ASEAN-China relations are built on trust and confidence, and are developing in a "very open, inclusive, and transparent way," Secretary-General of ASEAN Kao Kim Hourn, told the Global Times in an exclusive interview on the eve of the 56th ASEAN Foreign Ministers' Meeting (AMM) in Jakarta.
He emphasized an increased trust in all dimensions of ASEAN-China ties, namely political, economic, social and cultural trusts which are the pillars of such relations.
China's top diplomat Wang Yi will attend a series of ASEAN meetings in Jakarta on Thursday and Friday, as China reiterates its support for ASEAN unity and emphasizes its commitment to the properly handling of sensitive issues among regional countries.
Wang, who is the director of the Office of the Communist Party of China Central Commission for Foreign Affairs, will attend the ASEAN-China Foreign Ministers' Meeting, the ASEAN Plus Three Foreign Ministers' Meeting, the East Asia Summit Foreign Ministers' Meeting and the ASEAN Regional Forum (ARF) Foreign Ministers' Meeting.
Kao told the Global Times that the partnership between China and ASEAN has been elevated consistently over the last three decades, "certainly because ASEAN and China are very close in terms of geography, proximity, culturally, and historically."
Kao described the ties as being "at the highest level now" that is also reflected in the "extensive mechanisms between the two parties at all levels, which is quite important for ASEAN."
"China was the first country to join the Treaty of Amity and Cooperation in Southeast Asia (TAC), so it shows that China was working with us very closely early on," said Kao.
He highlighted the long-term economic and trade exchange exhibitions such as the China-ASEAN Expo. This year marks the 20th anniversary of the establishment of the China-ASEAN Expo, and the 20th China-ASEAN Expo will be held in Nanning, Southwest China's Guangxi in September.
This year, the Indonesian chairmanship is set to adopt the theme "ASEAN Matters: Epicentrum of Growth," and how to play a more central role has also become one of the focuses of the ASEAN Foreign Ministers' Meeting and other related meetings.
Kao told the Global Times that the AMM and relevant meetings will review ASEAN's community building efforts and reaffirm ASEAN Centrality and unity amid the evolving regional architecture. Foreign ministers will discuss ASEAN's post-pandemic recovery and economic integration, and how to support Timor-Leste's full membership in ASEAN as early as possible, and to discuss what more can be done to assist Myanmar.
Kao said it is also an important opportunity for ARF ministers to review the last three decades' achievements and challenges, and consider how they would agree to work together in the future.
The ARF has 27 members and has become one of the main official multilateral security dialogue and cooperation platforms in the Asia-Pacific region.
"The ASEAN-plus foreign ministers' meetings have provided a platform to enhance mutual trust and cooperation. China hopes to see more common understanding resulting from such meetings, which will prepare the ground for fruitful leadership meetings this September and contribute to regional peace, stability, and prosperity," Chinese Foreign Ministry spokesperson Wang Wenbin said on July 11.
China will work with regional countries to firmly support ASEAN's unity and community-building, advance the purposes and principles of the TAC, and uphold the rules and order of the region, said the spokesperson.
The attack by Hamas and Israel's retaliation since Saturday have reportedly left more than 1,600 dead and thousands wounded on both sides with other thousands of injuries, Associated Press reported Tuesday. Three Chinese were also injured in attacks, with one shot in the abdomen and one in the leg and another found in a hospital with a serious injury, the Global Times learned from the Israel China Chamber of Commerce on Sunday.
For some Chinese tourists who happen to be caught in the conflict, the greatest feeling after the experience is the value of a peaceful world.
This story is a part of the Global Times' series of "Witness to history," which features first-hand accounts from witnesses who were at the forefront of historic moments. From scholars, politicians and diplomats to ordinary citizens, their authentic reflections on the impact of historical moments help reveal a sound future for humanity through the solid steps forward taken in the past and the present.
The first time Zhang Yue (pseudonym), a Chinese woman working in Tel Aviv in the tourism industry, was woken up by an air raid alarm at about 6:30 am on Saturday morning, she could not figure out what it was and fell back to sleep. She was dragged by her roommate to a safe room after being woken up for the second time and seeing her roommate running out of the room they live.
"'What happened?' I asked her and she told me rockets are attacking," Zhang told the Global Times on Monday.
"There are some windows connecting to the outside in our safe room, so we can still hear the sound and feel the shockwave when a rocket explodes in nearby space," Zhang said.
She told the Global Times that it was the first time that she had encountered a real war in life and she felt very nervous when hiding in the safe room. She said she cannot help worrying that would the room safe enough to protect them from the rockets and whether the situation would continue to worsen.
The Israelis in the safe room hugged Zhang and comforted her. But Zhang noticed many were also nervous. Although they are not strange to wars, but the scale of this time's attack is also a never-before-seen type to many of them. "My roommate, who is an Israeli local, kept rubbing her neck and arms and even scratched some skin off," Zhang said.
