Bioengineering researchers have recently constructed the final steps required to engineer yeast to manufacture opiates, including morphine and other medical drugs, from glucose, drawing significant interest, and concern, from the media and academics in the science and policy fields, including at the Center for International Security and Cooperation (CISAC).  

“Researchers are getting better at building biology based platforms to create a wide variety of compounds that are difficult, inefficient, or sometimes impossible to create by other means,” Dr. Megan J. Palmer told National Public Radio in the weekly Science Friday segment.

She highlighted how these platforms can enable production of potentially safer, cheaper and more effective drugs. “But one significant concern is if we create the full pathway to go from glucose to this intermediate and then all the way to things like morphine, this could feed into illicit markets and bolster new illicit markets.”

Palmer is a William J. Perry Fellow in International Security at CISAC whose work focuses on developing best practices and policies for responsibly advancing biotechnology.

The media this week has focused on comments by researchers who pointed out that the modified yeast could be used to manufacture heroin, a synthesized version of morphine. The prospect of “home-brewed heroin” has been prominently featured in news coverage.

There are significant concerns, says Palmer, but she cautioned that focusing solely on that possibility could lead to bad policy outcomes.

“There is a big opportunity for researchers, policy makers, and industry to work together to figure out what controls they can put in,” she said in a separate interview. “We have time to get ahead of this problem. We now have choices in how we build and regulate the technology. The challenge for regulatory and technical communities will be to avoid reactive quick fixes. It’s encouraging to see researchers engaging in these issues early on.”

The challenge will be to find ways for researchers, law enforcers, and policy experts to work together to build safeguards into the biology itself as well as into organizations and institutions. 

“We really need to think about security as a design principle,” Palmer said. She hopes to foster thoughtful and rigorous analysis of how the design of biotechnology impacts future governance options.

“This issue highlights beautifully the nexus between public policy and science and technology, which is where CISAC has already, and will continue to make important contributions,” said CISAC Co-Director David Relman. Dr. Relman is also the Thomas C. and Joan M. Merigan Professor in the Departments of Medicine, and of Microbiology and Immunology at Stanford University. 

CISAC recently hosted a seminar led by Stanford’s Dr. Christina Smolke that discussed technology advances that are resulting in alternative supply chains for drugs, with particular attention to opiates.

Dr. Smolke is also troubled by the over-emphasis of the risks associated with the potential technology. “I believe it’s inflammatory, biased, and not grounded in an accurate representation of the technology. However, the commentary focuses on the risks of the supply chain and proposes regulations/governance for such a technology, without implementing a process to engage various parties in discussions to thoughtfully assess risks, opportunities, and regulatory needs in this context.”

“I think we need to frame this issue in the context of the larger systemic challenges involving the rearrangements of supply chains enabled through bio-manufacturing and how we spread responsible norms and practices,” Palmer said. “We need to think about governance options in terms of human capacities and technical capacities. What safeguards can we engineer into our technologies, and in turn what safeguards can we build into our organizations and institutions?”

The Europe Center Graduate Student Grant Competition

Call for Proposals:

The Europe Center is pleased to announce the Fall 2014 Graduate Student Grant Competition for graduate and professional students at Stanford whose research or work focuses on Europe. Funds are available for Ph.D. candidates from across a wide range of disciplines in the humanities and social sciences to prepare for dissertation research and to conduct research on approved dissertation projects. The Europe Center also supports early graduate students who wish to determine the feasibility of a dissertation topic or acquire training relevant for that topic. Moreover, funds are available for professional students whose interests focus on some aspect of European politics, economics, history, or culture; the latter may be used to support an internship or a research project. Grants range from $500 to $5000.

Additional information about the grants, as well as the online application form, can be found here.  The deadline for this Fall’s competition is Friday, October 17th. Recipients will be notified by November 7th. A second competition is scheduled for Spring 2015.
 

Highlights from 2013-2014:

In the 2013-2014 academic year, the Center awarded grants to 26 graduate students in departments ranging from Linguistics to Political Science to Anthropology. We would like to introduce you to some of the students that we support and the projects on which they are working. Our featured students this month are Michela Giorcelli (Economics) and Orysia Kulick (History).

