Bioethics Confronts Bioengineering

No one would minimize the real and potential benefits to be derived from genetic engineering. Yet, in our endorsement of this technology, we must also at least consider its possible adverse impact. Some alarmists feel that tampering with the genes of humans and other organisms is tantamount to playing God, and they predict dire sociological, ecological, and medical consequences. Jeremy Rifkin of the Foundation on Economic Trends voiced his group’s fear: 

         We are embarking on a very potentially troublesome journey, where we begin to reduce all other animals on this planet to genetically engineered products. . . . We will increasingly think of ourselves as just gene codes and blueprints and programs that can be tinkered with.

 Other  critics  argue  that  creating  entirely  new  organisms  and  releasing them into the earth’s habitats may upset the balance of nature. They point out that the same techniques that are used to engineer plants to resist herbicides and bacteria to make insulin could also create a virus that inserts into the human genome and causes cancer or other diseases.

The Problem with GMOs

 One of the most publicized issues has been the use of genetically modified  organisms in  food  crops. A serious  controversy  has  erupted  over transgenic corn and soybeans. The corn  is engineered  to contain an  insecticide gene from the bacterium, Bacillus thuringiensis (Bt). The soybeans contain genes for herbicide resistance. Over 50% of the soybeans and 20% of the corn planted worldwide are genetically modified. Although they are not  intended  for use  in human  food,  in several  instances,  they have wound up in processed products, leading to concerns about safety. In Europe and America, protesters have marched  to demand  the end to “frankenfoods.” One possible problem is that these foods may give rise to allergies or other sensitivities. Ecologists fear that the insecticide gene will be spread to other plants and destroy the “good” insects. It has already been found lethal to monarch butterflies. In the end, the advantages of these new plants must be weighed against their adverse impact.

Brave New World?

Other consequences of this technology are far reaching. For instance, is the world heading toward a time when normal children will be given genetically engineered growth hormone to increase size? A controlled study was conducted to assess the effects of recombinant growth hormone on the  development  of  children who  are  healthy  but  somewhat  small  for their age. Data from these trials indicate that hormone therapy does increase height if given early, but the increases are not dramatic. The perception of small size as a “disease” that needs to be treated is very distressing to some medical experts, and the treatment is currently limited to treating children who are deficient  in  this hormone. Yet supporters feel that the use of engineered hormones is really no different from cosmetic surgery and should be available to people who want it.

 Detailed analysis of  the genetic blueprint of human beings will not only provide a greater understanding of what causes genetic diseases, but it will also allow screening for any defective genes that could lead to disease. Such a possibility will also give rise to numerous ethical and legal questions. Opponents have already objected vehemently  to genetic screening as an invasion of privacy, not unlike requiring genetic “social security numbers.” Might such  tests be demanded as a means of determining one’s fitness for a job or insurance coverage? The federal government has announced its opposition to this use of screening, but has yet to offer legislation to control it. 

It  is  far more  likely  that  the ability  to profile an  individual’s genetic makeup will have beneficial effects. Children with serious or life- threatening defects may require prompt therapy to correct or alleviate the effects of the disease. In pinpointing the risk for cancer and other serious diseases, screening will help people make meaningful life style and medical decisions. In addition, genetic counseling would be greatly improved since parents with a complete genetic profile could determine in advance what potentially harmful genes their children might inherit. Tests are now available to determine the sex of an eight-cell-stage embryo and whether it carries certain genetic diseases. Will these techniques be used to promote sex selection, or will they influence decisions to terminate pregnancy on the basis of genetic defects? Although it has not yet been attempted in humans, gene line therapy (correcting genetic defects in the zygote or early embryo) will be a distinct possibility in the future. 

The most vocal critics imagine a day when parents will be able to create super babies by requesting that certain favorable genes be added to their  children’s  genomes. Others,  however,  feel  that  gene  line  therapy would be the ultimate solution to correcting genetic defects that diminish the quality of life.

