"The way that the economy has developed over the past generation is actually gone contrary to a lot of the existing economic models. The Simon Kuznetz phenomenon says it's not just globalization, it's economic growth. As the country is modernizing, as it's growing economically, it does lead to an increase in inequality. When you reach a  certain level of income, the inequality starts to decrease. That was the experience in Europe, in the 19th and 20th century, that was the case in the United States and so forth. That has not been the case of the countries that have been growing rapidly in recent years, where inequality has continued to increase," says CDDRL Mosbacher Director Francis Fukuyama. Watch here. 

The national opioid epidemic has grown at such breakneck speed that public health experts have been left scrambling to keep up. Though they understand the reasons behind the abuse — the solutions are complicated and costly.

Yet there appears to be some success at reducing at least one area of opioid abuse.

In new research by Health Research and Policy’s Eric Sun, the risk for chronic opioid use among patients with musculoskeletal pain actually decreased slightly between 2008 and 2014. 

The Stanford Medicine assistant professor of anesthesiology and pain medicine found that measures such as avoiding opioid use soon after diagnosis can further reduce the risk of addiction, especially among patients at highest risk for chronic opioid use.

"We found that early opioid use after diagnosis is predictive of opioid use longer term, suggesting that it may be prudent to minimize opioid use where possible for patients with musculoskeletal pain,” said Sun, whose research was published earlier this week in the Annals of Internal Medicine.

His co-authors are Jasmin Moshfegh, who is working on her PhD in health policy, and Steven Z. George, director of musculoskeletal research at Duke University School of Medicine.

Patients with lower back or chronic neck, shoulder and knee pain are at the highest risk for opioid abuse since pain meds are typically prescribed to help ease their spasms. 

Patients who suffer musculoskeletal pain may unwittingly transition to chronic opioid use, which means filling 10 or more prescriptions or having a supply for at least 120 days. The prescription drugs include hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and/or oxycodone. Those don’t include heroin and synthetic opioids such as fentanyl.

Sun and his fellow researchers at the Stanford University School of Medicine used a large health-care database to assess the risk and risk factors for chronic opioid use among more than 400,000 “opioid-naïve” patients — those who have never been prescribed painkillers before — recently diagnosed with pain in the knee, neck, lower back or shoulder. 

The sample was restricted to privately insured patients, thereby excluding other policy-relevant populations, such as those who were prescribed pain medications under Medicare or Medicaid.

They found that risk for chronic opioid use ranged from 0.3 percent for knee pain to 1.5 percent for multiple-site pan and decreased for some anatomical regions during the timeframe studied. They discovered a relative decline of 25 to 50 percent across all pain types from 2008 to 2014.

Opioid Abuse

Opioid abuse has its roots in the late 1990s when pharmaceutical companies assured the medical community that patients would not become addicted to pain relievers. Clinicians began prescribing them at greater rates because they worked so well and seemed safe.

Today, more than 130 people die every day from opioid-related drug overdoses from prescription pain relievers, heroin and synthetic opioids such as fentanyl, according to the U.S. Department of Health and Human Services, From 2002 to 2017, there was more than a fourfold increase in opioid deaths, with some 49,000 people dying in 2017.

The Centers for Disease Control and Prevention estimates that the total economic burden of prescription opioid misuse alone in the United States is $78.5 billion a year, including the costs of health care, lost productivity, addiction treatment and criminal justice involvement.

“While our research found that only about 1 percent of patients with musculoskeletal pain progress to chronic opioid use, this is potentially concerning because it’s an extremely common diagnosis,” Sun said. “By pointing out the scope of the issue and identifying factors that place patients at risk, we hope this research will guide further efforts aimed at reducing opioid use among patients with musculoskeletal pain.” 

While Americans may be well acquainted with China’s quest for influence through the projection of power in the diplomatic, economic, and military spheres, they are less aware of the various ways in which Beijing has more recently been exerting cultural and informational influence. According to a new report, some of these ways challenge and even undermine our democratic processes, norms, and institutions.

With a growing realization that the ambition of Chinese influence operations requires far greater scrutiny than it has been getting, a group of American scholars and policy practitioners set out to document the extent of China’s influence-seeking activities in American society. The working group, co-chaired by Larry Diamond, senior fellow at the Freeman Spogli Institute for International Studies and at the Hoover Institution, and Orville Schell, Arthur Ross director of the Asia Society’s Center on U.S.-China Relations, just released its findings and recommendations in a report that has drawn much attention, “Chinese Influence and American Interests: Promoting Constructive Vigilance.” On December 4, Diamond and Schell discussed the report’s findings and implications at a special roundtable organized by Shorenstein APARC’s U.S.-Asia Security Initiative (USASI).

Diamond and Schell described the report’s detailing of a range of assertive and opaque “sharp power” activities that China has stepped up within the United States in multiple sectors, including Congress, state and local government, universities, think tanks, media, corporations, technology and research, and the Chinese American community. These activities, they argue, penetrate deeply the social and political fabric of our democratic society and exploit its openness. Unlike legitimate “soft power” efforts within the realm of normal public diplomacy, they constitute improper interference that demands greater awareness and a calibrated response.

“The report was born out of a recognition that things have changed,” said Schell. “Our engagement with China has either failed or is teetering on the brink of failure. The report aims to put the question of our interaction and exchange with China within the context of policy.”

Diamond noted that “The question at least has to be asked whether there is a threat to U.S. national interests.” He emphasized that the members of the working group that produced the report seek a productive relationship between China and the United States. The report therefore advocates for perspective and framework that are built on three principles regarding U.S.-China relations: transparency, institutional integrity, and reciprocity.

Diamond and Schell were joined at the panel by Hwang Ji-Jen, a Taiwanese scholar in the Institute for East Asian Studies at the University of California - Berkeley, who helped situate the forms and effects of Chinese “sharp power” in the United States in comparison to its practice in and toward Taiwan. Karl Eikenberry, director of USASI, chaired the discussion.

The event was co-sponsored by the US-Asia Security Initiative in the Asia-Pacific Research Center, and FSI’s Center on Democracy, Development, and the Rule of Law.

Audio from the event is available for download or streaming:

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.