Covid-19’s economic implications will unfold for decades. The virus
will pass; people will go to baseball games and concerts again. But
economic policy will change in ways that will affect our lives for
generations. Presidential economic advisor Peter Navarro is advocating a
“Buy American” executive order
that would force federal agencies to buy American-made versions of some
medical and pharmaceutical equipment, drugs, and vaccines. One
justification for this proposal is the oft-cited statistic
that 80 percent of drugs in America come from China. Given that the
government is a primary purchaser of drugs, Navarro’s order would force
the pharmaceutical industry to restructure the way it manufactures and
distributes its products.
Even if that order doesn’t come to fruition, changes in how we source
drugs are probably inevitable. New York governor Andrew Cuomo uses his
daily updates to call for bringing more medical-supply manufacturing
back to America, to promote resilience. Economists and commentators, once unabashed champions of globalization, are rethinking our reliance on foreign suppliers in all industries.
The question is presented as a trade-off between resilience—the
ability to withstand a big, unpredictable shock—and efficiency, getting
stuff as cheaply and quickly as possible. Americans have just
experienced shortages of many goods, especially medical supplies, so
it’s tempting to argue that we should focus on resilience. But a “Buy
American” drug program does not promote resilience.
First, like it or not, beating Covid-19 will require international
cooperation. The best scientists and drug makers in each country are
working on treatments and vaccines. Making these treatments or vaccines
available to as many people as possible will require goods, knowledge, supplies, and chemicals from around the world.
Buy American would not just slow progress on Covid-19; pharmaceutical
companies would be left scrambling to produce other critical drugs, like
insulin.
Even as a longer-term strategy, a Buy American program would make us
less resilient. First, the 80 percent figure of drugs coming from China is false.
In fact, about 60 percent of American pharmaceutical spending is on
domestically produced drugs, though strictly speaking, American-made is
hard to define, because many intermediate inputs come from abroad.
Diversification is less risky than concentrating all your supply from
one place, even if it’s your own country. If something happens to
disrupt your domestic supply chain, like a disease outbreak, major
earthquake, or war, then sourcing from multiple, less affected countries
means less risk. Our supply chain is highly diversified and includes
150 countries; relying on one country is risky. Less trade would also
make drugs more expensive and increase health-care costs.
It’s possible, and even wise, to promote more domestic drug
manufacturing to improve efficiency and resiliency. But a major reason
why drugs aren’t made in America is tax and regulatory policy that makes
it prohibitively expensive to do so. Part of the executive order would
lessen FDA regulations and hold foreign suppliers to the same standard.
But instead of a Buy American policy, the U.S. should remove such
distortions and create a natural incentive to make more drugs here. With
increased investment and technical innovation, it may even become more
profitable and efficient to do so. Allison Schrager is a senior fellow at Manhattan Institute. https://www.city-journal.org/buy-american-drug-manufacturing
The Orange Dot, better known as Headspace, has closed on $47.7 million in equity funding, according to a filing with the U.S. Securities and Exchange Commission.
I reached out to the mindfulness and meditation startup for more
information and it confirmed that the financing is an extension to a
Series C that closed in February. Indeed, the filing comes nearly
exactly four months after Headspace secured $93 million in a Series C
round that we reported on here. That financing included $53 million in equity and $40 million in debt.
This latest infusion brings Santa Monica, California-based Headspace’s total venture and debt raised
since its inception in 2010 (Was it really founded a decade ago?!) to
about $216 million, according to Crunchbase data. The company declined
to disclose at what valuation the Series C was raised.
In an email statement, Headspace said: “We had always planned an
extension of our Series C. This extension is now complete and was led by
existing investors, adding $47.7 million to the $53 million raised in
February, bringing the total equity funding to $100.7 million for our
Series C.”
All Series A, B, and C lead investors participated, according to the company. Some of those backers include Blisce/,Waverley Capital,Times Bridge (the global investments and partnerships arm of The Times Group of India), The Chernin Group, Spectrum Equity and Advancit Capital.
To rise above the hype around meditation, Headspace claims to be “the
most science-backed digital mindfulness product in the market.” As an
example of that, the company said in February it was conducting over 70
clinical research studies with institutions such as Carnegie Mellon University and Stanford University.
Over the years, it’s branched out from its consumer app into
different product lines including “Headspace for Work,” its B2B segment
that counts Starbucks, Adobe, Hyatt and GE
among its 600 enterprise customers. It’s also offering “Headspace
Health,” an effort to integrate mindfulness into health care. In
general, the company says its goal is to help users apply mindfulness to
improve their health via content around stress, anxiety, sleep, focus
and other things.
