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Ustekinumab (Stelara)

Information regarding the psoriasis drug Ustekinumab (Stelara) can be found on the FDA’s page for this drug.

What Are Monoclonal Antibody Drugs?

Monoclonal antibodies are antibodies produced from clones of a single cell lineage of B immune cells. Human monoclonal antibodies are used to help treat a number of diseases ranging from Rheumatoid Arthritis, Hepatitis C, and various cancers. According to MedicineNet, human monoclonal antibodies are made by crating transgenic mice with human antibody producing genes. These mice are then vaccinated with the target peptide and consequently produce antibodies. Theses antibodies can then be harvested and used to treat human patients.

Ustekinumab’s Mechanism of Action in Treating Psoriasis

Psoriasis is an autoimmune disease that result in scaly rashes of the skin. While the exact causes of psoriasis are unknown, an immune stimulant is thought to ramp up T cell activity in the skin. Cytokines released from these activated T cells stimulate inflammation and cause defective over-growth of the skin; these result in the hallmark rashes of psoriasis. Ustekinumab is designed to bind to IL-12 and IL-23, according to MedicineNet’s Ustekinumab page. These two cytokines stimulate T cell response; therefore, blocking their binding to T cells can prevent this un-needed immune reaction and decrease signs and symptoms of psoriasis.

Side Effects

According to the Stelara manufacturer’s website, side effects include but are not limited to:

-nasal congestion,
-sore throat
-runny nose
-upper respiratory infections
-fever
-headache
-tiredness
-itching
-nausea and vomiting
-redness at the injection site
-vaginal yeast infections
-urinary tract infections
-sinus infection
-bronchitis
-diarrhea
-stomach pain
-joint pain

Immune System Compromised

As is reflected by the numerous potential side effects, Ustekinumab makes patients more susceptible to serious infections. This is because Ustekinumab targets and disbales IL-12 and IL-23. Both of these immune signalers enhance T cell actions. In addition, IL-12 is an important inducer of IFN-gamma. Thus, Ustekinumab weakens the aquired immune response and lowers the patient’s ability to fight infection. The website specifically states that the patient should inform his or her doctor of any current or re-occuring infection before starting Ustekinumab. The website also puts a large emphasis on patients with tuberculosis (latent or active) and on patients who have come into contact with someone who has TB. Anyone who has TB or has come into contact with someone who does should not take Ustekinumab. This emphasis on TB is likely due to the fact that Ustekinumab disbables IL-12 which induces the production of IFN-gamma. IFN-gamma is one of the most important cytokines in keeping tuberculosis infection “in-check” or in the latent phase. IFN-gamma is the most important activator of macrophages, which are essential to keeping TB infection in the latent phase. Individuals with decreased levels of IFN-gamma are very likely to develope active TB if infected with M. tuberculosis.

COVID-19 Antibody Testing and Its Implications

COVID-19 Testing: Genetic vs. Immune Response

The need for more widespread testing of COVID-19 is paramount. We need accurate tests, and a large number of them to determine who is infected and shedding the virus to others. The test that accomplishes this is a genetic test. Usually, a patient’s nasal cavity and/or throat are swabbed. The sample is then added to chemicals that breakdown the envelope and capsid of the virus, exposing its ssRNA. Reverse transcriptase and subsequently many rounds of PCR are performed. The resulting solution is run with a specific SARS-CoV-19 visible tag. The visibility of the tagged confirms the presence of active, productive infection. The individual is currently infectious for COVID-19.

But with the unprecedented financial sequelae of this pandemic, it is in everyone’s best interest to get the world up and running again, as soon as safely possible. For this to happen, it is important to know not only who is infected, but also who was infected and has since recovered. According to an article from Medical News Today, molecular, or genetic, tests are not able to do this. As we know, anyone who has recovered is at very low risk for contracting the virus again. To identify these people, more and more serology tests are being performed to detect the presence of IgM and/or IgM in a patient’s blood. These antibody tests involved taking a small amount of the patient’s blood and essentially mixing it with a number of SARS-CoV-19 antigens. If the patient has developed an immune response as a result of COVID-19 infection, he or she will have IgM and/or IgG that form complexes with the viral antigens. These complexes are then run over a membrane with separate fixed anti-IgM and anti-IgG antibodies. These regions will essentially grab on to the patient’s antibody-antigen complexes.

