Blood Rush 

Dr. Bruce Spiess and his new ideas for man-made blood have VCU Medical Center on the verge of a breakthrough.

In the politics of blood, Dr. Bruce D. Spiess is a rebel with an IV. He sees no future in hemoglobin, no cure in traditional blood transfusions. So go ahead and roll up your sleeve at the blood drive. Buy into the blood-shortage crisis promulgated by the American Red Cross if you want. The future, according to Spiess, is a milky white substance, a man-made, Teflon-like compound pulsating through your veins.

For the last 24 years, VCU Medical Center's esteemed anesthesiologist has been preaching the miracle of blood substitutes and their potential to treat brain trauma, heart attacks and other serious medical conditions. Yet few heeded his call.

Instead, the drug makers that produce blood substitutes rarely strayed from the more utilitarian applications of synthetic blood, namely as an alternative to the common blood transfusion practiced in operating and emergency rooms.

But synthetic substitutes for human blood can do so much more for needy patients, Spiess says. He and his colleagues are ready to prove it. They think they're on the verge of a breakthrough, and the scientific world, the federal government and the U.S. military are beginning to take notice.

Millions of dollars in government and corporate research grants have begun pouring into the concrete, basementlike confines of old West Hospital on Marshall Street, home base for Spiess and a wide-reaching contingent of some of VCU Medical Center's best and brightest.

The group is called VCURES — the Virginia Commonwealth University Reanimation Engineering Shock Center — and it's made up of some 90 scientists, physicians, clinicians, surgeons, engineers, professors and nurses, working as investigators on dozens of studies and research projects in trauma and shock therapies.

The group has advanced so much in the arena of traumatic surgery that the university has become one of only four institutions in the country training Army medics before they're sent to Iraq. And with the blessing of VCU President Eugene P. Trani, the group is in the early stages of launching a $150 million research institution known as Operation Purple Heart, an effort solely dedicated to treating wartime trauma. It would be the first of its kind in the United States.

The work on blood substitutes is only one piece of the project, but it's the most advanced, offering the biggest potential for breakthrough.

Quietly, the activity is generating a new buzz at VCU Medical Center and has some people beginning to recall the institution's glory days when the former Medical College of Virginia was at the forefront of medicine, perfecting the art of heart transplantation under the guidance of legendary surgeon Dr. Richard Lower. It's been more than a decade since VCU's medical college has been mentioned in the same breath with the Stanford, Duke and the Mayo Clinic. That may soon change.



Spiess, 51, left a prominent post at the University of Washington as chief of cardiothoracic anesthesia for, simply put, a woman. His wife, Heather, was from Richmond, and they decided to move to the East Coast.

In August 1999, Spiess landed a job at VCU. One of his close friends and colleagues, renowned heart surgeon Dr. Andrew Wechsler, warned him about the place, Spiess recalls, and its tendency to get bogged down in bureaucracy.

Wechsler had just spent 10 tumultuous years as chairman of cardiothoracic surgery at MCV before leaving in 1998 after a failed attempt to revive the university's storied heart program. He was handicapped, he says, by the university's unwillingness to partner with suburban hospitals to increase patient volume, critical to his research.

When Spiess got his job offer in 1999, VCU's heart program had hit its lowest point in decades, performing just one heart transplant and 175 open-heart surgeries according to the Virginia Health Network. (Comparably, CJW and Henrico Doctors' hospitals performed 995 open-heart surgeries the same year.)

Spiess took the job nevertheless and came to Richmond. He brought with him a passion for finding new ways to help heal patients using synthetic blood.

Biologically, the stuff is not human. Red blood cells carry oxygen through the body, the very process that keeps us alive. But it isn't as efficient as the fake stuff. Synthetic blood made in the lab does a superior job of transporting air to oxygen-starved tissues. Its molecules are much smaller than human red blood cells, which means it can move through blood vessels faster, getting oxygen to the body at lightning speed, even finding escape routes around the blood clots that kill during heart attacks.