Growth
Since its founding, Headspace said as of February it had experienced
over 62 million downloads in 190 countries and had more than 2 million
paid subscribers. No word yet on if it’s seen a spike in users due to
the COVID-19 pandemic.
In addition to growing its direct-to-consumer business, Headspace
said it will continue to invest in its Headspace for Work segment, which
has seen its revenue double year over year from 2017 to 2018 and most
recently in 2019. It also plans to continue putting money into its
health care segment.
In 2019, the company launched localized versions of the app in French and German, and appointed former Apple executive Renate Nyborg
as head of its European division to lead expansion in that region. Also
last year, Headspace launched in Latin America with versions in Spanish
and Brazilian Portuguese. It expanded into Asia through strategic
relationships with partners such as The Times of India. In February, the
company said it planned to use its new capital in part to continue
expanding internationally.
Of course, Headspace is not alone in the meditation app space. Last year, Calm announced the close of an $88 million Series B round that propelled it into unicorn status with a $1 billion valuation. In July, it announced a $27 million extension to that round.
Responsible investing based solely on avoiding certain
stocks is a “narrow-minded way of looking at the world,” suggests Man
Group’s CIO for ESG.
Investors should explore the “dark side” of responsible investing,
going beyond the common tactic of simply avoiding stocks for
environmental, social or governance reasons, according to Man Group.
“Why not short them?” asked Rob Furdak, Man Group’s chief investment
officer for ESG, in a phone interview. “You get more exposure to things
that matter to your set of values.”
Exclusionary screening of companies — the most prevalent way
investors express their ESG views — may be costing them returns,
according to research done by Man. But long-short strategies may pay
off. Long bets on companies with, say, strong board diversity may help
increase gains, he suggested, while shorting companies lacking diverse
leadership may provide even more return.
Shorting stocks as an ESG strategy is not common, partly because some
asset owners have policies prohibiting betting against companies,
according to Furdak. He said some institutional investors worry about
having any ties to stocks they wish to avoid — even if it’s a wager
against the shares of coal, tobacco, or nuclear weapons companies they
may be excluding from their portfolios.
“In the U.S., there’s a little bit more flexibility, a little bit
more openness to shorting the bad companies,” Furdak said. While some
asset owners are willing to “embrace the dark side of ESG,” he said
others are more aligned with the typical European investor’s opposition
to short selling “undesirable” companies.
Responsible investing done solely through restriction lists is “a
very narrow-minded way of looking at the world,” according to Furdak.
Man research has found that restricted stock portfolios, with the
exception of coal, have beaten the MSCI World Index over the past twenty
years. And while the return gap has been narrowing over the past five
years, he said the data suggest such exclusion strategies probably have
hurt the investment performance of asset allocators.
Digging deeper, Man found varying performance themes for excluded stocks since 2000.
For example, tobacco stocks have seen a particularly “dramatic regime shift” over the past couple decades, according to a new paper
Furdak co-authored on the research. They began with “massive
outperformance in the first dozen years,” and then, “after treading
water,” have significantly lagged the index over the past three years,
the paper said. Nuclear companies, meanwhile, have continued to post
strong performance versus the benchmark.
By shorting the worst offenders of ESG values, Furdak sees
opportunity for positive change along with stronger returns. Investors
don’t have to be a large shareholder of a company to capture its
attention.
“Most management cares about the short-selling community because they
know that short-sellers can have negative influence,” he said. “You
still have management’s ear because they want to do what they can to
have a positive perception of the company in the marketplace.” https://www.institutionalinvestor.com/article/b1m00mfvfl802r/The-Dark-Side-of-ESG
Dallas Fed President Robert Kaplan said Sunday that public health
procedures to combat the coronavirus were just as important as
government funding for the nascent economic recovery and that, to date,
the efforts to reduce coronavirus infections have been “uneven.”
In an interview on CBS’s “Face the Nation,” Kaplan said experts tell
him that it is “critical” that people “widely” wear masks and that there
is good testing and contact tracing.
“The extent we do that well will determine how quickly we recover.
We’ll grow faster if we do those things well,” Kaplan said. “And right
now, it’s relatively uneven.”
Fed officials say they are doing all they can to help the economy
recover. There is an undercurrent of concern in their comments over how
efforts to stem the pandemic, normally outside the purview of central
banking, are going.
