Organic Chemistry - Education and Industry

Recent Activities and Future Plans - I'm Still Here!!!

2012-02-01T21:29:00.000-08:00

My apologies for the long delay since my last post. Since beginning this blog, I strive to post at least once per month. Unfortunately, due to a very busy end-of-the-year, blogging slipped.

As you are aware from the content of my posts and from my personal website (www.DELbiopharma.com), I am a consultant providing the following services:

design and implementation of medicinal chemistry programs
chemistry outsourcing management
technical due diligence

As a consultant, it is absolutely essential for me to continually network and market my services. Time for these activities must be allotted in addition to the time that I spend working with my clients. From all aspects, the combination of scientific engagement and personal interactions is unparalleled to any employment situation I experienced prior to becoming a consultant. That being said, I would like to focus this post on both highlights of the past 6 months and events planned for the near future.

Recent Activities

During the second half of the summer, I had a full load of clients - all with unique needs. One in particular required the synthesis of several compounds within an extremely aggressive timeline. After contacting seven different contract research organizations (CROs), I was able to identify one that was willing to take on this project within the parameters of the required timeline. I am happy to say that this project, arguably the most difficult assignment I took on, was completed on time with all objectives met.

As indicated above, networking is critical to the establishment of a contract pipeline. As such, I regularly go to local networking events and conferences. The following is a list of groups I find particularly interesting in the San Francisco area:

BioScience Forum (www.biosf.org)
Bio2Device Group (www.bio2devicegroup.org)
Bay Area Biomedical Consultants Network (babcn.net)
CACO-PBS (caco-ca.org)
BioE2E (www.bioe2e.org)
QB3 (qb3.org)

In August, I was asked to present a talk at a BABCN event entitled "Creating Opportunities - Generating Consulting Income in a Hostile Market." This talk was well attended and I received a great deal of positive feedback.

In January, I participated in the CSU Biotechnology Symposium as a career mentor. The following week, I attended the JP Morgan Healthcare Conference. One week later, I attended the Personalized Medicine World Conference.

As a follow-up to my BABCN presentation in August, I was invited to write a guest blog covering a key component of my consulting activities - identifying, engaging and managing CROs. This blog was posted on January 31 and can be found at http://hamptonexecutivesearch.com/?p=1497.

Future Activities

Having brought you up to date from the past 6 months, the following is a list of plans for the near term.

As networking is essential to my ongoing consulting activities, I plan to attend the following conferences:

InformexUSA 2012 (www.informex.com)
Molecular Medicine Tri-Conference (www.triconference.com)
American Chemical Society National Meeting (www.acs.org)

During the American Chemical Society meeting, I will be speaking as part of a symposium discussing chemistry careers outside of the laboratory.

Finally, as a follow-up to the CSU Biotechnology Symposium in January, I will be posting blogs addressing all of the questions raised at my table during the career mentoring session. These posts will begin in February and continue until all questions are answered.

As always, I encourage you to bring up any topics you would like discussed in this forum.

Unnerving Trends in the Pharmaceutical Industry

2011-07-05T23:19:00.000-07:00

"Houston, we have a problem." This phrase, credited to the crew of the Apollo 13 lunar mission, has been used in many contexts (both seriously and comically) to describe difficult situations. In worst-case scenarios, like Apollo 13, profound and life-changing (challenging) consequences may emerge. In today's economy, one may paraphrase this to "ACS, we have a problem."

ACS (the American Chemical Society) is an organization dedicated to the promotion of the chemical sciences through educational programs, industry support and government lobbying. Twice a year, it brings together thousands of chemists to exchange thoughts on the future of science, the status of academia/industry and government policy. Additionally, career resources are continually provided to aid ACS members in advancing their careers or identifying opportunities to regain or maintain employment. Such resources are extremely valuable in these days of continued downsizing and outsourcing. However, even the ACS cannot create jobs where few exist. In previous years, the back of Chemical & Engineering News was full of job advertisements for chemists. Furthermore, the ACS sponsored career fairs were supported by hundreds of potential employers with jobs spanning all levels of experience. I am sad to say that these advertisements are sharply diminished compared to previous years. It is no secret that among sectors, the pharmaceutical industry is among the hardest hit.

Fully recognizing that these trends are industry-related and not the fault of the ACS, the question is now "what can be done to restore growth to the pharmaceutical industry?" In order to answer this question, it is important to understand the causes of the present multi-year downturn. These causes can be traced back to the marketing of "blockbuster" drugs and the resulting year-over-year double digit returns to investors. As patent protection for the existing inventory of "blockbuster" drugs expires, the pharmaceutical industry is forced to look at lower revenues and increased competition from generics. At the same time, the existing drug development pipeline is deficient in new "blockbuster" products to replace those going off patent. Lower revenues coupled with continued demands from investors for high returns forces corporate downsizings. Such downsizings are typically at the expense of research - the efforts generating long-term revenues. With research departments minimized or eliminated, there are fewer quality products entering development - the efforts generating short-term revenues. With fewer and/or premature compounds entering development, the likelihood of late-stage clinical failure is increased. This trend directly results in decreased investor confidence. With decreased investor confidence, there is less money available for investment in the pharmaceutical industry. Less money means fewer jobs and fewer products advancing into the clinic. IT IS THIS CYCLE THAT MUST BE BROKEN IN ORDER FOR THE PHARMACEUTICAL INDUSTRY TO RECOVER!!!

Emerging Trends in the Pharmaceutical Industry

Understanding the cycle leading to poor investor confidence is only the beginning. In order to reverse the pharmaceutical industry's downward spiral, we must implement new paradigms and develop them to their full potential. Such paradigms include:

personalized medicine - novel therapeutics with companion diagnostics
efficient use of both in-house and outsourced activities
streamlined processes enabling the "forced failure" of programs more likely to fail so efforts can be focused on programs most likely to succeed.

Regarding personalized medicine, I posted two articles on this subject (see postings on November 12, 2010 and February 27, 2011). Furthermore, the potential that can be realized through the ability to screen likely patients in order to assess their likelihood of responding to an experimental therapeutic is dramatic. To cite data presented by James Sabry (Vice President of Genentech Partnering) at a recent networking event, 4000 drugs were tracked from clinical trial to market from 2004-2010. Of this set of drug candidates, only 9% achieved FDA approval. Broken down to the clinical stages, 63% advanced through phase I clinical trials. Of the 63%, only 33% advanced through phase II clinical trials. Of that 33%, 55% advanced through phase III clinical trials. Finally, 80% of those advancing through phase III received approval. In order to restore investor confidence and rebuild our industry, these percentages must rise. Through exclusion of clinical trial participants lacking necessary biomarkers, these percentages will increase.

Regarding the combined use of in-house and outsourced activities, I continually comment on industry trends, employment challenges and novel career opportunities. Two postings on these topics (see postings on August 21, 2009 and October 25, 2009) go into great detail regarding current and emerging trends. The reality is, outsourcing is here to stay. Once accepting this reality, potential new opportunities come to light. In the May 9, 2011 issue of Chemical & Engineering News (pg 48-51), I was quoted regarding trends and opportunities in "Managing Outsourcing." Specifically, as organizations continue to view synthetic chemistry as "outsourceable," these same organizations recognize that management of these activities requires one both skilled and knowledgeable in the science of organic/medicinal chemistry. Problems always arise when working with CROs. Success is dependent upon how efficiently these problems can be addressed. Furthermore, simply being able to prepare compounds is not a replacement for the ability to design the right compounds to prepare. In my experience, the most efficient combination of in-house and external resources utilizes a small internal infrastructure for development of robust synthetic methodologies in concert with the technical talents of CROs for the synthesis of targeted compound series dependent upon these methodologies.

Regarding streamlined processes, early drug discovery efforts were somewhat linear with compounds advancing through one assay at a time. By utilizing batteries of assays to evaluate structural classes, early indications regarding pharmacokinetics, metabolism and toxicity can be established. Structural series failing to demonstrate early acceptable properties can be terminated in favor of those showing promise. Through "forced failure," more money is spent earlier to save even greater amounts by not advancing sub-optimal compounds into development. Finally, referring to the percentage of drug candidates advancing through phase I clinical trials mentioned above, the "forced failure" paradigm holds the potential to positively impact this statistic.

The Future of Employment in the Pharmaceutical Industry

While the above describes trends likely to result in greater success and return on investment, it does little to address the current state of employment in this industry. While the unemployment rate in the United States is around 9.1%, the unemployment rate in the pharmaceutical industry (including biotechnology) is almost twice that. While disheartening, I continually post on strategies for maintaining employability as well as what types of opportunities are available for those displaced in a shrinking job market. Additionally, in the April 18, 2011 issue of Chemical & Engineering News (pg 49-51), I was quoted in an article focused on "Survival Skills." The lessons are more relevant now than ever - those currently unemployed must find ways to stay active in this industry or risk not finding employment as conditions improve. In today's economy, there are plenty of reasons for not getting paid. However, there are no excuses for not working.

Even with the unemployment trends, there are those who have the potential to influence policy and, at least partially, restore growth to this industry. These individuals are our congressional leaders and big-pharma executives.

In the current state of the pharmaceutical industry, large companies have turned to small biotechnology companies to enhance their development pipelines. However, these deals, especially for earlier stage compounds, come with high milestone payments. Consequently, deals between large and small companies are dissolving in attempts to minimize these payments. The unfortunate result is small companies being forced to develop their products without the backing of larger organizations. The increased corporate expenses related to clinical development often result in significant corporate downsizings - thus compounding the current employment climate (Chemical & Engineering News, June 20, 2011, pg 15-20). In an industry where high risk yields high reward, the current risk adverse nature of those influencing the pharmaceutical industry continues to result in downward pressure on the economy. Downstream, these trends will inevitably be reflected in fewer new products and continued medical indications with no available effective treatments.

With the number of highly innovative scientists displaced due to mergers, outsourcing and downsizing, the talent pools in both local industry hotspots and nationwide are unprecedented. Even so, John Lechleiter (CEO of Eli Lilly & Co.) is lobbying for US immigration officials to issue more green cards for highly skilled immigrants. While I am all for opening up opportunities for the most qualified individuals, isn't it incumbent upon us to first look after those who, through no fault of their own, found themselves unemployed?

Regarding the rich pool of available talent, the trends and paradigms discussed in this posting should generate a great deal of optimism. Once the dust settles and new business models emerge, growth will return. Furthermore, with appropriate financial resources, the available talent pools will inevitably give rise to a new generation of start-up companies creating new opportunities for innovation. As Apollo 13 began with a problem and returned safely home, so too will the pharmaceutical industry. After all, we are a growing and aging population. We will always need to eat, we will always generate garbage and we will always require medication.

Organic Chemistry Degrees - Training in Thinking vs Training in Doing

2011-03-29T22:28:00.000-07:00

A recent editorial in Chemical & Engineering News, along with an accompanying article, has had me thinking about the future and quality of our educational programs. The editorial entitled "Too Many Ph.D.s?" and the article "Doctoral Dilemma" both appeared in the January 31 issue and, not surprising, have received significant interest and responses. Presently, I am attending the Anaheim ACS meeting and, in light of the high caliber of science being presented around me, I feel a need to add my thoughts to this discussion.

I received my PhD under the supervision of Professor Satoru Masamune at the Massachusetts Institute of Technology. As part of my graduate studies, I was responsible for the design and execution of synthetic strategies leading to the total synthesis of Calyculin A. Those of you who may be familiar with this natural product will recall that it is a highly structurally diverse molecule with an aminosugar unit, a heterocycle, a spiroketal and a tetraene. The two fragments I worked on were the aminosugar and the tetraene. In addition, I designed a novel approach for the introduction of necessary chirality adjacent to the heterocycle. In all cases, my efforts began with an exhaustive study of the target structures as matched with the structures of available starting materials and availability of key reagents. At no time did I receive instructions as to how I was to approach my assigned tasks. Instead, I was given the freedom to execute on my ideas and drive these efforts as far as they could go based upon the available technology. I would not be honest if I suggested that each attempt worked as planned. However, each strategy, successful or not, allowed me opportunities to ask questions, find answers and evaluate results. My technical experience was a byproduct of the extensive chemical studies I pursued. After all, how could I answer questions without doing the experiments.

My undergraduate research activities, in contrast to those in graduate school, fell under the tutelage of Professor Henry Rapoport. In his labs, I was assigned specific tasks with generally understood protocols. My role was initially to support the efforts of a post doc. Later, I was assigned more independent studies allowing me to begin thinking about chemistry rather than simply following instructions. So, when comparing my undergraduate experiences to my graduate studies, Rapoport taught me how to do chemistry and Masamune provided me the opportunity to teach myself how to think about chemistry. Both experiences were essential to my academic and professional development.

Current Educational Programs - Are We Training Too Many Ph.D.s?

In the present job climate, there is no question that medicinal chemists have endured more than their fair share of problems. With the continuing trend of corporate takeovers and subsequent shutdowns, there is plenty of available talent with nowhere near enough new jobs being formed to absorb the unemployed. At the same time, graduate programs continue to produce a new generation of chemists eager to enter the workforce. In anticipation of the extremely high level of competition for any available position, I have heard it argued that some graduate student mentors are tailoring their programs to meet specific needs of companies. If true, this type of "apprenticeship" risks compromising the quality of the PhD degree in favor of the short term benefit of "grooming" students for entry into chosen professions.

As I discussed in the first section of this post, a complete education involves a combination of technical and intellectual training. Without a firmly established ability to generate and test independent hypotheses, an advanced education would be incomplete. After all, as "PhD" stands for "doctor of philosophy," is it an unfair expectation that those holding such a degree should be capable of generating and testing their philosophies - even when they differ from more conventional thinking? Without new thoughts and ideas, progress will come to a complete standstill. That having been said, I have not been in the academic setting for many years and cannot evaluate the current trends beyond what is reported. I can only hope that the quality of advanced education today remains as high as it was when I received my PhD.