As Spiess' research began focusing on different applications for an experimental compound of a blood substitute, he began to understand how far-reaching its effects could be. Instead of using it solely as a substitute for human blood in emergency situations, the compound could become a kind of treatment itself.

Initial tests in Spiess' lab revealed that the right blood substitute could stave off heart attacks, improve survival from brain trauma and even eliminate the "bends" experienced by deep-sea divers. It also has the potential to cure Sickle Cell disease, or at least stave off the agonizing pain patients experience when sickle-shaped blood cells jam and cut off oxygen to the body. The implications were enormous.

His ideas didn't gain much ground commercially, however. Drug makers must justify spending millions of dollars on research and clinical trials. And there must be a clear market with profit on the horizon. To the corporate community, Spiess' pie-in-the-sky scenarios would have required too much additional research.

Besides, drug makers already had a clear market for synthetic blood, or so they thought. They were focused on the blood-transfusion business. About 4.5 million units of human blood are transfused every year, at a price of $200 to $350 a pint, a market of $8 billion to $10 billion. Unlike human blood, the synthetic stuff doesn't have a limited shelf life, and is free of viruses such as HIV and hepatitis that can be present in human blood.

But the blood-substitute industry found itself in a losing battle. First, making synthetic blood is far more expensive, and few physicians are clamoring for an alternative that costs anywhere from $500 to $1,500 a pint. Donated blood is also much safer than it was 10 years ago.

Meanwhile, synthetic blood proved to have its own set of dangers. Many of the companies producing it, using purified hemoglobin derived from discarded human blood and cows, showed spotty success in initial clinical trials. The results spooked the U.S. Food & Drug Administration. The fake stuff caused high blood pressure, often making conditions worse. In some patients, the treatment proved fatal. And institutions such as the American Red Cross, which pays for emergency services with the profits it receives from blood drives across the country, lobbied against it.

The Red Cross is a massive nonprofit synonymous with saving lives by the pint. Politically, the synthetic blood industry was looking like mad scientists trying to take on Mother Theresa.

Spiess tried to point the industry in a different direction.

"For years I was a pariah in the blood-substitute world because I would stand up at national meetings and say, 'Excuse me, but you guys are full of shit. You're wasting all of your time,'" Spiess says. "Go look at how you can change medicine for patients. Don't go up head to head with the American Red Cross."

The industry didn't listen. And while blood substitutes based on hemoglobin continued to bomb, Spiess had turned his attention to a different variation of synthetic blood — one that had not been tested as frequently and had undergone fewer clinical trials. The white,Teflon-esque blood substitute was derived from perfluorocarbons, and it included no hemoglobin, no human molecules.

Faced with the marred record of the other blood substitute, few companies were looking to invest the time and money to test the potential of the newer version in clinical trials — especially as an alternative to blood transfusions. But one company producing it, Synthetic Blood International Inc. of Costa Mesa, Calif., was starting to see the light.



Robert W. Nicora, chief executive of Synthetic Blood, recalls first hearing Spiess speak at a conference for anesthesiologists in Honolulu in late April 2004. Nicora's company is developing a perfluorocarbon-based blood substitute called Oxycyte, and he was familiar with Spiess' work. But after hearing him speak, he believed Spiess might be able to help his company.

"His talk was mainly focused on how blood deteriorates when it's stored. I made a note to contact him," Nicora says. "We are working primarily with anesthesiologists. I knew he was the guy we wanted to hook up with."

The two hit it off immediately. Synthetic Blood was already moving in the same direction as Spiess. Their competitors had struggled to sell hemoglobin-based blood substitutes, and he knew that his compound needed a different direction.

A little more than a year since the conference, Synthetic Blood is set to launch a pilot clinical study to see how Oxycyte works in treating traumatic brain injuries. The trials are expected to begin in September. And the U.S. Department of Defense has expressed keen interest in the research.