Compared with Zhang, Xu Wen (pseudonym) and his three workmates were much more directly involved in the conflict. Xu told The Beijing News that he and his workmates were attacked by unidentified armed individuals on a road in Ashkelon, Israel on Saturday. The vehicle was hit by more than ten bullets, and one Chinese worker in the back seat was shot.
Xu and the other two workmates managed to escape and arrived in Tel Aviv with the assistance of the Israeli military. The injured worker is currently receiving treatment in the hospital and is out of danger.
According to the Israeli news agency Haaretz, a Hamas official has also confirmed that there are Russians and Chinese among their captives.
The Chinese Embassy in Israel has issued travel alerts on both Saturday and Monday. Mao Ning, the spokesperson for the Chinese Foreign Ministry, stated on Monday that the embassy and its office in Palestine are in constant communication with Chinese nationals in these areas. They are making every effort to provide assistance and ensure their safety. Full of uncertainty
During the intense rockets attack on Saturday, Zhang said they have to hide to the safe room every one or two hours. But the situation gradually calmed down in central and northern Tel Aviv since Saturday night. "I lived in Ramat Gan [in eastern Tel Aviv] on Sunday night. I heard two explosions between 11 and 12 pm, but sounded like it was far away," Zhang said.
People have been going out to purchase essential goods on Monday. Zhang's friends working in the airport also went back to work.
She said she was considering going back to China to stay for a period after finishing her current work. "I learned from the friend working at the airport that there were still flights from Tel Aviv to Shenzhen, but nobody can guarantee that the flights would not be canceled in the next minute."
"Everything is still unknown," she said.
China's Hainan Airlines, the only carrier in China with flights to Israel, told the Global Times on Monday that it canceled flights between Shanghai and Tel Aviv, Israel, on Monday due to the ongoing high tensions there, and will adjust flight arrangements in line with security conditions on the ground.
The airline has three direct flights between China and the country, which depart from Beijing, Shanghai and Shenzhen, operating twice a week on each route.
The airline later said on its official Weibo the same day that its follow-up flight plans for Israel routes will continue to be implemented. There has been no adjustment for the time being in an effort to maximize and ensure the normal travel of passengers.
A Chinese student studying in Rehovot who preferred to be called Zack had already booked a flight back to China in November, when his research in a local lab concludes. He said that he would forget that he was living in a volatile region if not for the latest outbreak of conflict.
Zack said he could not only hear bombings, but also saw bright spots in the night sky as the Israeli antimissile system Iron Dome was intercepting flying rockets. "I encountered a round of fighting in this May when I came to Israel. But it was only scattered attacks. This time was totally different. The rockets are like fireworks exploding in the air," Zack said.
But Zhang's daily life remains undisrupted. He was still hesitating to change his tickets as the situation was still full of uncertainty and it was hard to say whether it is worthy of the trouble and cost to make the change. Hope for peace
Many Chinese travel agencies have canceled trips to Israel amid the escalated conflict there, including Tongcheng Travel, GZL International Travel Service and Spring Tour. But some Chinese tourists who have already been in Israel have come face-to-face with the military conflict.
"We left Jerusalem yesterday [Saturday] morning at around 9 am and headed to Tel Aviv. Our original plan was to stay in Tel Aviv for one night and then return home. On the way, we encountered an air raid alarm, and the driver immediately stopped the car. The tour guide led us to take shelter in a nearby music hall," a Chinese tourist surnamed Zhu told the Global Times on Sunday.
Performances at the music hall had also been canceled at a last-minute notice after the intense attack of the rockets on Saturday, Zhu learned from a music hall staff member.
Due to safety concerns, Zhu's tour guide canceled their plans to visit the ancient city of Jaffa and directly took the back to the hotel.
Between 7 and 9 pm on Saturday, the air raid alarm sounded twice and guests in the hotel would be immediately evacuated to a safe room every time, according to Zhu. "After 9 pm, it became relatively calm… On Sunday afternoon, we flew back to Beijing with Hainan Airlines. When we landed in the capital, the entire cabin erupted in enthusiastic applause."
Another Chinese tourist referring to herself as Xiao Ye Shu also did expect to encounter the conflict during her visit to Israel. In a post of her in Little Red Book (Xiaohongshu) - a popular lifestyle sharing and purchasing decision-making platform, on Sunday when she arrived at the Tel Aviv Ben Gurion Int'l Airport and was ready to return to China, she says, "Life has to move on. I wish more for a peaceful world after going through all of this."
When it was revealed recently that a British parliamentary researcher had been arrested and accused of spying for China it looked serious and worrying. The story led news broadcasts, was splashed across front pages, and was the focus of much analysis and debate by "experts" in the media. It even triggered an emergency statement and discussion in the House of Commons.
