Cover Story
A lab technician works at Scientific Protein Laboratories (SPL) of Waunakee, Wisconsin. SPL is the largest heparin producer in the US. It was founded by Oscar Mayer and the Univ. of Wisconsin.
 
Editor’s Note: In the early hours of Aug. 31, 2010, Aris Landon Chant made his entry into this world. In an otherwise normal delivery, Aris was born nine days premature. Common to preterm birth babies, he was born with respiratory distress syndrome (RDS). In this condition, the lungs are underdeveloped and unable to support normal breathing. Aris’ condition was particularly important to me – he is my grandson.

Respiratory distress syndrome is a condition marked by the insufficient presence of pulmonary surfactant. Pulmonary surfactant is a compound which allows the lungs to expand easier and more evenly. Without it, the lungs become damaged and oxygen absorption is greatly inhibited. Untreated, it often leads to death.

Years ago, a preterm baby with RDS had a 30 percent chance of survival. For years, scientists tried to create a synthetic surfactant to treat RDS, but were unsuccessful. In 1991, a Buffalo, New York, physician discovered that a surfactant extracted from bovine lungs called “calfactant” would effectively replace the missing surfactant from RDS lungs. A porcine surfactant soon followed. These animal-derived pharmaceuticals dramatically improved the survival rate for RDS to 95 percent. It’s likely that use of this compound saved Aris’ young life, as it has for tens of thousands of premature babies a year since then.


Animal-derived medicines today play a critical role in human health. My family experienced it firsthand with Aris’ birth, but the reality is that millions around the world benefit from animal-sourced pharmaceuticals without even knowing it.

To appreciate the importance of animal- sourced pharmaceuticals, it’s necessary to understand that not all compounds can be synthesized in the lab. Dan Schaefer, professor of Animal Sciences at the Univ. of Wisconsin-Madison, explains: “Anything that would be purely a protein in nature could be synthesized using biotechnology. Anything that would be a combination of protein and carbohydrate or a protein and a lipid is not possible to synthesize using biotechnology. Anything that is purely carbohydrate or purely lipid in nature couldn’t be synthesized using biotechnology.”

Pure proteins, such as insulin, can be made synthetically. Pulmonary surfactant, which is a combination of protein and lipid, cannot be synthesized, and by necessity must be harvested from natural resources.

Modern pharmacology traces its roots to the early 1800s, when the properties of the botanically derived drugs such as morphine, quinine and digitalis were finding human application. By the late 1800s, scientists began to find success in applying animal-derived medicines toward human health.

In the 1890s, products harvested from the adrenal glands of sheep began to be used to treat autoimmune disorders such as Addison’s disease. This marked the first successful instance of applying animal-derived drugs to save human lives. In 1916, the anticoagulant properties of heparin were discovered. In 1922, the successful application of porcine- and bovine-derived insulin became available to treat Type 1 diabetes, providing an immediate impact on what had previously been a death sentence. Since those early years, hundreds of applications of “farmaceuticals” have been found.

Animal-derived drugs perform such varied functions as: treating symptoms of menopause, helping the skin to heal from severe burns, controlling anemia, preventing blood clots and improving blood clotting ability. Beef and pork heart valves are more successful than synthetic valves for heart valve replacement. Autoimmune diseases, hay fever, asthma, heart disease, blood disease and skin allergies are all treated with drugs derived from animals. This only scratches the surface of modern applications. Current research is aimed at expanding the list dramatically.
 Cover Story
SPL-owned trucks go to various US slaughtering plants to procure the raw material used at its facility.

Heparin for life

Heparin is a good example of a drug whose use has not only expanded over time, but is finding new applications today. Heparin was discovered 100 years ago when its properties as a blood anticoagulant were recognized. It wasn’t until 1936, however, that clinical trials cleared the way for the safe application of heparin in human health. Heparin is one of the drugs on the World Health Organization’s (WHO) list of essential medicines.

Scientific Protein Laboratories (SPL) is the nation’s largest producer of heparin. The Waunakee, Wisconsin-based facility is a great example of the confluence of the meat industry, academic research and pharmacology to improve modern human health.

Mike Reardon, chief commercial officer at SPL, recounts the company’s origins: “SPL was created as a joint endeavor between the Univ. of Wisconsin and Oscar Mayer 40 years ago. In the early ’70s, Oscar Mayer owned their slaughterhouses. There was a joint activity between the Univ. of Wisconsin and Oscar Mayer that created the first heparin process and ultimately Scientific Protein Laboratories.”

SPL is very focused in its pharmaceutical production. “We are all porcine, all the time. When you walk up to SPL, you see a statue of a pig in front of the facility,” Reardon says. “Heparin is derived from the intestinal mucosa of the small intestines of the pig. The mucosa lining the small intestine in pigs is rich in heparin.”

How important is heparin to modern day medicine? “Heparin created the basis for modern surgery,” Reardon explains. Without heparin, surgery becomes problematic. “If you’re in for heart bypass surgery, or hip replacement, the last thing you want is a blood clot forming and causing a problem.

“Heparin introduced intravenously by the physician keeps the blood from clotting during surgery. When the surgery is complete, and you want the blood to clot, the anticoagulant activity can be switched off.

“Anywhere there is surgery, you’re going to find heparin. It’s a critical lifesaving, life enabling, life extending drug for surgical patients,” Reardon says.

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 Cover Story
SPL's Specialty Products Operations staff performs a small-batch purification process.
 
