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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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Hardly a day goes by without a research study or article published talking sh*t—or more precisely, talking about the gut microbiome. When it comes to cutting-edge innovations in medicine, all signs point to the microbiome. Maybe we should have listened to Hippocrates: “All disease begins in the gut.”
Your microbiome is mostly located in your gut and contains trillions of little guys and gals called microbes. If you want to optimize your health, biohack your body, make progress against chronic disease, or know which foods are right for you—almost all of this information can be found in your microbiome.
My company, Viome, offers technology to measure your microscopic organisms and their behavior at a molecular level. Think of it as the Instagram of your inner world. A snapshot of what’s happening inside your body. New research about the microbiome is changing our understanding of who we are as humans and how the human body functions.
It turns out the microbiome may be mission control for your body and mind. Your healthy microbiome is part best friend, part power converter, part engine, and part pharmacist. At Viome, we’re working to analyze these microbial functions and recommend a list of personalized food and supplements to keep these internal complex machines in a finely tuned balance.
We now have more information than ever before about what your microbiome is doing, and it’s going to help you and the rest of the world do a whole lot better. The new insights emerging from microbiome research are changing our perception of what keeps us healthy and what makes us sick. This new understanding of the microbiome activities may put an end to conflicting food advice and make fad diets a thing of the past.
What are these new insights showing us? The information is nothing short of mind-blowing. The value of your poop just got an upgrade.
Here are some of the amazing things we’ve learned from our work at Viome.
1. Was Popeye wrong? Why “health food” isn’t necessarily healthy.
Each week there is a new fad diet released, discussed, and followed. The newest “research” shows that this is now the superfood to eat for everyone. But, too often, the fad diet is just a regurgitation of what worked for one person and shouldn’t be followed by everyone else.
For example, we’ve been told to eat our greens and that greens and nuts are “anti-inflammatory,” but this is actually not always true. Spinach, bran, rhubarb, beets, nuts, and nut butters all contain oxalate. We now know that oxalate-containing food can be harmful, unless you have the microbes present that can metabolize it into a non-harmful substance.
30% of Viome customers do not have the microbes to metabolize oxalates properly. In other words, “healthy foods” like spinach are actually not healthy for these people.
Looks like not everyone should follow Popeye’s food plan.
2. Aren’t foods containing “antioxidants” always good for everyone?
Just like oxalates, polyphenols in foods are usually considered very healthy, but unless you have microbes that utilize specific polyphenols, you may not get full benefit from them. One example is a substance found in these foods called ellagic acid. We can detect if your microbiome is metabolizing ellagic acid and converting it into urolithin A. It is only the urolithin A that has anti-inflammatory and antioxidant effects. Without the microbes to do this conversion you will not benefit from the ellagic acid in foods.
Examples: Walnuts, raspberries, pomegranate, blackberries, pecans, and cranberries all contain ellagic acid.
We have analyzed tens of thousands of people, and only about 50% of the people actually benefit from eating more foods containing ellagic acid.
3. You’re probably eating too much protein (and it may be causing inflammation).
When you think high-protein diet, you think paleo, keto, and high-performance diets.
Protein is considered good for you. It helps build muscle and provide energy—but if you eat too much, it can cause inflammation and decrease longevity.
We can analyze the activity of your microbiome to determine if you are eating too much protein that feeds protein-fermenting bacteria like Alistipes putredinis and Tannerella forsythia, and if these organisms are producing harmful substances such as ammonia, hydrogen sulfide, p-cresol, or putrescine. These substances can damage your gut lining and lead to things like leaky gut.
4. Something’s fishy. Are “healthy foods” causing heart disease?
Choline in certain foods can get converted by bacteria into a substance called trimethylamine (TMA) that is associated with heart disease when it gets absorbed into your body and converted to TMAO. However, TMA conversion doesn’t happen in individuals without these types of bacteria in their microbiome.
We can see the TMA production pathways and many of the gammaproteobacteria that do this conversion.
What foods contain choline? Liver, salmon, chickpeas, split peas, eggs, navy beans, peanuts, and many others.
Before you decide to go full-on pescatarian or paleo, you may want to check if your microbiome is producing TMA with that salmon or steak.
5. Hold up, Iron Man. We can see inflammation from too much iron.
Minerals like iron in your food can, in certain inflammatory microbial environments, promote growth of pathogens like Esherichia, Shigella, and Salmonella.
