More on Entrepreneurship/Creators

DC Palter
2 years ago
Is Venture Capital a Good Fit for Your Startup?
5 VC investment criteria
I reviewed 200 startup business concepts last week. Brainache.
The enterprises sold various goods and services. The concepts were achingly similar: give us money, we'll produce a product, then get more to expand. No different from daily plans and pitches.
Most of those 200 plans sounded plausible. But 10% looked venture-worthy. 90% of startups need alternatives to venture finance.
With the success of VC-backed businesses and the growth of venture funds, a common misperception is that investors would fund any decent company idea. Finding investors that believe in the firm and founders is the key to funding.
Incorrect. Venture capital needs investing in certain enterprises. If your startup doesn't match the model, as most early-stage startups don't, you can revise your business plan or locate another source of capital.
Before spending six months pitching angels and VCs, make sure your startup fits these criteria.
Likely to generate $100 million in sales
First, I check the income predictions in a pitch deck. If it doesn't display $100M, don't bother.
The math doesn't work for venture financing in smaller businesses.
Say a fund invests $1 million in a startup valued at $5 million that is later acquired for $20 million. That's a win everyone should celebrate. Most VCs don't care.
Consider a $100M fund. The fund must reach $360M in 7 years with a 20% return. Only 20-30 investments are possible. 90% of the investments will fail, hence the 23 winners must return $100M-$200M apiece. $15M isn't worth the work.
Angel investors and tiny funds use the same ideas as venture funds, but their smaller scale affects the calculations. If a company can support its growth through exit on less than $2M in angel financing, it must have $25M in revenues before large companies will consider acquiring it.
Aiming for Hypergrowth
A startup's size isn't enough. It must expand fast.
Developing a great business takes time. Complex technology must be constructed and tested, a nationwide expansion must be built, or production procedures must go from lab to pilot to factories. These can be enormous, world-changing corporations, but venture investment is difficult.
The normal 10-year venture fund life. Investments are made during first 3–4 years.. 610 years pass between investment and fund dissolution. Funds need their investments to exit within 5 years, 7 at the most, therefore add a safety margin.
Longer exit times reduce ROI. A 2-fold return in a year is excellent. Loss at 2x in 7 years.
Lastly, VCs must prove success to raise their next capital. The 2nd fund is raised from 1st fund portfolio increases. Third fund is raised using 1st fund's cash return. Fund managers must raise new money quickly to keep their jobs.
Branding or technology that is protected
No big firm will buy a startup at a high price if they can produce a competing product for less. Their development teams, consumer base, and sales and marketing channels are large. Who needs you?
Patents, specialist knowledge, or brand name are the only answers. The acquirer buys this, not the thing.
I've heard of several promising startups. It's not a decent investment if there's no exit strategy.
A company that installs EV charging stations in apartments and shopping areas is an example. It's profitable, repeatable, and big. A terrific company. Not a startup.
This building company's operations aren't secret. No technology to protect, no special information competitors can't figure out, no go-to brand name. Despite the immense possibilities, a large construction company would be better off starting their own.
Most venture businesses build products, not services. Services can be profitable but hard to safeguard.
Probable purchase at high multiple
Once a software business proves its value, acquiring it is easy. Pharma and medtech firms have given up on their own research and instead acquire startups after regulatory permission. Many startups, especially in specialized areas, have this weakness.
That doesn't mean any lucrative $25M-plus business won't be acquired. In many businesses, the venture model requires a high exit premium.
A startup invents a new glue. 3M, BASF, Henkel, and others may buy them. Adding more adhesive to their catalogs won't boost commerce. They won't compete to buy the business. They'll only buy a startup at a profitable price. The acquisition price represents a moderate EBITDA multiple.
The company's $100M revenue presumably yields $10m in profits (assuming they’ve reached profitability at all). A $30M-$50M transaction is likely. Not terrible, but not what venture investors want after investing $25M to create a plant and develop the business.
Private equity buys profitable companies for a moderate profit multiple. It's a good exit for entrepreneurs, but not for investors seeking 10x or more what PE firms pay. If a startup offers private equity as an exit, the conversation is over.
Constructed for purchase
The startup wants a high-multiple exit. Unless the company targets $1B in revenue and does an IPO, exit means acquisition.
If they're constructing the business for acquisition or themselves, founders must decide.