Returning to the question of whether we are training too many PhDs, the ability to think is not restricted to an individual field of thought. If one is capable of imagining, endless possibilities become available. This applies not only to the advancement of technology, but also to professional development. Yes, the job market is unstable. Yes, there are few available jobs. Yes, there are many unemployed chemists. However, there are numerous areas where creativity can lead to exciting career options - even if not along envisioned paths. As I have communicated throughout this blog, the key to success is not along one path. Today, it is essential to continually learn new skills, reinvent oneself and be adaptable to opportunities presented. From this philosophy, it is not the number of PhDs that we need be concerned about, but rather what we are preparing our PhDs to do. If we train PhDs to think creatively, as I believe we do, there is no limit to what can be accomplished.

Personalized Medicine - Additional Thoughts

2011-02-27T00:30:00.000-08:00

Since my posting on personalized medicine (November 12, 2010), I had many discussions with my colleagues and peers regarding the true utility of genetic screening and the utility of biomarkers in establishing appropriate therapeutic regimens. While many agree with me regarding the promise of this approach, there are some dissenting opinions - most of which limit the reach of personalized medicine to cancer and bacterial infections. Regardless of opinion, a recent presentation by James Sabry (February 17, 2011 - www.growbold.com) would have been of great interest to all camps.

In his discussion, Sabry argued that the success rate for new drug approvals suffers, in part, from heterogeneous patient populations. Specifically, these patient populations include groups that are genetically pre-disposed to be non-responders. If we could screen out these non-responders from any clinical trial, drug response rates are likely to improve and more clinical endpoints will be met. The result, while relevant to smaller patient populations, will be better therapeutic agents. The key to all of this lies with the development of diagnostic tests for pre-screening patients prior to prescribing medications. In the cancer arena, Genentech is taking a lead position with the development of disease-specific antibodies tethered to chemotherapeutic agents. While, at present, this will not address all forms of cancer, I believe that this strategy is moving in the right direction.

The Rx/Dx Model - What it Means for Big Pharma

One of the challenges facing the pharmaceutical industry relates to the market potential of any given product. After all, the drug industry, like any other, is a money-making enterprise with financial responsibilities to investors. As such, the larger the market potential of a given product, the more attractive the program to large companies. To put this in another perspective, it is far easier for a company to earn one billion dollars per year from a single product than it is to earn the same amount from ten products with markets of one hundred million dollars per year. Aside from the reduced number of programs to manage, fewer dedicated personnel are required in areas such as sales/marketing, QA/QC and manufacturing.

In order to obtain blockbuster status, therapeutic agents must target the largest potential patient populations. However, these patient populations are heterogeneous and include various sub-populations - many of which will not respond. From an economic standpoint, this does not matter to business as long as the therapeutic does no harm. However, the waste associated with the money spent on products not benefiting patients is significant. Introduction of companion diagnostics, while beneficial to patients, will likely reduce the potential market size of therapeutic agents resulting in lower profits for drug companies. I FIRMLY BELIEVE THAT THIS SHOULD NOT BE A CONSIDERATION FOR DRUG COMPANIES! After all, if a patient will not respond to a given drug, that drug should not be sold to that patient. In further support of this assertion, Sabry, in his February 17 talk, argued that pharmaceuticals should only be paid for if they work. While such business models don't currently exist, there is a great deal of merit to this argument that can only result in better products.

Regarding the potential reduced markets for diagnostic-coupled therapeutics, this should not be a deterrent to the pharma industry. To the contrary, this paradigm has great potential. If diagnostics can differentiate large populations into smaller responsive populations, they can also define additional patient populations suffering from conditions with unmet medical needs. Furthermore, additional revenue will be realized from the diagnostics which, as a screening tool, will be used on all patients seeking treatment for ailments with established biomarkers. While the number of blockbuster drugs is likely to decline, the Rx/Dx paradigm is a potential gold mine of opportunities poised to improve the efficiency of drug discovery and the overall quality of healthcare to the general population.

Staying Employed, Maintaining Employability and Finding Work

2011-01-27T20:11:00.000-08:00

My apologies for the delay since my last post. Between the holidays and some major networking opportunities, my time has been very scarce.

In my last post, I reached out to you to learn what topics you wanted me to address. Among them was a series of questions focused on developing skills that are not "outsourcable" in today's global market. To directly address this question, I believe that all skills are essentially "outsourcable." However, that does not mean that all skills will be outsourced. There are a tremendous number of activities, necessary to the operation of a successful business, that are more efficient (based on time, money and logistics) when not outsourced. Among these is the ability to efficiently manage, maintain and troubleshoot projects from remote locations. Certainly, when faced with outsourcing problems, the ability to assess and correct without having to be on site is marketable.

While managing outsourced activities is a useful skill, this does not help undergraduates as they are not typically in positions requiring management of outsourced chemistry. Instead, I refer back to my assertions in previous posts that, at least in the drug discovery arena, the broadest knowledge/skills in organic synthesis are essential. Such skills, however, cannot be obtained through the requisite course material. Undergraduates seeking to expand their organic chemistry skills have to seek additional educational resources such as undergraduate research and industry-relevant summer internships.

While summer internships may introduce young chemists to industrial environments, they actually do little to provide broad educational experiences. However, finding a mentor via undergraduate research programs will. This is, in fact, how I prepared myself for graduate school. When I realized that I wanted to specialize in organic chemistry, I approached Professor Henry Rapoport. He was highly receptive to my joining his group. Through that experience, I began studying heterocyclic chemistry and explored the conversion of amino acids to 4-amino-4-deoxy sugars. Additionally, I was introduced to my first medicinal chemistry project - preparing rigid analogs of the glaucoma drug pilocarpine.

While there are many valuable skill sets, trends in outsourcing will continue to advance and decline - based on corporate needs, perspectives and strategies. However, the underlying knowledge required to navigate this "employment at will" environment will always be rooted in the foundation and breadth of acquired education.

Maintaining Employability through Networking - A Self-Taught Skill

While the preceding paragraphs emphasized the value of a strong education, they did not focus on skills important to finding and maintaining employment. Among the most important is networking. Sure, while social groups such as Facebook, Linked-in and Twitter can provide some resources, the greatest networking activities involve face-to-face introductions/conversations. These must also be accompanied by diligent follow-up.

For me, the first two weeks of January were packed with networking opportunities. The first was the JP Morgan Healthcare Investor Conference. This annual event, bringing together executives and venture capitalists from around the world, is the largest of its kind and conveniently takes place in San Francisco. Following JP Morgan was the New Paradigms for Biotechnology Funding and Development conference. Finally, during the following week, I attended the Personalized Medicine World Conference. Overall, these conferences allowed me to meet numerous individuals including executive recruiters, consultants, executives and industry analysts.

While major networking events, like those just described, present valuable opportunities to expand networks, one must not discount the smaller networking groups which usually meet monthly. The groups I frequently attend include BioSF, Bio2Device Group, BioE2E and BABCN. All of these groups have websites with valuable industry information.

In closing, most of one's success will always depend upon a strong knowledge and skill base. However, There is always a component that directly relates to who one knows and what opportunities are available at any given time. The value of networking will not always be immediately recognized - but when it pays off, the dividends are usually significant.

Organic Chemistry - What Do You Want to Hear About?

2010-12-05T23:06:00.000-08:00

Dear Readers,

For over a year, I have been posting my thoughts on organic chemistry issues from both academic and industrial perspectives. While the press emerging from many news agencies tends to be negative, I choose to view the chemical industries from a broader and more optimistic perspective. I view these philosophies as both realistic and necessary. After all, if chemistry touches almost every aspect of daily life, it seems illogical that this industry, while suffering in the current economy, will disappear. Furthermore, negative press may tend to dissuade younger individuals from pursuing careers in the life sciences. Through my efforts, I endeavor to convince students that the future will present many new and exciting opportunities.

While this blog generally reflects my thoughts and opinions on subjects I choose to address, I also want to speak to issues important to others. In this vein, I ask you to send me questions and/or concerns relevant to the scope of this blog. I look forward to your queries and the discussions that will follow.

Chemistry and the Teenage Mind

2010-11-17T21:22:00.000-08:00

Today, I had the unique experience of visiting my son's middle school science class. The teacher, as part of the curriculum, is bringing in guests to teach his class about real-world science. I was the first.

In preparation for this class, I thought about how I could impress upon the students the importance of chemistry. Initially, I thought about discussing anecdotes from my childhood that reflected my interest in science. However, realizing that some of my "experiments" were extremely dangerous and certainly not executed under adult (or parental) supervision, I opted to omit details in this area. After all, I did not want to give ideas to these young and impressionable (and somewhat unpredictable) teenagers. After some thought, I decided that a two-part discussion was appropriate. The first part was to focus on how chemistry impacts everyday life and the second part was to be a brief presentation based on one of the drug discovery projects I worked on.

When I was introduced to the class, I initially took questions from the students. These generally related to what my area of expertise is and what are the steps involved in the discovery of new medicines. These questions, as they related directly to my slide presentation, were tabled until the second half of the class.

The second half of class was uneventful. I described the drug discovery paradigms of past and current years along with exploratory research relating matrix metalloproteinase inhibitors to inhibitors of endothelin converting enzyme. The students were engaged and sufficiently grossed out when I discussed studying urine and feces for drug-related metabolites. While this discussion gave them a flavor for the exciting opportunities available to those pursuing careers in the life sciences, the students seemed much more enthusiastic about the chemistry in everyday life challenge presented in the first part of my visit.

Teenagers, by nature, take a great deal for granted. They are quite reliable in their abilities to not think about where things come from. For example, money comes from parents, toilet paper comes from Costco, gasoline comes from gas stations and food/medicine comes from stores. So, when I presented the possibility that chemistry was everywhere, the students actually thought about this idea. As a follow-up, I went around the class asking each student to name something that they felt was not related to chemistry. Interestingly, at least one fourth of the class felt that chemistry was everywhere. The other students managed to come up with rather creative questions. Such questions tended to involve biological processes (vision and movement of limbs) rather than materials. Still, realizing that biology involves numerous biochemical reactions, these questions were relevant.

Towards the end of this discussion, I directed the students to consider materials. A door, for example, is made of wood. The wood is held together by glue, laminated with a coating and stained to a desired color. While the wood may be from a natural source, agriculture plays an important role in obtaining such products. Thus, the finished door was the direct result of chemical substances including:

adhesives (glue)
pigments (stain)
polymers (laminate)
pesticides

As a direct result of this conversation, the class understood that chemistry does, in fact, impact practically every part of our daily activities including, but not limited to:

clothing (polymers, pigments)
toothpaste/soap/shampoo
food (pesticides, ingredients, preservatives, packaging)
water
medicine
building materials
cars
roads

Regarding the roads, one student suggested that if a road was made by hand using only gravel found on the adjacent hillside, and the road was only used by people walking barefoot and naked then there would be no chemistry involved. No chemistry, that is, except for the natural mineral composition of the gravel.

So, chemistry is truly everywhere.

Personalized Medicine - Treating the Patient vs Treating the Disease

2010-11-12T09:03:00.000-08:00

Through the evolution of the drug development process, many factors have been changed and policies adjusted to improve safety, to assure quality and to prove efficacy. Much work in this area was driven by a core philosophy, enforced by the FDA, that in order to protect patients, medications must be proven both safe and efficacious. In order to prove these claims, drug candidates are subjected to rigorous assays designed to assess the following responses in various patient populations:

maximum tolerated dosages
potential adverse effects (both chronic and acute)
disease/disorder/symptom response

Throughout this process, certain parameters must be standardized in order to design feasible animal and human protocols because the physical traits among animal and human populations are heterogeneous. Examples of such traits include metabolism and body weight.

Metabolism relates to the speed at which a therapeutic agent, once introduced into the body, is eliminated. Based on an individual's dietary habits and genetic profile, metabolic rates can range from rapid to slow. Such variances are often reflected in body weight where individuals with rapid metabolism may weigh less than those with slow metabolism. Where pharmaceutically active substances are concerned, patients with high metabolic rates will eliminate these agents more rapidly than those with slow metabolic rates.

Body weight is not necessarily a result of dietary habits. It is, in many cases, dependent upon an individual's genetic profile. While body weight is not necessarily an indication of one's health, it does impact how one will respond to pharmaceutically active substances. For example, a heavy person will generally be able to tolerate more alcohol consumption than a leaner companion. This effect easily translates to medications where a given dosage will induce a stronger pharmacological response in a leaner individual than in a heavier person.

Thus, from the simple perspectives of weight and metabolism, it is easy to see that all patients are not the same - even if they present with similar symptoms. If this is the case, why does the pharmaceutical industry market medications in a one-dose-fits-all paradigm? The answer is very simple. It is not practical to produce an individual dosage for an individual person based on the biological variables within our heterogeneous population. Medications must be standardized based upon the maximum tolerated dosages and then recommended for patients presenting with symptoms classifying them as suffering from a common disease/disorder. In this manner, the pharmaceutical industry has historically targeted the disease and not the patient. With advancements in personalized medicine, all that is changing.

Genetics - Links Between Patient Populations and Drug Efficacy

While weight and metabolism may explain the extent of a patient's response to a given medication, these factors provide little information as to why one patient with a given set of symptoms responds to a given therapeutic while another patient with a similar set of symptoms shows no response to the same treatment. In many cases, the cause of such variances in response rates lies within an individual's genetic code. Thus, in order to truly treat the patient, an understanding of genetics is essential.

Today, there are few examples of truly personalized medicine. One notable exception applies to breast cancer. While breast cancer is commonly classified as a single disease, it is actually a family of diseases - all affecting breast tissue. Because different types of breast cancer have different genetic profiles, specific biological markers have been identified which help to determine appropriate therapeutic regimens. One potential component of such regimens is the drug herceptin.

Herceptin is a monoclonal antibody targeting HER2 proteins. When a breast cancer cell line overproduces HER2, introduction of herceptin to the chemotherapeutic regimen increases both survival time and response rate compared to chemotherapy without herceptin. Furthermore, when the cancer is not HER2 positive, there is no significant therapeutic benefit to the use of herceptin. Thus, herceptin represents an example of a medication useful for a specific form of breast cancer in a specific population of patients.

