Category Archives: Genetic Medicine

Dr. Susan Baserga

Dr. Susan J. Baserga, recently appointed as the William H. Fleming, M.D. Professor of Molecular Biophysics and Biochemistry,studies fundamental aspects of ribosome biogenesis, the nucleolus, human diseases of making ribosomes (ribosomopathies), and the impact of ribosome biogenesis on cell growth, cell division and cancer.

Basergas laboratory uses a wide array of biochemical, genetic, and biophysical techniques to study the process and regulation of ribosome biogenesis.Her investigations of how ribosomes the cells protein-making machinery are created have been instrumental in identifying the cause of congenital diseases of making ribosomes and its impact on cell growth, cell division, and cancer. She holds three biotechnology patents related to her work in the field of eukaryotic ribosome biogenesis and its relation to cancer and human genetic diseases.

Baserga earned her B.S. and M. Phil degrees at Yale, her M.D. at the Yale School of Medicine, and her Ph.D. from Yales Department of Genetics. After a postdoctoral fellowship in the laboratory of Joan Steitz at Yale, Baserga began her academic career an assistant professor of therapeutic radiology and of genetics at the School of Medicine. In 2007, she was appointed full professor of molecular biophysics and biochemistry, of genetics, and of therapeutic radiology. Basergas current administrative positions include director of medical studies in the Department of Molecular Biophysics and Biochemistry and program director of the Predoctoral Program in Cellular and Molecular Biology.

Basergas research has been supported by grants from the National Institutes of Health and has been widely published in professional journals and book chapters in edited volumes.

Baserga has received the Connecticut Technology Council Women of Innovation in Research and Leadership award, the William C. Rose Award from the American Society of Biochemistry and Molecular Biology (for outstanding research and commitment to training young scientists), and the Charles W. Bohmfalk Prize for basic science teaching at the Yale School of Medicine. In 2018 she was elected as a fellow of the National Academy of Inventors.

See the article here:
Dr. Susan Baserga named the William H. Fleming Professor - Yale News

Genetic variants that are unrelated to the IOP are associated with a family history of glaucoma and play a role in the onset of primary open-angle glaucoma (POAG). Genetic variants that are related to the IOP are associated with the age at which glaucoma is diagnosed and are associated with disease progression.

What is known about POAG, the most prevalent form of glaucoma, is that increased IOP and myopia are risk factors for damage to the optic nerve in POAG.

Related: Stent offers IOP stability more than three years after surgery

A family history of glaucoma is a major risk factor for development of POAG, in light of which, therefore, genetic factors are thought to be important in the disease pathogenesis and a few genes mutations have been identified as causing POAG, according to Fumihiko Mabuchi, MD, PhD, professor, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Kofu, Japan.

Myopia has been shown to be a risk factor for POAG in several studies. However, it can be difficult to diagnose true POAG in myopic patients and controversy exists over whether it is real risk factor.

Myopic optic discs are notoriously difficult to assess, and myopic patients may have visual field defects unrelated to any glaucomatous process.

The prevalence of POAG increases with age, even after compensating for the association between age and IOP.

Related: Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows

Part of the storyDr. Mabuchi and his and colleagues, recounted that these factors are only part of the story.

According to Dr. Mabuchi and his colleagues, cases of POAG caused by these gene mutations account for several percent of all POAG cases, and most POAG is presumed to be a polygenic disease.

Recent genetic analyses, the investigators explained, have reported genetic variants that predispose patients to development of POAG and the additive effect of these variants on POAG, which are classified as two types.

The first genetics variants are associated with IOP elevation.

Related: Sustained-release implant offers long-term IOP control, preserved visual function

See the rest here:
Genetic variants linked with onset, progression of POAG - Modern Retina

The Covid-19 pandemic is teaching me that the world can change almost overnight when it faces a big problem.

