Last month, He Jiankui, a Chinese researcher, announced the birth of the world’s first gene-edited babies, whose DNA had been edited to reduce the risk of HIV infection. While the claim has not yet been verified, Chinese authorities have launched an investigation and ordered this researcher’s work to stop. In the discussion that follows, Stanford Law Professor Hank Greely, an expert in the ethical, legal, and social implications of new biomedical technologies, and a Stanford Health Policy Fellow, discusses the legal and ethical questions surrounding the new world of gene-editing.

First, can you explain what the Chinese researcher, He Jiankui, did?

I’ll try but, first, we don’t know whether He Jiankui** did anything except make YouTube videos and give a talk. There has been no independent verification that these babies exist, let alone that he edited their genes. It would be a very bold fraud, but bold frauds have been carried out before in bioscience, including, notably, Hwang Woo-Suk’s false claim in 2004-05 that he had successfully cloned human embryos.

Assuming He Jiankui did what he said he did, he used a fantastic new DNA editing tool called CRISPR (“Clustered Regularly Interspaced Short Palindromic Repeats”) in human embryos very shortly after the eggs were fertilized. His goal was to change a gene called CCR5. This gene makes a protein that sits on the outside of some our white blood cells, crucial to the immune system, called T cells. There is good evidence that T cells that lack CCR5 cannot be (or cannot easily be) infected with HIV; about 1% of Northern Europeans (and a smaller percentage of people elsewhere) have a particular change in their CCR5 gene that deleted 32 base pairs (“letters”) in the DNA sequence and they do not seem to get HIV infections. So, his stated goal was to provide these embryos (and the babies, teenagers, and adults they turn into) with immunity from HIV infection. The data he released, however, shows that one of the twins only had half of her cells modified. If half of her T cells have CCR5, she could still be HIV infected. The other twin had all of her cells changed but not in the way He Jiankui intended, and not in the way found in people. We have no idea whether she will be immune, wholly or partially, from HIV infection.

Is it legal in the U.S.—or anywhere? If not, why?

It is not legal in the U.S. The FDA takes the position, which I think courts would most likely uphold, that genetically altered human embryos are either drugs or biological products (or both) and so under its jurisdiction. It is illegal—a federal crime—to distribute a new drug without FDA approval. The FDA has not approved genome editing for embryos for clinical use. For research uses only, you can get FDA permission more easily. You need to submit an application to the FDA for what’s called an Investigation New Drug (IND) exemption. You need to show the FDA that there is good reason, based on non-human research, that this will not be too risky for the research participants and that there is a reasonable chance it will be effective. His work would not satisfy either side of this and so would not get an IND.

But that’s not relevant right now because since December 2015 Congress has regularly added an amendment to the FDA’s funding bill, prohibiting it from even considering any application, of any kind, for human germline editing. So, if you did this in the US now, you’d be doing it without FDA approval, which would make your use an illegal distribution of a new drug.

In many other countries, particularly in Europe, any germline human genome editing is illegal by specific statute (which it is not in the U.S.). In most countries there is no law on this—many poor countries have other things to worry about—so it is legal (at least, not specifically illegal) in most countries.

What are the dangers? What are the potential benefits?

One danger to the children is that CRISPR might have caused damage to other parts of their DNA. These so-called off-target effects are fairly common when CRISPR is used. In addition to changes in other parts of the genome, we know that He Jiankui did not accurately make the changes he aimed for in the CCR5 gene; it’s possible that the He Jiankui-modified gene would not only be ineffective at preventing HIV but affirmatively harmful.

A second danger is that life without a working CCR5 gene may have its own problems. The Northern Europeans without it include adults and appear healthy but they haven’t been closely followed to see if they are at higher risk for other problems. There is some early evidence, for example, that they might be more susceptible to West Nile Virus and influenza.

The potential benefit to the babies is HIV immunity but it is of very little weight. One twin cannot be immune because half of her cells have CCR5. The other may not be immune. And both are “saved” from the possibility, probably small, that they would become infected after being exposed to HIV (probably several decades in the future). HIV is already a manageable disease (though certainly not fun); we have no idea how easily preventable or treatable it may be in 20 years.

