Browsed by
Tag: nature

Alzheimer’s Disease Reversed by Editing a Single Gene – Article by Steve Hill

Alzheimer’s Disease Reversed by Editing a Single Gene – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on April 13, 2018. In this article, Mr. Hill reviews a new study published in Nature that supports the idea that Alzheimer’s disease research efforts should target the ApoE4 gene, and not consider the ApoE3 gene as much, even though  previous research that focused on the ApoE3 gene cured Alzheimer’s disease in mice models. This is a promising step forward for Alzheimer’s research.

~Bobby Ridge, Assistant Editor, July 2, 2019

Researchers at Gladstone Institutes in San Francisco report that a gene variant associated with Alzheimer’s works differently in mice and humans, and they also demonstrate how modifying this gene could potentially prevent the plaques associated with Alzheimer’s from forming and damaging the brain. The new study was published in the journal Nature in January 2018 [1].

An ApoE3 gene variant is associated with Alzheimer’s disease

The gene apolipoprotein E3 (ApoE3) has a variant known as ApoE4, which is associated with the development and progress of Alzheimer’s disease. People with just one copy of the ApoE4 gene are at twice the risk as people without this gene variant. Some people even have two copies of the ApoE4 gene, which makes their risk of Alzheimer’s a staggering twelve times greater.

Both the ApoE genes produce their own forms of ApoE protein, which differ in structure. The ApoE4 protein is fragile and fragments because it cannot function in the same way as the regular ApoE3 protein in human nerve cells. These fragmented protein pieces are associated with the increased production of amyloid-β peptides and tau phosphorylation that are typical of Alzheimer’s disease.

The researchers wanted to find out how ApoE4 is linked to Alzheimer’s disease. They considered the possibility that the increased amyloid-β and tau phosphorylation from the fragmentation of ApoE4 drives disease progression. Another possibility involved the negative consequences of a lack of ApoE3 proteins, as they were replaced by the ApoE4 variant. The team also considered a combination of both of these possibilities.

The team investigated these potential answers by examining the effects of ApoE3 and ApoE4 on human nerve cells. Neurons were created by using pluripotent stem cells taken from volunteers who had either two copies of ApoE3 or two copies of the ApoE4 gene, and the researchers programmed these cells to become the desired type of neuronal cell.

The team compared the ApoE3 and ApoE4 neurons against neurons that were unable to produce either type of the ApoE protein. They discovered that neurons that produced no ApoE protein worked the same as those that produced ApoE3. This confirmed that it was not a lack of ApoE3 causing the problem but that ApoE4 protein alone was linked to Alzheimer’s disease.

This finding also sheds light on why treatments for Alzheimer’s that work in mice fail to translate to humans. The production of amyloid-β in mice is not influenced by ApoE4; this means that treatments that prove effective in mice may not work in humans, as the mouse models of the disease do not emulate the ApoE4-related form of Alzheimer’s that humans get. However, therapies that focus on reducing amyloid-β have worked in mice [2], so while ApoE4 functions differently in mice and humans, this is not the full story of Alzheimer’s. This research does, however, clearly show a way in which mouse models differ from humans, helping to guide future research.

Converting ApoE4 to ApoE3

The results of the study suggest that therapies that seek to modify the ApoE4 gene protein before it fragments might be a way to combat Alzheimer’s. This is how traditional medicine would generally approach the problem, treating the symptoms and not the cause.

However, the researchers took this one step further to a far more robust solution. Rather than simply attempting to treat the consequences of having an ApoE4 gene producing sub-par proteins, they completely removed the problem by using gene therapy to edit the genes and convert them from ApoE4 to ApoE3.

The converted genes ceased to produce the unstable ApoE4 protein and produced the stable ApoE3 version of it instead. This served to correct the problem at the root rather than trying to slap a band-aid on the consequences.

Conclusion

With so many failures to combat Alzheimer’s disease, it is easy to become disillusioned. We have seen mice cured of the disease numerous times, but these cures have failed to translate to humans. These new findings help to progress knowledge in the field and offer potential new ways to defeat Alzheimer’s.

What is refreshing about this study is how the researchers have opted to attack the problem at the root cause: the production of misfolded proteins that lead to the progression of the disease. It is becoming ever more clear that if we are going to make progress on ending age-related diseases, we must target the aging processes themselves, which cause these diseases.