When President Trump declared a national emergency, my medical practice shifted almost instantly from in-person appointments to telehealth visits. The Drug Enforcement Administration allowed doctors like me to prescribe buprenorphine, a controlled substance used to combat opioid addiction, after a telephone consult, a move experts have been seeking for years. The Department of Health and Human Services waived privacy constraints for telehealth visits, which have long tied up this type of medicine, allowing doctors to use commonly available platforms like FaceTime, Facebook Messenger, Skype, and Zoom to provide medical care.

And Congress quickly passed the CARES Act, a $2 trillion aid package to fight Covid-19 that included sending $1,200 checks to individuals and families who were most vulnerable to job loss and other financial stressors.

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As a psychiatrist who treats opioid addiction and works at a minority-serving hospital, I am delighted by these long-sought changes. But I am also frustrated that they have happened so quickly. Frustrated because the U.S. has been facing an equally large and equally deadly problem racism for years and has done little to address it.

Black people are dying at alarming and disproportionate rates from Covid-19. In cities, the statistics are nothing short of tragic. In Chicago, for example, 70% of coronavirus deaths are among Black people, who make up only 30% of the citys population. A similar pattern is seen in other cities and counties across the country.

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Black and brown people have been seeking reparations to address the systemic injustices they have faced for decades. Yet there has never been an economic stimulus to address the impact of racism on health, quality of life, and advancement.

The countrys response to the new coronavirus does, however, suggest that we are taking steps toward addressing the damaging threat of racism.

First, though, we have to name it. Policy leaders across the country urged Trump to declare a national emergency because they understood the power of naming a crisis. In the same way, we need to declare that racism is a national emergency. It is a virus in the truest sense: a corrupting influence that spreads through communities and across the nation. Systemic racism has harmed and killed millions of Americans through its corruption of health care, criminal justice, and the economic marketplace.

Dr. Deborah Birx, who serves as the coronavirus response coordinator for the White House coronavirus task force, recently suggested that Black people are dying of Covid-19 at higher rates due to underlying medical conditions. She is right if she means that the underlying condition is racism, not its manifestations like high blood pressure and diabetes. Racism has created inequality in access to health care, housing, wealth, education, and employment, all of which undermine health. It is time to name racism as the crisis it is.

Second, we must shift policy to address the circumstances of those affected by the crisis. For Covid-19, that means finding unique ways to care for patients. To address racism, we must do that and go even further. We must not only come up with new ways to reach patients who have been disadvantaged but must also address the dire circumstances that racism has created.

The first time I ever used telehealth was after Covid-19 had emerged as a nationwide threat. My patient, who was homeless, had been sitting in a park all day, waiting for my call. He knew if we didnt connect, he would not be able to get the medication he needed to help him stay free from using heroin. He adjusted his life to meet health cares demands. Thats not the way health care should be it should meet patients where they are and address the circumstances they are in.

During that call, I didnt stick to my usual script: Any problems filling your prescription? Any medication side effects? Any cravings or heroin use since the last visit? Instead, I talked with him about the challenges he was facing at the shelter. He asked about how to manage his day since he couldnt stay inside. I also let him know where he could find a hot meal on a daily basis.

I wish our health care system would take a similar approach and see value in working on problems like housing and food insecurity. Some are calling this concept structurally competent care; it needs to become our new normal.

Third, we must deal with the economic consequences of the crisis. For Covid-19, thats the thrust of the CARES Act. In Boston, where I completed my medical training, the median net worth of white families was more than $200,000. The median net worth of black families was $8. Undoing racism means passing something like the CARES Act to provide funds for those disadvantaged by racism.

I respect Dr. Anthony Fauci, a key member of the White House coronavirus task force, who acknowledged the role of health disparities in Covid-19. He has said that we must deal with these issues once we get beyond the pandemic.

But I disagree with him on that. We must deal with them now.