If you want an indefinitely-running business, I applaud you. We need more long-term founders. Most successful organizations are founded around consumer demands, not venture capital's urge to grow fast and exit. Not venture funding.
if you don't match the venture model, what to do
VC funds moonshots. The 10% that succeed are extraordinary. Not every firm is a rocketship, and launching the wrong startup into space, even with money, will explode.
But just because your startup won't make $100M in 5 years doesn't mean it's a bad business. Most successful companies don't follow this model. It's not venture capital-friendly.
Although venture capital gets the most attention due to a few spectacular triumphs (and disasters), it's not the only or even most typical option to fund a firm.
Other ways to support your startup:
Personal and family resources, such as credit cards, second mortgages, and lines of credit
bootstrapping off of sales
government funding and honors
Private equity & project financing
collaborating with a big business
Including a business partner
Before pitching angels and VCs, be sure your startup qualifies. If so, include them in your pitch.

Alex Mathers
2 years ago
How to Produce Enough for People to Not Neglect You
Internet's fantastic, right?
We've never had a better way to share our creativity.
I can now draw on my iPad and tweet or Instagram it to thousands. I may get some likes.
With such a great, free tool, you're not alone.
Millions more bright-eyed artists are sharing their work online.
The issue is getting innovative work noticed, not sharing it.
In a world where creators want attention, attention is valuable.
We build for attention.
Attention helps us establish a following, make money, get notoriety, and make a difference.
Most of us require attention to stay sane while creating wonderful things.
I know how hard it is to work hard and receive little views.
How do we receive more attention, more often, in a sea of talent?
Advertising and celebrity endorsements are options. These may work temporarily.
To attract true, organic, and long-term attention, you must create in high quality, high volume, and consistency.
Adapting Steve Martin's Be so amazing, they can't ignore you (with a mention to Dan Norris in his great book Create or Hate for the reminder)
Create a lot.
Eventually, your effort will gain traction.
Traction shows your work's influence.
Traction is when your product sells more. Traction is exponential user growth. Your work is shared more.
No matter how good your work is, it will always have minimal impact on the world.
Your work can eventually dent or puncture. Daily, people work to dent.
To achieve this tipping point, you must consistently produce exceptional work.
Expect traction after hundreds of outputs.
Dilbert creator Scott Adams says repetition persuades. If you don't stop, you can persuade practically anyone with anything.
Volume lends believability. So make more.
I worked as an illustrator for at least a year and a half without any recognition. After 150 illustrations on iStockphoto, my work started selling.
With 350 illustrations on iStock, I started getting decent client commissions.
Producing often will improve your craft and draw attention.
It's the only way to succeed. More creation means better results and greater attention.
Austin Kleon says you can improve your skill in relative anonymity before you become famous. Before obtaining traction, generate a lot and become excellent.
Most artists, even excellent ones, don't create consistently enough to get traction.
It may hurt. For makers who don't love and flow with their work, it's extremely difficult.
Your work must bring you to life.
To generate so much that others can't ignore you, decide what you'll accomplish every day (or most days).
Commit and be patient.
Prepare for zero-traction.
Anticipating this will help you persevere and create.
My online guru Grant Cardone says: Anything worth doing is worth doing every day.
Do.

Sanjay Priyadarshi
2 years ago
Using Ruby code, a programmer created a $48,000,000,000 product that Elon Musk admired.
Unexpected Success
Shopify CEO and co-founder Tobias Lutke. Shopify is worth $48 billion.
World-renowned entrepreneur Tobi
Tobi never expected his first online snowboard business to become a multimillion-dollar software corporation.
Tobi founded Shopify to establish a 20-person company.
The publicly traded corporation employs over 10,000 people.
Here's Tobi Lutke's incredible story.
Elon Musk tweeted his admiration for the Shopify creator.
30-October-2019.
Musk praised Shopify founder Tobi Lutke on Twitter.
Happened:
Explore this programmer's journey.
What difficulties did Tobi experience as a young child?
Germany raised Tobi.
Tobi's parents realized he was smart but had trouble learning as a toddler.
Tobi was learning disabled.
Tobi struggled with school tests.
Tobi's learning impairments were undiagnosed.
Tobi struggled to read as a dyslexic.
Tobi also found school boring.
Germany's curriculum didn't inspire Tobi's curiosity.