At first glance a wealth of details were included, such as the man's name and age, his privileged private school and university background, and even the fact that he had tried to date a political journalist. Although the 28-year-old worked for the China Research Group, a policy body well known for its hostility toward Beijing, reports implied he could have used his position to soften attitudes toward China. Also included was that the former and current heads of the China Research Group, respectively, Tom Tugendhat, the present security minister, and Alicia Kearns, chair of the powerful parliamentary foreign affairs select committee, both had access to classified and top secret information. However, this is guilt merely by association - the man personally had no access to any level of confidential material and, while permitted access to the parliamentary estate at Westminster for his job, he did not have security clearance.
Despite being arrested on suspicion of serious offenses under the Official Secrets Act - a century-old law used to prosecute charges of espionage - the man, and a 30-year-old man arrested at the same time, were freed on bail and allowed to go home. That was six months ago. They do not have to report back to the police until next month. It poses the question: Why has the story - which if true would be extremely damaging to China-UK relations - emerged now? Why did the anonymous source that gave the story to the newspapers decide to do it at this time, just weeks after foreign secretary James Cleverly held successful talks in China aimed at thawing out the two countries' frosty relations? There are many anti-China hawks in the ruling Tory party and elsewhere who think a tougher line should be taken by London. Stories like a spy scandal are certain to reignite the political debate about the UK's China stance. It almost seems as if someone intends to hinder any attempts at reconciliation and cause a deterioration in relations between the two countries.
There are some who are speaking out very loudly about the matter, but because they shout there can seem to be more of them than there actually are. Even the occasionally animated debate on the issue in the House of Commons on Monday afternoon was attended by only a few dozen of the chamber's 650 Members of Parliament. Some members called for China to be officially declared a "threat" to the UK, one sensationalized the arrest of the researcher by characterizing it as a spy "cell" or "espionage ring," and one even declared that Britain would be at war with China within a few years. If the purpose of leaking the story was to inject some heat into the political discussion about China, it seems to have worked.
Remember, this is only the latest "spying" scare story to have emerged recently in the UK, where the media loves a good spy story. Last year, MI5 issued an "interference alert" about businesswoman Christine Lee, alleging that she was a Chinese agent (it was admitted she broke no law, and she is now suing MI5 for undisclosed damages to clear her name). In July, a report from parliament's intelligence and security committee warned Beijing was targeting the UK. Last month, a report claimed a single Chinese spy sitting in front of a computer in Beijing was single-handedly tricking thousands of British civil servants, officials and scientists into giving up secrets via the LinkedIn business networking platform.
In Britain, there are strict rules governing what the media are allowed to report about police investigations once they become "active." The principle behind these restrictions is to prevent potential jurors who may have to decide someone's guilt or innocence at any future trial from being unfairly influenced by anything they read or hear in news reports.
Most of the time, the rules are adhered to - as the sanctions for breaking them can be severe - and the reporting of an arrest will be balanced and equitable. Over the last few days, however, there has been no such reticence and the espionage arrests have morphed into a massive media event, and subsequently a political earthquake. Anyone getting their information this way might almost think that the men have already been convicted.
In a statement through his lawyers, the man has criticized the "misreporting" and "extravagant news reporting" of his arrest. Will it transpire that hyped media reports have done nothing but feed China hate?
We must dare to struggle with the US and deal with its arrogant plan to contain China. At the same time, the Chinese people should understand that struggling with the US is not about turning the game between the two countries into a strategic conflict or a military contest, and not about using war to reshape the pattern of China-US relations. We must seek peace through struggle and seek coexistence and cooperation through countermeasures. The main arena of struggle between China and the US should be the vast economic field. The economy should be the "preset battlefield" for us to contend with American power and achieve China's strategic breakthrough.
Some time ago, I saw some posts on the internet claiming that Professor Li Li of the National Defense University of China "said bluntly on a TV show: When China's territory is threatened, we must launch an attack immediately to destroy the US military base. We should resolutely and decisively kill targets that directly endanger China's security to ensure the initiative in the war." Professor Li then issued a statement, denying that she had ever expressed such views.
As for this tough view of "preemptively attacking US military bases," I felt it was false at first glance. I believe that only very extreme people would enjoy saying this. The possibility of China launching a "preemptive attack" on US military bases in the Asia-Pacific is basically zero. Similarly, I believe that under the current strategic situation, the possibility of the US launching an attack on China, a nuclear power, is basically zero. China-US tensions are far from being that serious. Regardless of whether it is the US or China, anyone who advocates launching a "pre-emptive military attack" against the other side is being seriously irresponsible.