The potential benefit to science/medicine is showing that CRISPR’d babies can be born but if that is worth establishing, it could and should be done in a different setting, with an embryo with a very serious disease for which no good alternative exists.

When might it become legal? 

It could become legal any time Congress lets the appropriations rider lapse (next fall) and FDA decided there was enough safety information to allow it to proceed. I expect that neither of those will happen anytime soon.

When/if it does, would it be governed or overseen by an international organization? How might it be regulated? 

Highly unlikely. In the U.S. it will be overseen by FDA and local IRBs. Not perfect but not terrible.

What are the ethical challenges we’ll face when it does become legal?

For me, really not much. The safety issues for the kids are key. Apart from that, based on our current knowledge of human genetics, there are very few situations where gene editing in embryos will be better than embryo selection. We don’t know enough to make super babies and are unlikely to anytime soon. For some people doing any genetic editing that could pass down to future generations is itself a major ethical issue, a “line in the sand” we should not pass. As I have written elsewhere, I don’t think that’s right. See https://leapsmag.com/much-ado-about-nothing-much-crispr-for-human-embryo-editing/

What legal issues do you anticipate?

If this is tried before it is legal, I would expect federal criminal charges against the clinics/scientists. That might raise the question of whether a gene-modified human embryo really is a drug or biological device for purposes of FDA law. If this is tried after it is legal and it goes wrong, big malpractice suits. If it gets used under appropriate regulation, not much.

___

Hank Greely is the Deane F. and Kate Edelman Johnson Professor of Law at Stanford Law School, Director of the Center for Law and the Biosciences, Professor (by courtesy) of Genetics, Stanford School of Medicine, Chair of the Steering Committee of the Center for Biomedical Ethics. And Director of the Stanford Program in Neuroscience and Society.

** He Jiankui was a postdoctoral scholar at Stanford in the laboratory of Prof. Stephen Quake from January 2011 to January 2012. His work in the Quake lab focused on computational analysis and was in no way related to gene-editing.

During the U.S.-Japan Council annual conference that was held in Tokyo on November 8 and 9, 2018, Rylan Sekiguchi was elected chair of the TOMODACHI Emerging Leaders Program (ELP). The ELP identifies, cultivates, and empowers a new generation of leaders in the U.S.–Japan relationship. Emerging Leaders participate in leadership education, design and implement original USJC programming, and develop powerful, lifelong personal and professional friendships. A new cohort of leaders aged 24–35 is selected annually through a highly competitive process. USJC Senior Vice President Kaz Maniwa, who oversees the ELP, commented, “We are delighted that Rylan Sekiguchi will lead the Emerging Leaders Program next year as the chair of the Steering Committee. Rylan has shown great passion, dedication, and commitment to the Emerging Leaders Program and we look forward to his leadership.”

Secretary Norman Mineta and Rylan Sekiguchi

During the conference, Sekiguchi gave an overview of the ELP and shared reflections of how his professional and personal lives have embraced the mission of the ELP. Sekiguchi spoke specifically about his current work at SPICE with USJC Vice Chair Norman Mineta, former Secretary of Commerce under President Bill Clinton and Secretary of Transportation under President George W. Bush. Mineta is the subject of a new documentary—An American Story: Norman Mineta and His Legacy—co-produced by Dianne Fukami and Debra Nakatomi, and Sekiguchi is finalizing web-based lesson plans that focus on the film’s key themes, including immigration, civil liberties, and leadership. The documentary was screened at the conference and is anticipated to air on PBS.

A short video that Sekiguchi shared during his speech brought applause from the audience. The video captured a snippet of a performance that he and other members of San Jose Taiko presented last year. The performance celebrated “swing music and the role it played in lifting people’s spirits amid the harsh reality of the Japanese-American internment,” shared Sekiguchi. “Through music and theater, we transported people back to a 1940s-era ‘camp dance’ to educate audiences about the painful, agonizing choices that incarcerees faced.” Mineta was a young boy when his family was uprooted from San Jose, California, and incarcerated in a camp for Japanese Americans in Heart Mountain, Wyoming. Mineta later became mayor of San Jose in 1971.

