by John Lange, M.D.
The quest for self-knowledge has been a central theme of discovery in the field of medicine. Over the past two years this quest has defined itself as the Human Genome Initiative. Researchers have taken on the challenge to sequence all the genetic material contained in the 48 chromosomes collectively known as the human genome. Since the time of Vesalius in the 1500s, scientists have been charting human anatomy with ever-increasing precision and finer detail. The delineations of the human genome will be the "last frontier" of human anatomy. We shall one day know the secrets of human nature as well as we know the topography of the human skeleton today.
Today I should like to discuss the human genome project from several viewpoints. You will meet the person whose genome is being sequenced. We will go on a journey through the laboratory of a molecular biologist where a gene is being cloned. Some time will be devoted to how all this applies to "the man on the street." And then we will moralize a little about our knowledge and its effect on human destiny. Finally, we will end with some "Urantia talk" about God as the connecting pattern.
I Am Joe's Genome
Imagine yourself in the year 2005; you are browsing through the newsstand, and you pick up Reader's Digest. The lead article is entitled, "I Am Joe's Genome," and it reads something like this.
Let me introduce myself to you. My story begins nearly two decades ago at the end of the 1980s when scientists under the leadership of Dr. James Watson set about to sequence or spell out the genes (sentences) in all the human chromosomes (paragraphs). Taken together, all these chromosomes are known as the human genome (the story of life). So you can know me better, I need to acquaint you with some definitions. I am composed of long molecules arranged in a double helical configuration known as DNA (deoxyribonucleic acid). The two strands are composed of deoxyribose sugars, and they are linked together by four nitrogen bases adenine (A), thymidine (T), cytosine (C), and guanine (G) bridging the two strands together at regular intervals. At the bridgepoint, an A always opposes a T and a C opposes a G. An A-T together or a C-G together are known as base pairs. The four bases A-T-C-G are the code words into which proteins are translated.
I am inside the nucleus of the cell and do not leave. I send messengers out into the cytoplasm to order the production of proteins that are engaged in biologic activity. I can self-replicate and move through time from one generation to the next using each individual as a culture medium, because the messages in my tape are immortal. Nearly 100,000 genes and 3 billion bases were sequenced in this project. Printing this in sequence would have filled fifteen volumes in the old Encyclopaedia Britannica. After the first two years of work, nearly 4,600 genes had been sequenced.
I am the pattern of biologic life, and now humankind, through application and endeavor, is gaining apparent control of this pattern. It is fortunate I gave up my secrets slowly, for the experts had the time to gain ethical maturity as this power was placed in their hands.
Cloning a Gene
We now travel to Dallas, Texas, to the laboratory of Drs. Brown and Goldstein where they have recently cloned the gene responsible for familial hypercholesterolemia. This body of work took fifteen years, and for their efforts and the prospects for health worldwide, they were awarded the Nobel Prize in medicine in 1985. In essence, there is a receptor on the surface of liver cells and other cells throughout the body which serve to remove cholesterol-carrying lipoproteins from the circulation. Thus plasma cholesterol is kept at a low level. There are certain people who have a mutation in the gene that codes for the receptor. Their cells cannot make these protein receptors, and they cannot remove lipoproteins from the plasma. Their cholesterol builds up to very high levels and they subsequently get atherosclerosis and heart attacks. The fact of a mutation in that gene was something they reasoned based on abstract thinking. They subsequently cloned the gene and isolated the gene from both normal people and patients with this mutation. They have been able to show that, indeed, there is a part of the gene missing in the patients.
Cloning genes these days involves somehow fishing out the messenger-RNA which encodes for the protein. Then it is treated with purified reverse transcriptase (an enzyme having the power to convert RNA back to DNA) and a DNA copy of the RNA is made. The DNA copy is taken and introduced into bacteria. The discovery of certain enzymes recently has made all this possible.
To clone the LDL receptor, the first thing is to isolate tissue making LDL receptor. The adrenal turned out to be the most abundant source. Human fetal adrenals from late abortions were used for this purpose. These adrenal glands were then ground up and the RNA taken out. The tissue contains millions of different kinds of RNA, and only one in 10,000 codes for our protein. The other 9,999 are coding for all the other proteins in the cell. Then DNA copies were made of the whole RNA by adding this enzyme reverse transcriptase. What you then have are single-strand copies with a special name, c-DNA, or, complementary DNA.