The Bottom Line

An inevitable outcome of bioengineering has been its potential for profit. By 2001, over a hundred bioengineered products are expected to earn as much as $30 billion in revenues. With thousands of biotechnology companies worldwide, each actively developing various drugs, research tools, or industrial applications, this industry will continue to expand. Research and development on new drugs and treatments often involves billion dollar monetary  investments. At  the  present  time,  pharmaceutical  companies are testing and requesting approval for over 400 new biotech medicines. Most of these are for treating cancer, AIDS, vaccines, and gene therapy. Most biotechnology companies would like to have rights to exclusive marketing of  the drugs, procedures, animals, plants, and microbes they  have  developed.  Several  hundred  patents  have  been  issued  for unique and commercially useful organisms and drugs, and over 10,000 have been applied for. Currently, one of the most provocative questions is: Who owns the human genome? Several companies have patented human databases for genes that influence breast cancer, colon cancer, and obesity. Because the DNA was isolated and characterized, it existed in a form different from nature. Such patents have been used to develop test kits  to detect defective genes and  to assess  risk, but  later  they may be used to develop therapies.

Protecting  the public’s best  interest will  require  that bioethicists and  representatives of many disciplines— science,  law, medicine, business, government, and education —continue to discuss  the basic moral and economic issues and to develop guidelines for the future. The main problem may well be whether laws can keep up with the rapid advances in the field. There is no doubt that bioengineering will eventually touch all of our lives and even change the ways we regard the world.

Starter Cultures, Bacteriophage Infections, and Plasmids

Cultures  of  lactic  acid  bacteria, called  starter  cultures, are added to milk during the preparation of many dairy products. For example, Streptococcus lactis and S. cremoris are used in the production of cheese. One of the greatest problems for the dairy industry  is  the presence of bacteriophages  that destroy  these starter cultures. Lactic acid production by a heavily phage-infected starter culture can come to a halt within 30 minutes. 

 

The industry has tried to overcome this problem by practicing aseptic techniques in order to reduce phage contamination, and by selecting for phage-resistant bacterial cultures. Most efforts at control have not been successful in the longer term. It has been  found  that  the very aseptic  techniques and phage-resistant pure cultures used to attempt to solve this problem actually were parts of the problem. The most stable and dependable cultures, called P starter cultures, contain  the bacteriophages  in a pseudolysogenic state.

 

When cultures  are  grown  without  phages  or  under  aseptic  conditions  (L starters), they lose their phage resistance. The key to this riddle appears to be plasmids, which can block phage adsorption. The loss of the plasmids in a subpopulation of the bacteria allows the phage carrier state to be  established. New  phages  can  develop  by  acquiring  restriction  enzymes  from plasmids.

Reye’ s and Guillain-Barré Syndromes

An occasional complication of influenza, chickenpox, and a few other viral diseases in children under 14 years of age is Reye’s syndrome. After the initial infection has disappeared, the child suddenly begins to vomit persistently and experiences convulsions followed by delirium and a coma. Pathologically, the brain swells with injury to the neuronal mitochondria, fatty infiltration into the liver occurs, blood  ammonia  is  elevated, and  both  serum  glutamic  oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) are elevated in the blood. Diagnosis is made by the measurement of the levels of these enzymes and ammonia. 

The relationship between the initial viral infection and the brain and liver damage is unknown. Treatment is nonspecific and directed toward reducing intracranial pressure and correcting metabolic and electrolyte abnormalities. Some  children who  recover  have  residual  neurologicaldeficits impaired mental capacity, seizures, and hemiplegia (paralysis on one side of the body). Mortality ranges from 10 to 40%. It is suspected that the use of aspirin or salicylate containing products to lower the initial viral fever increases one’s chances of acquiring Reye’s syndrome.