Through Sekiguchi’s reflections, audience members from both sides of the Pacific were prompted to reflect upon civil liberties during times of crisis—in this case, the incarceration of Japanese Americans following the Japanese attack on Pearl Harbor. My father was a high school student in a camp in Poston, Arizona, and the video prompted me to recall one of the few things that he shared with me about his life behind barbed wire—that camp dances and baseball brought some sense of normalcy to the lives of Japanese-American youth. By showing the video, Sekiguchi’s implicit message was clear: young Americans today—including of course, ELP members—must be aware of the sometimes fragile nature of civil liberties. I have the good fortune of working with another ELP member, Naomi Funahashi, and during the conference, it was rewarding for me to meet many ELP alumni and members of the newest cohort and to witness the beginnings of personal and professional friendships amongst them. Sekiguchi’s speech set the tone for the year ahead—like a “camp dance,” he wants the ELP members to have fun but to always remember the serious nature of what the ELP represents.

Shorenstein APARC's annual overview of the Center's 2017-18 activities  is now available to download. 

Feature sections look at the Center's seminars, conferences, and other activities in response to the North Korean crisis, research and events related to China's past, present, and future, and several Center research initiatives focused on technology and the changing workforce.

The overview highlights recent and ongoing Center research on Japan's economic policies, innovation in Asia, population aging and chronic disease in Asia, and talent flows in the knowledge economy, plus news about Shorenstein APARC's education and policy activities, publications, and more.

The Trump administration has proposed a new rule that would require direct-to-consumer TV advertisements for prescription drugs to disclose the price of their products.

The Centers for Medicare & Medicaid Services (CMS) said the disclosures would help consumers “make informed decisions that minimize not only their out-of-pocket costs, but also expenditures borne by Medicare and Medicaid, both of which are significant problems.”

The idea enjoys broad public support, since medical care and drug costs continue to skyrocket.  A U.S. Senate report earlier this year revealed that the cost of the 20 most commonly prescribed brand-name drugs have risen tenfold in the past five years.

In a June 2018 poll, 76 percent of Americans favored required drug advertisements to include a statement about how much the drugs cost.

But Michelle Mello, a Stanford Law School professor and Stanford Medicine professor of health research and policy, writes in this New England Journal of Medicine perspective that the proposed rule raises substantial public health and legal concerns.

A potential unintended consequence of price disclosure may be to dissuade patients from seeking care, writes Mello and her co-author, Stacie B. Dusetzina of Vanderbilt University School of Medicine, because of the perception that they cannot afford treatment. For example, Trulicity, a widely advertised drug for type 2 diabetes has a list price of $730 a month.

“Patients who could benefit from diabetes treatment may assume that they cannot afford it, when in fact insured patients’ costs for Trulicity may be much lower, and cheaper treatment options available,” they write. Metformin, for instance, costs $4 per month for patients who pay cash.

CMS would demand drug makers use the list prices from the Wholesale Acquisition Cost (WAC) in their television ads, including that costs “may be different” for those who are insured.

“This wording doesn’t communicate that costs to patients are probably much lower than the WAC,” writes Mello, a core faculty member at Stanford Health Policy.

This could have important legal implications as well, as compelled disclosures in advertising impinge on commercial speech protected by the First Amendment. Furthermore, they write, “disagreement about whether the WAC accurately represents a drug’s price could affect how courts assess the rule when constitutional challenges are inevitably filed.”

The researchers say three aspects of the proposed rule undercut the government’s ability to argue that it would improve patient decision-making and reduce drug spending: 

1. Price information does little to inform consumer decisions if it inaccurately represents actual cost.
2. Consumers can already obtain information on cash prices online and their own cost from their insurer.
3. The rule contains no meaningful enforcement mechanism; CMS plans only to list violators on its website, calling into question whether companies will comply.

“We think that a better alternative would be making patient-specific cost information accessible at the point of prescribing, “ the authors write. 

The cost of prescription drugs should become a routine part of clinician-patient discussions, although they acknowledge that this would put more time constraints on medical practices.

“Providing salient cost information at the right time could help reduce drug spending while preserving patient choice, but we believe that direct-to-consumer advertising is the wrong vehicle,” they write.

A national panel of medical experts is recommending for the first time that clinicians offer daily preventive medication to patients who are at high risk of acquiring HIV/AIDS.

