a matter of trust asher may 2009

5 WORLDVIEW 09

A GLOBAL BIOTECHNOLOGY PERSPECTIVE!"#$%&'()

INTERNATIONAL STRATEGIES IN CHALLENGING TIMES

CUTTING-EDGE SCIENCE & TECHNOLOGY

SOCIAL & POLITICAL DIMENSIONS OF LIFE SCIENCE PROGRESS

FEATURING THE

WORLDVIEW SCORECARD

A country-by-country assessment of innovation climates across the globe

CAN A NEW KIND OF ATM CHANGE GLOBAL HEALTHCARE?

70 SCIENTIFIC AMERICAN | WORLDVIEW SCIENCE & TECHNOLOGY 71

What sparked your interest in IT?

» MY INTEREST IN IT, essentially, occurred in the early eighties. In 1978, I founded Advanced Bioresearch Associates, ABA. We were helping a number of di!erent types of companies with a number of devices. One was the "rst human arti"cial heart, which came out of Stanford. #at arti"cial heart was actually in machine code. So I had to "gure out how to comfort the FDA with so$ware and hardware as it related to an arti"cial heart, which is a pretty signi"cant product as trust goes. So it really kind of brought me out of the closet of IT and really got me into the concepts of things like so$ware validation. In helping the FDA accept such technologies, I depended on a very simple word that’s guided me forevermore, and that’s trust. How do you trust the IT to do exactly what it claims it will, and—more important—that it wouldn’t harm somebody or cause a problem?

What range of issues gets impacted by trust in today’s com-putational information from biotechnology?

» IF WE TAKE A GLOBAL PERSPECTIVE and look at the global biotechnology centers, they develop around medical universities that spill out information and tech-nology and IP, intellectual property. So much of that IP is coming out of academic institutions that have used com-putational tools to characterize some of the IP. #e issue

Biomedical Information— A Matter of TrustA Q&A WITH HOWARD R. ASHER

Can a new kind of ATM change global healthcare?

Howard R. Asher, president and chief executive officer of Global Life Sciences in San Diego, Calif., not only watched, but participated in, the evolution of infor-

mation technology (IT). He started in product development at Pfizer, then Bax-ter and Bayer before founding a series of his own companies—now doing so for 30 years. During those years, Asher found that many technical advances depend on trust. Here, Worldview talks to Asher about trust in biomedical IT and how it might be enhanced. This is an edited ex-cerpt of that interview.

ILLUSTRATION BY CARMEN SEGOVIA

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h;p://www.saworldview.com/ar+cle/biomedical‐informa+on‐‐a‐ma;er‐of‐trust‐a‐qanda‐with‐howard‐r‐‐asher

What sparked your interest in IT?

» MY INTEREST IN IT, essentially, occurred in the early eighties. In 1978, I founded Advanced Bioresearch Associates, ABA. We were helping a number of di!erent types of companies with a number of devices. One was the "rst human arti"cial heart, which came out of Stanford. #at arti"cial heart was actually in machine code. So I had to "gure out how to comfort the FDA with so$ware and hardware as it related to an arti"cial heart, which is a pretty signi"cant product as trust goes. So it really kind of brought me out of the closet of IT and really got me into the concepts of things like so$ware validation. In helping the FDA accept such technologies, I depended on a very simple word that’s guided me forevermore, and that’s trust. How do you trust the IT to do exactly what it claims it will, and—more important—that it wouldn’t harm somebody or cause a problem?

What range of issues gets impacted by trust in today’s com-putational information from biotechnology?

» IF WE TAKE A GLOBAL PERSPECTIVE and look at the global biotechnology centers, they develop around medical universities that spill out information and tech-nology and IP, intellectual property. So much of that IP is coming out of academic institutions that have used com-putational tools to characterize some of the IP. #e issue

Biomedical Information— A Matter of TrustA Q&A WITH HOWARD R. ASHER

Can a new kind of ATM change global healthcare?

Howard R. Asher, president and chief executive officer of Global Life Sciences in San Diego, Calif., not only watched, but participated in, the evolution of infor-

mation technology (IT). He started in product development at Pfizer, then Bax-ter and Bayer before founding a series of his own companies—now doing so for 30 years. During those years, Asher found that many technical advances depend on trust. Here, Worldview talks to Asher about trust in biomedical IT and how it might be enhanced. This is an edited ex-cerpt of that interview.

ILLUSTRATION BY CARMEN SEGOVIA

! © C

there becomes interoperability if you will. As we take the intellectual property that has been developed by computa-tional means, is it something that we—in the big sense of “general public”—can trust?

!en, as we take that computational process and we move it into, say, an industrial environment that may actually start applying other computational processes to that core IP, we eventually get to a point where that is go-ing to be overviewed by a regulator. Of the 50 nations, we have 49 various views of: How do I trust the primary information, be it information that characterized a com-pound or information that was gathered in the nonclini-cal studies that proved safety or demonstrated e"cacy,

and how do I trust the IT and statistical assessments and all of the data management that has gone through not only the preclinical but including the clinical stages? From a regulator’s perspective, we want to trust that those are well-engineered, they are validated systems, and they are trustworthy in all respects.

With so many stages where IT is involved, you get a pretty big chain reaction in the requirement of trust.

