The Biggest Challenge for a COVID-19 Vaccine
Although no one has conducted a survey on the topic, it's safe to say that a single hope unites much of humanity at the present moment: the prospect of a vaccine for COVID-19, which has infected more than 9 million people worldwide, killed nearly 500,000, and sent the global economy into a tailspin since it first appeared in China last December.
"We've never delivered something to every corner of the world before."
Scientists are racing to make that vision a reality. As of this writing, 11 vaccine candidates are in clinical trials and over 100 others are in preclinical development, in a dozen countries. Pointing to new technology and compressed testing protocols, experts predict a winner could emerge in 12 to 18 months—a fraction of the four years it took to develop the previous record-holder, the mumps vaccine, in the 1960s. Teams at Oxford University and Boston-based Moderna Therapeutics say they could have a product ready even sooner, if the formulas they're testing prove safe and effective. A just-announced White House initiative, Operation Warp Speed, aims to fast-track multiple candidates, with the goal of delivering 100 million doses in November and another 200 million by January 2021.
These timetables could prove wildly over-optimistic. But even if the best-case scenario comes true, and a viable COVID-19 vaccine emerges this fall, a gargantuan challenge remains: getting the shot to everyone who needs it. Epidemiologists figure that at least 70 percent of Earth's population—or 5.6 billion people—would have to be inoculated to achieve "herd immunity," in which each person who catches the disease passes it to less than one other individual. "In order to stop the pandemic, we need to make the vaccine available to almost every person on the planet," Microsoft co-founder Bill Gates blogged in April, as his foundation pledged $300 million to the effort. "We've never delivered something to every corner of the world before."
The difficulties are partly logistical, partly political, and largely a combination of the two. Overcoming those obstacles will require unprecedented cooperation among national governments, international organizations, and profit-minded corporations—in an era when nationalist rivalries are rampant and global leadership is up for grabs.
That may be tougher than developing the vaccine itself.
Logistical Conundrums
Manufacturing and distributing billions of vaccine doses would be a daunting task even in the most harmonious of times. Take the packaging problem. The vaccines under development range from old-school (based on inactivated or weakened viruses) to cutting-edge (using snippets of RNA or DNA to train the immune system to attack the invader). Some may work better than others for different patient groups—the young versus the elderly, for example. All, however, must be stored in vials and administered with syringes.
Among the handful of U.S. companies that manufacture such products, many must import the special glass tubing for vials, as well as the polypropylene for syringe barrels and the rubber or silicone for stoppers and plungers. These materials are commonly sourced from China and India, where lockdowns and export bans restrict supply. Rick Bright, the ousted director of the federal Biomedical Advanced Research and Development Authority (BARDA), claims he was ignored when he warned the Trump Administration that a medical-glass shortage was looming before the coronavirus crisis hit; securing enough to vaccinate 300 million Americans, he told Congress in May, could take up to two years.
Getting the vaccine to poorer countries presents further hurdles. To begin with, there's refrigeration. Inactivated or live vaccines must be kept between 2 and 8 degrees Centigrade (or 35 to 46 degrees Fahrenheit); RNA vaccines typically require much colder temperatures—as low as -80 degrees. This makes storage and transport challenging in parts of the world that lack reliable electricity. DNA vaccines don't need cold storage, but (like RNA vaccines) they remain experimental. They've never been approved to treat any human disease.
Tracking vaccine distribution is another conundrum for low- to-middle-income countries. "Supply chain management is really about information," explains Rebecca Weintraub, assistant professor of global health and social medicine at Harvard Medical School and director of the Better Evidence project at Harvard's Ariadne Labs. "It's about leveraging data to determine demand, predict behavior, and understand the flow of the product itself." Systems for collecting and analyzing such data can be hard to find in poorer regions, she notes. What's more, many people in those areas lack any type of ID card, making it difficult to know who has or hasn't received a vaccine.
Weintraub and two coauthors published an article in April in the Harvard Business Review, suggesting solutions to these and other developing-world problems: solar direct-drive refrigerators, app-based data-capture systems, biometric digital IDs. But such measures—not to mention purchasing adequate supplies of vaccine—would require massive funding.
And that's where the logistical begins to overlap with the political.
Global Access Versus "Vaccine Nationalism"
An array of institutions have already begun laying the groundwork for achieving worldwide, equitable access to COVID-19 vaccines. In February, the World Bank and the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) cohosted a global consultation on funding vaccine development and manufacturing. In late April, the World Health Organization (WHO), in collaboration with dozens of governments, nonprofits, and industry leaders, launched a program called the Access to COVID-19 Tools Accelerator to expedite such efforts.
Soon afterward, the European Union, along with six countries and the Bill and Melinda Gates Foundation, held a Coronavirus Global Response telethon that raised $8 billion to support Gavi, the Vaccine Alliance—a public-private partnership that subsidizes immunization in low-income countries. The United States and Russia, however, chose not to participate.
