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2018 was bonkers for science.
From a woman who gave birth using a transplanted uterus, to the infamous CRISPR baby scandal, to forensics adopting consumer-based genealogy test kits to track down criminals, last year was a factory churning out scientific “whoa” stories with consequences for years to come.
With CRISPR still in the headlines, Britain ready to bid Europe au revoir, and multiple scientific endeavors taking off, 2019 is shaping up to be just as tumultuous.
Here are the science and health stories that may blow up in the new year. But first, a note of caveat: predicting the future is tough. Forecasting is the lovechild between statistics and (a good deal of) intuition, and entire disciplines have been dedicated to the endeavor. But January is the perfect time to gaze into the crystal ball for wisps of insight into the year to come. Last year we predicted the widespread approval of gene therapy products—on the most part, we nailed it. This year we’re hedging our bets with multiple predictions.
Gene Drives Used in the Wild
The concept of gene drives scares many, for good reason. Gene drives are a step up in severity (and consequences) from CRISPR and other gene-editing tools. Even with germline editing, in which the sperm, egg, or embryos are altered, gene editing affects just one genetic line—one family—at least at the beginning, before they reproduce with the general population.
Gene drives, on the other hand, have the power to wipe out entire species.
In a nutshell, they’re little bits of DNA code that help a gene transfer from parent to child with almost 100 percent perfect probability. The “half of your DNA comes from dad, the other comes from mom” dogma? Gene drives smash that to bits.
In other words, the only time one would consider using a gene drive is to change the genetic makeup of an entire population. It sounds like the plot of a supervillain movie, but scientists have been toying around with the idea of deploying the technology—first in mosquitoes, then (potentially) in rodents.
By releasing just a handful of mutant mosquitoes that carry gene drives for infertility, for example, scientists could potentially wipe out entire populations that carry infectious scourges like malaria, dengue, or Zika. The technology is so potent—and dangerous—the US Defense Advances Research Projects Agency is shelling out $65 million to suss out how to deploy, control, counter, or even reverse the effects of tampering with ecology.
Last year, the U.N. gave a cautious go-ahead for the technology to be deployed in the wild in limited terms. Now, the first release of a genetically modified mosquito is set for testing in Burkina Faso in Africa—the first-ever field experiment involving gene drives.
The experiment will only release mosquitoes in the Anopheles genus, which are the main culprits transferring disease. As a first step, over 10,000 male mosquitoes are set for release into the wild. These dudes are genetically sterile but do not cause infertility, and will help scientists examine how they survive and disperse as a preparation for deploying gene-drive-carrying mosquitoes.
Hot on the project’s heels, the nonprofit consortium Target Malaria, backed by the Bill and Melinda Gates foundation, is engineering a gene drive called Mosq that will spread infertility across the population or kill out all female insects. Their attempt to hack the rules of inheritance—and save millions in the process—is slated for 2024.
A Universal Flu Vaccine
People often brush off flu as a mere annoyance, but the infection kills hundreds of thousands each year based on the CDC’s statistical estimates.
The flu virus is actually as difficult of a nemesis as HIV—it mutates at an extremely rapid rate, making effective vaccines almost impossible to engineer on time. Scientists currently use data to forecast the strains that will likely explode into an epidemic and urge the public to vaccinate against those predictions. That’s partly why, on average, flu vaccines only have a success rate of roughly 50 percent—not much better than a coin toss.
Tired of relying on educated guesses, scientists have been chipping away at a universal flu vaccine that targets all strains—perhaps even those we haven’t yet identified. Often referred to as the “holy grail” in epidemiology, these vaccines try to alert our immune systems to parts of a flu virus that are least variable from strain to strain.
Last November, a first universal flu vaccine developed by BiondVax entered Phase 3 clinical trials, which means it’s already been proven safe and effective in a small numbers and is now being tested in a broader population. The vaccine doesn’t rely on dead viruses, which is a common technique. Rather, it uses a small chain of amino acids—the chemical components that make up proteins—to stimulate the immune system into high alert.
With the government pouring $160 million into the research and several other universal candidates entering clinical trials, universal flu vaccines may finally experience a breakthrough this year.
In-Body Gene Editing Shows Further Promise
CRISPR and other gene editing tools headed the news last year, including both downers suggesting we already have immunity to the technology and hopeful news of it getting ready for treating inherited muscle-wasting diseases.
But what wasn’t widely broadcasted was the in-body gene editing experiments that have been rolling out with gusto. Last September, Sangamo Therapeutics in Richmond, California revealed that they had injected gene-editing enzymes into a patient in an effort to correct a genetic deficit that prevents him from breaking down complex sugars.