Now you do what is called recombinant DNA. To clone a gene, you take advantage of the fact that bacteria have plasmids. They are autonomous pieces of genes in bacteria. (They were originally discovered by a microbiologist studying the development of antibiotic resistance.) Then, through a series of enzymatic steps known as restriction fragment polymorphism, the circular DNA in the plasmid is opened up, the gene inserted, closed or circularized again, and then reintroduced into the bacterial cell.
This process can be used not only to clone genes but to produce proteins. These special bacteria have been used to produce human growth hormone, human insulin, and tissue plasminogen activator, to mention a few. The potential in the field is limited by human imagination.
Fortunately, a bacteria takes up only one of these plasmids, so you have ten million bacteria, each taking up a different c-DNA. The challenge is to find the one that encodes for the LDL receptor. To accomplish this they worked with the microbiology department and, using the adrenal glands from cows, purified a small amount of receptor protein to homogeneity. Next they sequenced a small segment of this protein and then assembled a piece of DNA with the corresponding genetic code. This oligonucleotide probe produced in the test tube was then made very radioactive. It was placed on nitrocellulose paper which was in turn placed on a petri dish where these millions of bacteria were growing. The bacterial colonies grew up onto the filter and the small piece of DNA found its complementary plasmid containing our gene. The filter was washed carefully to eliminate unbound DNA and an X-ray was taken. A dark spot on the film represents your colony due to the radioactivity produced.
This specific colony is isolated and grown up in large quantities. The gene is cut out of the plasmid with another special restriction enzyme. The rest of the plasmid is thrown away. The gene is now sequenced and the proper reading frame determined. This is all done today by computer. Finally, having started out with only eight amino acids, they discovered the entire protein structure of over 6,000 amino acids. They also know the conformational status, how it is oriented in the cell membrane, and how it binds LDL.
Towards a Healthy World
Molecular biology and genetic research have given rise to a variety of clinical applications; i.e., things that help patients. The most debated topic in this area is gene therapy. One in 100 children is born with a serious genetic defect. Of the more than 4,000 known inherited disorders, most lack full effective therapies. Since the advances in gene cloning, scientists are imagining ways to introduce healthy genes into patients to cure the inherited illness. Genes can be transferred into germ cells (sperm, eggs, or early embryos) or somatic cells (those not destined to become sperm or eggs). Germ-line therapy is not an option for the foreseeable future, because the new genes would be passed from generation to generation, a prospect raising profound ethical concerns.
The most promising are diseases caused by single genes that have been isolated, cloned, and are available for transplant. This is accomplished by using retroviruses that have incorporated the gene, maintained their ability to infest somatic cells, but lost the power of replication. Efforts have focused on replacing the defective gene or supporting the work of the sick gene. It has been difficult to find ways to insure that therapeutic genes are expressed well and persistently in the body. Familial hypercholesterolemia, hemophilia, cystic fibrosis, and inherited emphysema are single-gene diseases under investigation at present.
This technology can also be used to delineate the origin of cancer, for the molecular targeting of drugs, and in the diagnosis of diseases. Great progress has been made with Huntington's chorea by using restriction enzymes in a process previously mentioned, known as restriction fragment polymorphism. Restriction enzymes are used to cut the DNA of affected individuals. This gives DNA fragments of many different lengths. All affected individuals will have an identical inherited fragment of the same length where the gene is located. In this manner the disease will soon be completely understood.
God as a Connecting Pattern
As humans unlock the secrets of nature, with each profound discovery we voluntarily assume a larger responsibility. With the delineation of the human genome, we are challenged to a higher identity of "created co-creator." This new knowledge subordinated to spirit direction provides the opportunity for attaining an unprecedented level of human health. A reasonable course is to foster the health resulting from random genetic recombination within the constraints of a reformulated commitment to human dignity.
The question is then posed: If the future is open, who is responsible for human transformation? Searching for an answer, we attempt to redefine the relationship between divine and human agency. Greater understanding is possible by viewing the life pattern as it encompasses the domains of finite reality. It includes not only the material (DNA), but also the mindal (archetype) and the spiritual (personality) domains. As described by Jung, the archetype per se is prepsychic in that it precedes and preforms human mind functions. It serves to focus the ministries of the adjutant and cosmic minds to develop psychologic integrity during a lifetime. Personality is that manifestation of the Father unifying the spiritual life and focusing the ministry of the Thought Adjuster culminating in morontia progression.
The life mechanism is the product of supermortal creative design, and as such mortals can never hope to totally control it. We have only partial vision and must depend on God as the pattern that connects. As we seek philosophic coordination between scientific knowledge and spiritual existence, we should first realize we live in a connected relationship of pattern between ancestral Deity and evolving Supremacy.
A service of
The Urantia Book Fellowship