Biden’s Administration Should Immediately Prioritize These Five Pandemic Tasks
Dr. Adalja is focused on emerging infectious disease, pandemic preparedness, and biosecurity. He has served on US government panels tasked with developing guidelines for the treatment of plague, botulism, and anthrax in mass casualty settings and the system of care for infectious disease emergencies, and as an external advisor to the New York City Health and Hospital Emergency Management Highly Infectious Disease training program, as well as on a FEMA working group on nuclear disaster recovery. Dr. Adalja is an Associate Editor of the journal Health Security. He was a coeditor of the volume Global Catastrophic Biological Risks, a contributing author for the Handbook of Bioterrorism and Disaster Medicine, the Emergency Medicine CorePendium, Clinical Microbiology Made Ridiculously Simple, UpToDate's section on biological terrorism, and a NATO volume on bioterrorism. He has also published in such journals as the New England Journal of Medicine, the Journal of Infectious Diseases, Clinical Infectious Diseases, Emerging Infectious Diseases, and the Annals of Emergency Medicine. He is a board-certified physician in internal medicine, emergency medicine, infectious diseases, and critical care medicine. Follow him on Twitter: @AmeshAA
Democratic U.S. presidential nominee and former Vice President Joe Biden puts his face mask back on after answering questions following a speech on the effects on the U.S. economy of the Trump administration's response to the coronavirus disease (COVID-19) pandemic during a campaign event in Wilmington, Delaware, U.S., September 4, 2020.
The response to the COVID-19 pandemic will soon become the responsibility of President-elect Biden. As is clear to anyone who honestly looks, the past 10+ months of this pandemic have been a disastrous litany of mistakes, wrong actions, and misinformation.
The result has been the deaths of 240,000 Americans, economic collapse, disruption of routine healthcare, and inability of Americans to pursue their values without fear of contracting or spreading a deadly infectious disease. With the looming change in administration, many proposals will be suggested for the path forward.
Indeed, the Biden campaign published their own plan. This plan encompasses many of the actions my colleagues and I in the public health and infectious disease fields have been arguing for since January. Several of these points, I think, bear emphasis and should be aggressively pursued to help the U.S. emerge from the pandemic.
Support More and Faster Tests
When it comes to an infectious disease outbreak the most basic question that must be answered in any response is: "Who is infected and who is not?" Even today this simple question is not easy to answer because testing issues continue to plague us and there are voices who oppose more testing -- as if by not testing, the cases of COVID cease to exist. While testing is worlds better than it was in March – especially for hospital inpatients – it is still a process fraught with unnecessary bureaucracy and delays in the outpatient setting.
Just this past week, friends and colleagues have had to wait days upon days to get a result back, all the while having to self-quarantine pending the result. This not only leaves people in limbo, it discourages people from being tested, and renders contact tracing almost moot. A test that results in several days is almost useless to contact tracers as Bill Gates has forcefully argued.
We need more testing and more actionable rapid turn-around tests. These tests need to be deployed in healthcare facilities and beyond. Ideally, these tests should be made available for individuals to conduct on themselves at home. For some settings, such as at home, rapid antigen tests similar to those used to detect pregnancy will be suitable; for other settings, like at a doctor's office or a hospital, more elaborate PCR tests will still be key. These last have been compromised for several months due to rationing of the reagent supplies necessary to perform the test – an unacceptable state of affairs that cannot continue. Reflecting an understanding of the state of play of testing, the President-elect recently stated: "We need to increase both lab-based diagnostic testing, with results back within 24 hours or less, and faster, cheaper screening tests that you can take right at home or in school."
Roll Out Safe and Effective Vaccine(s)
Biden's plan also identifies the need to "accelerate the development of treatments and vaccines" and indeed Operation Warp Speed has been one solitary bright spot in the darkness of the failed pandemic response. It is this program that facilitated a distribution partnership with Pfizer for 100 million doses of its mRNA vaccine -- whose preliminary, and extremely positive data, was just announced today to great excitement.
Operation Warp Speed needs to be continued so that we can ensure the final development and distribution of the first-generation vaccines and treatments. When a vaccine is available, it will be a Herculean task that will span many months to actually get into the arms (twice as a 2-dose vaccine) of Americans. Vaccination may begin for healthcare workers before a change in administration, but it will continue long into 2021 and possibly longer. Vaccine distribution will be a task that demands a high degree of competence and coordination, especially with the extreme cold storage conditions needed for the vaccines.
Anticipate the Next Pandemic Now
Not only should Operation Warp Speed be supported, it needs to be expanded. For too long pandemic preparedness has been reactive and it is long past time to approach the development of medical countermeasures for pandemic threats in a proactive fashion.
