The Book in Review- The Laws of Medicine (Field notes from an uncertain science) By Dr. Siddhartha Mukherjee

The Laws of Medicine, written by Dr. Siddhartha Mukherjee, comes as an easy to understand essay but leaves you with a profound impression of both the content and its writer- what in my opinion qualifies to be Magic!

In the very first few pages, the book serves you with what it is going to offer. Unlike what you may presume from its title- The Laws of Medicine; the book doesn’t elaborate the laws of the medical field, it rather, tells you about the laws of uncertainty, impression, and completeness- inherent and prevalent in this field. This book can change your perception of your doctors and care givers.

As Siddhartha Mukherjee states in his book, “Laws are statements of truth based on repeated experimental observations that describe some universal or generable attributes of nature”. Physics for example, has many laws; chemistry has lesser and biology seems to be lawless. Living creatures have been living with laws of physics and chemistry, converting forms of energy and sustaining their existence. We all have been taught that fundamental laws of nature govern matter and everything around us.

The obvious question that boggles our mind then is- if medicine too, is governed by universal guiding principles that lead into truth that applies to medicine at large. To our rescue comes Dr. Siddhartha Mukherjee, who offers a set of laws of medicine- that invigorate that there are, in fact, no laws in the literal sense. He puts together many examples and personal experiences to convince you that you have been thinking of medicine totally differently. Your perception of medicine as a field is set to take a U-turn.

Following are his three laws of medicine.

Law 1: A strong intuition is much more powerful than a weak test.

Dr. Siddhartha Mukherjee discovered this law by chance, through his own personal experience. He says, sometimes symptoms direct the doctor to order tests that are unrelated to the patient’s ailment. In such situations, intuition and observation become powerful tools to guide the doctor to look for the correct diagnosis, distinguish false positive and false negative test results- that would otherwise be missed in the absence of intuition.

Law 2: ‘Normals’ teach us rules; ‘outliers’ teach us laws.

Every outlier or non-normal patient offers the doctors with an opportunity to refine prior knowledge and challenge preconceived notions about an ailment and its management. Outliers provide new pieces of information that revamp any discipline and help discover its hidden inner logic.

Law 3: For every perfect medical experiment, there is a perfect human bias.

I loved this sentence. The reason for bias in medicine is “Hope”, and the solution is randomization and blinding.

He states that the uncertainty in medicine is not limited to these three laws; there could be, more laws, yet to be found and stated.  He has framed his three laws based on his personal experience during his medical internship, residency, and fellowship.

I was moved by how he concluded his essay. He quoted Voltaire, “Doctors are men who prescribe drugs of which they know little, to cure diseases of which they know less, to human beings of whom they know nothing”.  He says, “The pivotal word remains- to know”.

This book is a published version of his TED talk, but is equally pleasurable to read. This micro book that looks like a handout, leaves you with visuals of doctors in your head, whom you have visited in your lifetime- in pain or in doubt.  

It’s a kick-start for those planning to plunge themselves into science writing and communication. So, go for it!

Nano DNA lenses to see future!

Ramesh looked into the mirror, turned his head left, right and took a deep sigh! “I wish at seventeen, someone told me that I would turn bald, I could have been a little more careful”. A simple gene test could do that for him now. Research suggests that variations in a gene called AR increase the risk for the most common form of hair loss in both men and women. He could not get gene testing then, but his children may get it in 2017.

Something similar to this had happened in 2015, it was news when Angelina Jolie underwent double mastectomy. She chose surgery to remove her breasts.  This was after a test for mutated BRCA1 and BRCA2 genes that revealed that she was at a high risk for breast cancer. She could avoid that risk because she could sneak peak into her future. Men were also worried; of course she was the most admired woman at that time, they were worried more because breast cancer is not exclusive to women.

