4:00 P.M.

March 14, 2002

"Miracles and Perils
of the Genome Revolution

by David Baylink M.D.

Assembly Room, A. K. Smiley Public Library

Summary

We have the geography of the world and the geography of people, which we call anatomy.  The geography of people can be further reduced to the geography of the genome, which is a miniaturized blueprint of the molecules of human cells. There is a considerable difference in magnitude between the geography of the world and the geography of the cell. The circumference of the world is roughly 26,000 miles and the circumference of the cell is about 26 ten thousands of an inch.  However, because each tiny cell of the body contains six feet of DNA and because there are five trillion cells in the body, there is enough DNA to wrap around the surface of the Earth 200,000 times. 

The genome revolution, so far, has shown that we are 99.9% alike as humans, even though, when looking at your neighbor, you might wish that were not the case.  Even less comforting is the fact that C. elegans, which is the Earthworm, shares 65% homology with humans.

Where will the genome revolution lead?   Jeremy Rifkin, who is a popular futurist, has raised the consciousness of the significance of the genome revolution. Moreover, he has made both desirable and outrageous  predictions. For example, he suggests that there will be a revolution in agriculture so that we will abandon farms and, instead, produce food in giant bacterial baths by recombinant DNA technology. It is true that genetically engineered bacteria could produce the protein composition of a steak, but what would it taste like?  He also predicts that human/chimpanzee hybrids could be widely used as experimental subjects in medical research and also organ donors.  He also proposes that parents could choose to have their children conceived in test-tubes and gestated in artificial wombs, a technological advance that women may find a lot easier than the current method. He makes many additional predictions that are even more threatening to our individuality.

In conclusion, anything with the enormous potential of genetic engineering, when coupled with computer sciences, could vastly improve the human condition or could be misused to the extent that could produce a devastating threat to what we consider a free society.

Dr. Baylink went on to provide a short PowerPoint presentation of some of his advances in molecular genetics and gene therapy. He concludes that much of what Rifkin has predicted is hype and that the reality of the situation is that the advances that are being, and will be made in the future, will eliminate a considerable amount of human suffering but that this will not happen for several years.

Abbreviated Curriculum Vitae
of David J. Baylink, M.D.

After postdoctoral fellowships at Harvard Medical School and the Postgraduate Medical School of London, Hammersmith Hospital, in 1966 Dr. Baylink moved to the University of Washington in Seattle, Washington, where he subsequently rose to Professor of Medicine in 1977.  In 1981, Dr. Baylink moved to Loma Linda University, where he is currently Distinguished Professor of Medicine and Professor of Biochemistry. At the Jerry L. Pettis Veterans Administration Medical Center he is the Associate Vice-President for Medical Affairs for Research, as well as Director, Musculoskeletal Disease Center. Dr. Baylink belongs to many scientific organizations, including the American Society for Clinical Investigation, the American Association of Physicians, and Alpha Omega Alpha.  He is a member of the editorial board of several scientific journals. He has served on scientific study sections of the Veterans Merit Review System, the National Institutes of Health, the National Aeronautics and Space Administration, and, also, the review bodies of non-federal granting institutions.  Dr. Baylink has received several awards for his work on bone and mineral metabolism, including the Medical Investigator Award, Veterans Administration.  Dr. Baylink has published well over 500 papers in the musculoskeletal field, including molecular genetics, tissue regeneration, and gene therapy.

Dr. Baylink and his wife, Colleen, have three children and six grandchildren.

THE MIRACLES AND PERILS
OF THE GENOMIC REVOLUTION

            Let’s begin by discussing the term, genome.  Since ancient times humans have drawn geographical charts.  We have the geography of the galaxy, of the world, of our country, and even a geography of people (which we call anatomy).  The geography of people can be further reduced to the geography of the genome, which is a miniaturized blueprint of the molecules of human cells.  The mapping of the human genome is in the nucleus of the cell and is composed of DNA in the form of a double helix, a structure that was discovered by Crick and Watson in 1953.

            There is a considerable difference in magnitude between the geography of the world and the geography of the cell.  The circumference of the world is roughly 26,000 miles and the circumference of the cell is about 26 ten-thousandths of an inch.  The geography of the genome is even smaller, because the nucleus of the cell, which houses the genome, is only about 1/5 the size of a cell.  If the nucleus is so  tiny, one might expect that the length of DNA in the nucleus, or in the body, would be relatively small.   This is not the case.  For example, each cell contains six feet of DNA, and since there are 5 trillion cells in the body, a single human body contains 30 trillion feet of DNA, and since one mile equals 5,280 feet, and since the earth’s circumference equals approximately 26,000 miles, the total length of DNA in the body would wrap around the surface of the earth more than 200,000 times.  

