Science after the pandemic

Bright side of the moonshots

Covid-19 has brought together biomedical technologies that will transform human health

The first virus to have its genome read was an obscure little creature called ms2; the 3,569 rna letters it contained were published in 1976, the hard-won product of some ten years’ work in a well-staffed Belgian laboratory. 

The sars-cov-2 genome, almost nine times longer, was published just weeks after doctors in Wuhan first became concerned about a new pneumonia. 

That feat has since been repeated with getting on for 1m different samples of sars-cov-2 in the hunt for fearsome variants like the one ravaging Brazil. 

Within weeks of its publication, the original genome sequence became the basis for the vaccines that today are stymieing the virus wherever supplies, politics and public confidence allow.

It is hardly remarkable that medical science has moved on since 1976. 

But the covid-19 pandemic has brought the sharp joy of seeing decades of cumulative scientific progress in sudden, concerted action. 

The spate of data, experiments and insights has had profound effects on the pandemic—and, indeed, on the future of medicine. 

It is also an inspiration. Around the world, scientists have put aside their own work in order to do their bit against a common foe. 

Jealously guarded lab space has been devoted to the grunt work of processing tests. 

Covid-19 has led to some 350,000 bits of research, many of them on preprint servers that make findings available almost instantaneously.

The basis of all this is the application of genetics to medicine in a systematic and transformative way—not just in understanding the pathology of diseases but in tracking their spread and curing and preventing them. 

This approach could underpin what is becoming known as “natural security”—the task of making societies resilient in the face of risks stemming from their connection to the living world, whether because of disease, food insecurity, biological warfare or environmental degradation.

The application of genetics to medicine partly reflects huge, rapid gains in efficiency. 

Reading the dna in a human genome cost $10m in 2007, today it takes less than $1,000 and a fraction of the time. 

Coupled with ever-better ways of synthesising and editing genes, this has enabled cleverness little short of the miraculous. 

Before the pandemic, these trailblazing techniques were not much talked about beyond the laboratory. 

Having shown their mettle against a brand new disease, they have burst out into the open.

Take the vaccination technology rapidly developed by Moderna of America and BioNTech of Germany, building on years of patient and often unsung work on rna, a store of genetic information. 

It is remarkable that you can simply instruct the body’s cells to make the viral protein you have designed to prime the immune system. 

The rna vaccines are testament to the insight of Eddie Cantor, a comedian, that it takes 20 years to become an overnight success.

With this proof of concept, the investments of companies that have worked hard on rna may now pay off. 

To some extent, rna medicine divorces form from function. 

An rna vaccine against any disease is a message written in genetic code: a vaccine against malaria, or some form of cancer, can be made in the same way and with the same equipment as a sars-cov-2 vaccine. 

If this provides a platform for getting cells to do all sorts of specific things and to desist from others, as it promises to, medicine will become both more powerful and more personal. 

Therapies tailored to rare, even one-off, genetic abnormalities should become routine.

The pandemic has also demonstrated the value of gene-sequencing technologies. 

Observing sars-cov-2 as it mutates is essential if the world is to understand and defend itself against dangerous variants. 

Should covid-19 become endemic, as is likely, sequencing will become the basis for developing regular booster shots. 

More broadly, routine sequencing is one of the best ways of knowing what is out there. 

Companies have done brilliantly in producing powerful sequencing systems for trained technicians. 

Now the world needs cheap, ubiquitous and reliable systems that can be used in the prison sick bay or the rural health centre, on the farm or at the town sewage works, to act as early-warning systems for the spread of pathogens.

Another area of work is where the pandemic has revealed a gap. 

Even today’s progress has yet to produce small-molecule antivirals to combat sars-cov-2. 

A focus for natural security should be drugs aimed at the viral families most likely to cause trouble in the future. 

This is not something that the market will support on its own. 

New mechanisms that involve governments will be needed, such as funds for r&d and trials and to buy stockpiles of medicine. 

Similar approaches should also be used for the looming threat of antibiotic-resistant bacteria.

These innovations will have big consequences. 

General-purpose rna medicine asks new things of firms and regulators—as do other platforms, including some forms of gene therapy. 

Regulators will need to take advantage of the fact that, say, a malaria vaccine and a sars-cov-2 vaccine are both made on the same platform by streamlining approval for them, while continuing to ensure safety.

Drugs firms will have to adapt, as some chronic conditions may, in effect, be cured. 

Many are used to concentrating on the long-lasting afflictions that most trouble the rich world: heart disease, cancer, metabolic disorders, neurodegenerative conditions and the like. 