The U.S. Preventive Services Task Force estimates that 1.1 million Americans are currently living with HIV. More than 700,000 people have died from AIDS in the United States since the first cases were reported in 1981 and some 40,000 Americans are diagnosed with the virus each year.

Though HIV is treatable, there is still no vaccine and it has significant health consequences.

But the Task Force said in a published draft recommendation on Tuesday that it found “convincing evidence” that taking a daily pre-exposure prophylaxis, known as PrEP, provides a substantial benefit in decreasing the risk of HIV infection in people at high risk. 

PrEP is a combination of two drugs, tenofovir disoproxil fumarate and emtricitabine, taken in one daily pill. The Centers for Disease Control and Prevention says that PrEP reduces the risk of getting HIV from sex by more than 90 percent and by 70 percent for intravenous drug users.

“Unfortunately, HIV is still a major problem in the United States,” said Stanford Health Policy’s Douglas K. Owens, vice-chairman of the Task Force, an independent, voluntary panel of experts in prevention and evidence-based medicine. “But the evidence on this daily treatment is that, if you take it properly, it’s very effective.”

The Task Force, whose recommendations are followed by primary care physicians and clinical practices across the country, gave the recommendation its highest grade, an A. But it noted that PrEP currently is not being used in many persons at high risk of HIV infection. 

“We hope our recommendation will bring attention to a very effective preventative service,” Owens said. “We want clinicians to be aware that for patients at high risk of HIV, PrEP is an important preventive strategy to discuss.”

The global AIDS epidemic has slowed in recent year. AIDS-related deaths have been reduced by more than 50 percent since the peak of the AIDS crisis in 2004. In 2017, 940,000 people died from AIDS-related illnesses worldwide, compared to 1.4 million in 2010 and 1.9 million in 2004.

But many people remain at risk, including sex workers and people who have been trafficked.

The Task Force recommendation is only for those Americans who remain at high risk for contracting the virus, including:

1. Sexually active men whose male partners are already living with HIV, or have a recent sexually transmitted infection (STI) such as syphilis, gonorrhea, or chlamydia;
2. Heterosexual women and men who are sexually active and have an STI or partner living with HIV or who are inconsistent in their use of condoms with a partner at high risk of HIV;
3. People who inject drugs and either share drug injection equipment.

The Task Force reaffirmed its 2013 recommendation that people ages 15 to 65 and all pregnant women also be screened for HIV in an additional draft recommendation. Both recommendations are open for public comment until December 26.

Donald Trump has stated his intention to ditch the Intermediate-range Nuclear Forces (INF) Treaty. He and National Security Advisor John Bolton also appear unhappy with the New Strategic Arms Reductions Treaty (New START).

Withdrawal from New START would leave Russian strategic forces wholly unconstrained and end the flow of valuable information from the treaty’s verification and on-site inspection provisions.

Having won a majority in the House, the Democrats can protect New START and, with it, nuclear stability with Russia. To do so, they should steal a page from the playbook of Sen. Jon Kyl (R-Ariz.).

Read the rest at The Hill

Stanford-led group of young American and Russian scholars meet in Moscow on nuclear policy

Persistent nuclear threats and the recent erosion of relations between the United States and Russia paint a gloomy picture for the future of cooperation between nuclear powers. Despite these enormous challenges, Stanford is leading an effort to bring young nuclear scholars from the United States and Russia together to tackle urgent problems together and share ideas.

At the end of October, a group of six scholars from Stanford’s Center for International Security and Cooperation—Senior Fellow Siegfried Hecker, Visiting Scholar Chaim Braun, Postdoctoral Fellows Chantell Murphy and Kristen Ven Bruusgaard, Research Assistant Elliot Serbin and Senior Research Associate Alla Kassianova—and other American graduate students and postdoctoral fellows from Washington State University, University of Tennessee, Harvard, University of Michigan and Los Alamos National Laboratory traveled to Moscow for the Fourth Young Professionals Nuclear Forum.  The Americans joined a group of undergraduate, graduate, and postdoctoral students at the Moscow Engineering Physics University (MEPhI), Russia’s principal school training nuclear professionals.

