Biologicals

C-Suite: Focus On Collaboration, Not Credit

Thu, 22 Sep 2022 00:55:05 GMT

Mark Lyons became CEO of Alltech in 2018. He succeeded his father and company founder, Pearse. In a partnership announced in mid-June, Helm Agro will provide marketing, distribution and technical support for Alltech Crop Science’s biological products.

What is your business philosophy?

A big part of our philosophy revolves around entrepreneurialism and making sure culture remains strong throughout the business. As companies grow bigger, they become more bureaucratic and slow down in terms of decision-making. We want to have an empowered, entrepreneurial front line. The other word that comes to mind is collaboration. The world has become too connected for one company to say it is going to do it on its own.

How has the business changed over the years?

When I joined officially in 2001, we were going through a major push to broaden and add more technological capabilities. We were building our own production facilities, and I was involved in establishing a fermentation facility in Mexico, assisting with a large acquisition in Serbia and building a new yeast facility in Brazil.

Our growth cycle has allowed us to get closer to the end user and speed up innovation. In one regard, it’s the same family company, but we now have 5,000 people involved. That requires a certain discipline and determination on the part of management to keep our ethos in place.

What is your personal leadership style?

What was most important to my father was Alltech and its people would make a difference in our customers’ lives and in the communities in which our people live and work. We want our people to be empowered to make a difference, and we want to look back on the impact and see it was something we did together—focused on collaboration, not credit.

What will the business look like in 20 years?

Alltech will continue to focus on the fundamentals. Our science is the core of the business. Our team is so focused on curiosity and thinking about things in different ways that if we have an idea from outside, we can adapt it and make it part of our system. I also see us getting involved in some new areas, such as human life science, which could expand our ability to improve quality of life and create new avenues of growth. I also think there are many ag technologies that Alltech could partner with in the future. It doesn’t necessarily mean we have to own 100% of those businesses, but we’re offering a way to connect different parts of the industry.

Pigs ‘Escape Death’ By New Technology in Organ Revival

Thu, 04 Aug 2022 18:45:46 GMT

Pigs have more purpose than simply producing pork.

Frequently used in the medical field, pigs have served as organ donors, such as a heart and heart valves. They continue to serve as a vital part of medical research and advancements in technology.

Researchers at Yale University recently shared study results of a new technology used to restore circulation of blood flow and cell activity in vital organs of pigs, over one hour after the animal died, Nature reports.

What was once considered ‘irreversible’ when blood circulation and oxygenation stops, this technology showed otherwise.

The system, called OrganEx, pumps a blood substitute through the animal’s body to slow the decomposition of the body and restore some organ function, specifically the heart, liver and kidney. No coordinated brain activity was observed to indicate animals regained any consciousness.

The blood substitute includes a variety of compounds to suppress blood clotting and the immune system and slow decomposition of the animal’s body.

“We’re not saying it’s clinically relevant, but it’s moving in the right direction,” says Zvonimir Vrselja, a neuroscientist at Yale University.

During the study, after an induced cardiac arrest death, the pigs received the OrganEx technology, and after six hours, researchers detected activity in the heart, liver and cells in the vital organs. Other pigs were attached to an extracorporeal membrane oxygenation (ECMO) machine, which is used in hospitals today as a final effort to supply oxygen and remove carbon dioxide in the body.

The Organ Ex technology proved superior.

“If the findings of cellular restoration can be replicated in animals and eventually in humans, their implications for human longevity could be as “profound” as the advent of CPR and ventilators, says Nita Farahany, a neuroscientist at Duke University to Nature.

This could one day lead to increased preservation of transplant organs, allowing more time for the donor organs to reach the recipient.

While the study and technology remain in its early stages, these findings might someday lead to increased success in organ transplantation and save lives across the globe.

Self-eliminating Genes Tested on Mosquitoes

Tue, 03 May 2022 20:03:12 GMT

Texas A&M AgriLife Research scientists have tested a technology to make temporary genetic modifications in mosquitoes. The modifications self-delete over time.

The mechanism to make temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering wild populations’ genetic makeup.