If drug development is more targeted on instructing cells what to do, rather than finding novel molecules against specific proteins, some of the know-how on which old-style pharma is based will be less relevant. 

Firms will need new pricing models and a new focus to their research.

Natural protection

Technology will not, in itself, thwart pandemics. 

That goal also requires systems and institutions which use technology broadly and wisely. 

Without good systems, great technology will often provide only mediocre results, as it has in many covid-19 test-and-trace programmes. 

But the pandemic has shown that biomedical science has the tools and the enthusiasm to improve the world. 

The world must now build on both. 

What a stronger dollar means for the world

The currency’s turnround should boost US imports but have a negative impact on emerging markets

Megan Greene

The US economy looks set to outperform following the Biden administration’s $1.9tn rescue plan and increased vaccinations © Paul Yeung/Bloomberg

At the turn of the year, weak growth and poor management of the Covid-19 pandemic led to a consensus that the US dollar would weaken significantly in 2021. 

Instead, it’s been strengthening — a trend with significant implications for the US and the rest of the world.

The twin deficits argument of the 1980s underpins some of the forecasts for dollar depreciation. 

The budget deficit hit around 15 per cent of GDP in 2020 and is set to balloon further this year. 

The current account deficit was 3.5 per cent and rising in the fourth quarter of 2020. 

Investor reluctance to finance $2.8tn in stimulus packages might push up yields on US Treasuries, forcing the Fed to increase QE purchases to bring them back down. 

The dollar would follow.

Over the long term, the twin deficits should put downward pressure on the dollar, but the very reasons they are rising will overwhelm those structural issues for now. 

The dollar’s turnround began as the Biden administration pushed through the whole of its $1.9tn American Rescue Plan. 

At the same time, it significantly ramped up the pace of vaccinations, from about 900,000 a day to almost 3m.

Now the US economy looks set to outperform. 

According to the OECD, the rescue package alone should add 3 to 4 percentage points to 2021 GDP. 

Wall Street economists see GDP growth of as much as 8 per cent. 

That will mean higher sales and profits for American companies, inviting investments by foreigners, who will need dollars. 

The usual downside of such government-financed growth is inflation. 

If investors believe the US has lost fiscal discipline, inflation expectations could become unanchored; bad for stocks, bonds and the dollar. 

But the stewards of the American economy don’t see a danger. 

Federal Reserve policymakers say they won’t be applying the brakes anytime soon. Their dot plot this month suggests rates will be near zero until 2024. 

In a world where other central banks are keeping rates negative, that interest rate differential, small as it is, will be good for the American currency. 

New Treasury secretary Janet Yellen has ditched the long-held US “strong dollar” policy, insisting the currency’s value will be “market-determined”. 

At the same time, she has pledged not to interfere with the market’s determinations. 

That eases the risk the administration might work to weaken the dollar to help boost exports, which would be helpful in trying to revive the manufacturing sector. 

Stronger growth and a stronger currency should boost US imports, generating demand for the rest of the world. 

The OECD expects the rescue package to add one-quarter to one-half a point to eurozone and Chinese GDP, and even more for Canada and Mexico. 

This should also serve as a useful safety valve on inflation as the US imports disinflationary pressure.

A higher current account deficit for the US should mean a higher surplus for other countries, particularly in Europe where fiscal stimulus measures are comparatively small. 

But the maniacal focus of the Trump administration on bilateral trade balances is a thing of the past, and there is little risk that concerns about currency manipulation will come to the fore this year.

A stronger dollar isn’t a benefit to everyone. While faster US growth will provide support to emerging markets’ growth, the IMF says that is significantly mitigated by a strengthening dollar. 

It pushes down dollar commodity prices, resulting in lower real income and depressed domestic demand for EM commodities exporters. 

It would also make EM dollar-denominated debt more difficult to service. 

An EM sovereign debt crisis could drag on global growth, with negative blowback for the US. 

As long as US officials keep that in mind, the Biden administration looks set to continue enjoying the dollar’s exorbitant privilege. 

The writer is a senior fellow at Harvard Kennedy School

For Biden, a New Virus Dilemma: How to Handle a Looming Glut of Vaccine

As U.S. manufacturers hit their stride, vaccine scarcity will soon turn to plenty as much of the world goes begging. And vaccine makers need answers now about what to do with the coming surplus.

By Sharon LaFraniere and Noah Weiland

President Biden touring Pfizer’s manufacturing plant in Kalamazoo, Mich., last month. Pressure is growing for the United States to share its vaccine stock.Credit...Doug Mills/The New York Times

WASHINGTON — Biden administration officials are anticipating the supply of coronavirus vaccine to outstrip U.S. demand by mid-May if not sooner, and are grappling with what to do with looming surpluses when vaccine scarcity turns to glut.