While most new medications are still targeting the diseases, the concept/philosophy of personalized medicine is the driving force behind a new wave of interest in the biopharmaceutical industry. Since the first sequencing of the human genome, the time required for a complete human genetic profile has been reduced from years to days. Furthermore, the costs associated with genetic sequencing have been proportionately reduced. One leader in these endeavors is Pacific Biosciences - a company dedicated to the development of real-time genetic sequencing.

One problem slowing the realization of truly personalized medicine is the lack of information on genetic variations throughout human populations. In this area, efforts are underway to catalog genetic diversity amongst thousands of individuals. Pilot data has already revealed more than 15 million genetic differences in a population of only 179 people from various populations (C&EN Nov. 1, 2010, pg 8). Furthermore, each individual was found to average from 250-300 genetic mutations preventing normal gene function and 50-100 gene variants implicated in congenital disorders.

While true personalized medicine is still on the horizon, adoption of this philosophy to the life sciences is creating new opportunities in fields including:

cell biology
genetics
drug discovery
diagnostics

Through personalized medicine, our understanding of diseases will be improved, patients will receive appropriate medications and side effects will be reduced - resulting in better healthcare for all.

Consulting in Biopharma

2010-10-19T15:45:00.000-07:00

Just a quick note today. I was recently asked to describe my experiences as a consultant. Part 1 and part 2 of the resulting interview are posted on the Chemjobber blog.

New Paradigms in Drug Discovery

2010-10-15T16:08:00.000-07:00

With ongoing uncertainty in the economy, two issues impacting potential rebounds in industry are:

the lack of new funds available for investment, and
the need to deliver a rapid return on investment capital.

There is perhaps no sector impacted more by these two issues than pharmaceuticals. The reasons are in fact quite plain. Products cannot be advanced from research through the clinic without appropriate funding. Furthermore, the drug discovery process is inherently slow requiring up to 15 years for successful programs to reach market. As I have discussed in various postings, these issues, while formidable, can be addressed through creative business models. In this vein, at the ACS meeting in Boston, I learned of Lilly's PD2 program. This effort, effectively recruits small companies and academic laboratories by offering free and confidential compound screening with the intention of mining this chemical space for potential products to develop and/or potential collaborative relationships.

The PD2 program is innovative in that it utilizes the broad capabilities and chemical space provided by a broad network of settings for the purpose of advancing its drug discovery pipeline. Within the parameters of this program,

potential collaborators submit compound structures to a confidential on-line evaluation tool
following evaluation of submitted structures, those deemed interesting to Lilly's programs are selected for screening
following screening of interesting structures, those with promising activity profiles become subjects for collaborative development activities

If you are a small company or an academic group with limited screening capabilities, how can you lose? This is especially important regarding compounds that are not of interest to Lilly - companies/academics retain all IP rights. In the end, small companies/labs with limited resources identify potential development partners and Lilly gets to enhance its research/development pipelines. From the corporate perspective, this is truly a win-win scenario providing a new dimension to the paradigm shift impacting today's pharma/biotech sector.

Corporate Win-Win Scenarios - Where do Employees Fit In?

Looking at PD2 from inside of Lilly's corporate headquarters or from within the labs of a potential small company collaborator, compounds are changing hands and the no-cost synergistic resources available are enough to entice business personnel from both entities to enter into mutually beneficial contractual relationships. However, if viewed from above, one can see a slightly different scenario. On one side, small company scientists engaged in drug discovery activities find a sense of security through potential interest from big-pharma. On the other side, the potential influx of developable compounds might induce Lilly's drug discovery infrastructure to question its long-term importance to the company. After all, if Lilly can obtain drug discovery services for free, why should it employ its own efforts?

The above argument, while presenting a black-and-white picture, does illustrate a trend towards new paradigms in the pharmaceutical industry. Such paradigms clearly depend upon research activities. However, such research activities are executed through peripheral organizations and not within the infrastructure of parent companies. Nobody disputes the fact that without research, there can be no development pipelines. The only real questions are:

Who does the research?
Where will research activities be located?

While research activities will always require the talents of skilled and knowledgeable scientists, the location of such activities is still a point of discussion. As I mentioned in previous posts, research infrastructure is very expensive to maintain - especially when priorities shift to development. On the other hand, the ability to draw on research infrastructures without the umbrella of long-term commitments provides an attractive option to parent organizations invested in the success of drug development activities. Through decentralized research models such as PD2, scientists will be able to continue producing cutting-edge research and, at the same time, feed the development pipelines of companies possessing the financial resources capable of bringing new therapeutics to market.

The Pharmaceutical Industry - The Economy and The Press

2010-09-16T09:54:00.000-07:00

Over the past several months, articles appear in the news describing the bleak state of various industries contributing to the overall economic and employment situation facing both future graduates and workers of today. One such article, "The 10 American Industries That May Never Recover," was on Yahoo this morning. In this article, the pharmaceutical industry was listed as number 5. The bleak outlook presented read as follows:

"This industry has bled workers for three years, and that trend is likely to continue. The largest companies in the sector, such as Pfizer and Merck, have a number of blockbuster drugs that have lost their patent protection in the last decade. They have other pharmaceuticals that will lose that protection in the next decade. Sales of most of these drugs will move to generic companies that will sell them for far less, and erode critical revenue sources for the huge pharma firms. Most companies in the industry admit that they cannot replace the drugs that go off patent fast enough to keep their revenue high. The other reason employment in the sector will stay down and may drop further is that big drug companies are merging to save costs, and most of those costs are people. Pfizer has cut 30,000 people since the start of the recession. Merck has cut 25,000, and these companies and their peers expect that they will have to bring down costs even more."

While there is first amendment protection regarding freedom of speech and press, such abbreviated analyses of the present situation provide a far gloomier picture than what can be obtained by applying just a little rational thought. After all, among all of my colleagues and connections, no one is suggesting that the pharmaceutical industry will collapse altogether. Furthermore, there remains considerable need for the discovery of new and better therapeutics addressing indications for which there is an unmet medical need. As long as there is a need, there will be a market.

In looking at the above analysis of the pharmaceutical industry, the author is correct regarding the downsizing trend affecting this sector. Furthermore, with major products subject to patent expiration, this trend is likely to continue - at least in the short term. However, a greater understanding of the industry should provide hope. With products losing patent protection and becoming generic, one of the first casualties is sales and marketing. Employment in these areas is dependant upon two areas - currently marketed drugs and drugs soon-to-be marketed. With research pipelines being downsized to focus on development, the development pipeline has a limited lifetime. This trend would lead to the conclusion that employment in drug development may suffer. However, without research, there will be no new products to develop or market.

While research has been a primary casualty over the past 3-5 years, many experts (professionals and recruiters) are beginning to see a change in the market. This should bring some hope to those preparing to enter the workforce. To those graduating with BS/MS degrees, jobs have always been more abundant. To those completing PhD work, a little more time may be necessary before reasonable opportunities present themselves. In today's economy, pursuit of postdoctoral research activities may provide the necessary time and additional experience necessary to enter the workforce from the most competitive perspective.

The Pharma Industry Casualties - WHAT IS THERE TO DO?

The above discussion, while providing hope to those entering the workforce, does not really address the problem faced by the thousands of scientists who have lost their jobs due to downsizing, outsourcing and company closures. To this sector, I refer to the many previous posts I have published regarding maintaining up-to-date and diverse skill sets. There is work out there and one must be creative in order to identify the appropriate opportunities. Do not be hesitant to try your hand at consulting or applying your skills to related industries. Such industries include:

agrochemical
food
textiles
polymers
biofuels
medical devices
patent law
contract research organizations

While it may take some time to adapt to different industries, or to build a consulting practice, the payoff will be recognized in the diversity of new skill sets. Most importantly, it is critical to maintain a level of visible activity within your chosen sector. Potential employers will recognize continued efforts and creative thought. Remember, in today's economy, there are plenty of reasons for not getting paid. However, there is no excuse for not working.

Pharmaceuticals and Food Products - Regulation and Marketing

2010-09-14T15:50:00.000-07:00

Over the past few days, news has emerged focused on two areas of high importance to consumers - pharmaceuticals and food products. From the pharmaceutical side, attention focused on Genentech's Avastin and its potential as a cancer therapy. While approved for the treatment of lung and colon cancer, Avastin was also being marketed for the treatment of breast cancer - an indication not supported by clinical trials. This issue, covered in detail by Ed Silverman (see "BCA's Brenner: Avastin and FDA Approval Standards", Pharmalot, 9/14/10), goes hand-in-hand with a post by Derek Lowe (see "A New Way to Approve Drugs", In the Pipeline, 9/14/10) focused on new paradigms for accelerated drug approval through the combined use of biomarkers, conditional approval and adaptive clinical trials. I will not comment further on these areas, instead referring to the referenced posts, except to say that there still remains significant issues regarding pressure leading to premature drug approval and marketing to consumers.

From the food product side, recent news indicating that manufacturers of high fructose corn syrup are petitioning the FDA to rename the product "corn sugar" have emerged. Particularly appalling is the report that "two new commercials try to alleviate shopper confusion, showing people who say they now understand that whether it's corn sugar or cane sugar, your body can't tell the difference. Sugar is sugar." Let me make my perspective absolutely clear - THIS IS A COMPLETE DECEPTION! To back up this statement, the term "sugar" is loosely used to describe the class of organic molecules known as simple carbohydrates. More commonly, the term "sugar" relates to table sugar (sucrose, produced from sugar cane or sugar beets). Sucrose is one example from a class of molecules known as disaccharides (chemically joined combinations of two monosaccharide units). The monosaccharide (simple sugar) units making up sucrose are glucose and fructose.

High fructose corn syrup, obtained from corn starch, begins primarily as glucose. Enzymes are then added to convert the glucose into fructose. The resulting product is a mixture of two separate monosaccharides - glucose and fructose. This mixture is different from sucrose because the glucose and fructose molecules are not chemically bound to one another. It is interesting to note that fructose is not even the major sugar component isolated from corn - its presence in corn syrup is ENHANCED THROUGH ARTIFICIAL MEANS.

Reasons for wanting to include fructose in food products include cost of production and sweetness. High fructose corn syrup is cheaper to produce than sucrose due, in part, to corn subsidies. Regarding relative sweetness compared to sucrose, glucose is less sweet and fructose is almost twice as sweet.

In biology, glucose plays important roles in energy and metabolism. In fact, it is critical to the production of proteins and lipids and is a precursor to the production of vitamin C. Fructose has no such biological roles. Additionally, while fructose is introduced into our bodies through consumption of sucrose, this introduction is the result of natural sucrose metabolism. Consumption of high fructose corn syrup essentially results in flooding our bodies with a non-essential and non-nutritive sweetener. DOES THIS MAKE SENSE? DO WE REALLY WANT TO FEED THIS CONCOCTION TO OUR CHILDREN? The food, candy and soft drink industries were doing just fine before high fructose corn syrup. Certainly, we can do without it today.

Science and Ethics - CAN WE DO IT? vs SHOULD WE DO IT?

At the Boston ACS meeting, I had the pleasure of speaking with Professor Roald Hoffmann. Our conversation centered around the principle tenants of his lecture that morning entitled "Science and Ethics: A Marriage of Necessity and Choice for the Millennium." During his speech, Professor Hoffmann focused on public suspicion of science relating to ecological, environmental and ethical/moral issues. Of these three areas, I would like to focus on ethical/moral considerations.

In his lecture, Professor Hoffmann stated that "The invention or implementation of a tool without consideration of the consequences of its use is deeply incomplete. Science is not ethically neutral." He went on to say that "we must consider potential abuses of our well intended work." While both of these statements are absolutely true, scientists are also humans and subject to the same human flaws as the rest of society. This is never more apparent than when we make plans for selfish purposes or simply because there is a high likelihood that such plans can be successfully executed. From this philosophy, consider the following:

We can plagiarize or falsify data, but we shouldn't.
We can generate harmful chemical or biological warfare agents, but we shouldn't.
We can withhold negative clinical data from regulatory agencies, but we shouldn't.
We can promote pharmaceuticals for unproven off-label use, but we shouldn't.
We can promote herbal remedies and dietary supplements for unproven health benefits, but we shouldn't.
We can argue the equivalence between natural substances and manufactured alternatives, but we shouldn't.

For all of the above, there are examples highlighted by the press. Certainly, such examples are exceptions rather than common practice. However, such exceptions, when impacting high profile topics such as food and medicine, have the potential to make big headlines. As alternatives to the above, consider the following - all of which are standard practices:

We can maintain high ethical standards in all publications, and we should.
We can generate useful chemical and biological agents for the benefit of society, and we should.
We can fully disclose all clinical data to regulatory agencies, and we should.
We can promote pharmaceuticals, herbal remedies and dietary supplements for proven health benefits, and we should.
We can anticipate the potential for abuse of pharmaceutical and biological agents, and we should.
We can focus our efforts on commercialization of products for constructive uses and not simply because we can make money, and we should.

Whether arguing for Avastin as a treatment for breast cancer or that high fructose corn syrup is the same as table sugar, such examples do nothing more than degrade the trust that is essential between the public and the scientific community.

Academic Institutions and Drug Discovery - New Perspectives

2010-08-28T21:02:00.000-07:00

Last September, I posted a blog (Academic Institutions and Drug Discovery, 9/30/09) focused on the question of where the next generation of drug candidates will emerge. In that post, I described a movement to utilize graduate research programs as drug discovery engines. I also described why I believe that "this is a very bad idea." I still hold strongly to that philosophy and maintain that academic institutions are best suited for education. Any retooling to support commercial efforts as primary activities will serve little more than to dilute the quality of the education provided to graduate students. Notwithstanding, there has been a steady emergence of medicinal chemistry research emanating from academicians. This is perhaps most noticeable when browsing the poster sessions at the recent American Chemical Society meeting in Boston.