An article detailing their test results, “ Engineering a self-eliminating transgene in the yellow fever mosquito, Aedes aegypti ,” was published in Proceedings of the National Academy of Sciences’ PNAS Nexus. The authors, Zach Adelman , Ph.D., and Kevin Myles , Ph.D., both professors in the Texas A&M College of Agriculture and Life Sciences Department of Entomology , describe a method for programming the removal of edited genes within populations of mosquitoes over multiple generations.

The method is a first step toward building safeguards for genetic modifications developed to control populations of mosquitoes and the vector-borne diseases they carry. The idea is to test proposed changes without making the changes permanent and without the risk of transmitting them to wild populations, Adelman said.

“There are lots of ecological questions we don’t know the answers to, and when you are testing technology, you don’t want to get into a situation where you have to tell a regulatory agency or the public that ‘if something bad happens, we’re just out of luck,’” Adelman said. “This mechanism is about how we get back to normal whether the experiment does or doesn’t come out the way we expect.”

Adelman and Myles are co-directing a team of scientists who received a five-year, $3.9 million grant from the National Institute of Allergy and Infectious Diseases to test and fine-tune the self-eliminating transgene technology.

Back to normal in a few generations

To prevent mosquito-transmitted diseases, approaches based on genetic control of insect populations are being developed, Adelman said. However, many of these strategies are based on highly invasive, self-propagating transgenes that can rapidly spread the trait into other populations of mosquitoes.

Keun Chae, Ph.D., a post-doctoral researcher in Adelman’s group, led the experiments in Aedes aegypti mosquitoes, which are known vectors of diseases. Taking advantage of a form of DNA repair, Chae engineered a duplicated genetic code region along with two genes for fluorescent proteins into the middle of a gene important for eye pigment.

The result was a white-eyed mosquito, and also red and green fluorescence in the eyes and body. When combined with a site-specific nuclease, which is essential for many aspects of DNA repair, they acted as a precise set of molecular scissors that could cut the transgene sequences. Over several generations, mosquitoes regained their normal eye pigment and lost the modified genes.

Adelman said the work is proof of principle that scientists can do two important things – remove transgenes placed in mosquitoes and repair disrupted genes.

“Many groups are developing genetic methods for mosquito population control,” Adelman said. “Our method provides a braking system that can restore sequences in the wild.”

Self-editing transgenes could be leap for genetic research

Myles said creating this self-editing transgene is the first step in a longer process. The mosquito genome is not easy to manipulate, and the breakthrough is the culmination of around six years of experimental work.

But this first publication starts to address concerns about genetic modification in wild populations, he said. As genetic modification technology advances, Adelman and Myles believe this mechanism will allow researchers to evaluate the effects of changes more safely within the environment and on animals other than mosquitoes.

“These are highly conserved genetic pathways, and there is every reason to believe this method could be applied to a diverse range of organisms,” Myles said.

Both scientists are looking forward to expanding the application of their discovery in the context of highly active gene drive. They hope their method will be useful for geneticists and in pushing the boundaries of genetic research.

First Pig to Human Heart Transplant Ends in Patient Death

Wed, 09 Mar 2022 18:57:02 GMT

The first person to receive a pig heart transplant has died two months following procedure, according to the University of Maryland.

The 57-year-old male, David Bennett, previously suffered arrythmia but was forced to stay on cardiac support as his irregular heartbeat did not allow for a mechanical heart pump.

A Shot in The Dark

The decision to take a pig heart transplant was the final option for Bennett. He was ineligible for a human heart transplant. He told the University of Maryland, “it was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice.”

The Food and Drug Administration doesn’t approve of porcine heart transplants. However, due to Bennett’s heart failure, irregular heartbeat and previous lack of compliance with medical instructions, the administration cited the “compassionate use” rule, dubbed for emergency situations, as their way of approval.

Following the procedure, Bennett appeared to be recovering well. The Maryland hospital even released video of him working with his therapist while watching the Super Bowl.

What We Know

Maryland Medicine has not yet officially announced Bennett’s cause of death. Though the autopsy is likely to reveal rejection or infection as these are often the outcomes of deceased transplant patients.

Animal transplants to humans—xenotransplantation—have been somewhat unsuccessful in the past due to human bodies rejecting animal organs.