Results

We know that IgM is the first produced antibody in the acquired immune response to any primary infection, including COVID-19. Later, however, IgM production wanes and IgG production ramps up and hangs around for a while. Thus, results to a COVID-19 blood test are interpreted as follows:

-Primarily IgM: This patient is in the early stage of infection. He or she is likely contagious but may or may not be experiencing the signs or symptoms yet.

-Both IgM and IgG: This person is in the middle stage of infection. He or she is likely showing the signs and symptoms of the disease. If this patient is not showing signs or symptoms by now, he or she is likely an asymptomatic carrier.

-Primarily IgG: This person has likely contracted COVID-19 but has since recovered. At this point, the person is not infectious and is unlikely to get sick from COVID-19 again.

It is important to note that these antibody test can give false positives. While, antibodies are incredibly specific in what they binds, cross reactivity can occur. There are many different types of Coronaviruses and many people have been infected with them before. Some of these other Coronavirus may have caused a similar enough antibody response which caused the false positive to COVID-19. According to Med Page Today, “False positive results for IgM and IgG antibodies may occur due to cross-reactivity from pre-existing antibodies or other possible causes.”

Implications

Antibody testing is important for several different reasons. First off, it is a method by which we can know if someone currently infected with the virus. However, antibody testing can tell us who can re-enter the world. Patients exhibiting only IgG reactivity are immune and non-contagious so they can be allowed to go back to work. This is incredibly important because the economic side effects of this pandemic are putting some people in a worse situation than they would be if they got sick with COVID-19.

Another very important feature of the antibody test is that it allows us to identify those who could be serum donors. Sometimes, patients who are severely ill with COVID-19 can receive components of the blood of those who have recovered. While this person, may or may not be producing their own antibodies, the donor’s antibodies can help keep the infection in check. This is called passive immunity. According to an article from Scientific American, “Patients with severe cases of COVID-19 may be able to be treated with blood plasma from people who have developed antibodies and are immune to the disease in what is effectively an antibody-transfer operation.”

CAR T Cell Therapy

What is it?

While there are myriad new therapies that have emerged since the dawn of genetic engineering, one of the most promising and exciting is the one known as chimeric antigen receptor T cell therapy or CAR T cell therapy. Our immune system is very good at its job. On a weekly basis, we encounter many bacteria and viral particles. In addition, every day, many cells in our body mutate to become cancerous. However, most of us do not get deathly sick or develop cancer on any given week. This is thanks to our immune system, which is able to specifically target these pathogens or cancer cells and eliminate them from our body. CAR T cell therapy utilizes the human immune system to target a number of diseases, especially cancers. A sample of blood is taken from the patient and T cells are isolated. Then, these T cells are genetically modified to create a surface receptor that targets a given disease. The cells are cloned and then injected back into the patient. These cells will now target and kill whatever cells display the antigen the genetically modified T cells now recognize. According to an article released by the American Cancer Society, “the relationship between antigens and immune receptors is like a lock and key. Just as every lock can only be opened with the right key, each foreign antigen has a unique immune receptor that is able to bind to it”. CAR T cell therapy essentially gives our immune system the proper “key”.

CAR T Cell Therapy in Treating B Cell Lymphoma

A great example of CAR T cell therapy in action is its employment against a number of lymphomas and leukemia. I will specifically discuss its use against B cell lymphoma. According to a release from Eurekalert!, the CD19 antigen is expressed in B cell lymphoma and and other lymphatic cancers. This provides a target that is specific to the cancer cells, which should not target healthy cells. Thus, T cells are extracted from the patient and genetically modified to produce an anti-CD19 receptor. They are then grown up and reintroduced into the patient’s system where they find and kill cancerous B cells.

