Scientific Underpinnings of Modern Medicine - Vaccination

Summary. Our understanding of the human immune system made tremendous progress all through the 20^th century, continuing even to the present day.  As part of this effort, important advances have been made in vaccine development, saving millions of lives worldwide.  But false reports linking vaccination with autism have led to rejection of vaccination by many parents, who fear incorrectly that vaccination may trigger the later appearance of autism.

Science can only proceed by open-ended inquiry, untainted by preconceived biases.  Unscientific proposals that are counter to the results of objective inquiry, such as the harmful movement to shun vaccination, are unproductive.  They harm society at large by diverting attention and wasting resources.  Human progress relies on critical verification of scientific discovery, and on building further on the progress made.

 

Allison had married relatively late, and was happy to have her infant son and husband as her family setting. 

As a parent, she’s been aware of the controversy in the popular press surrounding the question of a possible link between administering vaccines to infants and the later development of autism.  Having done considerable research on the controversy during her pregnancy, Allison realized she needn’t have concerns about this. She concluded that a possible connection with autism was mistaken. She proceeded to give all the vaccines recommended for growing children to her son, who continued growing to become a healthy child. 

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The modern practice of medicine has benefited enormously from the results of scientific research in the biological and medical sciences.  We all are better off from the results of these efforts.  The previous post dealt with the discovery of the structure of DNA and the genetic code, and the immune system.  Here I discuss the immune system in vaccination, and fallacies surrounding use of vaccination. 

Antibodies.  One of the ways that the immune system reacts to, and fights against, a foreign (likely disease-causing) particle, such as a virus, cell, or parasite, is to generate antibodies (a group of special protein molecules) that specifically react against particular structures on the particle (the antigen).   The antibodies bind molecule-to-molecule to the antigen, inactivating the particle (see the previous post) and preventing the disease or minimizing its harmful effects. 

Vaccines.  Vaccination is another process involving the immune system.  It has long been used as a way of deliberately confronting the immune system of a healthy person with a component obtained from, or that is similar to, a foreign antigen that causes disease in humans, in order to generate protective immunity against appearance of the disease later on.  The process was originally developed by Edward Jenner in the 18^th century for preventing smallpox.  It was known anecdotally that milkmaids who contracted cowpox from infected cows rarely became infected with smallpox.  Cowpox causes a similar, but weaker, illness in humans than smallpox. 

Jenner’s scientific breakthrough was to take the fluid produced in the cowpox infection, and to introduce it under the skin of healthy people.  He found that the treated people did not develop smallpox.  (We now understand that his procedure induced the immune system to produce antibodies that specifically attack the cowpox- or smallpox-causing substance, a virus.  A protein on the cowpox virus is sufficiently like the corresponding protein on the smallpox virus that the human antibodies that bind to cowpox also bind to smallpox, thus inactivating it.)

Many vaccines have been developed since then to immunize people against infection from viruses or bacteria.  Today commercial vaccines contain a very small amount of a preservative to keep them sterile.  Most vaccination is for young infants and toddlers, to protect against diseases such as diphtheria, whooping cough and measles.

Vaccines and Autism.  Public fear over use of vaccines has developed over the past two decades. It started with an erroneous and misleading report of a connection between vaccination and autism in children.  (See Science (2017), Vol.356, pp.364-373.)

In 1998 a physician, Andrew Wakefield, published a report in a respected British medical journal suggesting that use of the measles-mumps-rubella triple vaccine could lead to later development of autism.  His report led to a 20% reduction in vaccinations in Britain.  But in 2004 a journalist found that Wakefield was involved in trying to patent a competing measles vaccine, which was a serious conflict of interest.  The journal, in further investigations of its own found serious ethics violations by Wakefield and retracted his original paper in 2010.  A short time later the British General Medical Council revoked his license to practice medicine at all.  Thus Wakefield’s original findings were definitively determined to be invalid.

There is also a more general suspicion by many parents of an unwelcome intrusion by government authorities into a family’s health care decisions, as well as other nonscientific fears.

More recently, the Journal of the American Medical Association reported no difference in rates of autism between vaccinated and unvaccinated children. (See Science, cited above.)

Thimerosal, a mercury-based preservative, had been used in very small amounts in vaccines until 2001, when its use was discontinued in almost all vaccine compositions.  Even so, four years later in 2005 the lawyer Robert F. Kennedy Jr. (late President John F. Kennedy’s nephew) alleged in Rolling Stone and Salon that the U. S. government was hiding evidence that use of thimerosal led to increased incidence of autism.  The data Kennedy cited were mistaken, and in 2011 Salon retracted his article. 