On Friday, Richmond Fed President Thomas Barkin called
on the government and business to develop a common set of standards so
consumers feel safe shopping and eating at restaurants.
Texas is one state seeing rising coronavirus cases, especially in Austin and Houston.
Kaplan said that officials assumed there would be more coronavirus cases as part of the reopening.
“The thing we’re watching is — are there so many cases it is
overwhelming the health-care system — and we’re not seeing that at all
here,” he said.
The Dallas Fed president said the unemployment rate was on its way down.
“We’re going to get positive job growth in June, July from here,” he said.
However, even with the job growth, the jobless rate will finish the year at 8% or higher, he said.
Congressional spending “is going to be very important from here,” Kaplan said.
Asked if he meant Congress should spend more money, Kaplan said: “I
am being careful as a central banker not to tell fiscal authorities what
to do.”
The Dow Jones Industrial Average DJIA, +1.90%
was down 1,505 points last week to 25,605. Stocks fell sharply after
Fed Chairman Jerome Powell gave a grim outlook for the economy.
As the novel coronavirus continues to spread, researchers are
searching for novel ways to stop it. But for two scientists, looking to
the future means drawing inspiration from the past.
In January of 2020, Andrey Kovalevsky and Daniel Kneller, researchers
at the Department of Energy’s (DOE’s) Oak Ridge National Laboratory
(ORNL), were preparing to use neutrons to study the relationship between
a certain HIV protease—a protein enzyme
that allows the virus to replicate itself within the human body—and a
class of anti-retroviral drugs known as HIV protease inhibitors. Some
types of HIV build resistance to these drugs. The researchers’ goal was
to gain a better understanding of how protease variations work, to aid
the development of cutting-edge treatments to overpower even the
toughest resistant strains of HIV.
When the team began their work, little did they know that,
coincidentally, their efforts to study HIV would quickly put them on a
new path to tackling COVID-19, the pandemic that now has the world in
its grip.
As it turns out, the protease enzymatic activity that enables HIV to
reproduce—the very mechanism Kovalevsky’s team was gearing up to
investigate with neutrons—is the same replication mechanism employed by
SARS-CoV-2, the virus that causes the disease COVID-19.
Now, the team has shifted the focus of the experimental approach they
intended to use to study HIV to combat the new global threat. HIV studies pivot to novel coronavirus
Kovalevsky has been studying HIV for 15 years. As a neutron
crystallographer, he studies small crystallized samples of biological
matter by bombarding them with neutrons. The neutron scattering
technique is highly effective in revealing how a sample’s atomic
structure is arranged and how its atoms are behaving. Depending on the
aim, insights gleaned can offer guidance on how to either improve or
even suppress certain properties of a biological material.
Neutrons are an ideal tool for studying biological structures and
behaviors because of their acute sensitivity to light elements such as
hydrogen and their ability to probe such materials without damaging
them.
In 2019, Kovalevsky set out to study HIV in a way that had never been
done before. Using inelastic neutron scattering would allow him to
collect data on the dynamics, or the motions, of an HIV protease, which
would add to the neutron diffraction data he’d been collecting for
years. Having both the structural and behavioral—or
dynamical—information would provide a more complete picture of how the
virus works and, in turn, could lead to new advances in treatments.
After using the VISION spectrometer at ORNL’s Spallation Neutron
Source (SNS)—a neutron scattering instrument that reveals the motions of
atoms based on their vibrations—Kovalevsky realized he needed help in
analyzing the data.
“Daniel brings in expertise in viral protease research,” explained
Kovalevsky on recruiting Kneller. “He knows how to work with the
proteins in the lab. He knows all the lab techniques in terms of protein
production, purification, crystallization, crystallographic data
collection, and analysis to obtain insights into drug design.”
It took about 8 months to hire Daniel after an extensive search,
Kovalevsky says. Kneller—who specializes in studying HIV protease using
crystallography—joined Kovalevsky’s team in January of 2020 to help with
the experimental and computational work on the HIV protease.
But just as the team was ready to dive in, COVID-19 had gone global, and the research hit a hard stop.
Switching gears, getting early results
In March, staff in ORNL’s Neutron Sciences developed a plan to study key components of COVID-19
by assembling research teams and reprioritizing the operating schedules
of essential instruments at the two neutron scattering facilities at
ORNL, SNS and the High Flux Isotope Reactor (HFIR).
