Wednesday, September 26, 2012

War Healer

 This is extraordinary good news. With military funding, medical restoration research is advancing now in real time. If it works, it is used ASAP and the results guide further application. The rest of medical science needs a sharp dose of this mentality for two good reasons. The first is that our knowledge base is deep enough to respond well to failure and to track lessons learned properly. Thus a protocol failure instructs immediately and real losses balance well against assured losses from continued failure to successfully treat and resolve health issues. The second is more subtle. It is ethically wrong to withhold risky unproven therapies from the patient's palette of choices. If the patient is fully aware of the risks he needs to be given the opportunity to roll the dice. He at least then knows that failure has the reward of helping the science.

A lot of good questions can be answered in a hurry in circumstances like this. At present we have a harm prevention protocol that barely allows well defined questions to be answered and nicely stalls innovative work.

I personally know a protocol that will plausibly reduce the impact of burn damage by close to ninety percent and naturally set the stage for any regrowth therapy that could come along. Advancing that knowledge requires an exponentially increasing amount of money starting with a couple of million to cleanup the loose ends.

Thus advancing even a clearly important technology is massively intimidating and instantly challenges individual credibility to the point of deterrance.

The great news is that the military knows better and is not letting this happen. We will have results.

War Healer

By Katie Drummond
    September 24, 2012

Dr. Joachim Kohn has never seen combat. He has never retaliated enemy fire, deployed with a platoon to some foreign, war-ravaged nation, or ridden shotgun in a tank. But from his first years of childhood to his military-funded, revolutionary scientific innovations, Kohn’s life has been indelibly marked by armed conflict.

One of my earliest memories is at three years of age, making a playground out of bombed-out buildings,” Kohn, now a spry 60 years old, recalls. “Houses, offices, these shells of buildings that were simply everywhere.”

In fact, Kohn’s playground was the urban carcass of Munich, Germany, where he was born to Jewish parents shortly after the end of World War II. Having lost much of his extended family, including grandparents and seven aunts and uncles, during the Holocaust, Kohn grew up with an intimate understanding of war’s human toll.

And the understanding seems to have stuck: More than five decades later, Kohn, a chemist, is at the helm of a $250 million, Pentagon-funded exploit into regenerative medicine called AFIRM. His goal: to take those people ravaged by war, and help put them — quite literally — back together.

Kohn himself pioneered a new class of degradable compounds that are now used inside the body to provide controlled drug delivery, as well as for tissue engineering and regenerative processes like bone and nerve repair. And during his leadership of the AFIRM program, scientists under Kohn’s guidance have already completed an array of futuristic therapies to heal wounded soldiers: Among them are the country’s first-ever face transplant; lab-grown ears nearly ready for human transplantation; and an engineered skin substitute that will soon be tested on soldiers with extensive burns.

When he emerges from his office, tucked into a wing on the first floor of Rutgers University’s sprawling Life Sciences building, Kohn looks more like a lawyer or an accountant than he does a chemist. Clad in a gray suit and tie, his cellphone — which vibrates incessantly — clipped to his belt, Kohn is trying to rub the glare of a computer screen from his eyes.

Before the launch of AFIRM in 2008, Kohn spent most of his career in the lab. But in his role as an AFIRM director, he now spends “99.9 percent” of his time managing the monumental undertaking from the confines of his campus office.

AFIRM, short for the Armed Forces Institute of Regenerative Medicine, was established by Pentagon brass to do what, just four short years ago, seemed nearly impossible: target the most common, debilitating injuries from this generation’s wars, including burns, lost limbs and invasive wounds, and use cutting-edge medical technology to heal them utterly and completely. Instead of prosthetic arms, create flesh-and-blood replacements. Rather than burned skin partially repaired with a messy patchwork of grafts, replace that skin using sheets of lab-grown epidermis. And in lieu of acquiescing to bones, muscles and nerves that will be permanently missing, spur the soldier’s body to regrow what they’d lost.

Not only that, but do it quickly: The Pentagon intended for AFIRM to accelerate the rate of regenerative medicine progress by decades, and later infused a handful of promising projects with extra money to garner even speedier results. “Ten years doesn’t satisfy any of us,” former Joint Chiefs of Staff Admiral Mike Mullen told AFIRM researchers in 2010 of the impetus to fast-track regenerative medicine from the lab into the human body.

To do it, the Pentagon assembled two consortia of scientists. One of them, the Rutgers-Cleveland Consortium, is directed by Kohn. He oversees dozens of research projects, performed by nearly 150 scientists at 21 different institutions, including Harvard, the Mayo Clinic and the Massachusetts General Hospital.

