Theres a segment of art fans who regularly demand the Mona Lisa be cleaned and restored. Its a touchy debate. If the painting were to be restored, it might better represent what Leonardo da Vinci intended as he created it. But if so much as a line of her smile was damaged during such attempts, a real possibility when dealing with a 500-year-old painting well, art fans dont like to consider the loss of even a single stroke of paint on that famous face.

There are similar debates throughout the art world as experts consider what was, what is and what will be for masterpieces of all kinds. Paintings. Classic architecture. Sculpture. The list goes on and on.

Even golf courses.

The early 20th century has been dubbed by many to be the golden age of course design in the United States, as 94 of the top 100 layouts on Golfweeks Best Classic Courses list were built in the four decades through the 1930s as cars proliferated and airplanes took off. The 1990s and early 2000s also were boom times, but nothing compared to that previous stretch in which famed designers artists, really produced so many masterpieces.

And just like famous paintings, these courses sometimes show their age. Throw in the effects of benign neglect or, even worse, well-intended alterations that abandon key characteristics, and many of the best golf courses have slowly lost much of their original designers intentions, even without considering the greater distances that modern golf balls travel.

Greens shrink and their internal contours are often subdued. Bunkers migrate, changing shapes, depths and sizes. Fairway widths are altered. Trees grow to block ideal lines of play. Golf courses are living, breathing creations that are subject to ever-changing budgets, growth patterns and whims of membership committees nothing remains static.

As with any work that might be done to the Mona Lisa, there are many considerations when tackling the problems of aging golf courses. But Mona Lisa doesnt live outside in a field, subject to weather and all kinds of dynamic forces. Golf courses do, and they need work to retain their artistry.

Enter the modern golf architect, many of whom have become restoration artists. For most of todays designers, much of their business since the financial crash of the late 2000s and subsequent drop in new golf course development is less about creating their own namesake layouts as it is restoring, renovating and otherwise touching up existing layouts.

In fact, its safe to say that in the past decade we have entered a golden era of restoration and renovation. The top courses on Golfweeks Best Classic Courses list is full of prime examples, many of which are on full, televised display during major championships. Even the list of top resort courses in the U.S. which tends to favor more modern layouts is dotted with significant renovations and restorations.

Theres been an appreciation building over time going back several decades, and I think whats been happening is, because of this golden age of restoration, not only is there an appreciation for the name architects A.W. Tillinghast, Donald Ross, Alister MacKenzie, C.B. Macdonald and several others theres a greater appreciation for their talents and their golf courses, said Gil Hanse, whose portfolio of restorations with design partner Jim Wagner continues to grow. Theres maybe more of an appreciation for those architects now. You can see that across the board for other modern architects and the courses they have touched, too.

Hanses restorations and renovations include but certainly are not limited to Merions East, most recently host of the 2013 U.S. Open; Winged Foots West, most recently host of the 2020 U.S. Open; The Country Club, next hosting the 2022 U.S. Open, and Los Angeles Country Clubs North Course (in collaboration with author and blogger Geoff Shackelford), next hosting the 2023 U.S. Open.

Its a long-winded kind of answer, Hanse continued, and theres been this kind of appreciation for a long time, but now because of all this good restoration work that is happening of which we are happy to do our part theres an even bigger appreciation of the older golf courses and those architects. Wow, we knew these guys were good, but we didnt know they were this good.

Bill Coore who with design partner Ben Crenshaw has worked on classics such as Pinehurst No. 2, Maidstone, Seminole, Riviera and many others agrees.

We do seem to be in an era where there are significant efforts going on to try to restore or, in some cases I guess you could say, address the current playing conditions of some of the classic old courses, Coore said. They are all living, breathing things like we are, and they change and evolve.

In the case of the best courses in the country, they have for the most part evolved in a very positive fashion. But they do change. Sometimes the changes are so incremental that theyre almost unnoticeable until years and years later. Then, you realize they were slightly better the way they were intended. You see a lot of that going on, I think. Were trying to recapture the original intent and playing characteristics of some of these old courses.

