Renaissance of Human Developmental Process and Age of Discovery

Chapter 21: Genomics, Pharmacogenomics, Pharmacodiagnostics and

The Future of Diagnosis and Treatment

The following information is difficult but warrants inclusion because it is on the cutting edge of diagnosing and treatment of mental disorders. I believe our current methods of diagnosing and treating children with medicine are primitive as compared to what will take place in the near future. Like in science fiction movies, the future doctor will be able to scan your child’s DNA to determine the disorder and then to make a formula of the correct medicine at the correct dose to treat the disorder. Roche Labs is predicting it will take 3 to 5 five to have a new diagnostic process. Perhaps the future is really right at our door!

Below is the current information which predicts that the future of psychiatric care is about to be realized.

1. The Future of Diagnosing and Prescribing Medication

In June 2000, the first draft of the human genome’s 3.2 billion base pairs was made. Surprisingly, humans have about 25,000 genes (not many more than an earthworm or a mouse, but perhaps closest to a dog and not to a monkey as once thought).

Pharmacogenetics explores the innovations in diagnosing which relies on DNA profiling. A new technology is being proposed that may eventually allow us to systematically diagnose a mental disorder and give us a more accurate “reading” of neurotransmitter levels which can be “adjusted.”

Genomics is defined as the study of flow of information in a cell, while Bioinformatics is the application of computers to make sense of the vast amount of information coming from Genomics.

Microarray technology which use laser scanners available today can scan a drop of blood to test for thousands of biomarkers linked to “illness” genes (like breast cancer, colon cancer, etc). Biomarkers or markers have been mapped throughout the human genome. Most notable are the biomarkers present in those who have certain cancers or who have certain mental disorders like, schizophrenia, depression, or autism. The microarray slides are read automatically by laser scanners, and the results, thanks to Bioinformatics, are fed directly into computers armed with appropriate software so that risk can be predicted.

Pharmacogenics also called Pharmacogenomics will tailor make drugs for individual patients according to their unique genomic makeup. The pharmaceutical companies are calling this “individualized medicine”.

There is no doubt that decipherment of the human genome will change our lives. Even though we have an imperfect understanding of how the genome is encrypted (and do not yet understand its language), we have in our hands the all of nature’s information on how to make and run a human being! The knowledge of the human genome will change almost everything we know about medicine, and these changes are rapidly approaching.

You will soon find the media using terms like:

*Target screening”

*Kinase inhibitors for the treatment of cancer”

*Biomarkers to monitor and predict disease progression and response to therapy”

*Translational medicine” an approach to drug discovery and development which

relies on the preclinical identification of biomarkers”

*Translational Oncology: Hitting the Right Target in the right patient at the right


*Pharmacogenomic studies: Personalized Medicine and Biomarkers”

Note the following description of a scientific paper that was presented at a Clinical Biomarker Summit conference on March 29, 2006:

“Blood gene expression analysis in Major Depression treated with Citalopram. Several studies have suggested the involvement of genetic factors in Major Depression (MD) which may also play a role in a patient’s response (responder) or lack of response (nonresponder) to antidepressant treatment. To identify gene targets that may mediate the response to Citalopram (Celexa) treatment, a commonly used SSRI (selective serotonin reuptake inhibitor) antidepressant, blood gene expression profiling studies are being conducted on patients administered Celexa for eight weeks. Differential expression analysis resulted in a unique set of genes with altered expression between pre-and post-treatment samples.”

The article goes on to say that patients who do not respond to Celexa treatment have a unique set of differentially expressed genes. These preliminary studies show the possibility of gender effect (probably because Major Depression is found more in females) and several biological processes were affected, including transcription and response to stress.

2. Individualized Medicine

This quote is taken from an article written after an interview with Jorge A. Leon,

President of Leomics Consulting. In this article, “Molecular Diagnostics Testing Represents New Business Opportunities and Health Care Implications: An Interview with Jorge A. Leon of Leomics Consulting” published in September 11, 2004 on the Cambridge Healthtech Institute website (, Mr. Leon discusses how information specialists are using the identified human genomes to completely change the face of psychiatry as we know it. He is predicting a shift to early detection of disease, and treatment targeted to a patient’s specific condition. Although, Mr. Leon is looking at all this from a marketing standpoint, but there are lessons inherent to his message.

Mr. Leon has this to say about the future of diagnosing diseases:

“Molecular diagnostics promises to transform disease diagnosis as we know it today, as diagnosis based on the use of surrogate markers is replaced by genomic and proteomic analysis. This fundamental shift offers for early disease detection, potentially before symptoms have even occurred. Further, the ability to perform proteomic studies using molecular diagnostic and pharmacogenomic tools will result in more effective treatment highly targeted to a patient’s specific condition and incur less risk of adverse drug reactions.”

Leon goes on to say that there are two ways that molecular diagnostic testing can build his markets. One is “service” by which he means genetic testing needs of Americans which is growing by about 60% - 75% per year. The clinical testing service industry has provided patients with robust tests for Cystic Fibrosis, HIV drug resistance, and more. Cancer testing accounts for part of this market. In 2004, there were no standardized analysis programs.