Both the U. S. Centers for Disease Control and Prevention and the United Nations’ World Health Organization have concluded that thimerosal causes no health problems in children. (See Science, cited above.)  By contrast, a report published online in Nature on July 12, 2017 compares social interactions of infants and toddlers among pairs of identical twins, pairs of fraternal twins, and paired but unrelated single-birth infants and toddlers.  A genetic component was detected among children in the study that later were diagnosed with autism but that was absent in normal children.  This work shows that our scientific understanding of autism is growing as rigorous investigation proceeds.

Public refusal of vaccination places the children of rejecting parents in considerable danger because the infections that the vaccines inhibit cause serious or fatal diseases.  If enough children remain unvaccinated contagion can spread the diseases among them.  On the other hand, the World Health Organization estimates that 2 to 3 million lives a year are saved because of successful vaccination programs.

Conclusion 

Remarkable advances in biological and medical science, including immunology, have been made since the end of World War II.  Among these is cancer immunotherapy, in which antibodies are created to antigens on cancer cells, as if the cancers were foreign invaders like viruses and bacteria (see the previous post). 

Immunological research has also led to use of new, effective vaccines, raising immunity to dangerous diseases in our bodies.  To our detriment, nonscientific, indeed antiscientific, campaigns against the use of vaccines in children have increased the number of susceptible children among the populations of many developed countries, including the U.S., potentially to dangerous levels.  The spread of virulent infections is enabled by the failure to vaccinate. (See Science, cited above.)

Scientific investigation seeks to expand our knowledge and understanding of the world we live in.  Reflecting on the state of knowledge at any time, a curious scientist poses a question or suggests a hypothesis.  Experiments directed toward answering the question or verifying the hypothesis are carried out as an objective pursuit, further characterizing the natural world, without introducing preconceived biases.  Conclusions are then drawn based on the new results obtained. These frequently lead to practical applications that improve our health and prolong lives. 

The intrinsic value of scientific study should be defended and supported by all to continue its progress, and to promote human welfare.

© 2017 Henry Auer

Scientific Underpinnings of Modern Medicine – DNA, Cancer and Immunotherapy

Summary. Biological science has made tremendous progress since James Watson and Francis Crick presented their model for the structure of deoxyribonucleic acid, DNA.  Their model built on, and provided explanation for, important findings about DNA that were already known. 

Since then, important progress has been made, for example, in analyzing the base sequences, i.e., the chemical code, of specific genes and using that information for diagnostic and therapeutic purposes. Gene sequences that identify mutations in breast cancer genes alert physicians to the possibility that virulent malignancies may develop later in life.  Another genetic aberration, in the HER2 protein, permits targeting it with a therapeutic antibody, a major step forward.

Science can only proceed by open-ended inquiry, untainted by preconceived biases.  Unscientific proposals that oppose the results of objective inquiry are unproductive.  They harm society at large by diverting attention and wasting resources.  Human progress relies on critical verification of scientific discovery, and on building further on the progress made.

Allison just left her gynecologist’s office, with a referral to have a breast biopsy.  She was apprehensive, of course, since she had married relatively late, and was worried about her infant son and husband. 

Allison had been particularly concerned about her biopsy, because she’s a relatively late-age mother.  While breast cancer can arise in women of all ages, she had only recently had her first child, a son. 

A couple of weeks later Allison went in for the biopsy procedure.  In addition to the well-established examination of the samples from the specimen under a microscope, a small portion was also sent for DNA analysis, which searches for a genetic match for a mutation associated with some breast cancer cases.  When such a match is found, the patient is more likely to develop breast cancer during her lifetime. The pathologist found no visual evidence for cancer in Allison’s samples, and the mutant DNA also was not present. 

Now, with the negative biopsy result, and the information from the genetic analysis, Allison can continue to enjoy watching her son develop.  But she will be under close medical scrutiny for the possibility that a cancer may develop later, as the years pass.

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The modern practice of medicine has benefited enormously from the results of scientific research in the biological and medical sciences.  Here I describe the discovery of the structure of DNA and the genetic code, and the immune system.  The next post discusses the immunology of vaccination and the unproven fears that vaccines may be connected to autism.

