Friday Five Podcast: New drug may slow the rate of Alzheimer's disease
The Friday Five covers important stories in health and science research that you may have missed - usually over the previous week, but today's episode is a lookback on important studies over the month of September.
Most recently, on September 27, pharmaceuticals Biogen and Eisai announced that a clinical trial showed their drug, lecanemab, can slow the rate of Alzheimer's disease. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend and the new month.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
This Friday Five episode covers the following studies published and announced over the past month:
- A new drug is shown to slow the rate of Alzheimer's disease
- The need for speed if you want to reduce your risk of dementia
- How to refreeze the north and south poles
- Ancient wisdom about Neti pots could pay off for Covid
- Two women, one man and a baby
Could epigenetic reprogramming reverse aging?
Ten thousand years ago, the average human spent a maximum of 30 years on Earth. Despite the glory of Ancient Greece and the Roman Empire, most of their inhabitants didn’t surpass the age of 35. Between the 1500s and 1800, life expectancy (at least in Europe) fluctuated between 30 and 40 years.
Public health advancements like control of infectious diseases, better diet and clean sanitation, as well as social improvements have made it possible for human lifespans to double since 1800. Although lifespan differs widely today from country to country according to socioeconomic health, the average has soared to 73.2 years.
But this may turn out to be on the low side if epigenetic rejuvenation fulfills its great promise: to reverse aging, perhaps even completely. Epigenetic rejuvenation, or partial reprogramming, is the process by which a set of therapies are trying to manipulate epigenetics – how various changes can affect our genes – and the Yamanaka factors. These Yamanaka factors are a group of proteins that can convert any cell of the body into pluripotent stem cells, a group of cells that can turn into brand new cells, such as those of the brain or skin. At least in theory, it could be a recipe for self-renewal.
“Partial reprogramming tries to knock a few years off of people’s biological age, while preserving their original cell identity and function,” says Yuri Deigin, cofounder and director of YouthBio Therapeutics, a longevity startup utilizing partial reprogramming to develop gene therapies aimed at the renewal of epigenetic profiles. YouthBio plans to experiment with injecting these gene therapies into target organs. Once the cargo is delivered, a specific small molecule will trigger gene expression and rejuvenate those organs.
“Our ultimate mission is to find the minimal number of tissues we would need to target to achieve significant systemic rejuvenation,” Deigin says. Initially, YouthBio will apply these therapies to treat age-related conditions. Down the road, though, their goal is for everyone to get younger. “We want to use them for prophylaxis, which is rejuvenation that would lower disease risk,” Deigin says.
Epigenetics has swept the realm of biology off its feet over the last decade. We now know that we can switch genes on and off by tweaking the chemical status quo of the DNA’s local environment. "Epigenetics is a fascinating and important phenomenon in biology,’’ says Henry Greely, a bioethicist at Stanford Law School. Greely is quick to stress that this kind of modulation (turning genes on and off and not the entire DNA) happens all the time. “When you eat and your blood sugar goes up, the gene in the beta cells of your pancreas that makes insulin is turned on or up. Almost all medications are going to have effects on epigenetics, but so will things like exercise, food, and sunshine.”
Can intentional control over epigenetic mechanisms lead to novel and useful therapies? “It is a very plausible scenario,” Greely says, though a great deal of basic research into epigenetics is required before it becomes a well-trodden way to stay healthy or treat disease. Whether these therapies could cause older cells to become younger in ways that have observable effects is “far from clear,” he says. “Historically, betting on someone’s new ‘fountain of youth’ has been a losing strategy.”
The road to de-differentiation, the process by which cells return to an earlier state, is not paved with roses; de-differentiate too much and you may cause pathology and even death.
In 2003 researchers finished sequencing the roughly 3 billion letters of DNA that make up the human genome. The human genome sequencing was hailed as a vast step ahead in our understanding of how genetics contribute to diseases like cancer or to developmental disorders. But for Josephine Johnston, director of research and research scholar at the Hastings Center, the hype has not lived up to its initial promise. “Other than some quite effective tests to diagnose certain genetic conditions, there isn't a radical intervention that reverses things yet,” Johnston says. For her, this is a testament to the complexity of biology or at least to our tendency to keep underestimating it. And when it comes to epigenetics specifically, Johnston believes there are some hard questions we need to answer before we can safely administer relevant therapies to the population.
“You'd need to do longitudinal studies. You can't do a study and look at someone and say they’re safe only six months later,” Johnston says. You can’t know long-term side effects this way, and how will companies position their therapies on the market? Are we talking about interventions that target health problems, or life enhancements? “If you describe something as a medical intervention, it is more likely to be socially acceptable, to attract funding from governments and ensure medical insurance, and to become a legitimate part of medicine,” she says.
Johnston’s greatest concerns are of the philosophical and ethical nature. If we’re able to use epigenetic reprogramming to double the human lifespan, how much of the planet’s resources will we take up during this long journey? She believes we have a moral obligation to make room for future generations. “We should also be honest about who's actually going to afford such interventions; they would be extraordinarily expensive and only available to certain people, and those are the people who would get to live longer, healthier lives, and the rest of us wouldn't.”
