2015 Nobel Prize Winners: Lindahl, Sancar, and Modrich

Göran K Hansson, the secretary general of the Royal Swedish Academy of Sciences said: “This year’s prize is about the cell’s tool box for repairing DNA.” Together, the repair mechanisms discovered by Lindahl, Sancar and Modrich fix thousands of DNA faults caused by UV rays, cigarette smoke, and other toxic substances. They are constantly at work to repair copying errors as cells divide. Without these repair mechanisms, the genomes would be riddled with errors, and cancer would be rife. (A)

PROCESS:

Lindahl, Modrich, and Sancar were honored for mapping and explaining how cells repair their DNA and safeguard genetic information. They worked out how cells repair faults that inevitably occur when DNA is copied several times allowing for mutations to arise under a wide variety of environmental factors such as UV rays in sunlight that could inevitably result in skin cancer.

Lindahl searched for enzymes that would repair faulty genetic material, focusing on the weaknesses of the DNA letters paired up. Cytosine pairs only with Guanine, however when Cytosine loses an amino group- it pairs up with Adenine instead. This error in pairing in the stands cultivates a mutation the next time it is copied. He realized that cells MUST have a way to protect themselves from this and in 1974 Lindahl published the details of the enzyme responsible. (A)

Aziz Sancar

Born: 1946, Savur, Turkey

Affiliation at the time of the award: University of North Carolina, Chapel Hill, NC, USA

Prize motivation: "for mechanistic studies of DNA repair"

Prize share: 1/3

Paul Modrich

Born: 1946

Affiliation at the time of the award: Howard Hughes Medical Institute, Durham, NC, USA, Duke University School of Medicine, Durham, NC, USA

Prize motivation: "for mechanistic studies of DNA repair"

Prize share: 1/3

Tomas Lindahl

Born: 1938, Stockholm, Sweden

Affiliation at the time of the award: Francis Crick Institute, Hertfordshire, United Kingdom, Clare Hall Laboratory, Hertfordshire, United Kingdom

Prize motivation: "for mechanistic studies of DNA repair"

Prize share: 1/3 

CONCLUSION: 

The committee stated that, “Their systematic work has made a decisive contribution to the understanding of how the living cell functions, as well as providing knowledge about the molecular causes of several hereditary diseases and about mechanisms behind both cancer development and ageing,” adding,  “All chemical processes are prone to random errors. Additionally, your DNA is subjected on a daily basis to damaging radiation and reactive molecules. In fact, you ought to have been a chemical chaos long before you even developed into a foetus." (A)

LINKS:

(A) http://www.theguardian.com/science/2015/oct/07/lindahl-modrich-and-sancar-win-nobel-chemistry-prize-for-dna-research

(B) nobelprize.org

Turning Leukemia Cells on themselves: Mission Accomplished

 What are Leukemia Cells?

Leukemia is by definition a malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. These suppress the production of normal blood cells, leading to anemia and other symptoms. This disease is very difficult to treat because the leukemia cells (which are cancer cells) affect the bone marrow and the RBCs have the tendency to relapse and resist treatment.

Cancer Research (Introduction) :

A major goal in cancer research is to discover agents that transform malignant cells into benign cells. The process in which researchers and scientists approach cancer therapy involves finding agents that have the ability to change the state of differentiation of cancer cells. In a recently discovered phenomenon 'receptor pleiotropism' conversion of acute myeloblastic leukemia cells into natural killer cells is very possible. (Receptor Pleiotropism is when agonist antibodies are against known receptors which induce the cell fates that are very different from those that are induced by the natural agonist to the same receptor.) (A)

In a recent new study, performed by scientists of the Scripps Research Institute, discovered an extremely rare human antibody that makes leukemia cells kill each other. The leukemia cells are convinced to transform into leukemia-killing immune cells, in which their biological programming has been rewritten. Antibody therapies has long been the main goal of many scientists as they have been trying to treat individuals whose bone marrow does not produce enough WBCs (aka: immune cell deficiency). Finding antibodies that could activate receptors on the immature bone marrow cells that would cause them to change into mature cells was the mission. (B)

When introduced to the antibody the leukemia cells enter a differentiation cascade where 80% of the starting leukemic cells can be differentiated. The antibody-induced killer cells make large amounts of perforin, IFN-γ, and granzyme B which attack, subsequently killing other members of the leukemic cell population. (A) It is important to note that induction of killer cells is confined to transformed cells because the normal bone marrow cells are not induced to form killer cells. It is therefore very possible to use agonist antibodies to change the differentiation state of cancer cells into those that attack and kill other members of malignant clone from which they originate. (A)

Those who suffered from AML (Acute Myeloid Leukemia) produce too many WBCs in their bone marrow interfering with the normal production of other blood cell types. This aggressive type of leukemia attacks the myeloid cells in the body that deal with bacterial infections, parasites, and prevent the spread of tissue damage. (B)

Concluding Results: 

When researchers decided to flood the human blood sample with AML cells (including the growth activating antibodies) the results were astonishing as these very same antibodies transformed the AML cells into dendrite cells. (Dendrite cells support the immune system) With extended exposure to these antibodies, the cells matured further into natural killer cells that behave similarly to cells that kill threats to the human body such as viruses, bacteria, and cancer cells. 