It can be a daunting task. How exactly does one go about touching up a masterpiece without damaging it? The first step typically involves some definition of intent.

Part of the process you go through is, what are the goals? Coore said. What are you trying to obtain if youre working at one of those great old courses? Is it purely trying to recapture the character and the aesthetics? Is it trying to recapture the playing characteristics? Is it trying to address issues pertaining to more modern golf? Is it all of the above?

The terms thrown about can muddle things. What exactly is a restoration? And what is a renovation? Do those terms ever cross, and how many shades of gray are present between them?

The easiest way for us to describe it, for Jim Wagner and myself, is that a restoration is when the original architects thoughts, style and design are the driving force behind every decision on the site, Hanse said. A renovation is when were interjecting our original design thoughts into an existing golf course, allowing our prejudices, thoughts, skills, etcetera, to influence what we think would make for a better golf course.

Hanse pointed to his and Wagners work at Winged Foots West course in New York as a restoration, with the duo trying to reclaim the characteristics instilled by the original designer, Tillinghast. Greens edges had crept in since the course opened in 1923, leaving fewer hole locations. Some bunkers had become irrelevant. Among all the work involved, perhaps key was Hanse and Wagners expansion of putting surfaces back to their original sizes and shifting of bunkers to better fit Tillinghasts intent of challenging players.

At the opposite end of Hanses redesign-renovation spectrum is Pinehurst No. 4, a Ross layout at the famed North Carolina resort that had been the subject of numerous subsequent redesigns since its opening as a full 18 in 1919. Defining it as a renovation and not a restoration from the start, Hanse and Wagner built what Hanse called close to being a whole new golf course through mostly existing corridors in the pines, and that renovation opened to play in 2018.

Pinehurst is a great example of the different ways to approach a renovation or restoration, as it has been 10 years since Coore and Crenshaw wrapped up what most certainly was a restoration of Pinehurst No. 2, the resorts flagship course that rests directly next to Hanses since-renovated No. 4.

Often cited as among the best of Rosss designs, No. 2 had changed considerably over the decades following its 1903 opening. The courses most famous features are its crowned greens, but much of the rest of the course might have been almost unrecognizable to Ross, who lived for years to the side of the third green. Most dramatically, the native sandy areas alongside fairways had been replaced with grass at rough heights, presenting totally different appearances and playing challenges.

No. 2 hosted U.S. Opens in 1999 and 2005, and even between those Opens the course changed, with fairways growing more narrow between ever-expanding fields of rough. After that 2005 Open, the resorts operators wanted to make drastic changes. Employing Coore and Crenshaw in 2010, they opted to take the course back in time, restoring what once was to replace what it had become.

Sometimes we look back at some of the architecture that has happened at Pinehurst, whether its golf course architecture or building architecture, and you scratch your head a little bit, Tom Pashley, now the president of Pinehurst Resort, said at Golfweeks Architecture Summit in November of 2020. How did this happen, how did that happen?

The decision was made, and it was a risk but it was obviously the right decision, to take No. 2 back. It had become a very manicured golf course, and the standing wire grass areas were only ornamental. It didnt look like a Sandhills course. Things had happened over the years, and the courses had evolved and all that, and we just said, look, this land is where Ross laid out the original four courses in Pinehurst, and we need to be true to some sort of aesthetic, the Ross aesthetic.

So Coore and Crenshaw were tasked with taking the course back, but to what, exactly? And for whom, Tour pros in the U.S. Open or resort guests? And how to do that?

At least for us, the single biggest priority is to take ourselves out of it, Coore said. If we leave signatures that weve been there, we failed, quite frankly. The goal is to recapture at least at places like Pinehurst or Maidstone or wherever the goal is to try to recapture what made that place so special in the beginning. And all those cases, they were built long before Ben and I were ever on this earth. So we take ourselves out of it, yet were so involved in it, trying to study the original intent. What did Donald Ross intend at Pinehurst No. 2? What was the focus? How did the course play and look?