That said, Johnston agrees there is a place for epigenetic reprogramming. It could help people with diseases that are caused by epigenetic problems such as Fragile X syndrome, Prader-Willi syndrome and various cancers.
Zinaida Good, a postdoctoral fellow at Stanford Cancer Institute, says these problems are still far in the future. Any change will be incremental. “Thinking realistically, there’s not going to be a very large increase in lifespan anytime soon,” she says. “I would not expect something completely drastic to be invented in the next 5 to 10 years. ”
Good won’t get any such treatment for herself until it’s shown to be effective and safe. Nature has programmed our bodies to resist hacking, she says, in ways that could undermine any initial benefits to longevity. A preprint that is not yet peer-reviewed reports cellular reprogramming may lead to premature death due to liver and intestinal problems, and using the Yamanaka factors may have the potential to cause cancer, at least in animal studies.
“Side effects are an open research question that all partial reprogramming companies and labs are trying to address,” says Deigin. The road to de-differentiation, the process by which cells return to an earlier state, is not paved with roses; de-differentiate too much and you may cause pathology and even death. Deigin is exploring other, less risky approaches. “One way is to look for novel factors tailored toward rejuvenation rather than de-differentiation.” Unlike Yamanaka factors, such novel factors would never involve taking a given cell to a state in which it could turn cancerous, according to Deigin.
An example of a novel factor that could lower the risk of cancer is artificially introducing mRNA molecules, or molecules carrying the genetic information necessary to make proteins, by using electricity to penetrate the cell instead of a virus. There is also chemical-based reprogramming, in which chemicals are applied to convert regular cells into pluripotent cells. This approach is currently effective only for mice though.
“The search for novel factors tailored toward rejuvenation without de-differentiation is an ongoing research and development effort by several longevity companies, including ours,” says Deigin.
He isn't disclosing the details of his own company’s underlying approach to lowering the risk, but he’s hopeful that something will eventually end up working in humans. Yet another challenge is that, partly because of the uncertainties, the FDA hasn’t seen fit to approve a single longevity therapy. But with the longevity market projected to soar to $600 billion by 2025, Deigin says naysayers are clinging irrationally to the status quo. “Thankfully, scientific progress is moved forward by those who bet for something while disregarding the skeptics - who, in the end, are usually proven wrong.”
The rise of remote work is a win-win for people with disabilities and employers
Disability advocates see remote work as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike.
Any corporate leader would jump at the opportunity to increase their talent pool of potential employees by 15 percent, with all these new hires belonging to an underrepresented minority. That’s especially true given tight labor markets and CEO desires to increase headcount. Yet, too few leaders realize that people with disabilities are the largest minority group in this country, numbering 50 million.
Some executives may dread the extra investments in accommodating people’s disabilities. Yet, providing full-time remote work could suffice, according to a new study by the Economic Innovation Group think tank. The authors found that the employment rate for people with disabilities did not simply reach the pre-pandemic level by mid-2022, but far surpassed it, to the highest rate in over a decade. “Remote work and a strong labor market are helping [individuals with disabilities] find work,” said Adam Ozimek, who led the research and is chief economist at the Economic Innovation Group.
Disability advocates see this development as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike. For decades before the pandemic, employers had refused requests from workers with disabilities to work remotely, according to Thomas Foley, executive director of the National Disability Institute. During the pandemic, "we all realized that...many of us could work remotely,” Foley says. “[T]hat was disproportionately positive for people with disabilities."
Charles-Edouard Catherine, director of corporate and government relations for the National Organization on Disability, said that remote-work options had been advocated for many years to accommodate disabilities. “It’s a little frustrating that for decades corporate America was saying it’s too complicated, we’ll lose productivity, and now suddenly it’s like, sure, let’s do it.”
The pandemic opened doors for people with disabilities
Early in the pandemic, employment rates dropped for everyone, including people with disabilities, according to Ozimek’s research. However, these rates recovered quickly. In the second quarter of 2022, people with disabilities aged 25 to 54, the prime working age, are 3.5 percent more likely to be employed, compared to before the pandemic.
What about people without disabilites? They are still 1.1 percent less likely to be employed.
These numbers suggest that remote work has enabled a substantial number of people with disabilities to find and retain employment.
“We have a last-in, first-out labor market, and [people with disabilities] are often among the last in and the first out,” Ozimek says. However, this dynamic has changed, with adults with disabilities seeing employment rates recover much faster. Now, the question is whether the new trend will endure, Ozimek adds. “And my conclusion is that not only is it a permanent thing, but it’s going to improve.”
Gene Boes, president and chief executive of the Northwest Center, a Seattle organization that helps people with disabilities become more independent, confirms this finding. “The new world we live in has opened the door a little bit more…because there’s just more demand for labor.”
Long COVID disabilities put a premium on remote work
Remote work can help mitigate the impact of long COVID. The U.S. Centers for Disease Control and Prevention reports that about 19 percent of those who had COVID developed long COVID. Recent Census Bureau data indicates that 16 million working age Americans suffer from it, with economic costs estimated at $3.7 trillion.
