did polling on the presidential race compare with the errors we saw with Senate races this year?
The Senate errors were a bigger deal. There were seven Senate races where the polling showed the races within three points in either direction. Roughly speaking, that meant a range of outcomes for between 49 and 56 Democratic seats. A small polling miss had a pretty consequential outcome because every percentage point missed would lead to, on average, another Senate seat going one way or the other. Missing a few points in the presidential race was not a big deal this year, but missing by a few points in Senate races mattered.
What would more accurate polling have meant for the Senate races?
The real reason polling matters is to help people determine where to put their energy. If we had a more accurate view of where the races were going to end up, it would have suggested political activists put more energy into the Georgia and North Carolina Senate races.
And it’s a weird error that the Senate polls were off by more than the presidential polls. One possible explanation would be that voters were paying less attention to Senate races than presidential races and therefore were unaware of their own preference. Very few Americans lack awareness of whether they prefer Trump or Biden. But maybe more people would be unaware of their own mental processes for say, [Republican incumbent] Thom Tillis versus [Democratic challenger] Cal Cunningham [in North Carolina’s Senate race]. Because American politics have been extremely polarized for the past 25 years, people tend to [end up] voting [a] straight ticket for their own party.
Considering that most of the polls overestimated Biden’s lead, is it possible pollsters were simply not adequately reaching Trump supporters by phone?
David Shor, a data analyst [who was formerly head of political data science at the company Civis Analytics], recently pointed out the possibility that people who respond to polls are not a representative sample. They're pretty weird in the sense that they’re willing to pick up the phone and stay on the phone with a pollster. He gave evidence that people are more likely to pick up the phone if they’re Democrats, more likely to pick up under the conditions of a pandemic and more likely to pick up the phone if they score high in the domain of social trust. It’s fascinating. The idea is that poll respondents score higher on social trust than the general population, and because of that, they’re not a representative sample of the population. That could be skewing the results.
This is also related to the idea that states with more QAnon followers experienced more inaccurate polling. The QAnon belief system is certainly correlated with lower social trust. And those might be people who are simply not going to pick up the phone. If you believe in a monstrous conspiracy of sex abuse involving one of the major political parties of the U.S., then you might be paranoid. One could not rule out the possibility that paranoid people would also be disinclined to answer opinion polls.
In Florida’s Miami-Dade County, we saw a surprising surge of Hispanic voters turning out for Trump. How might the polls have failed to take into account members of that demographic backing Trump?
Pollsters know Hispanic voters to be a difficult-to-reach demographic. In addition, Hispanics are also not a monolithic population. If you look at some of the exit polling, it looks like Hispanics were more favorable to Trump than they were to Clinton four years ago. It’s certainly possible Hispanic support was missed by pollsters this time around.
Given that the presidential polls have been off for the past two elections, how much attention should people pay to polls?
I think polling is critically important because it is a way by which we can measure public sentiment more rigorously than any other method. Polling plays a critical role in our society. One thing we shouldn’t do is convert polling data into probabilities. That obscures the fact that polls can be a few points off. And it’s better to leave the reported data in units of opinion [as a percentage favoring a candidate] rather than try to convert it to a probability.
It’s best not to force too much meaning out of a poll. If a race looks like it’s within three or four points in either direction, we should simply say it's a close race and not force the data to say something they can’t. I think pollsters will take this inaccuracy and try to do better. But at some level, we should stop expecting too much out of the polling data.


scientificamerican--2020-11-13--For COVID Drugs, Months of Frantic Development Lead to Few Outright Successes

During the past 10 months , as the COVID pandemic broke over the world , thousands of research laboratories and pharmaceutical companies rushed to study the novel coronavirus and develop a treatment .
Hundreds of clinical trials are testing at least 200 different treatments against COVID , according to the Milken Institute , a health care think tank .
About 100 more treatments are in earlier-stage lab tests .
Despite the huge effort , scientists and clinicians are finding the search for new drugs hard .
The U.S. Food and Drug Administration has granted full approval to only one new @ @ @ @ @ @ @ 9 the agency authorized another drug , called bamlanivimab , for emergency use in patients outside clinical trials .
But the treatment appears to be ineffective in the most severely ill individuals : its developer , Eli Lilly , suspended testing in that group last month .
Even remdesivir appears to only slightly improve patient outcomes .
And hydroxychloroquine , a malaria drug that kills viruses in the lab , turned out to do more harm than good once it was tested in patients .