Literature

[1] Yuang, Y. et al. (2018) Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nature Medicine doi:10.1038/s41591-018-0004-z

[2] Hu, X., Das, B., Hou, H., He, W., & Yan, R. (2018). BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions. Journal of Experimental Medicine, jem-20171831.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Kindness, the Greatest Temperer of Hubris – Article by Sarah Lim

Kindness, the Greatest Temperer of Hubris – Article by Sarah Lim

Sarah Lim


In light of the increasingly alarming reports on climate catastrophe that have been released in the past few months, more and more transhumanists are taking up the gauntlet and putting climate-change solutions on their political agenda. Sadly, the transhumanist movement hasn’t exactly been well-received by the environmentalist movement. Environmentalists such as Charles Eisenstein have blamed “scientism” and excessive faith in the scientific materialist worldview as being primarily responsible for the overexploitation of the natural world. Other environmentalists are hostile towards the transhumanist imperative to find a cure for biological aging, arguing that curing aging will further exacerbate the resource scarcity (a common criticism which LEAF has dealt with so extensively, they have a page dedicated to it).

It probably doesn’t help that a handful of transhumanists are very vocally “anti-nature”. One of transhumanism’s primary goals is to knock down fallacious appeals to nature which are propped up against the pursuit of radical human lifespan extension or cyborgification. However, the way we present these ideas could perhaps be phrased in a more palatable manner.

Environmentalists and bioconservatives are fond of claiming that transhumanism is the apogee of human hubris. They claim that transhumanism’s goals to overcome humanity’s biological limits are inseparable from the rapacious greed that has driven developed economies to violate the natural world to a point of near-collapse. Deep Greens go so far as to call for a total renunciation of the technological fruits of civilization, and a return to a hunter-gatherer lifestyle. Radical environmentalists claim that a return to Luddism is the only thing that can save humanity from pillaging the natural world to a point where it becomes utterly inhabitable. But I would argue that the either-or split between human progress through technological advancement and compassion towards non-human life is a false dichotomy.

Drawing on David Pearce’s hedonistic imperative, I will argue that transhumanism and environmentalism aren’t necessarily at loggerheads with each other. You could even say that transhumanism entails a benevolent stewardship of nature, and that care for all non-human life is a logical extension of human exceptionalism. If the core imperative of our movement is to minimize suffering caused by biological limitations, that should apply to minimizing non-human suffering as well.

Benevolent stewardship: the Aristotelian mean between Deep Green Ludditism and Radical Transhumanist Anti-Naturism

I don’t think I’ve ever met somebody whose ideas have so radically changed my views on existential teleology and the natural world as quickly as David’s have. What I love about David’s hedonistic imperative and his involvement in the Reducing Wild Animal Suffering (RWAS) movement is how radically his ideology reframes the idea of human exceptionalism.

“Human exceptionalism” is generally seen as a bad thing, and with good reason. For the better part of human civilisation’s history, humans have been exceptionally bad – exceptionally bad to ethnic minorities who didn’t have guns or cannons,  exceptionally bad to women by depriving them of equal status to men and bodily autonomy, and exceptionally bad to all the animals humans have needlessly slaughtered or whose habitats they obliterated. Human beings are stand out as being exceptionally intelligent amongst the animal kingdom, and they also stand out for using that intelligence in extremely innovative ways to amass vast amounts of resources for their “in” groups, by brutally exploiting “out” groups in the most unimaginably vile ways.

But the hedonistic imperative puts a new spin on “human exceptionalism”. The hedonistic imperative is the great Uncle Ben lesson for humanity. With our exceptional intelligence comes great responsibility – responsibility not just to currently marginalized ethnic groups, genders, and social classes within humanity, but to non-human species, too. If we have the intelligence to turn humanity into a planet-ravaging force, then we have the intelligence to find a way to repair the damage humans have done.

The hedonistic imperative movement has also been credited with helping to convert a growing number of transhumanists to veganism, and to supporting planet-saving initiatives.

Aristotle is best known for describing virtue as the golden mean between two vices. I wouldn’t go so far as to call Deep Green environmentalism or radically anti-naturist transhumanism “vices”, but I would say that the hedonistic imperative manages to gel the most effective aspects of both schools of thought while avoiding the practical blind spots of both.

Deep Green environmentalists like Charles Eisenstein tend to promulgate the idea of nature’s sacredness as entailing an acceptance of natural malaises. These include death due to biological aging, but a logical extension of this is that it is immoral for human beings to intervene in nature and prevent animals from harming each other, since it is part of the “natural order”. Radically anti-naturist transhumanists tend to view anything natural as being automatically inferior to whatever man-made alternatives can be technologically manufactured. While we shouldn’t accept invocations of naturalism prima facie, this view isn’t quite tenable for primarily practical reasons. It would probably be extremely unwise to replace all the organic trees in the world with man-made synthetic ones, because the Earth’s biosphere is an exceedingly complex system that even our best biologists and geologists still do not fully understand. Likewise, we cannot solely on carbon-capture technology or geoengineering to be the ultimate solutions to the ongoing climate crisis. Much more still needs to be invested in reforestation and the restoration of currently endangered animal and plant species which have been afflicted by habitat loss or resource depletion.