Giorc

elli’s project, “The Effects of Management and Technology on Firms’ Productivity: Lesson from the US Marshall Plan in Italy,” explores the role of productivity in the process of economic growth and development. It is typically difficult to isolate the causal effect of management training programs and technology transfer programs on business productivity because these measures are often endogenous to other unobservable factors. To overcome this concern, Giorcelli employed a unique research design to analyze the effects of the Marshall Plan’s transfer of US management and technology to Italian firms in the aftermath of WWII. 

Giorcelli collected and digitized balance sheets data for 6,035 Italian firms eligible to receive the US management and technology support between 1930 to 1970. She then exploited an exogenous change in policy implementation that randomly determined which firms actually received Marshall Plan support. Preliminary results show that all firms that received either support significantly increased their productivity. Moreover, firms that received both sets of support simultaneously showed an additional increase in productivity, suggesting that management and technology are complementary in production. (Inset: The archives where Giorcelli conducted her research)

Kulick’s project, “Regionalism in Ukraine and the Long Collapse of the Soviet Union, 1954--2014,” used original historical evidence collected from Ukrainian archives to study the political nexus between party elites in Kiev and in Moscow. For example, Kulick gleaned insights about the political economy of postwar industrial reconstruction from local archives in Dnipropetrovsk, a metallurgical powerhouse in the region. Previously inaccessible primary sources indicate that as the Soviet economy grew more complex, the state apparatus became more independent. Consequently, managerial specialists needed more autonomy to meet deadlines and quotas, making them--rather than the party--the source of innovation in postwar Ukraine. 

According to Kulick, “my research this summer opened up new ways of thinking about the relationship between the party and the institutions that made up the Soviet state and economy.” Kulick used insights from Soviet-era KGB documents to shed new light on the current propaganda emanating out of the Kremlin. For example, she found that the long-term pull toward greater improvisation has had ongoing consequences. The current conflict is not just about Ukraine’s geopolitical orientation; it is also the byproduct of the dissolution of intransigent and poorly understood late Soviet-era institutions. (Inset: Kulick documents military mobilization during her summer in Ukraine)
 

---

Undergraduate Internship Program: Highlights

The Europe Center sponsored four undergraduate student internships with leading think tanks and international organizations in Europe in Summer 2014.  Laura Conigliaro (International Relations, 2015) joined the Centre for European Policy Studies (CEPS), while Elsa Brown (Political Science, 2015), Noah Garcia (BA International Relations and MA Public Policy, 2015), and Jana Persky (Public Policy, 2016) joined Bruegel, a leading European think tank. Our featured student this month is Laura Conigliaro.

During her time at CEPS, Conigliaro worked on a 68-page research paper on genetically modified organisms (GMO) policy in the European Union. In the paper, she traces E.U. legislation and policy development on GMOs from 1990 onward, and also offers conclusions for the future trajectory of the E.U.’s GMO policy. Conigliaro argues that the evolution of the E.U.’s GMO policy is a topic of extreme relevance--and difficulty--because it is the source of high-level trade conflicts between Europe and the United States. Consequently, the study of GMO policymaking can help advance our understanding of E.U. institutions, E.U. “comitology” (policy process), and E.U.-U.S. bilateral relations. 

Conigliaro plans to incorporate the summer fellowship experience into her Stanford academic career, for example, by presenting research findings at Stanford’s Symposia of Undergraduate Research and Public Service (SURPS). Looking ahead, she writes: “I hope to use the knowledge and experience gained of the E.U. Institutions and policy process through the lens of the GMO issue to broaden and diversify my potential career opportunities and areas from my traditional area of concentration, East Asia, to also include the European Union.”

---

Recap:  Panel on Europe-Russia Relations and EU expansion

On September 30, 2014, Miroslav Lajčák, the Deputy Prime Minister and the Minister of Foreign and European Affairs of the Slovak Republic, participated in a panel discussion in which he shared his thoughts and opinions about Europe’s relationship with Russia, and about the E.U.’s management of its future membership and associations. The Minister’s viewpoints were of particular interest, given his role in the E.U. foreign policy establishment, and the Slovak Republic’s role in the E.U. and NATO.

