Bruce Alberts on Future of American Science

“I have seven grandchildren, and I worry about their future. The nation that I was raised in, the United States, has clearly lost its way at a time when the world badly needs wise leadership. Nations with a long-term view are making huge investments in their infrastructure—transportation, water, energy, waste, and recreation. And they have a laserlike focus on supporting science and engineering research with government resources. As examples, Germany, China, and South Korea come to mind. Meanwhile, the United States is living off its past. Not only do we face a crumbling infrastructure but our federal investments in fundamental long-term R&D have been stagnant, dropping from 1.25% of the gross domestic product (GDP) in 1985 to 0.87% in 2013.† Now, on top of that comes a mindless budget "sequester" that will make the situation considerably worse, causing the U.S. National Science Foundation to announce last week that it may award 1000 fewer research grants in 2013 than it did in 2012.”

                                                     - Bruce Alberts (Science 15 March 2013)

 

This is not a thought of an average US citizen. Dr. Alberts, a past president of National Academy of Sciences, Editor-in-Chief of famous journal “Science”, is also a path breaking scientist in this own right, a leader, and visionary in American Science. Almost everyone in our generation of molecular biologists grew up reading his classic book during our college days that inspired us making our career in this field. His concerns seem quite genuine.

 

One study predicts that 2023 may be the year that America loses its global Research & Development (R&D) leadership.

China is on its track to overtake the U.S. in spending on research and development in ~ 10 years, as federal R&D spending (in the U.S.) either declines or remains flat.

 

However, it should not be forgotten that the United States still maintains a large lead in R&D spending over China, with federal and private sector investment expected to reach $424 billion next year, a 1.2% increase.
 

By contrast, China's overall R&D spending is $220 billion next year, an increase of 11.6% over 2012, a rate similar to previous years, according to the 2013 Global R&D Funding Forecast prepared by Battelle, a research and technology development organization, and R&D Magazine. "The U.S. still has a significant lead and advantage in R&D over all of these countries," said Martin Grueber, one of the authors of the report and a lead researcher at Battelle, "but the concern is R&D is a long-term investment, and as these other countries continue to grow their R&D capabilities ... how long can we maintain that advantage?"

 

A major share of R&D research in the U.S. is funded by the federal government, which is expected to budget $129 billion for R&D next year, a decline of 1.4%. This figure could decrease even further if Congress does not resolve its budget impasse.
 

Government R&D spending is considered significant as  because, unlike the private sector, it funds basic research. This is research that often takes years or decades to yield results, but it can also lead to new industries and jobs. Basic research is the back bone of industrial growth in any economy.

Other emerging economies, besides China, are also spending more on R&D. India, for instance, will invest about $45 billion next year in R&D, an increase of just over 12%.
 

President Obama has called for national R&D expenditures equal to 3% of GDP, which includes private and government investment. The forecast for next year is 2.66% of GDP, according to the Battelle forecast.

The White House also believes that China may overtake the U.S. in R&D spending.

"China's investment as a percentage of its GDP shows continuing, deliberate growth that, if it continues, should surpass the roughly flat United States investment within a decade," said the President's Council of Advisors on Science and Technology.

One significant but often ignored aspect of R&D operations conducted by U.S. is offshoring, which according to the White House report, "has negative long-term consequences for the United States."

The report also said that R&D returns to the U.S. economy are "likely highest when the research is both generated and used within the United States."
 

With a battery of talented scientists, engineers, medical doctors, present in the country, future of American excellence in Science and Technology is still bright, provided political leadership is honest and strong enough to resolve this issue sooner and act faster. Unfortunately, this is the most disheartening part – US Congress does not appear likely to take steps in the near term to improve R&D spending. Hope they are listening to what Dr. Alberts is echoing in his editorial piece this week.  

 

Some 2,000 odd men each year are diagnosed with breast cancer

When we think of breast cancer we always typically think of women, but it is true that approximately 2,000 men per year are diagnosed with this disease in the United States alone. Yes, breast cancer may develop in men at any age but it has typically been seen in men between 60 and 70 years of age. While male breast cancer is still a rare type of cancer as it makes up less than 1% of all cases of breast cancer worldwide, it is worthwhile to understand what it is all about.