A corollary to the “post-genomics revolution” is clinical proteomics. Clinical proteomics involves the use of technologies and software to look at the whole proteome of the cell or serum in screening for illnesses, especially cancer. For example, in 2004 a company called Correlogic in collaboration with the National Cancer Institute (and made available by LabCorp and Quest Diagnostics) devises a proteomic serum test to detect ovarian cancer in high risk patients. Other tests for cancer are being developed. The unmet need in clinical medicine to make more accurate diagnoses will be met using this technology. Work by Correlogic and other companies will lead to tests for breast, lung, colon, and prostate cancers in the near future.

Leon questions whether pharmacogenomics will reach the market as quickly. Pharmaceutical companies are resistant to adopting molecular testing because by having more accurate drug response information they will not make the large sums of money from physicians prescribing medicine on a hit-or-miss basis. The idea is to develop the right drug for the right person at the right dose. Once the FDA accepts molecular testing information as the gold standard, it will change clinical trials requirements for the drug companies to get their drugs approved. Drug companies are scared by this new technology. But Leon has a remedy: If an Alzheimer’s drug is found effective for 30% of the population, Leon recommends that the drug companies develop a drug that will treat the other 70%.

Roche has an exclusive agreement with Affymetrix’s GeneChip DNA microarray technology for 18 years. The first product to come out of this alliance is a chip that characterizes a patient’s ability to metabolize certain drugs, based on the patient’s genetic profile. The microarray detects mutations in genes 2D6 and 2C19 on cytochrome P450 (the liver enzyme). These genes affect the ability of the liver to metabolize several drugs that include more than 25% of the drugs available on the market. The metabolic analysis performed by the chip will eventually offer practitioners a tool to aid them in prescribing more effective dosages of medication.

The test takes blood cells, or cells from the inside of the mouth and amplifies the area of the genes which control how the enzyme works. Scientists can read the genetic pattern to identify the problem. With this test, the physician will be able to categorize a patient into one of four metabolic types. Knowing a person’s metabolic genotype can prevent adverse reactions to prescribed drugs.

Roche Diagnostic’s communications manager, Melinda Baker, says that this technology can be particularly useful in the prescription of drugs for depression and other psychiatric disorders.

“Psychiatric drugs are notoriously difficult to effectively prescribe, because it can take a long time to get a person the correct dose level.”

The idea is to find “biomarkers” of response, a test that tells us if the patient will respond to the drug, giving drug companies a targeted selection of a patient population. Biomarker research will help in drug discovery, in addition to drug response capacity in a given population.

Understanding a person’s genotype can get them the right dosage faster and help them avoid a class of drugs that would cause them to suffer adverse reactions. This technology has been available since 2003. Roche expects to develop the technology into a fully automated system that can be marketed as a certified in vitro diagnostic in 3-5 years, putting the availability at 2006 to 2008. Roche talks about the obstacle of turnaround time and educating people about how the technology works and what benefits it holds. They want to sell the chip to be used in the pharmacogenomic arena.

. The discovery of the human genome will have both positive and negative repercussions. The perils of genetic engineering are as powerful as are the benefits. Gene therapy is one of these powerful benefits. In medicine, somatic gene therapy is used by doctors to cure a disease by inserting new genetic material into an existing patient, usually by piggybacking the new gene onto a virus. This prompts growth of healthy cells.

The second and deleterious effect of knowing the human genome is that of genetic engineering (called germline engineering). This engineering introduces fundamental genetic changes by removing a single cell from the earliest stages of a developing embryo, adding or removing genes, and then inserting the new cell into an egg whose nucleus has been removed. This new embryo would be implanted into a woman’s womb and allowed to grow. The obvious benefit is that we could “edit out” malfunctioning gene that causes, say, cystic fibrosis, or polio. Then we could remove genetic predisposition to conditions like obesity or depression. This is only one step away from satisfying those parents who will want to germinate a perfect fetus with beauty, intelligence or the muscular development leading to Olympic medals. Writer Bill McKibben predicts a “kind of biological arms race” available only to those who can afford such procedures. Those who can’t will become part of the biological underclass or the underprivileged.

As a parent and a professional, I see genome information more positively. Loving people who desire offspring will rest assured that they will be born free of destructive illnesses like, major depression, anxiety or schizophrenia. In the future we will contend with deadly viruses rather than mental illness, and as such, we will close a chapter of our collective history because we’ve conquered the brain, “the last frontier.”

5 views0 comments

Recent Posts

See All

BobDog Bob used to live on my block and he had a dog Dog was not Bob and Bob was not dog. I thought and thought about this but when that wagger Wagged his tail and licked Bob’s face, both of them smil

“Let the little children come to me, and do not hinder them, for of such is the kingdom of God” St. Luke 18:16 The 1990’s will be remembered as the Age of Little Murderers. I recall a stately modern r