The Forum, first launched between CISAC and MEPhI in 2016, provides a venue for young generation of American and Russian nuclear professionals to learn about current issues of nuclear safety, nuclear proliferation, and the role of nuclear power in the world’s evolving energy balance from a perspective of more than one country and more than one discipline.

In the weeks leading up to this Forum, participants on both sides of the ocean attended a series of online presentations by U.S. and Russian experts covering the complexity of the Iran nuclear program and the challenges facing further development of nuclear power.

When they met in person, the young scholars heard lectures from and participated in discussions with experts from Los Alamos National Laboratory, the Russian Center for Energy and Security, and others.

The participants then broke into small groups to work on tabletop problem solving activities. The first exercise, a crisis simulation concerning Iran’s nuclear program, brought together separate Russian and American teams to represent their government’s positions on Iran’s nuclear program and the Joint Comprehensive Plan of Action (JCPOA). Presented with a hypothetical problem—a scenario in which Iran decides to enhance its nuclear capabilities in violation of the JCPOA and President Trump threatens retaliation via Twitter—the participants gathered in small groups to see what type of cooperative Russian-American policies could be brokered in response.

The second exercise brought the group together to imagine the future of nuclear power and how to manage it. Working in small teams of 2-4 people, the participants formulated responses to eight pressing questions regarding the global future of nuclear power, including whether nuclear power is necessary to mitigate the consequences of climate change and whether nuclear proliferation challenges will limit the expansion of nuclear power. The teams presented their answers in Moscow and will continue to develop their assessments, to be published in a report next month.

Both Americans and Russians commonly remarked that the most valuable lesson they took from the exercises was the fact that both sides held remarkably different, but valuable, perspectives on issues of common concern. On the topic of nuclear energy, for example, Russians appreciated American perspectives on the value of startups in the nuclear power industry and new modes of thinking that encapsulated non-monetary aspects of nuclear power in broader economic analyses. Americans came to understand the deep Russian fascination with nuclear energy and optimistic views about the future role of nuclear energy in society, and how deeply that passion is engraved in the university system in a way wholly different from the United States.

Forum participants also had an opportunity to meet with the leadership of two committees of the Russian State Duma, the lower Chamber of the Russian legislature, the Committee on International Affairs and the Committee on Education and Science. The meeting was hosted by Ms. Inga Yumasheva,  an MP from the United Russia party. The Forum also included a visit to research labs and MEPhI facilities, which was hosted by their scientists.

View photos from the forum

About CISAC
The Center for International Security and Cooperation tackles the most critical security issues in the world today. Founded in 1983, CISAC has built on its research strengths to better understand an increasingly complex international environment. It is part of Stanford's Freeman Spogli Institute for International Studies (FSI). Though scholarly research, fellowships, and teaching, CISAC is educating the next generation of leaders in international security and creating policy impact on a wide variety of issues to help build a safer world.

Future Visions: Challenges and Possibilities of Korean Studies in North America — Social Science panel. From left to right: UC Berkeley's Laura Nelson, University of Michigan's Jordan Siegel, Stanford's Yong Suk Lee, USC's David Kang, Harvard's Paul Chang.

How can Korean studies faculty cultivate supportive and critical scholarly communities with graduate students? What can be done to overcome the severe constraints on Korean language training in North America? Why is there a dearth of Korea scholarship in academic literature? And how should Korean studies librarians prepare for the future in the light of new technologies and young researchers’ increasing interest in digital scholarship?

These were some of the questions examined at a two-day conference, “Future Visions: Challenges and Possibilities of Korean Studies in North America,” convened by the Korea Program of Stanford’s Shorenstein Asia-Pacific Research Center (APARC) on November 1-2. Co-sponsored by the Seoul-based Foundation Academia Platonica, the conference, the first of its kind, gathered distinguished Korean studies scholars from twelve North American institutions to consider the state of the field, assess its challenges, and carry forward a vision for its future direction and potential. Its six unique panels focused not only on the major disciplines of Korean studies—history, literature, and the social sciences—but also on language education, library collections and services, and Korean Wave.

“The presentations and discussions by our fellow experts reflected the breadth and depth of Korean studies in North America,” says APARC Director and the Korea Program Director Gi-Wook Shin. “Our program was established at Stanford in 2001 and has since become a leader in Korean studies in North America, so it is a special privilege for us to bring together colleagues from eminent institutions around the continent to further advance Korean studies education and research in the academic and policy worlds, and to build upon our track record of action and achievements.”