Although the identification of potential medications has been @ @ @ @ @ @ @ scientists are still stymied by the many outstanding questions about how the virus affects the human body .
“ Biologically , lots of things make sense , ” says Srinivas Murthy , a critical care physician at the University of British Columbia .
“ Remdesivir made sense , and hydroxychloroquine made sense .
In the end , it boils down to : Does it work in patients ?
” The better news is that ongoing clinical trials are beginning to separate the helpful treatments from the flops .
Research over recent months has @ @ @ @ @ @ @ and COVID ’ s disease progression , allowing scientists to target drugs to patients , depending on factors such as disease severity .
Amid the quickly spreading pandemic , investigators have found new ways of simultaneously testing treatments in as many people as possible .
“ If there ’ s any silver lining to this horrible situation , it ’ s that it accelerated the scientific community ’ s efforts to implement innovative trial designs and get answers quickly , ” says Carolyn Calfee , an anesthesiologist at the University of California , @ @ @ @ @ @ @ ’ s going to be a sea change for critical care.
” In their search , researchers are pursuing several different strategies , including antiviral drugs that prevent the novel coronavirus from replicating , synthetic immune molecules known as monoclonal antibodies ( mAbs ) that tag the pathogen for destruction before it can enter cells—Lilly ’ s bamlanivimab is one example—and treatments that prevent the patient ’ s immune system from overreacting to the virus and causing deadly symptoms .
Since the pandemic began , researchers and clinicians have made important progress in @ @ @ @ @ @ @ dropped significantly , in part because of improvements in strategies such as knowing when to put a patient on a ventilator and how to position them in a hospital bed .
And although only one drug , a steroid called dexamethasone , has proved to reduce the risk of death , scientists expect that the coming months will reveal better answers about the effectiveness of other medications .
But certain quirks of the coronavirus and COVID have complicated the research .
It was not initially apparent , for instance , that COVID is @ @ @ @ @ @ @ upper respiratory infection caused by the virus and a rarer , more severe immune reaction that can occur when the pathogen gets deep into the lungs .
That difference , it seems , determines how well a given type of treatment is likely to work .
Give an immunosuppressant such as dexamethasone too early , and you destroy the body ’ s ability to fight the virus on its own .
Give an antiviral therapy too late , and the virus will be out of control .
This timing could help explain why @ @ @ @ @ @ @ the sickest COVID-19 patients with new drugs .
In October a safety board found no improvements in severely ill patients receiving bamlanivimab .
Two weeks later Regeneron halted a trial of its mAb cocktail because of safety concerns .
“ It was definitely a disappointment , ” says Michael Matthay , a critical care specialist at U.C.S.F .
and a principal investigator of the bamlanivimab trial .
Myron Cohen , an infectious disease researcher at the University of North Carolina at Chapel Hill , is not surprised that the treatment did not work @ @ @ @ @ @ @ studies , mAbs and other antiviral treatments appear to be most effective early on in the disease , when the virus is still in the nose and has not caused severe complications .
Another explanation for these patients ’ poor outcomes , Matthay says , could be a phenomenon known as antibody-dependent enhancement , in which the sudden influx of antibodies clamps onto the virus inside airway tissues , recruiting other immune cells and causing inflammation .
While it is unclear whether this occurs with the mAbs used to treat COVID , the @ @ @ @ @ @ @ and even scuttled a promising dengue vaccine in 2017 .
But Matthay and others still have high hopes for mAbs in general .
“ One or two might not work , but that doesn ’ t mean the class wo n't work , ” he says .
As of this summer , eight mAbs were in clinical trials , with at least 80 more antibody-based drugs in development .
A number of companies , including Lilly and Regeneron , are currently testing their antibodies in less ill patients , as well as people @ @ @ @ @ @ @ COVID , such as nursing home workers .
These trials also could shed light on whether these treatments are useful when employed immediately in patients—such as President Donald Trump , who apparently received Regeneron ’ s antibody cocktail within a day of showing symptoms .
One frustrating issue , though , is the difficulty of getting mAbs to those patients with less severe symptoms .
The drugs must be infused through an IV , so they are easier to give in a hospital , where patients are more likely to be sicker ; @ @ @ @ @ @ @ cases where the drugs might be more effective .
Other medications , such as remdesivir , also appear to be most useful early in infection—especially if they can suppress the virus before the immune system knows it is there and has a chance to overreact .
More than 20 antiviral drugs , many of which were originally developed to treat other viruses , are currently in clinical trials .
