Hopes high for artificial organs, despite slow going

Fifty years ago, Ronald Herrick donated one of his kidneys to his identical twin, Richard. It was the first successful organ transplant, pioneering surgery performed at what is now Brigham and Women's Hospital. Richard Herrick lived for another eight years, thanks to the transplant. His brother is still with us, as is Joseph Murray, the surgeon who led the transplant team and who was later awarded the Nobel Prize in Medicine.

Organ transplants, while miraculous, have two major drawbacks.

They require the recipient to take expensive antirejection drugs for the rest of his life, which depress the immune system and have a host of other side effects.

And there's a perpetual shortage of organ donors. Right now, more than 1,300 people in Massachusetts are on the waiting list for a new kidney. Unfortunately, not everyone has a generous identical twin.

So why, half a century after the first kidney transplant, have not we developed a wide range of artificial organs that can be implanted in patients, just as organs from human donors are?

''If we were talking 10 years ago, I'd have said that the impact, commercially and medically, of tissue engineering and organ replacement by 2005 would be significant," said Michael Lysaght, a professor at Brown University who heads the Artificial Organs Laboratory. ''What time has proven is that we were just overly optimistic. This will take longer than people felt."

Several companies trying to bring products to the market have stumbled. Among them are Organogenesis in Canton, which makes artificial skin patches, and which emerged late last year from bankruptcy protection. Circe Biomedical of Lexington raised nearly $100 million to develop an artificial liver, which operated outside the body, but ran out of money before winning FDA approval. Danvers-based Abiomed was forced to redesign parts of its implantable artificial heart to reduce the possibility the device would cause blood clots, which can lead to strokes.

New England is a center of gravity for research into made-to-order organs, sometimes called ''bioreplacement," with initiatives not just at Brown, but at Massachusetts General Hospital, Brigham and Women's, and MIT. This month, two conferences will be held to assess the field's progress, one in Washington, D.C., the other in Seattle. (The former will include a display of the first Abiomed heart implanted into a patient.)

The research activity is encouraging. At Mass. General, Joseph Vacanti, who heads the Laboratory for Tissue Engineering and Organ Fabrication, is beginning to implant prototype artificial livers into rats. The device is about the size and thickness of a pad of yellow Post-It Notes. It combines polymers and living cells. ''We're hoping that it will do all the metabolic housekeeping of a normal liver," Vacanti said.

The primary focus of his lab has been to create a platform on which living replacement organs can be grown. Think of it as the sprinkler system underneath a yard, necessary for keeping the grass above healthy. The platform ensures the organ will receive adequate blood supply as it grows.

Vacanti and his colleague at MIT, Robert Langer, have used manufacturing techniques borrowed from the semiconductor industry to create microscopic channels through which blood can flow. But even though these replacement organs might be produced in a factory, they'd be different from a pacemaker or artificial heart; Langer and Vacanti intend for their polymer platforms to eventually dissolve into the body, replaced by a living organ that doesn't function any differently from the one you were born with.

Current medical devices, said Lysaght at Brown, ''are made with metals and plastics that aren't really different from the metals and plastics you can get at Home Depot. There's a desire to make things that are more compatible with the body, and get it to the next level."

But while research continues to percolate, there's not much start-up activity. Companies like Circe and Organogenesis ''attracted people's attention, but also made [investors] go cool," said Jean-Francois Formela, a senior partner at Atlas Venture in Waltham. First-generation products aren't necessarily good enough to treat many different types of patients. The start-ups that develop them sometimes don't have enough money to get through FDA trials, or to market their products. ''They realized the challenges of trying to do it with a first-generation approach. They all hit the same quicksand," Formela said.

Aside from Abiomed, one of the few New England companies that's currently doing trials of an organ replacement technology, there is Nephros Therapeutics in Lincoln, R.I.

Nephros, which sprang from research done at the University of Michigan, has raised $31 million and is trying to raise more. (One of its senior executives, coincidentally, came to Nephros from Circe. That company's assets were bought in April by a California company for less than $500,000.) Right now, rather than try to create a fully functional artificial kidney, Nephros is testing a system that would work outside the body to perform some kidney functions.

''We're focused on acute renal failure," said chief executive Richard Andrews. ''Patients may have an infection, or they have had trauma with blood loss, or blood loss from surgery. Their kidneys stop functioning."

Nephros runs the patient's blood through a cylindrical tube that's filled with living kidney cells taken from donor organs. (Nephros uses kidneys that don't meet the criteria for a transplant; they're surrounded by too much fatty tissue, for example.) The kidney cells are separated from the blood by a fiber membrane that allows nutrients and waste from the blood to cross -- but prevents the body's immune system from being aggravated by the foreign cells.

''This is different from dialysis," Andrews said. ''That's focused on separating waste from the blood. We're concentrating on replacing the metabolic and regulatory functions of the kidney, which are involved in helping the body fight infection and manage inflamma-tion."

Andrews said that today, between 55 and 70 percent of the people who experience acute renal failure don't survive it. Nephros is in the midst of a clinical trial that will test the system on 100 patients over the next year, including some at Mass. General.

''We do think a lot about building a fully implantable kidney," Andrews said. ''We have some designs. But we want to do it in a step-wise fashion, so you can make a contribution at each step." That step-wise approach may also help the company avoid major technical barriers, or running out of cash.

''Right now, we're focused on the acute market," he said. A second step would bring Nephros' technology to the patients who today rely on dialysis machines, ideally providing them with better treatment and improving their health. Stage three would be an implantable device.

Off-the-shelf kidneys aren't yet available, but some in the field are already thinking about the next milestone. ''The ultimate goal will be to get the body to repair its own parts," Lysaght said. ''We know that can happen. That's what Dolly the sheep told us, that any cell in the body is capable of creating any other cell in the body. All you've got to do is figure out how to do that." But Lysaght -- who admits his estimates on timing have been off before -- said getting there could take another 50 years.

Scott Kirsner is a contributing editor at Fast Company. He can be reached at skirsner@verizon.net.