There are several types of breast cancer found in men:

·         Infiltrating ductal carcinoma: Cancer that has spread beyond the cells lining ducts in the breast. Most men with breast cancer have this type of cancer.

·         Inflammatory breast cancer: A type of cancer in which the breast looks red and swollen and feels warm.

·         Ductal carcinoma in situ: Abnormal cells that are found in the lining of a duct; also called intraductal carcinoma.

·         Paget disease of the nipple: A tumor that has grown from ducts beneath the nipple onto the surface of the nipple.

One of the common types of breast cancer found in women is Lobular carcinoma in situ (abnormal cells found in one of the lobes or sections of the breast); this has not been seen in men.

Difference between Male and Female breast cancers

 

Male breast cancer seems to behave similarly to female breast cancer, and the disease in men is treated more or less similar to female disease. One difference between the two is in the timing of when men present with the disease, as versus when women seek care for the issue. Women typically undergo mammographic screening, bringing tumors that are not palpable to the attention of a doctor. Men do not undergo such screening because they usually have far less breast tissue and most tumors in the breast can be felt. Unfortunately however, while women are well aware that a breast lump is a concerning sign that should be brought to the attention of a doctor, many men still feel either embarrassed about seeking care for a breast lump, or are incredulous at the idea that they could have breast cancer or a serious illness that has become symptomatic. The consequence is that men tend to present to their doctors at a later stage, initially ignoring the finding more frequently than women do. When you compare the genders however, men do as well as women, stage for stage.

 

Risk factor for male breast cancer:

·         Being exposed to radiation.

·         Having a disease related to high levels of estrogen in the body, such as cirrhosis (liver disease) or Klinefelter syndrome (a genetic disorder.)

·         Having several female relatives who have had breast cancer, especially relatives who have an alteration of the BRCA2 gene.

·         Male breast cancer may sometimes be caused by inherited gene mutations (changes).

The genes in cells carry the hereditary information that is received from a person’s parents. Hereditary breast cancer makes up approximately 5% to 10% of all breast cancer. Some altered genes related to breast cancer are more common in certain ethnic groups. Men who have an altered gene related to breast cancer have an increased risk of developing this disease.

 

Men with breast cancer usually have lumps that can be felt.

Lumps and other symptoms may be caused by male breast cancer. Other conditions may cause the same symptoms. Check with your doctor if you notice a change in your breasts.

 

Treatment for male breast cancer

The typical treatment for men having breast cancer is a mastectomy, because there is little breast tissue to save, and resecting the tumor completely with “negative margins” (a margin of normal tissue surrounding the tumor, showing that it has been completely removed) may be more difficult.

 

In women, the cosmetic and sexuality issues surrounding the breast prompted investigation of lumpectomy with radiation as an alternative to mastectomy, and has been found to be equally safe. In men this has not been investigated sufficiently in trials to date to conclude this is safe. Men therefore have mastectomies as standard surgical treatment, along with assessment of lymph nodes.

 

When a man develops a breast lump, it is consequently important that he seek evaluation by a physician. While most lumps tend to be benign, a breast surgeon is best qualified to determine if this is something that may be normal or should be further assessed to rule out breast cancer.

Never ignore such a finding, and certainly don’t be embarrassed to seek advice from your doctor. Better to “overreact” and get attention of your doctor for something that’s benign, than ignore the problem and find out too late that it could have more easily been addressed earlier.

 For details, read following publication:

 

http://www.ncbi.nlm.nih.gov/pubmed/22987302

 

Robin Roberts Returns to ‘Good Morning America’ !!

It apparently looked like just another day for millions of Americans who start their day with “Good Morning America” while guzzling their coffee and getting ready for work, but for many of us, be them patients, caregivers, or scientists who are constantly fighting against this dreaded disease Cancer, it was a special day when we saw famous anchor Robin Roberts resuming her regular work on ABC, on Feb 20th, the Wednesday, after a 6 months battle against myelodysplastic syndromes. It was her second battle against cancer. Earlier in 2007, she was diagnosed with breast cancer and had fought it successfully. Yes, Robin is not only a survivor; she is a winner too, twice.