Coore and Crenshaw got a major boost when local resident Craig Disher presented them with aerial photos of Pinehurst No. 2 taken on Christmas Day in 1943. The design duo received another break when Pinehurst agronomist Bob Farren told them the current irrigation system had been laid in the same trenches as the water pipes installed during Rosss time, allowing them to figure out the previous center lines of the fairways while projecting their width based on how far water would have been sprinkled.

I said, Bob, if thats the case, we have not only a road map, we have the center of the road, Coore said of the old irrigation system.

Such sleuthing can be crucial to a true restoration. At Pinehurst, those kinds of efforts allowed Coore and Crenshaw, with a fairly high degree of certainty, to present the course as it looked in 1943, with wider fairways surrounded by native grasses and no traditional rough.

The U.S. Open returned to No. 2 in 2014, with Martin Kaymer winning on a firmer, faster and browner layout that looked almost nothing as it had in 1999 and 2005. It was a departure from the typical U.S. Open setup of tall rough, but the work was roundly praised. And with the U.S. Golf Association now slated to establish a second headquarters at Pinehurst, the U.S. Open will return with No. 2 as an anchor site in 2024, 2029, 2035, 2041 and 2047.

Were very proud of Pinehurst, because the people there are very proud of it, Coore said. I know there were people who said, what on earth are they doing, theyre going to destroy the place. But I think given the time since the work and its probably been enough time to begin to assess that this was a positive move.

I grew up in North Carolina and I played golf at Pinehurst as a kid, and I remembered it from what it was in the 1960s, and I just knew from my own memory that it had changed dramatically through the years. Ben and I certainly never would have gone there and said you need to change this, you need to restore this. All that influence came from the Pinehurst people, who said weve been listening and studying that this course is not the way it used to be. It was a huge leap of faith.

While Pinehurst serves as a great model for restorations and renovations, its hardly alone in efforts to refine a golf course, even among U.S. Open venues. Oakmont Country Club in Pennsylvania, host to nine Opens, for example famously removed thousands of trees in the 1990s and 2000s to restore playing corridors as intended by original designer Henry Fownes. That certainly would be one of the most visually impactful restorations for any television viewer.

None of this is exactly new. Robert Trent Jones Sr. was known for his work on championship courses, and his son Rees followed in his footsteps. Courses have been the targets of redesign efforts ever since the game developed. Old Tom Morris certainly was known to tinker.

But as courses continue to age, efforts have been stepped up at many private clubs and resorts alike, often with grander goals of revisiting previous work that was more limited in scope. Whereas announcements of course openings filled the news wires in the early 2000s, todays design news is more typically filled with restorations and renovations not a week goes by without announcements of such work across the U.S.

Its all a great opportunity for current architects, but it can be very different than creating a new course. In a sense, great restorations are more of a research endeavor than a design process.

When youre in the field, theres a ton of archaeology, Hanse said. Youll find old bunkers and things. Were working at Oakland Hills right now, and well be sifting through, and That looks like old bunker sand. Yep, theres a layer, chase it and find where it goes. So there are markers on the ground. Working at Baltusrol, weve been sort of peeling away layers of bunker sand buildup along the edges of greens. You have thatch and sort of top dressing, then all the sudden you hit this sort of blackish soil layer. You can chase that soil layer, and that sort of reestablishes where the edge of the bunker was. If youre paying attention, you can find these things.

Hanse said the greatest example may have come at Los Angeles Country Clubs North Course, a George C. Thomas Jr. original design from 1921 that had been reshaped and diminished through the decades. A skilled contractor on an excavator kept finding all kinds of clues to the original course beneath the sod, especially as to the placement of the second and sixth greens.