"This is becoming the so-called signature injury of the Iraq War," Nicora says. "[Soldiers] mostly suffer brain injuries from those concussive bombs. It's very much like picking up a baby and shaking them violently."

In animal tests conducted in the labs at VCURES, they've found that Oxycyte can limit the damage done when the brain smashes against the skull. Because it can deliver oxygen to the brain tissue quickly and effectively, Oxycyte could potentially increase the survival rate of soldiers in the battlefield dramatically, according to Nicora and Spiess.

Defense officials have latched onto Spiess and Oxycyte. "Lo and behold, the Department of Defense was enthusiastic about that relationship," Spiess says. He told the military officials that researchers at VCU could create a research model for the government to begin testing their shock treatments in animals. With human clinical trials set to begin this fall, with any luck Army medics could be using it within a year.

As for the FDA, Nicora holds out hope that the U.S. government can help facilitate the process in order to get Oxycyte to the battlefield as quickly as possible.

"The FDA is a political organization in the sense that it does respond to political pressure," Nicora says. "So if it had the Army or the Navy breathing down its neck because it wanted access out in the battlefield. … the study process could be shortened in certain ways."

In the end, the government could become a powerful ally in getting the blood substitutes to market — something drug makers have failed to do for more than 20 years. For the most part, Nicora credits Spiess for paving the way.

"He's like a godsend to our company," Nicora says, adding that the consortium of researchers working with Spiess at VCU are beyond impressive. "I have been in the industry for 35 or 40 years," he says. "I have not seen a group as broad, as deliberative and well-organized."

The VCURES and Purple Heart teams span both campuses and include almost every scientific discipline, primarily for the treatment of wartime injuries.

"It's not just the medical school," Spiess says. There's chemical and mechanical engineering, the department of biology, a center for biochips and biotechnology — even people from the philosophy and religion schools.

Their mission is to find answers, Spiess says: "What's the impact of shock? What's the impact to their sociology, their extended family? It goes far beyond what the docs are doing to try and save somebody's life."

In mid-July, donning a red, white and blue surgical cap, Spiess moves quickly through the halls of the hospital, into a cramped lab where a group of assistants halt to attention. There's small decompression chamber for testing his blood substitutes in pigs as part of his research with the U.S. Navy, one of the many clinical trials Spiess' team is working on. He rattles off the grants he and his colleagues at VCU have won over the past five years to treat everything from brain injuries, the bends in submariners and divers, and Sickle Cell — a grand total of about $23 million.

Spiess's work in blood substitutes jump-started the collaboration between his two primary partners at VCURES — Dr. Rao R. Ivatury, director of trauma and surgical critical care at the university, and Dr. Kevin Ward, director of research in the department of emergency medicine. As luck would have it, all three found their way to VCU in the late 1990s. It wasn't long before they were discussing ways to combine their research.

"We wanted to take the most horribly injured person, almost like the Coyote, and design whole new therapies," Ward says. "How are you going to save someone who has both their legs blown off? Like cancer, trauma is a very complex disease. This is simply the cancer-center approach to critical illness and injury."

Their collaboration worked. "It just snowballed," Spiess says. "And then we started finding that this university has a wealth of untapped talent."

For example, it didn't take long for Spiess to find Roland N. Pittman, a physiology professor renowned for his work in microcirculation, the study of the small blood vessels, or capillaries, "the tiny, tiny blood vessels where a single red blood cell goes through one at a time," Spiess explains. "That's where the oxygen is transferred to the tissues. That's sort of where the rubber meets the road."

Until Spiess came along, physicians in the operating room had never approached Pittman: "He'd never had a clinician from the operating rooms come to him and say, 'Here's a problem we deal with every day. Design me something in your lab that mimics what we deal with.'"