“The fact is that E.U.-Russia relations have worsened dramatically. That cannot be denied. But it’s not E.U. enlargement that played a major role in this.”  According to the Minister, Russia did not view E.U. enlargement with hostility, in part, because enlargement remained a transparent process. “But it all changed when Europe decided to enter into Russia’s immediate neighborhood...the former Soviet Republics. And this was something that

was seen by Russia as a hostile activity, and this was what Russia fiercely resisted.” The Minister spoke candidly about the potential conflicts of concepts between the E.U.’s Eastern Partnership policy, Russia’s Near Abroad policy, and the idea of a Eurasian Union. A fundamental and ongoing source of tension pertains to the geopolitical position of Russia’s immediate neighbors: “The fact is that Russia never accepted the full sovereignty of the former Soviet Republics.” Apart from discussing the escalation of tensions between the E.U. and Russia, the Minister spoke about the role of sanctions and reforms as a path for moving forward and achieving lasting peace in Europe.

Minister Lajčák’s brought a variety of experiences to the panel. He served as the European Union Chief Negotiator for the E.U.-Ukraine and E.U.-Moldova Association Agreements, and was the European Union Special Representative for Bosnia and Herzegovina, and Sarajevo. Additionally, he was previously the Ambassador of the Slovak Republic to the Former Republic of Yugoslavia, Albania and the Former Yugoslav Republic of Macedonia. 

After Minister Lajčák spoke, he was followed by comments by Michael McFaul, Professor of Political Science and Senior Fellow, Hoover Institute and Freeman Spogli Institute; Norman Naimark, the Robert and Florence McDonnell Professor in East European Studies in the History Department and The Director of Stanford Global Studies; and Kathryn Stoner, Senior Fellow at the Freeman Spogli Institute and Faculty Director of the Susan Ford Dorsey Program in International Studies.

---

Introducing “Immigration and Integration in Europe” Policy Lab

The Europe Center would like to introduce a new research project entitled, “Immigration and Integration in Europe:  A Public Policy Perspective,” led by Professors David Laitin and Jens Hainmueller. Duncan Lawrence has recently joined Stanford University to help direct the project. The project is part of the new Policy Implementation Lab at the Freeman Spogli Institute for International Studies.

The social and economic integration of its diverse and ever growing immigrant populations is one of the most fundamental and pressing policy issues European countries face today. Success or failure in integrating immigrants is likely to have a substantial effect on the ability of European countries individually and collectively as members of the European Union to achieve objectives ranging from the profound such as sustaining a robust democratic culture to the necessary such as fostering economic cooperation between countries. Various policies have been devised to address this grave political dilemma, but despite heated public debates we know very little about whether these policies achieve their stated goals and actually foster the integration of immigrants into the host societies. (Inset: David Laitin)

The goal of this research program is to fill this gap and create a network of leading immigration scholars in the US and Europe to generate rigorous evidence about what works and what does not when it comes to integration policies. The methodological core of the lab’s research program is a focus on systematic impact evaluations that leverage experimental and quasi-experimental methods with common study protocols to quantify the social and economic returns to integration policies across Europe, including polices for public housing, education, citizenship acquisition, and integration contracts for newcomers. This work will add to the quality of informed public debate on a sensitive issue, and create cumulative knowledge about policies that will be broadly relevant. (Inset: Jens Hainmueller)

---

The Europe Center Sponsored Events

We invite you to attend the following events sponsored or co-sponsored by The Europe Center:

Additional Details on our website
October 8-10, 2014
“War, Revolution and Freedom: the Baltic Countries in the 20th Century”
Stauffer Auditorium, Hoover Institution
9:00 AM onward

Save the Date
April 24-25, 2015
Conference on Human Rights

A collaborative effort between the International Human Rights and Conflict Resolution Clinic at Stanford Law School (IHRCRC), the Research Center for Human Rights at Vienna University (RCHR), and The Europe Center. The conference will focus on the pedagogy and practice of human rights. 