He found the old green surfaces that literally had been covered by dirt they hadnt even stripped the grass off it, Hanse said. Pulling this away, we even found old cup holes. It was remarkable. We were just able to pull away the dirt and have the old green edges and contours intact. That was one of the coolest things I have ever seen.

But the fact there are clues in the dirt doesnt necessarily make it any easier for the architects.

Without question, I think Ben and I would both say that theres more stress in (restoring a classic course than in building a new one), said Coore, who along with Crenshaw delivered one of the most-anticipated new courses of 2020, the Sheep Ranch at Bandon Dunes Golf Resort in Oregon. Its because youre not dealing with your product. Youre trying to return the greatest potential of somebody elses product, a product that has proved to be successful and sometimes even revered around the world for years.

So its way more stressful and intense than creating a new product where, even though the site might have great potential and expectations, the course doesnt exist yet. On a new course youre living up to what the potential of the site is, but youre not living up to what was. Youre not chasing a ghost.

This story originally ran in Golfweeks 2021 Ultimate Guide.

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The golden age of golf course renovation and restoration - usatoday.com

Understand the influence of COVID-19 on the Turf Grass and Turf Solutions market with our analysts monitoring the situation across the globe.Turf Grass and Turf Solutions market Analyasis 2021-2027

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About Us:Garner Insights is a Market Intelligence and consulting firm with an all-inclusive experience and vast knowledge of the market research industry. Our vast storage of research reports across various categories, gives you a complete view of the ever changing and developing trends and current topics worldwide. Our constant endeavor is to keep on improving our storage information by providing rich market reports and constantly improving them.

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Outstanding Growth Turf Grass and Turf Solutions Market Trends by Countries, Type and Application | Turf Star, Inc.,Turf & Garden, Inc.,Integrated...

As you contemplate your garden areas for next year, what is the most critical task? Correctly preparing the garden bed new or old.

New beds require more prep work if you are starting an area that has turf on it. Here are two ways to turn turf into a garden area.

One method is to use a non-selective herbicide to kill off the top growth. Once it is dead, use a flat bottom shovel to cut the top vegetative layer off and remove or rent a sod stripper. You can till it in, but you will have clumps of dead turf everywhere which makes cultivation with a hoe more difficult and you will be mad at yourself for years that you did it this way.

A non-chemical method would be to solarize the area using black plastic for a few weeks or until the plant material all dies back. Then remove the dead layer in the same fashion. Avoid tilling under living turf, you will never be able to grow in the lumpy, grassy weedy mess that it will become.

Vegetable gardeners often re-use the same site for many years and thats okay. For 3 years, I have used the same spot without tilling, and overall I have less weeds than if I tilled. Every time you till, weed seeds are brought to the surface to receive sun and, guess what, germinate!

If perennial weeds are an issue like dandelion, thistle and grasses, your best solution is to spray them with an herbicide. Chopping them up by hand or using a tiller, just creates more. Solarizing is ineffective on perennial weeds as it doesnt kill the root. Always use chemicals responsibly and dont spray when plants are blooming and bees are visiting.

The value and uses of plants differ greatly from one to another.

Some plants are mainly for personal enjoyment like the blooms of peonies and iris. Others have many medicinal qualities or are used for food. Which plant can you enjoy the bloom of, use in a bouquet, cook with its oil, make rope from its stalk, roast and eat its seed yourself; grow as a fence to hide your neighbors, grind to use as cattle feed, use it as bird food and make dye from its petals? The sunflower!

Sunflowers are one of the easiest annual flowering plants to grow. Sunflowers have become very popular over the past years, and there are many varieties to choose from.

The height can range from 10 inches to 10 feet! Sunflower petals come in a variety of colors: yellows, oranges, reds, whites, browns and burgundy. Centers or seed heads, can also vary in colors. Some varieties like Teddy Bear are similar to a giant chrysanthemum.

Seeds should be planted directly in the garden soil as they grow rapidly and starting them indoors will result in a weak stem. Seeds are large, and easy for kids to plant.