Side Effects

When I was initially researching CAR T cell therapy, I thought that there would be little to no side effects since the modified T cells are were part of the patient’s own body. However, I soon realized this was a silly assumption. According to the previously mentioned American Cancer Society article, there are several side effects of CAR T cell therapy. These can include flu-like symptoms and cytokine release syndrome or CRS. T cytotoxic cells, the cells used in CAR T cell therapy, kill targeted cells with toxic cytokines. Unfortunately, these can accumulate in the blood of the patient and cause these flu-like symptoms. Less often, the T cells can target healthy B cells, which can leave the patient more prone to infection of pathogens.

AJ’s Thoughts on COVID-19

Health

It is a very interesting time to be alive. These pandemics are a once in a century occurrence and while this novel coronavirus is scary, it is very interesting watching the world, governments and the average Joe alike, react to this disease. I will say, I am not personally scared of contracting the virus. As a 20-year-old that does not smoke and is relatively active, I am not at major risk for hospitalization or death. Part of me even wants to contract the virus, if I haven’t already contracted it, just to get it over with. However, my grandparents live down the street and they are 84 and 85 years old. I don’t think I am quite ready to part with them so I am very hesitant to visit and I am certainly not hugging them. I really hope that we can develop a cure or vaccine quickly and I have great confidence we will, especially considering COVID-19 is the focus of the entire world right now.

Humanity

I have very mixed feelings about the way people are reacting to this virus. The first one I will discuss is anger. Stop hoarding, people. Your unwarranted panic is causing people to have un-wiped butts. People are even struggling to find food. My dad runs a primary care clinic that almost had to close because we could not find toilet paper to stock the bathrooms; this is not a lie. Take what you NEED and leave the rest for others. I am also angry about how some have reacted to the news that hydroxychloroquine and/or chloroquine could serve as a possible treatment for COVID-19, according to NPR. This drug is normally used to treat malaria and rheumatoid arthritis. According to NPR, some healthcare workers have been prophylactically prescribing it for themselves and their families/friends. This is proof that its not just the ignorant people that are hoarding essentials. Many people that have RA are not able to fill their (hydroxy)chloroquine prescriptions due to this.

At the same time, I am encouraged that most people are making the best of the current situation. For example, a bunch of my friends and I created our own Zoom meeting just because we had not seen each other in a while. There are also countless funny memes on social media. I particularly enjoy this one:

Instagram, posted by @pubity

Education

While I am happy to see more of my family at home, online classes suck overall. I am saving a lot of time by not having to walk from class to class or to get food, but online classes are inevitable going to lessen our quality of learning. UNC implemented this Pass/Fail policy but many of us, especially in MCRO 251 will not be able to utilize it because we are applying to nursing, dental, PA, or medical school which will not accept a “Pass” mark. I have already experienced many online class “fails” such as not being able to access work. In addition, we will not get the hands on experience of lab.

Gonorrhea

Overview

Gonorrhea is a bacterial sexually transmitted disease. It is caused by the bacterium Neisseria gonorrhoeae, which is a Gram-negative diplococci. Most victims are asymptomatic which allows the bacterium to spread easily; individuals who do not know they are infected with the bacterium are more likely to continue to engage in sexual intercourse with others. Gonorrhea can be transmitted though oral, anal, and vaginal sex. Gonorrhea is usually curable with antibiotic treatment. However, as is the case with almost every bacterium, antibiotic resistance is growing quickly. To combat this, the CDC has changed its Gonorrhea treatment regimen several times over the past 20 years, according to an article from the Outbreak Observatory.

Increasing Rates of Gonorrhea

Incidence of almost every STD in the United States. This trend holds true for Gonorrhea as well. According to the above mentioned Outbreak Observatory article, Gonorrhea rates were up 63% in 2018 compared to 2014. I think much of this has to due with the fact that Gonorrhea is often a asymptomatic disease coupled with the fact that our current antibiotic treatments are becoming more and more ineffective. According to an article from the Washington Post, half of these new cases are people aging from 15-24. According to the same article, one big reason for this is due to a lack of funding to health departments due to other crises such as the opioid epidemic.

My Take

I believe that Gonorrhea and other STDs are becoming more and more prevalent for a number of reasons. For one, our sexual education in the United States is mediocre at best. “Sex-ed” in the United States focuses on abstinence. Unfortunately, most people will not adhere to abstinence; it is simply unrealistic. We should be teaching teens (including college students) about how to have safe, and hopefully monogamous, sex. Not only this, but high schools should mimic the common college practice providing free access to condoms. Most students do not understand how STDs work, and STD testing should be stressed more for college students.