Having already laid the groundwork to study protease, Kovalevsky and
Kneller promptly pivoted from HIV to the novel coronavirus.
Specifically, they are currently focused on the main protease of
SARS-CoV-2, the virus that causes the COVID-19 disease.
“The SARS-CoV-2 protease is an enzyme that cuts proteins that enable
the virus to reproduce. Understanding how the protease is assembled and
how it functions is a critical first step to finding effective drug
inhibitors to block the virus’s replication mechanism,” said Kovalevsky.
“Similar to the HIV protease, the main protease from the SARS-CoV-2
virus is one of the most attractive drug targets right now for designing
specific inhibitors.”
As with the original plan of the HIV work, the team is preparing to
use instruments at SNS and HFIR to gain fundamental insights into how
the atoms in the protease are arranged. Using the MaNDi and IMAGINE
instruments, the researchers will be able to piece together the
protease’s atomic structure by using neutrons to track the hydrogen
atoms within the crystallized protein samples.
But first, they have to obtain crystals of high quality that are
large enough for neutron experiments. This is where the team has made
significant strides early on.
Crystal quality is first determined by how well they diffract, or
scatter, X-rays. Typically, this process is conducted at a synchrotron
facility, where the crystals might be frozen to around 100 K (or about
-280°F).
The team used the Protein Crystallization and Characterization lab at
SNS to grow SARS-CoV-2 protease crystals, which took about a week to 10
days. To analyze the quality of the crystals, they used the local X-ray
machine, a Rigaku HighFlux HomeLab, which provided several key findings.
First, the X-ray experiments confirmed the crystals were of high
quality and that the method used to grow them might produce larger
crystals suitable for neutron experiments. Second, having a local
machine allowed them to collect X-ray measurements at room temperature,
around 70°F.
The room-temperature measurements enabled them to observe the
plasticity, or flexibility, of the protease structure, providing
discernable information about how the structure behaves in conditions
close to the virus’s physiological environment. Those data could not
have been obtained using frozen samples.
“This is an important milestone in our effort to do neutron
diffraction. The investment in a local X-ray machine has paid off quite
well,” said Kneller. “In one instance, we grew crystals on Monday and
collected data on them on Tuesday. Otherwise, to obtain that information
you would have to send your crystals to a synchrotron, which could take
days to weeks.”
“And right now, because of the pandemic, you can’t go to a
synchrotron,” added Kovalevsky. “And to analyze crystals at room
temperature, you have to be there.”
“The information we learned from the room-temperature structure has
the ability to immediately impact the computational directions
researchers are using. We found some differences between our
room-temperature near-physiological structure and the frozen structures
from the synchrotrons, which may be important for the computational
work, such as the small-molecule docking studies being done on ORNL’s
supercomputer Summit,” said Kneller.
“So far, we’ve been very successful in our early studies of COVID-19.
We’ve already submitted a manuscript for publication about our
structural findings, in which we’ve essentially conducted two months of
research that normally might have taken a year.”
Aiding Kovalevsky and Kneller in the data and structure analysis of
the protein crystals was Leighton Coates, an instrument scientist on the
SNS MaNDi diffractometer who is also a member of the crystallographic
team studying the SARS-CoV-2 protease.
The data generated over the next several months will be shared with
other national laboratories, universities, and the broader science
community to build more accurate models for computational simulations
used to identify potential drug candidates to stop the virus.
“The scientific community has responded swiftly to the COVID-19
pandemic. We are fortunate to be able to make our own contributions by
leveraging years of experience studying HIV to build a better
understanding of how the novel coronavirus replicates and how we can
battle it by inhibiting its essential protease,” said Kovalevsky. Researching HIV resistance
Before the pandemic turned their attention and efforts to researching
SARS-CoV-2, Kovalevsky and Kneller had a clear plan for attacking HIV.
Thirty-nine million people around the world are infected with HIV.
Providing these people with better treatment options would not only
improve their quality of life but also prevent this disease from
spreading further.
The HIV protease works by cleaving harmless, or nonfunctional,
strands of proteins into smaller proteins, turning them into functional
viral proteins that enable the virus to assemble and continue infecting
healthy human cells. In general, HIV protease inhibitors are quite
effective at blocking protease during HIV replication, but some
variations of protease have developed an ability to resist drug
inhibitors.
“If we can learn more about the molecular mechanisms that make HIV
protease variants drug resistant, we can design drugs that are better
equipped to outsmart its defenses,” said Kneller.