Homo Deus: Already Here

For all the utter destruction that humanity has wrought over the past 10,000 years, we can’t overlook the great capabilities we hold as stewards of nature. Say what you will about humanity, but we’re literally the only species on Earth that has evolved to a point where we can use science to resurrect the dodo bird, the woolly mammoth, and the pterodactyl. And we can do that with all the other species we’ve driven to extinction. Perhaps those will be the reparations we pay to the animal kingdom for the previous damage done.

Humanity is also the only species in existence that actually has the power to contradict the forces of natural selection and end natural suffering in its tracks. We just choose not to because we can’t be bothered to. I had never in my life thought about how powerful the implications of this were until I listened to David speak about it. We are the only species with the requisite technological power to end hunger, disease, and infant mortality amongst animals, if we so choose.

Basically put: we’re already gods and goddesses.

We are literally gods in the eyes of animals.

But many humans have chosen to emulate the very worst behaviours of the Old Testament Biblical God rather than being the kind of God all human civilizations would long hope would care for them kindly.

One of Ben Goertzel’s major life goals is to create the most benevolent possible AI nanny who will be programmed to watch over humanity, make us immortal and create a post-scarcity condition where all of our physical needs can be met through the application of nanotechnology. Ben acknowledges that deliberately programming an AI to be as benevolent and compassionate is possible, because at present, everyone and their mother is preparing for a possible Terminator scenario where AI goes rogue and decides that it is under no obligation to be kind to its human creators.

If you would like to know exactly how badly an indifferent or uncompassionate posthuman AI could treat us, you need only look at how badly humans treat chickens and cows. You would only have to look up YouTube videos of desperate orangutans feebly trying to push aside construction cranes that are in the midst of pulverising the trees in which they reside.

And it wasn’t too long ago that humans treated different races of human beings in a similar fashion (although they weren’t slaughtered for consumption).

A posthuman ultra-intelligent AI inflicting the same treatment on humans in developed industrial economies might just be karma coming to pay what’s long been due.

“The benevolent AI god who will resurrect the dead and keep us prosperous forever” is the one wild fantasy which transhumanist forums are constantly salivating over. But why should we expect the AI god to be so propitious to us when humans are not even showing a fraction of that expected mercy to the elephants, cows, and salmon alive today?

Gandhi said, “be the change you want to see in the world.” Pearce and the RWAS movement crank this imperative up a notch:

“Be the ultra-intelligent, highly-evolved benevolent steward whom you’d like to see overseeing the well-being and survival of your species.”

The New Narrative of Human Exceptionalism

At their core, the primary message of the Deep Green environmentalism and the transhumanist hedonistic imperative aren’t so different. Both movements say that the narrative of Man as the Mighty Colonizer must now come to an end. Charles Eisenstein and Jason Godesky propose we get there by returning to having Animism as the overarching religious paradigm of global society, and by returning to a more hunter-gatherer-like lifestyle.

Julian Savulescu argues that we nip the problem in its biological bud by using biotechnological intervention to delete the human genes that predispose us to excessive aggression towards “out” groups, excessive resource hoarding, and rape. For reasons I’ve explained in detail elsewhere, I tend to side more with Savulescu. But put aside the means, and you’ll realise that both the Deep Greens and more pacifist-humanitarian transhumanists are both proponents of the same end.

One reason why I tend more towards siding with Savulescu and Pearce is because I think that forsaking technological advancement would be a mistake. If transhumanism is about transcending our biologically-saddled limitations through the application of technology, it follows that the shortcomings of primate-based moral psychology shouldn’t be an exception. As leading primatologist Richard Wrangham points out in his often-cited Demonic Males, our primate ancestors evolved to wage war on hominids from other “out” groups and to be predisposed towards hyper-aggression and selfishness, as a means of surviving on the resource-scarce savannah. And our neurobiological hardwiring hasn’t changed significantly since then. One of Savulescu’s favorite argument points is claiming that had genetic moral editing been available earlier, we’d probably have averted the climate catastrophe altogether. Savulescu sees the climate catastrophe as being a glaring symptom of still-dominant monkey brains’ failures to consider the long-term consequences of short-term consumer capitalist satisfaction.