What we do for other national security threats should be the paradigm for infectious disease threats that too often are subject to a mind-boggling cycle of panic and neglect. There are an estimated 200 outbreaks of viral diseases per year. Luckily and because of hard work, for many of them we have tools at our hands to control them, but for the unknown 201st virus outbreak we do not –as we've seen this year. And, the next unknown virus will likely appear soon. A new program must be constructed guaranteeing that we will never again be caught blindsided and flatfooted as we have been with the COVID-19 pandemic.
A new dedicated "Virus 201" strategy, program, and funding must be created to achieve this goal. This initiative should be a specific program focused on unknown threats that emanate from identified classes of pathogens that possess certain pandemic-causing characteristics. For example, such a program could leverage new powerful vaccine platform technologies to begin development on vaccine candidates for a variety of viral families before they emerge as full-fledged threats. Imagine how different our world would be today if this action was taken after SARS in 2003 or even MERS in 2012.
Biden should remove the handcuffs from the Centers for Disease Control and Prevention (CDC) and allow its experts to coordinate the national response and to issue guidance in the manner they were constituted to do without fear of political reprisal.
Resurrect Expertise
One of the most disheartening aspects of the pandemic has been the denigration and outright attacks on experts in infectious disease. Such disgusting attacks were not for any flaws, incompetence, or weakness but for their opposite -- strength and competence – and emanated from a desire to evade the grim reality. Such nihilism must end and indeed the Biden plan contains several crucial remedies, including the restoration of the White House National Security Council Directorate for Global Health Security and Biodefense, a crucial body of experts at the White House that the Trump administration bafflingly eliminated in 2018.
Additionally, Biden should remove the handcuffs from the Centers for Disease Control and Prevention (CDC) and allow its experts to coordinate the national response and to issue guidance in the manner they were constituted to do without fear of political reprisal.
Shore Up Hospital Capacity
For the foreseeable future, as control of the virus slips away in certain parts of the country, hospital capacity will be the paramount concern. Unlike many other industries, the healthcare sector is severely constrained in its ability to expand capacity because of regulatory and financial considerations. Hospital emergency preparedness has never been prioritized and until we can substantially curtail the spread of this virus, hospitals must remain vigilant.
We have seen how suspensions of "elective" procedures led to alarming declines in vital healthcare services that range from childhood immunization to cancer chemotherapy to psychiatric care. This cannot be allowed to happen again. Hospitals will need support in terms of staffing, alternative care sites, and personal protective equipment. Reflecting these concerns, the Biden plan outlines an approach that smartly uses the Departments of Defense and Veterans Affairs assets and medical reserve corps, coupled to the now-flourishing telemedicine innovations, to augment capacity and forestall the need for hospitals to shift to crisis standards of care.
To these five tasks, I would add a long list of subtasks that need to be executed by agencies such as the Centers for Medicare and Medicaid, the Food and Drug Administration, and many other arms of government. But, to me, these are the most crucial.
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As COVID-19 has demonstrated, new deadly viruses can spread quickly and easily around the globe, causing significant loss of life and economic ruin. With nearly 200 epidemics occurring each year, the next fast-moving, novel infectious disease pandemic could be right around the corner.
The upcoming transition affords the opportunity to implement a new paradigm in pandemic response, biosecurity, and emerging disease response. The United States and President-elect Biden must work hard to to end this pandemic and increase the resilience of the United States to the future infectious disease threats we will surely face.
Dr. Adalja is focused on emerging infectious disease, pandemic preparedness, and biosecurity. He has served on US government panels tasked with developing guidelines for the treatment of plague, botulism, and anthrax in mass casualty settings and the system of care for infectious disease emergencies, and as an external advisor to the New York City Health and Hospital Emergency Management Highly Infectious Disease training program, as well as on a FEMA working group on nuclear disaster recovery. Dr. Adalja is an Associate Editor of the journal Health Security. He was a coeditor of the volume Global Catastrophic Biological Risks, a contributing author for the Handbook of Bioterrorism and Disaster Medicine, the Emergency Medicine CorePendium, Clinical Microbiology Made Ridiculously Simple, UpToDate's section on biological terrorism, and a NATO volume on bioterrorism. He has also published in such journals as the New England Journal of Medicine, the Journal of Infectious Diseases, Clinical Infectious Diseases, Emerging Infectious Diseases, and the Annals of Emergency Medicine. He is a board-certified physician in internal medicine, emergency medicine, infectious diseases, and critical care medicine. Follow him on Twitter: @AmeshAA
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman