On The Nature of Grad School

As I prepare to enter grad school, I've been pondering on the nature of the beast that I will soon be jumping into.

I believe that the purpose of graduate study (at least for the science Ph.D.s) is to move the individual from a "student" to a "fully functional independent researcher". That when you get your diploma, you should be able to start your career later that hour. Granted there might be a training period where you will get up to speed on current literature (especially in industry), but other than that you are ready to go.

I think that this is applicable to students pursuing a career in either academia or industry.

Although there are often no formal classes required after a few years, students will still be learning as much as if they were. If your research delves into the depth of some topic that you are unfamiliar with, you are going to have to master it to be able to persevere. Signifying a move from class-oriented learning to self-oriented learning.

Genetically Modified Organisms in Drug Production

I believe that the importance of the synthetic chemistry in large scale drug production will be overshadowed and eventually eliminated by synthetic biology via genetically modified organisms (GMOs). Furthermore, I surmise that this shift will occur before I retire from my research career (of which I am just beginning).

The traditional methods used to manufacture drugs rely on organic chemistry. While time tested and effective, these methods often create large amounts of toxic waste and require high amounts of energy (such as temperature or pressure).

Nature, on the other hand, has the evolved the ability to create molecules of equal (and much greater) complexity at normal atmospheric pressure, with no toxic waste products and with whatever the temperature happens to be. For mammals, the temperature is typically constant (body temperature) but unicellular organisms are at the mercy of ambient temperature.

With an optimized GMO, one literally feeds the thing sugar and it spits out any product that it was modified to create with little to no toxic by products.

The notion that a bacteria produced your heart medication might seem far fetched and slightly futuristic. But Dr. Keasling was awarded the distinction of Scientist of the Year in 2006 by Discover Magazine for his research on using GMOs to produce an anti-malarial drug.

I believe that as pressures for "green" or eco-friendly science increase and as GMO technology is further validated and refined, it will quickly become the main method of choice for drug production.

The Pros of GMOs

I believe that GMOs will quickly become a more cost effective method in drug production than traditional synthetic chemistry due to the:

• low cost of starting materials (Sugar, or other cheap carbon source)
• lack of toxic waste products (Saving disposal costs)
  
• low cost to escalate production (As many GMOs can be created from the same base organism, the required manufacturing infrastructure would also be similar)
  

One Photosynthetic Organism To Synthesize Them All
- The Pinnacle of GMO Tech

In theory, a GMO could contain the genetic instructions to create thousands of drugs. A manufacturer might create a GMO that could produce every drug that the company has the rights to produce. The company would then tell the organism which set of genes to turn on via some messaging pathway, and then extract the product.

One could even create the GMO from a photosynthetic organism. Now the GMO gets its energy from the sun and uses naturally occurring carbon dioxide as the carbon source. Imagine a world, where carbon dioxide emissions are partly controlled by the production of the current erectile dysfunction pill. I shudder at the potential marketing campaigns.

Where the Technology Stands Today

Instead of a GMO creating the entire drug, the technology is at a stage where a GMO completes only one step in the process. This is due to the difficulty of getting several artificial genes to work together in the cell.

Realistically as companies start to take advantage of this technology, it will not immediately replace traditional synthetic chemistry but work in tandem with it. Where five steps of the synthesis are done via traditional methods, two steps might be completed with GMOs.

As it takes a long period of time to validate the safety of new drug manufacturing methods, it will be a while before GMO manufacturing really hits full steam.

Why Synthetic Chemistry Will Never Disappear Completely from Drug Manufacturing

Although synthetic biology will be the main choice for large scale drug production, I think that drug manufacturers will still have a need for synthetic chemistry.

The greatest strength of synthetic chemistry is that it has a quicker turn around time, in terms of from the drawing board to the bench top, than synthetic biology does. This means that if a company needed a batch of some previously never before synthesized compound for preliminary testing, it would be quicker (and probably cheaper) to utilize synthetic chemistry.

Synthetic chemistry is faster because it allows an "any means available" paradigm to the synthesis process. If the most effective process employs a toxic agent, thats okay. By utilizing an a-biotic reaction system, the scientists are free from the constrains of only using compounds that are non-toxic to the GMO. This allows a scientists to use the most effective compound regardless of its affect on some organism.