Save the Date
May 20-22, 2015
TEC Lectureship on Europe and the World 
Joel Mokyr
Robert H. Strotz Professor of Arts and Sciences, and Professor of Economics and History, Northwestern University

We welcome you to visit our website for additional details.

The Ebola epidemic, which could affect hundreds of thousands of West Africans, can only be contained by rebuilding public trust and local health systems decimated by years of neglect, according to a panel convened by the Freeman Spogli Institute for International Studies and Stanford Medicine. FSI Senior Fellows David Relman, Paul Wise, Stephen Stedman, Michele Barry and Douglas Owens were among the panelists.

The World Health Organization estimates 2,811 people have died of the virus since the outbreak began earlier this year and that 5,864 people currently are infected in Sierra Leone, Liberia, Guinea, Senegal and Nigeria.

In this Stanford Medicine news story, Owens, a professor of medicine and director of the Center for Health Policy at FSI, cites a new report by the Centers for Disease Control and Prevention that estimates that even with "very aggressive" intervention, there would be at least 25,000 cases by late December. If intervention is delayed by just one month, the CDC estimates there would be 3,000 new cases every day; if it's delayed by two months, there will be 10,000 new cases daily. "It gives you a sense of the extraordinary urgency in terms of time," Owens told the audience.

Relman and CISAC biosecurity fellow Megan Palmer have also done a Q&A about the virus.

And you can listen to a KQED Public Radio talk show about Ebola that included Relman. 

 

 

 

 

(Updated Nov. 7, 2014)

The Centers for Disease Control and Prevention reported on Nov. 4 that the death toll from the Ebola outbreak in West Africa has risen to above 4,960 and that an estimated 8,168 people, mostly in Liberia, Sierra Leone and Guinea, have contracted the virus since March. It is the largest and most severe outbreak of the Ebola virus since it was first detected four decades ago. All but nine of the deaths were in those three countries; eight were in Nigeria and one patient died in the United States.

The CDC in October proclaimed that in the worst-case scenario, Sierra Leone and Liberia could have 1.4 million cases by Jan. 20, 2015, if the disease keeps spreading without immediate and immense intervention to contain the virus.

Two American aid workers infected with Ebola while working in West Africa were transported to a containment unit at Emory University in Atlanta for treatment, raising public fears about international spread of the highly virulent virus that has no known cure. The two were released from the hospital after being the first humans to receive an experimental Ebola drug called ZMapp. Another man who recently helped an Ebola victim in Liberia traveled to Texas and died in a Dallas hospital. Two of the nurses who treated him caught the virus as well, but have been released from the hospital. Some states have struggled with the moral 

We ask CISAC biosecurity experts David Relman and Megan Palmer to answer several questions about Ebola and the public health concerns and policy implications. Relman is the co-director of the Center for International Security and Cooperation who has served on several federal committees investigating biosecurity matters. He is the Thomas C. and Joan M. Merigan Professor in the Departments of Medicine and of Microbiology and Immunology at Stanford University School of Medicine, and Past-President of the Infectious Diseases Society of America.

Palmer is the William J. Perry Fellow in International Security at CISAC and a Researcher at the UC Berkeley Center for Quantitative Biosciences (QB3), and served as Deputy Director of Policy & Practices for the Multi-University NSF Synthetic Biology Engineering Research Center (SynBERC).

The two of them have answered the questions together.

What is Ebola and how dangerous is it compared to other diseases?

Ebola is an acute viral infectious disease, often associated with severe hemorrhagic fever. While initial symptoms are flu-like, they can rapidly progress, and include vomiting, reduced ability to regulate immune responses and other physiological processes, sometimes leading to internal and external bleeding. The disease has an incubation period that can last up to 21 days, but patients typically become ill four to nine days after infection, and die about seven to ten days later. Fatality rates for the current Ebola outbreak are nearing 60% (according to the CDC), while past outbreaks in the Republic of Congo have seen rates as high as 90%. This outbreak to date has resulted in nearly 1,000 deaths, more than any previous Ebola outbreak.