 Another condition that involves the central nervous system and is associated with  influenza  infections  is Guillain-Barré syndrome (some- times called French polio). In  this disorder  the  individual suffers a delayed reaction (usually within 8 weeks) either to the actual virus infection or to vaccines against influenza. The virus or viral antigen in the vaccine damages the Schwann cells that myelinate the peripheral nerves and thus causes demyelination. As a result a prominent feature of this syndrome is a symmetric weakness of the extremities and sensory loss. Fortunately recovery usually is complete because the remaining undamaged Schwann cells eventually proliferate and wrap around the demyelinated nerves.

Donor Selection for Tissue or Organ Transplants

The likelihood of tissue or organ transplant acceptance can be in- creased by using persons who have a great degree of genetic similarity. The greater the similarity, the more likely the persons will have similar MHC complexes. The reason for this is that 77 histocompatibility  alleles  are  determined  by  just  four  human  histocompatibility genes A, B, C, and D (which includes DQ, DR, and DP). 

These genes are transmitted from parents to offspring according to Mendelian genetics.  For  example, two  siblings  (brother  and  sister) may  have  approximately a 25% chance of being B identical, a 50% chance of sharing one B gene, and only a 25% chance of having completely different B genes. Therefore, when tissue or organ transplants are performed, a deliberate at- tempt is made to use tissues from siblings or other genetically related, histocompatible people. Once a tissue donor has been selected, various in vitro tests are per- formed to find how closely the MHCs match. The greater the degree of similarity, the greater the chances are that the transplant will be successful. One such test is the lymphocytotoxic cross-match test. In this test the recipient’s serum is mixed with the donor’s lymphocytes to determine whether anti- bodies are present that will cause tissue rejection. The cellmediated lymphocytosis test, in which recipient leukocytes are mixed with donor serum, is used to test for acute rejection. After a prolonged incubation period, the presence of activated killer cells is an indication that rejection will occur.

Soils,Termites, and Intestinal Microorganisms: Understanding Atmospheric Methane Changes

Termites  are  important  components  of  tropical  ecosystems, where  their  use  of  cellulose  plant  materials  allows  rapid recycling  of  plant materials.  Termites harbor significant populations of archaea that use products of cellulose digestion, including CO2 and hydrogen, to produce methane. Termites occur on 2/3 of the Earth’s land surface, and, based on lab- oratory studies, 0.77% of the carbon ingested by termites can be released as methane. In tropical wet savannas and cultivated areas, termite populations are increasing rapidly. This increase is being accelerated by the destruction of tropical forests, which results in the accumulation of dead plant materials on the soil surface. 

This provides an ideal environment for the growth of termites. Termites are estimated to be contributing annually at least 1.5  x10¹⁴ CO2, to the atmosphere. This is believed to be contributing to measurable grams of methane, together with hydrogen and increases  in  the atmospheric methane  level. Thus unseen  termites and their associated gut microorganisms may be affecting global warming.

Life above 100°C

Until  recently  the  highest  reported  temperature  for  procaryotic growth was 105°C. It seemed that the upper temperature limit Ufor life was about 100°C, the boiling point of water. Now thermophilic procaryotes have been reported growing in sulfide chimneys or “black  smokers,” located  along  rifts  and  ridges on  the ocean  floor, that spew sulfide-rich superheated vent water with temperatures above 350°C . 

 

Evidence has been presented  that  these microbes can grow and reproduce at 113°C. The pressure present in their habitat is suf ficient to keep water liquid (at 265 atm; seawater doesn’t boil until 460°C). The  implications of  this discovery are many. The proteins, membranes, and nucleic acids of these procaryotes are remarkably tempera- ture  stable  and provide  ideal  subjects  for  studying  the ways  in which macromolecules and membranes are stabilized. In the future it may be possible to design enzymes that can operate at very high temperatures. Some  thermostable enzymes  from  these organisms have  important  industrial and scientific uses. For example, the Taq polymerase from the thermophile Thermus aquaticus is used extensively  in  the polymerase chain reaction.