“The field of Korean studies, however,” notes Shin, “has significantly changed over the past seventeen years and it isn’t without its challenges. This is our opportunity to consider frankly where we go next and how we could explore the path ahead together.”

Conference participants indeed engaged in deep conversations and shared ideas and dilemmas regarding teaching in the different disciplines of Korean studies in North America. Harvard sociologist Paul Chang listed three types of challenges facing the field: publication, academic, and professional challenges. David C. Kang, professor of international relations and director of the Korean Studies Institute at the University of Southern California, emphasized the publication challenge: why is it, asked Kang, that top academic journals in the discipline of political science and international relations publish so much more scholarship about Europe than they do about Korea and Asia at large, even while the rise of Asian nations is surely one of the most consequential issues of the twenty-first century? The onus, Kang argued, comes back to East Asia scholars “to produce better and more compelling scholarship, and to better train graduate students.”

University of British Columbia's Ross King and conference participants.

Yet complex issues surround the question of how to broaden graduate coursework—and whether to do so. Korean language and linguistics expert Ross King, head of the department of Asian Studies at the University of British Columbia in Vancouver, Canada, was one of several panelists who considered the obstacles to graduate training, among different aspects of academic challenges facing the field of Korean studies. King probed into how Sinocentrism and what he called the “Mandarin conceit”—that is, the notion that training in Literary Sinitic should be predicated on a near-native proficiency in modern Mandarin Chinese—are emerging as a major stumbling block to the study of premodern Korean literary culture. He also pointed to the constraints on language training in both Korean and hanmun in North America, which, he claimed, is why we can probably anticipate continued decrease in the number of ethnically non-Korean (non-Korea-educated) graduate students undertaking graduate study in Korean literature.

University of Washington's Hyokyoung Yi (left) and Stanford's Joshua Capitanio at a panel on library collections and service.

Sung-Ock Sohn, who coordinates the Korean language program in the department of Asian languages and cultures at the University of California – Los Angeles, further shed light on King’s prediction. She explained that while enrollments in Korean language classes have shown a sharp increase in American higher education institutions in the past decade, particularly at the introductory level and among ethnically non-Korean students, there is a high attrition rate of students from an introductory to advanced Korean classes nationwide.

How should the field move forward?

Participants proposed a host of ideas to that end. These included helping graduate students collaborate with colleagues in Korea; dedicating funding for junior faculty to spend periods of time before tenure conducting research and honing language skills in Korea at appropriate institutions, and for mid-career scholars to spend a year in Korea; emphasizing the application of social science theories and methods to premodern and modern East Asia; motivating scholars to apply a comparative lens to the study of the historical and contemporary experience of East Asia; and integrating linguistic and cultural diversity in Korean language classes by, for example, incorporating service learning in authentic contexts and extending the content spectrum to include topics such as Korean popular culture.

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Korean Wave was the focus of the conference’s widely attended closing panel that featured K-pop star Siwon Choi, a member of Korean boy band Super Junior, and multi-platinum music producer Dominique Rodriguez, managing director of SM Entertainment USA. They spoke about the global reach of Korean pop music and some of the ways in which Korean popular culture could stimulate interest in Korean studies. Dafna Zur, assistant professor in Stanford’s department of East Asian languages and cultures, who chaired the panel, challenged her students to consider “what it means not just to monetize culture but to design culture with specific markets and audience in mind.” The Stanford Daily published a detailed article on the panel.

“We are grateful to Foundation Academia Platonica for its generous support of Stanford’s Korea Program at Shorenstein APARC and for making this conference possible through our shared vision for the future of Korean studies in North America,” said Gi-Wook Shin. “Our thanks also go to our many other friends and partners, including the Korea Foundation that has helped achieve great results through its commitment to promoting understanding of Korea in academia and beyond and its support of the overseas Korean Studies Program since its establishment in 1991.”

South Korean TV company SBS NBC filmed the conference that will be featured in an upcoming documentary about Korean studies in the United States.

Read the conference report or listen to the audio recordings of the sessions, below.