Morgan Medlock, M.D., is an assistant professor of psychiatry at Howard University College of Medicine in Washington D.C. and the editor of Racism and Psychiatry: Contemporary Issues and Interventions (Springer, 2019)

More:
Covid-19 will pass. What about the racism it has illuminated? - STAT

Glaucoma is the most common cause of irreversible blindness in the world. Its estimated that by 2040 there will be about 112 million people in the world with glaucoma mostly in Africa and Asia. The best that medical science can do at present is identify it early and slow or halt its progression.

The disease affects the optic nerve, which normally sends signals from the eye to the brain. With glaucoma, this nerve doesnt work properly. The first sign is loss of peripheral vision. This gradually progresses to tunnel vision and, ultimately, blindness.

The most important risk factor for developing glaucoma is having high pressure inside the eyeball. Reducing this pressure is currently the only way to treat glaucoma. Its done with eye drops, laser treatment or surgery.

The most common type of glaucoma is primary open-angle glaucoma, which typically begins in middle to older age. Visual loss is only noticeable at an advanced stage of the disease. Its more common in populations of African descent than in those with European or Asian ancestry. In African populations it starts at an earlier age and progresses faster. The prevalence of primary open-angle glaucoma in Africans between the ages of 40 and 80 is about 4.2%.

The cause and mechanisms underlying this condition are poorly understood. But its known that family members of affected individuals are much more likely to get the disease. We conducted a study to identify genetic risk factors for primary open-angle glaucoma in African populations.

Identifying glaucoma associated genetic factors could make it easier to identify patients at risk before they develop the disease. It could also shed light on the cause and unlock new treatments.

We found a new genetic association that may help us achieve these goals.

Most primary open-angle glaucoma is inherited in a complex manner. In other words there is not just one mutation in a single gene that is sufficient to cause the disease. Rather there are small variations in several genes that contribute to an increase in risk for the disease.

Genetic risk factors have been identified using association studies. In these studies thousands of affected individuals are compared with even larger numbers of unaffected individuals. This identifies associations between certain genes and either glaucoma or characteristics associated with glaucoma (like high pressure inside the eye). Each association provides information about the diseases.

Most of these studies have been performed on European populations. Genetic enquiry in African populations is challenging because there is so much more diversity within African genomes.

The genome is the complete set of genetic material we carry in all the cells of our bodies. Genes are the parts of the genome that contain instructions to make proteins. All humans genomes are almost identical but tiny variations occur. It is these variants that determine our individuality. The more ancient a population, the more time there has been for variants to develop and the more genetic diversity there will be in that population.

Read more: What we've learnt from building Africa's biggest genome library

This diversity means that African populations are valuable in studies of the links between genes and diseases like glaucoma.

Our group of researchers (the Genetics of Glaucoma in People of African Descent Consortium) recently published an association study of close to 10,000 primary open-angle glaucoma patients of African descent.

We identified a new association, with a gene called APBB2. It occurs in all populations but the variant associated with glaucoma was only found in Africans.

We demonstrated that this genetic variant results in increased amyloid deposition in both the eye and the part of the brain responsible for vision. Amyloid is a protein that is toxic to brain tissue and is associated with Alzheimer-type and related dementias. We cant yet say for certain that amyloid depositions cause glaucoma, but this seems likely. If further studies can prove this, then drugs that were developed to treat dementias might be useful to treat primary open-angle glaucoma.

Read more: Alzheimer's: the 'switch-on moment' discovered

There is no evidence that glaucoma occurs more frequently in individuals with dementia or vice versa. But this study found a genetic link that could help explain how the optic nerve is damaged in glaucoma.

We recently confirmed this direct genetic link in a large analysis of data from different studies all over the world. The analysis identified another three genes that are known to cause Alzheimer-type dementias and are also associated with primary open-angle glaucoma.

Discovering the genetic associations of an inherited disease is an important step. It identifies biological pathways that may cause the disease.