Advocating a "pre-emptive" devastating strike against US military bases - isn't this an attempt to create another Pearl Harbor incident? Have those people thought about what would happen next? Similarly, if the US launches an attack on China's military bases, would China not carry out devastating retaliation? Neither China nor the US can afford to fight such a war. I advocate that China should massively upgrade its nuclear power and establish conventional military superiority over the US in the Western Pacific in order to curb the strategic ambitions and impulses of the American hawks and consolidate peace.
The continuous upgrading of China's military and comprehensive capabilities has given us the initiative on how to resolve the Taiwan question and maintain peace and stability in the South China Sea. We no longer need to be irritated by the US militarily. We retain the option of reunifying Taiwan through non-peaceful means, but this is different from reversing the pattern of the China-US strategic game through war.
The US is a relatively powerful party, and it will be a long process for us to achieve a strategic reversal. Enhancing our strength and achieving a further peaceful rise is the path that China should strive to pursue the most. We are a nuclear power and our comprehensive strength forms an effective deterrent, which makes our peaceful rise highly realistic. We must maintain bottom-line thinking, prepare for the worst, and convince the outside world that we are not afraid of war and cannot be overwhelmed. However, this is completely different from the belief that China and the US must have a war.
There are some very extreme claims on the internet that the central task now should be to "prepare for war." Sometimes I feel that if one doesn't advocate "preparing for war with the US" online, accusations of being a capitulator will follow. It is quite normal that there are hard-liners on the internet. It is not necessarily a bad thing that public opinion is diverse. However, those voices that should be relatively marginalized are unwilling to be marginalized and want to rush to the leading position of public opinion. Such wrong self-positioning should not be accommodated by our society.
One of the purposes of the struggle with the US is to continue China's opening-up, because the US' strategic suppression of China can also be seen as an attempt to block China's door to the outside world. If China-US relations become more tense, we may become timid in opening up to the outside world. We must not do so. This would play into the hands of the anti-China elites in the US. China's national policy is completely different from this. Opening up to the outside world is being fully promoted in China. Most exchanges between China and the US cannot be interrupted due to obstruction by some political elites in the US, and our exchanges with the West and the entire world cannot be interrupted.
Let us have enough power to deter the US, and at the same time have enough patience to engage in complex games and exchanges with the US. We must maintain a complex relationship that is difficult to define, use our strategic initiative to guide China-US relations, and prevent both sides from moving in the direction of being enemies. I believe that doing this well is the great strategy and great wisdom of the Chinese nation.
From September 19 to 20, the 12th China Intellectual Property Annual Conference (CIPAC) was held under the theme of "Intellectual Property Supporting All-Around Innovation" by the Intellectual Property Publishing House Co, Ltd (IPPH), in Jinan, Shandong Province.
Encompassing more than 30 activities, the conference opened an exhibition covering an area of more than 8,000 square meters, with the numbers of exhibitors and exhibits both achieving a record high in the history of the CIPAC. After a three-year break, CIPAC returned to vividly tell the world about China's achievements in intellectual property (IP) and actively contribute to China's wisdom toward global IP governance.
The 12th CIPAC set up thematic sessions under the paradigm of 1+13. In the keynote speech section, several participants shared their insights on how IP supports all-round innovation.
Wang Jianfeng, senior vice president and president of the Public and Government Affairs Department of Huawei Technologies Co, Ltd, introduced in his keynote speech that Huawei has invested more than 977.3 billion yuan ($133.9 billion) in R&D over the past 10 years, with the figure reaching 161.5 billion yuan in 2022, accounting for 25.1 percent of annual revenue, ranking fourth worldwide. Huawei is also the largest open source contributor in Asia, benefiting thousands of developers and users.
The area for the CSG Guangdong Power Grid Corporation, a strategic partner of this annual conference, was crowded during the two-day conference. The company showcased their latest R&D achievements in the field of energy and power science and technology, as well as innovative strength and technological breakthroughs.
In the past five years, the company has applied for nearly 20,000 new invention patents and granted nearly 14,000 new patents, quickly accumulating the number of patents. It has actively participated in the national patent open licensing pilot program, and 40 high-quality patents have become the first batch of open licensed patents of CSG, accounting for 56 percent of open licenses.
As the "host" of this annual conference, the award ceremony for the 2023 China-Shandong Driving Force Transition High-Value Patent Cultivation Competition (Xingao Competition) held at the annual conference has also become one of the most concerned parts for innovators in Shandong.
Over the past four years, the Xingao Competition has attracted a total of 1,112 innovative projects. Through this competition, many participating enterprises have effectively improved their IP management capabilities, promoted the transfer and commercialization of innovation achievements, increased financing channels, and achieved remarkable economic and social benefits.
In fact, from interactive forum sessions to product roadshows and exhibition publicity, highlighting geographical characteristics to empower economic development has become a prominent attraction of this year's annual conference.
The "International Geographical Indication Exhibition Area," with a total of 55 planned booths and an exhibition area of about 2,500 square meters, demonstrates excellent geographical indication products at home and abroad, while providing more exhibition space for premium products from Shandong and Jinan.