Furthermore, renouncing the fruits of technology and modern medicine would make us far less effective stewards of the animal world. If we go back to a hunter-gatherer existence, we’ll be renouncing the technology needed to resurrect both long and recently extinct species. Another major goal of the RWAS movement is to use CRISPR gene-editing to help reduce the propensity towards suffering in wild animals, and to engage in fertility regulation. Pearce claims that we might even be able to make natural carnivorism and mating-season-induced violence obsolete using gene-editing in various aggression-prone species. While we’re at it, we could edit the physiological basis for craving meat out of human beings, since our primate ancestors evolved to be omnivorous. Or we could at the very least try to create a future where all of our meat is lab-grown or made from plant-based substitutes.

It’s also worth noting that human beings are the only species on the planet to find out about the ultimate fate of life on Earth. We’ve very, very recently found out that the duration of the planet’s habitability has an expiry date, and that the Sun will eventually turn into a red dwarf and fry the Earth into an inhospitable wasteland. Given that human beings are the only species which has the necessary intelligence to engage in space travel and colonization, the survival of every single non-human species on the planet falls into our hands. The sole hope for the perpetuation of non-human species lies in future humans setting up space colonies in other habitable planets outside our solar system, and taking all of Earth’s animal species with us. Again, this isn’t something we can achieve if we renounce technological progress.

Conclusion

Yuval Noah Harari’s Homo Deus has become a staple read for many in the transhumanist movement. But in the eyes of the world’s animals, we have already become all-powerful gods, who can dole out exploitative cruelty or interventional mercy on a whim. The criticisms of the Deep Green environmentalist movement are increasingly forcing techno-utopians to confront this question; exactly what kind of gods and goddesses will we continue to be to the non-humans of the Earth? If we are going to reconceptualize human exceptionalism from being associated with exceptional human greed and exploitation, to being based on exceptional human wisdom and interventionary benevolence, we need to heed the words of both Savulescu and Eisenstein, and pursue a different human narrative. We’re generally kinder towards women, ethnic minorities, sexual minorities, and the working class than we were three hundred years ago, so there is hope that we’re steadily changing course towards a more altruistic track. If every great moral school of thought has an overarching axiom, the one that defines the hedonistic imperative should be this: “Treat less sentient animals the way you would like the posthuman AI god to treat you and your family.”

Sarah Lim is a fourth-year political science major at the National University of Singapore. She is a proud supporter of the transhumanist movement and aims to do her best to promote transhumanism and progress towards the Singularity.

How Transhumanism Changed My Views on Teleology – Article by Sarah Lim

How Transhumanism Changed My Views on Teleology – Article by Sarah Lim

Sarah Lim


My views on teleology and existentialism have changed considerably since I’ve joined the transhumanist movement. This is my attempt at reconciling my views on humanity’s quest for cosmological purpose with the role of human agency and value creation.

I used to have a rosier view of the universe and nature before I got more involved in transhumanism. I’ve been quite heavily influenced by Brian Swimme’s The Universe Story and Thomas Nagel’s Mind and Cosmos. Swimme invokes cosmological fine-tuning as proof that the universe wants humans to be around and cares about us (to some degree). Even the Earth itself has carefully regulated its temperature to ensure that life could thrive on it, despite the fact that the heat emitted from the Sun has gone up thousands of degrees since the inception of homo sapiens. If you agree with Paul Davies’s interpretation of cosmology, then you could say that the universe is happy to have intelligent creatures around because the universe “wants” to be observed. Davies and Swimme argue that the universe created intelligent life so that it could understand itself through us, via our higher cognitive faculties and our ability to conceptualise mathematics and physics. We are the universe experiencing itself, a la Carl Sagan. Andrei Linde shares this sentiment with Davies.

Some of my readers will disagree with me on this, but I do think that there is some merit in what Davies, Swimme, and Linde claim. Swimme points out that almost all the major traditions in the world have a creation myth which points to the celestial realm as being the home of the creative force. This can’t be a mere coincidence, Swimme argues. It’s almost as if the universe was subconsciously nudging our ancestors towards the greater scientific truth of Big Bang cosmology. Obviously, this isn’t a claim that can be empirically falsified (yet, anyway), but it’s at least food for thought.

As I began to read up more on transhumanist philosophy, however, a nagging objection to this teleological value claim dawned on me.

If the universe did indeed intend to create intelligent animals to observe itself, it didn’t do a very efficient job of it. It wouldn’t be an exaggeration to say it made an exceedingly clumsy, slow, and wasteful job of it.