In a complex condition like primary open-angle glaucoma, it is likely that there are several different pathways involved which all end up with damage to the optic nerve. Only by studying multiple populations will a true picture of all the genetic associations emerge. There may already be treatments available that target the biological functions of these associated genes which could then be used to treat glaucoma. Alternatively, new treatments targeting these functions could be developed specifically for glaucoma.

Knowing about genetic associations in specific populations will make it possible to focus prevention and treatment on those who will benefit most, sparing expense and side effects from those who will not.

Ultimately genetics could pave the way for precision medicine in glaucoma: tailoring care to the individual patient.

Read more:
How African genetic studies offer hope for preventing a common cause of blindness - The Conversation Africa

Dr. Concepcion is chief clinical urologist officer, Integra Connect, West Palm Beach, FL, and clinical associate professor of urology, Vanderbilt University School of Medicine, Nashville, TN.

Prostate cancer is a clinically heterogenous disease with variability in progression once diagnosed, ranging from the very indolent cases that may require no therapy to patients who present with de novo metastasis. In 2019, there were approximately 174,650 newly diagnosed prostate cancer cases in the United States and a cancer-specific mortality of 31,620 directly attributable to the disease or 5.2% of all cancer deaths.1

A number of newer therapies (all mechanistically different) and treatment regimens have been approved for the management of both patients with metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC). A unique dynamic progressive model estimates the incidence of these two subsets may approach 42,970 patients in 2020.2

Unfortunately, despite the availability of superior agents, optimal sequences or a combination of these oncolytics have yet to determined, as there are no predictive biomarkers to inform the provider what is the most ideal initial line of therapy (LOT) and as patients progress, what will be the most appropriate next LOT. What makes this situation even more challenging is that these newer therapies, as well as those that we anticipate will be approved in 2020 and beyond, are targeted for molecular drivers of prostate cancer. For the patient with mCSPC or mCRPC, how can we best determine the initial and subsequent LOTs, given the limitations of the monotherapy registration trials?

A number of key genomic mutations have been consistently identified in patients with prostate cancer (hormone naive and mCRPC). These mutations include gene fusion/chromosomal rearrangements (TMPRSS2-ERG), androgen receptor (AR) amplification, inactivation of tumor suppressor genes (PTEN/PI3-K/AKT/mTOR, TP53, Rb1), and oncogene activation (c-myc, RAS-RAF).3 More significantly, defects in DNA repair appear to be central in increasing ones susceptibility to malignant transformation.

Germline vs. somatic mutations

It is critical to patient management that we determine whether these mutations are inherited (germline) or acquired (somatic). Germline mutations are changes in DNA that are present in the patients reproductive cells (sperm or ovum) and are thus passed from generation to generation and will be identified in every cell of the body. Therefore, germline testing can be conducted with just a swab from the mouth, saliva, or blood from the patient. There are many companies in the United States that currently offer germline testing.

It is paramount that in order to obtain the most comprehensive analysis and report, genetic testing through next-generation sequencing in a diagnostic laboratory is mandatory. This type of testing should be compared with many of the direct-to-consumer tests that are currently marketed to patients. The testing platforms deployed by many of these companies are much less robust and often include a very limited number of known genetic mutations in their panels.

For example, thousands of identified BRCA mutations have been identified, but only a handful may be tested in some of these direct-to-consumer testing kits. This situation can lead to an unacceptable number of studies with false-negative results and should not be used for clinical decision-making.

Acquired or somatic mutations can be defined as any alteration in DNA that occurs after conception. These can occur in any cell of the body (except the reproductive cells) and usually arise as a result of exogenous or environmental exposures, such as tobacco smoking or UV radiation. Therefore, somatic testing requires next-generation sequencing of cells extracted from the tumor itself and cannot be performed by using a sample of saliva or blood.