These repurposed drugs ’ advantage over new mAbs is that they have already been tested in humans and proved to be safe , says @ @ @ @ @ @ @ Columbia University .
Old Drugs , New Uses Ju is testing whether the hepatitis C drug sofosbuvir also can be used to treat COVID .
The medication mimics letters in a virus ’ s genetic code—except these imposters do not actually code for viral proteins .
When the virus tries to replicate , its enzymes incorporate the drug into the new genome , and the replication fails .
Other drugs currently in clinical trials , such as the HIV drug lopinavir , are known as protease inhibitors and prevent the virus from breaking @ @ @ @ @ @ @ through the body .
But “ most repurposed drugs have not been as exciting as we ’ d have liked , ” Murthy says .
“ Whether we ’ re working down the wrong pathways or we need to be exploring different things remains to be seen.
” Dexamethasone , the 60-year-old steroid that reduces death rates in severely ill patients , is one repurposed drug that has worked .
The drug ’ s effectiveness is undeniable , established in a large trial that gave the medication to 2,100 people .
But it @ @ @ @ @ @ @ , Calfee says , because steroids can target a number of different immune pathways .
And researchers say they would prefer a more specific treatment that targets only the immune pathways affected by the coronavirus without exposing patients to powerful steroids .
One possibility is tocilizumab , a mAb made by F. Hoffmann–La Roche .
Rather than targeting the virus , the drug attacks a signaling molecule called interleukin 6 ( IL-6 ) , which is thought to play a role in immune system overreactions .
Although a large observational study of nearly @ @ @ @ @ @ @ chance of death , randomized controlled studies of it and other IL-6 inhibitors have found no benefit , leaving their use still questionable .
Some of the questions around the mechanisms and effectiveness of new drugs will be difficult , if not impossible , to determine at this point .
Treatments such as dexamethasone and remdesivir are now the standard of care , so patients in both test and placebo groups receive them , making it hard for researchers to tease apart the effects of any new drug .
And if physicians are @ @ @ @ @ @ @ on an emergency basis , scientists may struggle to recruit patients into placebo-controlled trials .
“ Who ’ s going to enter a trial and wants to be in the control group ?
” says Eric Toner , a public health researcher at the Johns Hopkins Center for Health Security .
Calfee points out another testing trouble : COVID-19 patients are not a homogeneous group , and certain treatments might work better for some people than others .
Yet if drugs are rushed into the clinic before they have been proved , it @ @ @ @ @ @ @ patients are most likely to benefit from different combinations .
Still , Calfee concedes that in a pandemic , getting answers quickly is important .
“ It ’ s the challenge with a rapidly evolving disease area , ” she says .
On a more positive note , researchers such as Toner believe the trials of monoclonal antibodies , in particular , could lead to permanent shifts in the way infectious diseases are treated .
These drugs can be produced as soon as researchers know the genetic sequence of a new virus .
@ @ @ @ @ @ @ manufacture in large quantities could allow them to be rapidly rolled out for future viral diseases .
And if COVID clinical trials result in the development of an antiviral drug that can attack a range of viruses , he says , “ that ’ ll be a potential game changer.
” Read more about the coronavirus outbreak from Scientific American here .
And read coverage from our international network of magazines here .

During the past 10 months, as the COVID pandemic broke over the world, thousands of research laboratories and pharmaceutical companies rushed to study the novel coronavirus and develop a treatment. Hundreds of clinical trials are testing at least 200 different treatments against COVID, according to the Milken Institute, a health care think tank. About 100 more treatments are in earlier-stage lab tests.
Despite the huge effort, scientists and clinicians are finding the search for new drugs hard. The U.S. Food and Drug Administration has granted full approval to only one new antiviral drug: remdesivir. On November 9 the agency authorized another drug, called bamlanivimab, for emergency use in patients outside clinical trials. But the treatment appears to be ineffective in the most severely ill individuals: its developer, Eli Lilly, suspended testing in that group last month. Even remdesivir appears to only slightly improve patient outcomes. And hydroxychloroquine, a malaria drug that kills viruses in the lab, turned out to do more harm than good once it was tested in patients.
Although the identification of potential medications has been remarkably fast by clinical research standards, scientists are still stymied by the many outstanding questions about how the virus affects the human body. “Biologically, lots of things make sense,” says Srinivas Murthy, a critical care physician at the University of British Columbia. “Remdesivir made sense, and hydroxychloroquine made sense. In the end, it boils down to: Does it work in patients?”
