NORMAL BIOCHEMICAL PROCESSES ARE THE BASIS OF HEALTH
The World Health Organization (WHO) defines health as a state of "complete physical, mental, and social well-being and not merely the absence of disease and infirmity." From a
strictly biochemical viewpoint, health may be considered that situation in which all of the many thousands of intra- and extracellular reactions that occur in the body are proceeding at
rates commensurate with the organism's maximal survival in the physiologic state. However, this is an extremely reductionist view, and it should be apparent that caring for the health
of patients requires not only a wide knowledge of biologic principles but also of psychologic and social principles.
Biochemical Research Has Impact on Nutrition & Preventive Medicine
One major prerequisite for the maintenance of health is that there be optimal dietary intake of a number of chemicals; the chief of these are vitamins, certain amino acids, certain
fatty acids, various minerals, and water. Because much of the subject matter of both biochemistry and nutrition is concerned with the study of various aspects of these
chemicals, there is a close relationship between these two sciences. Moreover, more emphasis is being placed on systematic attempts to maintain health and forestall disease, that is,
on preventive medicine. Thus, nutritional approaches to—for example—the prevention of atherosclerosis and cancer are receiving increased emphasis. Understanding nutrition
depends to a great extent on knowledge of biochemistry.
Most & Perhaps All Diseases Have a Biochemical Basis
We believe that most if not all diseases are manifestations of abnormalities of molecules, chemical reactions, or biochemical processes. The major factors responsible for causing
diseases in animals and humans are listed in Table 1–2. All of them affect one or more critical chemical reactions or molecules in the body. Numerous examples of the biochemical
bases of diseases will be encountered in this text. In most of these conditions, biochemical studies contribute to both the diagnosis and treatment. Some major uses of biochemical
investigations and of laboratory tests in relation to diseases are summarized in Table 56–1. Chapter 56 describes many aspects of the field of clinical biochemistry, which
is mainly concerned with the use of biochemical tests to assist in the diagnosis of disease and also in the overall management of patients with various disorders. Chapter 57 further
helps to illustrate the relationship of biochemistry to disease by discussing in some detail biochemical aspects of 16 different medical cases.
Table 1–2 The Major Causes of Diseases1
1. Physical agents: Mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, radiation, electric shock.
2. Chemical agents, including drugs: Certain toxic compounds, therapeutic drugs, etc.
3. Biologic agents: Viruses, bacteria, fungi, higher forms of parasites.
4. Oxygen lack: Loss of blood supply, depletion of the oxygen-carrying capacity of the blood, poisoning of the oxidative enzymes.
5. Genetic disorders: Congenital, molecular.
6. Immunologic reactions: Anaphylaxis, autoimmune disease.
7. Nutritional imbalances: Deficiencies, excesses.
8. Endocrine imbalances: Hormonal deficiencies, excesses.
1Note: All of the causes listed act by influencing the various biochemical mechanisms in the cell or in the body.
Source: Adapted, with permission, from Robbins SL, Cotram RS, Kumar V: The Pathologic Basis of Disease, 3rd ed. Saunders, 1984. Copyright © 1984 Elsevier Inc. with permission
from Elsevier.
Some of the major challenges that medicine and related health sciences face are also outlined very briefly at the end of Chapter 57. In addressing these challenges, biochemical
studies are already and will continue to be interwoven with studies in various other disciplines, such as genetics, cell biology, immunology, nutrition, pathology, and pharmacology.
Many biochemists are vitally interested in contributing to solutions to key issues such as how can the survival of mankind be assured, and also in educating the public to support the use
of the scientific method in solving major problems (eg, environmental and others) that confront us.
Impact of the Human Genome Project (HGP) on Biochemistry, Biology, & Medicine
Remarkable progress was made in the late 1990s in sequencing the human genome by the HGP. This culminated in July 2000, when leaders of the two groups involved in this effort
(the International Human Genome Sequencing Consortium and Celera Genomics, a private company) announced that over 90% of the genome had been sequenced. Draft versions of
the sequence were published in early 2001. With the exception of a few gaps, the sequence of the entire human genome was completed in 2003, 50 years after the description of the
double-helical nature of DNA by Watson and Crick.
The implications of the HGP for biochemistry, all of biology, and for medicine and related health sciences are tremendous, and only a few points are mentioned here. It is
now possible to isolate any gene and usually determine its structure and function (eg, by sequencing and knockout experiments). Many previously unknown genes
have been revealed; their products have already been established, or are under study. New light has been thrown on human evolution, and procedures for tracking disease genes
have been greatly refined. Reference to the HGP will be made in various chapters of this text.
As the ramifications of the HGP increase, it is vital for readers to understand the major contributions to understanding human health and disease that have been made, and
are being made, by studies of the genomes of model organisms, particularly Drosophila melanogaster (the fruit fly) and Caenorhabditis elegans (the round worm). This has
been clearly stated by Bruce Alberts (2010) in reflecting on the recent impressive progress made in deciphering the genomes of these two organisms. Because these organisms can be
experimentally manipulated and have short generation times, relatively rapid progress can be made in understanding the normal functions of their genes and also how abnormalities of
their genes can cause disease. Hopefully these advances can be translated into approaches that help humans. According to Alberts, "As incredible as it seems, future research on flies
and worms will quite often provide the shortest and most efficient path to curing human diseases." This applies to disorders as different as cancer and Alzheimer disease.
Figure 1–2 shows areas of great current interest that have developed either directly as a result of the progress made in the HGP, or have been spurred on by it. As an outgrowth
of the HGP, many so-called -omics fields have sprung up, involving comprehensive studies of the structures and functions of the molecules with which each is concerned. Definitions of
the fields listed below are given in the Glossary of this chapter. The products of genes (RNA molecules and proteins) are being studied using the technics of transcriptomics and
proteomics. One spectacular example of the speed of progress in transcriptomics is the explosion of knowledge about small RNA molecules as regulators of gene activity. Other -omics
fields include glycomics, lipidomics, metabolomics, nutrigenomics, and pharmacogenomics. To keep pace with the amount of information being generated, bioinformatics
has received much attention. Other related fields to which the impetus from the HGP has carried over are biotechnology, bioengineering, biophysics, and bioethics.
Nanotechnology is an active area, which, for example, may provide novel methods of diagnosis and treatment for cancer and other disorders. Stem cell biology is at the center of
much current research. Gene therapy has yet to deliver the promise that it offers, but it seems probable that will occur sooner or later. Many new molecular diagnostic tests have
developed in areas such as genetic, microbiologic, and immunologic testing and diagnosis. Systems biology is also burgeoning. Synthetic biology is perhaps the most intriguing of
all. This has the potential for creating living organisms (eg, initially small bacteria) from genetic material in vitro. These could perhaps be designed to carry out specific tasks (eg, to
mop up petroleum spills). As in the case of stem cells, this area will attract much attention from bioethicists and others. Many of the above topics are referred to later in this text.