Pritchard and colleagues were among the first to demonstrate the value of assessing inherited genetic changes in prostate cancer. Among 692 patients with metastatic prostate cancer, they examined the prevalence of mutations in 20 DNA repair genes.4 Mutations were identified in 82 men (11.8%) with significant geographic heterogeneity, even among these recognized cancer centers (prevalence of 8.8% in patients treated at the University of Washington and 18.5% in those treated at Memorial Sloan Kettering), potentially reflecting referral biases. Subsequently, Castro et al found a prevalence of germline DNA damage repair gene mutations of 16.2% in patients with mCRPC.5

Unlike other disease states in which commonly identified germline mutations may be actionable, actionable germline mutations are relatively uncommon in patients with prostate cancer. Nicolosi and colleagues found that actionable mutations were identified in 1.74% of their study cohort with a diverse patient population.6 In previous analyses, Robinson et al reported clinically actionable pathogenic germline mutations in 8% of 150 patients with mCRPC, in contrast to clinically actionable aberrations in the AR in 63% and aberrations in other cancer-related genes in 65% of patients.7 It is likely not surprising that actionable underlying germline mutations would be more common in a cohort with more advanced prostate cancer.

In patients with regional or metastatic prostate cancer, somatic tumor testing may also be considered on the basis of the observation that nearly 90% of men have potentially actionable mutations at the tumor level, whereas only a relatively small proportion of men would have actionable germline mutations (approximately 9% of patients with mCRPC, according to the National Comprehensive Cancer Network). In these patients, testing may be undertaken for somatic homologous recombination repair (HRR) gene mutations (eg, BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, and CHEK2) and for microsatellite instability (MSI) or mismatch repair (MMR).7

In patients with advanced prostate cancer, identification of underlying germline mutations may guide treatment selection to determine the most appropriate next LOT, especially in those who have progressed through multiple lines of prior therapy, including AR signaling agents. Patients with identified MSI-high status, defects in DNA MMR genes, or CDK12 biallelic loss may respond to checkpoint inhibition therapy.8

Pembrolizumab (KEYTRUDA), an FDA-approved PD-1 inhibitor, is the first immunotherapy to win approval in a tumor-agnostic manner and not based on organ type. Further, patients with mutations in HRR genes (including BRCA1/2, CHEK2, and genes that cause Fanconi anemia) may be better suited for treatment with PARP inhibitors, many of which are in ongoing phase III trials with expected approval in 2020.

Finally, patients with DNA repair defects may have increased sensitivity to platinum-based chemotherapeutics.9 Given the uncertainty regarding optimal treatment selection and pending approval of current agents in trial, the National Comprehensive Cancer Network prostate cancer guideline panel recommends clinical trial enrollment for all men with prostate cancer and identified DNA repair gene mutations. In addition, somatic testing for specific gene variants may be undertaken.

For the most part, this approach is used in patients with advanced disease with the goal of identifying specific actionable targets. For example, mutations in HRR or MMR genes and identification of MSI-high versus MSI-low status may suggest certain treatments are more likely to be beneficial.

In addition to genetic testing of tumor tissue, assessing circulating tumor cells may offer important information. For example, testing of AR variant status can be performed using circulating tumor cells and may be predictive of disease.

Generally, genetic testing yields results that are unambiguous and will show that a gene mutation is present or absent. However, the reporting of the significance and association of that mutation relative to a disease state can be quite variable. Given that the coding sequence for a particular gene has been defined and the sequencing machines are fairly similar, what is considered positive or deleterious versus negative or favorable/no mutation relative to risk of disease is predicated on the number of patients tested.

As noted, a number of genes have been identified as associated with an increased susceptibility risk for prostate cancer. Multigene panels are becoming used more often, but the makeup of these panels is not uniform. A recent analysis looking at various commercially available multigene panels shows that the average number of genes tested is 12 (range, 4-16). BRCA1/BRCA2 are included in all the panels, but 20% did not include HOXB13 or MMR genes.10

The clinical experience and number of patients tested with BRCA1/2 is more extensive compared with other genes. More and more mutations continue to be discovered, but the significance to the patient has yet to be determined until even further samples are processed. These discoveries, classified as variants of unknown significance (VUS), represent a gray area in which there is a change in the genetic sequence; however, it is still unknown whether this change is associated with a deleterious or favorable prognosis. Among women with breast cancer, detection of a VUS is more common than identification of known pathogenic variants.11 Although ongoing work seeks to better delineate the importance of these VUS, the involvement of a genetic counselor is key to helping patients navigate this uncertain situation.