Ebola virus is believed to reside in animals such as fruit bats where it does not cause disease, but is then transmitted to and among humans and other primates, in whom disease typically does occur. The route by which the virus crosses between species remains largely unknown. People become infectious once they become symptomatic. Ebola is transmitted via blood or bodily fluid, but can persist outside the body for a couple days. Infection can occur through unprotected contact with the sick, but also when contaminated equipment such as needles cut through healthcare workers’ protective gear, and also through contact with infected individuals postmortem.

David Relman Photo Credit: Rod Searcey

Ebola’s horrific symptoms provoke public fear, and it becomes easy to lose perspective on the relative spread and toll of this outbreak. Ebola is relatively difficult to transmit. This means the latest Ebola outbreak is still small in comparison to the hundreds of thousands of people killed each year via more easily transmitted airborne influenza strains and other diseases such as malaria and tuberculosis. It’s important that we not lose sight of more chronic, but less headline-grabbing diseases that will be pervasive, insidious long-standing challenges for Africa and elsewhere.

Is there a vaccine or cure?

There is no vaccine for Ebola and no tried-and-true cure. Health workers can only give supportive care to patients and try to stop the spread to new victims.

Several experimental therapies for Ebola are under development. One receiving attention is ZMapp, a mix of antibodies produced by mice exposed to the virus that have been adapted to improve their human compatibility. Limited tests in primates show early promise, but the drug had not been tried on humans -- until now. Two Americans transported back to the U.S. from West Africa received the experimental therapy. While the two seem to be improving, it isn’t clear that ZMapp was responsible; another issue is that ZMapp and other potential therapies have not been cleared by the FDA for wider use in humans.

The process for approval, and who gets priority access to such drugs, are complex policy issues. The WHO will be convening leaders and medical ethicists next week to discuss how to develop and distribute experimental therapies. This is not a simple task; many factors need to be taken into consideration and balanced with limited information to guide decisions.

Successful or not, and despite any approval, it’s still uncertain whether enough of such drugs could even be produced quickly enough to respond to this particular outbreak, and if not - whether they’d be effective in a future outbreak.

 

You can listen to Relman in this KQED Public Radio talk show.

Relman joins other experts in a Stanford panel on Ebola

 

Why has this Ebola outbreak involved so many more people, and spread to a wider geographic area,  than previous outbreaks?

This is an evolving investigation and many potential contributing factors are being examined by scientists racing to collect information that can help them get ahead of the outbreak.

One factor is population density. This latest outbreak spread early into denser population areas within Liberia and Sierra Leone, rather than remain confined to isolated villages, as in earlier outbreaks in Central Africa. With a greater number of people being exposed within a smaller geographic area, the likelihood of transmission increases. Of particular concern is the prospect that the virus might take hold in Lagos, Nigeria, where a handful of cases have been recently identified. If this were to spread in Lagos, Africa’s most populous city, the death toll would likely increase dramatically.   

Another factor is the ability of affected regions to mount an effective public health response. This outbreak is occurring in three of the poorest African countries: Sierra Leone, Liberia, and Guinea. Civil wars have likely contributed to degradation of an already relatively poor public health infrastructure. This is also the first Ebola outbreak in the region, and the inexperience of local authorities can delay responses and fuel fearful community responses, undermining the ability to deal with the outbreak early when it’s more easily contained.

Cultural practices around the care of the sick and the dead can also fuel progression of an outbreak. In some parts of Western Africa, washing deceased relatives is commonplace. Customs like these increase the likelihood of the infection spreading through proximity between infected individuals and their family members

 

What can be done to curtail the outbreak?

Isolation and quarantine are key to fighting the spread of Ebola. Isolation involves removing infected individuals from the general population to prevent the spread of disease. Quarantine, however, involves removing uninfected or potentially infected individuals from the general population to limit the spread of disease.

Thus far, the strategy to fight Ebola is dependent on isolating infected patients. Unsurprisingly, isolation efforts have proven hard to enforce. Some families, faced with the prospect of being confined to their homes, have denied the existence of Ebola in their localities, or refuted doctors who claim that one of their family members is sick. This is not unique to Africa; Americans had violent reactions to quarantine during the spread of smallpox. Some regions are now taking more extreme measures: Sierra Leone has deployed its army to enforce isolation at clinics and infected families’ homes, but this also risks civil unrest.

