Teeth - We're Going To Grow Them Back!

Cathy Areu-Jones

by Cathy Areu-Jones | August 17, 2010 @ 10:00AM

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With the recent advancements in genetic research-namely those of the Human Genome Project-the question is being asked: How will all of this affect dentistry? The answer is, completely.

According to researchers throughout the country, genetics could entirely change everyday dental practice. One day, for example, dentists may be able to grow teeth, engineer salivary gland tissues, conduct genetic testing for periodontal disease susceptibility, and more.

Is this science fiction? No. In fact, some of these projections are not too far off, and some are already a reality in laboratories. So, the question dentists must ask is, "When will the recent advancements in genetic research affect dentistry?"

The Human Genome Project

"The fact is that every human disease, with the exception of trauma, is caused by a gene-a defect in the gene. Any disease. And that applies to dental diseases as well," explains Rene D'Souza, DDS, associate professor in the department of orthodontics at the University of Texas (UT) Houston Dental Branch. "Everything we deal with has a genetic basis."

To relate to Dr. D'Souza's excitement over genetics, one must go back to basics. The human genome, which is the complete set of instructions for constructing all living organisms, is estimated to comprise approximately 50,000 genes-most of which, until now, had not been identified. Genes are the units of a DNA molecule that contain the organism's code for a specific function. DNA (deoxyribonucleic acid) carries genetic information necessary for the replication of cells and for the production of proteins. The human genetic code is the language in which DNA's instructions are written.

In 1990, the internationally funded Human Genome Project began to map and sequence the human genetic code. In June 2000, to the science world's surprise, the international scientific group and a private biotechnology company, Celera Genomics Inc., Rockville, Maryland, announced that they had sequenced a rough draft of the entire human genetic code. It marked one of the biggest advances in genetics.

With the deluge of data and related technologies generated by the Human Genome Project, scientists can now identify thousands of genes.

"The Human Genome Project is going to revolutionize and already has begun to change the shape of medicine," says Dr. D'Souza.

Genetics and dentistry

The implications of DNA mapping for dentistry are profound, according to Max Anderson, DDS, co-chairperson of the quality and outcomes task force for Delta Dental Plans Association and a speaker on the application of science in the prevention of dental diseases.

"The same technology used to map the human genome is being used to map the genomes of the major pathogens of human kind," Dr. Anderson explains. "This includes the mapping of the genome for Streptococcus mutans-the bacterium that causes dental cavities-and for the major periodontal pathogens. Mapping these, along with the human genome, will give us incredible opportunities to defeat these two diseases in our lifetime."

Dr. D'Souza explains, "If you know the genes that are necessary for normal development, then you can develop therapies, which are called designer drug therapies, which are aimed at one area of the gene or the other." These designer drugs will be safer than today's medicines because they would only affect the defect in the gene, clearly identified through genetic research. "You look to see if the gene is abnormal. If it is, you can do preventive things to avoid it."

Designer drugs for preventing cavities and periodontal disease-as well as for other oral, dental, and craniofacial conditions-may be available within the next decade. The drugs will be delivered locally and in a more efficient way.

For now, there is one test, Interleuken 1, commercially available for testing periodontal susceptibility.

"We're doing some studies right now to determine whether it's cost effective to cover this test right now," says Dr. Anderson. "In other words, does the test give the dentist sufficient information with which to alter a treatment plan so that he can alter the course of the disease?"

Changing terminologies

Genomic medicine, which is the application of personal genetic information to medicine bringing about more accurate diagnoses and treatments, will also help identify a patient's genetic profile and allow the dentist to prescribe the best available drug therapy from day one. Dentists will be able to customize treatments according to each patient's genetic profile-choosing a drug custom-designed to match an individual's needs, and providing for more accurate dosing based on an individual's metabolism instead of traditional methods like weight and age.

With the emergence of genomic medicine in everyday dental practice, Dr. Anderson predicts that dentists may need to practice only cosmetic- and trauma-related dentistry. After all, dentistry's primary diseases would be well controlled and treated, allowing new strategies to enter dentistry.

"Eventually, when you lose a tooth, you'll be able to regrow one inside your mouth," Dr. Anderson predicts.

Dr. D'Souza anticipates this reality-she has already begun growing mouse teeth in her lab.

Growing teeth

Through a series of clinical and lab tests, Dr. D'Souza and a team of scientists from UT-Houston Dental Branch and the Baylor College of Medicine found PAX9, a master gene critical for tooth development. Its discovery brings scientists one step closer to understanding the genetic code to human dentition and sets the path for more discoveries. But the PAX9 discovery would not have been possible without an astute clinician, says Dr. D'Souza.