Conclusion

Urologists will need to incorporate comprehensive genomic testing, just as we embraced PSA testing back in the 1990s. A recent survey conducted among 52 single-specialty independent urology community practices identified the following three issues related to incorporation and development of a comprehensive testing program12:

medical/legal liability for unaddressed identified mutations

reimbursement concerns and cost of testing

complexity and time involved to enter a complete family history and pedigree into the electronic health record.

None of these considerations, however, is insurmountable if the practice has a commitment to enhance and deliver precision medicine for our patients with prostate cancer.

References

1. Siegel RL, Miller KD Jemal A. Cancer statistics, 2019. Cancer J Clin. 2019; 69:7-34.

2. Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the United States: estimates using a dynamic progression model. PLoS ONE. 2015; 10:e0139440.

3. Rubin MA, Maher CA, Chinnaiyan AM. Common gene rearrangements in prostate cancer. J Clin Oncol. 2011; 29:3659-68.

4. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016; 375:443-53.

5. Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019; 37:490-503.

6. Nicolosi P, Ledet E, Yang S, et al. Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol. 2019; 5:523-8.

7. Robinson D, Van Allen EM, Wu YM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161:1215-28.

8. Wu YM, Cielik M, Lonigro RJ, et al. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer. Cell. 2018; 173:1770-82.

9. Humeniuk MS, Gupta RT, Healy P, et al. Platinum sensitivity in metastatic prostate cancer: does histology matter? Prostate Cancer Prostatic Dis. 2018; 21:92-9.

10. Aldubayan SH. Considerations of multigene test findings among men with prostate cancerknowns and unknowns. Can J Urol. 2019; 26:14-6.

11. van Marcke C, Collard A, Vikkula M, et al. Prevalence of pathogenic variants and variants of unknown significance in patients at high risk of breast cancer: a systematic review and meta-analysis of gene-panel data. Crit Rev Oncol Hematol. 2018; 132:138-44.

12. Concepcion RS. Germline testing for prostate cancer: community urology perspective. Can J Urol. 2019;26:50-1.

Read more:
Role and rationale for molecular testing in advanced prostate cancer - Urology Times

(CNN) -- Despite all his medical knowledge, 31-year-old medical student and Ph. D. candidate Sean Doyle couldn't know for certain all the risks of the injection he had just received in his right shoulder at Emory University Hospital. Yes, of course he was told of the potential side effects, such as soreness in his arm, a fever, malaise. But when you are among the first people in the world to receive a vaccine injection, the real answer about the risks is simply "we don't know."

In fact, it's those very questions that he is helping us answer.

Sean is helping all of us figure out if it is safe, by putting up his hand first and volunteering. With that injection, Sean had become a critical part of the fastest moving vaccine trials in the history of the world, a vaccine for Covid-19.

During a pandemic, the urgency is understandable. In just a few months, the virus has spread to nearly every corner of the globe and sadly taken more lives than several wars or natural disasters combined. It is also true that no one on the planet is immune to this; such is the nature of a novel or new coronavirus. As you process all that, remember that last Thanksgiving, this wasn't even a real concern for human beings, and not even a topic of idle conversation. And, now it is the only thing being discussed in hospitals, boardrooms and at kitchen tables every night, often by Zoom. So, yes. The urgent pace is quite understandable but we have to make sure we can sprint, while also not tripping, falling and getting hurt.