Some types of sunflowers are pollen-less. These types are mostly bred for the cut flower industry as pollen can be messy and stain your clothes while harvesting or arranging in bouquets. Naturally pollen attracts bees and cut flower producers prefer the bees do not visit.

Once the flower is pollinated it begins to decline, as does its beauty and shelf life. Pollinated flowers begin to mature on to seed development, losing their petals along the way. When you are planning to use them for bouquets, cut them when the petals are just starting to lift off the face of the flower for the longest vase life.

Sunflowers that produce seed can be left in the garden for the birds to feed on over winter. The biggest drawback from growing sunflowers is chopping out the stalk when the season is done. Yes, even the next spring you might still need a hatchet or an axe depending on the type you grew.

Commercial production is huge to our west in the Dakotas, growing the majority of the sunflowers in the United States. If you are interested in seeing fields of sunflowers, the North Dakota Tourism tracks the bloom of numerous fields across the state and provides GPS coordinates for enthusiasts to locate. Over half a million acres in North Dakota are planted in sunflowers.

The flower heads on young plants actually follow the sun from east to west. Older mature plants face mostly east. Having lived in North Dakota for a spell, I can say the sunflower fields between the fields of sugar beets and potatoes were spectacular!

Stop by the Mankato Farmers Market at Drummers Garden Center. All times are 10 a.m. noon.

Remaining Winter Market dates are: Jan. 23 and Feb. 6.

We are making critical coverage of the coronavirus available for free. Please consider subscribing so we can continue to bring you the latest news and information on this developing story.

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Gardening column: Sunflowers have become popular over the years - Mankato Free Press

Housing costs: 700 rent including all bills. Super cheap for my area, especially as I live alone.Savings? 63,000: 3,000 in my savings account, 30,000 in a LISA, 30,000 in a SIPP. Both the LISA and SIPP are courtesy of my parents saving for me throughout my life. I know I'm extraordinarily lucky to have parents who can afford to invest money on my behalf and are financially literate enough to do so. They also paid for my university tuition so I don't have any debt. I know I'm very privileged and am beyond grateful to my parents for their hard work and generosity. All other monthly expenses: 29 gym membership (currently on hold as we're in tier 4). 5 New York Times subscription. 18.99 phone contract (unlimited data worldwide. Wish the worldwide part was still relevant...). 9.75 British Medical Association membership. Approximately 200 savings. 10 to Oceana, a charity helping tackle marine pollution and raise awareness of the plight of the oceans. 50 therapy. I should probably go more often than monthly but it's so expensive. I have suffered from an eating disorder in various forms for about five years, which I'm still trying to squish. On a Spotify family plan, mooch Netflix off my brother.

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Money Diary: A Junior Doctor On The South Coast On 29k - Refinery29

Richard Adlington, of Penistone, took the plunge after seeing desperate pleas for tradespeople in an online community forum.

He had business support from the Sheffield City Region Launchpad programme and borrowed 7,000 from Finance for Enterprise - becoming the 1,000th recipient of an FFE Start Up Loan.

Mr Adlington oversaw kitchen installations in pubs and hotels across the country until the first lockdown forced the hospitality sector to close. He was made redundant after 250 projects fell to one.

Convinced of the demand for plumbers, and using skills he mastered as an apprentice, he set up Radlington PHS.

He said: I knew I had the technical skills and experience to work as a plumber, but I also knew running my own business meant getting the fundamentals right from day one.

Since launching he has grown his customer base despite Tier 3 restrictions a three national lockdowns and is now planning to create an apprenticeship.

Radlington PHS is the 1,000th new business to receive a Start Up loan from Finance For Enterprise.

Ian Howson, business advisor at Finance for Enterprise said: It was clear from our first meeting that Richard had spent a great deal of time planning his business.

The financial projections he used to support his application were well thought out and by producing figures which took into account the impact of Covd-19, it was clear the loan would help him secure the equipment and transport his business needed and provide a cash buffer to protect it during the pandemic.