“The curriculum in Germany was taught like here are all the solutions you might find useful later in life, spending very little time talking about the problem…If I don’t understand the problem I’m trying to solve, it’s very hard for me to learn about a solution to a problem.”
Studying computer programming
After tenth grade, Tobi decided school wasn't for him and joined a German apprenticeship program.
This curriculum taught Tobi software engineering.
He was an apprentice in a small Siemens subsidiary team.
Tobi worked with rebellious Siemens employees.
Team members impressed Tobi.
Tobi joined the team for this reason.
Tobi was pleased to get paid to write programming all day.
His life could not have been better.
Devoted to snowboarding
Tobi loved snowboarding.
He drove 5 hours to ski at his folks' house.
His friends traveled to the US to snowboard when he was older.
However, the cheap dollar conversion rate led them to Canada.
2000.
Tobi originally decided to snowboard instead than ski.
Snowboarding captivated him in Canada.
On the trip to Canada, Tobi encounters his wife.
Tobi meets his wife Fiona McKean on his first Canadian ski trip.
They maintained in touch after the trip.
Fiona moved to Germany after graduating.
Tobi was a startup coder.
Fiona found work in Germany.
Her work included editing, writing, and academics.
“We lived together for 10 months and then she told me that she need to go back for the master's program.”
With Fiona, Tobi immigrated to Canada.
Fiona invites Tobi.
Tobi agreed to move to Canada.
Programming helped Tobi move in with his girlfriend.
Tobi was an excellent programmer, therefore what he did in Germany could be done anywhere.
He worked remotely for his German employer in Canada.
Tobi struggled with remote work.
Due to poor communication.
No slack, so he used email.
Programmers had trouble emailing.
Tobi's startup was developing a browser.
After the dot-com crash, individuals left that startup.
It ended.
Tobi didn't intend to work for any major corporations.
Tobi left his startup.
He believed he had important skills for any huge corporation.
He refused to join a huge corporation.
Because of Siemens.
Tobi learned to write professional code and about himself while working at Siemens in Germany.
Siemens culture was odd.
Employees were distrustful.
Siemens' rigorous dress code implies that the corporation doesn't trust employees' attire.
It wasn't Tobi's place.
“There was so much bad with it that it just felt wrong…20-year-old Tobi would not have a career there.”
Focused only on snowboarding
Tobi lived in Ottawa with his girlfriend.
Canada is frigid in winter.
Ottawa's winters last.
Almost half a year.
Tobi wanted to do something worthwhile now.
So he snowboarded.
Tobi began snowboarding seriously.
He sought every snowboarding knowledge.
He researched the greatest snowboarding gear first.
He created big spreadsheets for snowboard-making technologies.
Tobi grew interested in selling snowboards while researching.
He intended to sell snowboards online.
He had no choice but to start his own company.
A small local company offered Tobi a job.
Interested.
He must sign papers to join the local company.
He needed a work permit when he signed the documents.
Tobi had no work permit.
He was allowed to stay in Canada while applying for permanent residency.
“I wasn’t illegal in the country, but my state didn’t give me a work permit. I talked to a lawyer and he told me it’s going to take a while until I get a permanent residency.”
Tobi's lawyer told him he cannot get a work visa without permanent residence.
His lawyer said something else intriguing.
Tobis lawyer advised him to start a business.
Tobi declined this local company's job offer because of this.
Tobi considered opening an internet store with his technical skills.
He sold snowboards online.
“I was thinking of setting up an online store software because I figured that would exist and use it as a way to sell snowboards…make money while snowboarding and hopefully have a good life.”
What brought Tobi and his co-founder together, and how did he support Tobi?
Tobi lived with his girlfriend's parents.
In Ottawa, Tobi encounters Scott Lake.
Scott was Tobis girlfriend's family friend and worked for Tobi's future employer.
Scott and Tobi snowboarded.
Tobi pitched Scott his snowboard sales software idea.
Scott liked the idea.
They planned a business together.
“I was looking after the technology and Scott was dealing with the business side…It was Scott who ended up developing relationships with vendors and doing all the business set-up.”
Issues they ran into when attempting to launch their business online
Neither could afford a long-term lease.
That prompted their online business idea.
They would open a store.
Tobi anticipated opening an internet store in a week.
Tobi seeks open-source software.
Most existing software was pricey.
Tobi and Scott couldn't afford pricey software.