» THAT’S ABSOLUTELY TRUE. As I’ve been #ying around the world and visiting with companies in di$er-ent countries, the issue of trust makes me ask: When have we—as the general public—experienced this before? Many years ago, we’d take money to our branch of our bank and deposit our cash. !ey would put it in their vault, and if we needed to remove some of that money, we had to go back to that branch and that vault, from which the money was provided back to us. But now, we have the global ATM. !e only IT that the general public—as a world public—will trust is the ATM. !ey do not trust the telephone IT. !ey don’t trust the credit-card IT. !ey don’t trust many, many other billing mechanisms and other IT stu$, but they do trust the ATM.

How can the technology behind a money machine improve biotechnology?

» LET’S GO THROUGH A SCENARIO of what this might look like in the future. What if right beside our money set our entire health record? So we have the automated teller machine, ATM, and next to that we have the automated telemedicine machine, the new ATM of our medical infor-mation from birth. What if we uploaded into our health-care information our genotype and then—as we experi-ence the environment of life ongoing—we could add our phenotype? !en, every dental X-ray, every medical record, every drug, everything we take is uploaded into our medi-

cal record. !en let’s imagine that we have hundreds of millions of people around the world with their medical records uploaded into their “ATM.” What then could theoretically occur is that—just like we can check a box to say we are an organ donor—we could say that we are a genetic-information donor. !en, we as an industry can bene%t from real human genomic and therapeutic information related to disease types. We could structure and stratify that data. It would be real human data at the genetic level. We could then look at how di$erent drug

therapeutics a$ected di$erent phenotypes and so on. We could look at biomarkers and start harvesting real informa-tion associated with real disease. All of a sudden, we would have a goldmine of information that we would trust more when applying it to therapeutic compounds.

Do you say “trust more” in this case partly—or almost entirely—because the sample size would be big enough to be really trustworthy?

» EXACTLY. We would now be dealing with biostatistical signi%cance that healthcare professionals must truly trust. Not only would we understand the therapeutic dynamics, but we would also understand the biomarker outliers.

If we’re at the molecular level and the cellular level, might we be able to harvest out the information of where something will therapeutically be e$ective, what is the mechanism of action, and where might we get a bad out-come or unanticipated e$ect that we’re not wanting?

We hear a lot about the medical and pharmaceutical com-munities wanting to do things like personalized medicine or gene therapy, but doing this e!ectively seems to depend

on—or even require— the kind of database of information that you are describing.

» THAT IS REALLY THE ESSENCE OF THE POINT. !e biotech industry is really at an embryonic state with IT. Part of that is that when we are dealing with data that are at the cellular and genomic level, we very quickly start looking at petabytes of information and terabytes of data. One simplistic concept many times escapes us, and it is: We want to go from data to information and then to knowledge. What’s happening is that the interpretation of volumes of data into truly meaningful and trustworthy information is not yet complete. We haven’t quite %gured out how to make sure that we have adequate data sample sizes to make an in-formational set of facts that we as a people can trust. !en, as we convert the information and set of facts that we can trust—based on the adequacy of data—then we start get-ting into the knowledge that we as an industry so desper-ately need. Vioxx and many other drugs serve as troubling examples where we have not known what we did not know when we put a drug or therapeutic to the market.

!e current mechanism, the current model, does not work. We know that fact. We know that the animal data give us much misinformation. We know that some of the Phase I, Phase II clinical studies add to the misinforma-tion, partially because the inclusion and exclusion criteria

have become so stringent. !en all of a sudden, we’re into a Phase III, not really getting the data that we really need, except at the organ level. We’re still in the art form of med-icine. We’re not in the science of medicine.

We have to take some harsh looks at what is happen-ing to drug development and therapeutic development, and it’s not very pretty. We’re seeing about a 99.9 percent failure rate. So for, say, every 10,000 compounds targeted, we’re seeing one really get through the process and get market ap-provals. !at’s horrifying when we look at the economics.

Given those bad odds, how can biotechnology put your ATM analogy into operation to improve the situation?

» WE COULD HARVEST the genomic and cellular data of humans, associate that with a disease, and look at the therapeutic potentials with computational predictive modeling. !en, we could determine in the modeling what biomarkers are expressed, where a potential therapeutic would be most e$ective in which population and equally important—if not more important—the populations we should avoid and actually contraindicate—meaning that if you have a speci%c biomarker, you should not have this drug because it will be a bad outcome.

Let’s talk about the toxicological information that we gain when we go through our current paradigm. We are actually taking histology and toxicological informa-tion from animals. We are trying to associate that with humans. We are saying that the animal must be pure, a laboratory controlled animal—not anything re#ective of a human, who would be eating all kinds of di$erent diets, consuming all kinds of supplemental products, and envi-ronmentally they are exposed to everything under the sun. So right there, just look at the contrast between the human patient and that animal from which we’re gaining toxico-logical knowledge. !e information provided by that kind of data is just wrong.

It’s hard to miss the international potential behind your idea of a medical ATM. If health information from around the world could be made available, a pharmaceutical company could access data from most anywhere. Likewise, this could bring better healthcare to developing countries if more information were available about medical histories of their people.

» ABSOLUTELY TRUE. If we are going to build a suc-cessful therapeutic, it is nothing but naïve if we think that we only need to conduct our clinical assessments and our development within, let’s say, the United States. !at is very nearsighted. We have to be global.

What if we uploaded into our healthcare information our geno-type and then—as we experience the environment of life ongoing—we could add our phenotype?

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