Ben Hawley, business adviser at Launchpad, said: Richard came to Launchpad with a clear idea of how he wanted to grow his business but he wasnt sure what steps would be needed.

He spent time taking part in wide range of training sessions and it was clear hed spent a great deal of time developing and refining his ideas. The business plan he produced clearly illustrated a need for additional investment and the work he undertook enabled him to secure the funds to give his business the best possible start.

Thank you to all who support local journalism with a digital or print subscription to The Star.

The events of 2020 mean trusted, local journalism is more reliant than ever on your support.

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Redundant South Yorkshire hospitality boss retrains as a plumber to beat the pandemic - The Star

A black plumber said he suspects his race may have factored into a decision to arrest him after a client reported 10,000 missing from her home.

Paul Peters, from Aigburth, spent five hours in police custody and two months on bail before the charges were dropped, despite Merseyside Police being aware that his client hadn't seen the money for months before realising it was gone.

His arrest became even more shocking when it was revealed that 12 workmen had been in the property since she had seen the money, none of whom were arrested or questioned.

The Liverpool Echo reports that the 63-year-old had never been in legal trouble before, and worries that his reputation as an honest tradesman, his good character and his freedom was at risk after the accusation.

Merseyside Police were ordered to pay 8,000 in damages and 16,000 legal costs after a judge at Liverpool County Court ruled in Mr Peters' favour, saying that his arrest was "not objectively necessary" and unlawful.

Have you had a similar experience? Let us know in the comments below.

The force denied that racial bias played a role in his arrest and pointed out that the case didn't make any claim of discrimination.

In his statement to the court, Mr Peters said: "Following my arrest I was very anxious, worried, depressed and angry about being accused of theft, being arrested and then being on bail for two months.

"I worried about being charged, having to attend court and being found guilty of an offence for which I was entirely innocent.

"I worried that other customers would find out about my arrest and that it would affect my reputation and business...

"I knew that Mrs Mace had a lot of work done on her house and a number of workmen had been in and out of the house at the time the money went missing. There were then a number of suspects.

"I was disappointed to establish that out of all the other potential suspects I was the only one to be arrested. I am black and I wonder to this day as to whether my arrest was racially motivated."

The court heard that Mr Peters and his son were called to Ms Mace's house in Knotty Ash in June 2013 to inspect a leak in the bathroom of a home undergoing a major extension.

They had to go through an adjoining wall to access the leak and moved a wardrobe which had been used as a hiding place for 10,000 cash.

Ms Mace said she grew suspicious as their "manner changed" when they left the house, prompting her to check the wardrobe and discover the money missing.

She asked a neighbour to call Mr Peters and inform him the money was missing, and tried to reassure him that "we aren't blaming you" when he protested.

The issue was reported to the police two weeks later, and Detective Constable Kevin Mitchell, who led the investigation didn't arrest Mr Peters until October 8.

Solicitor Iain Gould, from DPP Law, handled Mr Peters' case and found revealing notes written by DC Mitchell weeks before the arrest, which suggested he didn't think there was enough evidence against him.

An entry in July said "there was no immediate need" to search the homes of suspects due to the delay in the crime being reported.

In September he said: "There is not enough to proceed at this time against Paul Petersthere is not enough in Peters background to support the notion that he has taken the money."

Despite this, Mr Peters, who is diabetic, was held for five hours in custody.

Mr Peters said: "It was just all nonsense from start to finish."

After the case Mr Gould said: "Mr Peters will now also be able to use this judgment to assist him in getting Merseyside Police to expunge all records of his wrongful arrest so that it will not besmirch his character in the future or hamper his ability to work and travel where he choses.

"The importance of this victory goes far beyond the counting of pounds and pence.

"Indeed, it was only half way through the Police barristers closing speech that Merseyside Police finally conceded that they now accepted that Paul had no involvement whatsoever with the alleged theft...