The effort is markedly different than the better-known CAR-T therapy, which extracts cells from the body for genetic engineering before returning them to the hosts. Rather, Sangamo’s treatment directly injects viruses carrying the edited genes into the body. So far, the procedure looks to be safe, though at the time of reporting it was too early to determine effectiveness.
This year the company hopes to finally answer whether it really worked.
If successful, it means that devastating genetic disorders could potentially be treated with just a few injections. With a gamut of new and more precise CRISPR and other gene-editing tools in the works, the list of treatable inherited diseases is likely to grow. And with the CRISPR baby scandal potentially dampening efforts at germline editing via regulations, in-body gene editing will likely receive more attention if Sangamo’s results return positive.
Neuralink and Other Brain-Machine Interfaces
Neuralink is the stuff of sci fi: tiny implanted particles into the brain could link up your biological wetware with silicon hardware and the internet.
But that’s exactly what Elon Musk’s company, founded in 2016, seeks to develop: brain-machine interfaces that could tinker with your neural circuits in an effort to treat diseases or even enhance your abilities.
Last November, Musk broke his silence on the secretive company, suggesting that he may announce something “interesting” in a few months, that’s “better than anyone thinks is possible.”
Musk’s aspiration for achieving symbiosis with artificial intelligence isn’t the driving force for all brain-machine interfaces (BMIs). In the clinics, the main push is to rehabilitate patients—those who suffer from paralysis, memory loss, or other nerve damage.
2019 may be the year that BMIs and neuromodulators cut the cord in the clinics. These devices may finally work autonomously within a malfunctioning brain, applying electrical stimulation only when necessary to reduce side effects without requiring external monitoring. Or they could allow scientists to control brains with light without needing bulky optical fibers.
Cutting the cord is just the first step to fine-tuning neurological treatments—or enhancements—to the tune of your own brain, and 2019 will keep on bringing the music.
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“You really can’t justify tuna in Chicago as a source of sustenance.” That’s according to Dr. Sylvia Earle, a National Geographic Society Explorer who was the first female chief scientist at NOAA. She came to the Good Food Institute’s Good Food Conference to deliver a call to action around global food security, agriculture, environmental protection, and the future of consumer choice.
It seems like all options should be on the table to feed an exploding population threatened by climate change. But Dr. Earle, who is faculty at Singularity University, drew a sharp distinction between seafood for sustenance versus seafood as a choice. “There is this widespread claim that we must take large numbers of wildlife from the sea in order to have food security.”
A few minutes later, Dr. Earle directly addressed those of us in the audience. “We know the value of a dead fish,” she said. That’s market price. “But what is the value of a live fish in the ocean?”
That’s when my mind blew open. What is the value—or put another way, the cost—of using the ocean as a major source of protein for humans? How do you put a number on that? Are we talking about dollars and cents, or about something far larger?
Dr. Liz Specht of the Good Food Institute drew the audience’s attention to a strange imbalance. Currently, about half of the yearly global catch of seafood comes from aquaculture. That means that the other half is wild caught. It’s hard to imagine half of your meat coming directly from the forests and the plains, isn’t it? And yet half of the world’s seafood comes from direct harvesting of the oceans, by way of massive overfishing, a terrible toll from bycatch, a widespread lack of regulation and enforcement, and even human rights violations such as slavery.
The search for solutions is on, from both within the fishing industry and from external agencies such as governments and philanthropists. Could there be another way?
Makers of plant-based seafood and clean seafood think they know how to feed the global demand for seafood without harming the ocean. These companies are part of a larger movement harnessing technology to reduce our reliance on wild and domesticated animals—and all the environmental, economic, and ethical issues that come with it.
Producers of plant-based seafood (20 or so currently) are working to capture the taste, texture, and nutrition of conventional seafood without the limitations of geography or the health of a local marine population. Like with plant-based meat, makers of plant-based seafood are harnessing food science and advances in chemistry, biology, and engineering to make great food. The industry’s strategy? Start with what the consumer wants, and then figure out how to achieve that great taste through technology.
So how does plant-based seafood taste? Pretty good, as it turns out. (The biggest benefit of a food-oriented conference is that your mouth is always full!)
I sampled “tuna” salad made from Good Catch Food’s fish-free tuna, which is sourced from legumes; the texture was nearly indistinguishable from that of flaked albacore tuna, and there was no lingering fishy taste to overpower my next bite. In a blind taste test, I probably wouldn’t have known that I was eating a plant-based seafood alternative. Next I reached for Ocean Hugger Food’s Ahimi, a tomato-based alternative to raw tuna. I adore Hawaiian poke, so I was pleasantly surprised when my Ahimi-based poke captured the bite of ahi tuna. It wasn’t quite as delightfully fatty as raw tuna, but with wild tuna populations struggling to recover from a 97% decline in numbers from 40 years ago, Ahimi is a giant stride in the right direction.
