Over the past decade, there has been a rising cacophony of predictions that genetic discoveries emerging from the Human Genome Project would revolutionize primary medical care. However, despite these predictions, genetic practice in primary care has undergone little change. This paradox is in part due to the exuberance and optimism of the genetic community about genetic testing that has its roots in the early successes of newborn screening and prenatal carrier testing. However, the lack of effective interventions for people with these disorders or who are carriers of genetic diseases and increasing public apprehension about genetic testing will slow down adoption of genetic technologies into primary care medicine. It also appears likely that before widespread genetic testing will be offered, practice guidelines, educational materials for providers and patients, informed-consent protocols and laboratory standards for genetic testing will need to be developed.

Many review articles and descriptions of programs designed to teach primary care physicians the basics of new genetic technologies have been appearing in medical journals¹ and are accessible online.² Twelve years ago, the following millennial prediction appeared in U.S. News and World Report:

Even though little change has taken place in medical genetic testing in primary care since that prediction, the 1998 Presidential Address to the American Society of Human Genetics predicted:

While certainly subdued compared with the prediction of a decade ago, it remains appropriate to ask, “Where's the beef?” Genetic discovery has led to noteworthy advances in the ability to better understand and diagnose many rare genetic disorders. However, the lack of effective interventions and public resistance suggest that genetic technologies will indeed be slow to be adopted into primary care medicine.

Why is there such exuberance and optimism in the genetics community about the wholesale adoption of genetic screening and testing by the general medical community and the public? Much of this appears to do with the early, idealized successes in the introduction of genetics technology. For example, newborn screening for phenylketonuria (PKU), initiated in the 1960s, unquestionably has been successful in preventing mental retardation in persons with classic PKU.⁵ However, the unfortunate morbidity and mortality of a few infants from hastily initiated programs instituting improper diets before adequate treatment information was available is often overlooked.⁶ Also, the onerous nature of the highly restrictive diet, the frequent medical follow-ups and the devastating effects of untreated maternal PKU on offspring⁷ are frequently minimized in reviews of this program's success.⁸

Similarly, the introduction of pre-reproductive screening for Tay-Sachs disease among the ethnic Jewish population living in North America has been touted as a paradigm for a successful genetic carrier-screening program.⁹ The fact that pregnancy termination, assisted reproduction and genetic matchmaking in arranged marriages are the only means to prevent liveborns with this disease is often not stressed.

While geneticists seem to remember their successes, the disastrous population-screening programs for sickle cell anemia that were legislatively mandated in 17 states during the 1970s¹⁰ have been seemingly forgotten. New York passed legislation requiring sickle cell anemia screening before issuing a marriage license, which, coupled with confusion about carrier and disease status, resulted in stigmatization of carriers.¹¹

The myopic and nostalgic view of the history of newborn screening for PKU and genetic carrier testing for Tay-Sachs disease led many geneticists to be optimistic that these models would be widely applicable to a host of other genetic conditions. However, these disorders have unique features that allowed the development of successful screening methods that cannot be generalized to most genetic disorders. The successful treatment of PKU was dependent on the novel feature that phenylalanine is an essential amino acid, and serum levels can be tightly controlled by dietary restriction.¹² Tay-Sachs disease is unique in having an early-onset, a rapidly fatal course in childhood, no available treatment and a high incidence in a small ethnic group,¹³ leading to little opposition to carrier screening programs in the Ashkenazi Jewish population.

Another reason for the optimism about genetic screening and testing has been the mercurial expansion of genetic knowledge stimulated by the Human Genome Project.¹⁴ Two years ahead of schedule and below budget, this keystone of genetic research is mapping and sequencing the human genome, resulting in the recurring theme that once a gene has been mapped and sequenced, treatment is just around the corner.¹⁵ Unfortunately, successful mapping does not necessarily translate into effective treatment. For example, the genetic alteration that causes sickle cell anemia has been known for almost 50 years; yet, this information has not translated into any therapies for persons with this disease.¹⁶ Conventional treatments have extended the quality and length of life for persons with sickle cell anemia, but gene therapy remains a distant future goal. The Human Genome Project might be better thought of as representing the beginning of the age of genetic discovery rather than the end.

While the optimism and exuberance of many geneticists about genetic screening seem boundless, the interest of the general public has been greatly overestimated. The wide belief that people who know their genetic risks would have the added impetus to effect reproductive planning and lifestyle changes³ may not be accurate. One study¹⁷ that offered carrier testing to siblings of patients with cystic fibrosis (who might be assumed to be knowledgeable about this disease and more likely to use genetic testing) found notably low interest among participants for testing. The authors concluded that remaining unaware of one's carrier status might serve as a significant psychologic function for persons considered at risk.