          When we talk about the geography of the genome, are we talking about a single, individual person, or everyone?  The genome contains 3 billion nucleotide-based pairs, which are the chemical units of genes.  If we examine 2 individuals, we find only 3 million base pair differences out of the total of 3 billion.  As such, we are 99.9 percent alike and, therefore, when we talk about the geography of the human genome, we are basically talking about all of us.  Less comforting is the fact that C. elegans, which is the earthworm, shares a 65% homology with humans.  Almost as astounding is that chimpanzees are 98% homologous with humans.

            So much for the geography of the genome.  Now, let’s discuss where knowledge of the genome will lead us, and lead us it will, as you will see in a moment.  One individual who has raised the consciousness of the significance of mapping the human genome is Jeremy Rifkin, who holds a degree in economics from the Wharton School of Finance and Commerce of the University of Pennsylvania and a degree in International Affairs from the Fletcher School of Law and Diplomacy at Tufts University.

            Jeremy Rifkin, in his best-selling book, The Biotech Century,” proposed that the recent marriage between computers and genetic science will enable us to harness the gene and remake the world.  As a result, our way of life is likely to be more fundamentally transformed in the next several decades than in the previous 1,000 years.  By the year 2025, we and our children may be living in a world utterly different from anything human beings have ever experienced in the past.  Let’s see if you agree with some of his assertions or my comments which follow each of Rifkin’s assertions:

1. Global agriculture could find itself in the midst of one of the greatest transitions in world history, with an increasing volume of food and fiber being grown indoors in tissue culture in giant bacterial baths, all at a fraction of the price of growing such staples on the land.  Millions of farmers in both the developing and the developed world would be uprooted from the land, sparking one of the great social upheavals in world history.

            Could this ever be a reality?  On the positive side, we are already producing enormous amounts of protein by this bacterial incubation method of genetic engineering.  However, to be able to produce the entire globe’s need of food sources by this means may not be economically feasible.  Besides, genetically-engineered bacteria might be able to produce the protein composition of a steak, but what would it taste like?

2. Tens of thousands of novel transgenic bacteria, viruses, plants, and animals could be  released into the earth’s ecosystems for commercial tasks, tasks ranging from bioremediation, to the production of alternative fuels.  Such advances could wreak havoc with the planet’s biosphere, spreading genetic pollution across the world.

            We already have bacteria which can digest petroleum spills in the ocean.   It seems likely that in the future this principle will be applied in ways that we find unimaginable at present.  Because the motivation for such advances will most likely be profit, environmentalists beware.

3.   Military uses of the new technology arising from the marriage of the computer with the gene could lead to the development of genetically-engineered biological warfare agents which could pose a more serious threat to global security than nuclear weapons.

                        It is hard to imagine anything more destructive than nuclear weapons.  If  there is anything, biological warfare would be the prime candidate.

4.   Human cloning will become commonplace, with replication partially replacing reproduction.

            Human cloning will, undoubtedly, happen, but at the same time, laws will be enacted to prevent human cloning from becoming widespread.

5.   Genetically customized animals will be cloned to produce chemical factories to produce large volumes of drugs for human use.

            This is already being accomplished.  For example, cows have been engineered to produce high concentrations of certain types of drugs in their milk.  The transgenic cow method has been found to be cheaper than the method to produce the same drugs by bacterial baths.

6. Human/chimpanzee hybrids could be widely used as experimental subjects in medical research, and also as organ donors for human transplantation.

            It seems doubtful that this will ever be commonplace, unless we are overcome by a society of transgenic humans whose governing principle is eugenics.

7. Parents could choose to have their children conceived in test tubes and gestated in artificial wombs.

          Women may find this a lot easier than the current method.

8. Genetic changes could be made in human fetuses in the womb to correct deadly diseases and also to enhance mood, behavior, intelligence, and physical traits.   Parents would be able to design some of the characteristics of their own children to produce customized babies, which would give rise to a eugenic civilization in the 21^st century.

            This issue will provoke an enormous amount of debate in the future.