"Neither the Officer nor his Force showed any humility or contrition until thanks to Pauls courageous decision to see this case through to Trial despite all the financial and emotional risks entailed they were finally brought to book in front of a Judge."

A spokesperson for Merseyside Police said they "accepted the findings of the court" after the "technical claim."

They added: "The court found that the officer did have reasonable grounds to suspect that the claimant was guilty of the offence for which he was arrested at the time.

"The court did, however, state that he should have been dealt with by way of voluntary attendance for interview at a police station rather than arrest.

"There was no suggestion in the case at court that the arrest was racially-motivated, and an internal investigation carried out in 2014 following a formal complainant found no case to answer in relation to the complainants allegations relating to his arrest.

"However, we continually review proportionality in our interactions with our communities, and through recruitment campaigns work hard to ensure our workforce is representative of the diverse communities we help to protect in Merseyside."

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Plumber fears his race 'was involved' in client's false accusation over missing 10k - Mirror Online

16 January 2021, 12:22 | Updated: 16 January 2021, 14:16

Pimlico Plumbers chief Charlie Mullins reveals he won't employ anyone who hasn't been vaccinated against Covid-19, once the jab is widely available.

"It's an employers right to protect and look after their employees[...]and that's what we're doing," said Charlie Mullins, founder of Pimlico Plumbers.

He told Andrew Castle that he believes "if you're in a position to have a vaccine, you should have it," adding that he will not put his staff and customers at risk unnecessarily.

"In the future once the vaccination is circulated correctly...we won't be taking on anybody that hasn't had the vaccination."

Andrew argued that Mr Mullins' policy can be seen as discriminatory, but the entrepreneur insisted that health and safety policies are on his side.

Read More: Young people may have to stay in lockdown until vaccinated

Read More: Covid-19 crisis in numbers: LBC brings you the stats you need to know

"We're not prepared to bring people into the building that have not been vaccinated," Mr Mullins insisted, adding that "safety is the priority here."

He reiterated to Andrew that it is not only a policy of protecting customers, he insisted that "we need to protect our employees."

Finally, Andrew wondered if Mr Mullins thought it should "be mandatory in society to have the vaccination?"

"I think that's what it's going to lead to," Mr Mullins concluded.

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'I won't employ anyone that refuses vaccination,' claims plumbing boss - LBC

One of Moderna co-founder Derrick Rossis favorite things to say is that there are three keys to life on Earth: DNA makes mRNA makes protein makes life.

The experimental technology behind Moderna and Pfizers coronavirus vaccines harnesses the power of one of those keys messenger RNA, or mRNA. They are the first medical products to use mRNA in this way, but they certainly wont be the last. A Covid-19 vaccine is just one of the near-infinite possibilities the technology offers, Rossi said.

Being able to control mRNA would allow scientists to manipulate life in astonishing new ways. It could open the door to new treatments for diseases like cystic fibrosis, cancer, and HIV. Now, bolstered by the apparent success of the Covid vaccine, Rossi said, those other applications may soon come to fruition.

Within 10 years time, well see probably dozens of mRNA therapeutics. In maybe 15 years time, well see maybe 50 or 60 mRNA therapeutics, he said.

Before Rossi co-founded Moderna, he was a biologist at Harvard tinkering with mRNA. DNA is often described as the building block of life, but DNA is essentially a database of information cells need to create proteins. RNA is the molecule that actually does the work of creating those proteins.

For years, Rossi and other scientists tried designing strands of mRNA that would force cells to make specific proteins. But long before this technique created the worlds highest profile vaccines, they failed.

It totally didnt work, Rossi said. What it looked like to the cell was that the mRNA was a virus. And the cell, like a good soldier, would elicit a very robust antiviral response.

Every time Rossi tried to insert the mRNA, the cell would either destroy the molecule or kill itself not at all what he wanted. He felt like hed hit a wall. The solution came from another part of the cell and two scientists at the University of Pennsylvania discovered it.