Maybe it wasn’t just that raw chicken that gave you food poisoning, but your toxic microbiome that made you sick.
On the other hand, when you don’t have enough iron, you could become anemic leading to weakness and shortness of breath.
So, just like Iron Man, it’s about finding your balance so that you can fly.
6. Are you anxious or stressed? Your poop will tell you.
Our gut and brain are connected via the vagus nerve. A large majority of neurotransmitters are either produced or consumed by our microbiome. In fact, some 90% of all serotonin (a feel-good neurotransmitter) is produced by your gut microbiome and not by your brain.
When you have a toxic microbiome that’s producing a large amount of toxins like hydrogen sulfide, the lining of your gut starts to deteriorate into what’s known as leaky gut. Think of leaky gut as your gut not having healthy borders or boundaries. And when this happens, all kinds of disease can emerge. When the barrier of the gut breaks down, it starts a chain reaction causing low-grade chronic inflammation—which has been identified as a potential source of depression and higher levels of anxiety, in addition to many other chronic diseases.
We’re not saying you shouldn’t meditate, but if you want to get the most out of your meditation and really reduce your stress levels, make sure you are eating the right food that promotes a healthy microbiome.
7. Your microbiome is better than Red Bull.
If you want more energy, get your microbiome back into balance.
No you don’t need three pots of coffee to keep you going, you just need a balanced microbiome.
Your microbiome is responsible for calorie extraction, or creating energy, through pathways such as the Tricarboxylic acid cycle. Our bodies depend on the energy that our microbiome produces.
How much energy we get from our food is dependent on how efficient our microbiome is at converting the food into energy. High-performing microbiomes are excellent at converting food into energy. This is great when you are an athlete and need the extra energy, but if you don’t use up the energy it may be the source of some of those unwanted pounds.
If the microbes can’t or won’t metabolize the glucose (sugar) that you eat, it will be stored as fat. If the microbes are extracting too many calories from your food or producing lipopolysaccharides (LPS) and causing metabolic endotoxemia leading to activation of toll-like receptors and insulin resistance you may end up storing what you eat as fat.
Think of your microbiome as Doc Brown’s car from the future—it can take pretty much anything and turn it into fuel if it’s strong and resilient enough.
8. We can see your joint pain in your poop.
Got joint pain? Your microbiome can tell you why.
Lipopolysaccharide (LPS) is a key pro-inflammatory molecule made by some of your microbes. If your microbes are making too much LPS, it can wreak havoc on your immune system by putting it into overdrive. When your immune system goes on the warpath there is often collateral damage to your joints and other body parts.
Perhaps balancing your microbiome is a better solution than reaching for the glucosamine. Think of your microbiome as the top general of your immune army. It puts your immune system through basic training and determines when it goes to war.
Ideally, your immune system wins the quick battle and gets some rest, but sometimes if your microbiome keeps it on constant high alert it becomes a long, drawn-out war resulting in chronic inflammation and chronic diseases.
Are you really “getting older” or is your microbiome just making you “feel” older because it keeps giving warnings to your immune system ultimately leading to chronic pain?
Before you throw in the towel on your favorite activities, check your microbiome. And, if you have anything with “itis” in it, it’s possible that when you balance your microbiome the inflammation from your “itis” will be reduced.
9. Your gut is doing the talking for your mouth.
When you have low stomach acid, your mouth bacteria makes it down to your GI tract.
Stomach acid is there to protect you from the bacteria in your mouth and the parasites and fungi that are in your food. If you don’t have enough of it, the bacteria in your mouth will invade your gut. This invasion is associated with and a risk factor for autoimmune disease and inflammation in the gut.
We are learning that low stomach acid is perhaps one of the major causes of chronic disease. This stomach acid is essential to kill mouth bacteria and help us digest our food.
What kinds of things cause low stomach acid? Stress and antacids like Nexium, Zantac, and Prilosec.
10. Carbs can be protein precursors.
Rejoice! Perhaps carbs aren’t as bad as we thought (as long as your microbiome is up to the task). We can see if some of the starches you eat can be made into amino acids by the microbiome.
Our microbiome makes 20% of our branched-chain amino acids (BCAAs) for us, and it will adapt to make these vital BCAAs for us in almost any way it can.