Since the beginning of my affiliation with the American Chemical Society, I have consistently paid dues to the division of organic chemistry and the division of medicinal chemistry. Both divisions had solid strengths and identities. Specifically, the division of organic chemistry provided a forum for academic institutions to highlight the most cutting edge developments in organic chemistry - whether total syntheses, new methodologies or the identification of novel natural products. On the other hand, the division of medicinal chemistry provided an appropriate forum for the presentation and discussion of efforts emerging from industry. This division made a great deal of sense - especially since these complementary divisions frequently collaborated on symposia where the bridges between organic and medicinal chemistry could be highlighted.

One particular observation from last week's meeting in Boston centered around the fact that the distinctions between the organic and medicinal chemistry divisions are becoming blurred. I am not implying that the quality of the contributions is suffering. Walking through the organic posters, the strength of the research presented is clearly represented by the diversity of work emanating from academic institutions worldwide. What truly surprised me was the number of academic institutions presenting posters in the division of medicinal chemistry. I estimate that academic posters exceeded industrial posters by at least 60%. Based on my previously published convictions, I am concerned with this trend. So, if academic institutions insist on supporting drug discovery programs, how can these activities support education and not result in diverting efforts away from the cutting edge research essential to the training of the next generation of scientists?

Dual Purpose Chemistry - The Merging of Education and Drug Discovery

At the Boston ACS meeting, I attended a session on the concept of open-source chemistry. In one lecture, I learned about the Distributed Drug Discovery (D3) effort developed by researchers at Indiana University-Purdue University Indianapolis. The model was loosely compared to the SETI project in which computers around the world, not in use by their owners/institutions, were used to analyze data. Applied to chemistry, this translates to the use of undergraduate laboratory activities simultaneously being used to generate compounds for biological evaluation.

Before going deeper into this topic, when I was an undergraduate at the University of California - Berkeley, solid supported chemistry was in its infancy. There were a few supports (Wang resins, TentaGel resins) being studied for use, but mainstream combinatorial chemistry was still a few years off. Notwithstanding, Affymax was one of the first companies to emerge using this technique for commercial purposes and the resulting libraries were generally limited to peptides.

As the field of combinatorial chemistry developed, new solid supports became available - many of which were complemented by novel deconvolution techniques allowing for the identification of a single structure amongst millions. Furthermore, techniques became available for the generation of compound libraries via parallel synthesis of discreet compounds. No matter which approach, combinatorial chemistry, in general, is limited because only a subset of chemical reactions are compatible with the solid supports essential for generation of compound libraries. That being said, combinatorial chemistry is now considered a valuable tool for the mining of structural space in order to identify potential lead molecules suitable for further structure-activity analysis.

With the utility of solid phase chemistry to industrial applications, it is not surprising that undergraduate programs are beginning to teach these techniques in their educational labs. As such, it seems logical to simultaneously and peripherally involve undergraduate students in drug discovery efforts. Through the D3 effort, students are expected to prepare a library of six compounds using solid-phase parallel synthetic techniques. In this program, each student prepares the same reference compound along with 5 unique compounds. If the reference compound is correct, the assumption is that the novel compounds were prepared as expected.

Because target compounds are designed using the combined computational power of multiple personal computers around the world (similar to the SETI efforts), these efforts are truly open-source in nature. Through these efforts, Professor William Scott and Professor Martin J. O'Donnell have successfully introduced a way to utilize academic institutions for drug discovery activities without compromising the education process. In fact, these activities only add to the educational experiences of numerous undergraduate chemistry students. Through this type of creativity, I believe that solutions to the difficult issues at the heart of early-stage drug discovery can be found.

Knowledge and Experience - Answers to Questions from Soon-To-Be-Graduates

2010-07-26T11:09:00.000-07:00

We are now in the middle of summer and many of those participating in the career networking session of January's CSU Biotechnology Symposium have graduated. As this class, and those following, come to the realization that today's economy presents significant challenges to those entering the workforce, questions regarding required knowledge and experience become relevant. As I address the last group of questions raised at the symposium, it is important to understand that knowledge and experience are very subjective metrics. Many skills can be obtained on the job while other skills require advanced training and/or further education. The best advice I can offer to those of you entering the workforce is for you to evaluate what you want to do and then to make sure that your knowledge and experience is current and reflects the state-of-the-art of chemistry-related technologies. There is a great deal of competition for jobs today and your greatest assets live within the breadth and depth of your skill sets.

How important are analytical techniques (NMR/HPLC/MS/etc.) for new hires?

In industries dependent upon chemistry and biology, solid understanding of modern analytical techniques is essential. Specifically, nuclear magnetic resonance (NMR) spectroscopy is the workhorse technique used to prove molecular structures. High pressure liquid chromatography (HPLC) is important to assess chemical purity, to purify chemicals and to identify chemical components in complex chemical or biological mixtures. Mass spectrometry (MS) provides information regarding molecular weights of pure chemicals or, when used in conjunction with HPLC, helps to identify components of interest in complex mixtures.

While the instrumentation utilized among various companies varies, the type of data generated will be more consistent. Therefore, it is more important to understand the basic principles associated with data analysis than it is to know how to operate the instruments. Instrument operation is learned on the job but understanding data requires more in-depth knowledge and education.

What opportunities exist for BS/MS level chemists in this economy?

Throughout the pharmaceutical industry, there has always been a greater demand for BS/MS level contributors compared to candidates with higher degrees or significant years of experience. This trend reflects the hierarchical nature of organizational charts where those with more experience generally manage those with less experience. In today's economy, corporate structures are generally the same as those in better economies. The difference lies with the size of corporate structures. In lean economic times, there are fewer opportunities available across the board. The good news is that, compared to senior level contributors, research associate candidates are in higher demand.

In short, there are opportunities for BS/MS level chemists in today's economy. However, candidates for these jobs must be able to present themselves as the most qualified and knowledgeable candidates available if they are to be competitive.

What are the requirements for an entry level chemistry job?

Requirements for entry level chemistry jobs in the biopharmaceutical industry vary depending upon the needs of a given program. I have personally hired individuals with BS, MS and PhD degrees. At the BS level, I generally look for individuals who have significant laboratory experience beyond laboratory coursework. This experience can be obtained through working with a professor as an undergraduate researcher, working as a summer intern or working in a company environment.

At the MS level, most candidates have some academic research experience. When hiring MS level candidates, I generally look for a documented abilities to independently follow protocols and to work in a laboratory environment with minimal supervision.

At the PhD level, candidates should be able to demonstrate their abilities in working independently in a laboratory environment, identifying/solving problems and evaluating the direction of their projects based upon emerging data.

How do supervisors interact with BS/MS level chemists in the lab?

I cannot speak for all supervisors in this area. However, having interacted with many BS/MS level chemists, I can describe the way I work. From my perspective, all members of my team are valuable contributors. Regardless of the level of experience, I always emphasize that my direct reports work with me and not for me. I try to give each member of my team ownership over various aspects of our projects. Through this structure which focuses on collaboration and empowerment, I have had tremendously successful and productive team relationships.

How can I learn more about molecular modeling?

Molecular modeling/computational chemistry is a technique used to predict the structure and properties of chemicals, enzymes and polymers using computer algorithms. When applied to medicinal chemistry, computational chemistry can provide insight into the binding modes of potential inhibitors as they interact with enzymes. Use of this tool has the potential to speed up the drug design process and guide chemistry efforts to more potent and useful compounds.

Many universities offer degrees in computational chemistry - both at the MS and PhD levels. For independent study, two recent books were published addressing the principles of molecular modeling:

Molecular Modelling for Beginners

Molecular Modeling: Basic Principles and Applications

With this posting, I have now addressed all of the questions raised during my participation in the career networking program at January's CSU Biotechnology Symposium. I hope that my answers have been helpful. Moving forward, as I continue writing this blog, I am happy to address topics raised by my readers and look forward to hearing your thoughts.

Empolyment Opportunities Part 2 - Answers to Questions from Soon-To-Be-Graduates

2010-06-03T22:56:00.000-07:00

In these challenging economic times, it is natural to wonder where employment opportunities can be found. This question is not unique to the many students preparing to enter the workforce. In fact, everyone working to protect their career options, from the gainfully employed to those seeking new employment, is continually evaluating options. In my last post, I began addressing questions focused on employment opportunities. In this post, the following questions raised by graduating life sciences students are addressed:

Are part time opportunities with tuition assistance available in pharma/biotech companies?
For new hires, what degrees are more valuable - organic chemistry or medicinal chemistry?
Is there job security in the life sciences?
What are the trends in outsourcing?

Are part time opportunities with tuition assistance available in pharma/biotech companies?

Having worked for companies of varying sizes, benefits extended to employees can vary widely. The larger organizations I have seen, having more available operating capital, tend to be more generous regarding career development benefits. Some even offered tuition reimbursement programs to employees wishing to enhance their skill set through education. However, such programs did not include provisions for part-time work. While I am sure that arrangements of this type are available, they are not common and employees eligible for tuition assistance programs should be prepared to study at night while working full time.

For new hires, what degrees are more valuable - organic chemistry or medicinal chemistry?

This is an excellent question because while most research universities offer degrees in organic chemistry, degrees in medicinal chemistry are also available. In my post of September 30, 2009 (Academic Institutions and Drug Discovery), I addressed this question in detail and stand by my assertion that organic chemistry degrees are far more valuable to drug discovery efforts than degrees in medicinal chemistry.

Is there job security in the life sciences?

While some employment is associated with unions, most jobs - including those in the life sciences - are not. However, even with union-backed employment contracts, the nature of at-will employment virtually assures that employment is not guaranteed to those working at a given company. Furthermore, in today's climate of mergers and acquisitions, job security is non-existent.

While we cannot count on any level of job security, there are steps we can take to preemptively enhance our employability as we transition from one job to the next. In my posting of August 21, 2009 (Maintaining Marketability in a Shrinking Job Market), I talk at length about employment trends and the opportunities they provide. Remember, while jobs come and go, we all have the ability to adapt and enhance our skill sets to meet the needs of our future employers. It is our responsibility to develop our careers if we want to continue to be employable.

What are the trends in outsourcing?

In my post of October 25, 2009 (Chemistry Outsourcing - New and Challenging Career Opportunities), I discussed outsourcing in great detail.

In today's industrial climate, there is likely to be more dependence on outsourcing as a means of slowing cash burn rates and minimizing the need for dedicated infrastructure. However, I do not see this as a sustainable alternative to the development of novel technologies at dedicated facilities controlled by parent companies. If we are to maintain a competitive edge in a global marketplace, it is essential that we maximize productivity and fully control all intellectual property supporting our innovations. In the meantime, outsourcing provides novel opportunities for the management of complex and diverse infrastructures - in many cases, extending across cultures. Such opportunities should be embraced, as associated skill sets are broadly valued throughout the biopharmaceutical industry.

Empolyment Opportunities Part 1 - Answers to Questions from Soon-To-Be-Graduates

2010-05-15T21:32:00.000-07:00

Due to the current turmoil with the economy and job market, many of my postings focus on areas where chemistry expertise is a desirable commodity. While these discussions broadly focus on different industries and technologies, there are many employment-related issues I have yet to discuss. Many of these were, in fact, brought to light at January's CSU Biotechnology Symposium. As a career mentor, I was asked many good questions by life sciences students approaching graduation. Those of you who follow this blog know that I have been addressing these questions over the past few months. Beginning with this post, I will focus on those questions specifically related to employment opportunities. The specific questions to be addressed are:

What will industrial employment opportunities look like in the next 5 years?
What is the future of in-house dedicated medicinal chemistry programs?
Are opportunities available in pharma/biotech for people with experience outside of the life sciences?
Are part time opportunities with tuition assistance available in pharma/biotech companies?
For new hires, what degrees are more valuable - organic chemistry or medicinal chemistry?
Is there job security in the life sciences?
What are the trends in outsourcing?

In this post, the first three of these are answered.

What will industrial employment opportunities look like in the next 5 years?

As most people are aware, the industrial landscape in biotechnology and pharmaceuticals is undergoing massive transition. This cannot be more apparent than through the trend of layoffs that began approximately five years ago and continues today. Recent examples include the closure of Xenoport and a 40% downsizing of Exelixis. Thus, it is understandable that significant students entering the workforce do so with some trepidation. In order to maintain focus, all employees must understand that JOB SECURITY IS ONLY AN ILLUSION. Once this fact is realized, it becomes easy to embrace the possibilities presented through a career that not only spans many years but also extends across many companies. The breadth of experience to be had through career growth and development truly dwarfs that available to individuals dedicated to the same corporate organization for the full tenure of their professional careers. This would not be possible without some instability in the job market. I, myself, have been employed by four different companies - all of which have been shut down. Being again on the hunt for new employment, I embrace the potential opportunities and look forward to entering the next phase of my career - whatever that may be.

Regarding the employment outlook over the next five years, I believe that that landscape will look very much like that of today. Our society and economy have long evolved away from the model of dedicated employment for the duration of one's career. In the wake of this evolution, we are forced to protect our professional aspirations by the continual expansion of skill sets. I cannot emphasize enough the importance of performing both within and outside of comfort zones in order to establish expertise that is valuable to both current and future employers. Finally, all wishing to contribute their talents to industrial activities must be open-minded regarding where and how to express their interests and exercise their expertise.

What is the future of in-house dedicated medicinal chemistry programs?

Having served as a medicinal chemist since the beginning of my career, I have seen the role of outsourcing slowly increase. Presently, significant outsourcing efforts are utilized to supplement the activities of in-house chemists. In addition, many small companies rely solely on outsourced chemistry as a means of meeting their needs. Reasons for this trend include less overhead dedicated to laboratory facilities and reduced commitment to dedicated personnel. However, there are some factors that strategically preclude some companies from fully utilizing contract organizations in favor of in-house activities. These include protection of intellectual property and the development of more rapid solutions to project-critical activities. With both of these viewpoints in mind, I believe that there will always be a need for dedicated in-house chemistry (or its equivalent) where such dedicated resources lay groundwork enabling optimal use of supplemental contract synthesis programs.

Are opportunities available in pharma/biotech for people with experience outside of the life sciences?