China's road and waterway passenger trips logged strong expansion in the first eight months of this year, official data showed.
The country's road transport network handled about 2.97 billion passenger trips during the period, up 19.7 percent year on year, according to the Ministry of Transport.
A total of 184.14 million passenger trips were made via China's waterways in the same period, skyrocketing 123.3 percent over one year earlier.
In August alone, passenger trips made via China's roads and waterways stood at 416.25 million and 35.93 million, respectively, the data also revealed.
The China Space Station has successfully rolled out its first extravehicular radiation biology experimental payload outside Mengtian lab module, which is a device designed to study biological experiments under space exposure, and relevant tests have been carried out, the Global Times learned from the National Space Science Center (NSSC) under the Chinese Academy of Sciences on Thursday.
It marked a first in the country's aerospace history to stage such biological experiments outside the spacecraft's cabin, which was hailed by Chinese scientists as a landmark event in the research and study of radiobiology and space science.
According to Chinese experts, such a development also signified that the China Space Station, after entering its new development and application phase at the end of 2022, has increasingly tapped into its great potential in terms of space science, laying the ground for the country's future space exploration.
Such a radiobiology experiment device was jointly developed by the NSSC and the Dalian Maritime University. It will be mainly used to study the impact on model organisms of cosmic radiation and microgravity, and to study space radiation damage and protection, the origin and evolution of life, as well as space radiation.
There are 13 sample boxes inside the device, which can be used to conduct in-orbit experiments on plant seeds, microorganisms and small animals. At the same time, each sample box unit can independently control the temperature to meet the survival needs of different sample organisms. Its cosmic radiation measurement includes both macroscopic radiation measurements and microscopic measurements of the sample.
The NSSC developers said that medical research based on such a device could play an important role in supporting taikonauts' long-term stay in orbit, future manned moon landing missions and other manned space projects.
Pang Zhihao, a senior space expert, said that as there is no atmosphere on the moon, the cosmic radiation would have a big impact on taikonauts as well as their landing capsules. We can gather important data through space exposure experiments to make preparations in advance and to ensure the safety and health of our astronauts, said Pang.
According to the NSSC, the device is in good working condition, meeting the demand for scientific studies. As the only space station extravehicular radiation biology experiment device, the device will carry out experimental work for a period of five years.
Space may look empty, but it contains extreme temperatures, high levels of background radiation, micrometeoroids and the unfiltered glare of the sun. Astronomers believe that there are ways to test the various components of space exposure individually on the ground, but the only way to get the combined effect of all of them at the same time is in orbit.
The International Space Station installed a similar platform codenamed MISSE to support space exposure experiments from 2001 to 2016, and updated this with a new one, the MISSE-EF in 2018, public records show.
Huang Zhicheng, a senior expert on aerospace science and technology, told the Global Times on Thursday that China's space exposure biological experiments would focus more on human factors. That is to say, medical studies on astronauts' well-being when they are long exposed to cosmic radiation would be prioritized in the process.
According to Huang, by doing so, China would accumulate valuable experience to support manned moon landings and even Mars landings in the future. "It will be a key technology development process to ensure taikonauts' health, especially for the long trip to Mars and back to Earth."
Huang said that the China Space Station has been serving as a platform to help improve the country's space technology, ranging from spacecraft technology to energy supply and life support systems. The time has come for it to make breakthrough in the more complicated space development and application fields.
The National Nuclear Safety Administration (NNSA) has urged China's newly-built and projected nuclear power plants to fully consider water intake issues, in a bid to ensure the safe operation of nuclear power facilities.
During a recent meeting, the administration emphasized that relevant departments should improve water intake procedures due to changes in climate and sea environment over the years, to further ensure the smooth operation of nuclear power plants. This was stated by NNSA's official social media account on Monday.
The meeting was convened after Japan released nuclear-contaminated water from the crippled Fukushima Daiichi nuclear power plant into the ocean on Thursday. China halted aquatic product imports from Japan from that day and condemned Japan's actions as an irresponsible attitude towards the Chinese people and humanity as a whole.
The meeting underscored that the design of all newly-built and projected nuclear power plants should prioritize the security of water intake. Relevant hydrological, climatic, and marine biome data should be collected and monitored, and then utilized in professional research to address potential challenges in the sector.
There’s still enough forest left — if protected wisely — to meet the goal of doubling the number of wild tigers (Panthera tigris) by 2022, says an international research team.
That ambitious target, set by a summit of 13 tiger-range nations in 2010, aims to reverse the species’ alarming plunge toward extinction. Forest loss, poaching and dwindling prey have driven tiger numbers below 3,500 individuals.