“In 2004, I was sitting in front of my computer absolutely stunned realising that we hadn’t figured out how to create software for online stores.”
They required software to:
to upload snowboard images to the website.
people to look up the types of snowboards that were offered on the website. There must be a search feature in the software.
Online users transmit payments, and the merchant must receive them.
notifying vendors of the recently received order.
No online selling software existed at the time.
Online credit card payments were difficult.
How did they advance the software while keeping expenses down?
Tobi and Scott needed money to start selling snowboards.
Tobi and Scott funded their firm with savings.
“We both put money into the company…I think the capital we had was around CAD 20,000(Canadian Dollars).”
Despite investing their savings.
They minimized costs.
They tried to conserve.
No office rental.
They worked in several coffee shops.
Tobi lived rent-free at his girlfriend's parents.
He installed software in coffee cafes.
How were the software issues handled?
Tobi found no online snowboard sales software.
Two choices remained:
Change your mind and try something else.
Use his programming expertise to produce something that will aid in the expansion of this company.
Tobi knew he was the sole programmer working on such a project from the start.
“I had this realisation that I’m going to be the only programmer who has ever worked on this, so I don’t have to choose something that lots of people know. I can choose just the best tool for the job…There is been this programming language called Ruby which I just absolutely loved ”
Ruby was open-source and only had Japanese documentation.
Latin is the source code.
Tobi used Ruby twice.
He assumed he could pick the tool this time.
Why not build with Ruby?
How did they find their first time operating a business?
Tobi writes applications in Ruby.
He wrote the initial software version in 2.5 months.
Tobi and Scott founded Snowdevil to sell snowboards.
Tobi coded for 16 hours a day.
His lifestyle was unhealthy.
He enjoyed pizza and coke.
“I would never recommend this to anyone, but at the time there was nothing more interesting to me in the world.”
Their initial purchase and encounter with it
Tobi worked in cafes then.
“I was working in a coffee shop at this time and I remember everything about that day…At some time, while I was writing the software, I had to type the email that the software would send to tell me about the order.”
Tobi recalls everything.
He checked the order on his laptop at the coffee shop.
Pennsylvanian ordered snowboard.
Tobi walked home and called Scott. Tobi told Scott their first order.
They loved the order.
How were people made aware about Snowdevil?
2004 was very different.
Tobi and Scott attempted simple website advertising.
Google AdWords was new.
Ad clicks cost 20 cents.
Online snowboard stores were scarce at the time.
Google ads propelled the snowdevil brand.
Snowdevil prospered.
They swiftly recouped their original investment in the snowboard business because to its high profit margin.
Tobi and Scott struggled with inventories.
“Snowboards had really good profit margins…Our biggest problem was keeping inventory and getting it back…We were out of stock all the time.”
Selling snowboards returned their investment and saved them money.
They did not appoint a business manager.
They accomplished everything alone.
Sales dipped in the spring, but something magical happened.
Spring sales plummeted.
They considered stocking different boards.
They naturally wanted to add boards and grow the business.
However, magic occurred.
Tobi coded and improved software while running Snowdevil.
He modified software constantly. He wanted speedier software.
He experimented to make the software more resilient.
Tobi received emails requesting the Snowdevil license.
They intended to create something similar.
“I didn’t stop programming, I was just like Ok now let me try things, let me make it faster and try different approaches…Increasingly I got people sending me emails and asking me If I would like to licence snowdevil to them. People wanted to start something similar.”
Software or skateboards, your choice
Scott and Tobi had to choose a hobby in 2005.
They might sell alternative boards or use software.
The software was a no-brainer from demand.
Daniel Weinand is invited to join Tobi's business.
Tobis German best friend is Daniel.
Tobi and Scott chose to use the software.
Tobi and Scott kept the software service.
Tobi called Daniel to invite him to Canada to collaborate.
Scott and Tobi had quit snowboarding until then.
How was Shopify launched, and whence did the name come from?
The three chose Shopify.
Named from two words.
First:
Shop
Final part:
Simplify
Shopify
Shopify's crew has always had one goal:
creating software that would make it simple and easy for people to launch online storefronts.
Launched Shopify after raising money for the first time.
Shopify began fundraising in 2005.
First, they borrowed from family and friends.
They needed roughly $200k to run the company efficiently.
$200k was a lot then.
When questioned why they require so much money. Tobi told them to trust him with their goals. The team raised seed money from family and friends.