The clinician is one of the professor's students, Monica Goldberg. Ms. Goldberg recognized a unique dental pattern in a Houston family. Twenty-one out of 43 family members were missing their first and second molars. After collecting samples of the family's DNA, the scientists discovered a mutation in the PAX9 gene. By finding that gene, they uncovered one of the body's essential ingredients for making teeth. Now the possibilities are endless.

"You can actually grow a mouse tooth in a culture dish," says Dr. D'Souza.

Scientists remove tooth tissues from a mouse embryo, add the molecules necessary for tooth development, or PAX9, to the culture dish, and create mouse dentition.

"The hope is that if we can advance fast enough with the human genetics that we will be able to bioengineer human teeth for replacement," says Dr. D'Souza, "the same principal as [tissue engineering]."

Tissue engineering

Gene therapy is a new approach to treat, cure, and ultimately prevent disease by changing the person's genes. It is done by introducing a normal-functioning gene into a cell where the gene is defective.

"Gene therapy is gene manipulation," explains Paul M. Fernhoff, MD, associate professor of pediatrics and medical director of Emory genetics laboratory, in Atlanta. "It's really learning how to control a series of genes that are already there making the cell do what you want it to do. Another approach to gene therapy is actually taking the cells that are already there and adding new genes."

Although gene therapy is still experimental, Dr. Fernhoff predicts that in the next 25 to 30 years doctors will be able to use gene therapy, or gene transfer, with their patients. Currently, researchers are optimistic about a gene therapy technique most likely to affect dentistry-tissue engineering, specifically the engineering of salivary gland function. National Institute of Dental and Craniofacial Research (NIDCR) researchers have found a way to inject non-saliva producing cells with secretory tissue to turn these cells into secretory cells.

Engineering salivary gland function is important to patients who have experienced irreversible salivary gland damage due to radiation treatment for head and neck cancer. Because the genes that carry out the process for salivary glands are known, researchers are able to manipulate the glands and turn them on or off.

"It's happening in the lab," says Indu Ambudkar, PhD, chief of the Secretory Physiology Section of the Gene Therapy and Therapeutics Branch of the NIDCR in Bethesda, Maryland. "We're doing those sort of experiments in lab animals, for example, mice and rats. The goal would be ultimately to apply it to humans, to patients."

About two years ago Bruce J. Baum, DMD, and David J. Mooney, PhD, initiated a pilot program to develop artificial salivary glands to patients with damaged secretory tissue. They described their program in the article "The Impact of Tissue Engineering on Dentistry" in the Journal of the American Dental Association. "We have made substantial initial progress, proceeding from fairly rudimentary studies using a natural substratum (denuded trachae) to the use of engineered polymer scaffolds," they wrote.

Dr. Ambudkar believes that the limitation of the salivary gland gene therapy is at the level of the vector that is currently used to transfer the genes. The vectors induce immune reactions in the individuals or they may do other things, so their use is still fairly controversial.

Vectors are the carriers for the genes in gene therapy. They deliver the genes into the patient's cells. The most common vectors are viruses, which encapsulate and deliver their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of virus biology and manipulate its genome to remove disease-causing genes and insert therapeutic genes. But, as they have discovered, the body still considers viruses foreign particles and fights them. Unfortunately, scientists simply do not know how to turn viruses on and off yet. Alternatives to viruses are being considered, including complexes of DNA with lipids and proteins. Many researchers are working currently on vector technology for all types of gene therapy, which will be more common in medicine soon.

"We believe that there is a realistic opportunity to develop a first generation artificial salivary gland suitable for initial clinical testing relatively soon (within 10 years)," write Drs. Baum and Mooney.

Researchers are also interested in the genetics of saliva for the prevention of dental caries and periodontal disease. Dr. D'Souza says scientists now believe certain populations are at higher risk for dental caries because they are genetically susceptible to the disease - their saliva is genetically different. Clinical studies are analyzing saliva in order to determine the genes contributing to the risk exposure to these diseases.

Dr. Anderson predicts that, once the genes have been identified, corrective genes could be delivered to patients passively, perhaps in food, to enhance their saliva. Current research is already underway to develop foods to deliver traditional disease vaccines.

"We're talking Franken-food," Dr. Anderson says. "Where you genetically alter foods. Will the public take those [for cavity prevention]? Probably not for the next 20 years."

But he says scientists working on altering saliva are already two years into human trials.