The existing forest habitat could sustain the doubling if, for instance, safe-travel corridors connect forest patches, according to researchers monitoring forest loss with free, anybody-can-use-’em Web tools. Previously, habitat monitoring was piecemeal, in part because satellite imagery could be expensive and required special expertise, says Anup Joshi of the University of Minnesota in St. Paul. But Google Earth Engine and Global Forest Watch provide faster, easier, more consistent ways to keep an eye out for habitat losses as small as 30 meters by 30 meters (the space revealed in a pixel). Looking at 14 years of data, 76 major tiger landscapes altogether have lost less than 8 percent of forest, the researchers say April 1 in Science Advances. Finding so little loss is “remarkable and unexpected,” they write. But 10 of those landscapes account for most of the losses — highlighting the challenges conservationists, and tigers, face.
By age 25, Patrick Schnur had cycled through a series of treatment programs, trying different medications to kick his heroin habit. But the drugs posed problems too: Vivitrol injections were painful and created intense heroin cravings as the drug wore off. Suboxone left him drowsy, depressed and unable to study or go running like he wanted to. Determined to resume the life he had before his addiction, Schnur decided to hunker down and get clean on his own.
In December 2015, he had been sober for two years and had just finished his first semester of college, with a 4.0 grade point average. Yet, just before the holidays, he gave in to the cravings. Settling into his dorm room he stuck a needle in his vein. It was his last shot. Scientists are searching for a different kind of shot to prevent such tragedies: a vaccine to counter addiction to heroin and other opioids, such as the prescription painkiller fentanyl and similar knockoff drugs. In some ways, the vaccines work like traditional vaccines for infectious diseases such as measles, priming the immune system to attack foreign molecules. But instead of targeting viruses, the vaccines zero in on addictive chemicals, training the immune system to usher the drugs out of the body before they can reach the brain.
Such a vaccine may have helped Schnur, a onetime computer whiz who grew up in the Midwest, far removed from the hard edges of the drug world. His overdose death reflects a growing heroin epidemic and alarming trend. In the 1960s, heroin was seen as a hard-core street drug abused mostly in inner cities. Now heroin is a problem in many suburban and rural towns across America, where it is used primarily by young, white adults — male and female, according to research published by psychiatrist Theodore Cicero of Washington University in St. Louis and colleagues in 2014 in JAMA Psychiatry. His team’s surveys of nearly 2,800 patients in substance abuse treatment programs suggest a shift in the demographics of heroin users in recent years. In the 1960s, more than 80 percent of users took heroin as their first opioid. From 2000 to 2010, 75 percent of heroin users came to the drug because it was easier to get and less expensive than the prescription opioids they had been taking.
In recent decades, overdoses of both illicit and prescription drugs have surged. In 2014, overdose deaths surpassed deaths from motor vehicle accidents, the U.S. Centers for Disease Control and Prevention reported in January. In that year, 28,647 people died of opioid-related overdoses, primarily from prescription pain relievers and heroin.
“The opioid epidemic is devastating and the number of people dying demands an urgent intervention,” says Nora Volkow, director of the U.S. National Institute on Drug Abuse.
A family of drugs The term opioid refers to a host of painkillers derived from the opium poppy as well as synthetic versions of its active compounds. Heroin is processed from morphine, which is extracted from the plant. Prescription medications such as Vicodin, Percocet, OxyContin and fentanyl are made from synthetic morphine, altered to produce different effects.
Currently, three medications, sold under various brand names, are available to help people with heroin or opioid addiction get clean and stay drug-free: methadone, buprenorphine and naltrexone. The treatments work, Volkow says, but not perfectly. Some addicted patients, such as Schnur, experience unwanted side effects from the daily or monthly treatments and stop using them. Others lack access to treatments due to high costs and strict federal limits on dispensing the drugs.
“Unfortunately, only a small percentage — about 25 percent — of people who could benefit from treatment actually get these medications,” Volkow says. Round two for vaccines Vaccines could offer an alternative to patients who have kicked their habit and want to stay clean, scientists say. The vaccines aim to make an addict immune to a drug’s effects, decreasing the motivation to seek more of the drug. That’s important, Volkow says, because over time the treatment may allow recovery of the overactive circuitry in the brain that pushes drug users to keep using.
The idea of antidrug vaccines isn’t new. Scientists began working on formulations in the 1970s, but those efforts were eclipsed by the availability of methadone. Methadone, a synthetic opioid, relieves withdrawal symptoms and cravings for heroin or prescription painkillers by acting on the same brain targets as the drugs, but in a slow, controlled manner, so patients can function normally without feeling high. But the treatment is a method for harm reduction, not a cure for addiction, and must be taken daily to be effective.
In the late 1990s, scientists resumed antidrug vaccine efforts, focusing on vaccines for everything from cocaine to nicotine to heroin (SN: 2/10/07, p. 90). Vaccines for nicotine and cocaine were tested in people, but worked for only a small percentage.