These tensions underscore the necessity of improved education and enforcement mechanisms within public health strategies. Response measures involve fundamental tradeoffs between liberty and safety. Because negotiations occur through complex local, national and international processes, one of the biggest risks is that decisions don’t keep pace with disease spread.

It’s important that we not lose sight of more chronic, but less headline-grabbing diseases that will be pervasive, insidious long-standing challenges for Africa and elsewhere."

How likely is it that the disease will spread into and within the United States?

Currently, airports in Liberia, Sierra Leone, and Guinea are screening all outbound passengers for Ebola symptoms such as fever. This includes asking passengers to complete healthcare questionnaires. However, it is difficult to reliably know who has been infected until they are symptomatic. Individuals could theoretically board a plane before they show symptoms, but develop them upon landing in the United States or elsewhere. This makes containing Ebola difficult, but not impossible.

If the virus were to enter the United States, it would be easier to contain and harder to spread. This virus does not transmit that easily to other humans, especially in settings with good infection control and isolation.

As viruses spread, the chances of genetic variation increase. Yet despite all the concerns from the current outbreak, Ebola is relatively bad at spreading in comparison to respiratory viral diseases such as influenza or measles. The likelihood of a pandemic Ebola virus in the near future seems slim as long as it cannot be transmitted via air.  While it’s possible that the Ebola virus could evolve, there is little evidence to suggest major genetic adaptations at this time.

What are some broader lessons about the dynamics and ecology of emerging infectious diseases that can help prevent or respond to outbreaks now and in the future?

These latest outbreaks remind us that potential pathogens are circulating, replicating and evolving in the environment all the time, and human action can have an immense impact on the emergence and spread of infectious disease.

We are starting to see common factors that may be contributing to the frequency and severity of outbreaks. Increasing human intrusion into zoonotic disease reservoir habitats and natural ecosystems, increasing imbalance and instability at the human-animal-vector interface, and more human population displacement all are likely to increase the chance of outbreaks like Ebola.

Megan Palmer Photo Credit: Rod Searcey

The epicenter of this latest outbreak was Guéckédou, a village near the Guinean Forest Region. The forest there has been routinely exploited, logged, and neglected over the years, leading to an abysmal ecological status quo. This, in combination with the influx of refugees from conflicts in Guinea, Liberia, Sierra Leone, and Cote d’Ivoire, has compounded the ecological issues in the area, potentially facilitating the spread of Ebola. There seems to be a strong relationship between ecological health and the spread of disease, and this latest outbreak is no exception.

While forensic analyses are ongoing, unregulated food and animal trade in general is also a key factor in the spread of infectious diseases across large geographic regions. Some studies suggest that trade of primates, including great apes, and other animals such as bats, may be responsible for transit of this Ebola strain from Central to Western Africa.

What are some of the other political and security implications of the outbreak and response?

Disease outbreaks can catalyze longer-term political and security issues in addition to more acute tensions.

There are complex international politics involved in emergency response and preparedness. Disease outbreaks often occur in poor regions, and demand help from more wealthy regions. The nature of the response reflects many factors - technical, social, political, legal and economic. Leaders often lack the expertise to take all these factors into account. It is an ongoing challenge to adapt our governance processes to be more reliable and move from damage control to planning. Organizations like the World Health Organization can provide guidance, but more resources and expertise are needed to get ahead of future disasters.

When help is provided, there is often mistrust of non-local workers, who can even be seen as sources of the disease. At a political level, distrust has been fueled by disguising political missions as health interventions, as was the case with the effort that led to the locating of Osama Bin Laden.

There are other security implications of this latest epidemic. This outbreak has led to a dramatic increase in the availability of Ebola virus in unsecured locations across West Africa, as well as to a growing number of labs across the world studying the disease. The immediate need to study the disease and develop beneficial interventions needs to be coupled to considerations of safety and security. From a safety standpoint, a rise in the handling of Ebola samples risks accidental transmission. From a security standpoint, those who wish to cause harm with this virus could acquire it from bodies, graves and other natural sources in the affected region. Both of these risks demand attention and efforts at mitigation.