Pittman's research turned up intriguing results. For instance, in animal tests he found the chances of surviving blood loss could be much greater than what's generally accepted in the emergency room. Red blood cells make up 45 percent of a healthy person's blood. Patients are considered to be in immediate need of a blood transfusion when their red blood count drops below 15 percent. But Pittman's research found that when animal subjects receive a hemoglobin-based blood substitute, they can survive reasonably well when red blood counts drop below 10 percent.

The implication? Patients may be able to survive for much longer without transfusions during extreme blood loss — a profound discovery — which means that surgeons may have more time, and need less blood, than few thought possible.

Branching out to collaborate with physicians for the first time, Pittman says the work helped his lab secure a research grant from the National Institutes of Health, which has greatly improved the quality of research he and his graduates have undertaken.

"It really requires collaborations between basic scientists like myself and clinicians," Pittman says of the work. "The potential for making advances in the treatment of diseases and other syndromes is much greater than it would be otherwise."

Ivatury says the environment at VCU is a rarity in medicine.

"This is the first time that clinicians like myself collaborate with basic scientists and look at the cell and the very microscopic parts of the cell and apply that knowledge to the patient," says Ivatury, who gained international recognition when he saved a victim of the 2003 sniper rampage in Northern Virginia. "That is a tremendous advance." (Ivatury has been credited with perfecting a unique method of surgical "staging," wherein he performed a series of surgeries spread over a period of days, allowing the patient to recover and rehabilitate more effectively.)

With so few massive egos roaming the halls, Ward says he and his partners were able to cross-pollinate research throughout the university with ease, something that is decidedly more difficult at bigger, more renowned medical colleges.

Meanwhile, a free-flowing research philosophy has slowly begun to energize VCU's medical campus, Ward says. "Nothing is too crazy to try, no idea is too bizarre," he says proudly, pointing to one of their more recent studies: suspended animation in trauma patients — in essence, slowing down the body's metabolism to decrease the loss of blood. If it works, think Buck Rogers after a terrorist attack.

"You can give all the blood you want, but if you can't stop the bleeding, you're going to have a bad outcome," Ward says. "We're trying to be as holistic as we can. … We want people to live long enough to get heart disease or cancer."

Robert T. Skunda, president and chief executive of the Virginia BioTechnology Research Park, says the group has real potential. He's advising VCURES on its marketing and fund-raising efforts, and says the timing — because of the situation in Iraq — couldn't be better for more research on battlefield injuries.

"It's another kind of undiscovered treasure," Skunda says of VCURES being located in Richmond. "I think they recognize that the need is there because the U.S. military does not devote the research dollars to this area … of battlefield injury."



In the end, even if the blood-substitute research comes up short, Spiess' work will live on at VCU. As an outgrowth of his research, he's also helped the cardiac-surgery team greatly reduce the number of blood transfusions needed in the operating room with better blood management. It's saving more than $500,000 a year.

In 1999, the year Spiess arrived, 80 percent of all the university's heart-surgery patients received blood transfusions. Today, only about 15 percent of heart-surgery patients are receiving blood transfusions.

"We have a seen a benefit for the patients," says heart surgeon Dr. Abe DeAnda, associate professor of cardio-thoracic surgery. "There are a series of problems with blood transfusions. Old blood is not necessarily good blood.

"And there are times when we are notified that the blood bank is drying up. It's not something that's always on the shelf."

Indeed, Spiess says changes in blood management and the addition of blood substitutes, could provide a new anchor for a medical college with a long history of saving lives. He hopes with his work in blood substitutes, the advances in treating trauma and the efforts of Operation Purple Heart can catapult VCU to an international audience. Who knows, it just might work.

"Boeing last year made $50 billion from the department of defense. Why can't they give $5 million to help save the wounded soldier?" Spiess muses. "It's like mom and apple pie. You can hear the 'Star-Spangled Banner' in the background. Well, to me, I can't see anybody who's going to say no to that." S



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