Dolly, the first mammal cloned from an adult, made headlines worldwide in early 1997. A brief decade earlier, leading scientists had declared that cloning an adult animal was theoretically impossible.
At the earliest point in life, an embryo contains the complete DNA required to develop a mature adult. Only with subsequent cell divisions do differentiated cells of skin, bone and hair emerge. Before Dolly, the belief that a differentiated cell could be reset to grow a whole organism was likened to traveling back in time.
Unlike scientists, healthcare executives were not overwhelmed by the successful cloning. Our muted response may have reflected our preoccupation with everyday demands, which temporarily blinds us to the revolutionary changes that technology has presented -- and will continue to present in the coming century.
Four major technological breakthroughs are emerging to change the course of human disease: the cloning of human cells and proteins, the completion of the human genome project, combinatorial chemistry in the discovery of new drugs, and computer/organic interfaces, which are commonly called bionics. These fields will converge on the life sciences to combat the scourge of disease and improve the quality and length of life.
Dolly the sheep was created by Ian Wilmut at the Roslin Institute in Scotland. Funding came from PPL Therapeutics, a pharmaceutical company looking for an efficient way to produce advanced biotech drugs in animals that have been "transgenically" altered -- that is, animals that have been changed to produce human proteins or cellular structures that their immune systems won't reject.
Some members of the scientific world were skeptical of Wilmut's claim, since the adult ewe was no longer living when Dolly was delivered from a surrogate mother, making it impossible to simultaneously compare Dolly's DNA with a living mother's to verify the cloning. (The DNA evidence was frozen tissue samples from the presumably dead parent.)
Within months however, an independent effort in Madison, Wis., cloned a calf named Gene from a living cow using the Wilmut technique. The naysayers were quieted.
Another important milestone in cloning was reached when Wilmut announced that Molly and Polly had been born as transgenic sheep. As they mature, the sheep will produce human blood-clotting factors VIII and IX in their milk. Traditionally, these clotting factors have been used by hemophiliacs and have been isolated from human blood donations.
The importance of cloning animals cannot be overstated, since producing the first transgenic animal was extremely expensive.
If we are to benefit from the abundant sources of transgenic proteins, tissues and eventually human body parts, cloning and natural breeding will remain important parts of this science for the foreseeable future. Medical ethicists are scrambling to make sense of rapidly expanding knowledge about cloning.
Chicago-based scientist Richard Seed has publicly announced his grand scheme "to open a clinic and produce 500 human clones per year." The ethical implications of human cloning have no natural court of debate. Unfortunately the technology is advancing at its own speed -- with or without intelligent discourse among healthcare executives.
Human cloning could be irresistible to scientists, who would love to be the first to achieve it, and to some wealthy renegade who wants a genetic duplicate of himself or herself or a loved one. I believe I will live to see the announcement of a human clone.
Genome project at full tilt
The $3 billion federally funded effort to define the genetic sequence in the human genome is ahead of schedule. Those close to the project predict it will be completed in 2001. Knowing the human genome sequence will allow us for the first time to understand the 3,000 to 4,000 genetic mutations principally involved in certain inheritable diseases.
Cautious enthusiasm is appropriate. While the recording of the human genome has been compared with the invention of the Gutenberg printing press, full understanding and manipulation of the human genome are decades away. After all, the first plays of Shakespeare followed the printing press by about 135 years.
Technology futurists are predicting healthcare breakthroughs that may result from this new understanding of the human genome. One area of speculation is the creation of silicon microchips with embedded genome information. The first chip expected to be available commercially will probably be a test for the BRCA1 and BRCA2 genes, which are present in inheritable breast cancer.
The DNA chip is a microchip that has an individual's unique DNA material embedded in it. Diagnosticians will be able to run a series of tests against the chip, instead of using the physical body as the experimental site. The chip can be compared against a large computer database of millions of people who have gene sets that point toward possible cancer. The chip could indicate a susceptibility to cancer later in life.
This may allow oncologists more tools to alter the course of cancer. Early, minimal intervention will replace some of today's long-term cancer treatments.
The chip could also be used in gene therapy. It may be possible to interfere with the genetic makeup of an individual in the womb, to replace bad genes with good genes, cell by cell by cell.