When I sat outside with Sean recently at Emory School of Medicine in Atlanta, where he is studying and I am on the neurosurgery faculty, it may have appeared to be just another meeting between student and teacher. If you looked a little closer, however, you would've noticed that we were sitting several feet apart, masks tucked around our necks, raising our voices a bit to make sure we could be heard. I really wanted to understand how Sean had decided to volunteer for an experimental vaccine. I wanted to understand how he processed and assessed risk. As a dad, I wanted to know what his parents thought.

It was no surprise to me that, despite the fact he hadn't been born yet, Sean was familiar with the story of the swine flu vaccine of 1976. In January of that year, a new or novel virus began spreading at Fort Dix in New Jersey. Fearful that this new virus might cause a pandemic like the one in 1918, the United States rushed a vaccine through development. Within a year, nearly 25% of Americans had been vaccinated, around 45 million people. Without enough time to perform adequate safety trials, however, devastating side effects started to emerge. Hundreds of people developed Guillain-Barre syndrome, a paralysis that starts in the feet and slowly marches up your body. Several people also died, and for some, a fear of vaccination remains to this day.

"That was definitely a concern," Sean told me, "potentially developing things like Guillain-Barre. It is a risk.

"With this particular vaccine, no one knows what the chances of that are. But those potential risks are outweighed, I think, by the potential benefits of this vaccine, because right now there are no great preventative measures for containing this virus."

Dr. Amesh Adalja, a senior scholar focused on emerging infectious disease at the Center for Health Security at Johns Hopkins University, notes the timeline for this vaccine is quick compared to others. U.S. health officials have said a vaccine could be ready in 12 to 18 months -- lighting speed in the world of vaccine development.

"Vaccine development is usually measured in years and sometimes even decades," Adalja said. "And there are some infectious diseases for which we have no vaccine after decades and decades of work, like HIV or hepatitis C, for example."

"The only way that we're going to really contain this virus is with the vaccine," Adalja said.

Dr. Peter Hotez, a leading expert on infectious disease and vaccine development at Baylor College of Medicine, believes the 12-to-18-month timeline may be wishful thinking.

"I can't think of another example where things have gone that quickly," Hotez said. The quickest vaccine ever developed was against mumps. After vaccine inventor Maurice Hilleman isolated the mumps virus from his 5-year-old daughter in 1963, it sped to market in four years.

Doing that in a fraction of the time would be a challenge, Hotez believes.

"We're certainly trying, I mean, our scientists are working day and night in the lab now," he said.

Safety is always paramount, but especially with vaccines. Unlike therapeutics, which are often first trialed in people with the late stage of a disease, vaccines are given to healthy people to prevent the disease. The risk of causing illness or even death in an otherwise healthy person haunts everyone involved in the coronavirus response.

Dr. Mike Ryan, executive director of WHO's health emergencies programme, said in a briefing last month that time is needed to test the new vaccines.

"Many people are asking, 'Well why do we have to test the vaccines? Why don't we just make the vaccines and give them to people?' Well the world has learned many lessons in the mass use of vaccines and there's only one thing more dangerous than a bad virus, and that's a bad vaccine," Ryan said. "We have to be very, very, very careful in developing any product that we're going to inject into potentially most of the world population. We have to be very, very, very careful that we first do no harm. So that's why people are being careful."

The 1976 swine flu vaccine debacle is one of the best-known instances, but there have been more recent failures. In 2017, a campaign to vaccinate nearly 1 million children for mosquito-borne dengue virus in the Philippines had to be stopped because the vaccine actually raised the risk of severe dengue infection in some people. Ten children died.

In the rush to protect kids against an infection that makes 400 million people sick and kills 22,000 every year globally, officials ignored warnings that the vaccine should only be used in people who have already been infected once. Dengue is actually caused by four different viruses and the first infection is usually mild, while the later infections are more dangerous. In this situation, vaccinating people who had never been infected sometimes raised their risk of complications if they were then infected with a different strain.