The better news is that ongoing clinical trials are beginning to separate the helpful treatments from the flops. Research over recent months has revealed new information about the immune system and COVID’s disease progression, allowing scientists to target drugs to patients, depending on factors such as disease severity. Amid the quickly spreading pandemic, investigators have found new ways of simultaneously testing treatments in as many people as possible. “If there’s any silver lining to this horrible situation, it’s that it accelerated the scientific community’s efforts to implement innovative trial designs and get answers quickly,” says Carolyn Calfee, an anesthesiologist at the University of California, San Francisco. “I think it’s going to be a sea change for critical care.”
In their search, researchers are pursuing several different strategies, including antiviral drugs that prevent the novel coronavirus from replicating, synthetic immune molecules known as monoclonal antibodies (mAbs) that tag the pathogen for destruction before it can enter cells—Lilly’s bamlanivimab is one example—and treatments that prevent the patient’s immune system from overreacting to the virus and causing deadly symptoms.
Since the pandemic began, researchers and clinicians have made important progress in treating COVID-19 patients. Death rates have dropped significantly, in part because of improvements in strategies such as knowing when to put a patient on a ventilator and how to position them in a hospital bed. And although only one drug, a steroid called dexamethasone, has proved to reduce the risk of death, scientists expect that the coming months will reveal better answers about the effectiveness of other medications.
Timing Matters
But certain quirks of the coronavirus and COVID have complicated the research. It was not initially apparent, for instance, that COVID is a multistage disease: there is an upper respiratory infection caused by the virus and a rarer, more severe immune reaction that can occur when the pathogen gets deep into the lungs. That difference, it seems, determines how well a given type of treatment is likely to work. Give an immunosuppressant such as dexamethasone too early, and you destroy the body’s ability to fight the virus on its own. Give an antiviral therapy too late, and the virus will be out of control.
This timing could help explain why it has proved so difficult to treat the sickest COVID-19 patients with new drugs. In October a safety board found no improvements in severely ill patients receiving bamlanivimab. Two weeks later Regeneron halted a trial of its mAb cocktail because of safety concerns. “It was definitely a disappointment,” says Michael Matthay, a critical care specialist at U.C.S.F. and a principal investigator of the bamlanivimab trial. Myron Cohen, an infectious disease researcher at the University of North Carolina at Chapel Hill, is not surprised that the treatment did not work in very sick patients. In animal studies, mAbs and other antiviral treatments appear to be most effective early on in the disease, when the virus is still in the nose and has not caused severe complications.
Another explanation for these patients’ poor outcomes, Matthay says, could be a phenomenon known as antibody-dependent enhancement, in which the sudden influx of antibodies clamps onto the virus inside airway tissues, recruiting other immune cells and causing inflammation. While it is unclear whether this occurs with the mAbs used to treat COVID, the syndrome has been seen in other diseases and even scuttled a promising dengue vaccine in 2017.
But Matthay and others still have high hopes for mAbs in general. “One or two might not work, but that doesn’t mean the class won't work,” he says. As of this summer, eight mAbs were in clinical trials, with at least 80 more antibody-based drugs in development.
A number of companies, including Lilly and Regeneron, are currently testing their antibodies in less ill patients, as well as people who are likely to be exposed to COVID, such as nursing home workers. These trials also could shed light on whether these treatments are useful when employed immediately in patients—such as President Donald Trump, who apparently received Regeneron’s antibody cocktail within a day of showing symptoms. One frustrating issue, though, is the difficulty of getting mAbs to those patients with less severe symptoms. The drugs must be infused through an IV, so they are easier to give in a hospital, where patients are more likely to be sicker; hospitals are less likely to see milder cases where the drugs might be more effective.
Other medications, such as remdesivir, also appear to be most useful early in infection—especially if they can suppress the virus before the immune system knows it is there and has a chance to overreact. More than 20 antiviral drugs, many of which were originally developed to treat other viruses, are currently in clinical trials. These repurposed drugs’ advantage over new mAbs is that they have already been tested in humans and proved to be safe, says Jingyue Ju, a chemical engineer at Columbia University.
Old Drugs, New Uses
Ju is testing whether the hepatitis C drug sofosbuvir also can be used to treat COVID. The medication mimics letters in a virus’s genetic code—except these imposters do not actually code for viral proteins. When the virus tries to replicate, its enzymes incorporate the drug into the new genome, and the replication fails. Other drugs currently in clinical trials, such as the HIV drug lopinavir, are known as protease inhibitors and prevent the virus from breaking its proteins down into particles that spread through the body.