This raises a disturbing question: How programmed do we want human life to be? The possibilities are scary. Against major cancers, we have a clear set of ethical precepts to guide us. But when we get down to, "I can afford to give my child blue eyes; I never liked my brown eyes," it's time to pause and regroup.
From treatments to cures
A revolution has occurred in the discovery of drugs, which will allow the creation of pharmaceuticals that are precisely targeted at specific diseases. This will allow a shift from treatment to cure for many of the major diseases that plague mankind.
Drugs have been targeted to specific diseases in the past, but nowhere near the extent they will be in the future. The trial-and-error methods of tradition will yield to very specific search techniques, based on our growing knowledge of the genome of foreign proteins.
Combinatorial chemistry provides a way to automate the discovery of drugs. It allows scientists to rapidly synthesize and test variations on chemicals.
As foreign proteins of bacteria and viruses invade the body, they unlock cell walls to enter healthy cells. The active end of a virus contains protein snippets with which a healthy cell will "shake hands." By locking up the foreign protein in a lot of handshakes while the protein is circulating in the bloodstream, scientists can halt the invasion.
New efficiencies in the discovery of drugs will produce medications that are far more effective against disease and have fewer side effects. In traditional drug discovery, a single chemist might produce 12 new chemical compounds in three months. Using combinatorial chemistry, chemists are producing as many as 10,000 chemical compounds in the same time period. Choosing one of 10,000 similar compounds to advance to human clinical trials will dramatically improve patient care.
The often discussed biotechnology revolution has already produced significant breakthroughs to enhance our lives. The pace of discovery has picked up, and we are on the verge of phenomenal new classes of medications.
Typical of the breakthroughs will be methods of promoting and inhibiting angiogenesis, the ability of the body to grow new blood vessels, which occurs naturally in pregnancy. These methods will be useful in treating cardiovascular disease and cancer. Researchers have found that they can "turn on" vessel growth in patients who have blockage in peripheral veins and around the heart. The approach could eliminate the need for certain cardiovascular procedures, a staple of modern hospitals.
While benefits to patients are obvious, this shift from procedures by subspecialists toward interventions by generalist physicians will likely create turf conflicts.
Scientists have been able to reduce tumors in mice to the point that the growths can no longer be measured. (They hesitate to use the word "cured" for such results.) Using angiogenesis inhibitors, physicians have blocked the vessel growth of tumors. Without a constant supply of fresh blood, the tumors shrivel up and disappear. What is particularly exciting about this work is that all tumors require vessel growth. Although this approach is still experimental, it holds promise across a wide range of human cancers.
2001: An inner-space odyssey
Medical care has entered the computer age, but computers are still nascent science. In fact, some futurists believe the next wave of computers will be bio-digital, superior to the personal computers and Internet portals we use today. Clearly, telemedicine, consumer Internet sites and e-commerce will explode. My predictions are in another realm -- the twilight zone of bionics.
Consider the ability to shrink genomically active devices so small that they not only can circulate in the bloodstream but can enter unique human cells to carry out immunosupportive tasks. These so-called nanodevices (a nanometer is one-billionth of a meter) have been researched for more than a decade.
The ability to manipulate matter at the molecular level, one atom at a time, suggests the potential for devices that can circulate throughout the body with lifesaving applications. A consumer could conceivably order an anti-cellulose inhalant, which would meander through the body, stealthily seeking excess adipose tissue. Using the body's heat as an energy source, these micromachines would busily chew up specific fat tissue and then be deactivated. What a way to lose weight!
Only the beginning
Recent breakthroughs in genomics, cloning, chemistry and bionics are creating a time like no other in modern medicine. It is as if an invisible hand were shining a light across the universe, illuminating what was previously hidden from mankind's understanding. As the light rays spread, their effects will touch more areas of our existence.
Medicine is beginning to shine new light on old diseases. Now the questions are: Will we be wise stewards of these novel technologies? Are we prepared for the ethical dilemmas raised by their arrival? Can we find a way to share the progress across all of America (and the world), not just with those who have health insurance?
With more than 43 million uninsured U.S. citizens today, these breakthroughs will widen the health gap between those with and without insurance. Those who are investing in innovations hope that the innovations will produce efficiencies of such magnitude that our society will be able to afford coverage for all.