Another huge problem is the United States’ healthcare system. There are many who do not have health insurance and cannot afford to visit the doctor’s office even if they suspect they have contracted some sort of STD. Thus, they go on and continue to infect other people while not getting proper treatment. We need a better form of national healthcare. Let’s stop spending so much on the military.

Antibiotic Resistance

Antibiotics

Antibiotics are life-saving drugs. Ever since Alexander Fleming accidentally discovered penicillin from a mold-contaminated growth plate, millions have been saved and cured of bacterial infections. While penicillin and its family members act only on bacterial cell walls, we have since developed many more methods of action to manage and cure bacterial infections. For example, we have antibiotics that inhibit prokaryotic transcription, prokaryotic translation, and even specific metabolic pathways in bacteria, such as folate production. However, as much as these drugs have served us, they are losing their efficacy at an increasingly alarming rate.

Antibiotic Resistance: The Emergence of “SuperBugs”

Bacteria replicate very quickly. Just a few E. coli cells can divide into millions in a short time under the proper conditions. Each time a cell divides, it must replicate its genome. While this task is incredibly accurate, errors are made. Most of the time, these errors are deleterious to the effected bacterium. Sometimes, however, these mutations may provide an advantage, such as an amino acid change that disallows ampicillin to bind its target molecule. This renders the bacterium (which can then divide into millions more clones) resistant to one or more antibiotics. While these mutations are inevitable, improper use of antibiotics can exacerbate their effects. What’s more, many bacteria also posses the ability to share antibiotic resistance genes via a R plasmid. These bacteria can pass on resistance code during conjugation through a special sex pilus. Not only do we see this within species, but species have been known to pass on resistance genes to other completely other species. This has led to the emergence of “superbugs”, or bacteria that are resistant to some or all of the medications used to kill them. For example, XDR-TB is a strain of Mycobacterium tuberculosis (the pathogen that causes tuberculosis) that is resistant to first-line antibiotics in addition to even more toxic last-resort drugs. According to a Medical New Today article, superbugs like these are the cause of 35,000 deaths in the United States alone, a figure that will continue to grow if we continue are poor use of antibiotics discussed later. In fact, we are on the horizon of an era where our life-saving antibiotics have become completely ineffective, according to a WHO article.

How Humans Contribute

Antibiotics resistance is accelerated by humans in a number of ways. These include:

  • Taking antibiotics for viral infections:
    • There is a common belief that antibiotics can be used to treat viral infections such as the flu or a common cold. However, antibiotics are completely ineffective against viruses. Nonetheless, people will take leftover antibiotics for viral infections, thereby deploying the drug for no reason. This allows an present microbiota to developed resistance, which they could potentially pass on to pathogenic bacteria via conjugation.
  • Taking the wrong antibiotic for the disease-causing bacterium
    • This is very similar to the first reason. Many people will take leftover antibiotics when they feel ill. Even if they are feeling ill due to a bacterial infection, the antibiotic they are taking my not be effective against that particular pathogen. Some antibiotics only work on Gram-positive bacteria and some only work on Gram-negative bacteria. In addition, some antibiotics only work on particular families or even species of bacteria. Again, the medicine mismatch leads to normal microbiota developing resistance while not even helping cure the disease. These resistance bacteria again have the potential of spreading resistance via conjugation.
  • Not adhering to antibiotic prescription schedules
    • Many patients will stop taking their prescribed antibiotics when they begin to feel better. Unfortunately, many antibiotic regimens are lengthy and have undesirable side effects. Thus, when the patient feels better, they may stop taking their medicine even though the infection is not cleared. This allows bacteria that were somewhat resistant to the antibiotic to replicate, thereby increasing the chance that one will undergo another beneficial mutation that makes it completely unaffected by the antibiotics at all concentrations.
  • Feeding livestock antibiotics in the absence of disease
    • Long-term use of antibiotics can have the effect of increased weight gain in livestock. Thus, farmers often feed their livestock antibiotics in the absence of infection in order to increase profits. Again, this unnecessary use of antibiotics allows bacteria to “learn” how to develop resistance to a drug. At the store, you can buy meat that is labeled as “antibiotic-free”. However, this generally does not mean that the animal was not fed antibiotics, it merely indicates that there was no antibiotic left in the blood of the animal at the time of slaughter. In other words, antibiotics were used but discontinued a couple of weeks before slaughter.