This is an excellent question. While the vast majority of pharma/biotech opportunities require relevant experience, there are some that can fall outside of this paradigm. Such opportunities, however, are not likely to fall within drug discovery/development efforts. These opportunities are more likely found in areas such as:

human resources
facilities management
environmental health and safety
finance/purchasing
IT support
program management

All of these roles are critical to successful business operations and should not be discounted. In fact, many opportunities in these areas require advanced degrees and/or significant years of experience in order to be efficiently executed. Finally, careers in these areas can have advantages because they are fully transferable from one industry to another, whereas individuals with life sciences expertise are generally committed to careers within life sciences companies.

Medicinal Chemistry Part 3 - Answers to Questions from Soon-To-Be-Graduates

2010-04-14T20:50:00.000-07:00

In this post, I am returning to questions asked at January's biotechnology symposium. In particular, the final two medicinal chemistry questions are addressed. These questions are:

What is the impact of small protein design?
What are the advantages/disadvantages of biologics vs small molecule drugs?

Future postings will address questions relevant to employment opportunities as well as what kinds of knowledge and experience are helpful in the biopharmaceutical industry.

What is the impact of small protein design?

Proteins are highly complex structures assembled by nature from the complement of naturally occurring amino acids. The complexity of proteins comes not only from the structural diversity of the amino acid residues contained in the protein chain, but also from the secondary structure obtained as the protein chain folds into its biologically relevant conformation. To this end, many academic research groups are studying how various amino acid sequences fold into the different structural motifs found within proteins and enzymes. Additionally, many software platforms were developed to help predict how proteins fold.

With the complexity associated with amino acid sequence and secondary structure, it seemed somewhat unlikely that amino acid sequences can be designed to both fold like proteins and induce an intended biological response. However, in 1997, at least this first part was realized. As reported (J. Am. Chem. Soc. 2007, 129, 1532) Professor Alanna Schepartz and her group succeeded in designing a synthetic protein sequence capable of folding in much the same was as natural proteins do. This synthetic protein was prepared from beta-amino acids as compared to naturally occurring alpha-amino acids.

While the design of therapeutically useful synthetic proteins is still a long way off, shorter peptide sequences have contributed to the arsenal of therapeutically useful structures for years. Such peptide-based therapeutics include hematide (treating anemia), integrilin (treating acute coronary syndrome) and natrecor (treating congestive heart failure). To this end, synthetic peptides provide valuable therapeutic agents for indications which, in many cases, have no conventional small-molecule drug alternatives.

What are the advantages/disadvantages of biologics vs small molecule drugs?

Currently, there are two classes of therapeutic agents - biologics and small molecule drugs. Classical drug discovery efforts generally target small molecules (average molecular weight is ~500) as therapeutic agents. These are advantageous because they are generally easy to synthesize and can be administered orally. Furthermore, small molecule drugs can be designed as either agonists or antagonists of biological processes for use against either extracellular or intracellular targets. Unfortunately, small molecules cannot presently modulate all biological targets with the specificity and potency required for useful therapeutics. Additionally, the lead identification and lead optimization processes can be slow for this class of drugs.

Complementary to traditional small molecule drugs is the class of therapeutics collectively referred to as biologics. This class includes proteins, enzymes and antibodies. Such large molecules (molecular weights range from ~10,000-50,000) are generally not suitable for oral administration and must be delivered by injection or infusion. This is inconvenient because these methods of use are generally not compatible with patient self-administration. Like small molecule drugs, biologics are useful as either agonists or antagonists of biological processes. However, unlike small molecules, biologics are only useful for extracellular targets. Additionally, biologics are generally highly selective and highly potent against target processes. Finally, like small molecules, lead identification and lead optimization are very slow processes.

For many years, the pharmaceutical industry focused on small molecule drugs. With the advent of the biotechnology industry, biologics have become increasingly important as evidenced by commercial successes from companies such as Genentech, Amgen and Biogen. Through the combined efforts of traditional drug discovery and the development of biologics, advances will continue to provide treatments for medical disorders providing improved qualities of life for all.

Green Chemistry and Drug Discovery

2010-04-01T20:48:00.000-07:00

In my recent posts, I have been focusing on questions raised by soon-to-be graduates from life science programs. While these posts have been well received and I still have many questions to answer, one event of the recent week warrants a brief detour. Last week, at the San Francisco American Chemical Society meeting, I was invited to participate in a panel discussion on green chemistry and its role in industry. This was an interesting opportunity for me because, while I am aware of and fully support the philosophies behind green chemistry, I had never reduced these philosophies to practice in the execution of my laboratory responsibilities. When asked to serve as a panelist, I was forced to reflect on the following questions:

Why have I not utilized green chemistry?
What I contribute to this discussion?
How I can incorporate green chemistry into my department?

For those of you who have never heard of green chemistry, green chemistry is defined as the design of products and processes that minimize the use and generation of hazardous substances. This definition is supported by the 12 principles of green chemistry developed by Paul Anastas and John C. Warner. The 12 principles are:

It is better to prevent waste than to treat or clean up waste after it is formed.
Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
Chemical products should be designed to preserve efficacy of function while reducing toxicity.
The use of auxiliary substances (e.g. solvents, separation agents, etc.) should be made unnecessary wherever possible and, innocuous when used.
Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure.
A raw material or feedstock should be renewable rather than depleting wherever technically and economically practicable.
Reduce derivatives - Unnecessary derivatization (blocking group, protection/deprotection, temporary modification) should be avoided whenever possible.
Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products.
Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
Substances and the form of a substance used in a chemical process should be chosen to minimize potential for chemical accidents, including releases, explosions, and fires.

In accordance with this definition and principles, green chemistry aims to incorporate the highest efficiency reactions with generation of the least amount of waste - in most cases a very formidable challenge. However, for the commercial manufacture of medications such as Lyrica and Ibuprofen, green chemistry has led to reductions of greater than 80% of their respective toxic waste streams! Therefore, the manufacture of pharmaceuticals is, in fact, well-suited for incorporation of environmentally friendly production processes. However, this is generally not the case for research oriented activities.

Adapting Green Chemistry to Discovery Research

One of the most intriguing areas of green chemistry involves the use of chemical reactions that conserve atoms - that is, all atoms in reactants and reagents are incorporated into the reaction product. While, in principle, this philosophy reduces waste, in practice, such chemistry is not available in a diverse enough toolbox to allow for the synthesis of compounds with structural diversity necessary for success in drug discovery.

Compare green chemistry to the promise advertised for combinatorial chemistry. Combinatorial chemistry utilizes polymer supports on which reactions can be executed. However, the diversity of reactions compatible with the polymers limited the applicability of solid-phase chemistry to a subset of pharmaceutically interesting molecular scaffolds. Thus, while combinatorial chemistry is a useful tool for some structural classes, this technique is currently not the answer to the rapid discovery of novel drug candidates. This may, one day, change with a large enough toolbox of reactions that can be utilized on various types of polymer supports.

From another perspective, consider that the definition of green chemistry relates to the design of products that minimize the use and generation of hazardous substances. If we, in the pharmaceutical industry, were to design our target structures with waste streams in mind, we would be limited in the types of reagents we could use and we would certainly not have access to the diversity of structures necessary to succeed. While, at first glance, this reality might lead one to believe that green chemistry is not applicable to discovery research, the first of the 12 principles reverses that perception. In the execution of research activities, waste is generated - the vast majority being solvent waste. Some strategies for solvent waste reduction are:

responsible execution of reactions utilizing minimal amounts of solvents
non-use of environmentally toxic solvents such as carbon tetrachloride and benzene
replacement of column chromatography with recrystallization techniques whenever possible
using supercritical carbon dioxide as an HPLC solvent
segregation of waste solvents and solvent recovery through distillation

Through incorporation of these techniques, coupled with efficient containment of waste streams, discovery research can be environmentally friendly. Furthermore, upon reflecting on these philosophies, I feel justified in saying that:

I daily utilize green chemistry through maximizing reaction concentrations and minimizing solvent use.
I routinely incorporate green chemistry into my department through efforts to minimize and contain waste streams.
I have a great deal to contribute to this ongoing philosophy through advocacy in favor of environmentally friendly practices.

Finally, as academic groups continue to develop reactions that adhere to the 12 principles of green chemistry, such reactions will find their way into broader industrial use.

Medicinal Chemistry Part 2 - Answers to Questions from Soon-To-Be-Graduates

2010-03-20T23:13:00.000-07:00

At January's CSU Biotechnology Symposium, soon-to-be graduates from life sciences programs had many questions about relevant career paths. This is the second of three posts addressing questions specifically related to medicinal chemistry. The questions addressed in this post are:

How does molecular modeling influence medicinal chemistry?
How does natural product research relate to medicinal chemistry?
How can natural products be matched to enzyme activity?

How does molecular modeling influence medicinal chemistry?

In my last post, the question "What is medicinal chemistry?" was answered. In that post, I discussed the role of a medicinal chemist in the context of a drug discovery program. In such a program, success is dependent upon the synergistic activities of scientists of many disciplines. Some of these disciplines are:

organic chemistry
biochemistry
biology
pharmacology
analytical chemistry
computational chemistry

Organic chemistry is necessary for the generation of drug candidates. Biochemistry is used to design the enzyme-based assays used to test drug candidates. Likewise, biology is used to design the cell-based assays and animal models of diseases. Pharmacology is applied to the actual testing of drug candidates in live animals and analytical chemistry is necessary to provide meaningful data regarding blood serum concentrations as well as initial drug purity assessments. Based on these specific roles, it is entirely appropriate to wonder where computational chemistry fits in.

Computational chemistry utilizes mathmatical algorithms and computer technology to:

predict the achievable structural conformations of drug candidates
image protein/enzyme structures based on X-ray crystallographic data
predict protein/enzyme structures based on X-ray crystallographic data of related proteins/enzymes
compare biological data of related structures as a tool to predict the activity of planned compounds
study the enzyme binding site in the presence and/or absence of drug candidates
design novel structures optimized to the shape and properties of relevant enzyme binding sites.

Because all of the above applications of computation chemistry effectively visualize what cannot be directly seen, each of these systems is a model designed to represent intended interactions within biological systems. Because these systems are models, computational chemistry is frequently termed "molecular modeling." While this technology was routinely unavailable to medicinal chemists until the 1980s, such technology is now indispensable in guiding the activities of medicinal chemists to more rapid successes.

How does natural product research relate to medicinal chemistry?

Nature has provided numerous biologically active compounds useful for medicinal purposes. Such compound classes include opiods, antibiotics and antifungals. While some compounds from these classes are commonly used as medicines (morphine, cocaine, penicillin, erythromycin, taxol, nystatin), most induce undesirable and potentially toxic side effects when administered to humans. The reason for this is clear - these compounds were designed by nature to benefit their non-human host organisms.

Because of nature's relatively inefficient optimization of biologically active molecules for human use, most natural products are best utilized as lead molecules in drug discovery programs. Through the systematic modification of natural substances, drug-like properties can be enhanced while minimizing undesirable and/or off-target effects. Thus, natural product research provides medicinal chemists a rich and valuable goldmine of lead molecules and potential drug candidates.

How can natural products be matched to enzyme activity?

Natural products are organic molecules produced by living organisms. While there are numerous living organisms that produce interesting substance, plants fungi and marine creatures generally receive the most attention.

The process of natural product discovery generally involves homogenization of large quantities of a given species such as a marine sponge. The liquefied sponge is then extracted with organic solvents. The materials being dissolved into the organic solvents are then isolated and separated by techniques such as high pressure liquid chromatography (HPLC). This initial chromatography step produces fractions that contain multiple natural compounds. As only natural products with biological activity are generally of interest, these crude fractions are screened against various enzymes. If a given fraction shows interesting activity, it is further purified to isolate its individual molecular components. These components are then screened against the enzymes of interest and the most active component is identified.

From this point, a map from a given sponge to a given natural product is identified. Using this map, the natural product of interest can be repeatedly isolated from the same species. However, the structure of the natural product is not yet known. In order to establish the structure, larger quantities must be isolated and subjected to analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Additional structural information can be obtained by studying the products of chemical degradation. When a final structure is proposed, often the best proof of structure is total synthesis - the process of preparing a natural product from non-natural sources using synthetic organic chemistry. In fact, it is this process of total synthesis that provides some of the best training for graduate students interested in entering industries dependent on the discovery of pharmaceuticals, polymers and agrochemicals.

Medicinal Chemistry Part 1 - Answers to Questions from Soon-To-Be-Graduates

2010-03-07T21:13:00.000-08:00

Students preparing to enter the workforce have a great many questions. Some of these relate generally to career paths while others relate more specifically to various professions. In my last two posts, I focused on career paths. I hope the answers I provided are helpful and look forward to reading your comments.

At January's CSU Biotechnology Symposium, I had the opportunity to listen to both questions and concerns of soon-to-be graduates from life science programs. Those participating at my table (medicinal chemistry) provided me with a forum to address qustions specific to my area of expertise. These questions, related to medicinal chemistry, are:

What is medicinal chemistry?
Do medicinal chemists participate in the testing of compounds?
What is a typical day like for a medicinal chemist?
How does molecular modeling influence medicinal chemistry?
How does natural product research relate to medicinal chemistry?
How can natural products be matched to enzyme activity?
What is the impact of small protein design?
What are the advantages/disadvantages of biologics vs small molecule drugs?

In this and the following posts, I will address all of these questions.

What is medicinal chemistry?

Medicinal chemistry is the discipline focused on the discovery of new medications.

Many medications are derived from natural sources such as plants, sponges and animal toxins/venoms. Specific examples include aspirin, morphine and cocaine. However, while nature provides many biologically important molecules, these molecules are the result of evolutionary pressure upon the organisms from which they are isolated. As such, they are not necessarily optimal for use in humans. In order to make use of such naturally occurring compounds, medicinal chemists work to modify these structures in order to enhance desirable properties and minimize toxic side effects.

Complementary to naturally occurring compounds are the vast libraries of chemicals available for biological screening. These compounds are generally man-made and provide equally enticing structures as lead molecules for drug discovery programs.