Essentially, your microbiome is hooking up carbons and hydrogens into different formulations of BCAAs, depending on what you feed it. The microbiome is excellent at adapting and pivoting based on the food you feed it and the environment that it’s in.
So, good news: Carbs are protein precursors, as long as you have the right microbiome.
Stop Talking Sh*t Now
Your microbiome is a world class entrepreneur that can take low-grade sources of food and turn them into valuable and useable energy.
You have a best friend and confidant within you that is working wonders to make sure you have energy and that all of your needs are met.
And, just like a best friend, if you take great care of your microbiome, it will take great care of you.
Given the research emerging daily about the microbiome and its importance on your quality of life, prioritizing the health of your microbiome is essential.
When you have a healthy microbiome, you’ll have a healthy life.
It’s now clear that some of the greatest insights for your health will come from your poop.
It’s time to stop talking sh*t and get your sh*t together. Your life may depend on it.
Viome can help you identify what your microbiome is actually doing. The combination of Viome’s metatranscriptomic technology and cutting-edge artificial intelligence is paving a brand new path forward for microbiome health.
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In 2017, artificial intelligence attracted $12 billion of VC investment. We are only beginning to discover the usefulness of AI applications. Amazon recently unveiled a brick-and-mortar grocery store that has successfully supplanted cashiers and checkout lines with computer vision, sensors, and deep learning. Between the investment, the press coverage, and the dramatic innovation, “AI” has become a hot buzzword. But does it even exist yet?
At the World Economic Forum Dr. Kai-Fu Lee, a Taiwanese venture capitalist and the founding president of Google China, remarked, “I think it’s tempting for every entrepreneur to package his or her company as an AI company, and it’s tempting for every VC to want to say ‘I’m an AI investor.’” He then observed that some of these AI bubbles could burst by the end of 2018, referring specifically to “the startups that made up a story that isn’t fulfillable, and fooled VCs into investing because they don’t know better.”
However, Dr. Lee firmly believes AI will continue to progress and will take many jobs away from workers. So, what is the difference between legitimate AI, with all of its pros and cons, and a made-up story?
If you parse through just a few stories that are allegedly about AI, you’ll quickly discover significant variation in how people define it, with a blurred line between emulated intelligence and machine learning applications.
I spoke to experts in the field of AI to try to find consensus, but the very question opens up more questions. For instance, when is it important to be accurate to a term’s original definition, and when does that commitment to accuracy amount to the splitting of hairs? It isn’t obvious, and hype is oftentimes the enemy of nuance. Additionally, there is now a vested interest in that hype—$12 billion, to be precise.
This conversation is also relevant because world-renowned thought leaders have been publicly debating the dangers posed by AI. Facebook CEO Mark Zuckerberg suggested that naysayers who attempt to “drum up these doomsday scenarios” are being negative and irresponsible. On Twitter, business magnate and OpenAI co-founder Elon Musk countered that Zuckerberg’s understanding of the subject is limited. In February, Elon Musk engaged again in a similar exchange with Harvard professor Steven Pinker. Musk tweeted that Pinker doesn’t understand the difference between functional/narrow AI and general AI.
Given the fears surrounding this technology, it’s important for the public to clearly understand the distinctions between different levels of AI so that they can realistically assess the potential threats and benefits.
As Smart As a Human?
Erik Cambria, an expert in the field of natural language processing, told me, “Nobody is doing AI today and everybody is saying that they do AI because it’s a cool and sexy buzzword. It was the same with ‘big data’ a few years ago.”
Cambria mentioned that AI, as a term, originally referenced the emulation of human intelligence. “And there is nothing today that is even barely as intelligent as the most stupid human being on Earth. So, in a strict sense, no one is doing AI yet, for the simple fact that we don’t know how the human brain works,” he said.
He added that the term “AI” is often used in reference to powerful tools for data classification. These tools are impressive, but they’re on a totally different spectrum than human cognition. Additionally, Cambria has noticed people claiming that neural networks are part of the new wave of AI. This is bizarre to him because that technology already existed fifty years ago.
However, technologists no longer need to perform the feature extraction by themselves. They also have access to greater computing power. All of these advancements are welcomed, but it is perhaps dishonest to suggest that machines have emulated the intricacies of our cognitive processes.