 

Ms. Roberts had just made a television comeback unlike any other, as a host of the program for the first time since she was forced to leave it in August 2012 to fight a life-threatening illness. The return, promoted two weeks ahead of time by ABC, was celebrated by fans, tens of thousands of whom sent well-wishes on social networking sites. Many of them watch the program specifically for Ms. Roberts, who is, according to industry research, the most-liked host on any American morning news program by a wide margin. Both Mr. and Mrs. Obama sent her a video recorded welcome wish and Michelle Obama promising her a meeting soon. But the most important part was Robin was beaming with pride and gratitude as she returned to the broadcast, defying the expectations of some in the television industry who had predicted she would be unwilling or unable to anchor again.

 

Many of you may have seen such brave people around who have survived their cancers too, and Robin being in media, just symbolizes that hope, strength, and will power one need to come in terms with such things if they happen on our lives. While it is time to celebrate the life of Robin and consider her as a role model of cancer patients/families, let us understand what this disease called “Myelodysplastic syndromes” is all about, that forced her out of her work for almost 6 months…  

 

 

Myelodysplastic syndromes are diseases of the blood and bone marrow.

 

Myelodysplastic syndromes are a group of diseases in which the bone marrow does not make enough healthy blood cells. Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. A lymphoid stem cell becomes a white blood cell. A myeloid stem cell becomes one of three types of mature blood cells:

 

1.   Red blood cells that carry oxygen and other substances to all tissues of the body.

2.   White blood cells that fight infection and disease.

3.   Platelets that form blood clots to stop bleeding.

 

 

To understand the process of Blood cell development, let us look at the flow-sheet diagram below. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

 

 

 

In myelodysplastic syndromes, the blood stem cells do not mature into healthy red blood cells, white blood cells, or platelets. The immature blood cells, called blasts, do not function normally and either die in the bone marrow or soon after they enter the blood. This leaves less room for healthy white blood cells, red blood cells, and platelets to form in the bone marrow. When there are fewer blood cells, infection, anemia, or easy bleeding may occur.

 

 

Types of myelodysplastic syndromes:

 

Myelodysplastic syndromes have too few of one or more types of healthy blood cells in the bone marrow or blood. Myelodysplastic syndromes are comprised of following diseases:

 

§  Refractory anemia.

§  Refractory anemia with ringed sideroblasts.

§  Refractory anemia with excess blasts.

§  Refractory anemia with excess blasts in transformation.

§  Refractory cytopenia with multilineage dysplasia.

§  Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality.

§  Unclassifiable myelodysplastic syndrome.

 

Age and past treatment with chemotherapy or radiation therapy affect the risk of a myelodysplastic syndrome.

 

 

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get a disease; not having risk factors doesn’t mean that you will not get a disease. Talk with your doctor if you think you may be at risk.

 

Risk factors for myelodysplastic syndromes include the following:

§  Being male or white.

§  Being older than 60 years.

§  Past treatment with chemotherapy or radiation therapy.

§  Being exposed to certain chemicals, including tobacco smoke, pesticides, and solvents such asbenzene.

§  Being exposed to heavy metals, such as mercury or lead.

 

Possible signs of a myelodysplastic syndrome include feeling tired and shortness of breath.

 

Myelodysplastic syndromes often do not cause early symptoms and are sometimes found during a routine blood test. Other conditions may cause the same symptoms. Check with your doctor if you have any of the following problems:

 

Shortness of breath.

Weakness or feeling tired.

Having skin that is paler than usual.

Easy bruising or bleeding.

Petechiae (flat, pinpoint spots under the skin caused by bleeding).

Fever or frequent infections.

 

 

Tests that examine the blood and bone marrow are used to detect (find) and diagnose myelodysplastic syndromes.

 

The following tests and procedures may be used:

 

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

 

Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:

 

The number of red blood cells and platelets.

 

The number and type of white blood cells.

 

The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.

 

The portion of the blood sample made up of red blood cells.

 

Peripheral blood smear: A procedure in which a sample of blood is checked for changes in the number, type, shape, and size of blood cells and for too much iron in the red blood cells.

 

Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under amicroscope to look for certain changes in the chromosomes.

 

Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.

 

 

Diagnosis is made by observing certain changes in the blood cells and bone marrow.