Plenty of the consortium’s projects remain firmly in the lab, but a handful are either already treating wounded soldiers, or are expected to enter clinical trials within the next few years. “Our field of regenerative medicine is today wildly overhyped,” Kohn says. “We have done very impressive things, but I don’t want to make promises about therapies that maybe work in a lab, but [end up] not working in a person.”

But with six clinical trials already under way or slated to start soon, the team is already treating some injured servicemembers. At the University of Virginia, surgeons are using transplants of a patient’s own fat to accelerate the healing of burn wounds — which account for 12 percent of injuries among today’s soldiers — and prevent rampant scarring that was once inevitable. At the Cleveland Clinic, doctors continue to hone extensive facial transplants, and are actively enrolling and operating on soldiers and civilians who qualify for the extreme procedure.

Other therapies will soon be tested on patients. Among them is a procedure developed at the University of Cincinnati, which will grow fresh reams of skin within the lab — a process that takes merely three weeks — and use the skin to replace a patient’s burned flesh. Yet another, nearly underway at the Mayo Clinic, will one day restore sensation lost to devastating injuries by using an implanted scaffold to spur nerve regeneration across large gaps.

Kohn is responsible for keeping those projects on-track. “The man is the single best research manager I have ever met,” says Col. (Dr.) Bob Vandre, who spearheaded and later directed the AFIRM program. “Under him, [this research] is already looking to make a huge difference for patients.”

Kohn’s role in AFIRM successes actually started decades ago: That was when, thanks to a lab experiment gone serendipitously wrong, Kohn invented an entirely new class of polymers that are ideal for use in the human body.

In 1972, Kohn left Germany for what he intended to be a one-year exchange program at Israel’s Hebrew University. “Of course,” he smiles, “Then I met a girl.”

One year in Israel turned into 11, that girl became his wife, and Kohn completed his undergraduate degree and Ph.D. in the country.

Midway through his studies, Kohn was conscripted into two years of mandatory military service, though he never endured combat. Instead, a 25-year-old Kohn found himself working in the Army Surgeon General’s office during the aftermath of the 1973 Yom Kippur War.

He remembers seeing soldiers suffering from often-deadly burn wounds — the signature injury of that conflict. Shortly thereafter, Kohn started the scientific investigations that would one day, albeit unintentionally, catalyze regenerative treatments for the very same affliction.

I never set out thinking, ‘Oh, in my career I want to treat these war injuries,’” he says. “Somehow, though, that’s the path I found myself taking.”

Kohn’s investigations started during his PhD, under the leadership of Dr. Meir Wilchek, a renowned biochemist. Wilchek, now 78, remembers Kohn — known affectionately as “Micha” after the Hebrew-speaking registrar’s office translated his first name from right-to-left, spelling it backwards — as his best-ever student, and one who would often join him “to drink beer and talk chemistry,” on the rooftop of Wilchek’s apartment building.

Those chats sometimes revolved around the art of enzyme immobilization, which was the focus in Wilchek’s lab and of Kohn’s Ph.D. studies. Scientists at Israel’s Weizmann Institute of Science were trying to figure out how an enzyme could be permanently bound to polymers, large molecular structures comprised of repeating sub-units. But in his efforts to keep those enzymes attached, Kohn discovered a reaction that yielded the opposite effect.

I found a side reaction; an unwanted reaction that created an unstable bond,” he says. “The bond would fall apart in water, and free the enzyme to go away.”

The unwanted side reaction took on unexpected importance in 1983, when Kohn emigrated to Boston and pursued a post-doctorate in the biomedical engineering lab of Dr. Robert Langer at MIT.

There, Langer encouraged Kohn to invent totally new polymers that would be affixed with drugs, and slowly fall apart inside the body of the patient. In so doing, the polymers would release the medication over a prolonged period — the basic principle behind a new field known as “controlled drug release.”

Kohn had an idea: Using the unwanted side reaction from his thesis work in Israel, he designed a new family of degradable polymers that would fall apart when exposed to water inside the body. To avoid toxicity, he used naturally occurring amino acids as building blocks for the polymers, making them safe for implantation.

When he invented these polymers, I don’t think anybody really was aware how far they’d take him; how they’d set the stage for his entire career,” Langer recalls. “But the impact he has had is enormous.”

Kohn took his polymer creations, which he named pseudo-poly(amino acids), to Rutgers in 1986. There, he hoped to refine them for use in additional medical applications. “MIT scientists are like the Apollo guys of science, the ones that shoot for the moon,” he says. “Rutgers was better for those smaller projects, the years of tweaking you need to turn a lab project into something practical.”