These are all preventable causes of antibiotic resistance. I believe it is a fault in our education system for not teaching students about antibiotic resistance, which is a central issue the interest of our general health. For example, I graduated high school knowing how to identify metaphors in poems, yet not knowing how to do taxes, how to effectively prevent STIs besides strict abstinence, and how I shouldn’t just take any old antibiotic when I have a sore throat. What’s more, I believe our healthcare system is at fault. Antibiotics and doctor’s visits are expensive; it is understandable that someone would take stop taking antibiotics early to “save some for next time” and then take that leftover antibiotic for the wrong disease in the future. Not only does this practice increase antibiotic resistance, it also allows the infection persist longer, thus potentially spreading the pathogen to many others. Thus, I think it is essential that we have some better form of universal healthcare in the United States. Lastly, we need to stop feeding antibiotics to our livestock in the absence of infection, not only in the U.S., but around the globe.

Polio, IPV, and OPV

What is Polio?

To the average American living in 2020, the word “polio” conjures an image of a crippling disease that only existed well in the past. However, this is far from the truth. While it has not been prevalent in the Untied States for some time now, polio, caused by the poliovirus, is still a major global health threat, not only to countries with endemic polio, but also countries like the United States which have been polio-free for decades. The full name for polio is poliovirus, and it is a disease which can result in paralysis and death. Broadly, there are two kinds of poliovirus: wild poliovirus (WPV) and vaccine-derived polio virus (VDPV). According to an article posted by the International Association for Medical Assistance to Travelers (IAMAT), there are three types of wild-type poliovirus (types 1, 2, and 3); types 2 and 3 are thought to have been completely eradicated, yet WPV1 (wild poliovirus type 1) is still seen in outbreaks around the world and is even endemic in countries such as Pakistan and Afghanistan.

Polio: The Past 6 Months

In the past six month, we have seen an increase in the number of polio outbreaks around the world. According to the previously mentioned IAMAT article, in 2019 168 WPV1 cases were reported, all of which occurred in either Pakistan or Afghanistan. However, according to the same source, the number of vaccine-derived poliovirus outbreaks has increased recently. IAMAT reports that these outbreaks occurred in 16 countries located in the regions of Africa, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. It also reports that an outbreak occurred in the Philippines, a country that had not reported a polio case for 19 years prior to 2019. While the United States has been polio-free since 1979 according to a CDC post, it only takes one traveler from a country experiencing polio to reintroduce the virus to an increasingly unvaccinated American population.

IVP and OPV

IVP and OPV are the shorthand terms for the two widely used polio vaccines. They stand for inactivated polio vaccine and oral polio vaccine, respectively. According to our textbook, the IPV or Salk vaccine was developed in the mid-1950s and is a subunit vaccine consisting of key poliovirus particles. While this vaccine effectively invokes an immune response, it requires multiple doses which both increases cost of administration and decreases patient adherence. The OPV or Sabin vaccine came about in 1961. The OPV is an attenuated form of the poliovirus. This means that it is a non-virulent virus that is still capable of replicating inside a susceptible host. For this reason, the OPV requires only one oral dose, as the attenuated virus is able to replicated and thus induce a more sustained and powerful immune response. However, because the attenuated strain in the OPV is actively replicating, it does have the possibility of mutating. Sometimes, a mutation can cause the virus to become virulent, causing disease in the recipient. For this reason, the United States has discontinued use of the OPV in light of the fact that the country has been polio free for a long time. However, I think if polio were reintroduced into the United States, we would return to an IPV and OPV dosing schedule.