Shopify.com has a landing page. A demo of their goal was on the landing page.
In 2006, Shopify had about 4,000 emails.
Shopify rented an Ottawa office.
“We sent a blast of emails…Some people signed up just to try it out, which was exciting.”
How things developed after Scott left the company
Shopify co-founder Scott Lake left in 2008.
Scott was CEO.
“He(Scott) realized at some point that where the software industry was going, most of the people who were the CEOs were actually the highly technical person on the founding team.”
Scott leaving the company worried Tobi.
Tobis worried about finding a new CEO.
To Tobi:
A great VC will have the network to identify the perfect CEO for your firm.
Tobi started visiting Silicon Valley to meet with venture capitalists to recruit a CEO.
Initially visiting Silicon Valley
Tobi came to Silicon Valley to start a 20-person company.
This company creates eCommerce store software.
Tobi never wanted a big corporation. He desired a fulfilling existence.
“I stayed in a hostel in the Bay Area. I had one roommate who was also a computer programmer. I bought a bicycle on Craiglist. I was there for a week, but ended up staying two and a half weeks.”
Tobi arrived unprepared.
When venture capitalists asked him business questions.
He answered few queries.
Tobi didn't comprehend VC meetings' terminology.
He wrote the terms down and looked them up.
Some were fascinated after he couldn't answer all these queries.
“I ended up getting the kind of term sheets people dream about…All the offers were conditional on moving our company to Silicon Valley.”
Canada received Tobi.
He wanted to consult his team before deciding. Shopify had five employees at the time.
2008.
A global recession greeted Tobi in Canada. The recession hurt the market.
His term sheets were useless.
The economic downturn in the world provided Shopify with a fantastic opportunity.
The global recession caused significant job losses.
Fired employees had several ideas.
They wanted online stores.
Entrepreneurship was desired. They wanted to quit work.
People took risks and tried new things during the global slump.
Shopify subscribers skyrocketed during the recession.
“In 2009, the company reached neutral cash flow for the first time…We were in a position to think about long-term investments, such as infrastructure projects.”
Then, Tobi Lutke became CEO.
How did Tobi perform as the company's CEO?
“I wasn’t good. My team was very patient with me, but I had a lot to learn…It’s a very subtle job.”
2009–2010.
Tobi limited the company's potential.
He deliberately restrained company growth.
Tobi had one costly problem:
Whether Shopify is a venture or a lifestyle business.
The company's annual revenue approached $1 million.
Tobi battled with the firm and himself despite good revenue.
His wife was supportive, but the responsibility was crushing him.
“It’s a crushing responsibility…People had families and kids…I just couldn’t believe what was going on…My father-in-law gave me money to cover the payroll and it was his life-saving.”
Throughout this trip, everyone supported Tobi.
They believed it.
$7 million in donations received
Tobi couldn't decide if this was a lifestyle or a business.
Shopify struggled with marketing then.
Later, Tobi tried 5 marketing methods.
He told himself that if any marketing method greatly increased their growth, he would call it a venture, otherwise a lifestyle.
The Shopify crew brainstormed and voted on marketing concepts.
Tested.
“Every single idea worked…We did Adwords, published a book on the concept, sponsored a podcast and all the ones we tracked worked.”
To Silicon Valley once more
Shopify marketing concepts worked once.
Tobi returned to Silicon Valley to pitch investors.
He raised $7 million, valuing Shopify at $25 million.
All investors had board seats.
“I find it very helpful…I always had a fantastic relationship with everyone who’s invested in my company…I told them straight that I am not going to pretend I know things, I want you to help me.”
Tobi developed skills via running Shopify.
Shopify had 20 employees.
Leaving his wife's parents' home
Tobi left his wife's parents in 2014.
Tobi had a child.
Shopify has 80,000 customers and 300 staff in 2013.
Public offering in 2015
Shopify investors went public in 2015.
Shopify powers 4.1 million e-Commerce sites.
Shopify stores are 65% US-based.
It is currently valued at $48 billion.
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Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.

Bob Service
3 years ago
Did volcanic 'glasses' play a role in igniting early life?
Quenched lava may have aided in the formation of long RNA strands required by primitive life.
It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.
Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.
The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.
Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.
However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.
Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.
He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."
Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.
The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.
Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."
Scott Hickmann
3 years ago Draft
This is a draft
My wallpape