Furthermore, GMO creation is a time-intensive and empirical process. Inserting additional genetic material into a cell is analogous to adding car manufacturing capabilities into an aircraft carrier. The system already is already chalk full of cellular machinery and one is trying to insert more. If the newly inserted genetic material affects any of the other pathways operating in the cell, it can easily cause the cell to die.

Additionally, the required genes need to be found (taken from other organisms) or created (if an adequate match does not exist).

What These Production Plants May Look Like

To surmise what plants based on synthetic biology technology may look like, we can look towards current systems that employ organisms in the production process. Beer. Beer production employs yeast, a unicellular organism. The yeast is added to vats containing the reaction mixture, allowed to react for a specific time and then the mixture is removed and separated.

I believe that other production plants utilizing GMOs would be very similar in nature. The beer industry has very high standards for constant sanitizing, which would be necessary in any plant utilizing microorganisms. It is interesting to think that the plants that make our life sustaining medication might look oddly similar to the plants that make our beer.

What This All Means for the Chemist

As GMOs gain prevalence in the industry, there would be a corresponding decrease in demand for synthetic chemists as GMOs fall in the domain of biologists. So what can a chemist do to maintain employability?

When synthetic chemistry first started, its goal was the creation of compounds utilizing any means available. In the past, these means were mainly inorganic. Today, these means include living organisms. To maintain competitive in the synthesis domain, chemists will have to become more familiar with the technology offered through synthetic biology.

The truly competitive individual will not label themselves as a synthetic chemist or synthetic biologist but as a synthetic biochemist - utilizing "any means available" for the synthesis of a target compound.

My Nerdiest Possesion - An Autographed Periodic Table

My most prized science related possession is a periodic table signed by Dr. Seaborg.

Dr. Seaborg is (and will be) the only person to have an element named after him while he was still alive.

Dr. Seaborg's research included the discovery and characterization of 10 undiscovered elements and 100 undiscovered isotopes. His research mainly focused on the heavy f-block elements.

Few researchers are able to claim so many fundamental discoveries to their name. As Lois and Clark's exploration revealed a plethora of information about the U.S., Dr. Seaborg's scientific career did the same for our understanding of the heavier atoms. Not only did he discover a large number of elements but he also elucidated the fundamental theories regarding their behavior, allowing for the prediction of undiscovered isotopes and the placement of these elements into the Periodic Table. This is quite amazing, if you think about it. It is analogous to Lois and Clark not only charting much of America's terrain for the first time, but then also elucidating the major geological processes that created them.

Dr. Seaborg was awarded a Nobel Prize in 1951.

On the Complexity Molecular Pathways

I remember the first cellular transduction pathway I encountered at the college level. Well, mainly I recall my bewilderment. Why on earth, I thought, would you need a 10 (or more) step sequence to get some desired result? I remember thinking that the corresponding diagram for the pathway made a Rube Goldberg device seem completely straightforward and rather elementary.

At first glance, it appears that cellular processes are the epitome of an inefficient red-tape laden bureaucratic system. That before messenger "A" can cause response "B" it might need 17 signatures, two stamps of approval, three forms and an official endorsement all in triplicate.

The mechanics and intricacies of these system is simply astounding. When studying most cellular pathways, one would be almost certain to find that:

• Each protein in the pathway will have numerous sites for activation and inhibition.
  
• Each protein, itself, can be made of multiple proteins, all working in unison.
  
• Internal messengers will be made to tell the system to "Start" but without any chemical alterations to that messenger, they will eventually cause the system to stop.
  
• The activity for each step in the pathway can be individually tweaked to create an astoundingly large range of possible rates for the entire pathway.
  
• Each activated molecule in this pathway is likely to play a key role in some completely different cellular pathway, which will initiate even more cellular responses.
  
• Despite the number of steps involved the message gets to the end destination on the millisecond time scale.
  

While the complexity of signal transduction is humbling, it does offer us some promising insights that we might be able to pass onto our everyday life. Mainly, if a non-thinking entity, such as a cell, is able to negotiate a highly regulated multi-level controlled system instantaneously, surely, we (a race of some-what intelligent beings) can one day figure out how to make it so we don't wait for hours at the local D.M.V.