The Human Microbiome

Outnumbered in Our Own Bodies

All humans are hosts for billions of bacteria, archea, and other microorganisms. There are a myriad of species living within us. In fact, there are between 500 and 1,000 species of bacteria living in most people’s intestinal tract alone, according to a Nature article. This is not even taking into account the many more species that live elsewhere on our bodies. In a way, we are outnumbered in our own bodies. According to Dr. Cramer, the ratio of human microbiota cells to actual human cells can be as large as 3 to 1! Despite the large number of non-human cells living on and in us, the human microbiota account for only about 1 kg of our weight. This is because of the very small size of the prokaryotes. Nonetheless, while this may seem like a small percentage of our total weight, there are many organs that are measured to have the same weight. But why do we have so many small friends hanging around inside us?

A New Organ

The human microbiome is vital to our health. Many bacteria in our gut produce compounds that we need and cannot produce on our own. For example, bacteria in our gut produce vitamin K, some vitamin Bs, and butyrate which we can then absorb. There are even studies that show our microbiota produce certain neurotransmitters which can stimulate the nervous system, communicate with our brain, and, as a result, contribute strongly to our mood. In addition, normal microbiota helps protect us from harmful pathogens by covering pathogen binding sites, competing for nutrients, and/or producing compounds that are toxic to pathogens. For example, Clostridioides dificile, a bacterium that causes potentially fatal colitis, can only infect humans if there is a decrease in competition from our normal microbiota, usually caused by antibiotic medications. For these reasons, many scientists consider the human microbiome to be its own organ.

Depression and the Microbiome

Many studies show that there is an association between a disturbed or unusual microbiome and depression. According to a Psychiatry Advisor article, “the gut-brain-microbiota axis is a bidirectional communication system allowing gut microbes to communicate with the brain and for the brain to then send signals to the gut”. This direct communication with the brain could mean that not only intestinal disturbances and diseases could affect long-term mood, but even the food we eat could affect our daily attitude. The same Psychiatry Advisor article reports that the majority of irritable bowel syndrome patients experience depression. Needless to say, a better understanding of our microbiome could lead to improved depression therapies. However, according to a Nature article, a major challenge is the incredible diversity in microbiota between “apparently healthy” individuals. In other words, what’s good for one person’s gut may not be the best for another’s. Nonetheless, research is ongoing, and someday we could be treating depression patients exclusively with probiotic smoothies!

2019-2020 Flu Season

AJ Robinson

A Bad Season

The United States is currently experiencing the worst flu season it has had in several years. According to a Healthline article, there have been over 12,000 deaths with over 9 million cases. Many of those cases were people who got their flu shot. The flu “season” takes place during the fall and winter, generally starting in October and finishing in March. As is such, we are likely swiftly approaching, or currently experiencing, the season’s peak, which can take place anywhere from December to February. But why do flu seasons vary in severity and why is this particular season worse than normal?

The Vaccine

Every year, the world’s best flu scientists meet to discuss what the composition of that year’s vaccine should be. However, there are many different strains of flu. There are types A, B, C, and D which all have special characteristics that set them apart from each other. For example, type A has a wider variety of host organisms while type B infects humans only, according to a McLaren article. To further complicate things, there are several subtypes for each main type. For example, the H1N1 strain differs greatly from the H3H2 strain (‘H’ designates the type of hemagglutinin antigen the virus has and ‘N’ designates the type of neuraminidase antigen the virus has. Thus, when scientists are deciding what strains the vaccine should resemble, they are faced with a pretty tough task. According to a CNN article, this vaccine conference can be summed up as a “guessing game”. This season, we are seeing more of the influenza B/Victoria strain, according to Healthline. As Dr. Marie-Lousie Landry tells Healthline, “58 percent of influenza B/Victoria strains and only 34 percent of influenza A/H3 tested matched the vaccine strains”. In other words, this years vaccine is not a great match for what is currently circulating. Nonetheless, everyone should still get their flu shot as it does offer some protection and may shorten your symptoms or even save your life if you contract the flu.