But “most repurposed drugs have not been as exciting as we’d have liked,” Murthy says. “Whether we’re working down the wrong pathways or we need to be exploring different things remains to be seen.”
Dexamethasone, the 60-year-old steroid that reduces death rates in severely ill patients, is one repurposed drug that has worked. The drug’s effectiveness is undeniable—established in a large trial that gave the medication to 2,100 people. But it is not entirely clear why dexamethasone works, Calfee says, because steroids can target a number of different immune pathways. And researchers say they would prefer a more specific treatment that targets only the immune pathways affected by the coronavirus without exposing patients to powerful steroids. One possibility is tocilizumab, a mAb made by F. Hoffmann–La Roche. Rather than targeting the virus, the drug attacks a signaling molecule called interleukin 6 (IL-6), which is thought to play a role in immune system overreactions. Although a large observational study of nearly 4,000 patients found that tocilizumab reduced the chance of death, randomized controlled studies of it and other IL-6 inhibitors have found no benefit, leaving their use still questionable.
Testing Challenges
Some of the questions around the mechanisms and effectiveness of new drugs will be difficult, if not impossible, to determine at this point. Treatments such as dexamethasone and remdesivir are now the standard of care, so patients in both test and placebo groups receive them, making it hard for researchers to tease apart the effects of any new drug. And if physicians are allowed to use drugs such as bamlanivimab on an emergency basis, scientists may struggle to recruit patients into placebo-controlled trials. “Who’s going to enter a trial and wants to be in the control group?” says Eric Toner, a public health researcher at the Johns Hopkins Center for Health Security.
Calfee points out another testing trouble: COVID-19 patients are not a homogeneous group, and certain treatments might work better for some people than others. Yet if drugs are rushed into the clinic before they have been proved, it will be more difficult to determine which patients are most likely to benefit from different combinations. Still, Calfee concedes that in a pandemic, getting answers quickly is important. “It’s the challenge with a rapidly evolving disease area,” she says.
On a more positive note, researchers such as Toner believe the trials of monoclonal antibodies, in particular, could lead to permanent shifts in the way infectious diseases are treated. These drugs can be produced as soon as researchers know the genetic sequence of a new virus. Now technology that makes mAbs easier to manufacture in large quantities could allow them to be rapidly rolled out for future viral diseases. And if COVID clinical trials result in the development of an antiviral drug that can attack a range of viruses, he says, “that’ll be a potential game changer.”
Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.


scientificamerican--2020-11-13--Scientists and Health Experts Need to Be Advocates

As a physician , climate advocate and health equity educator , I feel like I ’ ve been sitting within the eye of the storm for months on end .
My vantage point has allowed me to see the painful human toll of our country ’ s intersecting crises .
The COVID-19 pandemic , the climate crisis , economic contraction and reckoning on racial justice have converged upon my patients and their communities , resulting in immense human suffering .
My work as a clinician is rooted in studying the best medical literature , educating my patients and caring for @ @ @ @ @ @ @ clinical abilities .
But these unprecedented times make it clear that is not enough .
I also have a professional responsibility to do a structural and root cause analysis of our current public health crises .
Such an analysis makes clear that to turn the page on these dark times , health care professionals and scientists should embrace the work of making structural change .
Structural change that improves the social , economic , and planetary underpinnings of health is good medicine , and it 's good science .
That 's because human @ @ @ @ @ @ @ thriving planet .
And robust scientific inquiry is predicated on a stable , thriving democracy .
Building public health infrastructure , fighting voter suppression , legislating a green economic recovery that ends the use of fossil fuels , and eradicating structural racism are essential medicines that will make us a more fair and healthy society .
While medicine and science have a rich history of advocacy , some in our field have felt that assuming such a public role runs counter to our principles .
But things are changing quickly .
Publications like @ @ @ @ @ @ @ endorsing Joe Biden , its first presidential endorsement in its 175 year history .
The New England Journal of Medicine , likewise , has published a perspective advocating that the Trump administration be voted out of office because of its historic failures amidst this pandemic and its undercutting of trust in science and public health interventions .
We need scientists and clinicians to testify at the statehouse , write op-eds , protest in the streets and run for public office as an anecdote to a corrosive public discourse that has been maliciously corrupted @ @ @ @ @ @ @ of our work and threaten to reverse our progress .