Certainly, many of these so-called long-haulers experience relatively mild symptoms - such as loss of smell - which, while troublesome, are not disabling. But other symptoms are serious enough to be disabilities.
According to a recent study from the Federal Reserve Bank of Minneapolis, about a quarter of those with long COVID changed their employment status or working hours. That means long COVID was serious enough to interfere with work for 4 million people. For many, the issue was serious enough to qualify them as disabled.
Indeed, the Federal Reserve Bank of New York found in a just-released study that the number of individuals with disabilities in the U.S. grew by 1.7 million. That growth stemmed mainly from long COVID conditions such as fatigue and brain fog, meaning difficulties with concentration or memory, with 1.3 million people reporting an increase in brain fog since mid-2020.
Many had to drop out of the labor force due to long COVID. Yet, about 900,000 people who are newly disabled have managed to continue working. Without remote work, they might have lost these jobs.
For example, a software engineer at one of my client companies has struggled with brain fog related to long COVID. With remote work, this employee can work during the hours when she feels most mentally alert and focused, even if that means short bursts of productivity throughout the day. With flexible scheduling, she can take rests, meditate, or engage in activities that help her regain focus and energy. Without the need to commute to the office, she can save energy and time and reduce stress, which is crucial when dealing with brain fog.
In fact, the author of the Federal Reserve Bank of New York study notes that long COVID can be considered a disability under the Americans with Disability Act, depending on the specifics of the condition. That means the law can require private employers with fifteen or more staff, as well as government agencies, to make reasonable accommodations for those with long COVID. Richard Deitz, the author of this study, writes in the paper that “telework and flexible scheduling are two accommodations that can be particularly beneficial for workers dealing with fatigue and brain fog.”
The current drive to return to the office, led by many C-suite executives, may need to be reconsidered in light of legal and HR considerations. Arlene S. Kanter, director of the disability law and policy program at the Syracuse University College of Law, said that the question should depend on whether people with disabilities can perform their work well at home, as they did during Covid outbreaks. “[T]hen people with disabilities, as a matter of accommodation, shouldn’t be denied that right,” Kanter said.
Diversity benefits
But companies shouldn’t need to worry about legal regulations. It simply makes dollars and sense to expand their talent pool by 15% of an underrepresented minority. After all, extensive research shows that improving diversity boosts both decision-making and financial performance.
Companies that are offering more flexible work options have already gained significant benefits in terms of diverse hires. In its efforts to adapt to the post-pandemic environment, Meta, the owner of Facebook and Instagram, decided to offer permanent fully remote work options to its entire workforce. And according to Meta chief diversity officer Maxine Williams, the candidates who accepted job offers for remote positions were “substantially more likely” to come from diverse communities: people with disabilities, Black, Hispanic, Alaskan Native, Native American, veterans, and women. The numbers bear out these claims: people with disabilities increased from 4.7 to 6.2 percent of Meta’s employees.
Having consulted for 21 companies to help them transition to hybrid work arrangements, I can confirm that Meta’s numbers aren’t a fluke. The more my clients proved willing to offer remote work, the more staff with disabilities they recruited - and retained. That includes employees with mobility challenges. But it also includes employees with less visible disabilities, such as people with long COVID and immunocompromised people who feel reluctant to put themselves at risk of getting COVID by coming into the office.
Unfortunately, many leaders fail to see the benefits of remote work for underrepresented groups, such as those with disabilities. Some even say the opposite is true, with JP Morgan CEO Jamie Dimon claiming that returning to the office will aid diversity.
What explains this poor executive decision making? Part of the answer comes from a mental blindspot called the in-group bias. Our minds tend to favor and pay attention to the concerns of those in the group of people who seem to look and think like us. Dimon and other executives without disabilities don’t perceive people with disabilities to be part of their in-group. They thus are blind to the concerns of those with disabilities, which leads to misperceptions such as Dimon’s that returning to the office will aid diversity.
In-group bias is one of many dangerous judgment errors known as cognitive biases. They impact decision making in all life areas, ranging from the future of work to relationships.
Another relevant cognitive bias is the empathy gap. This term refers to our difficulty empathizing with those outside of our in-group. The lack of empathy combines with the blindness from the in-group bias, causing executives to ignore the feelings of employees with disabilities and prospective hires.
Omission bias also plays a role. This dangerous judgment error causes us to perceive failure to act as less problematic than acting. Consequently, executives perceive a failure to support the needs of those with disabilities as a minor matter.
Conclusion
The failure to empower people with disabilities through remote work options will prove costly to the bottom lines of companies. Not only are limiting their talent pool by 15 percent, they’re harming their ability to recruit and retain diverse candidates. And as their lawyers and HR departments will tell them, by violating the ADA, they are putting themselves in legal jeopardy.
By contrast, companies like Meta - and my clients - that offer remote work opportunities are seizing a competitive advantage by recruiting these underrepresented candidates. They’re lowering costs of labor while increasing diversity. The future belongs to the savvy companies that offer the flexibility that people with disabilities need.