“Companies are just looking at tricks to create a behavior that looks like intelligence but that is not real intelligence, it’s just a mirror of intelligence. These are expert systems that are maybe very good in a specific domain, but very stupid in other domains,” he said.
This mimicry of intelligence has inspired the public imagination. Domain-specific systems have delivered value in a wide range of industries. But those benefits have not lifted the cloud of confusion.
Assisted, Augmented, or Autonomous
When it comes to matters of scientific integrity, the issue of accurate definitions isn’t a peripheral matter. In a 1974 commencement address at the California Institute of Technology, Richard Feynman famously said, “The first principle is that you must not fool yourself—and you are the easiest person to fool.” In that same speech, Feynman also said, “You should not fool the layman when you’re talking as a scientist.” He opined that scientists should bend over backwards to show how they could be wrong. “If you’re representing yourself as a scientist, then you should explain to the layman what you’re doing—and if they don’t want to support you under those circumstances, then that’s their decision.”
In the case of AI, this might mean that professional scientists have an obligation to clearly state that they are developing extremely powerful, controversial, profitable, and even dangerous tools, which do not constitute intelligence in any familiar or comprehensive sense.
The term “AI” may have become overhyped and confused, but there are already some efforts underway to provide clarity. A recent PwC report drew a distinction between “assisted intelligence,” “augmented intelligence,” and “autonomous intelligence.” Assisted intelligence is demonstrated by the GPS navigation programs prevalent in cars today. Augmented intelligence “enables people and organizations to do things they couldn’t otherwise do.” And autonomous intelligence “establishes machines that act on their own,” such as autonomous vehicles.
Roman Yampolskiy is an AI safety researcher who wrote the book “Artificial Superintelligence: A Futuristic Approach.” I asked him whether the broad and differing meanings might present difficulties for legislators attempting to regulate AI.
Yampolskiy explained, “Intelligence (artificial or natural) comes on a continuum and so do potential problems with such technology. We typically refer to AI which one day will have the full spectrum of human capabilities as artificial general intelligence (AGI) to avoid some confusion. Beyond that point it becomes superintelligence. What we have today and what is frequently used in business is narrow AI. Regulating anything is hard, technology is no exception. The problem is not with terminology but with complexity of such systems even at the current level.”
When asked if people should fear AI systems, Dr. Yampolskiy commented, “Since capability comes on a continuum, so do problems associated with each level of capability.” He mentioned that accidents are already reported with AI-enabled products, and as the technology advances further, the impact could spread beyond privacy concerns or technological unemployment. These concerns about the real-world effects of AI will likely take precedence over dictionary-minded quibbles. However, the issue is also about honesty versus deception.
Is This Buzzword All Buzzed Out?
Finally, I directed my questions towards a company that is actively marketing an “AI Virtual Assistant.” Carl Landers, the CMO at Conversica, acknowledged that there are a multitude of explanations for what AI is and isn’t.
He said, “My definition of AI is technology innovation that helps solve a business problem. I’m really not interested in talking about the theoretical ‘can we get machines to think like humans?’ It’s a nice conversation, but I’m trying to solve a practical business problem.”
I asked him if AI is a buzzword that inspires publicity and attracts clients. According to Landers, this was certainly true three years ago, but those effects have already started to wane. Many companies now claim to have AI in their products, so it’s less of a differentiator. However, there is still a specific intention behind the word. Landers hopes to convey that previously impossible things are now possible. “There’s something new here that you haven’t seen before, that you haven’t heard of before,” he said.
According to Brian Decker, founder of Encom Lab, machine learning algorithms only work to satisfy their preexisting programming, not out of an interior drive for better understanding. Therefore, he views AI as an entirely semantic argument.
Decker stated, “A marketing exec will claim a photodiode controlled porch light has AI because it ‘knows when it is dark outside,’ while a good hardware engineer will point out that not one bit in a register in the entire history of computing has ever changed unless directed to do so according to the logic of preexisting programming.”
Although it’s important for everyone to be on the same page regarding specifics and underlying meaning, AI-powered products are already powering past these debates by creating immediate value for humans. And ultimately, humans care more about value than they do about semantic distinctions. In an interview with Quartz, Kai-Fu Lee revealed that algorithmic trading systems have already given him an 8X return over his private banking investments. “I don’t trade with humans anymore,” he said.
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