To promote the human bodies acceptable of the pig heart, scientists modified the pig’s genes by removing three rejection triggers while adding six human immune acceptance genes.

Are Animal Hearts the Answer?

Bennett’s gene-edited pig heart survived the longest in terms of experimental xenotransplantation. Before Bennett, the most successful heart xenotransplantation was an infant named Baby Fae who survived with a baboon’s heart for 21 days.

Following the transplant, Dr. Bartley P. Griffith from the University of Maryland Medicine said “this was a breakthrough surgery and brings us one step closer” to solving the organ shortage.

Griffith worked alongside Dr. Muhammad Mohiuddin, who worked to establish the Maryland Medicine Cardiac Xenotransplantation Program. Mohiuddin believes Bennett’s passing doesn’t indicate heart xenotransplantation is impossible.

“We are grateful for every innovative moment, every crazy dream, every sleepless night that went into this historic effort,” David Bennett Jr. said in a statement released by the University of Maryland School of Medicine. “We hope this story can be the beginning of hope and not the end.”

More from Pork Business:

> Man Receives Heart from Genetically Modified Pig in Groundbreaking Surgery

> German Researchers to Breed Pigs for Human Heart Transplants This Year

> Neonatal Pig Hearts Can Heal From Heart Attack

Cargill, Bill Gates Bet on Lab-Grown Meat

Fri, 20 Nov 2020 05:48:53 GMT

Cargill Inc., one of the largest global agricultural companies, has joined Bill Gates and other business giants to invest in a nascent technology to make meat from self-producing animal cells amid rising consumer demand for protein that’s less reliant on feed, land and water.

Memphis Meats, which produces beef, chicken and duck directly from animal cells without raising and slaughtering livestock or poultry, raised $17 million from investors including Cargill, Gates and billionaire Richard Branson, according to a statement Tuesday on the San Francisco-based start up’s website. The fundraising round was led by venture-capital firm DFJ, which has previously backed several social-minded retail startups.

This is the latest move by an agricultural giant to respond to consumers, especially Millennials, that are rapidly leaving their mark on the U.S. food world, whether it’s through surging demand for organic products, increasing focus on food that’s considered sustainable, or greater attention on animal treatment. Big poultry and livestock processors have started to take up alternatives to traditional meat.

“The world loves to eat meat, and it is core to many of our cultures and traditions,” Uma Valeti, co-founder and CEO of Memphis Meats, said in the statement. “The way conventional meat is produced today creates challenges for the environment, animal welfare and human health. These are problems that everyone wants to solve.”

‘Clean Meat’

To date, Memphis Meats has raised $22 million, signaling a commitment to the “clean-meat movement,” the company said.

Cargill has “taken an equity position in Memphis Meats’ first series of funding,” Sonya Roberts, the president of growth ventures at Cargill Protein, said in an email, without disclosing the investment amount.

“Our equity position with Memphis Meats gives Cargill entry into the cultured protein market and allows us to work together to further innovate and commercialize,” Roberts said. “We believe that consumers will continue to crave meat, and we aim to bring it to the table, as sustainably and cost-effectively as we can. Cultured meats and conventionally produced meats will both play a role in meeting that demand.”

The investment is just the most recent by traditional meat companies

Tyson Foods Inc., the largest U.S. meat producer, has created a venture capital fund focused on investing in companies “to sustainably feed” the world’s growing population and in December announced a stake in plant-based protein producer Beyond Meat, which counts Gates among its early funders.

Weaponizing Oxygen to Kill Infections and Disease

Wed, 11 Nov 2020 05:08:33 GMT

The life-threatening bacteria called MRSA (methicillin-resistant Staphylococcus aureus) can cripple a hospital since it spreads quickly and is resistant to treatment. But scientists report that they are now making advances in a new technique that avoids antibiotics. Instead, they are using light to activate oxygen, which then wipes out antibiotic-resistant bacteria. The method also could be used to treat other microbial infections, and possibly even cancer.

The researchers presented their results at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, featured more than 10,000 presentations on a wide range of science topics at its meeting.