 

Refractory anemia: There are too few red blood cells in the blood and the patient has anemia. The number of white blood cells and platelets is normal.

 

Refractory anemia with ringed sideroblasts: There are too few red blood cells in the blood and the patient has anemia. The red blood cells have too much iron. The number of white blood cells and platelets is normal.

 

 

Refractory anemia with excess blasts: There are too few red blood cells in the blood and the patient has anemia. Five percent to 19% of the cells in the bone marrow are blasts and there are a normal number of blasts found in the blood. There also may be changes to the white blood cells and platelets. Refractory anemia with excess blasts may progress to acute myeloid leukemia. See the PDQ Adult Acute Myeloid Leukemia Treatment summary for more information.

 

Refractory anemia with excess blasts in transformation: There are too few red blood cells, white blood cells, and platelets in the blood and the patient has anemia. Twenty percent to 30% of the cells in the bone marrow are blasts and more than 5% of the cells in the blood are blasts. Refractory anemia with excess blasts in transformation is sometimes called acute myeloid leukemia.

 

Refractory cytopenia with multilineage dysplasia: There are too few of at least two types of blood cells. Less than 5% of the cells in the bone marrow are blasts and less than 1% of the cells in the blood are blasts. If red blood cells are affected, they may have extra iron. Refractory cytopenia may progress to acute leukemia.

 

Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality: There are too few red blood cells in the blood and the patient has anemia. Less than 5% of the cells in the bone marrow and blood are blasts. There is a specific change in the chromosome.

 

Unclassifiable myelodysplastic syndrome: There are too few of one type of blood cell in the blood. The number of blasts in the bone marrow and blood is normal, and the disease is not one of the other myelodysplastic syndromes.

 

Certain factors affect prognosis and treatment options.

 

The prognosis (chances of having a better treatment outcome) depends on the following:

 

Whether the myelodysplastic syndrome occurred after chemotherapy or radiation therapy for another disease.

 

The number of blast cells in the bone marrow.

 

Whether one or more types of blood cells are affected.

 

Certain changes in the chromosomes.

 

 

Treatment options depend on the following:

 

Whether the myelodysplastic syndrome occurred after chemotherapy or radiation therapy for another disease.

 

Whether the myelodysplastic syndrome has progressed after being treated.

 

The age and general health of the patient.

 

Courtesy: http://www.cancer.gov/cancertopics/pdq.

Palliative Care: a Realistic Goal in 'War on Cancer'

In the last 40 years since President Nixon launched the ‘War Against Cancer’, we have achieved a lot in the terms of understanding the biology of variety of cancers but when it comes to cure let us evaluate our successes. After worth of several billions of dollars of research where are we?  Let us first understand the parameters that define ‘cure’ in biomedical terminology. The National Cancer Institute (NCI) defines ‘cure’ as “to heal or restore health”. Many people mistake “5‑year disease‑free survival rates” - an end point used in many clinical trials, as cure rates. Although 5‑year disease‑free survival is a quick end point that can easily be measured as a parameter of success of a therapeutic agent, an ideal definition of cure would be when the annual death rate of post‑treatment cancer patients is the same as the normal population adjusted for the same age, in other words, when the cancer does not come back and people die due to some other reason in while they are cancer-free.


As per above definition of cure, what we have been able to achieve is indeed a “significant increase in the ‘disease-free survival’ for majority of cancers” which is not a small feat by any measures. However, it is still far behind the original goal of finding a complete cure when Nixon declared the “war on cancer” in 1971. Just one government organization, NCI, has spent approximately $90 billion on research and treatment during in these 40 years, let alone other government funding agencies and pharmaceutical industry. Despite our best efforts, truth of the matter is that approximately a third of patients diagnosed with cancer in high‑income countries, let alone third world countries like India, will not be ‘cured’ and will ultimately succumb to complications caused by cancer.

So what we could and should do about it? ………While continuous research and development efforts to develop new therapeutic modalities to treat cancer must go on, it is equally, if not more, important to understand the immediate needs of the cancer patients that can help improve the quality of their remaining lives. We should start talking about living with cancer as the “new normal.”  Legendary Cancer Biologist and Nobel Laureate Dr. Harold Varmus, also Director of NCI, recently suggested including a new and probably more realistic goal in the field of cancer research, “making cancer a disease you can live with and go to work with.” He went on to say, “We have many, many patients with lethal cancers who are actually feeling pretty good and are working full time and enjoying their families. As long as their symptoms can be kept under control by radiotherapy and drugs that control symptoms and other modalities, we’re doing right by our patients.”