These plant-based alternatives aren’t the only game in town, however.
The clean meat industry, which has also been called “cultured meat” or “cellular agriculture,” isn’t seeking to lure consumers away from animal protein. Instead, cells are sampled from live animals and grown in bioreactors—meaning that no animal is slaughtered to produce real meat.
Clean seafood is poised to piggyback off platforms developed for clean meat; growing fish cells in the lab should rely on the same processes as growing meat cells. I know of four companies currently focusing on seafood (Finless Foods, Wild Type, BlueNalu, and Seafuture Sustainable Biotech), and a few more are likely to emerge from stealth mode soon.
Importantly, there’s likely not much difference between growing clean seafood from the top or the bottom of the food chain. Tuna, for example, are top predators that must grow for at least 10 years before they’re suitable as food. Each year, a tuna consumes thousands of pounds of other fish, shellfish, and plankton. That “long tail of groceries,” said Dr. Earle, “is a pretty expensive choice.” Excitingly, clean tuna would “level the trophic playing field,” as Dr. Specht pointed out.
All this is only the beginning of what might be possible.
Combining synthetic biology with clean meat and seafood means that future products could be personalized for individual taste preferences or health needs, by reprogramming the DNA of the cells in the lab. Industries such as bioremediation and biofuels likely have a lot to teach us about sourcing new ingredients and flavors from algae and marine plants. By harnessing rapid advances in automation, robotics, sensors, machine vision, and other big-data analytics, the manufacturing and supply chains for clean seafood could be remarkably safe and robust. Clean seafood would be just that: clean, without pathogens, parasites, or the plastic threatening to fill our oceans, meaning that you could enjoy it raw.
What about price? Dr. Mark Post, a pioneer in clean meat who is also faculty at Singularity University, estimated that 80% of clean-meat production costs come from the expensive medium in which cells are grown—and some ingredients in the medium are themselves sourced from animals, which misses the point of clean meat. Plus, to grow a whole cut of food, like a fish fillet, the cells need to be coaxed into a complex 3D structure with various cell types like muscle cells and fat cells. These two technical challenges must be solved before clean meat and seafood give consumers the experience they want, at the price they want.
In this respect clean seafood has an unusual edge. Most of what we know about growing animal cells in the lab comes from the research and biomedical industries (from tissue engineering, for example)—but growing cells to replace an organ has different constraints than growing cells for food. The link between clean seafood and biomedicine is less direct, empowering innovators to throw out dogma and find novel reagents, protocols, and equipment to grow seafood that captures the tastes, textures, smells, and overall experience of dining by the ocean.
Asked to predict when we’ll be seeing clean seafood in the grocery store, Lou Cooperhouse the CEO of BlueNalu, explained that the challenges aren’t only in the lab: marketing, sales, distribution, and communication with consumers are all critical. As Niya Gupta, the founder of Fork & Goode, said, “The question isn’t ‘can we do it’, but ‘can we sell it’?”
The good news is that the clean meat and seafood industry is highly collaborative; there are at least two dozen companies in the space, and they’re all talking to each other. “This is an ecosystem,” said Dr. Uma Valeti, the co-founder of Memphis Meats. “We’re not competing with each other.” It will likely be at least a decade before science, business, and regulation enable clean meat and seafood to routinely appear on restaurant menus, let alone market shelves.
Until then, think carefully about your food choices. Meditate on Dr. Earle’s question: “What is the real cost of that piece of halibut?” Or chew on this from Dr. Ricardo San Martin, of the Sutardja Center at the University of California, Berkeley: “Food is a system of meanings, not an object.” What are you saying when you choose your food, about your priorities and your values and how you want the future to look? Do you think about animal welfare? Most ethical regulations don’t extend to marine life, and if you don’t think that ocean creatures feel pain, consider the lobster.
Seafood is largely an acquired taste, since most of us don’t live near the water. Imagine a future in which children grow up loving the taste of delicious seafood but without hurting a living animal, the ocean, or the global environment.
Do more than imagine. As Dr. Earle urged us, “Convince the public at large that this is a really cool idea.”
Ahimi (Ocean Hugger)
New Wave Foods
Heritage Health Food
The Vegetarian Butcher
Table based on Figure 5 of the report “An Ocean of Opportunity: Plant-based and clean seafood for sustainable oceans without sacrifice,” from The Good Food Institute.
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Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.
Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.
Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.
Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.
However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.
Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.
De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.
Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.
“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”
Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.
“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”
What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.
“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”
Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.
“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”
De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.
“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”
It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.
BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.
“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.
Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.
“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”
Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.
The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.
However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.
“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.
“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.
Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.
“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”
Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.
Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.
“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.
And does anyone truly want to live forever?
“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.
“They should be careful what they wish for.”
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