President Biden has promised enough doses by the end of May to immunize all of the nation’s roughly 260 million adults. 

But between then and the end of July, the government has locked in commitments from manufacturers for enough vaccine to cover 400 million people — about 70 million more than the nation’s entire population.

Whether to keep, modify or redirect those orders is a question with significant implications, not just for the nation’s efforts to contain the virus but also for how soon the pandemic can be brought to an end. 

Of the vaccine doses given globally, about three-quarters have gone to only 10 countries. At least 30 countries have not yet injected a single person.

And global scarcity threatens to grow more acute as nations and regions clamp down on vaccine exports. 

With infections soaring, India, which had been a major vaccine distributor, is now holding back nearly all of the 2.4 million doses manufactured daily by a private company there. 

That action follows the European Union’s decision this week to move emergency legislation that would curb vaccine exports for the next six weeks.

Biden administration officials who are inclined to hold on to the coming U.S. surplus point to unmet need and rising uncertainty: Children and adolescents are still unvaccinated, and no one is certain if or when immunity could wear off, which could require scores of millions of booster shots.

“We want to, largely, be a part of the global solution here,” Jen Psaki, the White House press secretary, said this week. 

But she added, “There are still a number of factors that are unpredictable that we need to plan for to the best of our ability, including the variants and the impact and what will be most effective, as well as what will work best with children.”

Vaccine manufacturers and some top federal officials say decisions about what to do with extra orders must be made within weeks, or the uncertainty could slow production lines. 

The manufacturing process can take up to 10 weeks, and changes for a foreign market need time. The regulatory rules that govern vaccine shipments present another hurdle, as does the limited storage life of the drug substances that make the vaccine.

Vials in the nation’s bottling plants in Michigan and Indiana are being labeled for use at home. 

If their destination is unclear, either the production line must pause or vials directed for overseas may need to be relabeled.

Once the doses are shipped out to states, federal regulations prohibit recalling them even if they are not needed domestically. 

And vials cannot sit in storage forever: While vaccine itself can last up to a year in a frozen state, once bottled it must be used within four to six months.

All these variables threaten to complicate what so far has been relatively smooth sailing for the Biden administration. 

Thanks in part to the federal government’s determined assistance over many months, vaccine manufacturers have been steadily increasing their output, and states have snapped up new doses as fast as the government could deliver them.

Where to go from here is a matter of intense debate.

Clinical trials to determine which vaccines work for the nation’s adolescents and children are continuing and most likely will not neatly wind up at the same time. 

By the end of spring, for example, Moderna and Pfizer are hoping for interim results on how their vaccines would work for the nation’s 30-some-million adolescents. 

But Moderna, at least, does not expect results for children under 12 until after the school year starts next fall.

The administration could hang on to doses from those two manufacturers while it awaits findings, only to discover later that another vaccine whose trials began later — say Johnson & Johnson’s — is a better option.

If one or more of the three authorized vaccines turn out to provide only brief protection against Covid-19, scores of millions of more doses could be required for booster shots. 

But when that answer will come is also uncertain.

A woman received one of New Jersey’s first Johnson & Johnson vaccine doses this month. Of all the vaccine doses given globally, about three-quarters have gone to only 10 countries.Credit...Bryan Anselm for The New York Times

Federal health officials have also discussed canceling or reducing some orders from Moderna and Pfizer in return for the promise of a fresh supply this fall of either pediatric doses or shots of a new vaccine that has been reconfigured to work against the fast-spreading variants.

There is some push for that from the manufacturers, whose vaccines are coveted by other high-income countries. 

But it would also deprive federal officials of the power to decide which nations get the surplus doses, as well as the humanitarian and diplomatic credit it would reap from sending the vaccine to countries in greater need.

For all these reasons, senior officials say, the administration is leaning toward keeping the doses it has ordered then at some point directing the excess to other nations in bilateral deals or giving it to Covax, an international nonprofit organization backed by the World Health Organization that is trying to coordinate equitable distribution of vaccine. 

The Biden administration has already donated $4 billion to that international effort.

Mr. Biden has stressed that his top priority is to protect Americans, but pressure is growing to share the U.S. stock. 

The United States has ordered a billion doses from the three federally authorized manufacturers and AstraZeneca, whose vaccine is not yet cleared for emergency use in the States but has been authorized by more than 70 countries. 

It recently announced that it was negotiating a deal with Johnson & Johnson for enough doses to cover another 100 million.