It has taken 13.8 billion years for the universe to give rise to modern homo sapiens who know how to execute the requisite mathematics and science necessary for the physics of cosmology. And we only exist in a ridiculously minuscule corner of a galaxy, which is itself one out of a hundred billion galaxies in our observable universe. And 90% of the universe is still unobserved.

Even within the confines of the pale blue dot we call home, the process of life hasn’t exactly been a cake walk. Like most kids my age raised on Animal Planet and school field trips to flower parks, I had a relatively rose-tinted view of the natural world. I hadn’t really taken time to think about the nastiest parts of Darwinian natural selection and the last five major mass extinctions that have occurred throughout Earth’s history. I hadn’t thought about how death and starvation were biological inevitabilities only because the forces of natural selection dictated that they had to be. Natural selection itself is an apparently purposeless process. The only goal of a species is to ensure that its genes survive to the next generation, by any means possible. Hence why rape and infanticide are common amongst various species.

Even Swimme himself views suffering in nature as being unavoidable and something that must be gracefully accepted rather than stamped out. “Humans and animals are cruel because the universe that created them is cruel; even galaxies eat each other,” says Swimme. But transhumanist philosophers argue otherwise. David Pearce asserts that the witticism, “suffering is inevitable; misery is a choice,” is just that – a hackneyed saying. It’s a cop-out that encourages intelligent agents to resign themselves to fate instead of finding ways to overcome that suffering. Until I discovered the transhumanist movement, it had never occurred to me that we could one day phase out suffering amongst wild animals through a combination of genetic alteration and deliberate healthcare and food-supply intervention. And I had no idea how much progress had been made in terms of anti-aging research, whole-brain emulation and the development of prosthetics.

To paraphrase Nick Bostrom, “Mother Nature is a crappy parent.”

To my mind, the big question of teleology and humanity’s search for meaning isn’t so much “Does the universe want intelligent apes to observe it?” as much as it is, “Does the universe actually care enough about us to keep us around well into the future?”

Even if the universe does have a purpose for intelligent creatures, it wouldn’t necessarily follow that it has to keep the human species going. Given the sheer number of stars in the observable part of the universe alone, there could be thousands, if not millions, of alien civilisations which are vastly more advanced than we currently are. It would be exponentially more unlikely for us to be the sole sentient species in the universe, than it would for there to be more highly advanced alien civilisations out there. We could be one of millions of sentient species that the universe creates and then disposes of on a cosmic whim.

But does it really matter if the universe cares about us or not?

An analogy I hadn’t really thought of came to my mind while I was waxing lyrical about this topic with Adrian Chia. Adrian said that even if the universe doesn’t give a toss about whether humanity survives or perishes, it shouldn’t stop us from caring about ourselves and seeking an enhanced transhuman future. I told Adrian that that’s exactly the kind of advice I give when I counsel people who grew up in abusive homes with parents who clearly have no interest in their well-being. I’ve counseled people whose parents have tried to throw them out of windows as children, gashed wounds into their backs with knives or beaten them so badly they had the majority of the bones in their legs broken and were forced to crawl around their homes on their forearms. I tell them that even if their parents fail to care for them as a parent should, it shouldn’t stop them from loving or valuing themselves.

So what if the universe doesn’t have any vested interest in taking care of us? We shouldn’t expect it to. Rather, we owe it to ourselves to overcome the biological limitations nature has slapped on us. We no longer pray to gods for a good harvest; we’ve invented modern agriculture and GMO crops. We no longer make sacrifices and hold rituals to beg the gods to heal the sick; that’s what we invented modern medicine for. We no longer sacrifice animals in an attempt to appease the gods so that earthquakes will not devastate our villages; that’s why we’re getting better at developing disaster-evacuation plans and earthquake-proof infrastructure. And hopefully one day, our immortal post-human descendants will look back at us and snicker at how we used to pray that some transcendental deity would answer our prayers for eternal life.

The forces of natural selection and whatever whims the universe may have, have gotten us up to a certain point; but ensuring a better future for ourselves lies squarely on our shoulders now. Plenty of neglectful parents have children without any particularly strong commitment to ensuring those children’s welfare. But I’ve also seen lots of kids from broken homes grow up to become successful doctors, lawyers, and CEOs and go on to lead very fulfilling lives.

This article is dedicated to David Pearce and Andres Gomez Emilsson. Shine on, you crazy diamonds.

Sarah Lim is a fourth-year political science major at the National University of Singapore. She is a proud supporter of the transhumanist movement and aims to do her best to promote transhumanism and progress towards the Singularity.