Another study¹⁸ offered cystic fibrosis carrier testing to pregnant women and found that those women who had the most knowledge about the disease tended to be the least interested in carrier screening. Not knowing their carrier status means not having to confront difficult prenatal issues like pregnancy termination.

Another recent study¹⁹ offered genetic testing results to family members at risk for hereditary nonpolyposis colon cancer. These persons had participated in a research study and a specific DNA mutation had been detected in a family member. An astonishing 60 percent of the participants did not want to receive the results. The authors concluded that despite having significantly elevated risks of developing colon cancer, a relatively small proportion of family members were likely to use genetic testing. The researchers identified less formal education and the presence of depression, especially among women, as barriers to test acceptance.

In a unique initiative for government-sponsored research, the Human Genome Project established the Ethical, Legal and Social Implications (ELSI) Program and set aside 3 to 5 percent of its budget to study the ethical, legal and social impact of genetic discovery.²⁰ Many of the early studies focused on anticipated insurance and job discrimination and ascribed reluctance to undergo genetic testing to fears of genetic discrimination.²¹

However, the results of a failed newborn screening program for alpha1-antitrypsin deficiency in Sweden point to more complex reasons for resistance to genetic screening and testing.²² This deficiency is an autosomal recessive genetic condition that predisposes to adult, early-onset emphysema particularly in the presence of environmental factors such as cigarette smoking. Avoidance of cigarette smoke and smoky or dusty environments would presumably be a beneficial action if persons with this genetic predisposition could be identified.

Using this hypothesis, an experimental newborn screening program was established in Sweden and involved approximately 200,000 newborns.²² The program was prematurely cancelled after severe, negative psychologic consequences (that were still evident at a five- to seven-year follow-up evaluation) were identified in more than one half of the families.²³ Families reported viewing affected children as “different” and their anxiety about the disease led many of the parents to increase their cigarette smoking rather than decrease it as recommended. Thus, the negative impact of genetic information on patients and their families, even in a situation where environmental avoidance was available, is poorly understood and needs much more study. Many persons view genetic testing information as different and less alterable then other medical testing information and are reluctant to use it without clear benefit.

Another factor leading to slow adoption of genetic testing into practice is that the technical and biologic complexities of genetic information are far greater than expected. Following the identification of the cystic fibrosis gene in 1989 and expecting huge public interest in carrier testing, the American Society of Human Genetics issued a cautionary statement arguing against immediate general population screening.²⁴ Ten years later, after numerous pilot studies, a growing consensus believe that pre-reproductive screening should be targeted to white northern Europeans, Ashkenazi Jewish populations, persons with a family history of cystic fibrosis and those who have a partner with the disease.²⁵ It is also clear that before screening can be offered to this segment of the population, practice guidelines, educational materials for providers and patients, informed-consent protocols and laboratory standards for testing must be developed.

Similarly, when the BRCA1 breast cancer gene was located, the American Society of Human Genetics again felt obligated to issue a cautionary statement against what they felt would be widespread public demand for general population screening.²⁶ Now, five years later, a debate continues as to whether presymptomatic testing for mutations is beneficial and, if so, who should be offered testing.²⁷ The low-estimated frequency of detectable BRCA1 mutations (one in every 833 women), the hundreds of different DNA mutations and the absence of an undisputed cancer prevention option²⁸ have led advisory bodies including the American Society for Clinical Oncology to recommend that testing be restricted to women from high-risk breast or ovarian cancer families.²⁹

The discovery of several BRCA1 and BRCA2 founder mutations in the Jewish population³⁰ resurrected hope among geneticists that at least a limited population-screening program might yet be established. However, a recent study³¹ suggests that the penetrance of these mutations may be lower than estimated; thus, even in this defined ethnic population, screening may not be useful.

Therefore, while advertising beef, the genetics community only seems to be delivering tofu. The complexity of genetic diseases has been far greater than anticipated, and the public's interest in learning about genetic predispositions is unexpectedly low. So, will genetics ever impact primary care? It already has and will continue to do so, but it is likely to continue in an evolutionary rather than revolutionary manner. Primary health care providers who keep current by reading the medical literature and attending professional meetings will not be left in the dust. And, in time, the benefits of genetic technology will benefit our patients.