Specifically, Kneller and Kovalevsky wanted to explore PRS-17, a
unique HIV protease variant that is 10,000 times less likely than other
nonresistant variants to be inhibited by the most effective clinical HIV
protease inhibitors currently available. Kovalevsky explained that
while HIV treatment programs have come a long way since the HIV pandemic
first began in the 1980s, mutant variants like PRS-17, resulting from
prolonged treatment, could compromise years of pharmaceutical innovation
and progress and result in failed antiviral therapies.
“Drug resistance is now the biggest problem for HIV patients. With
proper treatment, patients can live long and happy lives with
undetectable levels of HIV in their system. They won’t develop AIDS or
spread HIV to others. But PRS-17 and other drug-resistant HIV protease
variants make it difficult for physicians to combat HIV in their
patients,” said Kovalevsky.
Understanding exactly how PRS-17 neutralizes the efficacy of HIV
protease inhibitors is difficult, say the researchers. Viruses’
constituent proteins are complex systems, and PRS-17 has the ability to
employ several different mechanisms to guard itself against
anti-retroviral drugs.
“Figuring out how PRS-17 resists HIV protease inhibitors is a
challenge, but one that we absolutely have to overcome. PRS-17 is a
clinical isolate, which means it came from an actual patient struggling
to combat this disease,” explained Kneller. “Learning more about it
could save the lives of many patients, because the knowledge we gain
using neutrons on PRS-17 will be transferrable to other similar
extremely drug-resistant protease variants.”
The team intended to create a map of the PRS-17 protease to better
understand the molecular mechanisms behind its drug resistance. That
involved using the MaNDi and VISION instruments at SNS and the IMAGINE
instrument at HFIR.
“It was very much the same approach we are now trying with COVID-19,” said Kovalevsky.
With MaNDi and IMAGINE, Kneller and Kovalevsky were planning to probe
crystallized samples of PRS-17 protease to generate detailed data on
its static atomic structure.
Using VISION would enable them to probe powdered samples of PRS-17
protease to provide insights into its dynamic properties by measuring
the molecular vibrations.
Neutrons are particularly well-suited to study components of viruses
such as HIV (or SARS-CoV-2) because of their sensitivity to hydrogen, an
important component of all proteins. With neutron crystallography, the
team could precisely locate each hydrogen atom within PRS-17’s protease,
giving them unprecedented insight into how the protein functions and
what interactions it undergoes with a protease inhibitor.
“Use neutron crystallography at MaNDi and IMAGINE to locate hydrogen
atoms in crystals of PRS-17 protease, would enable us to build a
comprehensive profile of its static structure,” said Kneller. “With
VISION, we would also track hydrogen atoms, but we would use powdered
samples of PRS-17 protease that have been rehydrated to mimic the
crowded conditions of an HIV viral particle. That would allow us to see
its dynamic properties and learn more about how it might move when it is
working within a viral particle.”
Kneller explained that getting information about both the static and
dynamic properties of PRS-17 is important for developing a complete
understanding of this virus’s resistance to anti-retroviral drugs.
“If I tracked your location just once a day at midnight, I would
think you spend all of your time at home. But really, you move around
quite a bit throughout the day. That’s why it’s important to collect
both static and dynamic measurements of our sample. It lets us build a
fuller picture of protease’s behavior,” said Kneller.
“Without neutron crystallography, researchers have to make educated
guesses about where hydrogen atoms are in a protein whenever they
attempt to understand how the protein does its job,” added Kneller.
“These types of experiments that Andrey has done previously have
actually been able to confirm the locations of these hydrogen atoms in
nonresistant HIV protease variants, but never in an extremely
drug-resistant protease variant. That means we would be able to produce
truly unique and novel data about this protease.”
Kneller and Kovalevsky hope to one day generate data through their
experiments that will become an invaluable resource for researchers
looking to combat drug-resistant strains of HIV.
“It’s a team effort. Chemists, biologists, and professionals from the
pharmaceutical industry all have to work together to combat illness,”
said Kneller. “Together, we can develop effective treatments for
drug-resistant strains of HIV.”
Research was supported by the DOE Office of Science through the
National Virtual Biotechnology Laboratory, a consortium of DOE national
laboratories focused on response to COVID-19, with funding provided by
the Coronavirus CARES Act. https://phys.org/news/2020-06-history-insightful-hiv-neutron-approach.html