These NK cells destroyed 15% of the cancerous cells in a single day. However, these NK cells only seem to target their former AML cell type, not other types of cancer cells.(B) Future Goals: The finding that agonist antibody converts leukemic cells into killer cells could be the key to treating or even healing patients diagnosed with cancer. Along with the transformation of cancer cells into less aggressive form, cells that have been recently induced have within them a killer phenotype as they kill other unconverted members of the malignant clone. (A) Researchers aim to use this technique that they call the 'Fraticidin Therapy' to transform a range of cancer cells into specific NK cells to cure a cancer patient all together. (B)

Links:
(A) http://www.pnas.org/content/early/2015/10/20/1519079112
(B)http://www.iflscience.com/health-and-medicine/scientists-can-now-make-leukemia-cells-kill-each-other

Making Rounds: Medical Education Documentary Film

Rising Costs of Hospitals:

Hospitals throughout the United States can save $50 billion annually simply by converting to a similar system such as the one in Canada where there is less paperwork and only one form of health insurance claim for all. If all patients were to carry basic coverage, then hospitals can rely on a consistent form of income without losing finances in treating the uninsured.

Those who are uninsured tend to rely on hospital emergency rooms for primary care. These emergency services are extremely expensive and such inappropriate use contributes to the rising health care costs in America. This is especially true when the cost of care cannot be recovered.

Hospitals are forced, by federal law, to accept patients who cannot pay until their condition is stabilized regardless of insurance status. Subsequently, this encourages uninsured individuals to use emergency rooms for primary care.

Private insurance companies took steps to set fixed rates so that hospital expenses for publicly insured patients would not be passed on to them. Whenever the prices of goods and services in general increase the cost of health care and hospitalization can be expected to rise.

Rising costs in hospitals are also due to the aging population creating a greater and growing demand for the elderly who need health care. This increases hospital expenses and doctor fees as well as other health care providers. 

The increasing pricing for health insurance correlates directly to these rising costs in hospitals and health care. As the number of prescriptions given by doctors to patients has created a greater shift and use in higher priced drugs.

*I do not own these images. They were found on various tumblr sites. If any are yours please let me know so that I can give you credit for them- Thanks so much!

Improving Access to Health Care

 

 Major Problem in Medical Field:

Many individuals who are uninsured, have chronic illnesses, and many who live in rural areas have a difficult time in accessing health care whether it is due to long distances, shortage of physicians, work hours, as well as cultural and language barriers. These are just some of the reasons as why access to health care is such a big issue in the medical field affecting so many people throughout the United States. Doctors also have a difficult time in finding ways to reach wide populations or be reached by patients. (A)

How do we improve the access to health care?

The solution to better meeting patient needs whether it is in increasing productivity or the time spent with sicker patients are just some of the ways in which physicians can begin to approach this problem. Then there are healthcare delivery organizations whose main concerns vary from rural and community hospitals where their aim is to attain medical specialties especially during after work hours, having tertiary and specialty providers to be able to give their services to hospitals reaching wider areas, and having access to assisted living facilities such as rehabs so that patients can be treated without the obstacle of transportation. (A)

Some communities have volunteers and staff members who find patients medical homes, enroll them into public programs, ensure transportation to health care appointments. They also provide translation and interpretation services or case manage those with chronic and costly diseases. Insurance agents, health care providers, and pharmacies donate or severely discount their services to support these new systems. (B)

Physicians could also delegate their responsibilities to other providers when appropriate. The Agency for Healthcare Research and Quality has estimated that in 2010, there were approximately 56,000 NPs and 30,000 PAs who were practicing in primary care. (C) These individuals could be the key to reaching more patients who are sicker or live far away who can be consistently cared for by PAs an NPs. Having nurses practice at the top of their license and deliver high quality care that they are capable to patients something to really be considered.

Subsequently, there are many ways in which we, as a nation, can improve access to health care. Now, we just need to ask ourselves, "How can we implement or better implement these solutions throughout the United States?"

Links:
(A) http://www.sbrhealth.com/improving-access-to-care
(B)http://www.policyconsensus.org/publications/reports/docs/Healthcare.pdf
(C) http://managedhealthcareexecutive.modernmedicine.com/managed-healthcare-executive/content/tags/access-care/7-ways-improve-access?page=full

*I do not own these images, they were found on various tumblr sites. If you recognize any or they are yours please let me know so I can give you credit! Thanks so much :)