Clinical facilities currently have few alternatives when trying to rid their patients of MRSA. The Veterans Health Care System, for example, hires infection prevention staff to track hand hygiene. Going even further, one recent study found that disinfecting every patient admitted to an acute-care setting cut the rate of bloodstream infections in half. However, this procedure isn’t feasible at most hospitals.

An Alternative to Antibiotics
“Instead of resorting to antibiotics, which no longer work against some bacteria like MRSA, we use photosensitizers, mostly dye molecules, that become excited when illuminated with light,” Peng Zhang, Ph.D., says. “Then, the photosensitizers convert oxygen into reactive oxygen species that attack the bacteria.”

Although other teams have experimented with using these types of photocatalysts to kill bacteria, they did not destroy enough microorganisms to effectively shake off infections. Photosensitizers in a molecular form tend to not be corralled enough to do significant damage. In addition, many of them are hydrophobic. This makes it difficult to disperse them in aqueous media where microorganisms typically exist. To overcome these challenges, Zhang’s group collaborated with Neil Ayres, Ph.D., and his team; also located at the University of Cincinnati. They set out to design a new, water-dispersible, hybrid photosensitizer — one that includes noble metal nanoparticles decorated with amphiphilic polymers to entrap the molecular photosensitizers.

Much More Effective
The team showed that the new nanoparticle photosensitizer was much more effective at killing a variety of bacteria than corresponding formulations that did not contain the metal particles. According to Zhang, these nanoparticles provide two benefits. The metal has a plasmonic enhancement effect that promotes the generation of more reactive oxygen species, while also concentrating the photosensitizers in one place for a more localized hit to the bacterial cells.

Zhang explains it this way: “If you want to attack a castle, and you just let all these people attack individually, it is not very effective. Instead, if you have the same number of people grouped together attacking the castle at one point, it is possible to cause more damage.”

Zhang has a patent related to the design of hybrid photosensitizers, which can be formulated into a spray or gel. He says that once the spray is developed into a product, medical professionals could put it on any surface and then illuminate it with blue or red light to clean away the bacteria, including MRSA that may be present. Zhang also says that the method shows promise in direct wound applications to eliminate infection and assist in healing. He has recently performed experiments on laboratory samples of human skin and found that the photosensitizer didn’t kill skin cells.

Also Effective on Skin Cancer Cells
In addition to eradicating MRSA, the nanoparticles are ideal for destroying skin cancer cells, Zhang says. The nanoparticles perform effectively with the illumination of red light, which has a long wavelength that penetrates deep below the skin — something that’s important for a skin cancer treatment. Finally, the nanoparticles have been shown to eliminate nail bed fungus.

Editor’s Note: The researchers acknowledge support and funding from a University of Cincinnati Technology Accelerator award and the donors of the American Chemical Society Petroleum Research Fund . The American Chemical Society, the world’s largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

CRISPR Diversifies: Cut, Paste, and Now– Evolve

Wed, 11 Nov 2020 05:08:28 GMT

Life is astoundingly diverse. By taking antibiotics to stop infections or using yeast to brew beer, we are co-opting useful products and processes that evolved naturally. But what happens when the trait we want can’t be found in nature?

Scientists at the Innovative Genomics Institute have concocted a transformative new way to harness the power of evolution. Today in Nature, researchers led by PhD student Shakked Halperinworking in the laboratories of David Schaffer and John Dueber at UC Berkeley describe yet another creative application for CRISPR: a platform to spur evolution of specific genes inside cells. Their inventive new system, “EvolvR,” lets scientists shake up the DNA letters in their gene of choice until they find the variation that’s just right. The technology opens up countless possibilities, like engineering yeast that efficiently turn waste into biofuels, or developing new human therapeutics.

Not Just Monkeying Around
Imagine a monkey sitting at a keyboard. If given an infinite amount of time to press keys at random, the monkey would almost surely type the complete work of William Shakespeare. At least, that’s according to the “ infinite monkey theorem .” Natural DNA variation is akin to this process – as time goes by, random changes pop up across the genomes of different individual organisms. In theory, over infinite time, every possible variation of the genetic letters will have existed. On a practical human timeline, however, only a very small fraction of possible variations will ever appear.