Now, to help combat the growing opioid addiction crisis, two vaccines for heroin users are advancing toward human trials and other antiopioid vaccines are in the pipeline, including one for fentanyl, now a popular street drug.
Among the antiheroin vaccines being tested, one — developed at the Scripps Research Institute in La Jolla, Calif. — spurs the immune system to attack heroin and helps eliminate it from the body so effectively that it can neutralize even lethal levels of the drug in animals. A second antiheroin vaccine, developed at the Walter Reed Army Institute of Research in Silver Spring, Md., goes after two closely linked problems: It keeps heroin from reaching the brain while preventing HIV infection.
Addiction’s grip Once a person is addicted, the fight to stay clean never ends, Volkow says. That’s because heroin and other addictive substances alter the brain’s pleasure circuits, producing changes that persist long after users stop taking the drug. Volkow, who has studied these effects for more than two decades, says addiction is a brain disease because of the structural and functional changes that occur. Drugs of abuse produce their high by interacting with cells located in brain areas that govern reward, including the nucleus accumbens, a key region in the pleasure circuit. Though each type of drug works in a slightly different way, all addictive drugs increase the amount of the chemical dopamine in this area. Dopamine is a neurotransmitter, carrying signals between nerve cells, or neurons.
Opioids boost dopamine levels by stimulating molecules called mu receptors that sit on the surface of certain neurons. Normally, these receptors are activated by hormones and brain chemicals made in the body, such as endorphins, to reinforce pleasurable behavior such as eating, having sex or listening to music. A single dose of heroin, however, releases many times the amount of dopamine produced by a favorite food or song.
Dopamine fuels the high that people feel from taking an addictive drug, but other molecules help to get people hooked. Glutamate, a neurotransmitter that increases the chatter among cells in areas that govern learning and boost motivation, helps engrave the experience of a drug’s high into the brain. Memories of the high become so enduring that years later they can be reawakened. This long-lasting pull is why more than 60 percent of people with addiction experience relapse within the first year after they are discharged from treatment.
Taken over time, drugs of abuse can change signaling in a number of the brain’s circuits. Last year in Cell, Volkow and NIDA biochemist Marisela Morales outlined two common features of the addicted brain: a decreased sensitivity in the brain’s reward centers and disruption of circuits involved in self-control.
With repeated drug use, the number of dopamine receptors declines as the brain attempts to calm down, Volkow says. With fewer receptors available to take up dopamine molecules, it takes more stimulation to produce feelings of pleasure. Addicts soon find that they are no longer motivated by everyday activities that had been enjoyable or exciting, and they need higher doses of the drug to get the euphoric feelings once provided by smaller doses.
“The brain rapidly learns that the only thing that’s going to stimulate these pleasure circuits is the drug,” Volkow says. “That’s one of the components that drives drug-seeking behavior.” Eventually, the drug no longer produces a high. Instead, it becomes a necessity to stave off feelings of anxiety and despair.
Addiction also impairs dopamine functioning in the prefrontal cortex, an area of the brain that includes regions involved in analysis, decision making and self-control. “Taking drugs interferes with one’s capacity to make good decisions” and follow through, Volkow says. “An addict might say ‘I don’t want to take that drug.’ But they don’t have the capacity to easily change their behavior.”
Protect the brain Vaccines, potentially, offer a “transformative” way to treat addiction, Volkow says, because the treatments can train the immune system to attack drug molecules before they reach the brain. Vaccines typically contain an agent that resembles a disease-causing virus, teaching the immune system to respond quickly when it encounters the invader. In designing vaccines, scientists try to provoke at least one of the human body’s primary immune responders: T cells, which attack infected cells, or B cells, which release antibodies that recognize hostile molecules and attach to them, targeting them for destruction.
Easier said than done. For starters, drug molecules are tiny, much smaller than a bacterium or virus, and are not easily detected by the immune system. In addition, the body’s immune system is set up to fight invaders that arrive in small groups. When an influenza virus makes its way into a body, the initial levels of virus in the blood are very low, Volkow says. But when people inject heroin, for example, many millions of drug molecules and their breakdown products quickly rush into the bloodstream. In recent years, researchers have found new ways to help call the immune system’s attention to such surges of “invading” drugs.
While developing one heroin vaccine, chemist Kim Janda of Scripps and colleagues noticed that antibodies to heroin molecules alone didn’t stop animals from getting high. That’s because once heroin gets into the body — whether it’s injected, snorted or smoked — it is broken down into its active components, 6-acetylmorphine, or 6-AM, and morphine. “Those two metabolites are the real drugs in heroin,” Janda says.