 

 
A Silk Purse

Extracting heparin from the raw material involves complex logistics, and includes the transition from a messy slaughter environment to an ultra-purified product. This includes close management of the process. As the largest producer of heparin in the US market, at SPL every detail is critical.

“It’s a fairly complicated process,” Reardon states. “We start with the intestinal mucosa derived from the small intestines of pigs. These can be collected from the slaughterhouses in the US and Canada in varying forms depending upon location and distance from the processing site. We have a fleet of trucks, and own the trucking company that goes to the various slaughterhouses and picks up the raw material and brings it to our facility.

“This fleet includes dedicated tanker trucks, stainless steel tankers full of intestines that weigh 50,000 lbs. Out of that you get maybe 8 to 10 kg (17 to 22 lbs.) of pristine Heparin Sodium USP. It’s a highly purified product; we manage it very well, and nothing is wasted. The protein component of the intestines is usable as animal feed, and the choice white grease goes to biodiesel.”

Another important element, Reardon says, is SPL’s “pristine environment. It’s a highly regulated, incredibly high purity, incredibly clean operation. This doesn’t look like the slaughterhouse floor at all. We’re regulated by USDA as well as FDA, so maintaining Good Management Practices for our products is vitally important. Fully a third of the people we employee here are in quality.”

SPL also produces pancreatic enzymes, which are made from pancreas glands of pigs. A lot of people identify the porcine pancreatin product with cystic fibrosis. When children are born with cystic fibrosis, the pancreas gets compromised. Then the pancreas can’t produce the enzymes for food digestion, primarily protease, amylase and lipase.

“In the old days,” Reardon says, “those children would die young, often by the age of nine. Now by supplementing their diet at each meal with those pancreatic enzymes, those enzymes do what their pancreas cannot. People are living into their 50s.” While scientists are still searching for a genetic cure, “it’s an amazing thing that these enzymes are enabling these patients to thrive well into adulthood. It’s not just for CF patients, but anyone that has a compromised pancreas, including from pancreatic cancer, alcoholism, disease or any condition which negatively affects its function leading to pancreatic insufficiency. You can treat it with pancreatic enzyme therapy.

“These drugs from nature, derived from natural materials, are highly complicated and incredibly bioactive. Pancreatic enzymes for example are not simply lipase, protease and amylase. There are not just three enzymes, there are 30 or more such enzymes which comprise the natural product. What is not entirely understood is precisely how those different bioactive substances within the natural product coexist and interrelate to affect each other to produce the synergistic therapeutic effect. It’s not simple to construct something that complicated in a synthetic pathway. Nature is not so easy to duplicate.”
 Cover story
The Univ. of Wisconsin recently opened a new meat science and muscle biology laboratory on the Madison campus.
 
 
 

A Biological Chemist

 

Dr. Yan Wang, Ph.D., president of SPL, sees endless opportunities for the development of new pharmaceuticals to improve human health and fight diseases.

“There is a lot of product you can expect from natural resources including animals and plants. There are people doing new drug development which is a multi-year development process, and when they do that, they need someone with experience on dealing with natural material, because there are a lot of other issues beyond just the complexity of managing the supply chain in a highly quality-focused manner – things such as indigenous viruses, bacteria – those kind of things, you need to manage, control and purify to very low levels of a finished Active Pharmaceutical Ingredient prior to formulation. SPL has been in this business for 40 years, and we have the experience, so we help them to develop processes to successfully produce drugs at commercial scale and they take them on to clinical studies.”

Reardon adds, “One of the products we have been working on in collaboration with a biopharmaceutical development company for almost a decade is in late Phase III FDA clinical trials and showing great and novel promise for the treatment of autism in children. This product has been granted US FDA “Fast-Track Status” (priority review) given the great therapeutic need and is nearing the point of completing their filing for FDA review and approval. This is the kind of thing we live for at SPL…to help to enable our partner’s success and ultimately contribute to helping make patients and their family’s lives better as a result.”

Heparin has proved to be a highly versatile drug. It’s been fractionated to produce a number of different products. It is also being tested for antiviral and antibacterial qualities, and as a treatment for asthma, malaria, and some cancers, among other applications.

Another Forefront in Biological Discovery

Like Wang, UW’s Schaefer believes there are a lot of undiscovered products that can aid human and animal health, and the time is right for harvesting them.

“The gut pile is a place where you can get molecules that cannot be made by means of biotechnology. There are a lot of molecules that can only be found in animals. Because animals, on a minute-to-minute basis, have to defend themselves from the microbial world in which they live, they have to rely on their own natural defense mechanism. Could these molecules have relevance in modern human health? Probably.

“So we think there’s a lot of opportunity to find additional molecules that have an added value purpose other than tallow, or lard, or meat and bone meal,” Schaefer says.

Despite the number of products being harvested today, Schaefer refers to the biodiversity of the gut pile: “There are many, many other molecules there.” And he feels that UW-Madison is the right place to get it done. “There is no other place in the world that is looking to do this kind of research, and we think we can do it here.”

The Mission

The Univ. of Wisconsin is taking a unique approach to the discovery of new medical applications of animal co-products. This renewed focus came out of its goal to build a new meat science and muscle biology laboratory on the Madison campus.

Schaefer says, “One of our advisory committee members suggested ‘You’re not going the get the kind of financial support from the private sector that you need to build this new building if you try to base your efforts purely on philanthropy. You need to bring some value to the businesses you’re approaching.’”