It will soon be a reality for anyone to get DNA sequenced, for pleasure or for purpose. It was no less than a sci-fi thriller to read the human DNA sequence until the early 2000s when it cost ~ $3 billion and fifteen years. It seemed to be still on the cloud with ~$14 million in 2006. By mid 2015 when newer technologies caught it at ~$4000, researchers aimed to stoop it to ~$1000 in three days. Until recently, the cost of sequencing crashed but scientists had to shed a hefty few million dollars to buy the bulky machines.

Rejoice! It would soon become a reality to know your DNA sequence in a single affordable test. A game changer technology, Oxford Nanopore MinION (ONM) aims to do it in much less penny and time. It doesn’t serve all that it promises at present, when the test costs ~$500, it is still less burdening because the machine costs less than $1000. It can be carried in a shirt pocket, as it is the size of a USB stick weighing 87 grams that has to be plugged into a laptop with an ordinary configuration to read DNA sequence. It is possible for an ordinary lab technician without rigorous training to give you a snippet of your genes in less than six hours.

This technology is alarmingly simple. Applied voltage is used to pass DNA through a minute hole called Nanopore that rests on a non-conducting membrane. The changes in current flowing through the pore are used as readouts of DNA sequence. This approach encompasses time consuming and tedious processes of DNA labeling and amplification, hence, can be scaled up for high-throughput sequencing. 

This technique gives a tough competition to other technology giants like lllumina who has filed a patent lawsuit against Oxford Nanopore. They have withdrawn the lawsuit by settling on some monetary and regulatory terms.    

To give you a flavor of what this machine can do, Joe Parker and his team from Jordell Laboratory, UK have shared a breath taking video of sequencing a fungal genome amidst a dense forest in a camp. He jumps to joy when he says “you work but not in the lab anymore”. He is thrilled that now he can go in the wild to sequence wild species. He doesn’t have to limit the DNA sequencing research to lab organisms anymore. In another setting, researchers at Stanley Royd Hospital, UK could identify a serotype variant of Salmonella enterica during a gastroenteritis outbreak by sequencing its genome using ONM in less than 50 minutes, a process that would otherwise have taken a few weeks or months.

It is a DNA sequencing machine that could be used where the resources are critical, electricity availability is a problem, lab space and computational capacities are limiting. It provides the option to “Read till” a sequence in real time where the user can choose to read the DNA of interest and skip regions that aren’t required. Hence we can read many genes in one go in less time.

Apart from being portable, user friendly and cheaper: it can be used to wand another wonder. Alas! Direct RNA sequencing. You can now sequence viruses from patient samples, soil or plants and name what not. We know that viruses like HIV and influenza mutate at incredible speeds, by the time we have one set of sequences, they have already changed. Now we could sequence them on a hospital site within no time. If genome wide RNA sequencing can be done at minimal cost in the coming years, it could change the medical field completely. During the recent Ebola outbreak, scientists at New Guinea traced the spread of the virus in less than 40 minutes. A separate group of researchers at University of California, San Francisco detected Ebola, Chikungunya and Hepatitis C virus in human samples within four to forty minutes of the sequencing run. This technology is giving many researchers serious shopping goals.

It is the first DNA sequencer to fly off to space in July 2016. It would be the first of its kind to be out of the world, literally!

In May 2016, Oxford Nanopore announced that it is developing a techno variant SmidgION that would read DNA to your smartphone. It would cut costs considerably and read long sequences in few hours.

This technology is banging the doors of future. When sequencing becomes a $20 reality, we could screen newborn infants for several inheritable diseases such as pancreatic, ovarian, prostrate, breast cancer and some brain developmental disorders soon after delivery. We could screen bacteria and viruses from patient samples, sequence the antibiotic resistance genes and know which drugs will be ineffective. Without randomly dosing all patients with antibiotics, we could prescribe them with perfect pills. Ladies and gentlemen, fasten your seatbelts and get ready to go, the era of personalized medicines is here!