Taken together, the supply would be enough to vaccinate 650 million people — nearly twice the U.S. population. 

With the world’s highest death toll from Covid-19, the United States has fully vaccinated 14 percent of its population.

Last week, the White House announced that it would share four million doses of AstraZeneca’s vaccine with Mexico and Canada, but emphasized that no Americans would lose out because the vaccine has not been deployed here yet.

That is a trickle compared with the 300 million AstraZeneca doses the federal government has ordered, enough to cover 150 million people with the two-dose regimen. 

Senior administration officials say tens of millions of those doses can be released now or imminently, and tens of millions of unbottled doses possibly could also be given away.

Brazil is particularly eager for help. With more than 300,000 lives lost, the country has the second-highest death toll and has fully vaccinated less than 2 percent of its population.

“After we do take care of the really difficult situation we’ve had in our own country with over 535,000 deaths, we will obviously, in the future, have surplus vaccine, and there certainly is a consideration for making that vaccine available to countries that need it,” Dr. Anthony S. Fauci, the government’s top infectious disease expert, said at a White House news conference on Wednesday.

He has cast early May, when the Biden administration wants states to open up vaccinations to all adults, as a turning point. In an interview this week, he said it was likely that anyone who wants a vaccine would be able to get one then.

Some will not want to be vaccinated, although their numbers appear to be dwindling. According to a Pew Research Center poll this month, 69 percent of the public intends to get inoculated or already has.

In the summer, the U.S. production outlook brightens further. Pfizer and Moderna together have promised enough doses to cover another 100 million people by the end of July.

Pfizer continues to beef up its production lines. 

And Moderna is hoping to win regulatory approval to increase the number of doses in each vial by at least 40 percent, although shortages of specialized syringes might hinder that plan.

A shipment of the AstraZeneca vaccine arriving in Ethiopia this month, as part of the United Nations-led Covax program.Credit...Amanuel Sileshi/Agence France-Presse — Getty Images

Johnson & Johnson has been slower to scale up its manufacturing in the United States and is now racing to deliver as many as 24 million doses manufactured at its Dutch plant by the end of the month, according to federal officials. 

The Food and Drug Administration just certified its new bottling operation in Indiana and is expected any day to approve its vaccine production lines at a Baltimore plant.

But while Johnson & Johnson has lagged behind the other manufacturers, its technology carries enormous promise for mass production because it can deliver many more doses per lot.

Later this year, when Merck & Company is expected to begin producing Johnson & Johnson’s vaccine, it could churn out 100 million doses a month — or as much as Pfizer and Moderna together deliver monthly. 

The White House hailed the deal between Johnson & Johnson and Merck, but by the time production gets up to speed, those doses may be bound for a growing surplus or for export.

One option is to ship the frozen vaccine that will be manufactured in Merck’s plant overseas, where it can be bottled much more cheaply. 

Of the $10 that the federal government has agreed to pay for a dose of Johnson & Johnson’s vaccine, the drug substance itself accounts for only about 30 cents, federal officials said. 

The rest is the so-called fill-and-finish cost.

If AstraZeneca wins emergency use authorization from U.S. regulators, that will throw still more shots into the mix. 

Officials expect about 50 million doses to be ready for delivery in May.

But Biden administration officials are skittish about AstraZeneca’s vaccine. 

It appears to be roughly as effective as Johnson & Johnson’s but requires an additional shot, meaning a more complicated rollout. 

Some health officials worry that if there are already enough doses in the pipeline to cover every adult who wants a shot, introducing a fourth vaccine will just confuse people.

On the other hand, if the administration decides to donate the AstraZeneca doses without offering any to its own citizens, other countries might conclude that the United States lacks confidence in the vaccine’s safety or effectiveness.

“As we gain more confidence in the doses that we have and the ability or the need or not to be boosting, then we can make a more definitive statement about what the role of the AZ product is going to be in the United States” should it gain clearance, Dr. Fauci said in an interview this week, “but right now I think it’s too premature to say anything.”

Sheryl Gay Stolberg, Benjamin Mueller and Matina Stevis-Gridneff contributed reporting. Kitty Bennett contributed research.

Boxed In On China

Trapped in a groundswell of anti-China sentiment, US President Joe Biden’s team appears to be staying the course set by the previous administration. A better way would be for both sides to go back to basics – the economics and trade issues that have long anchored the US-China relationship.

Stephen S. Roach

NEW HAVEN – It wasn’t just the weather that was cold when senior US and Chinese officials convened recently in Anchorage, Alaska to try to reset their countries’ relations after four years of mounting tension. 