Sketch of the “infinite monkey theorem” as it applies to EvolvR. A monkey types genetic code under the direction of CRISPR-Cas9. Credit: Maya Kostman, IGI

Now imagine that we can tell the monkey to rewrite just a specific page in Shakespeare’s Macbeth. Limited to just this narrow window, the monkey will type out every possible variation of the page’s text much, much faster. This is what EvolvR lets scientists do. They only want new versions of a single gene, so rewriting the entire genome is impractical and likely toxic to living cells. By limiting the scrambling to just one gene at a time, it becomes possible to sample an enormous number of variations.

Flicking on the “Evolve” Switch
EvolvR lets scientists push a gene through the entire process of evolution in just one day in the lab. The system is built on the programmable DNA cutting protein Cas9, making EvolvR the latest ingenious device in the CRISPR toolbox. The IGI team leashed Cas9 to an enzyme called DNA polymerase. Cas9 is programmed to find a specific target sequence in an organism’s DNA. EvolvR uses a special “nicking” version of Cas9 that only cuts one of the two DNA strands. Cas9 makes a nick, signaling for DNA polymerase to peel back the strand and replace it with new DNA. The polymerase makes errors, writing in a different DNA sequence than the original, like the proverbial monkey at the keyboard.

Step-by-step, how EvolvR targets a specific sequence for diversification.

Since diversity is the goal, the polymerase’s “typos” are a good thing. Scientists can use EvolvR to deliberately make random mutations, creating millions of different sequence combinations and likely finding at least one that has the effect they want.

Directed Evolution Technology Evolves
This method is a fundamentally new way to diversify biological systems, opening doors that remained locked with earlier strategies. Other methods relied on forcing a vast “library” of randomized DNA pieces into cells. This is time-consuming, expensive, and not all cells will easily take up external DNA. EvolvR gets around these and several other drawbacks of previous approaches. “It doesn’t require a double-strand break like many other technologies do,” notes Dueber. “Double-strand breaks are toxic to many cells. It also doesn’t require sophisticated repair pathways, which many interesting organisms don’t have.”

The tool should therefore work in any species, and testing this idea is one of the team’s immediate next steps. Though its proving ground was in bacteria, the versatile platform will be even more powerful when used in eukaryotes, like human or plant cells. “EvolvR has huge potential as a species-independent tool for directed evolution,” says Schaffer. “It can already make single mutations or combinations of changes across regions of DNA ranging from about a dozen to a few hundred base pairs long.” Dueber adds, “We’re interested in making a modest toolkit of EvolvRs. We envision systems that have higher mutation rates or that affect much larger windows. There are a lot of ideas to try.”

Halperin points out another key strength of the system. Earlier methods for evolving traits in the lab include just a few, labor-intensive rounds of diversification and selection. “In previous directed evolution experiments, we stepped away from what nature does. Because our tool can continuously provide diversity at a target gene, we can continuously enrich for better and better traits, closer to the natural evolutionary process.” An EvolvR experiment can go on as long as the researcher wants, shuffling the gene’s sequence over and over again and creating more opportunities for success.

A DNA tree branching out into diverse leaf types. Credit: Shakked Halperin

Off to the Races
There are almost too many possibilities to envision up front, and the team behind EvolvR hopes that other scientists will take their creation and run with it. “We’re excited about other people joining us to use this tool and improve it,” says Halperin. Schaffer is eager to implement the tool to “accelerate the development of biomolecules for human therapeutic applications, from new drugs to new drug delivery technologies.”

The researchers are especially excited about combining EvolvR with another CRISPR toolbox favorite, high-throughput CRISPR screening. This potent pairing of technologies would let them diversify thousands of different genes in a single experiment, potentially creating brand new functions instead of just turning genes on and off.

A single drop of bacteria diversified with EvolvR contains immense diversity. What groundbreaking potential might be hiding in that single drop? As Kahlil Gibran once wrote, “In one drop of water are found all the secrets of all the oceans.” While Gibran’s poetic vision is not quite realized, we are quickly approaching it.

Editor’s Note: This study was published in the online edition of the journal Nature as “ CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window .” In addition to Dueber, Halperin, and Schaffer, co-authors of the work are Connor Tou, Eric Wong, and Cyrus Modavi. This research was funded by the Innovative Genomics Institute.