The ethics of genetics

Several fears come to mind when the public thinks about genetics, including loss of privacy and genetic manipulation, or the altering of a human's genes to create "designer people." Many agree the mishandling of genetic information is a valid privacy concern. However, the fear of a world made up of designer people is still highly unlikely according to experts. No researcher seems ready for the consequences of those types of experiments. Nor is research and technology far enough along to perform such experiments on a routine basis.

To prepare for the influx of patients' genetic information in their everyday dental practice, Tracy Field, a lawyer from Arnall, Golden, Gregory, LLP, in Atlanta, warns dentists to learn about the laws regarding the privacy of patient medical information right away. Indeed, on December 28, 2000, the Department of Health and Human Services published final regulations that require health care providers to implement standards to protect the privacy of certain protected personal health information. Several states already have stringent privacy laws in effect that practitioners may need to review. It is important that the dental community be aware of the possible application of these laws to their practices.

"People are very sensitive about their privacy," explains Ms. Field, who worked in the area of genetics before graduating from law school. "So, if I were advising a dentist, anyone who has confidential health information, you need to consider how you are protecting that information and how you control access to it. Are you taking what people would consider reasonable steps to ensure that such private information is protected?"

Currently, no federal law exists to specifically address genetic discrimination in insurance and in the workplace. On the political front, Democrats and Republicans have each proposed legislation to protect a patient's privacy. Democrats in Congress have their Genetic Non-Discrimination in Health Insurance and Employment Act and the Republicans have their Patients' Bill of Rights. Each side says that their bill would protect the Americans from discrimination based on their health information, namely their genetic health information. Undoubtedly, the decoding of the human genome in June has pushed lawmakers into action.

"The concerns related to privacy and ethical uses of data are legitimate and compelling," says Dr. Anderson. "Our society will need to answer a series of questions related to this central issue. For one, the cost of health services can be significantly diminished with the broad application of genetic information tied to health outcomes data. Society with limited health care resources will be forced to decide how best to use these data and protect against their misuse. It's a complex social issue."

"It's hard to tell what will happen," says Ms. Field. "Genetics is an area that's evolving and people are still struggling with how to balance legal concerns regarding the field, yet allow for innovation."

But according to Dr. Anderson, America has an emerging model to look to -  Iceland. The country has hired an independent firm to gather all the genetic data from its citizens, along with their genealogical and health data. Iceland, a model for the rest of the world, will face the significant issues that genetics introduces years before the US.

Cathy Areu-Jones is a freelance writer in Vienna, Virginia.

AGD IMPACT, April 2001


Genetics education

Because of the gap between the actual application of genetic research and the daily delivery of services to patients, researchers fear that clinicians are not yet interested in the recent advancement in genetics.

"Education is an area that we're all worried about-making sure that both physicians and dentists have a basic understanding of genetics," says Paul M. Fernhoff, MD, associate professor of pediatrics and medical director of Emory genetics laboratory, in Atlanta, Georgia.

Rene D'Souza, DDS, associate professor in the department of orthodontics at the University of Texas (UT)-Houston Dental Branch shares Dr. Fernhoff fears, saying, "In general clinicians just say, Oh this is too scientific. I don't want to listen to it.' The DDS in me just wishes that gap would be bridged so that we could educate clinicians and basic scientists as to what's going on in the clinics."

According to Jordan J. Cohen, MD, president of the Association of American Medical Colleges (AAMC), only 66 medical schools had a required course in genetics in 1998, and only 72 in 1999 despite the avalanche of information from the Human Genome Project. Dr. Cohen acknowledges that other courses also cover genetics, but medical students want and need more information. A recent AAMC Graduation Questionnaire revealed that some 44 percent of graduating seniors thought that genetics study time was inadequate.

Realizing the need to educate health care professionals in all fields, the National Coalition for Health Professional Education in Genetics (NCHPEG) was founded by the American Medical Association, the American Nurses Association, and the National Human Genome Research Institute in 1996. The interdisciplinary group defines itself as "a national effort to promote health professional education and access to information about advances in human genetics...comprising leaders from more than 100 diverse health professional organizations, consumer and voluntary groups, government agencies, private industries, managed-care organizations, and genetics professional societies."

In February 2000, NCHPEG endorsed a list of core competencies in genetics its members considered essential for all health-care professionals. The core competencies, posted on NCHPEG's Web site, www.nchpeg.org, currently serve as one of the only guides for genetic education in dentistry. Other core competencies and curriculum for genetics vary from dental school to dental school. But that may change.

"I will predict that, as time goes by, there will be a growing recognition of genetics in dental training," says Dr. Fernhoff. "But it will be an evolution, not a revolution."

This article provided by www.healthnewsdigest.com.

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