DNA and the Genetic Code.  Modern understanding of genetics has progressed dramatically since 1953, when the double helical molecular structure of DNA, the material containing the genetic code of all cells, was worked out by James Watson and Francis Crick (based on additional contributions from Rosalind Franklin). Other renowned scientists of the time had tried but failed to predict the structure.  Watson and Crick discovered that the structure can only be correctly constructed if, considering the four DNA building blocks, an adenine on one strand of the helix is paired with thymine on the opposing strand; and guanine is paired with cytosine (see the graphic below). 

 

Diagram showing the double helix structure of the DNA molecule.  Guanine (green) on one strand can only bind with cytosine (red) on the other, and thymine (orange) only with adenine (blue).

Source: https://ijarovic.files.wordpress.com/2012/02/dna_helix.jpg?w=580

 

The sequence of the four building blocks, generally called nitrogenous bases, along the DNA strand, defines a code that specifies how each protein is synthesized in the cell. Proteins are the large molecules that variously define a) how cells go about their molecular business, b) provide structural elements that give cells their sizes and shapes, or c) communicate with neighboring and distant cells of the organism.

Breast Cancer Susceptibility.  As time passed, the base sequences of many single genes in cells have been worked out.  Among them were the two breast cancer, or BRCA, genes, BRCA1 and BRCA2.  A mutant, or variant, form of either of the BRCA genes can be easily identified by a genetic analysis that seeks the occurrence of the mutant base sequence in a subject’s DNA.  Having the mutant form increases the risk for later development of breast cancer by about 50%. 

Antibody therapy.  Certain breast cancers can be treated with some new drugs that are the result of major recent advances.  A breast cancer biopsy specimen can be assessed for the presence of a larger than normal level of a surface protein, the human epidermal growth factor receptor 2 (HER2) protein, which makes the cancer highly malignant.  Such breast cancers can be treated with a new biotechnology product, a monoclonal antibody drug called Herceptin®, that binds to and inactivates HER2.

Polyclonal antibodies.  One of the ways that the immune system reacts to, and fights against, a foreign (likely disease-causing) particle, such as a virus, cell, or parasite, is to generate antibodies (a group of special protein molecules) that specifically react against particular structures on the particle (the antigen).   The antibodies bind molecule-to-molecule to the antigen, inactivating the particle. 

Our natural immune system works by creating many antibody proteins that differ at the molecular level one from another, but that all bind to the foreign particle.  Each antibody protein arises from a distinct, specific cell in the immune system.  Because the natural immune reaction generates this large number of antibody species, collectively they are called polyclonal antibodies (see the image below). 

Left: Polyclonal antibody molecules (dark gray) in a sample bind different portions (colored pairs) of an antigen.  Right:  After selection of one of the antibody species, the antibody sample contains only one kind of antibody molecule, a monoclonal antibody, that binds only one portion of the antigen (blue pairs).
Source: http://absoluteantibody.com/antibody-resources/antibody-overview/antibodies-as-tools/

Monoclonal antibodies. Immunological research revealed that different antibody molecules in the polyclonal set bind differently to the antigen (see the image above).  Some that bind weakly only partly inactivate the antigen, whereas others that bind quite tightly are efficient as inactivators.

In 1975, Georges Köhler and César Milstein (Nature, 1975 Aug 7;256(5517):495-7), developed a technique that separated immune cells from one another, as well as creating hybrid cell fusions that never died. They cultured each isolated immune cell in a growth medium so that each culture now contained the daughter cells originating from a single fusion cell.  Now the antibody molecules in each culture were all identical to one another.  These are called monoclonal antibodies (see the image above).  The resulting monoclonal antibodies could be tested for how well they neutralized the antigen.

Herceptin® is the trade name for a monoclonal antibody drug that reacts specifically with the HER2 protein on a tumor cell surface, preventing the normal functioning of the receptor and inhibiting tumor growth.  In essence Herceptin® treats HER2, a normal constituent of human cells, as a foreign substance, attacking and inactivating it.

Conclusion 

Remarkable advances in biological and medical science have been made since the discovery of the DNA double helix and the identification of the genetic code.  Since about 2000 we have the sequences of all the genes in human DNA.  This permits identification of normal and pathological conditions in humans.  Understanding of the origins of many cancers has resulted, and has led to new therapies.  Among these is cancer immunotherapy, in which antibodies are created to antigens on cancer cells, as if the cancers were foreign invaders like viruses and bacteria. 

Science advances by the objective pursuit of new information about the natural world.  The results frequently lead to practical applications that improve our health and prolong lives.  The intrinsic value of scientific study should be defended and supported by all to continue its progress.

© 2017 Henry Auer