Ensnaring Cyanide

Cassava feeds 300 to 500 million people per year globally. It is very nutritious but contains cyanide. If not cooked properly it causes acute cyanide intoxication or even partial paralysis. Drinking water that is contaminated by industrial waste occasionally contains cyanide, which when consumed causes vitamin B12 deficiency, chronic effects on the thyroid gland and the nervous system as the gastrointestinal tract readily takes up the toxin and only 10-15 percent is excreted.

Researchers at the University of Delhi have collaborated with Colorado State University to make a test that allows naked eye detection of cyanide in water. The test uses a sensor, CoII-bis(terpyridine) complex which gives a colored complex when added to water. This could help decision makers to know if drinking water meets EPA and WHO guidelines on quality by an on the spot test on a small volume of water.

Reference: Sensors and Actuators B-chemical 235: 325-329.

A Better Material for Lithium Batteries

A new material magnesium ferrite is a better candidate in lithium batteries, a recent study done by scientists at Pudducherry and Andhra Pradesh in collaboration with Amara Raja Batteries Ltd, Andhra Pradesh and Clemson University, South Carolina, USA suggests.

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Lithium batteries are commonly used in household appliances such as torch, table lamp, and TV remote. Consumers desire extended battery life and longer discharge time from a battery that also makes it cost effective.

Magnesium ferrite is an ecofriendly, nontoxic, cost-effective and electrical conductive material that hasn’t been evaluated for use in lithium batteries so far. A recent study by scientists at the Pondicherry University, Pudducherry and Vignan’s University, Andhra Pradesh have collaborated with Amara Raja Batteries Ltd, Andhra Pradesh and Clemson University, South Carolina, USA to test magnesium ferrite in lithium batteries at the anode or positive terminal for its electrical behavior and qualities.

Researchers have synthesized magnesium ferrite by mixing solutions of ferric nitrate and magnesium nitrate, and heating the mixture under constant stirring in the presence of citric acid, urea and adding ammonia to complete the reaction. The sample is then heated at 700°C for 2 hours to obtain magnesium ferrite nanoparticles smaller than 40nm.

It shows improved electrical conductivity, higher discharge capacity, which is better than commercially used graphite. The scientists proclaim, “The observed electrochemical properties of the fabricated lithium battery indicate that the newly developed magnesium ferrite may be a better anode material for lithium battery applications”.

Many day-to-day appliances such as our wall clock and torch use lithium batteries. Researchers need to develop newer materials that help industries make better batteries with enhanced life and longer discharge time that could cut down costs and save time.

Reference: Ceramics International 42 (15): 16789-­16797.

A Biometric System Resistant to Spoof Attacks

A working model for developing a biometric system that is resistant to spoof attacks has been developed by researchers at the National Institute of Technology, Raipur and TCS Innovation Labs, Mumbai in their recent study.

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A large number of organizations presently use biometric systems for person authentication, in an easy and reliable manner to manage data from a large number of users. However, biometric systems that use fingerprint matching as the sole strategy to authenticate person are prone to spoof attacks. During a spoof attack, an imposter uses the fingerprint of a genuine user that may be obtained by unethical means for obtaining unduly authentication.

Researchers at the National Institute of Technology, Raipur and TCS Innovation Labs, Mumbai have developed a new model that uses fingerprint matching and fingerprint dynamics for authentication in biometric machines. Fingerprint dynamics requires the users to scan fingers multiple times. It uses parameters such as the sequence of fingers used for scan, repeated use of a finger, the length of finger area used during scan, time taken between consecutive scans to add another dimension during person authentication.

Since, this model uses software-based intervention, it is cost effective, convenient, reliable and automated. Fusion of these two parameters, fingerprint matching and fingerprint dynamics improved the overall efficiency and performance of biometric system remarkably. The researchers proclaim, “ (their system)… provides commendable spoof resistance while minimizing the error rates. The increased spoof resistance of the proposed system is because of the use of behavioral characteristic, fingerprint dynamics”.

The new proposed model can be used to devise spoof-resistant biometric systems thereby enabling more security to organizations and their data.

Reference: Pattern Recognition 62: 214-2­22.