Sounds reasonably good! Well, people live with diabetes, cardiac disease, many genetic conditions, so why can’t they live with cancer and resume their normal lives as with other diseases? Yes they can, but to ensure this happens in the life of every cancer patient, one of the most important aspects of cancer management is palliative care which has to play a very critical role in here, unfortunately which is most ignored and underdeveloped field so far. For those who are new to this, palliative care (from Latin palliare, to cloak) is medical care provided by a team of physicians, nurses and social workers that specializes in the relief of the pain, symptoms and stress of a serious illness such as cancer. While in recent years, medical researchers and healthcare providers in the west have recognized the importance of this growing field of medicine and already have started focusing in this direction, copycats counterparts in developing countries such as in India are still busy wasting their scarce resources in repeating basic research in cancer biology, in which they are anyways 50 years behind the international level.

Immediate development of basic infrastructure to support palliative care facilities for cancer patients should certainly be top priority for government healthcare agencies in India, where these patients are anyways deprived of basic care for their disease because of lack of dedicated cancer hospitals, oncologists, and new generation targeted (personalized) therapies to treat their cancers. It is quite understandable that governments in developing countries too busy struggling with corruption, bureaucracy, and lack of basic infrastructure to fight seasonal flu, and malaria, can’t provide their citizens the luxury of cancer treatments, but what they could do easily is to ensure the rest of the life of a cancer patient goes smoothly and without pain. The paradoxes of a so-called ‘growing economic power’ India can well be noticed by pathetic state of cancer care in following example. In my native place Lucknow, a vibrant mid-size city of 2.4 million people, located in North India, you can easily pick-up a juicy cheeseburger at McDonald, famous single malt whiskey Glenfiddich at any hour of the day from hundred odd joints, but if you have a family member/friend suffering from unbearable cancer pain, and looking for morphine, you have only one medical store/pharmacy in the whole city, and you are indeed lucky if you find this shop open at the hour of need and morphine is available there at that time. No doubt, cancer patients in India deserve a more peaceful and painless last days of their lives, and a dignified death which can only be ensured in palliative care centers (currently nonexistent) especially designed to meet the needs of terminally ill cancer patients.  

To understand the increasing role of palliative care in cancer management even in best places on earth, please read this article which explains needs, current status, and future directions of this new discipline in oncology:

http://www.nature.com/nrclinonc/journal/v10/n2/pdf/nrclinonc.2012.211.pdf

Alternative Medicine and Pseudoscience

When they first started National Center for Complementary and Alternative Medicine (NCCAM) as Federal Government’s lead agency for scientific research on the diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine particularly age old traditions of Chinese and Indian herbal medicines in early 90s, it was certainly a right step to find more alternatives to treat diseases worldwide using traditionally available wisdom and resources by validating or disapproving them scientifically. Many such folk medicines turn out to be really effective in treating common diseases/conditions such as traditional use of chicken soup in western world is now even recommended and preferred by many pediatricians to treat common cold than over the counter cold medications. 

However, many proponents of alternative medicine have become too enthusiastic to suggest folk medicine or practices such as acupuncture, herbal concoctions, or even yoga/meditation as "cure" for life threatening diseases including cancers and this trend is really alarming. Hasty conclusions based on incomplete/inconclusive studies especially those coming from places of repute in medicinal research may mislead patients who can in turn end up deviating from otherwise effective standard/conventional therapeutic modalities and by the time they realize the ineffectiveness of such “alternative” medicine, all they are left with is deep regret. Steve Jobs’ unsuccessful fight against pancreatic cancer using herbal medicine is such an example. Here is a very interesting article that summarizes how things can be twisted from “facts” to support their unproven theories/beliefs. Unfortunately, science does not run on beliefs, it needs evidence. Let us save science from pseudoscientists….

http://www.forbes.com/sites/stevensalzberg/2013/02/11/bad-medicine-infiltrates-md-anderson-cancer-center/