Sadly, the meeting was more reminiscent of the Cold War era than of a fresh start. That needs to change quickly – before it is too late.

Trapped in the politics of America’s bipartisan groundswell of anti-China sentiment, President Joe Biden’s team appears to be staying the course set by the previous administration, even upping the ante on the trade and technology conflict by raising human rights and geopolitical concerns, which Biden’s predecessor ignored. 

And China, trapped in a mindset born of a “century of humiliation,” compounded the problem with its assertive and defensive response. 

In full view of the media, the opening exchange was laced with charges and counter charges, with no discernible path for de-escalation.

A better way would be for both sides to go back to basics – the economics and trade issues that have long anchored the US-China relationship. That doesn’t mean dismissing other tough issues. 

It means reestablishing common ground and mutual trust before expanding the agenda. 

This is where the Biden administration needs to rethink its combative approach. On economics and trade, it has been boxed in by the “phase one” trade deal negotiated by the “former guys,” as Biden refers to the previous administration. And that is where there is greatest leverage for change.

Yes, the American public favors the phase one approach. The latest Pew Research Center survey, conducted in February, shows widespread support for a continuation of tariffs, with more people interested in getting tougher on trade with China than in building stronger ties. 

The unrelenting focus on China over the past four years as the source of much that ails the United States now has a firm grip on popular sentiment.

But that doesn’t mean the American public’s view is correct. The phase one deal was flawed from the start, mainly because it offers a bilateral fix for a multilateral trade deficit with many countries, some 96 in 2020. 

Thus, the deal never delivered. It didn’t reduce the US trade deficit, and it imposed a new layer of costs on American businesses and consumers.

Just as the US trade deficit was not made in Japan 30 years ago, it is not made in China today. Unsurprisingly, in both instances, the largest share of the US trade deficit could be traced to America’s largest trading partner – Japan then, China now.

But this concentration is more a reflection of comparative advantage (buying goods that can be produced more cheaply abroad than at home) and supply-chain efficiencies (assembling components and parts made in other countries) than of unfair trading practices.

But, as I have written ad nauseam over the years, the US trade deficit is the result of a deeper problem of America’s own making: a shortfall of domestic saving. 

America’s net national saving rate – the broadest measure of the combined depreciation-adjusted saving of businesses, households, and the government sector – is in negative territory for the first time in a decade (and only the second time on record). 

According to the latest available data, it averaged -0.8% of national income in the second and third quarters of 2020. And in light of outsize federal budget deficits, there is a good chance that national saving will plunge further.

Lacking domestic savings, the US borrows surplus saving from abroad in order to invest and grow. 

That, in turn, sustains an outsize balance-of-payments deficit, which averaged -3.3% of GDP in the second and third quarters of last year – the widest since late 2008. 

In exchange for foreign capital, Americans buy goods from overseas. Balance-of-payments deficits, not the so-called China problem, are the macroeconomic source of America’s overall trade deficit.

The phase one deal is a political effort to micro-manage a macro problem. 

Even if it worked in narrowing the bilateral trade deficit with China, the persistent shortfall of domestic saving implies that the US trade gap would be diverted to other foreign producers – which is exactly what has happened. 

Moreover, that trade diversion has gone to higher-cost foreign producers, the functional equivalent of a tax hike on American companies and consumers.

None of this is to say that the Biden administration should wave the white flag and surrender to China. 

But it needs to shift its focus and abandon the unworkable bilateral framework of the phase one deal and the tariffs that support it. 

What is required, instead, is a robust structural agenda that addresses the far more serious problems of intellectual property rights, innovation policy, forced technology transfer, cyber security, and subsidies to state-owned enterprises. 

A bilateral investment treaty (BIT) is the best way to accomplish that, as well as to scrutinize the veracity of structural grievances. Actively negotiated for a decade prior to 2017, a US-China BIT would provide a framework to resolve structural tensions while encouraging growth in both economies through expanded market access.

These are not popular arguments in the US, thanks to four years of venomous rhetoric that has convinced many Americans that China poses an existential threat. Unfortunately, America’s corrosive politics of blame and victimization is fertile ground for allegations of being mistreated by others.

But it is time for a more clear-eyed approach – especially by a new US administration that is off to such a strong start in so many important areas.

China is a challenge for the US – but also an opportunity. 

Unfortunately, Biden has been boxed in by his predecessor. 

It will take political courage, wisdom, and creativity to break with the failed approach of the past four years. 

The US-China relationship is far too important to do anything less.

Stephen S. Roach, a faculty member at Yale University and former chairman of Morgan Stanley Asia, is the author of Unbalanced: The Codependency of America and China.