Katalin Karik, then a junior scientist at UPenn and now a senior vice president at BioNTech, another company that has developed a Covid vaccine, was trying to do the same thing that Rossi was and coming up empty, too. But a colleague of Karik at UPenn, Dr. Drew Weissmansuggested that Karik try using modified chemical letters in her mRNA code.

By modifying the RNA, it cloaks the RNA. Its like giving it a fake passport, said Timothy Springer, an immunologist at Boston Childrens Hospital and Harvard Medical School. And it worked brilliantly.

The modified chemical letters disguised the mRNA, making it appear more or less innocent to the cell. When Rossi read about Karik and Weissmans work, he immediately startedincorporating their technique into his own research. In one experiment, he directed cells to create proteins called Yamanaka factors that converted mature cells into stem cells. In another, he injected mice with mRNA encoded for the protein that makes fireflies light up.

And then you know, an hour later, we put the mice into this machine, and we could see this glowing spot, Rossi said.

The experiments were working, and now Rossi knew how to control one of the three most fundamental keys to life. He took the new data to Springer, also an accomplished entrepreneur, and asked him to help start a company based on the new technology.

Springer jumped on board, becoming the companys first investor. They called it Moderna short for modified and RNA. Both still own stock in the company.

The possibilities were unlimited, Springer said. You know, the RNA can encode for anything. They could be encoding secreted protein or an enzyme in the cell or a vaccine unit, you know, to protect against SARS-CoV-2.

Over the last decade, Modernaand other companies like BioNTech have been studying modified mRNA technology as a way to develop treatments fora wide variety of diseases including heart failure and chikungunya virus. Other researchers have found ways to use modified mRNA to makeadvancesin anti-aging research.

And modified mRNA is particularly suited to creating vaccines, Springer said. Thats because while those modified chemical letters allow the molecule to sneak past cellular defenses, the compoundstill looks somewhat suspicious. It doesnt completely sneak by, he said, theres a little bit of interest. Maybe the eyebrows of the immune system perk up.

The mRNA in a vaccine carries the code for a pathogen protein like the spike protein from the coronavirus. When the cell begins executing the code from the vaccine and manufacturing that protein, the already wary immune system flares into action and produces a particularly strong immune response. That might be one reason why the coronavirus vaccines from Moderna and Pfizer have beenso effectiveso far in clinical trials, Springer said.

That property, along with others, makes modified mRNA an attractive option for cancer vaccines, said Dr. Cathy Wu, an oncologist at the Dana Farber Cancer Institute. These vaccines train the immune system to attack tumors, but creating them takes a long time and its expensive. Thats a problem for cancer patients.

If someone has advanced cancer, you cant really wait that long, she said. Being able to build vaccines in a timely fashion is probably whats going to be needed to make this actually work. mRNA vaccines can be made lightning fast. All thats needed to create a new one is rewrite the genetic code in the vaccine. The Covid vaccine took only days to design once researchers had the novel coronaviruss genome. This could also be an advantage if the coronavirus mutates in a way that makes the current vaccines less effective.

The technology provides a nimble platform that you can switch things up quickly, Wu said.

Now that the Covid vaccine is being produced on a massive scale, Wu said, that might also help drive down some costs for the technology, as manufacturers find more efficient ways of making the mRNA. The last step remaining for cancer vaccines is to be tested in large clinical studies.

Thats true of other applications for modified mRNA, too. Wu pointed out that with two mRNA COVID-19 vaccines now in use, billions of dollars are going into the new technology. Other therapeutics arent likely to be too far behind.

This article was published by WBUR 90.9FM on Jan. 11. WBUR and the Reporter share content through a media partnership.

Originally posted here:
Plumbing the marvels of 'mRNA' in creating vaccines, therapeutics - Dorchester Reporter

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Plumbing Hardware Market Segmentation, By Type

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