This snub by the world's remaining superpower and one of its principal challengers worried many observers. "I am concerned about what I call vaccine nationalism," CEPI executive director Richard Hatchett told the Los Angeles Times. "That's the tension between obligations elected leaders will feel to protect the lives of their citizens" versus the imperative for global sharing.
Some signs point to a possible rerun of the hoarding that accompanied the 2009 H1N1 influenza pandemic, when wealthy nations bought up virtually all vaccine supplies—denying them to poorer countries, and sometimes to one another. Operation Warp Speed has declared an "America First" policy for any vaccine arising from its efforts. Pharma giant Sanofi recently suggested that it would take a similar approach, since the U.S. was first to fund the company's COVID-19 research. (Sanofi's CEO backtracked after officials in France, where the firm is headquartered, protested.) The Oxford group, which is partnering with British-based drug maker AstraZeneca, intends to prioritize Great Britain.
Yet momentum is building for more generous strategies as well. In May, over 100 current and former world leaders, along with prominent economists and public health experts, issued an open letter calling for a "people's vaccine" for COVID-19, which would be patent-free, distributed globally, and available to all countries free of charge. At the WHO's annual World Health Assembly, all 194 member states accepted a resolution urging that vaccines for the disease be made available as a "global public good"—though the U.S. dissociated itself from a clause proposing a patent pool to keep costs down, which it argued might disincentivize "innovators who will be essential to the solutions the whole world needs."
Gavi, for its part, plans to launch a mechanism designed to encourage those innovators while promoting accessibility: an advance market commitment, in which countries pledge to purchase a vaccine, with no money down. Future contributions will be based on the value of the product to their health systems and their ability to pay.
"It's essential to realize that a threat anywhere is a threat everywhere."
A few private-sector players are stepping up, too. U.S.-based Johnson & Johnson, which has received nearly half a billion dollars from the federal government for COVID-19 vaccine research, has promised to provide up to 900 million doses on a not-for-profit basis, if its trials pan out. Other companies have agreed to produce vaccines on a "cost-plus" basis, with a smaller-than-usual profit margin.
How Sharing Can Pay Off
No one knows how all this will work out if and when a vaccine becomes available. (Another wild card: Trump has announced that he is cutting U.S. ties to the WHO over its alleged favoritism toward China, which could hobble the agency's ability to coordinate distribution -- though uncertainty remains about the process of withdrawal and reversing course may still be possible.) To public health experts, however, it's clear that ensuring accessibility is not just a matter of altruism.
"A historic example is smallpox," Rebecca Weintraub observes. "When it kept getting reintroduced into high-income countries from low-income countries, the rich countries realized it was worth investing in the vaccine for countries that couldn't afford it." After a two-decade campaign led by the WHO, the last case of this ancient scourge was diagnosed in 1977.
Conversely, vaccine nationalism doesn't just hurt poor countries. During the H1N1 pandemic, which killed an estimated 284,000 people worldwide, production problems led to shortages in the United States. But Australia stopped a domestic manufacturer from exporting doses to the U.S until all Aussies had been immunized.
Such considerations, Weintraub believes, might help convince even the most reluctant rich-country leaders that an accessible vaccine—if deployed in an epidemiologically targeted way—would serve both the greater good and the national interest. "I suspect the pressures put on our politicians to act globally will be significant," she says.
Other analysts share her guarded optimism. Kelly Moore, who teaches health policy at Vanderbilt University Medical Center, oversaw Tennessee's immunization programs for more than a decade, and later became a member of the Sabin-Aspen Vaccine Science & Policy Group—a panel of international experts that in 2019 released a report titled "Accelerating the Development of a Universal Influenza Vaccine." The 117-page document provided a road map toward a long-sought goal: creating a flu shot that doesn't need to be reformulated each year to target changing viral strains.
"One lesson we learned was that it's crucial to deploy financial resources in a systematic way to support coordination among laboratories that would typically be competitors," Moore says. And that, she adds, is happening with COVID-19, despite nationalist frictions: scientists from Sanofi joining forces with those at rival GSK; researchers at other companies allying with teams at government laboratories; university labs worldwide sharing data across borders. "I have been greatly encouraged to see the amount of global collaboration involved in this enterprise. Partners are working together who would normally never be partners."
For Moore, whose 77-year-old mother survived a bout with the disease, the current pandemic has hit close to home. "It's essential to realize that a threat anywhere is a threat everywhere," she says. "Morally and ethically, we have a tremendous obligation to ensure that the most vulnerable have access to an affordable vaccine, irrespective of where they live."
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online. For this reprinting of the article, we have updated the latest statistics on COVID-19 and related global news.]
CORRECTION: A sentence about DNA vaccines incorrectly stated that they require cold storage, like RNA vaccines. The error has been fixed.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.