The earliest vaccines, such as the smallpox vaccine used for hundreds of years, involved inoculating people with a real, live, virus in the hope that a controlled dose and infection would provide immunity. It was a gamble, and many people became very ill or died from such attempts.

Later vaccines used related but less harmful viruses. In the 20th century, scientists learned how to kill or weaken viruses and bacteria in the lab and use those to vaccinate.

Hotez believes safety controls are better now, but the timeline still presents a challenge.

"The question is, will a year to 18 months be adequate time to monitor for safety?" he asked.

Typically, vaccines are first tested in the lab and then in animals before they get to the three-stage clinical trials stage. Phase I clinical trials look at whether the vaccine is safe in a few people. The second phase involves more people, who are often given varying doses to test whether the vaccine causes the desired immune response and which dose might work best. The third and final phase gathers data on whether the vaccine really protects people, usually in real-life conditions.

Because coronavirus is such an overwhelming threat, this careful and ponderous timeline is being compacted enormously. Vaccines started human testing just months into the pandemic, and some tests are being run simultaneously on humans and animals. Remember, vaccines work on a simple principle: priming the body's immune system to recognize, attack and neutralize a bacterial or viral infection.

Vaccine makers got a head start on a Covid-19 vaccine because work had already started on vaccines against two related coronaviruses: severe acute respiratory syndrome or SARS, which infected about 8,000 people and killed close to 800 before it was stopped in 2004, and Middle East respiratory syndrome virus or MERS, which causes occasional outbreaks.

So scientists already knew a great deal about the mechanism by which this particular virus used its spike protein to enter human cells and how to inhibit that process.

One new approach relies on using genetic material that looks like bits of a microbe and that stimulates the body to produce an immune response. There's no chance of accidental infection, because no virus is actually used. For coronavirus, one hope is that using messenger RNA -- the genetic material that directs cells to produce something -- will offer the quickest and safest path.

In this case, the RNA vaccine would stimulate cells to make those spike proteins that look like pieces of coronavirus. If it works properly, upon being exposed to those engineered fragments of the virus, the body would be taught to recognize them, and be prepared to defend against them if there was a future attack or infection.

RNA vaccines are quick and relatively easy to make, which is why they are already being tested in people. All a lab needs is the genetic sequence of the virus. But no such vaccine has ever been approved for use in the population.

Another, more time-tested approach to fighting coronavirus employs viral vector vaccines. These use viruses harmless to people, genetically engineered to carry bits of the target virus -- in this case, the Covid-19 virus. The harmless virus causes a symptom-free infection, and the immune system learns to recognize the harmful genes.

But while the technology means quick progress, Adalja said they are also still new.

They can fail, or produce unexpected side effects.

When it comes to RNA vaccines, "there is no precedent yet for them being approved for use and, and we don't know everything about them in terms of how they're going to behave in large numbers of people and what the side effect profile they might be," Adalja said.

It's something that Sean Doyle has considered not only now, but once before as well. Back in 2017, he raised his hand to be among the first to be injected with the Ebola vaccine. He was a first-year medical student at the time, and watched as the first patient in the United States was treated at his medical school, Emory. Sean remembers exactly what led him to participate.

"I remember the fear that was surrounding both the outbreak in West Africa," he said. "The fear for the folks there and their health, but also fear about whether or not the virus could get out from West Africa and spread to other places around the world."

And while the outbreak was contained before the vaccine trial began, he knew taking part of the trial meant if it ever happened again, there could be a vaccine that would hopefully be deployed quickly.

Then, like now, Sean knows it's volunteers like him who put themselves at risk for the greater good -- whatever that entails.

"There were conversations that I had with friends and family," he said. "They all expressed concerns about getting an experimental vaccine like this where no one knows what the side effects might be. But they trusted my judgment."

CNN's Mallory Simon contributed to this report.

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He signed up for a coronavirus vaccine trial using a method that's never been used in humans. Here's why. - KCTV Kansas City