Because medicinal chemistry involves the systematic modification of natural or man-made organic molecules, a background in organic chemistry is essential to the medicinal chemist.

Do medicinal chemists participate in the testing of compounds?

Medicinal chemistry is only one component essential to the drug discovery process. Another aspect of this process involves the testing of the compounds that are produced by medicinal chemists. The biological assays generally include enzyme assays, cell-based assays and biologically relevant animal models of diseases. These studies are generally designed and carried out by biologists and pharmacologists.

Medicinal chemists do not carry out biological assays. However, the feedback generated by biologists and pharmacologists is essential to helping medicinal chemists design their next modifications to lead molecules. Thus by correlating the structures of related compounds to their respective biological data, medicinal chemists can determine if they are moving towards or away from improved drug candidates.

Although medicinal chemists do not generally participate in compound screening, it is not unheard of. Early in my career, I was curious as to whether a class of matrix metalloproteinase inhibitors (MMPI)s would act as inhibitors of endothelin converting enzyme (ECE). At the time, there was no enzyme assay available for ECE. However, there was an way to measure ECE activity in rats by measuring their blood pressure in response to dosages of big endothelin (big-ET) in the presence or absence of an MMPI. With this knowledge, a colleague of mine in the pharmacology department taught me how to surgically cannulate rat carotid arteries and, together, we were able to demonstrate that MMPIs could inhibit ECE. This was the only time in my career that I actually participated in biological assays and it taught me a great deal about the role and importance of pharmacologists to the drug discovery process.

What is a typical day like for a medicinal chemist?

Medicinal chemists typically spend their days making target molecules for biological testing. Approximately 70% of their time is spent initiating reactions, completing reactions and isolating/purifying products. The remaining 30% may be spent generating analytical data (NMR, HPLC, MS) for isolated compounds, reviewing biological data provided by biologists, searching scientific literature for information/procedures needed for chemical transformations, and attending group meetings.

The role of a medicinal chemist is highly intertwined with related operational groups such as biology, pharmacology, formulations and process chemistry. The medicinal chemist must be able to effectively communicate with all of these disciplines in order to share necessary information and glean important insight valuable to program advancement. Each day is different from the last and each day begins with the hope of new discoveries.

Career Paths Part 2 - Answers to Questions from Soon-To-Be Graduates

2010-02-16T07:01:00.000-08:00

In my previous post, I began to address questions regarding career paths. In this post, the remaining career path questions are answered.

What are the differences between academic and industrial careers?

The differences between academic and industrial careers are significant. Beginning with academic careers, professors are expected to:

teach classes
raise funding
train graduate students

Each of these areas require exceptional scientific knowledge/expertise, excellent people skills and outstanding communication skills. For example, to successfully teach classes, professors must be able to engage the students and coherently communicate concepts. Furthermore, to raise funds, professors must be able to influence decision makers. They must be able to articulate the rationale and intent of the program for which funding is desired, and to do so in a dynamic and convincing manner. These programs must maintain a high level of competitiveness in order to compete with the large number of programs that are vying for the limited amount of funds available. Finally, training graduate students requires clear communication, strong people skills and an outstanding ability to attract potential students through a solid scientific reputation.

With all of the above in mind, there are several different academic career tracks including:

non-tenure track
tenure track
administrative track

Non-tenure track positions generally involve class instruction only. Such programs can, in some cases, include research activities.

On the other hand, tenure track positions require both class instruction and research activities, and are much more involved. Success in tenure track positions depends upon an ability to obtain funding for programs and on a consistent stream of peer-reviewed publications - professors must be prepared to write interesting and innovative publications on a regular basis.

Administrative opportunities can come from both non-tenure track and tenure track roles. However, higher profile opportunities are generally filled by tenured professors. It is important to note that to participate in any of these roles, a PhD is required.

Finally, anyone considering a career in academia must recognize that the goals of academia are education and basic research. In contrast, the goals of industry are to bring products to market and generate returns for investors. Bearing this in mind, it is easy to understand why salaries in academia, particularly during the first few years, are considerably lower than those available from industry.

Industrial careers offer opportunities to contribute to the development of products for introduction to commercial and consumer markets. Such products have direct applications to healthcare (pharmaceuticals and medical devices), food (packaging materials, food preservation, artificial flavors/sweeteners, etc), electronics (semiconductors, memory media, etc.) and energy (synthetic fuels, catalysts, recycling, etc.).

The industrial career track generally begins at the scientist level (PhD) or the associate level (BS/MS). Projects are assigned based on corporate priorities. Unlike academic careers where projects are selected based on scientific interest, projects in industry are selected based upon marketing potential. Thus, while those participating in industrial programs may not be able to select their programs, they can use their individual creativity to devise novel strategies to solve their assigned problems. Furthermore, corporate fundraising activities are generally under the realm of corporate executives - leaving the scientists to concentrate solely on the science.

In industry, there are generally two career paths:

scientific
managerial

Both of these tracks start at the scientific level. However, when a scientist reaches a certain level, that individual may choose to pursue roles such as group leader/director or research fellow. While these titles may differ from one company to the next, group leaders generally have more managerial opportunities while research fellows generally are active scientists on the bench. Both of these paths offer unique opportunities for professional development.

In summary, both academic and industrial careers provide exciting opportunities for those interested in contributing to the sciences. There are differences in each path that may appeal to certain individuals and I encourage all students to better understand themselves and their goals as they evaluate the numerous variables when choosing where to apply their talents.

Is there more competition for academic positions in this economy?

There is considerably more competition for academic postions than for industrial positions because:

Professorships are high profile
There are more available industrial positions than professorships.

Career Paths Part 1 - Answers to Questions from Soon-To-Be Graduates

2010-01-25T21:36:00.000-08:00

In my last post, I discussed my experience as a career mentor and summarized the questions asked by soon-to-be graduates of life sciences programs. Over the next several posts, I will address each of these questions.

How did I decide upon my career path?

Ever since I was a child, I knew I wanted to be a chemist. The funny thing was that I did not know what a chemist was, or what a chemist did. My influence clearly came from the cool racks of tubes and bubbling solutions shown in sci-fi movies.

As I advanced through school, I was very good at math and science. Furthermore, I was frequently and dangerously curious about electricity, gunpowder and fire. While I am not inclined to elaborate at this time, it is interesting to note that one of the hallmark experiences of almost every chemist I know is an early desire to experiment, coupled with a lack of fear of the consequences.

Entering college I enrolled as a chemistry major at the UC Berkeley and enthusiastically pursued the required curriculum. However, at that time, I still had not decided on what I wanted to do as a chemist. All this changed when I began to study organic chemistry. When I realized how organic compounds interact with and influence biological processes, I knew that I wanted to work towards improving the quality of life for people suffering from conditions for which there was no treatment. From that point on, I embraced organic chemistry, took all available organic chemistry courses, and pursued undergraduate research under the direction of Professor Henry Rapoport.

Through Professor Rapoport's guidance, I began to develop my laboratory skills in preparation for graduate school. While I knew that a PhD was required in order for me to fully achieve my goals, I had not yet decided if I wanted to pursue a career in academics or in industry. That decision developed during my graduate studies at MIT under the direction of Professor Satoru Masamune.

Having always been attracted to the idea of designing my own research programs, I initially felt that my best opportunities would be in academics. However, while in graduate school, I realized that there was an intense amount of competition for funding, tremendous politics regarding the tenure track and significant non-scientific activities required in order to keep a research group running. These observations were contrasted to the fact that in industry, while I would not be required to fund my own programs, I would be required to work on programs to which I was assigned. Both sides had tremendous advantages. In the end, I felt that even though I would be assigned programs, industry does not dictate how I solve the problems to which I would be assigned. To this day, I enjoy the tremendous freedom to contribute novel solutions to the design and development of pharmaceutical agents.

Can you describe your industrial experiences and career path?

Industry has been very good to me. Following completion of my PhD, I took a scientist position at Glycomed. This was a great fit for me because the pharmaceutical technologies being studied at Glycomed made excellent use of my graduate school experiences involving the chemical modification of sugars. At Glycomed, I contributed to the design of anti-inflammatory agents (selectin inhibitors and fucosyl transferase inhibitors) as well as drugs targeting angiogenesis, cancer and multiple sclerosis (matrix metalloproteinase inhibitors). As I developed my experience, I ultimately led the matrix metalloproteinase inhibitor efforts and took responsibility over three direct reports.

Following Ligand Pharmaceuticals' acquisition and the subsequent closure of Glycomed, I joined COR Therapeutics. My charge was to develop a chemistry program targeting selective inhibition of type V adenylyl cyclase for use in the treatment of congestive heart failure. In this role I developed my knowledge of heterocylic compounds and synthetic nucleoside mimics. While this project yielded extremely potent compounds with activity in whole cell assays, corporate priorities resulted in termination of the adenylyl cyclase project. For the remainder of my tenure at COR, I contributed to the design and synthesis of novel ADP receptor antagonists for use in treating deep vein thrombosis.

When COR Therapeutics was purchased and subsequently closed by Millennium Pharmaceuticals, I took a group leader position at Scios, Inc. My role as group leader was to design and execute a medicinal chemistry program targeting calmodulin dependent kinase for the treatment of post-operative arrhythmia. This was by far the largest team I had ever managed. At the peak of this effort, I had a team of ten dedicated scientists and associates. Furthermore, I managed additional resources operating from contract research organizations (CROs) in the United States and India. Unfortunately, this program was terminated when Scios was purchased by Johnson & Johnson and subsequently shut down.

The closure of Scios was particularly difficult for me because it led to my first significant stretch of unemployment. Jobs were scarce - especially for more experienced scientists looking for leadership roles. I networked every day and built relationships with many industry insiders and recruiters. Realizing that I could not simply wait for new opportunities to present themselves, I decided to start consulting. Through my consulting efforts I was able to secure laboratory space. With this resource available to me, I was able to build on a networking connection and start an independent custom synthsesis effort. My client was Intradigm Corporation and I was hired to prepare a compound critical to their development programs. My efforts were actually in competition with a CRO preparing the same compound. In the end, I was able to prepare the target, provide necessary starting materials to the CRO and transfer synthetic protocols enabling the CRO to scale up the process. Because of my work on this program, Intradigm created the role of Director of Synthetic Chemistry for me - a position which I currently hold.

While I do not know what opportunities lie in the future, I always strive to embrace the possibilities.

Life Science Careers - Questions from Soon-To-Be Graduates

2010-01-11T21:18:00.000-08:00

With the tremendous uncertainty regarding today's economy, students are understandably concerned about their job prospects and the overall availability of career opportunities - regardless of the sector they choose to join. Those with the greatest concern are the ones closest to graduation. During the course of my education and career development, I had many opportunities to meet with career counselors and mentors to develop strategies for my long term success. I am eternally grateful for the solid advice that was extended to me. Indeed, it is largely because of the dedication of those individuals who provided their time and expertise to encourage young and enthusiastic science students that I decided to write this blog.

Last week, I was invited to participate as a mentor in the career networking session of the CSU Biotechnology Symposium. The goal of this program was to educate students pursuing degrees in the life sciences about the varied career tracks that are available to them. In all, there were 18 tables able to accommodate up to 10 students each in 4 rotations. Topics covered at each table were:

Finding a job in today's economy
How to apply/interview
Medicinal chemistry
Clinical trials management
Intellectual property management
Discovery research
Biodevice product development
Quality and regulatory affairs
Product development
Business development
Engineering
Food and Drug Administration
Medical marketing
Cliical laboratory sciences
Health IT
Pharmaceutical manufacturing
Bioinformatics
Start up a company

Those of you who follow this blog will recognize that I routinely highlight topics, skills and career opportunities in almost all of the above areas. With respect to the career mentoring session, I was asked to participate at the medicinal chemistry table and, along with a long-time colleague, had the opportunity to address a wide array of questions from some very bright students eager to contribute to all facets of the life sciences industries.

Questions Asked by Life Science Students

I was truly impressed with the questions asked at the mentoring session. These questions, paraphrased below, reflect the ongoing discussions encompassed by this blog. The questions raised, organized by topic, are:

Questions About Medicinal Chemistry

What is medicinal chemistry? (Answered 3/7/10)
Do medicinal chemists participate in the testing of compounds?(Answered 3/7/10)
What is a typical day like for a medicinal chemist? (Answered 3/7/10)
How does molecular modeling influence medicinal chemistry?(Answered 3/20/10)
How does natural product research relate to medicinal chemistry?(Answered 3/20/10)
How can natural products be matched to enzyme activity?(Answered 3/20/10)
What is the impact of small protein design? (Answered 4/14/10)
What are the advantages/disadvantages of biologics vs small molecule drugs? (Answered 4/14/10)

Questions About Career Paths

How did we decide upon our career paths? (Answered 1/25/10)
What are the differences between academic and industrial careers? (Answered 2/16/10)
Is there more competition for academic positions in this economy? (Answered 2/16/10)
Can you describe your industrial experiences and career path?(Answered 1/25/10)

Questions About Employment Opportunities

What will industrial employment opportunities look like in the next 5 years? (Answered 5/15/10)
What is the future of in-house dedicated medicinal chemistry programs? (Answered 5/15/10)
Are opportunities available in pharma/biotech for people with experience outside of the life sciences? (Answered 5/15/10)
Are part time opportunities with tuition assistance available in pharma/biotech companies? (Answered 6/3/10)
For new hires, what degrees are more valuable - organic chemistry or medicinal chemistry? (Answered 6/3/10)
Is there job security in the life sciences? (Answered 6/3/10)
What are the trends in outsourcing? (Answered 6/3/10)

Questions About Relevant Knowledge and Experience

How important are analytical techniques (NMR/HPLC/MS/etc.) for new hires? (Answered 7/26/10)
What opportunities exist for BS/MS level chemists in this economy? (Answered 7/26/10)
What are the requirements for an entry level chemistry job?(Answered 7/26/10)
How do supervisors interact with BS/MS level chemists in the lab? (Answered 7/26/10)
How can I learn more about molecular modeling? (Answered 7/26/10)

While some of the above questions were addressed or touched on in previous postings, most present opportunities to share insight in areas highly relevant to our continually evolving job climate. Future blogs will address each of these questions in turn. Furthermore, it is my hope that those of you following this blog will add your voices and opinions thus enhancing the breadth of insight provided herein.

