WHERE once they seemed utopian, early promises by genetic engineers to stave off disease, replenish stocks of organs and rejuvenate populations now appear unacceptable, even intimidating. To work these miracles of modern medicine, biologists need to explore genetic modification, stem-cell research and xenotransplantation (use of animal organs in humans). But the public outcry against such research has resulted in most of it being heavily regulated or banned outright.
Making matters worse, these research tools have proved difficult to use in therapy. Even one of the least controversial, but most valuable, applications of such research—growing healthy adult organs from adult stem cells—now seems decades off. Without such technology, the shortage of donor organs and the growing toll of diabetes and heart disease will only get worse.
The good news is that a number of companies are seeking remedies for such afflictions that avoid the political and scientific challenges posed by cloning. They are developing substitute blood and guts using traditional engineering metals, chemicals and plastics held together with nuts and bolts. Within a couple of years, repairing patients could be more like fixing worn out motor cars.
According to the World Health Organisation, heart disease is the deadliest ailment in the world. Thousands of patients need new hearts annually; most die waiting. In the next 25 years, as the number of diabetics worldwide doubles to 300m, the demand for fake pancreases will soar. Add to that an ageing population that is going to need better hearing, eyesight and livers. No surprise that the bionics industry is enjoying such robust growth.
One of the most eagerly-awaited products is artificial blood. Getting people to donate blood of different types in sufficient quantities is costly and time-consuming for clinics. Much of it goes to waste. After six weeks, stored blood starts to spoil and must be discarded. Collection clinics must certify each donation to be free of diseases such as HIV and hepatitis. But as recent tragedies have shown, such tests are far from foolproof. When labour costs are included, the price of a typical 250-millilitre unit of blood is $200-250. A proposal to filter out white blood cells, which may irritate some patients, could raise the price by a further $30-40.
Companies that make artificial blood are eager to cater for this demand, which amounts to some 14m units a year in America alone. The market for artificial blood in the United States is supplied by a Canadian firm called Hemosol and three American companies, Biopure, Northfield Laboratories and Alliance Pharmaceuticals. Hemosol, Biopure and Northfield manufacture solutions of purified haemoglobin, the molecule in blood that transports oxygen throughout the body. The Hemosol and Northfield products use haemoglobin that is harvested from human blood, while Biopure uses haemoglobin purified from cows. Such products are a sort of “eau de blood”, providing haemoglobin's oxygen-carrying capacity without any of its infectious or abrasive ingredients.
Alliance's product, called Oxygene, takes this a step further. Oxygene contains no animal or human blood products whatsoever, being a milky emulsion of salt water and a compound called perflubron. The attraction of perflubron is that its molecules stow oxygen in their core. When they float past oxygen-starved tissue, the perflubron molecules swap their oxygen for carbon dioxide more readily than does human haemoglobin. After a day or so in the bloodstream, the perflubron evaporates and is exhaled harmlessly by the patient. All of these blood substitutes are disease-free, cost about the same as natural blood, and have a shelf life of one to three years.
The best thing about artificial blood is that, containing no nasty proteins, it works with all blood types. Man-made organs are similarly compatible. Some get their universal appeal from the innocuous materials out of which they are made. Others make themselves acceptable by hiding their potential threats from the body's immune system. This special attribute of artificial organs in general—universal compatibility—is what has kick-started the business and attracted the hot money.
Not without reason. More than 75,000 Americans are waiting for a suitable organ to be donated. Only one in three will be lucky enough to get a transplant. And those that do will have to remain on a harsh regimen of drugs for the rest of their lives—to prevent their immune systems from rejecting the foreign tissue.
Have a heart
The idea of a totally artificial heart has set medical pulses racing. The first working attempt to make such a device, Jarvik-7, was tried out in several patients during the early 1980s. The problem with Jarvik-7 was that it required patients to remain constantly tethered to a machine the size of a refrigerator. Worse still, it caused deaths from clots and infection. Since then, artificial hearts have been used only as “bridges to transplant”—to tide patients over while a donor heart was found.
That has begun to change. Several American and Canadian firms are now getting regulatory approval for artificial heart devices that will remain in the body permanently. One device called AbioCor, which is made by Abiomed of Danvers, Massachusetts, replaces the natural heart entirely. Others, such as the HeartSaver from World Heart of Ottawa, replace or augment only the activity of the left ventricle—the lower chamber that pumps the blood through the body. Since it is the left ventricle that collapses in most cases of heart failure, such a “left-ventricular assist device” often provides enough help to allow the heart to start beating again with much of its natural tissue intact.
Made from materials such as titanium and Dacron, artificial hearts use a sensor to gauge the blood flow and a chamber to hold the blood while it is pumped by a battery-powered rotor. Oddly, a pulse is optional. Both the AbioCor and the HeartSaver generate one to keep the patient happy. The device rests in the chest cavity adjacent to the real heart. The internal batteries that power the device are recharged through the skin without the need for wires. A magnetic coil laid against the abdomen induces an electrical current in a matching magnetic coil stowed inside the patient's body.