Before long, Kohn was using the polymers in drug-delivery systems and tissue engineering. He patented more than 40 of them, and helped develop computational simulations that allowed for rapid tweaking to create polymers with myriad physical properties (stiff or flexible, quickly or slowly degradable).

Kohn helped found three companies, and licensed his technology to several more. One of his early creations, a sleeve that holds pacemakers and defibrillators in place, delivers antibiotic medication, and then dissipates into the body, has been implanted into 30,000 patients. Some of his other innovations include a drug-delivery system that administers medications from within a patient’s eyeball, and a resorbable stent — currently in clinical trials — to heal arteries following a coronary angioplasty.

Within his AFIRM consortium, the technology that Kohn developed has taken on additional import. His polymers are at the basis of an absorbable patch that, when applied to recent burns, delivers drugs able to prevent progression (a second-degree burn turning into a third-degree burn) and scarring. They’re also the key element to bone regeneration, a project that aspires to bridge bone defects — and eliminate the need for bone screws or plates — using an implanted scaffold that spurs new bone growth.

The Pentagon didn’t take note of Kohn’s work until 2003, when he set out to launch an institute at Rutgers specifically geared towards using biomaterials — like his polymers — to meet the needs of military medicine.

Kohn received a $1.5 million congressional earmark to launch the institute, called the Center for Military Biomaterials Research. But the award didn’t exactly endear him to military brass. After all, until their ban in 2011, congressional earmarks were widely criticized, renowned for foisting limp, ill-conceived projects on government agencies.

There’s a reason we used to call earmarks ‘pork’,” Vandre says. “In my experience, a lot of the recipients ended up not performing very well at all. I wasn’t convinced that this project was even worthwhile.”

Vandre’s skepticism didn’t last. The center’s earliest research, which Kohn oversaw, was essentially a precursor to AFIRM: preliminary investigations of polymer-based regenerative therapies, including degradable tissue scaffolds, drug-delivery systems to hasten wound repair and implants to prompt bone regeneration. Impressed, Vandre in 2006 “was pleased” to see Kohn assemble a team of scientists and apply for the Pentagon’s newly conceived regenerative medicine program.

When his consortium was one of two to receive funding, the size of Kohn’s research center at Rutgers doubled almost immediately, and his own professional existence transformed “pretty much overnight,” he says. “Suddenly this one immense program overwhelms any other activity,” he says. “For me, there is now nothing beyond AFIRM.”

In his role as director, Kohn keeps abreast of every research project, guides scientists, and works to find industry partners interested in commercializing fully developed therapies — a move that could soon see some regenerative treatments available to civilians. He also holds the purse strings: Of the more than $120 million invested into his consortium, he leads the deliberations that determine which projects and proposed trials merit funding.

Maybe I used to be the quarterback, and now I’m more like the football coach,” he says of his behind-the-scenes role in AFIRM’s high-profile projects. In the countless media reports recounting AFIRM breakthroughs, Kohn’s name rarely garners a mention.

But Kohn is happy to remain unnoticed and uncredited for his work. That’s in part because, as Kohn has seen firsthand his entire life, any struggles he endured are nothing compared to the plights of those he’s helping to treat.

I didn’t endanger my life in anyway, and I didn’t put myself on the line to save anyone,” he says. “I was just sitting in my laboratory, waving my hands around, sometimes having good ideas.”

1 comment:

Anonymous said...

Carbon and Life

-It is hard to overstate the importance of carbon; its unique capacity for forming multiple bonds and chains at low energies makes life as we know it possible, and justifies an entire major branch of chemistry – organic chemistry – dedicated to its compounds. In fact, most of the compounds known to science are carbon compounds, often called organic compounds because it was in the context of biochemistry that they were first studied in depth.

-What makes carbon so special is that every carbon atom is eager to bond with as many as four other atoms. This makes it possible for long chains and rings to be formed out of them, together with other atoms – almost always hydrogen, often oxygen, sometimes nitrogen, sulfur or halides. The study of these is the basis of organic chemistry; the compounds carbon forms with metals are generally considered inorganic. Chains and rings are fundamental to the way carbon-based life forms – that is, all known life-forms – build themselves.

-Silicon is capable of forming the same sorts of bonds and structures, but opinion is divided on whether silicon-based life forms are a realistic prospect – in part because it needs higher energies to form them, and in part because whereas carbon dioxide (one of the main by-products of respiration, a process essential to all known life) is a gas and therefore easy to remove from the body, its counterpart silicon dioxide (silica) has an inconveniently high melting point, posing a serious waste disposal problem for any would-be silicon-based life form.

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