9. Millions of people could obtain a detailed genetic readout of themselves, allowing them to gaze into their own biological futures.  There is a disadvantage to the availability of this information, however, in that it could be used by schools, employers, insurance companies, and governments to determine educational tracks, employment prospects, insurance premiums, and security clearances, giving rise to a new, virulent form of discrimination based on one’s genetic profile.

            My own personal experience with this type of research indicates that this genetic information is so difficult to achieve from a technical standpoint that it would take decades to develop even a rudimentary genetic print out of an individual such that we have plenty of time to develop the necessary safeguards to avoid this type of discrimination.

                     A general conclusion that can be made from the foregoing is that information technology and genetic science are slowly fusing into a single technological and economic force to provide the ultimate technology frontier, which is both exciting to behold and chilling to contemplate.  Clearly, advances in medicine to improve the human lifespan and quality of life, advances in agriculture to make food available even to the poorest of people, and discovering new sources of energy are common goals for most sensible people.  However, anything with the enormous potential of genetic engineering, when coupled with computer sciences, can be misused to the extent that it could produce a devastating threat to what we consider a free society.  Some of these frightening predictions could happen.  It is important for us, as a society, to make certain that the miracles of the Genome Revolution are realized and that the perils are avoided.

            The potential marvels that can be reaped from the interfacing of computer informatics with the sciences have also been echoed by one of the pioneers in gene therapy, Dr. W. French Anderson, who has recognized that gene therapy is not only one of our greatest potential assets, but also one of our greatest potential liabilities.  He describes this concept of gene therapy very cryptically as follows:  “Gene therapy is a cure that may cost us ourselves.”  In other words, by revising nature’s blueprint of ourselves, we could lose our individuality.   Despite these potential liabilities, Dr. Anderson’s views on gene therapy are very positive.   To emphasize the importance of gene therapy, he points to four revolutions in the history of medicine:  The first occurred in 1854, when Dr. John Snow discovered that cholera could be spread by contaminated water; the second occurred shortly thereafter with the discovery of anesthesia, which allowed doctors to cure otherwise lethal ailments, such as appendicitis and bowel obstruction; the third revolution was the introduction of antibiotics and vaccines; and, the fourth revolution is, of course, genetic engineering and gene therapy.

          So far, we have discussed visionary issues with respect to genetic engineering.   In my final subject for discussion, I would like to touch on the reality of genetic engineering by showing you some of our progress on gene therapy for battlefield injury; specifically, injury to soft tissues and to bones.   We are taking two entirely different approaches for he regeneration of these two types of tissues.  For soft tissue regeneration, we are taking a molecular genetic approach to discover the genes involved in soft-tissue regeneration.  The assumption is that if we identify these genes in the mouse, we will then be able to induce soft-tissue regeneration in humans.  This project has been tremendously aided by the finding that there is a specific strain of mouse that is naturally capable of soft tissue regeneration.  What we would like to learn is how this mouse is able to regenerate, while other mouse strains are unable to regenerate.  We find that the regeneration mouse can completely heal an ear punch hole in less than 30 days.  In contrast, other mice can only heal an ear punch hole by about 50 percent, no matter how long they are given to heal the wound.  To discover these regeneration genes, we are interfacing computer methods with genetic methods.  Up to this point, we have discovered several candidate genes for regeneration.  I will illustrate some of our results in this project in a few moments in my PowerPoint presentation.

            The approach that we are using for regenerating hard tissue is a gene therapy approach, rather than a gene search approach.  In our gene therapy studies we sought 1) to heal a large experimentally produced bony defect and, 2) to accelerate fracture healing both in rat models.  Accordingly, we developed an animal model to evaluate gene therapy to fill in a large bony defect, such as might occur as a result of a battlefield injury or terrorist attack.  Next, we developed a rat fracture model for the development  of a gene therapy to accelerate the healing of fractures, which, again, is an injury frequently sustained in response to serious trauma.

            Regarding our first gene therapy goal, we have now successfully regenerated a large defect produced experimentally in the skull of a rat.  Twenty-one days after a single injection of genetically-engineered cells, there was a complete healing of a large bony defect.  I will illustrate this in my PowerPoint presentation in a few moments.

            We have also made substantial progress on our goal of accelerating the healing of fractures.  We developed a femur fracture model in the rat.  We engineered a virus to produce a chemical healing factor and then inoculated the virus into the fracture site of the rat.  As you’ll see from my PowerPoint presentation, this gene therapy resulted in a remarkable increase in healing tissue at the fracture site.