Both Abiomed and World Heart have incorporated additional sensors to monitor such vital signs as heart rate and blood pressure. The HeartSaver will be able to transmit such data to a local controller using an infra-red wireless signal. With the control unit linked to the Internet, hospitals will be able continuously to monitor patients fitted with artificial hearts. Better still, a doctor in a hospital who notices that the device is beating too slowly could send instructions over the Internet to tell it to speed up.
World Heart already has approval for long-term use of its HeartSaver in Europe. The company hopes to start human trials in Canada before the end of the year. And now that the FDA has approved clinical trials in America, the first AbioCor could be implanted in a human patient by June. Initially, such a mechanical heart would cost as much as $60,000-100,000, though the price could fall by half once the device goes into mass production. Even after adding a further $40,000 for surgery, the total bill for installing an artificial heart would be considerably less than the $200,000 that transplanting a donor heart costs today.
The body electric
Despite its ingenuity, the mechanics of the natural heart are relatively straightforward. Even severed from nerves, it will continue to beat when placed in a bucket of correctly salted water. By contrast, other organs of the body are more multifunctional. And simulating them requires more complicated equipment.
Take the pancreas. This senses levels of glucose in the blood and releases insulin accordingly. MiniMed, a firm based in Northridge, California, manufactures external insulin pumps that can be programmed by patients to deliver appropriate doses of insulin. It is also testing a sensor that can continuously monitor blood sugar levels. Once the company mates these two technologies, the external pump could automatically gauge and administer microdoses of insulin. MiniMed hopes to make an implantable pump-and-sensor, thus erasing all evidence of the disease and its cure.
Nature's own materials
But designing and building such sensors and chemical pumps is costly. One alternative is to use nature's own equivalents—ie, living cells. Circe Biomedical of Lexington, Massachusetts, is testing an implantable “bio-artificial” pancreas that contains living pancreatic cells taken from pigs. The patient's blood flows through a graft into a membraneous tube that is surrounded by the pig pancreatic tissue. Through the membrane, the cells detect the level of glucose in the human bloodstream and release insulin as required. But since the pig cells are encased in a plastic housing, the patient's immune system never detects their presence—and therefore never mounts an attack. Every few months, the supply of pig pancreas cells is washed out and replenished through portholes that are embedded in the patient's abdomen.
Circe and other firms are pursuing a similar approach with artificial livers. No mechanical device has yet come close to replicating the host of chemical actions performed by liver cells. They cleanse the blood, break down and build complex molecules, and keep the blood volume on an even keel. So the artificial livers in development use actual liver cells—from pigs as well as from people—to do their chemical work for them. Such machines could be used to support patients in critical condition while they wait for a liver to be found for transplant.
Artificial livers work in much the same way as do kidney-dialysis machines. Blood is taken from the body, cleaned, treated and then replaced. As blood is collected from the patient's body, the fluid portion (“plasma”) is extracted and the blood cells and other solid matter set aside. The plasma is then pushed through a charcoal column to extract the toxic chemicals. Next, it is oxygenated so that it can do its basic job and then enters a so-called bioreactor.
The bioreactor contains up to 5,000 hollow tubes made of a flexible membrane, clustered together in a plastic cylinder. Liver cells that have been cultured to grow on the outer surface of these tubes freely exchange biological molecules and water with blood passing through the membrane. As with the artificial pancreas, the membrane screens the foreign cells from the patient's immune system, which never realises that interlopers are meddling with its blood supply.
VitaGen of La Jolla, California, takes a similar approach, but with an important difference. Instead of pig cells or normal human cells, the firm uses a patented line of cloned human cells that are bred to be immortal. VitaGen's device is being tested in America. Meanwhile, Circe's HepatAssist should finish its clinical trials by the end of 2001.
Spare parts for the body shop
Such technologies for making artificial organs are only the beginning. Every part of the human body is now being studied to see how it can be replicated artificially or augmented in some way. Biomedical engineers at the University of Pittsburgh Medical Centre are developing prototypes of an artificial lung that can be strapped on a belt, rather like a mobile phone or personal digital assistant. A team led by William Federspiel, a veteran of Abiomed's artificial heart team, is working on an intravenous oxygenator that exchanges gas with the blood as it passes through a set of hollow fibres. A firm called Optobionics, based in Wheaton, Illinois, is trying to create a silicon chip that stimulates the visual cortex and may help to restore sight to the blind. And various types of substitute cartilage, bone and skin are working their way through clinical trials.
The technical hurdles that such firms have already overcome also lay the groundwork for future achievements. Most notably, they extend the range and capabilities of membranes that are safe to put inside the human body. They provide means for inserting power supplies within flesh. They allow animal tissue to be used safely in people. And, best of all, they detach the whole business of organ replacement from the tricky ethical questions associated with genetics, returning the endeavour to the practical, non-controversial realm of chemical and electronic engineering.