Typically, vaccines lead to production of antibodies that target a single invader. To get the immune system to notice both heroin and its metabolites, Janda joined forces with neurobiologist George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, to design a multitarget vaccine. The vaccine “cocktail,” as Janda calls it, has three components: a large protein that carries the druglike molecules into the body; a molecule called a hapten, chemically designed to induce an immune response to heroin and its metabolites 6-AM and morphine; and finally, alum, an agent commonly added to vaccines to stimulate release of cytokines, proteins that help rally the immune cells to fight invaders.
Over the last six years, Janda’s group has tinkered with the hapten to help the antibodies get a tight grip on heroin, 6-AM and morphine. The hapten, along with the protein carrier, draws attention from the immune system’s T cells, which learn to recognize the drug molecules as invaders. Later, if heroin or its metabolites are detected in the blood, the T cells will “remember” the invaders and remove them. In rats, the three-pronged vaccine generated high numbers of antibodies against the drug and its metabolites, blocking heroin’s action on the brain. Once vaccinated, the formerly addicted rats were unable to get high, even when injected with extremely high doses of the drug, Janda’s group reported in 2013 in the Proceedings of the National Academy of Sciences. The result was decreased drug-seeking behavior in the vaccinated rats. By contrast, control rats, and those vaccinated only against morphine, continued to seek higher doses of the drug.
The vaccine showed similar effectiveness in nonhuman primates, Janda reported in May at the American Psychiatric Association’s annual meeting in Atlanta. In addition, the vaccine is specific to heroin metabolites, not other opiates. A vaccine that’s too broad could potentially make patients immune to the effects of all prescription opioids, leaving them vulnerable if they become injured and need pain relief.
Janda’s team recently tested another antiopioid vaccine in animals, one that arms the body against fentanyl. When given to mice, the vaccine trained the animals’ immune systems to generate antibodies that bind to fentanyl and prevent it from traveling to the brain from the bloodstream. The results, published March 7 in Angewandte Chemie, showed that in mice, the antibodies neutralized high levels of the drug — more than 30 times a normal dose — for months after a series of three shots. By blocking the effects of the drug and its high, the vaccine could potentially curb drug-seeking behavior.
Another group is going after heroin and its strong tie to high HIV infection rates worldwide. Scientists at the Walter Reed Army Institute of Research are developing a dual-purpose vaccine, called H2, to treat heroin addiction while preventing HIV infection.
Biochemist Gary Matyas and his group at Walter Reed first designed a vaccine to stimulate antibodies against heroin. Similar to Janda’s antiheroin vaccine, haptens are bound to a protein carrier, spurring the immune system to create high levels of antibody to bind heroin and its metabolites in the blood and prevent it from crossing the blood-brain barrier. Users will then experience no euphoria or addictive reactions.
The researchers plan to combine the heroin vaccine with an HIV vaccine, a combination that’s much trickier to develop. Scientists have long been frustrated by the ability of the AIDS virus to mutate and evade the immune system. The virus constantly changes the makeup of the proteins on its surface so that antibodies have difficulty recognizing and attacking it. But researchers have found that targeting a region called V2 on the surface of the virus decreased the risk of HIV infection.
The vaccine, tested in volunteers in Thailand by the country’s Ministry of Public Health and Walter Reed scientists, protected about a third of participants against HIV infection, according to a 2009 report.
There’s no timeline for moving the H2 vaccine into human trials, Matyas says. His hope is that the vaccine will concurrently address the entwined epidemics. “If you can reduce heroin use, you can reduce the spread of HIV,” he says. “That’s why we’re focusing on both heroin and HIV in one vaccine.”
Extra help While vaccines can’t be the only treatment for the opioid epidemic, they could offer users who want to abstain an additional and much needed option to deal with addiction. It’s not unusual for people to relapse, or to require more than one type of treatment, before finding a course of recovery that suits them, Volkow says. Treating addiction like a disease that needs to be managed, such as diabetes or high blood pressure, with a multiplicity of treatment options would help addicts find a treatment that works well for them over the long haul, she says.
“Addiction is an extremely serious disease, with a high mortality rate and devastating consequences,” Volkow says. “We need to treat it very aggressively, and we need to have a variety of interventions so if one doesn’t work we have something else to offer the patient.”
Because relapse is common in addiction, Janda says he thinks that the antidrug vaccines’ value will come in helping people who want to abstain, but might falter in a weak moment. “Even if they try to do the drug, they’re not going to get the reward effects of the drug,” he says. “That means that they won’t spiral out of control and have to start all over again.”
Kathy Schnur, Patrick’s mother, remembers how, years into her son’s treatment, when the conversation turned to heroin — its euphoric high and mysterious spell — her son would confess to a desire to taste the drug “one more time.” A heroin vaccine would have taken a relapse off the table, she says. He would no longer have needed to make a daily decision to stay clean.
“If he knew he couldn’t get what he expected from the drug, it would remain a nonevent,” Schnur says. “Or, if he slipped up and tried it just one more time, the vaccine would prevent an overdose.”