Green Technology and "Climategate" - Opportunities in Environmentally Friendly Chemistry

2009-12-16T22:14:00.000-08:00

Recent news suggesting the use of manipulated and/or manufactured data supporting the global warming phenomenon has simultaneously created a political nightmare for advocates and perceived vindication for skeptics. Regardless of the politics behind climate change, one thing is absolutely clear - ALL TRUE FACTS CAN BE BACKED UP WITH DATA. This axiom applies as much to scientific disciplines as it does to the media. If data is manipulated in order to support a hypothesis, the validity of that hypothesis becomes questionable. Furthermore, if a journalist presents data out of context, the credibility of that journalist becomes questionable. Finally, if a scientist manipulates data to support a hypothesis, the credibility of that scientist becomes questionable. As a scientist, I can tell you that there is nothing more important to me than my credibility.

In disciplines where ongoing activities and policies rely on developing data, the introduction of manufactured data or the convenient omission of recorded data serves no one except those with vested interests in validating their theories. Whether an advocate or a skeptic of global warming, there is one philosophy that we can all agree upon - it is a good idea to take care of our environment. This philosophy, applied to both established and developing industries, automatically gives rise to tremendous opportunities in the sciences. For example:

the finite supply of accessible natural resources gives rise to the development of alternative fuels and more efficient means of utilizing currently accessible fuels,
the current reliance upon combustion of fossil fuels gives rise to the development of emission containment technology, and
the constant accumulation of waste materials gives rise to the development of technologies for the recycling and/or reprocessing of discarded products.

While the current "climategate" scandal may impinge upon idealistic views of science and politics, it should not be a barrier to innovation. Each of the points mentioned above have direct implications to the carbon cycle and, through the creative minds of our current and emerging scientific talent, economically viable technologies will emerge. Already, academic institutions are designing curricula focused on "green chemistry" or chemistry incorporating solvents, reagents and reaction conditions that are compatible with the health of the environment.

Organic Chemistry and Clean Technology

Since the industrial revolution, our economy has become increasingly more dependent upon the combustion of fossil fuels. After all, the energy provided by oil, coal and natural gas is already contained within the natural materials mined for human use. All we have to do is recover the fuel. Furthermore, these natural resources also provide components useful as, for example,

raw materials for the manufacture of chemicals,
monomeric units for polymer synthesis, and
paving materials for roads.

While organic chemistry is the core science in the processing of petroleum-based materials, organic chemistry also provides solutions to dealing with the abundance of petroleum-based materials being discarded on a daily basis. Just as an understanding of the chemical composition and properties of oil, coal and natural gas led to advances in efficiency of recovery and refinement, similar understandings of polymer chemistry led to creative ways to reuse discarded polymeric materials and reclaim useful decomposition products.

Expanding on the above, the study of organic chemistry opens doors to careers in the development of environmentally friendly technologies including:

biodiesel,
synthetic/semi-synthetic fuels,
motor oil from polymer waste,
catalysts for more efficient fuel combustion, and
biodegradable polymers.

Finally, it is comforting to know that the development of these technologies will continue - even if climate change is identified as a purely natural and cyclic process.

Drug Discovery - The Cost of Innovation

2009-12-07T21:53:00.000-08:00

In today's political and economic climate, all industries are forced to respond to public perceptions/pressure and adjust business plans accordingly. Perhaps the most visible sector, and the one receiving the most scrutiny, is the healthcare industry. Unfortunately, this scrutiny is generally politically motivated and therefore, information is filtered to the public to support various agendas. Oftentimes, the information is misleading and incomplete.

The healthcare industry is comprised of multiple sectors including insurance companies, healthcare providers, and pharmaceutical companies. Without delving into the intricacies influencing the overall cost of healthcare, it is important to understand that healthcare is dependent upon both medical services and medical products. Furthermore, in order to advance the quality and efficiency of healthcare, medical products must continually evolve to incorporate state of the art technology guaranteeing that future generations of products perform better than their predecessors. This philosophy is continually relevant in the design and development of new pharmaceutical agents.

Pharmaceuticals, being medical products, require years of research in order to understand the properties enabling them to be safely marketed. The processes associated with the development of new medicines include:

initial screening of thousands of chemicals against a biological target
identification of hit compounds that show activity against the desired biological target
chemical optimization of hit compounds to generate pharmaceutical lead molecules
optimization of lead molecules to impart favorable pharmacological properties
evaluation of optimized lead molecules in disease efficacy models, toxicology and stability
design of processes for the synthesis and formulation of drug candidates
execution of pre-clinical animal studies
submission of an IND (investigational new drug) application to the FDA
execution of human clinical trials
submission of an NDA (new drug application) to the FDA

While the above list seems straightforward, it is not a complete representation of the entire drug discovery process. In fact, the full process of bringing a new drug to market takes approximately 15 years and costs around $800 million dollars. Furthermore, as only 1 in 8 drug candidates entering clinical trials ever reach market, the cost of failed programs must be added to the $800 million dollar investment. The net result is that pharmaceutical companies must recover the costs associated with one successful product and seven failed programs just to break even!

As with the development of any new product intended for market, the company presenting new products is entitled to recover its investment and recognize some profit. This is a fundamental incentive at the core of a capitalist society. If companies are restricted from selling their products at market-competitive prices, there is little incentive for the development of new and/or next-generation innovations.

Due to set limits on patent lifetimes, pharmaceutical companies have approximately 5 years of market exclusivity post FDA approval to recoup thier $800 million dollar (plus the costs associated with failed programs) investment. Realization of this fact helps us to understand how pharmaceutical companies price their products. Of course, this fact does nothing to appease concerns associated with out-of-pocket expenses incurred by those requiring medications not covered by their insurance policies. To this point, I respectfully argue that this is an issue better addressed with insurance companies and not through government imposed price controls.

Chemistry Opportunities and the Impact of Price Limits

The previously stated processes associated with the development of new medicines also defines opportunities for those interested in careers in the sciences. For example:

initial screening of thousands of chemicals against a biological target
identification of hit compounds that show activity against the desired biological target

Biochemists and biologists are employed to design relevant assays required in the above two points. Patent attorneys provide legal protection for novel compounds/formulations throughout the discovery/development process.

chemical optimization of hit compounds to generate pharmaceutical lead molecules

Organic and medicinal chemists design new molecules. Biologists and biochemists execute biological screening. Analytical chemists determine molecular composition and purity.

optimization of lead molecules to impart favorable pharmacological properties

In addition to those listed in the above point, biologists design relevant disease models in animals. Pharmacologists study the effects of drug candidates on animals. Bioanalytical chemists study drug metabolites. Formulation chemists develop drug formulations for administration to animals. Computational chemists help in understanding the interactions between potential drug candidates and biological targets.

evaluation of optimized lead molecules in disease efficacy models, toxicology and stability

In addition to those listed in the above points, toxicologists and analytical chemists are required.

design of processes for the synthesis and formulation of drug candidates

Process chemists develop routes for the efficient synthesis of drug candidates on industrial scales. Analytical chemists assess the quality of large-scale synthesis at each synthetic step.

execution of pre-clinical animal studies

Pharmacologists and biologists study drug effects on higher animals. Analytical chemists evaluate drug metabolites through blood, urine and feces.

submission of an IND (investigational new drug) application to the FDA

Contributions from synthetic chemists, analytical chemists, pharmacologists, biologists and biochemists are required to generate a complete IND package. In addition, clinicians must design clinical trials and define trial endpoints.

execution of human clinical trials

Clinicians, medical doctors, pharmacologist, analytical chemists and statisticians all contribute to the generation and evaluation of human clinical data.

submission of an NDA (new drug application) to the FDA

In addition to those contributing to an IND package, statistical evaluation of clinical endpoints, final synthetic/formulation processes and analytical specifications of drug product contribute to successful NDA packages.

Summarizing the above, drug discovery efforts require:

analytical chemistry
organic/medicinal chemistry
formulation chemistry
computational chemistry
cell biology
molecular biology
biochemistry
pharmacology
clinical medicine
animal care
patent law

Thus, the pharmaceutical industry provides numerous science-based career opportunities - all of which require some study of organic chemistry. However, if we allow government-imposed restrictions on the pricing of pharmaceuticals, the results will be fewer new products, less innovation and fewer available jobs. Considering the benefits to

society from the development of new therapeutic agents,
the economy from employment of professionals with scientific backgrounds, and
the government from the generation of tax revenues based on personal and corporate profits,

let's keep the pharmaceutical industry out of the healthcare debate and maintain the values of our free-market society.

Chemistry Outsourcing - New and Challenging Career Opportunities

2009-10-25T22:56:00.000-07:00

Recent years have seen increased chemistry outsourcing activities - largely perceived as corporate strategies designed to maintain productivity while reducing the load of full time staff. From a business perspective, this makes a great deal of sense. For example:

in-house projects require in-house staff
in-house staff requires dedicated equipment, facilities and overhead
dedicated equipment, facilities and overhead require sufficient operating capital that is inherently more expensive than simple office space.

Outsourcing, on the other hand, provides reasonable solutions. Specifically:

outsourced projects require off-site staff
off-site staff requires off-site equipment, facilities and overhead
off-site equipment, facilities and overhead require support from corporate clients with a need for outsourcing activities.

As a bonus, commitments to contract organizations are limited by the duration of contracts, while commitments to full time staff are generally long-term relationships.

From the above arguments, we must all come to the realization that OUTSOURCING IS HERE TO STAY. While the above arguments support the decisions of businesses to incorporate outsourcing as part of their corporate strategies, they do little to offer hope and comfort to those individuals who see their jobs vanishing in favor of low-cost offshore contract activities. From a pragmatic point of view, this does not matter. Hope and comfort are highly overrated and they do not pay the bills. Now is the time to take charge of our career paths, create opportunities for ourselves and forget about hope and comfort.

Careers in Chemistry - Defining Our Own Roles

From the moment we decide to study chemistry, we are faced with choices such as:

whether to enter the workforce or pursue an advanced degree
whether to pursue a career in academics or in industry
what industry to contribute to
whether to follow a scientific path or a management path

Each of these decision points lead to additional choices which, if we are not careful, can ultimately define us. In this rapidly changing corporate world, we are far better off if we can control how we are defined by maintaining significant diversity/flexibility in our skill sets. We don't have to lose our jobs to changing markets if we can adapt our skill sets to changing needs.

When I first entered the workforce, my supervisor made a very disturbing prediction. He observed the growing trend in outsourcing and knew that opportunities would begin to diminish. This was approximately 15 years ago and, to this day, I credit my former supervisor for his warning and for his foresight. In fact, it was largely because of this prediction that I began reaching out into different areas related to drug discovery. Such areas include:

management
intellectual property
due diligence
contract synthesis

Management skills are essential and relate not only to working with other people, but also working within our own time/resource constraints. These skills enable meeting personal objectives, meeting cross-departmental goals, and interacting with others - whether in-house or overseas.

Understanding intellectual property law and strategies enables us to organize our contributions into recognizable inventions essential for the strength of the technology base of companies for which we work. Furthermore, we are able to directly contribute to the design of patent strategies, work with patent attorneys and address concerns from the patent office.

Corporate due diligence is essential for investors to make decisions on where to invest their funds. It is also essential for employment candidates to make decisions on which companies best suit their professional and scientific goals. Through due diligence, rational decisions can be made regarding program resource allocation, academic/industrial collaborations and projected headcount needs.

Contract synthesis is not only a service for hire, it is also a tool for temporary expansion of in-house resources. Decisions to utilize contract research organizations are made based on the requirements of individual programs. Those chosen to manage these activities must be skilled in due diligence, intellectual property and management. Specifically, in working with CROs, due diligence is essential for evaluation and selection of appropriate firms. Furthermore, understanding intellectual property is essential for the protection and preservation of present and future inventions being developed with the assistance of CROs. Finally, regardless of domestic or offshore locations, management skills are required for the successful negotiating and engagement of CRO activities, troubleshooting project issues and guiding programs to successful outcomes.

Reiterating that we don't have to lose our jobs to changing markets if we can adapt our skill sets to changing needs, the skills I addressed above are of tremendous importance. With core competencies in these area, employment is available in parent companies, contract research organizations, law firms, consulting firms and venture capital firms. The trick is to face this changing market with confidence, focus on present and future needs, and make ourselves essential professional resources.

Academic Institutions and Drug Discovery

2009-09-30T22:04:00.000-07:00

The ability to manipulate the chemical composition of matter has led to new products and technologies emanating from almost every sector of industry. Of these sectors, among the most challenging and time-intensive activities is the discovery and development of new therapeutic agents. These challenges stem from:

our increased need for safer and more effective products
inherently long timelines from discovery to market
the desire of the venture community to realize rapid returns on investments.

Examining these points from the perspective of cause and effect, the well justified need for safer and more effective products results in longer timelines from discovery to market. Unfortunately, long timelines are not compatible with rapid returns on investments. As such, investment capital has been shifting from high risk discovery programs to less risky development programs. In fact, it is not uncommon for investors to reserve capital for products already in clinical trials. The unfortunate consequence of this paradigm shift is that reduced capital for discovery programs has led to a reduced number of products transitioning from discovery to development. This transition begs the question FROM WHERE WILL THE NEXT GENERATION OF DRUG CANDIDATES EMERGE?

In previous posts, I highlighted issues relevant to this question including:

Where big pharmaceutical companies will rebuild their pipeline of new drug candidates
Large pharmaceutical firms turning to biopharmaceutical companies to fill their discovery pipelines
Paradigm shifts incorporating outsourced services as replacements for high cost internal capabilities
Academic institutions must continue to provide solid educational programs and degrees in chemistry - incorporating broad based and generally useful knowledge/skills

With the shrinking volume of venture capital funds available for early stage discovery startups and the continuing trend of large pharmaceutical companies filling their discovery pipeline through small company acquisitions, there is a sector looking to academic institutions to fill this gap. Having both attended graduate school and contributed to industrial drug discovery efforts, I can state with complete certainty that THIS IS A VERY BAD IDEA!!!