We must find ways for the studies that live within scientific journals to have impact in a complex world and inform public discourse and policy .
Our patients ’ lives depend on it .
That is especially true of communities of color and poor communities .
Medical and scientific institutions have a responsibility to support their faculty and students in taking on advocacy roles .
At the center I help lead , we create courses and space for health care professionals to explore @ @ @ @ @ @ @ make change .
In our residency training program , doctors in training are required to take a 100-hour advocacy curriculum .
Our courses improve knowledge base and skill sets .
But they also ask participants to distill and declare their values , and to reflect on what roles and identities they would like to assume to improve health equity .
Our curriculum explicitly seeks to help clinicians find community and shared purpose .
It empowers them with a sense of self efficacy—so that they can look at the hard challenges of our time @ @ @ @ @ @ @ world needs .
We have found that the inspiration that comes out of such values-based work is a partial answer to the burnout so many health care professionals feel today .
We have found a hunger for this work .
And so often , it has been our students who have had the greatest clarity on the path forward .
An important part of our responsibility is to create the institutional culture change to nurture these change makers .
Often , we should step aside and center their voices .
Our current crises @ @ @ @ @ @ @ imagine what is possible in a different kind of world .
We didn ’ t need a virus to animate the harmful and unhealthy fault lines in our society .
But we must use this moment in history to do the deep , structural work our patients and future generations deserve .
Health care professionals and scientists play an essential role in creating the change that will allow that future to manifest .

As a physician, climate advocate and health equity educator, I feel like I’ve been sitting within the eye of the storm for months on end. My vantage point has allowed me to see the painful human toll of our country’s intersecting crises. The COVID-19 pandemic, the climate crisis, economic contraction and reckoning on racial justice have converged upon my patients and their communities, resulting in immense human suffering.
My work as a clinician is rooted in studying the best medical literature, educating my patients and caring for the ill to the best of my clinical abilities. But these unprecedented times make it clear that is not enough. I also have a professional responsibility to do a structural and root cause analysis of our current public health crises. Such an analysis makes clear that to turn the page on these dark times, health care professionals and scientists should embrace the work of making structural change. Structural change that improves the social, economic, and planetary underpinnings of health is good medicine, and it's good science.
That's because human health is predicated on a stable, thriving planet. And robust scientific inquiry is predicated on a stable, thriving democracy. Building public health infrastructure, fighting voter suppression, legislating a green economic recovery that ends the use of fossil fuels, and eradicating structural racism are essential medicines that will make us a more fair and healthy society.
While medicine and science have a rich history of advocacy, some in our field have felt that assuming such a public role runs counter to our principles. But things are changing quickly. Publications like this one entered the political debate, endorsing Joe Biden, its first presidential endorsement in its 175 year history. The New England Journal of Medicine, likewise, has published a perspective advocating that the Trump administration be voted out of office because of its historic failures amidst this pandemic and its undercutting of trust in science and public health interventions.
We need scientists and clinicians to testify at the statehouse, write op-eds, protest in the streets and run for public office as an antidote to a corrosive public discourse that has been maliciously corrupted by public figures who make a mockery of our work and threaten to reverse our progress. We must find ways for the studies that live within scientific journals to have impact in a complex world and inform public discourse and policy. Our patients’ lives depend on it. That is especially true of communities of color and poor communities.
Medical and scientific institutions have a responsibility to support their faculty and students in taking on advocacy roles. At the center I help lead, we create courses and space for health care professionals to explore how they can improve their capacity to make change. In our residency training program, doctors in training are required to take a 100-hour advocacy curriculum. Our courses improve knowledge base and skill sets.
But they also ask participants to distill and declare their values, and to reflect on what roles and identities they would like to assume to improve health equity. Our curriculum explicitly seeks to help clinicians find community and shared purpose. It empowers them with a sense of self efficacy—so that they can look at the hard challenges of our time and see within themselves the solutions the world needs. We have found that the inspiration that comes out of such values-based work is a partial answer to the burnout so many health care professionals feel today.
We have found a hunger for this work. And so often, it has been our students who have had the greatest clarity on the path forward. An important part of our responsibility is to create the institutional culture change to nurture these change makers. Often, we should step aside and center their voices.
Our current crises challenge us to have the courage to imagine what is possible in a different kind of world. We didn’t need a virus to animate the harmful and unhealthy fault lines in our society. But we must use this moment in history to do the deep, structural work our patients and future generations deserve. Health care professionals and scientists play an essential role in creating the change that will allow that future to manifest.