The Future

As shown by this year’s flu season, our current system for protecting ourselves against this deadly virus is imperfect at best. Scientists have to meet every Spring and give their best guess at what strains will be the most prominent many months later. This is because manufacturing the disease takes a long time, anywhere from six to nine months, according to a CNN bit. What’s more, the vaccine is made in chicken eggs, which, in addition to taking a long time to produce, actually can alter the original strain that was injected, thereby making much of the final product an even worse match to the circulating strains. But there is hope. Much research is being done to create a universal flu vaccine that protects its recipients from all strains of flu for life. According to CNN, there are already prototypes of this vaccine that have been used on many volunteers. But for now, it is important that everyone receives their flu shot as it may save their life.

Wakefield and the MMR Vaccine

Wakefield Attributes Autism Development to the MMR Vaccine

In a paper published in The Lancet in 1998, Andrew Wakefield et al suggest the MMR (measles, mumps, and rubella) is causing autism in children. Despite several scientific faults and conflict of interest, Wakefield’s paper is largely accredited with kick starting the global anti-vaccination movement. An article titled The MMR vaccine and autism: Sensation, refutation, retraction, and fraud by T. S. Sathyanarayana Rao and Chittaranjan Andrade on the NCBI database discusses the faults of the 1998 Wakefield paper that has since been retracted.

Sample Size and Characteristics

This article first mentions how the Wakefield study only included a sample size of 12. This is a very small sample size for a medical study and is not sufficient to test whether a vaccine is causative of a developmental disorder. In addition, Rao and Andrade mention that “a temporal link between the two [MMR vaccine and autism development] is almost predestined” as both events take place in very early childhood. It is almost like testing whether entering the 7th grade induces puberty; both events take place around the same time but are certainly not causative of one another. Perhaps Wakefield could have stengthened his study if he had not only had a much larger sample size, but also included older individuals who had recently received the MMR vaccine and/or had not received the vaccine but still developed autism. Shockingly, Rao and Andrade reveal that Wakefield falsely reported his method of sampling. After investigation, Wakefield’s study was found to have used selective sampling to obtain its cohort. This means that Wakefield and his colleagues picked subjects on their own, discriminating as they saw fit. This is already a no-no in medical study, worsened by the fact that Wakefield lied about it.

Financial Motives and Further Misconduct

At this point, readers may ask themselves “Why would Wakefield risk his scientific credibility to attack vaccines?”. This is also something that Rao and Andrade discuss in their article. It turns out that Wakefield was funded by lawyers who were engaged in lawsuits against vaccine-producing companies. This was not revealed to The Lancet before publication. Furthermore, Wakefield and colleagues were found guilty of improper “invasive investigations” on the children subjects as they had not obtained the necessary clearance to do so, according to Rao and Andrade. Finally, Wakefield even blatantly lied about the diagnosies of many subjects, quite loosely and freely using the word “colitis” despite non-abnormal findings.

Implications

Vaccination with the MMR vaccine has declined since the publication of Wakefield’s paper in 1998, according to a PBS article titled The Autism-Vaccine Myth. More and more people are refusing to vaccinate their children, which puts both individuals who are too young to be vaccinated and the immunocompromised at risk. The goal of vaccination is to create herd immunity with the ultimate result of eradicating human-resivoir diseases. If most people are immune to a disease, then that disease will have a very difficult time spreading and replicated in multiple hosts. When people do not vaccinate their children, they are increasing the number of susceptible hosts a disease has and thus increasing the chance the disease will infect others. This is especially unfair to the too-young-to-be-vaccinated and the immunocompromised. Vaccination involves injecting a weakened form of a disease in order to mount an immune response and the consequent production of antibodies against that disease. While not 100% effective, vaccines are highly effective and generally result in lifetime immunity to a disease. However, because vaccines require a functioning immune system, they sometimes cannot be given to immunocompromised individuals as well as the very young (infants do not have a fully functioning immune system). Thus, these are the very groups that would have the most severe complications to a disease like measles, which generally is not. Unfortunately, vaccination rates have greatly declined since the 1998 publication of Wakefield’s paper, despite its retraction and the overwhelming evidence of fraud against it. According to the above mentioned PBS article, measles vaccination rates fell to only 80% in 2003-2004 in the UK, with similar trends in other previously high vaccination rate countries. While 80% may seem high to those not familiar with epidemiology, according to an article in Stanford Medicine, a 5% drop in MMR vaccination among children would cause a tripling in the number of measles cases for that group.