Yes, I said it. I mean it and I make no apologies for the frankness of my statement. Academic institutions are not suitable engines for both drug discovery and the training of our next generation of scientists. To qualify this statement, consider that the drug discovery process requires activities including:

Compound synthesis/purification/analysis
Enzyme assays
Cell-based assays
Animal models of disease
Pharmacology
Formulations
Metabolite ID/bioanalytical

Each one of these activities requires the involvement of highly trained and knowledgeable scientists. Furthermore, each of these areas must be coordinated with one another in order to enable generation of the data required to accurately evaluate all potential drug candidates. In an academic setting - the setting responsible for much of the cutting edge advancements ultimately benefiting the pharmaceutical industry - such activities are not likely to be implementable without a detrimental effect on the training grounds of the next generation of scientists.

Put another way, where are we to generate the next generation of innovative, highly trained and knowledgeable scientists if our educational resources are diverted to commercial interests?

Organic Chemistry vs Medicinal Chemistry

During my undergraduate research activities with Professor Henry Rapoport at UC Berkeley, I found that my greatest interest was in the discovery of new medicines. Recognizing that the career opportunities I sought required an advanced degree, I began asking about which type of graduate program to pursue - organic chemistry or medicinal chemistry. The input I received overwhelmingly favored a PhD in organic chemistry. The rationale behind this bias was quite simple - the most important skill for a chemist in drug discovery is the mastery of organic chemistry.

Education in organic chemistry programs is not limited solely to reactions. The diverse set of skills, generally applicable to drug discovery (and other industries) are:

Synthetic organic chemistry technique
Practice in hundreds of different reactions
Exposure to many more reaction types
Scales from mg to multigram
Training in the logic behind synthetic pathway selection
Training in all spectroscopic/analytic/purification techniques

While organic chemistry and medicinal chemistry programs both teach organic chemistry, medicinal chemistry programs tend to dilute the breadth of chemistry exposure with the biological aspects of drug discovery activities. These biological aspects, as my colleagues explained to me, are skills that can be learned on the job. However, the on-the-job expansion of organic chemistry knowledge is considerably more difficult to accomplish. From this philosophy, it is not surprising that at every company I worked, the most successful job candidates had degrees in organic chemistry with a strong focus on synthesis.

In my August 21 post, I pointed out that in order to motivate our next generation of scientists,

Industry must work to prevent chemistry, a discipline requiring intensive education/training, from evolving into a service
Academic institutions must continue to provide solid educational programs and degrees in chemistry - incorporating broad based and generally useful knowledge/skills

I am, and always have been, enthusiastically in favor of graduate and undergraduate level curricula focusing on the practical and philosophical aspects of the pharmaceutical industry. Such coursework can only serve to prepare students for what will be expected of them as they progress through their professional development. However, replacing or diluting the development of core skills can only compromise our next generation's ability to maintain a competitive edge in a global marketplace. Industry must look elsewhere for its discovery pipeline lest the current trickle of new drug candidates dries up completely.

Fear Mongering: Good for Nutraceuticals, Bad for You

2009-09-14T09:31:00.000-07:00

Until now, my posts focused on philosophies regarding the current state of education and industry. In fact, when I started this blog, my intent was to focus solely on issues which are constructive to the advancement of science and innovation. I had no desire whatsoever to address divisive political topics. However, with the continued onslaught of negative press and political agendas targeting the pharmaceutical industry, I feel compelled to add my voice. To this end, I want to thank Dr. Andrew Weil for providing me with material for this posting.

While I do not know Dr. Weil and I doubt that I will ever have any personal interaction with him, I know that he is extremely knowledgeable and well respected. It is not my intent to detract from his stature and I apologize if this posting does that. My intent here is to engage in an intelligent debate based upon Dr. Weil's blog of September 2, 2009 as published in the Huffington Post (http://www.huffingtonpost.com/andrew-weil-md/disease-mongering-good-fo_b_275616.html). In this posting, Dr. Weil, discusses the term "disease mongering" as a mechanism used by the pharmaceutical industry to take advantage of uninformed consumers. As Dr. Weil states,

"A central disease-mongering tactic is to attach polysyllabic, clinical-sounding names to what used to be seen as trivial or transient conditions. In most cases, the new, formidable names come complete with acronyms, which add even more gravitas."

Before I go any further, I would like to point out that when a significant population experiences a common symptom, illness, syndrome or disorder, it makes good sense to classify these indications under a common name. This helps doctors to identify patient populations they may be able to help. Furthermore, patients are supported through the knowledge that there are others sharing their discomfort. Finally, pharmaceutical companies are assisted through the identification of populations suffering (for whatever reason) from indications for which there is no treatment. Through the identification of disorders with established unmet medical needs, pharmaceutical firms are able to identify markets and drive research activities to the eventual benefit of these patient populations.

Dr. Weil, in his September 2 posting, highlights five indications that are established disorders requiring, in many cases, medical intervention. These indications, along with Dr. Weil's "disease mongering" examples are:

Occasional heartburn becomes "gastro-esophageal reflux disease" or GERD.
Impotence becomes "erectile dysfunction" or ED.
Premenstrual tension becomes "premenstrual dysphoric disorder" or PMDD.
Shyness becomes "social anxiety disorder" or SAD.
Fidgeting legs becomes "restless leg syndrome" or RLS.

In listing these example, Dr. Weil does nothing more than trivialize these indications and the patients who suffer from them. I, myself, suffer from GERD. For many years, I experienced chronic heartburn independent of diet. At one point, the pain was so severe that it was debilitating. I began taking proton pump inhibitors and eventually had surgery to tighten my lower esophageal sphincter muscle. While I am doing much better, I still have to take occasional medication to control lingering symptoms. I must also submit to periodic esophageal endoscopy procedures to monitor my Barrett's esophagus - a precancerous condition caused by GERD. For me, GERD is not an indication that can be treated by giving my body's "healing mechanisms a chance to find equilibrium."

Pharmaceuticals and Nutraceuticals - Marketing on an Equal Playing Field

In reading Dr. Weil's posting, I understand that part of his message relates to the practice of drug companies marketing their products directly to consumers. Personally, I see no problem with this practice. If a consumer is to be able to make informed decisions regarding healthcare, that consumer should know about all possible medical treatments - including pharmaceuticals. After all, if vitamins, dietary supplements and herbs (all classified as nutraceuticals) can be directly marketed to consumers, why can't prescription medications?

In the interest of fairness, I fully support the right of consumers to seek whatever medical interventions are best for them. I fully respect the history behind folk remedies and I do not pass any judgement upon those who choose alternatives to prescription medications. After all, herbs have served as sources for many modern therapeutics from aspirin to morphine.

While nutraceuticals, derived from herbal remedies, may deliver some potential therapeutic benefits, they are not regulated or controlled under the same requirements as prescription drugs. For example:

Prescription drugs must be proven safe and efficacious through human clinical trials - nutraceuticals are not held to this standard
Prescription drugs, when marketed, must have a package insert detailing adverse effects, dosage information and potential drug-drug interactions - nutraceuticals are not held to this standard

Because herbal remedies and dietary supplements contain naturally occurring pharmaceutically active components, patient who use these alternatives through self medication are putting themselves at risk based upon uncontrolled or arbitrary dosing and potential interactions with medications they may be taking by prescription.

If consumers are to have the ability to make informed choices regarding their healthcare options, all products marketed as potential health remedies must be held to the same standards. Unfortunately, they are not. This is the result of two issues:

It is not in the best interests of nutraceutical companies to fund clinical trials demonstrating efficacy when they are not required to do so
It is not in the best interest of pharmaceutical companies to fund head-to-head clinical trials of any competing product against their own

WHERE DO THE BEST INTERESTS OF THE CONSUMERS COME IN???

In order for consumers to be able to make the most informed healthcare decisions, all alternative medications must be held to the same clinical and regulatory standards as prescription medications. Only in this scenario can patients, with the assistance of their doctors, objectively evaluate the best course of care while minimizing adverse events and drug-drug interactions.

Maintaining Marketability in a Shrinking Job Market

2009-08-21T19:19:00.000-07:00

In recent years, the biopharmaceutical industry has experienced a seemingly endless series of mergers, downsizings and company closures. Reasons for this trend are numerous and include:

• Dwindling capital available for research ventures

• Corporate shifts in priority from discovery to development

• Large pharmaceutical firms turning to biopharmaceutical companies to fill their discovery pipelines

• Paradigm shifts incorporating outsourced services as replacements for high cost internal capabilities

Regarding this last point, let's face it - DISCOVERY RESEARCH IS EXPENSIVE!!! This is not to imply that product development, manufacturing, marketing and legal capabilities are not expensive - they are! They are also among the facets of industry that are routinely farmed out. Furthermore, product development, manufacturing and marketing all fall into place once products begin to emerge from discovery research efforts.

Since many small biopharmaceutical firms are focused on research, outsourcing provides a way to, at least on paper, save money. This extra cash is valuable when a firm is being considered as an acquisition target or when planning to move products into early development. Furthermore, in these lean economic times, preservation of cash is a solid strategy against less availability of venture funds.

Having addressed the bullet points listed above, I would like to re-examine the issues listed in my last posting. These are:

• The future shape of the biopharmaceutical industry

• How healthcare reform will impact the pharmaceutical industry

• How to manage the trend in offshoring chemistry activities to CROs

• Where big pharmaceutical companies will rebuild their pipeline of new drug candidates

• Where the chemists of the future will fit into this changing industrial environment

Through my postings, I will address and expand upon each of these areas - though not all at the same time. Primarily, I will focus on answering the question HOW TO MOTIVATE THE NEXT GENERATION OF SCIENTISTS TO PURSUE CAREERS IN CHEMISTRY.

In the first few paragraphs of this posting, I presented an image of a shrinking industry with rationalizations for the four trends listed. From this point on, I want to emphasize that these trends are not indications of an industry hostile to growth - THEY ARE OPPORTUNITIES FOR CREATIVITY AND INNOVATION!!! To be more specific:

• Dwindling capital available for research ventures invites the development of creative financing strategies

• Corporate shifts in priority from discovery to development invites those involved in discovery to utilize their skills in the development arena

• Large pharmaceutical firms turning to biopharmaceutical companies to fill their discovery pipelines invites increased innovation to make small companies attractive to alliances

• Paradigm shifts incorporating outsourced services as replacements for high cost internal capabilities invites development of managerial skills that can cross borders and bridge cultures

In order for these opportunities to become fully open to all, we must all recognize that CHANGE IS A FORCE OF NATURE THAT CANNOT BE STOPPED. We can either adapt or give up. I choose to adapt and continually embrace opportunities to work in all areas related to the pharmaceutical industry. A few examples from my experiences in drug discovery include:

• Recognizing corporate synergies between companies and bridging dialogs between companies

• Participating in intellectual property activities and building experience in patent drafting

• Taking advantage of funding allocated for off-shore activities and driving research projects with international teams

• Maintaining an ability to be conversant across all functional areas of drug discovery and development

While it is crucial for individual contributors to take all opportunities to expand upon their knowledge and skill base, additional forward-looking factors will contribute to successful personnel transitions. Specifically:

• Industry must work to prevent chemistry, a discipline requiring intensive education/training, from evolving into a service

• Academic institutions must continue to provide solid educational programs and degrees in chemistry - incorporating broad based and generally useful knowledge/skills

Through these commitments, scientists will be able to continue to provide innovative solutions and be rewarded through patents and publications. More importantly, the next generation of students will believe that there is a future in chemistry - even in the shadow of a continually evolving industrial setting.

Organic Chemistry - Preparing for the Future

2009-08-17T20:01:00.000-07:00

Today is the first day of this blog...

For some time, I have been contemplating issues such as:

• The future shape of the biopharmaceutical industry

• How healthcare reform will impact the pharmaceutical industry

• How to manage the trend in offshoring chemistry activities to CROs

• Where big pharmaceutical companies will rebuild their pipeline of new drug candidates

• Where the chemists of the future will fit into this changing industrial environment

As if these topics aren't enough, there is always the question of

HOW CAN WE MOTIVATE THE NEXT GENERATION OF SCIENTISTS TO PURSUE CAREERS IN CHEMISTRY???

Regardless of the bullet points listed above, there can be no continuity in our scientific endeavors without an ability to guide the best and brightest of our youth into the direction of pursuing careers in applied sciences. While this is an obvious statement, I cannot emphasize enough that one of the main gate keeping subjects is organic chemistry. When students are first expected to confront this subject, they are presented with a textbook encyclopedic in size. The amount of information they are expected to absorb is daunting for anyone and many students believe that their only hope is to commit their coursework to memory. THIS WAS MY FIRST EXPERIENCE IN THIS SUBJECT!!!

As I progressed into my first semester of organic chemistry, I came to realize that memorization of the multitude of name reactions and all of their variants was nowhere near as important as developing an understanding of the fundamental mechanisms that underlie each reaction presented in organic chemistry. I abandoned all attempts to use chemical reaction flash cards and allowed my association of reaction names with chemical transformations to develop through osmosis. Instead, I practiced chemical reactions while incorporating each mechanistic step into my scratch pad. Using curved arrows, I kept track of the movement of electrons and gradually developed a strong appreciation for the value of this "arrow pushing" technique. My grades in organic chemistry improved and I continued to study this subject.

All of the above took place in 1984 - 25 years ago. Since then, I earned my PhD at MIT and am now a synthetic organic chemist having led and contributed to drug discovery efforts for over 17 years. During that time, I have experienced many facets of the pharmaceutical industry impacted by chemistry. These areas include:

• Drug discovery/development

• Patent law

• Business development

• Environmental health and safety

• Quality assurance/control

To those of you who feel apprehensive about studying organic chemistry, please stick with it. Numerous study aids are now available that present strategies to approach and master this subject. Remember, there is a huge world of opportunities that open to those with an understanding of this basic science - the chemistry of carbon.